Glyn Johnson, Ph.D.

Treatment-Related Change Versus Tumor Recurrence in High-Grade Gliomas: A Diagnostic Conundrum--Use of Dynamic Susceptibility Contrast-Enhanced (DSC) Perfusion MRI
Fatterpekar, Girish M; Galheigo, Diogo; Narayana, Ashwatha; Johnson, Glyn; Knopp, Edmond
2012 Jan;198(1):19-26, American journal of roentgenology
OBJECTIVE: The purpose of this article is to address radiation necrosis, pseudoprogression, and pseudoresponse relative to high-grade gliomas and evaluate the role of conventional MRI and, in particular, dynamic susceptibility contrast-enhanced perfusion MRI in assessing such treatment-related changes from tumor recurrence. CONCLUSION: Posttreatment imaging assessment of high-grade gliomas remains challenging. Familiarity with the expected MR imaging appearances of treatment-related change and tumor recurrence will help distinguish these entities allowing appropriate management
— id: 147218, year: 2012, vol: 198, page: 19, stat: Journal Article,

Systematic differences between lean and obese adolescents in brain spin-lattice relaxation time: a quantitative study
Cazettes, F; Tsui, W H; Johnson, G; Steen, R G; Convit, A
2011 Dec;32(11):2037-2042, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Emerging evidence suggests that obese adolescents show changes in brain structure compared with lean adolescents. In addition, obesity impacts body development during adolescence. We tested a hypothesis that T1, a marker of brain maturation, can show brain differences associated with obesity. MATERIALS AND METHODS: Adolescents similar in sex, family income, and school grade were recruited by using strict entry criteria. We measured brain T1 in 48 obese and 31 lean adolescents by quantitative MR imaging at 1.5T. We combined MPRAGE and inversion-recovery sequences with normalization to standard space and automated skull stripping to obtain T1 maps with a symmetric voxel volume of 1 mm(3). RESULTS: Sex, income, triglycerides, total cholesterol, and fasting glucose did not differ between groups, but obese adolescents had significantly lower HDL, higher LDL, and higher fasting insulin levels than lean adolescents. Intracranial vault volume did not differ between groups, but obese adolescents had smaller intracranial vault-adjusted brain parenchymal volumes. Obese adolescents had 4 clusters (>100 contiguous voxels) of T1 relaxation that were significantly different (P < .005) from those in lean adolescents. Three of these clusters had longer T1s in obese adolescents (in the orbitofrontal and parietal regions), and 1 cluster had shorter T1s, compared with lean adolescents. CONCLUSIONS: Our results suggest that obesity may have a significant impact on brain development, especially in the frontal and parietal lobes. It is unclear if these changes persist into adulthood or whether they indicate that obese subjects follow a different developmental trajectory during adolescence
— id: 150559, year: 2011, vol: 32, page: 2037, stat: Journal Article,

An improved model for describing the contrast bolus in perfusion MRI
Patil, Vishal; Johnson, Glyn
2011 Dec;38(12):6380-6380, Medical physics
Purpose: Quantification of perfusion measurements using dynamic, susceptibility-weighted contrast-enhanced (DSC) MRI depends on estimating the size and shape of the tracer bolus. Typically, the bolus is described as a gamma variate function (GV) fitted to the bolus portion of tracer concentration time curve (CTC). However, the last point to fit is arbitrary which can lead to considerable variation in the fitted curve in the presence of noise. In this technical note, we present a model which takes into account recirculation explicitly and fits robustly to the entire CTC in the presence of noise.Methods: Signal data measurements from ten DSC MRI patients were fitted with our new model and a GV function using four different methods of estimating the end of the bolus. Estimates of the area under the curves (AUC) and first moments (FMs) of the bolus were compared at different noise levels.Results: The new model gave errors similar to or smaller than those of the most effective methods for fitting a GV.Conclusions: The single compartment recirculation (SCR) model is the most robust fitting technique with respect to noise both for bias and variability
— id: 146258, year: 2011, vol: 38, page: 6380, stat: Journal Article,

Relative cerebral blood volume measurements of low-grade gliomas predict patient outcome in a multi-institution setting
Caseiras, Gisele B; Chheang, Sophie; Babb, James; Rees, Jeremy H; Pecerrelli, Nicole; Tozer, Daniel J; Benton, Christopher; Zagzag, David; Johnson, Glyn; Waldman, Adam D; Jager, H R; Law, Meng
2010 Feb;73(2):215-220, European journal of radiology
BACKGROUND/PURPOSE: The prognostic value of defining subcategories of gliomas is still controversial. This study aims to determine the utility of relative cerebral blood volume (rCBV) in predicting clinical response in patients with low-grade glioma at multiple institutions. MATERIALS AND METHODS: Sixty-nine patients were studied with dynamic susceptibility contrast-enhanced perfusion MRI at two institutions. The pathologic diagnoses of the low-grade gliomas were 34 astrocytomas, 20 oligodendroglioma, 9 oligoastrocytomas, 1 ganglioglioma and 5 with indeterminate histology. Wilcoxon tests were used to compare patients in different response categories with respect to baseline rCBV. Kaplan-Meier curve and log-rank tests were used to predict the association of rCBV with time to progression. RESULTS: At both institutions, patients with an adverse event (progressive disease or death) had a significantly higher baseline rCBV than those without (complete response or stable disease) (p value=0.0138). The odds ratio for detecting an adverse event when using rCBV was 1.87 (95% confidence interval: 1.14-3.08). rCBV was significantly negatively associated with time to progression (p=0.005). The median time to progression among subjects with rCBV>1.75 was 365 days, while there was 95% confidence that the median time to progression was at least 889 days among subjects with rCBV<1.75. CONCLUSION: Our study suggests not only that rCBV measurements correlate well with time to progression or death, but also that the findings can be replicated across institutions, which supports the application of rCBV as an adjunct to pathology in predicting glioma biology
— id: 92909, year: 2010, vol: 73, page: 215, stat: Journal Article,

Brain tissue sodium concentration in multiple sclerosis: a sodium imaging study at 3 tesla
Inglese, M; Madelin, G; Oesingmann, N; Babb, J S; Wu, W; Stoeckel, B; Herbert, J; Johnson, G
2010 Mar;133(Pt 3):847-857, Brain
Neuro-axonal degeneration occurs progressively from the onset of multiple sclerosis and is thought to be a significant cause of increasing clinical disability. Several histopathological studies of multiple sclerosis and experimental autoimmune encephalomyelitis have shown that the accumulation of sodium in axons can promote reverse action of the sodium/calcium exchanger that, in turn, leads to a lethal overload in intra-axonal calcium. We hypothesized that sodium magnetic resonance imaging would provide an indicator of cellular and metabolic integrity and ion homeostasis in patients with multiple sclerosis. Using a three-dimensional radial gradient-echo sequence with short echo time, we performed sodium magnetic resonance imaging at 3 T in 17 patients with relapsing-remitting multiple sclerosis and in 13 normal subjects. The absolute total tissue sodium concentration was measured in lesions and in several areas of normal-appearing white and grey matter in patients, and corresponding areas of white and grey matter in controls. A mixed model analysis of covariance was performed to compare regional tissue sodium concentration levels in patients and controls. Spearman correlations were used to determine the association of regional tissue sodium concentration levels in T(2)- and T(1)-weighted lesions with measures of normalized whole brain and grey and white matter volumes, and with expanded disability status scale scores. In patients, tissue sodium concentration levels were found to be elevated in acute and chronic lesions compared to areas of normal-appearing white matter (P < 0.0001). The tissue sodium concentration levels in areas of normal-appearing white matter were significantly higher than those in corresponding white matter regions in healthy controls (P < 0.0001). The tissue sodium concentration value averaged over lesions and over regions of normal-appearing white and grey matter was positively associated with T(2)-weighted (P < or = 0.001 for all) and T(1)-weighted (P < or = 0.006 for all) lesion volumes. In patients, only the tissue sodium concentration value averaged over regions of normal-appearing grey matter was negatively associated with the normalized grey matter volume (P = 0.0009). Finally, the expanded disability status scale score showed a mild, positive association with the mean tissue sodium concentration value in chronic lesions (P = 0.002), in regions of normal-appearing white matter (P = 0.004) and normal-appearing grey matter (P = 0.002). This study shows the feasibility of using in vivo sodium magnetic resonance imaging at 3 T in patients with multiple sclerosis. Our findings suggest that the abnormal values of the tissue sodium concentration in patients with relapsing-remitting multiple sclerosis might reflect changes in cellular composition of the lesions and/or changes in cellular and metabolic integrity. Sodium magnetic resonance imaging has the potential to provide insight into the pathophysiological mechanisms of tissue injury when correlation with histopathology becomes available
— id: 108789, year: 2010, vol: 133, page: 847, stat: Journal Article,

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival
Narayana, Ashwatha; Kelly, Patrick; Golfinos, John; Parker, Erik; Johnson, Glyn; Knopp, Edmond; Zagzag, David; Fischer, Ingeborg; Raza, Shahzad; Medabalmi, Praveen; Eagan, Patricia; Gruber, Michael L
2009 Jan;110(1):173-180, Journal of neurosurgery
Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1-19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1-7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3-7.7) and 9 (95% CI 7.6-10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored
— id: 90721, year: 2009, vol: 110, page: 173, stat: Journal Article,

Robust quantification of contrast agent (CA) concentration with magnetic field correlation (MFC) imaging
Patil, Vishal; Johnson, Glyn; Jensen, Jens H
2009 Aug 11;62(4):1002-1006, Magnetic resonance in medicine
Contrast-enhanced perfusion studies of the brain by means magnetic resonance imaging (MRI) are used to estimate a number of important brain tissue parameters, including cerebral blood flow and volume. In order to calculate these parameters, the contrast agent (CA) concentration must first be estimated. This is usually accomplished by measurement of a nuclear magnetic resonance (NMR) relaxation rate with the assumption of a linear relationship between the rate and the CA concentration. However, such a linear relationship does not necessarily hold in biological tissues due to compartmentalization of the CA in either the intravascular or extracellular spaces. Here we propose an alternative MRI method of CA quantification based on measurement of the magnetic field correlation (MFC), which is theoretically predicted to have a robust quadratic dependence on the CA concentration even when the CA is compartmentalized. In this study, CA concentration estimation by means of MFC is shown to be more accurate than established methods based on relaxation rates in yeast cell suspensions. Magn Reson Med, 2009. (c) 2009 Wiley-Liss, Inc
— id: 101580, year: 2009, vol: 62, page: 1002, stat: Journal Article,

White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis
Varga, Andrew W; Johnson, Glyn; Babb, James S; Herbert, Joseph; Grossman, Robert I; Inglese, Matilde
2009 Jul 15;282(1-2):28-33, Journal of the neurological sciences
BACKGROUND: Hypoperfusion has been reported in lesions, normal-appearing white (NAWM) and gray matter (NAGM) of patients with clinically definite multiple sclerosis (MS) by using perfusion MRI. However, it is still unknown how early such changes in perfusion occur. The aim of our study was to assess the presence of hemodynamic changes in the NAWM and subcortical NAGM of patients with clinically isolated syndrome (CIS) in comparison to healthy controls and to patients with early relapsing-remitting (RR) MS. METHODS: Absolute cerebral blood flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the periventricular and frontal NAWM, thalamus and putamen nuclei of 12 patients with CIS, 12 with early RR-MS and 12 healthy controls using dynamic susceptibility contrast enhanced (DSC) T2-weighted MRI. RESULTS: Compared to controls, CBF was significantly decreased in the periventricular NAWM of CIS patients and in the periventricular NAWM and putamen of RR-MS patients. Compared to CIS, RR-MS patients showed a significant CBF decrease in the putamen. CONCLUSIONS: CBF was decreased in the NAWM of both CIS and RR-MS patients and in the subcortical NAGM of RR-MS patients suggesting a continuum of tissue perfusion decreases beginning in white matter and spreading to gray matter, as the disease progresses
— id: 95061, year: 2009, vol: 282, page: 28, stat: Journal Article,

Perfusion magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis
Inglese, Matilde; Adhya, Sumita; Johnson, Glyn; Babb, James S; Miles, Laura; Jaggi, Hina; Herbert, Joseph; Grossman, Robert I
2008 Jan;28(1):164-171, Journal of cerebral blood flow & metabolism
Although cognitive impairment is common in multiple sclerosis (MS), its pathophysiology is still poorly understood. Abnormalities of cerebral blood flow (CBF) have long been acknowledged in MS and advances in perfusion magnetic resonance imaging (MRI) allow for their assessment in vivo. We investigated the relationship between regional perfusion changes and neuropsychological (NP) dysfunctions in patients with relapsing-remitting and primary-progressive MS. Absolute CBF, cerebral blood volume (CBV) and mean transit time were measured in 32 MS patients and 11 healthy controls using dynamic susceptibility contrast-enhanced T2(*)-weighted MRI. A comprehensive NP test battery was administered to all patients. A mixed model analysis of covariance was performed for group comparisons in terms of perfusion measures in normal-appearing white matter (NAWM) and deep gray matter (GM). Pearson's correlations were used to describe the association of perfusion metrics with NP Z-scores. CBF and CBV values were significantly decreased in both NAWM and deep GM in MS patients compared with controls (P=0.01). In all patients, deep GM CBF was significantly associated with Rey Complex Figure Test (RCFT)-Copy (r=0.5; P=0.001) and deep GM CBV and NAWM CBV were significantly associated with Color-Word Interference Inhibition Switching test (D-KEFSIS) (r=0.4; P=0.008 and r=0.4; P=0.02). However, the only associations that remained significant after Bonferroni correction were between deep GM CBF and RCFT-Copy (P=0.006), and deep GM CBV and D-KEFSIS (P=0.04). Our results suggest a role for tissue perfusion impairment in NP dysfunction in MS. Large-scale studies are needed to characterize better this association.Journal of Cerebral Blood Flow & Metabolism advance online publication, 2 May 2007; doi:10.1038/sj.jcbfm.9600504
— id: 74676, year: 2008, vol: 28, page: 164, stat: Journal Article,

Gliomas: predicting time to progression or survival with cerebral blood volume measurements at dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging
Law, Meng; Young, Robert J; Babb, James S; Peccerelli, Nicole; Chheang, Sophie; Gruber, Michael L; Miller, Douglas C; Golfinos, John G; Zagzag, David; Johnson, Glyn
2008 May;247(2):490-498, Radiology
PURPOSE: To retrospectively determine whether relative cerebral blood volume (CBV) measurements can be used to predict clinical outcome in patients with high-grade gliomas (HGGs) and low-grade gliomas (LGGs) and specifically whether patients who have gliomas with a high initial relative CBV have more rapid progression than those who have gliomas with a low relative CBV. MATERIALS AND METHODS: Approval for this retrospective HIPAA-compliant study was obtained from the Institutional Board of Research Associates, with waiver of informed consent. One hundred eighty-nine patients (122 male and 67 female patients; median age, 43 years; range, 4-80 years) were examined with dynamic susceptibility-weighted contrast material-enhanced perfusion magnetic resonance (MR) imaging and were followed up clinically with MR imaging (median follow-up, 334 days). Log-rank tests were used to evaluate the association between relative CBV and time to progression by using Kaplan-Meier curves. Binary logistic regression was used to determine whether age, sex, and relative CBV were associated with an adverse event (progressive disease or death). RESULTS: Values for the mean relative CBV for patients according to each clinical response were as follows: 1.41 +/- 0.13 (standard deviation) for complete response (n = 4), 2.36 +/- 1.78 for stable disease (n = 41), 4.84 +/- 3.32 for progressive disease (n = 130), and 3.82 +/- 1.93 for death (n = 14). Kaplan-Meier estimates of median time to progression in days indicated that patients with a relative CBV of less than 1.75 had a median time to progression of 3585 days, whereas patients with a relative CBV of more than 1.75 had a time to progression of 265 days. Age and relative CBV were also independent predictors for clinical outcome. CONCLUSION: Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can be used to predict median time to progression in patients with gliomas, independent of pathologic findings. Patients who have HGGs and LGGs with a high relative CBV (>1.75) have a significantly more rapid time to progression than do patients who have gliomas with a low relative CBV
— id: 91375, year: 2008, vol: 247, page: 490, stat: Journal Article,

Predicting grade of cerebral glioma using vascular-space occupancy MR imaging
Lu, H; Pollack, E; Young, R; Babb, J S; Johnson, G; Zagzag, D; Carson, R; Jensen, J H; Helpern, J A; Law, M
2008 Feb;29(2):373-378, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: MR imaging can measure tissue perfusion and the integrity of the blood-brain barrier. We hypothesize that a combined measure of cerebral blood volume and vascular permeability using vascular-space occupancy (VASO) MR imaging, a recently developed imaging technique, is of diagnostic value for predicting tumor grade. MATERIALS AND METHODS: Thirty-nine patients (9 World Health Organization [WHO] grade II, 20 grade III, and 10 grade IV as determined by histopathologic assessment) were examined using VASO MR imaging, and regions-of-interest analysis was performed in tumoral regions, as well as in regions contralateral to the tumor. A Mann-Whitney test was conducted on the resulting VASO indices for a pairwise comparison across tumor grades. Nominal logistic regression was used to evaluate the use of VASO parameters for predicting group membership (by the percentage of correct classifications). RESULTS: The ratio between tumor side and contralateral side, VASO(Ratio), showed significant differences in all 3 of the pairwise comparisons (P < .01). VASO values in the tumoral regions, VASO(Tumor), showed significant difference between grade II and III and between II and IV but not between III and IV. Both VASO(Tumor) and VASO(Ratio) were found to be significant predictors of tumor grade, giving diagnostic accuracies of 66.7% and 71.8%, respectively. When testing to discriminate grade II tumors from higher grade tumors, the areas under the receiver operating characteristic curve were found to be 0.974 and 0.985 for VASO(Tumor) and VASO(Ratio), respectively. CONCLUSION: VASO MR imaging can be used for noninvasive tumor grade prediction based on cerebral blood volume and vascular permeability. VASO is more effective in separating WHO grade II from higher grades than in separating grade III from grade IV
— id: 78348, year: 2008, vol: 29, page: 373, stat: Journal Article,

Short-term DTI predictors of cognitive dysfunction in mild traumatic brain injury
Miles, Laura; Grossman, Robert I; Johnson, Glyn; Babb, James S; Diller, Leonard; Inglese, Matilde
2008 Feb;22(2):115-122, Brain injury
PRIMARY OBJECTIVE: To explore whether baseline diffusion tensor imaging (DTI) metrics are predictive of cognitive functioning 6 months post-injury in patients with mild traumatic brain injury (MTBI). RESEARCH DESIGN: Seventeen patients with MTBI and 29 sex- and age-matched healthy controls were studied. METHODS AND PROCEDURES: Participants underwent an MRI protocol including DTI, at an average of 4.0 (range: 1-10) days post-injury. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the following white matter (WM) regions: centra semiovale, the genu and the splenium of the corpus callosum and the posterior limb of the internal capsule. Participants underwent neuropsychological (NP) testing at baseline and at 6-month follow-up. Least squares regression analysis was used to evaluate the association of MD and FA with each NP test score at baseline and follow-up. MAIN OUTCOMES AND RESULTS: Compared to controls, average MD was significantly higher (p = 0.02) and average FA significantly lower (p = 0.0001) in MTBI patients. At the follow-up, there was a trend toward a significant association between baseline MD and response speed (r = -0.53, p = 0.087) and a positive correlation between baseline FA and Prioritization form B (r = 0.72, p = 0.003). CONCLUSIONS: DTI may provide short-term non-invasive predictive markers of cognitive functioning in patients with MTBI
— id: 91954, year: 2008, vol: 22, page: 115, stat: Journal Article,

Ventral striatal blood flow is altered by acute nicotine but not withdrawal from nicotine
Tanabe, Jody; Crowley, Thomas; Hutchison, Kent; Miller, David; Johnson, Glyn; Du, Yiping P; Zerbe, Gary; Freedman, Robert
2008 Feb;33(3):627-633, Neuropsychopharmacology
Neural mechanisms underlying the reinforcing effects of nicotine and other drugs have been widely studied and are known to involve the ventral striatum, which is part of the mesocorticolimbic dopamine system. In contrast, mechanisms of nicotine withdrawal have received less attention although subjective withdrawal likely contributes to the difficulty of quitting. The goal of this study was to determine if nicotine withdrawal was associated with alterations of cerebral blood flow (CBF) in ventral striatum. Twelve smokers, moderately dependent on nicotine, underwent MR dynamic susceptibility contrast (DSC) imaging at baseline, after overnight withdrawal from nicotine, and after nicotine replacement. DSC images were used to calculate CBF in three regions of interest: ventral striatum, thalamus, and medial frontal cortex. Subjective withdrawal symptoms were measured at each time point. In spite of significant subjective withdrawal symptoms, there was no main effect of withdrawal on CBF in the three regions. However, there was a significant correlation between the increase in withdrawal symptoms and a reduction in thalamic CBF. In contrast to withdrawal, nicotine replacement significantly increased CBF in ventral striatum. Our findings are consistent with the known role of ventral striatum in drug reward. The lack of a main effect on withdrawal, but correlation of thalamic blood flow with withdrawal symptoms suggests that more complex mechanisms mediate the subjective features of the withdrawal state
— id: 96752, year: 2008, vol: 33, page: 627, stat: Journal Article,

Statistical mapping of sound-evoked activity in the mouse auditory midbrain using Mn-enhanced MRI
Yu, Xin; Zou, Jing; Babb, James S; Johnson, Glyn; Sanes, Dan H; Turnbull, Daniel H
2008 Jan 1;39(1):223-230, Neuroimage
Manganese-enhanced MRI (MEMRI) has been developed to image brain activity in small animals, including normal and genetically modified mice. Here, we report the use of a MEMRI-based statistical parametric mapping method to analyze sound-evoked activity in the mouse auditory midbrain, the inferior colliculus (IC). Acoustic stimuli with defined frequency and amplitude components were shown to activate and enhance neuronal ensembles in the IC. These IC activity patterns were analyzed quantitatively using voxel-based statistical comparisons between groups of mice with or without sound stimulation. Repetitive 40-kHz pure tone stimulation significantly enhanced ventral IC regions, which was confirmed in the statistical maps showing active regions whose volumes increased in direct proportion to the amplitude of the sound stimuli (65 dB, 77 dB, and 89 dB peak sound pressure level). The peak values of the activity-dependent MEMRI signal enhancement also increased from 7% to 20% for the sound amplitudes employed. These results demonstrate that MEMRI statistical mapping can be used to analyze both the 3D spatial patterns and the magnitude of activity evoked by sound stimuli carrying different energy. This represents a significant advance in the development of MEMRI for quantitative and unbiased analysis of brain function in the deep brain nuclei of mice
— id: 74214, year: 2008, vol: 39, page: 223, stat: Journal Article,

Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T
Inglese, Matilde; Park, Sun-Jung; Johnson, Glyn; Babb, James S; Miles, Laura; Jaggi, Hina; Herbert, Joseph; Grossman, Robert I
2007 Feb;64(2):196-202, Archives of neurology
OBJECTIVES: To assess the presence of perfusion abnormalities in the deep gray matter of patients with relapsing-remitting and primary progressive multiple sclerosis (MS) in comparison with healthy controls and to investigate the impact of perfusion impairment on clinical disability and fatigue. DESIGN: Survey. SETTING: Research-oriented hospital. Patients Twenty-two patients with MS and 11 age- and sex-matched healthy volunteers. Intervention Absolute cerebral blood flow, cerebral blood volume, and mean transit time were measured in the thalamus, putamen, and caudate nuclei. MAIN OUTCOME MEASURES: Decrease of cerebral blood flow in the deep gray matter of patients with MS and correlation between perfusion impairment and the severity of fatigue. RESULTS: The cerebral blood flow value averaged over the thalamus, putamen, and caudate nuclei was significantly lower in patients with primary progressive MS (P<.001) and in patients with relapsing-remitting MS (P = .01) compared with controls, and there was a trend for patients with primary progressive MS to have lower average cerebral blood flow than patients with relapsing-remitting MS (P = .06). With respect to cerebral blood volume, there was a significant difference between patients with primary progressive MS and controls (P<.001) and between the 2 groups of patients (P = .03) but not between patients with relapsing-remitting MS and controls (P>.30). The fatigue score was significantly correlated with cerebral blood flow (r = 0.4; P<.001) and cerebral blood volume (r = 0.5; P = .004). CONCLUSION: The decrease of tissue perfusion in the deep gray matter of patients with MS is associated with the severity of fatigue
— id: 70830, year: 2007, vol: 64, page: 196, stat: Journal Article,

Histogram analysis versus region of interest analysis of dynamic susceptibility contrast perfusion MR imaging data in the grading of cerebral gliomas
Law, M; Young, R; Babb, J; Pollack, E; Johnson, G
2007 Apr;28(4):761-766, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Histogram analysis can be applied to dynamic susceptibility contrast (DSC) perfusion MR imaging datasets and can be as effective as traditional region-of-interest (ROI) measurements of relative cerebral blood volume (rCBV), an operator-dependent method. We compare the routine ROI method with histogram analysis in the grading of glial neoplasms. MATERIALS AND METHODS: Ninety-two patients underwent conventional and DSC MR imaging. Routine rCBV (rCBVmax) measurements were obtained from ROIs of the maximal abnormality within the glioma. Histogram analysis rCBVT was performed with an ROI drawn around the maximal tumor diameter. Spearman rank correlations measured associations among glioma grade, rCBVmax, and histogram measures. Mann-Whitney tests compared grade with respect to rCBV and histogram measures. Logistic regression and McNemar test compared the utility of rCBVmax and histogram measures for detecting high grade gliomas. RESULTS: Routine rCBVmax analysis showed significant correlation with grade (r = 0.734, P < .001). Histogram rCBVT metrics showed significant correlation with grade (P < .008); the 3 highest were rCBVT SD, SD50, and mean25 (r = 0.718, 0.684, and 0.683, respectively). Grade could be predicted by rCBVmax (P < .001) as well as rCBV(T) (P < .008). Three rCBVT histogram measures (SD, SD25, and SD50) detected high-grade glioma with significantly higher specificity than rCBVmax when the diagnostic tests were constrained to have at least 95% sensitivity. CONCLUSION: rCBVT histogram analysis is as effective as rCBVmax analysis in the correlation with glioma grade. Inexperienced operators may obtain perfusion metrics using histogram analyses that are comparable with those obtained by experienced operators using ROI analysis.
— id: 72815, year: 2007, vol: 28, page: 761, stat: Journal Article,

High cerebral blood volume in human gliomas predicts deletion of chromosome 1p: Preliminary results of molecular studies in gliomas with elevated perfusion
Law, Meng; Brodsky, Jennie E; Babb, James; Rosenblum, Marc; Miller, Douglas C; Zagzag, David; Gruber, Michael L; Johnson, Glyn
2007 Jun;25(6):1113-1119, Journal of magnetic resonance imaging
PURPOSE: To determine if increased perfusion using dynamic susceptibility contrast perfusion MRI (DSC MRI) in gliomas may be predictive of 1p19q deletions. Loss of heterozygosity of chromosomes 1p and 19q confers responsiveness to chemotherapy improving survival in gliomas. MATERIALS AND METHODS: We retrospectively reviewed 16 patients who had DSC MRI and molecular studies of their excised gliomas for 1p19q deletions. Allelic status was assessed by loss of heterozygosity using polymerase chain reaction (PCR). DNA was extracted from paraffin curls of brain tumor sections and nail clippings. Relative cerebral blood volume (rCBV) measurements were then statistically compared with the presence of 1p and 19q deletions. RESULTS: Patients with 1p19q deletions (N = 7) demonstrated rCBV values of 10.54 +/- 2.93. Patients without 1p deletions (N = 9) had rCBV values of 4.84 +/- 2.4 (P = 0.012). Logistic regression demonstrated that rCBV was able to predict the presence of a 1p deletion to significance levels of 0.038 and 0.044, adjusted and not adjusted for age and sex, respectively. The kappa coefficient for the agreement between predicted deletion status using rCBV and the truedeletion status was 0.746 (P = 0.0028). Deletions of 19q alone, or together with 1p deletions, were not associated with high rCBV. CONCLUSION: Histopathologic, molecular, and imaging evidence supports increased neovascularity in gliomas with 1p deletions in this preliminary study. We propose a diagnostic algorithm to obtain molecular studies in gliomas demonstrating high rCBV.
— id: 73001, year: 2007, vol: 25, page: 1113, stat: Journal Article,

Brainstem corticospinal tract diffusion tensor imaging in patients with primary posterior fossa neoplasms stratified by tumor type: a study of association with motor weakness and outcome
Lui, Yvonne W; Law, Meng; Chacko-Mathew, Jeena; Babb, James S; Tuvia, Keren; Allen, Jeffrey C; Zagzag, David; Johnson, Glyn
2007 Dec;61(6):1199-1207, Neurosurgery
OBJECTIVE: Diffusion tensor imaging (DTI) allows in vivo delineation of brainstem white matter tracts. The purpose of this study was to determine whether or not abnormalities of DTI metrics and fiber tractography correlate with neurological deficits and clinical status in patients with primary posterior fossa tumors. METHODS: A review of patients with primary posterior fossa tumors who underwent magnetic resonance imaging with DTI was performed. Patients were stratified by tumor type (well-circumscribed or infiltrating lesions). Fractional anisotropy (FA) color maps were used to localize the corticospinal tracts within the brainstem. FA, mean diffusivity, and eigenvalues were measured. Tractography was performed. Correlations between DTI metrics and clinical status and between DTI metrics and neurological examination findings were assessed within each patient group using Bonferroni correction for multiple comparisons. Comparisons of DTI metrics were also made between patient groups (infiltrating lesions versus well-circumscribed lesions). RESULTS: Thirty patients were studied (mean age, 14.1 yr; 16 male, 14 female). Eighteen patients had infiltrating lesions and 12 had well-circumscribed lesions. Twelve patients (four well-circumscribed and eight infiltrating) demonstrated motor weakness on physical examination (four right, three left, five bilateral). Patients with well-circumscribed lesions and weakness had higher mean diffusivity and lower FA in the contralateral corticospinal tract (P < 0.05). No such association was seen in patients with infiltrating tumors. In 102 total patient-years of follow-up (average follow-up period, 4.2 yr), 17 patients (six well-circumscribed and 11 infiltrating lesions) demonstrated complete response or stable disease and six patients (three well-circumscribed and three infiltrating lesions) demonstrated progressive disease or death. No differences were seen in terms of DTI metrics between patients with infiltrating lesions and those with well-circumscribed lesions. Patients with well-circumscribed tumors and a bad outcome had significantly lower transverse eigenvalue measures in the corticospinal tracts compared with those with a more favorable clinical status (P < 0.05). CONCLUSION: In patients with well-circumscribed primary posterior fossa masses, higher mean diffusivity and lower FA in the brainstem corticospinal tract are associated with contralateral motor deficits; lower transverse eigenvalue may be observed with an unfavorable clinical outcome
— id: 92914, year: 2007, vol: 61, page: 1199, stat: Journal Article,

Correlation of diffusion tensor and dynamic perfusion MR imaging metrics in normal-appearing corpus callosum: support for primary hypoperfusion in multiple sclerosis
Saindane, A M; Law, M; Ge, Y; Johnson, G; Babb, J S; Grossman, R I
2007 Apr;28(4):767-772, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Hypoperfusion of the normal-appearing white matter in multiple sclerosis (MS) may be related to ischemia or secondary to hypometabolism from wallerian degeneration (WD). This study evaluated whether correlating perfusion and diffusion tensor imaging (DTI) metrics in normal-appearing corpus callosum could provide support for an ischemic mechanism for hypoperfusion. MATERIALS AND METHODS: Fourteen patients with relapsing-remitting MS (RRMS) and 17 control subjects underwent perfusion MR imaging and DTI. Absolute measures of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated. Mean diffusivity (MD) and fractional anisotropy (FA) maps were computed from DTI data. After visual coregistration of perfusion and DTI images, regions of interest were placed in the genu, central body, and splenium of normal-appearing corpus callosum. Pearson product-moment correlation coefficients were calculated using mean DTI and perfusion measures in each region. RESULTS: In the RRMS group, CBF and CBV were significantly correlated with MD in the splenium (r = 0.83 and r = 0.63, respectively; both P < .001) and in the central body (r = 0.86 and r = 0.65, respectively; both P < .001), but not in the genu (r = 0.23 and 0.25, respectively; both P is nonsignificant). No significant correlations were found between MTT and DTI measures or between FA and any perfusion measure in the RRMS group. No significant correlations between diffusion and perfusion metrics were found in control subjects. CONCLUSION: In the normal-appearing corpus callosum of patients with RRMS, decreasing perfusion is correlated with decreasing MD. These findings are more consistent with what would be expected in primary ischemia than in secondary hypoperfusion from WD.
— id: 72816, year: 2007, vol: 28, page: 767, stat: Journal Article,

Comparison of region-of-interest analysis with three different histogram analysis methods in the determination of perfusion metrics in patients with brain gliomas
Young, Robert; Babb, James; Law, Meng; Pollack, Erica; Johnson, Glyn
2007 Oct;26(4):1053-1063, Journal of magnetic resonance imaging
PURPOSE: To compare routine ROI analysis and three different histogram analyses in the grading of glial neoplasms. The hypothesis is that histogram methods can provide a robust and objective technique for quantifying perfusion data in brain gliomas. Current region-of-interest (ROI)-based methods for the analysis of dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) data are operator-dependent. MATERIALS AND METHODS: A total of 92 patients underwent conventional and DSC MRI. Multiple histogram metrics were obtained for cerebral blood flow (CBF), cerebral blood volume (CBV), and relative CBV (rCBV) maps using tumoral (T), peritumoral (P), and total tumoral (TT) analysis. Results were compared to histopathologic grades. Statistical analysis included Mann-Whitney (MW) tests, Spearman rank correlation coefficients, logistic regression, and McNemar tests. RESULTS: The maximum value of rCBV (rCBV(max)) showed highly significant correlation with glioma grade (r = 0.734, P < 0.001). The strongest histogram correlations (P < 0.0001) occurred with rCBV(T) SD (r = 0.718), rCBV(P) SD(25) (r = 0.724) and rCBV(TT) SD(50) (r = 0.685). Multiple rCBV(T), rCBV(P), and rCBV(TT) histogram metrics showed significant correlations. CBF and CBV histogram metrics were less strongly correlated with glioma grade than rCBV histogram metrics. CONCLUSION: Histogram analysis of perfusion MR provides prediction of glioma grade, with peritumoral metrics outperforming tumoral and total tumoral metrics. Further refinement may lead to automated methods for perfusion data analysis. J. Magn. Reson. Imaging 2007;26:1053-1063. (c) 2007 Wiley-Liss, Inc
— id: 74215, year: 2007, vol: 26, page: 1053, stat: Journal Article,

Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T
Adhya, Sumita; Johnson, Glyn; Herbert, Joseph; Jaggi, Hina; Babb, James S; Grossman, Robert I; Inglese, Matilde
2006 Dec;33(4):1029-1035, Neuroimage
This study aimed to determine regional pattern of tissue perfusion in the normal-appearing white matter (NAWM) of patients with primary-progressive (PP), relapsing-remitting (RR) multiple sclerosis (MS) and healthy controls, and to investigate the association between perfusion abnormalities and clinical disability. Using dynamic susceptibility contrast (DSC) perfusion MRI at 3 T, we studied 22 patients with clinically definite MS, 11 with PP-MS and 11 with RR-MS and 11 age- and gender-matched healthy volunteers. The MRI protocol included axial dual-echo, dynamic susceptibility contrast enhanced (DSC) T2*-weighted and post-contrast T1-weighted images. Absolute cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the periventricular, frontal, occipital NAWM and in the splenium of the corpus callosum. Compared to controls, CBF and CBV were significantly lower in all NAWM regions in both PP-MS patients (p values from <0.0001 to 0.001) and RR-MS (p values from <0.0001 to 0.020). Compared to RR-MS, PP-MS patients showed significantly lower CBF in the periventricular NAWM (p=0.002) and lower CBV in the periventricular and frontal NAWM (p values: 0.0029 and 0.022). EDSS was significantly correlated with the periventricular CBF (r=-0.48, p=0.0016) and with the periventricular and frontal CBV (r=-0.42, p=0.015; r=-0.35, p=0.038, respectively). This study suggests that the hemodynamic abnormalities of NAWM have clinical relevance in patients with MS. DSC perfusion MRI might provide a relevant objective measure of disease activity and treatment efficacy
— id: 70833, year: 2006, vol: 33, page: 1029, stat: Journal Article,

Comparison of microvascular permeability measurements, K(trans), determined with conventional steady-state T1-weighted and first-pass T2*-weighted MR imaging methods in gliomas and meningiomas
Cha, S; Yang, L; Johnson, G; Lai, A; Chen, M-H; Tihan, T; Wendland, M; Dillon, W P
2006 Feb;27(2):409-417, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: The widely accepted MR method for quantitating brain tumor microvascular permeability, K(trans), is the steady-state T1-weighted gradient-echo method (ssT1). Recently the first-pass T2*-weighted (fpT2*) method has been used to derive both relative cerebral blood volume (rCBV) and K(trans). We hypothesized that K(trans) derived from the ssT1 and the fpT2* methods will correlate differently in gliomas and meningiomas because of the unique differences in morphologic and functional status of each tumor vascular network. METHODS: Before surgery, 27 patients with newly diagnosed gliomas (WHO grade I-IV; n = 20) or meningiomas (n = 7) underwent conventional anatomic MR imaging and 12 dynamic ssT1 acquisitions followed by 60 dynamic fpT2* images before and after gadopentate dimeglumine administration. The 3 hemodynamic variables-fpT2* rCBV, fpT2* K(trans), and ssT1 K(trans)-were calculated in anatomically identical locations and correlated with glioma grade. The fpT2* K(trans) values were compared with ssT1 K(trans) for gliomas and meningiomas. RESULTS: All 3 hemodynamic variables displayed distinct distributions among grades 2, 3, and 4 gliomas by using the Kruskal-Wallis test. Only K(trans) values, and not rCBV, could differentiate between grade 4 and lower-grade gliomas by using the Wilcoxon rank sum test. The fpT2* K(trans) was highly predictive of ssT1 K(trans) for gliomas, with an estimated regression coefficient of 0.49 (P < .001). For meningiomas, however, fpT2* K(trans) values correlated poorly with ssT1 K(trans) values (r = 0.26; P = .74). CONCLUSION: Compared with rCBV, K(trans) values derived from either ssT1 or fpT2* were more predictive of glioma grade. The fpT2* K(trans) was highly correlated with ssT1 K(trans) in gliomas but not in meningiomas
— id: 67927, year: 2006, vol: 27, page: 409, stat: Journal Article,

Diffusion tensor imaging in multiple sclerosis: assessment of regional differences in the axial plane within normal-appearing cervical spinal cord
Hesseltine, S M; Law, M; Babb, J; Rad, M; Lopez, S; Ge, Y; Johnson, G; Grossman, R I
2006 Jun-Jul;27(6):1189-1193, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Evaluation of the spinal cord is important in the diagnosis and follow-up of patients with multiple sclerosis. Our purpose was to investigate diffusion tensor imaging (DTI) changes in different regions of normal-appearing spinal cord (NASC) in relapsing-remitting multiple sclerosis (RRMS). METHODS: Axial DTI of the cervical spinal cord was performed in 24 patients with RRMS and 24 age- and sex-matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated in separate regions of interest (ROIs) in the anterior, lateral, and posterior spinal cord, bilaterally, and the central spinal cord, at the C2-C3 level. Patients and control subjects were compared with respect to FA and MD with the use of an exact Mann-Whitney test. Logistic regression and receiver operating characteristic (ROC) curve analysis assessed the utility of each measure for the diagnosis of RRMS. RESULTS: DTI metrics in areas of NASC in MS were significantly different in patients compared with control subjects; FA was lower in the lateral (mean +/- SD of 0.56 +/- 0.10 versus 0.69 +/- 0.09 in control subjects, P < .0001), posterior (0.52 +/- 0.11 versus 0.63 +/- 0.10, P < .0001), and central (0.53 +/- 0.10 versus 0.58 +/- 0.10, P = .049) NASC ROIs. Assessing DTI metrics in the diagnosis of MS, a sensitivity of 87.0% (95% confidence interval [CI], 66.4 to 97.1) and a specificity of 91.7% (95% CI, 73.0 to 98.7) were demonstrated. CONCLUSION: The NASC in RRMS demonstrates DTI changes. This may prove useful in detecting occult spinal cord pathology, predicting clinical course, and monitoring disease progression and therapeutic effect in MS
— id: 67533, year: 2006, vol: 27, page: 1189, stat: Journal Article,

Whole-brain N-acetylaspartate spectroscopy and diffusion tensor imaging in patients with newly diagnosed gliomas: a preliminary study
Inglese, M; Brown, S; Johnson, G; Law, M; Knopp, E; Gonen, O
2006 Nov-Dec;27(10):2137-2140, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Glial cancer cells can be found well beyond the MR imaging T2 signal-intensity hyperintensity. To quantify the extent of the diffuse microstructural tissue damage possibly due to the presence of these satellite tumor cells, we investigated the relationships between global metabolic and microstructural abnormalities in the normal-appearing brain regions of patients with newly diagnosed glioma. MATERIAL AND METHODS: Ten patients (6 men, 4 women) with radiologically suspected untreated supratentorial glial tumors and 9 healthy controls (5 men, 4 women) were studied with T1- and T2-weighted MR imaging, diffusion-weighted echo-planar MR imaging, and whole-brain N-acetylaspartate (WBNAA) proton MR spectroscopy. The relationship between the WBNAA concentration, the mean diffusivity (MD), and fractional anisotropy (FA) values in a large contralateral normal-appearing white matter (NAWM) brain region was investigated with the Spearman rank correlation test. RESULTS: WBNAA values were significantly lower (P < .001) in patients (9.7 +/- 1.7 mmol/L) than controls (13.1 +/- 1.1 mmol/L). MD values were higher (P = .0001) in patients (0.95 +/- 0.07 mm(2)s(-1)) than in controls (0.61 +/- 0.04 mm(2)s(-1)). FA values did not differ between patients (0.42 +/- 0.08) and controls (0.43 +/- 0.041). A strong inverse correlation between WBNAA and MD (r = -0.88, P = .0008) was found in the patients but not in controls (r = 0.012, P = .975). CONCLUSION: The correlation between the WBNAA and MD in the contralateral NAWM suggests that the microstructural damage possibly related to the presence of infiltrative tumor cells contributes to WBNAA decline in these patients
— id: 71205, year: 2006, vol: 27, page: 2137, stat: Journal Article,

Magnetic field correlation imaging
Jensen, Jens H; Chandra, Ramesh; Ramani, Anita; Lu, Hanzhang; Johnson, Glyn; Lee, Sang-Pil; Kaczynski, Kyle; Helpern, Joseph A
2006 Jun;55(6):1350-1361, Magnetic resonance in medicine
A magnetic resonance imaging (MRI) method is presented for estimating the magnetic field correlation (MFC) associated with magnetic field inhomogeneities (MFIs) within biological tissues. The method utilizes asymmetric spin echoes and is based on a detailed theory for the effect of MFIs on nuclear magnetic resonance (NMR) signal decay. The validity of the method is supported with results from phantom experiments at 1.5 and 3 T, and human brain images obtained at 3 T are shown to demonstrate the method's feasibility. The preliminary results suggest that MFC imaging may be useful for the quantitative assessment of iron within the brain
— id: 67099, year: 2006, vol: 55, page: 1350, stat: Journal Article,

Predicting time to progression/survival in gliomas with cerebral blood volume measurements using dynamic susceptibility contrast perfusion MR imaging
Law, M; Babb, J; Peccerelli, N; Young, R; Chheang, S; Gruber, M; Golfinos, J; Miller, D; Zagzag, D; Johnson, G
2006 OCT ;8(4):494-495, Neuro-oncology
— id: 70330, year: 2006, vol: 8, page: 494, stat: Journal Article,

Comparing perfusion metrics obtained from a single compartment versus pharmacokinetic modeling methods using dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade
Law, M; Young, R; Babb, J; Rad, M; Sasaki, T; Zagzag, D; Johnson, G
2006 Oct;27(9):1975-1982, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Numerous different parameters measured by perfusion MR imaging can be used for characterizing gliomas. Parameters derived from 3 different analyses were correlated with histopathologically confirmed grade in gliomas to determine which parameters best predict tumor grade. METHODS: Seventy-four patients with gliomas underwent dynamic susceptibility contrast-enhanced MR imaging (DSC MR imaging). Data were analyzed by 3 different algorithms. Analysis 1 estimated relative cerebral blood volume (rCBV) by using a single compartment model. Analysis 2 estimated fractional plasma volume (V(p)) and vascular transfer constant (K(trans)) by using a 2-compartment pharmacokinetic model. Analysis 3 estimated absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) by using a single compartment model and an automated arterial input function. The Mann-Whitney U test was used make pairwise comparisons. Binary logistic regression was used to assess whether rCBV, V(p), K(trans), CBV, CBF, and MTT can discriminate high- from low-grade tumors. RESULTS: rCBV was the best discriminator of tumor grade ype, followed by CBF, CBV, and K(trans). Spearman rank correlation factors were the following: rCBV = 0.812 (P < .0001), CBF = 0.677 (P < .0001), CBV = 0.604 (P < .0001), K(trans) = 0.457 (P < .0001), V(p) = 0.301 (P =.009), and MTT = 0.089 (P = .448). rCBV was the best single predictor, and K(trans) with rCBV was the best set of predictors of high-grade glioma. CONCLUSION: rCBV, CBF, CBV K(trans), and V(p) measurements correlated well with histopathologic grade. rCBV was the best predictor of glioma grade, and the combination of rCBV with K(trans) was the best set of metrics to predict glioma grade
— id: 70023, year: 2006, vol: 27, page: 1975, stat: Journal Article,

Low-Grade Gliomas: Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging--Prediction of Patient Clinical Response
Law, Meng; Oh, Sarah; Babb, James S; Wang, Edwin; Inglese, Matilde; Zagzag, David; Knopp, Edmond A; Johnson, Glyn
2006 Feb;238(2):658-667, Radiology
Purpose: To determine retrospectively whether relative cerebral blood volume (CBV) measurements can be used to predict clinical response in patients with low-grade gliomas. Materials and Methods: Approval for this retrospective HIPAA-compliant study was obtained from the Institutional Board of Research Associates, with waiver of informed consent. Thirty-five patients (23 male and 12 female patients; median age, 39 years; range, 4-80 years) with histologically diagnosed low-grade gliomas (21 low-grade astrocytomas and 14 low-grade oligodendrogliomas and low-grade mixed oligoastrocytomas) were examined with dynamic susceptibility-weighted contrast material-enhanced perfusion magnetic resonance (MR) imaging. Wilcoxon tests were used to compare patients in different response categories (complete response, stable, progressive, death) with respect to baseline relative CBV. Kaplan-Meier survival curves, log-rank tests, and Weibull survival models were used to characterize and evaluate the association of baseline relative CBV with time to progression. Tumor volumes and relative CBV measurements were obtained at initial examination and follow-up. Results: Lesions with relative CBV less than 1.75 had a median time to progression of 4620 days +/- 433 (standard deviation), and lesions with relative CBV more than 1.75 had a median time to progression of 245 days +/- 62. Patients who had an adverse event (either death or progression) had significantly higher (P = .003) relative CBV than did patients without adverse events (either complete response or stable disease). Lesions with low baseline relative CBV had stable tumor volumes at follow-up over time, whereas those with high baseline relative CBV (>1.75) had progressively increasing tumor volumes over time. Conclusion: Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can help to identify low-grade gliomas that will progress rapidly and a subset of low-grade gliomas that have a propensity for malignant transformation. (c) RSNA, 2006
— id: 61304, year: 2006, vol: 238, page: 658, stat: Journal Article,

Perfusion magnetic resonance imaging predicts patient outcome as an adjunct to histopathology: a second reference standard in the surgical and nonsurgical treatment of low-grade gliomas
Law, Meng; Oh, Sarah; Johnson, Glyn; Babb, James S; Zagzag, David; Golfinos, John; Kelly, Patrick J
2006 Jun;58(6):1099-1107, Neurosurgery
OBJECTIVE: To determine whether relative cerebral blood volume (rCBV) can predict patient outcome, specifically tumor progression, in low-grade gliomas (LGGs) and thus provide a second reference standard in the surgical and postsurgical management of LGGs. METHODS: Thirty-five patients with histologically diagnosed LGGs (21 low-grade astrocytomas and 14 low-grade oligodendrogliomas and low-grade mixed oligoastrocytomas) were studied with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging. Wilcoxon tests were used to compare patients in different response categories (complete response, stable, progressive, death) with respect to baseline rCBV. Log-rank tests were used to evaluate the association of rCBV with survival and time to progression. Kaplan-Meier time-to-progression curves were generated. Tumor volumes and CBV measurements were obtained at the initial examination and again at follow-up to determine the association of rCBV with tumor volume progression. RESULTS: Wilcoxon tests showed patients manifesting an adverse event (either death or progression) had significantly higher rCBV (P = 0.003) than did patients without adverse events (complete response or stable disease). Log-rank tests showed that rCBV exhibited a significant negative association with disease-free survival (P = 0.0015), such that low rCBV values were associated with longer time to progression. Kaplan-Meier curves demonstrated that lesions with rCBV less than 1.75 (n = 16) had a median time to progression of 4620 +/- 433 days, and lesions with rCBV more than 1.75 (n = 19) had a median time to progression of 245 +/- 62 days (P < 0.005). Lesions with low baseline rCBV (< 1.75) demonstrated stable tumor volumes when followed up over time, and lesions with high baseline rCBV (> 1.75) demonstrated progressively increasing tumor volumes over time. CONCLUSION: Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging may be used to identify LGGs that are either high-grade gliomas, misdiagnosed because of sampling error at pathological examination or that have undergone angiogenesis in the progression toward malignant transformation. This suggests that rCBV measurements may be used as a second reference standard to determine the surgical management/risk-benefit equation and postsurgical adjuvant therapy for LGGs
— id: 65798, year: 2006, vol: 58, page: 1099, stat: Journal Article,

Advantages of parallel imaging in conjunction with hyperpolarized helium--a new approach to MRI of the lung
Lee, Ray F; Johnson, Glyn; Grossman, Robert I; Stoeckel, Bernd; Trampel, Robert; McGuinness, Georgeann
2006 May;55(5):1132-1141, Magnetic resonance in medicine
Hyperpolarized helium (3He) gas MRI has the potential to assess pulmonary function. The non-equilibrium state of hyperpolarized 3He results in the continual depletion of the signal level over the course of excitations. Under non-equilibrium conditions the relationship between the signal-to-noise ratio (SNR) and the number of excitations significantly deviates from that established in the equilibrium state. In many circumstances the SNR increases or remains the same when the number of data acquisitions decreases. This provides a unique opportunity for performing parallel MRI in such a way that both the temporal and spatial resolution will increase without the conventional decrease in the SNR. In this study an analytical relationship between the SNR and the number of excitations for any flip angle was developed. Second, the point-spread function (PSF) was utilized to quantitatively demonstrate the unconventional SNR behavior for parallel imaging in hyperpolarized gas MRI. Third, a 24-channel (24ch) receive and two-channel (2ch) transmit phased-array system was developed to experimentally prove the theoretical predictions with 3He MRI. The in vivo experimental results prove that significant temporal resolution can be gained without the usual SNR loss in an equilibrium system, and that the entire lung can be scanned within one breath-hold (approximately 13 s) by applying parallel imaging to 3D data acquisition
— id: 68279, year: 2006, vol: 55, page: 1132, stat: Journal Article,

Diffusional kurtosis imaging in the lung using hyperpolarized 3He
Trampel, Robert; Jensen, Jens H; Lee, Ray F; Kamenetskiy, Igor; McGuinness, Georgeann; Johnson, Glyn
2006 Oct;56(4):733-737, Magnetic resonance in medicine
Diseases of the small airspaces represent an increasingly important health problem. Asthma is primarily a disease of airway dysfunction, while chronic obstructive pulmonary disease (COPD) is associated with abnormalities in both the small airways and the alveoli. Conventional diffusion magnetic resonance imaging (MRI) of hyperpolarized noble gases, because of the short T(2)* of the gas, is only capable of monitoring diffusion over short times and hence only short distances. Diffusion imaging is therefore only sensitive to changes in small structures of the lung (primarily the alveoli), and will not adequately interrogate diffusion along the longitudinal axes of bronchi and bronchioles. In this communication we present a new method, termed diffusional kurtosis imaging (DKI), that is particularly sensitive to diffusion over longer distances. DKI may therefore be more sensitive to abnormalities in the bronchioles and bronchi than conventional diffusion imaging. Preliminary DKI measurements on healthy human subjects and one patient with symptoms suggestive of small airway disease are presented. Although the apparent diffusion coefficient (ADC) in the patient was similar to that in the normal controls, diffusional kurtosis was markedly reduced. This suggests that DKI measurements may be useful for assessing diseases of the small airways. Magn Reson Med, 2006. (c) 2006 Wiley-Liss, Inc
— id: 68278, year: 2006, vol: 56, page: 733, stat: Journal Article,

Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis lesions: characterizing hemodynamic impairment and inflammatory activity
Ge, Yulin; Law, Meng; Johnson, Glyn; Herbert, Joseph; Babb, James S; Mannon, Lois J; Grossman, Robert I
2005 Jun-Jul;26(6):1539-1547, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Perfusion measurement in multiple sclerosis (MS) may cast light on the disease pathogenesis and lesion development since vascular pathology is frequently demonstrated in the disease. This study was performed to investigate the perfusion characteristics in MS lesions using dynamic susceptibility contrast MR imaging (DSC-MRI) to better understand the hemodynamic changes in MS. METHODS: Seventeen patients with relapsing-remitting MS were studied with DSC-MRI. Perfusion measurements included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), were obtained in enhancing, non-enhancing lesions covered by DSC-MRI and contralateral normal appearing white matter (NAWM) in patients as well as normal white matter in seventeen control subjects. RESULTS: DSC-MRI data demonstrated reduced perfusion with significantly prolonged MTT (P < 0.001) in lesions and NAWM in patients compared with normal white matter in controls. Compared to contralateral NAWM, enhancing lesions demonstrate increased CBF (P = 0.007) and CBV (P < 0.0001), indicating inflammation-mediated vasodilatation. A K means cluster analysis was performed and identifies approximately 63.8% of non-enhancing lesions (Class 1) with significantly decreased perfusion (P < or = 0.0001) when compared with contralateral NAWM. In contrast, the remainder 36.2% non-enhancing lesions (Class 2) show increased CBV (P = 0.02) in a similar fashion to enhancing lesions and can be observed on quantitative color-coded maps even without blood-brain barrier breakdown. CONCLUSION: DSC-MRI measurements demonstrate potential for investigating hemodynamic abnormalities that are associated with inflammatory activity, lesion reactivity and vascular compromise in MS lesions. Non-enhancing lesions showed both low and high perfusion suggesting microvascular abnormalities with hemodynamic impairment and inflammatory reactivity that cannot be seen on conventional MRI
— id: 55965, year: 2005, vol: 26, page: 1539, stat: Journal Article,

Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study
Inglese, Matilde; Makani, Sachin; Johnson, Glyn; Cohen, Benjamin A; Silver, Jonathan A; Gonen, Oded; Grossman, Robert I
2005 Aug;103(2):298-303, Journal of neurosurgery
OBJECT: Diffuse axonal injury (DAI) is a major complication of traumatic brain injury (TBI) that leads to functional and psychological deficits. Although DAI is frequently underdiagnosed by conventional imaging modalities, it can be demonstrated using diffusion tensor imaging. The aim of this study was to assess the presence and extent of DAI in patients with mild TBI. METHODS: Forty-six patients with mild TBI and 29 healthy volunteers underwent a magnetic resonance (MR) imaging protocol including: dual-spin echo, fluid-attenuated inversion recovery, T2-weighted gradient echo, and diffusion tensor imaging sequences. In 20 of the patients, MR imaging was performed at a mean of 4.05 days after injury. In the remaining 26, MR imaging was performed at a mean of 5.7 years after injury. In each case, mean diffusivity and fractional anisotropy were measured using both whole-brain histograms and regions of interest analysis. No differences in any of the histogram-derived measures were found between patients and control volunteers. Compared with controls, a significant reduction of fractional anisotropy was observed in patients' corpus callosum, internal capsule, and centrum semiovale, and there were significant increases of mean diffusivity in the corpus callosum and internal capsule. Neither histogram-derived nor regional diffusion tensor imaging metrics differed between the two groups. CONCLUSIONS: Although mean diffusivity and fractional anisotropy abnormalities in these patients with TBI were too subtle to be detected with the whole-brain histogram analysis, they are present in brain areas that are frequent sites of DAI. Because diffusion tensor imaging changes are present at both early and late time points following injury, they may represent an early indicator and a prognostic measure of subsequent brain damage.
— id: 58178, year: 2005, vol: 103, page: 298, stat: Journal Article,

Novel approach to the measurement of absolute cerebral blood volume using vascular-space-occupancy magnetic resonance imaging
Lu, Hanzhang; Law, Meng; Johnson, Glyn; Ge, Yulin; van Zijl, Peter C M; Helpern, Joseph A
2005 Dec;54(6):1403-1411, Magnetic resonance in medicine
Quantitative determination of cerebral blood volume (CBV) is important for understanding brain physiology and pathophysiology. In this work, a novel approach is presented for accurate measurement of absolute CBV (aCBV) using vascular-space-occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T(1) shortening property of Gd-DTPA. Two VASO images with identical imaging parameters are acquired before and after contrast agent injection, resulting in a subtracted image that reflects the amount of blood present in the brain, i.e., CBV. With an additional normalizing factor, aCBV in units of milliliters of blood per 100 mL of brain can be estimated. Experimental results at 1.5 and 3 T systems showed that aCBV maps with high spatial resolution can be obtained with high reproducibility. The averaged aCBV values in gray and white matter were 5.5 +/- 0.2 and 1.4 +/- 0.1 mL of blood/100 mL of brain, respectively. Compared to dynamic susceptibility contrast techniques, VASO MRI is based upon a relatively straightforward theory and the calculation of CBV does not require measurement of an arterial input function. In comparison with previous pre/postcontrast difference approaches, VASO MRI provides maximal signal difference between pre- and postcontrast situation and does not require the use of whole blood for signal normalization
— id: 62393, year: 2005, vol: 54, page: 1403, stat: Journal Article,

Correlation of apparent diffusion coefficient with neuropsychological testing in temporal lobe epilepsy
Lui, Yvonne W; Nusbaum, Annette O; Barr, William B; Johnson, Glyn; Babb, James S; Orbach, Darren; Kim, Alice; Laliotis, Georgia; Devinsky, Orrin
2005 Aug;26(7):1832-1839, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Patients with nonlesional temporal lobe epilepsy have long been known to have abnormalities of memory. Recently, these patients have been shown to have increased diffusivity in the hippocampus. We hypothesized that in these patients, a negative correlation would exist between diffusivity measures of the mesial temporal lobe and performance on neuropsychological tests. METHODS: Twenty presurgical patients with temporal lobe epilepsy and 20 age- and sex-matched healthy controls underwent MR imaging of the brain. Apparent diffusion coefficient region of interest measures were taken in both hippocampi and parahippocampal gyri by 2 independent observers. Mean whole brain diffusivity was calculated. All patients completed neuropsychological testing. Electroencephalogram and pathology results were collected. Patients and controls were compared with respect to each apparent diffusion coefficient measure. In patients, apparent diffusion coefficients ipsilateral and contralateral to the seizure focus were compared. Associations were assessed between diffusivity measures and neuropsychological scores. RESULTS: Eleven patients had right-sided seizure foci and 9 had left-sided seizure foci. Patients demonstrated higher apparent diffusion coefficient values than controls over the whole brain, in the hippocampi, and in the parahippocampal gyri (P < .05). Patients demonstrated higher apparent diffusion coefficient within the ipsilateral hippocampus (1.19 +/- 0.22 x 10(-3) s/mm2) and parahippocampal gyrus (1.02 +/- 0.12 x 10(-3) s/mm2) compared with the contralateral side (1.02 +/- 0.16 x 10(-3) s/mm2 and 0.96 +/- 0.09 x 10(-3) s/mm2, respectively) (P < .05). Negative correlations were seen between hippocampal apparent diffusion coefficients and multiple memory tests (P < .05). CONCLUSION: Quantitative diffusion measurements in the hippocampus correlate with memory dysfunction in patients with temporal lobe epilepsy
— id: 57871, year: 2005, vol: 26, page: 1832, stat: Journal Article,

Preferential occult injury of corpus callosum in multiple sclerosis measured by diffusion tensor imaging
Ge, Yulin; Law, Meng; Johnson, Glyn; Herbert, Joseph; Babb, James S; Mannon, Lois J; Grossman, Robert I
2004 Jul;20(1):1-7, Journal of magnetic resonance imaging
PURPOSE: To investigate the feasibility of diffusion tensor imaging (DTI) assessment of microscopic fiber tract injury in the corpus callosum (CC) and other normal-appearing white matter (NAWM) in patients with early multiple sclerosis (MS). MATERIALS AND METHODS: DTI was performed in 12 healthy volunteers and 15 patients who have relatively short disease duration (mean = 2.7 years). Both fractional anisotropy (FA) and mean diffusivity (MD) were obtained in different regions of normal-appearing CC (NACC) and NAWM in frontal and occipital regions. RESULTS: The data showed significantly lower FA (P < 0.001) and higher MD (P < 0.04) for NACC regions, but not for frontal and occipital NAWM regions, in patients than in those in healthy volunteers after Bonferroni adjustment. The increase of MD in the entire NACC regions was correlated with the total cerebral lesion volume (r = 0.75, P = 0.001) in patients. CONCLUSION: The water diffusion changes indicate that in the early phase of disease there is a preferential occult injury of CC, which is likely due to the Wallerian degeneration from distant lesions
— id: 43221, year: 2004, vol: 20, page: 1, stat: Journal Article,

Measuring blood volume and vascular transfer constant from dynamic, T(2)*-weighted contrast-enhanced MRI
Johnson, Glyn; Wetzel, Stephan G; Cha, Soonmee; Babb, James; Tofts, Paul S
2004 Jun;51(5):961-968, Magnetic resonance in medicine
Dynamic, contrast-enhanced MRI (deMRI) is increasingly being used to evaluate cerebral microcirculation. There are two different approaches for analyzing deMRI data. Intravascular indicator dilution theory has been used to estimate blood volume (and perfusion), usually from T(2)- or T(2) (*)-weighted images of the first pass of the bolus. However, the theory assumes that the tracer (i.e., contrast agent) remains intravascular, which is often not the case when the blood-brain barrier (BBB) is damaged. Furthermore, the method provides no information on the vascular transfer constant. Pharmacokinetic modeling analyses of T(1)-weighted images after first pass do give values of the vascular transfer constant and the volume of the extravascular, extracellular space (EES), but they generally are unable to give estimates of blood volume. In this study we apply pharmacokinetic modeling to dynamic T(2) (*)-weighted imaging of the first pass of a tracer bolus. This method, which we call first-pass pharmacokinetic modeling (FPPM), gives an estimate of the blood volume, vascular transfer constant, and EES volume. The method was applied to a group of 26 patients with surgically proven tumors (10 glioblastomas multiforme (GBMs), six lymphomas, and 10 meningiomas). The measurements of the blood volume and transfer constant were consistent with the known physiology of these tumors
— id: 45978, year: 2004, vol: 51, page: 961, stat: Journal Article,

Differentiating surgical from non-surgical lesions using perfusion MR imaging and proton MR spectroscopic imaging
Law, Meng; Hamburger, Micole; Johnson, Glyn; Inglese, Matilde; Londono, Ana; Golfinos, John; Zagzag, David; Knopp, Edmond A
2004 Dec;3(6):557-565, Technology in Cancer Research & Treatment
Advanced MRI techniques, such as MR spectroscopy, diffusion and perfusion MR imaging can give important in vivo physiological and metabolic information, complementing morphologic findings from conventional MRI in the clinical setting. Combining perfusion MRI and MR spectroscopy can help in patients with brain masses in who the pre-operative differential diagnosis is unclear. This review demonstrates the use of dynamic, susceptibility weighted, contrast-enhanced MR imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI) to distinguish surgical from non-surgical lesions in the brain. There is overlap in the MRI appearance of many enhancing and ring-enhancing lesions such as gliomas, metastases, inflammatory lesions, demyelinating lesions, subacute ischemia, abscess and some AIDS related lesions. We review examples of histopathologically confirmed high-grade glioma, a middle cerebral artery territory infarct, a tumefactive demyelinating lesion and a metastasis for which conventional MR imaging (MRI) was non-specific and potentially misleading and demonstrate how DSC MRI and MRSI features were used to increase the specificity of neurodiagnosis. At several institutions, many patients routinely undergo MRI as well as MRSI and DSC MRI. Cerebral blood flow (CBF), mean transit time (MTT), and relative cerebral blood volume (rCBV) measurements are obtained from regions of maximal perfusion as determined from perfusion color overlay maps. Metabolite levels and ratios are determined for Choline (Cho), N-Acetyl Aspartate (NAA), Lactate and Lipids (LL). Metabolite levels are obtained by measuring the peak heights of each metabolite and the ratios are obtained from these measurements for Cho/Cr, Cho/NAA and NAA/Cr. Neurosurgical intervention carries substantial morbidity, mortality, financial and potential emotional cost to the patient and family. Making a pre-operative diagnosis allows the neurosurgeon to be confident in the choice of treatment plan for the patient and allays considerable patient anxiety. The utility of combining clinical findings with multi-parametric information from perfusion and spectroscopic MR imaging in differentiating surgical lesions from those which do not require surgical intervention is discussed
— id: 48876, year: 2004, vol: 3, page: 557, stat: Journal Article,

Dynamic susceptibility contrast-enhanced perfusion and conventional MR imaging findings for adult patients with cerebral primitive neuroectodermal tumors
Law, Meng; Kazmi, Khuram; Wetzel, Stephan; Wang, Edwin; Iacob, Codrin; Zagzag, David; Golfinos, John G; Johnson, Glyn
2004 Jun-Jul;25(6):997-1005, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Preoperative differentiation of primitive neuroectodermal tumors (PNETs) from other tumors is important for presurgical staging, intraoperative management, and postoperative treatment. Dynamic, susceptibility-weighted, contrast-enhanced MR imaging can provide in vivo assessment of the microvasculature in intracranial mass lesions. The purpose of this study was to determine the perfusion characteristics of adult cerebral PNETs and to compare those values with low and high grade gliomas. METHODS: Conventional MR images of 12 adult patients with pathologically proved cerebral PNETs were analyzed and provided a preoperative diagnosis. Relative cerebral blood volume (rCBV) measurements and estimates of the vascular permeability transfer constant, K(trans), derived by a pharmacokinetic modeling algorithm, were also obtained. These results were compared with rCBV and K(trans) values obtained in a group of low grade gliomas (n = 30) and a group of high grade gliomas (n = 55) by using a Student t test. RESULTS: On conventional MR images, PNETs were generally well-defined contrast-enhancing masses with solid and cystic components, little or no surrounding edema, and occasional regions of susceptibility. The rCBV of cerebral PNETs was 4.76 +/- 1.99 SD, and the K(trans) was 0.0033 +/- 0.0035. A comparative group of patients with low grade gliomas (n = 30) had significantly lower rCBV (P <.0005) and lower K(trans) (P <.05). Comparison with a group of high grade gliomas showed no statistical significance in the rCBV and K(trans) (P =.53 and.19, respectively). CONCLUSION: Dynamic, susceptibility-weighted, contrast-enhanced MR imaging shows areas of increased cerebral blood volume and vascular permeability in PNETs. These results may be helpful in the diagnosis and preoperative differentiation between PNETs and other intracranial mass lesions (such as low grade gliomas), which have decreased perfusion but may sometimes have a similar conventional MR imaging appearance
— id: 43222, year: 2004, vol: 25, page: 997, stat: Journal Article,

Conventional MR imaging with simultaneous measurements of cerebral blood volume and vascular permeability in ganglioglioma
Law, Meng; Meltzer, Daniel E; Wetzel, Stephan G; Yang, Stanley; Knopp, Edmond A; Golfinos, John; Johnson, Glyn
2004 Jun;22(5):599-606, Magnetic resonance imaging
The conventional MR imaging appearance of gangliogliomas is often variable and nonspecific. Conventional MR images, relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) measurements were reviewed in 20 patients with pathologically proven grade 1 and 2 gangliogliomas (n = 20) and compared to a group of grade 2 low-grade gliomas (n = 30). The conventional MRI findings demonstrated an average lesion size of 4.1 cm, contrast enhancement (n = 19), variable degree of edema, variable mass effect, necrosis/cystic areas (n = 8), well defined (n = 12), signal heterogeneity (n = 9), calcification (n = 4). The mean rCBV was 3.66 +/- 2.20 (mean +/- std) for grade 1 and 2 gangliogliomas. The mean rCBV in a comparative group of low-grade gliomas (n = 30), was 2.14 +/- 1.67. p Value < 0.05 compared with grade 1 and 2 ganglioglioma. The mean K(trans) was 0.0018 +/- 0.0035. The mean K(trans) in a comparative group of low-grade gliomas (n = 30), was 0.0005 +/- 0.001. p Value = 0.14 compared with grade 1 and 2 ganglioglioma. The rCBV measurements of grade 1 and 2 gangliogliomas are elevated compared with other low-grade gliomas. The K(trans), however, did not demonstrate a significant difference. Gangliogliomas demonstrate higher cerebral blood volume compared with other low-grade gliomas, but the degree of vascular permeability in gangliogliomas is similar to other low-grade gliomas. Higher cerebral blood volume measurements can help differentiate gangliogliomas from other low-grade gliomas
— id: 44804, year: 2004, vol: 22, page: 599, stat: Journal Article,

Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter
Law, Meng; Saindane, Amit M; Ge, Yulin; Babb, James S; Johnson, Glyn; Mannon, Lois J; Herbert, Joseph; Grossman, Robert I
2004 Jun;231(3):645-652, Radiology
PURPOSE: To prospectively determine hemodynamic changes in the normal-appearing white matter (NAWM) of patients with relapsing-remitting multiple sclerosis (RR-MS) by using dynamic susceptibility contrast material-enhanced perfusion magnetic resonance (MR) imaging. MATERIALS AND METHODS: Conventional MR imaging (which included acquisition of pre- and postcontrast transverse T1-weighted, fluid-attenuated inversion recovery, and T2-weighted images) and dynamic susceptibility contrast-enhanced T2*-weighted MR imaging were performed in 17 patients with RR-MS (five men and 12 women; median age, 38.4 years; age range, 27.6-56.9 years) and 17 control patients (seven men and 10 women; median age, 42.0 years; age range, 18.7-62.5 years). Absolute cerebral blood volume (CBV), absolute cerebral blood flow (CBF), and mean transit time (MTT) (referenced to an arterial input function by using an automated method) were determined in periventricular, intermediate, and subcortical regions of NAWM at the level of the lateral ventricles. Least-squares regression analysis (controlled for age and sex) was used to compare perfusion measures in each region between patients with RR-MS and control patients. Repeated-measures analysis of variance and the Tukey honestly significant difference test were used to perform pairwise comparison of brain regions in terms of each perfusion measure. RESULTS: Each region of NAWM in patients with RR-MS had significantly decreased CBF (P <.005) and prolonged MTT (P <.001) compared with the corresponding region in control patients. No significant differences in CBV were found between patients with RR-MS and control patients in any of the corresponding areas of NAWM examined. In control patients, periventricular NAWM regions had significantly higher CBF (P =.03) and CBV (P =.04) than did intermediate NAWM regions. No significant regional differences in CBF, CBV, or MTT were found in patients with RR-MS. CONCLUSION: The NAWM of patients with RR-MS shows decreased perfusion compared with that of controls
— id: 43784, year: 2004, vol: 231, page: 645, stat: Journal Article,

Comparison of cerebral blood volume and vascular permeability from dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade
Law, Meng; Yang, Stanley; Babb, James S; Knopp, Edmond A; Golfinos, John G; Zagzag, David; Johnson, Glyn
2004 May;25(5):746-755, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) permit in vivo assessment of glioma microvasculature. We assessed the associations between rCBV and K(trans) derived from dynamic, susceptibility-weighted, contrast-enhanced (DSC) MR imaging and tumor grade and between rCBV and K(trans). METHODS: Seventy-three patients with primary gliomas underwent conventional and DSC MR imaging. rCBVs were obtained from regions of maximal abnormality for each lesion on rCBV color maps. K(trans) was derived from a pharmacokinetic modeling algorithm. Histopathologic grade was compared with rCBV and K(trans) (Tukey honestly significant difference). Spearman and Pearson correlation factors were determined between rCBV, K(trans), and tumor grade. The diagnostic utility of rCBV and K(trans) in discriminating grade II or III tumors from grade I tumors was assessed by logistic regression. RESULTS: rCBV was significantly different for all three grades (P </=.0005). K(trans) was significantly different between grade I and grade II or III (P =.027) but not between other grades or combinations of grades. Spearman rank and Pearson correlations, respectively, were as follows: rCBV and grade, r = 0.817 and r = 0.771; K(trans) and grade, r = 0.234 and r = 0.277; and rCBV and K(trans), r = 0.266 and r = 0.163. Only rCBV was significantly predictive of high-grade gliomas (P <.0001). CONCLUSION: rCBV with strongly correlated with tumor grade; the correlation between K(trans) and tumor grade was weaker. rCBV and K(trans) were positively but weakly correlated, suggesting that these parameters demonstrate different tumor characteristics. rCBV is a more significant predictor of high-grade glioma than K(trans)
— id: 43846, year: 2004, vol: 25, page: 746, stat: Journal Article,

Dynamic susceptibility contrast-enhanced MR imaging of low-grade gliomas: Clinical and MRI follow up of lesions with low and high cerebral blood volumes
Law, N; Knopp, E; Oh, S; Wang, E; Babb, J; Inglese, M; Zagzag, D; Johnson, G
2004 OCT ;6(4):367-367, Neuro-oncology
— id: 48919, year: 2004, vol: 6, page: 367, stat: Journal Article,

Diffusion-tensor MR imaging of intracranial neoplasia and associated peritumoral edema: introduction of the tumor infiltration index
Lu, Stanley; Ahn, Daniel; Johnson, Glyn; Law, Meng; Zagzag, David; Grossman, Robert I
2004 Jul;232(1):221-228, Radiology
PURPOSE: To determine whether diffusion-tensor magnetic resonance (MR) imaging metrics of peritumoral edema can be used to differentiate intra- from extraaxial lesions, metastatic lesions from gliomas, and high- from low-grade gliomas. MATERIALS AND METHODS: In this study, diffusion-tensor MR imaging was performed preoperatively in 40 patients with intracranial neoplasms, including meningiomas, metastatic lesions, glioblastomas multiforme, and low-grade gliomas. Histograms of mean diffusivity (MD) and fractional anisotropy (FA) were used to analyze both the tumor and the associated T2 signal intensity abnormality. An additional metric, the tumor infiltration index (TII), was evaluated. The TII is a measure of the change in FA presumably caused by tumor cells infiltrating the peritumoral edema. Student t test and least-squares linear regression analyses were performed. RESULTS: Peritumoral MD and FA values indicated no statistically significant difference between intra- and extraaxial lesions or between high- and low-grade gliomas. Regarding intraaxial tumors, the measured mean peritumoral MD of metastatic lesions, 0.733 x 10(-3) mm(2)/sec +/- 0.061 (SD), was significantly higher than that of gliomas, 0.587 +/- 0.093 x 10(-3) mm(2)/sec (P <.05). There was also a statistically significant difference between the TIIs of the edema surrounding meningiomas and metastases (mean, 0 +/- 35) and the TIIs of the edema surrounding gliomas (mean, 64 +/- 59) (P <.05). CONCLUSION: Peritumoral diffusion-tensor MR imaging metrics enable the differentiation of solitary intraaxial metastatic brain tumors from gliomas. In addition, the TII enables one to distinguish presumed tumor-infiltrated edema from purely vasogenic edema
— id: 43223, year: 2004, vol: 232, page: 221, stat: Journal Article,

Dynamic, contrast-enhanced perfusion MRI in mouse gliomas: Correlation with histopathology
Cha, Soonmee; Johnson, Glyn; Wadghiri, Youssef Zaim; Jin, Olivier; Babb, Jim; Zagzag, David; Turnbull, Daniel H
2003 May;49(5):848-855, Magnetic resonance in medicine
The aim of this study was to develop an MRI protocol to evaluate the growth and vascularity of implanted GL261 mouse gliomas on a 7T microimaging system. Both conventional T(1)- and T(2)-weighted imaging and dynamic, contrast-enhanced T(2)*-weighted imaging were performed on 34 mice at different stages of tumor development. MRI measurements of relative cerebral blood volume (rCBV) were compared to histological assessments of microvascular density (MVD). Enhancement on postcontrast T(1)-weighted images was compared to histological assessments of Evan's blue extravasation. Conventional T(2)-weighted and postcontrast T(1)-weighted images demonstrated tumor growth characteristics consistent with previous descriptions of GL261 glioma. Furthermore, measurements of rCBV from MRI data were in good agreement with histological measurements of MVD from the same tumors. Postcontrast enhancement on T(1)-weighted images was observed at all stages of GL261 glioma progression, even before evidence of angiogenesis, indicating that the mechanism of conventional contrast enhancement in MRI does not require neovascularization. These results provide quantitative support for MRI approaches currently used to assess human brain tumors, and form the basis for future studies of angiogenesis in genetically engineered mouse brain tumor models. Magn Reson Med 49:848-855, 2003
— id: 34729, year: 2003, vol: 49, page: 848, stat: Journal Article,

Perfusion MR and proton spectroscopic MR in the grading of cerebral gliomas
Law, M; Yang, S; Wang, H; Babb, I; Johnson, G; Cha, S; Knopp, EA; Zagzag, D
2003 DEC ;16(6):1074-1075, Rivista di Neuroradiologia
— id: 46628, year: 2003, vol: 16, page: 1074, stat: Journal Article,

Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging
Law, Meng; Yang, Stanley; Wang, Hao; Babb, James S; Johnson, Glyn; Cha, Soonmee; Knopp, Edmond A; Zagzag, David
2003 Nov-Dec;24(10):1989-1998, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of conventional MR imaging in predicting glioma grade are not high. Relative cerebral blood volume (rCBV) measurements derived from perfusion MR imaging and metabolite ratios from proton MR spectroscopy are useful in predicting glioma grade. We evaluated the sensitivity, specificity, PPV, and NPV of perfusion MR imaging and MR spectroscopy compared with conventional MR imaging in grading primary gliomas. METHODS: One hundred sixty patients with a primary cerebral glioma underwent conventional MR imaging, dynamic contrast-enhanced T2*-weighted perfusion MR imaging, and proton MR spectroscopy. Gliomas were graded as low or high based on conventional MR imaging findings. The rCBV measurements were obtained from regions of maximum perfusion. Metabolite ratios (choline [Cho]/creatine [Cr], Cho/N-acetylaspartate [NAA], and NAA/Cr) were measured at a TE of 144 ms. Tumor grade determined with the three methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic analyses were performed to determine optimum thresholds for tumor grading. Sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas were also calculated. RESULTS: Sensitivity, specificity, PPV, and NPV for determining a high-grade glioma with conventional MR imaging were 72.5%, 65.0%, 86.1%, and 44.1%, respectively. Statistical analysis demonstrated a threshold value of 1.75 for rCBV to provide sensitivity, specificity, PPV, and NPV of 95.0%, 57.5%, 87.0%, and 79.3%, respectively. Threshold values of 1.08 and 1.56 for Cho/Cr and 0.75 and 1.60 for Cho/NAA provided the minimum C2 and C1 errors, respectively, for determining a high-grade glioma. The combination of rCBV, Cho/Cr, and Cho/NAA resulted in sensitivity, specificity, PPV, and NPV of 93.3%, 60.0%, 87.5%, and 75.0%, respectively. Significant differences were noted in the rCBV and Cho/Cr, Cho/NAA, and NAA/Cr ratios between low- and high-grade gliomas (P <.0001,.0121,.001, and.0038, respectively). CONCLUSION: The rCBV measurements and metabolite ratios both individually and in combination can increase the sensitivity and PPV when compared with conventional MR imaging alone in determining glioma grade. The rCBV measurements had the most superior diagnostic performance (either with or without metabolite ratios) in predicting glioma grade. Threshold values can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome
— id: 43847, year: 2003, vol: 24, page: 1989, stat: Journal Article,

Peritumoral diffusion tensor imaging of high-grade gliomas and metastatic brain tumors
Lu, Stanley; Ahn, Daniel; Johnson, Glyn; Cha, Soonmee
2003 May;24(5):937-941, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is an advanced MR technique that describes the movement of water molecules by using two metrics, mean diffusivity (MD), and fractional anisotropy (FA), which represent the magnitude and directionality of water diffusion, respectively. We hypothesize that alterations in these values within the tissue surrounding brain tumors reflect combinations of increased water content and tumor infiltration and that these changes can be used to differentiate high-grade gliomas from metastatic lesions. METHODS: DTI was performed in 12 patients with high-grade gliomas and in 12 with metastatic lesions. DTI measurements were obtained from regions of interest (ROIs) placed on normal-appearing white matter and on the vasogenic edema, the T2 signal intensity abnormality surrounding each tumor. RESULTS: The peritumoral region of both gliomas and metastatic tumors displayed significant increases in MD (P <.005) and significant decreases in FA (P <.005) when compared with those of normal-appearing white matter. Furthermore, the peritumoral MD of metastatic lesions measured significantly greater than that of gliomas (P <.005). Peritumoral FA measurements, on the other hand, showed no such discrepancy. CONCLUSION: When compared with an internal control, diffusion metrics are clearly altered within the vasogenic edema surrounding both high-grade gliomas and metastatic tumors, reflecting increased extracellular water. Although peritumoral MD can be used to distinguish high-grade gliomas from metastatic tumors, peritumoral FA demonstrated no statistically significant difference. The FA changes surrounding gliomas, therefore, can be attributed not only to increased water content, but also to tumor infiltration
— id: 66603, year: 2003, vol: 24, page: 937, stat: Journal Article,

Imaging of the intracranial venous system with a contrast-enhanced volumetric interpolated examination
Wetzel, Stephan G; Law, Meng; Lee, Vivian S; Cha, Soonmee; Johnson, Glyn; Nelson, Kim
2003 May;13(5):1010-1018, European radiology
A contrast-enhanced interpolated, three-dimensional (3D) gradient-echo MR sequence with asymmetric k-space sampling, which we refer to as volumetric interpolated brain examination (VIBE), was evaluated for its depiction of the normal intracranial venous system and compared with two-dimensional (2D) time-of-flight (TOF) MR venography (MRV). Fifteen subjects underwent contrast-enhanced VIBE imaging (TR/TE 8 ms/4.4 ms, flip angle 18 degrees, acquisition time, 2 min 20 s, voxel size approximately 1.5 mm(3)) and standard 2D TOF MRV (TR/TE 27 ms/9 ms, flip angle 35 degrees ). The presence of 19 venous structures per subject was assessed on maximum intensity projections (MIP) of the whole data set (whole-brain MIP) and on MIP images reconstructed spontaneously from source images (interactive MIP/source images). Results from a consensus reading where all imaging techniques and display modalities were available were taken as the standard of reference for the presence of venous structures. In addition, 10 subjects underwent both unenhanced and enhanced VIBE imaging. The value of subtracted data sets (unenhanced VIBE subtracted from enhanced VIBE) was then evaluated. Overall, VIBE provided a superior visualization of the cerebral veins than 2D TOF MRV (VIBE, sensitivity (reader 1/reader 2): 98%/99%, negative predictive value 64%/71%; TOF sensitivity: 85%/84%, negative predictive value 15%/15%; Wilcoxon signed-rank test VIBE vs TOF, p<0.001 for both readers). The VIBE interactive MIP/source images were superior to whole-brain MIP reconstructions. Image subtraction was not necessary for delineation of venous structures but improved small vein conspicuity. Contrast-enhanced VIBE acquisitions are faster and enable a visualization of the normal intracranial venous system superior to that of 2D TOF MRV
— id: 43243, year: 2003, vol: 13, page: 1010, stat: Journal Article,

Utility of endothelial permeability measurements in differentiation between atypical and typical meningiomas using perfusion-weighted MRI
Yang, S; Johnson, G; Law, M; Cha, S; Zagzag, D; Knopp, EA; Litt, AW
2003 DEC ;16(6):1061-1062, Rivista di Neuroradiologia
— id: 46627, year: 2003, vol: 16, page: 1061, stat: Journal Article,

Dynamic contrast-enhanced perfusion MR imaging measurements of endothelial permeability: differentiation between atypical and typical meningiomas
Yang, Stanley; Law, Meng; Zagzag, David; Wu, Hope H; Cha, Soonmee; Golfinos, John G; Knopp, Edmond A; Johnson, Glyn
2003 Sep;24(8):1554-1559, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: The measurement of relative cerebral blood volume (rCBV) and the volume transfer constant (K(trans)) by means of dynamic contrast-enhanced (DCE) perfusion MR imaging (pMRI) can be useful in characterizing brain tumors. The purpose of our study was to evaluate the utility of these measurements in differentiating typical meningiomas and atypical meningiomas. METHODS: Fifteen patients with pathologically confirmed typical meningiomas and seven with atypical meningiomas underwent conventional imaging and DCE pMRI before resection. rCBV measurements were calculated by using standard intravascular indicator dilution algorithms. K(trans) was calculated from the same DCE pMRI data by using a new pharmacokinetic modeling (PM) algorithm. Results were compared with pathologic findings. RESULTS: Mean rCBV was 8.02 +/- 4.74 in the 15 typical meningiomas and 10.50 +/- 2.1 in the seven atypical meningiomas. K(trans) was 0.0016 seconds(-1) +/- 0.0012 in the typical group and 0.0066 seconds(-1) +/- 0.0026 in the atypical group. The difference in K(trans) was statistically significant (P <.01, Student t test). Other parameters generated with the PM algorithm (plasma volume, volume of the extravascular extracellular space, and flux rate constant) were not significantly different between the two tumor types. CONCLUSION: DCE pMRI may have a role in the prospective characterization of meningiomas. Specifically, the measurement of K(trans) is of use in distinguishing atypical meningiomas from typical meningiomas
— id: 42024, year: 2003, vol: 24, page: 1554, stat: Journal Article,

Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging
Cha, Soonmee; Knopp, Edmond A; Johnson, Glyn; Wetzel, Stephan G; Litt, Andrew W; Zagzag, David
2002 Apr;223(1):11-29, Radiology
Dynamic contrast agent-enhanced perfusion magnetic resonance (MR) imaging provides physiologic information that complements the anatomic information available with conventional MR imaging. Analysis of dynamic data from perfusion MR imaging, based on tracer kinetic theory, yields quantitative estimates of cerebral blood volume that reflect the underlying microvasculature and angiogenesis. Perfusion MR imaging is a fast and robust imaging technique that is increasingly used as a research tool to help evaluate and understand intracranial disease processes and as a clinical tool to help diagnose, manage, and understand intracranial mass lesions. With the increasing number of applications of perfusion MR imaging, it is important to understand the principles underlying the technique. In this review, the essential underlying physics and methods of dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging are described. The clinical applications of cerebral blood volume maps obtained with perfusion MR imaging in the differential diagnosis of intracranial mass lesions, as well as the pitfalls and limitations of the technique, are discussed. Emphasis is on the clinical role of perfusion MR imaging in providing insight into the underlying pathophysiology of cerebral microcirculation
— id: 32125, year: 2002, vol: 223, page: 11, stat: Journal Article,

Frontal white matter microstructure, aggression, and impulsivity in men with schizophrenia: a preliminary study
Hoptman, Matthew J; Volavka, Jan; Johnson, Glyn; Weiss, Elisabeth; Bilder, Robert M; Lim, Kelvin O
2002 Jul 1;52(1):9-14, Biological psychiatry
BACKGROUND: Aggression and impulsivity may involve altered frontal white matter. METHODS: Axial diffusion tensor images were acquired in 14 men with schizophrenia using a pulsed gradient, double spin echo, echo planar imaging method. White matter microstructural measures (fractional anisotropy and trace) were calculated from these data. Regions of interest were placed in frontal white matter on four slices. Impulsivity was measured using the Motor Impulsiveness factor of the Barratt Impulsiveness Scale. Aggressiveness was measured using the Assaultiveness scale of the Buss Durkee Hostility Inventory and the Aggression scale of the Life History of Aggression. RESULTS: Lower fractional anisotropy in right inferior frontal white matter was associated with higher motor impulsiveness. Higher trace in these regions was associated with aggressiveness. CONCLUSIONS: Inferior frontal white matter microstructure was associated with impulsivity and aggression in men with schizophrenia. These results implicate frontal lobe dysfunction in aggression and certain aspects of impulsivity
— id: 32486, year: 2002, vol: 52, page: 9, stat: Journal Article,

High-grade gliomas and solitary metastases: differentiation by using perfusion and proton spectroscopic MR imaging
Law, Meng; Cha, Soonmee; Knopp, Edmond A; Johnson, Glyn; Arnett, John; Litt, Andrew W
2002 Mar;222(3):715-721, Radiology
PURPOSE: To determine whether perfusion-weighted and proton spectroscopic MR imaging can be used to differentiate high-grade primary gliomas and solitary metastases on the basis of differences in vascularity and metabolite levels in the peritumoral region. MATERIALS AND METHODS: Fifty-one patients with a solitary brain tumor (33 gliomas, 18 metastases) underwent conventional, contrast material--enhanced perfusion-weighted, and proton spectroscopic MR imaging before surgical resection or stereotactic biopsy. Of the 33 patients with gliomas, 22 underwent perfusion-weighted MR imaging; nine, spectroscopic MR imaging; and two underwent both. Of the 18 patients with metastases, 12 underwent perfusion-weighted MR imaging, and six, spectroscopic MR imaging. The peritumoral region was defined as the area in the white matter immediately adjacent to the enhancing (hyperintense on T2-weighted images, but not enhancing on postcontrast T1-weighted images) portion of the tumor. Relative cerebral blood volumes in these regions were calculated from perfusion-weighted MR data. Spectra from the enhancing tumor, the peritumoral region, and normal brain were obtained from the two-dimensional spectroscopic MR acquisition. The Student t test was used to determine if there was a statistically significant difference in relative cerebral blood volume and metabolic ratios between high-grade gliomas and metastases. RESULTS: The measured relative cerebral blood volumes in the peritumoral region in high-grade gliomas and metastases were 1.31 +/- 0.97 (mean +/- SD) and 0.39 +/- 0.19, respectively. The difference was statistically significant (P <.001). Spectroscopic imaging demonstrated elevated choline levels (choline-to-creatine ratio was 2.28 +/- 1.24) in the peritumoral region of gliomas but not in metastases (choline-to-creatine ratio was 0.76 +/- 0.23). The difference was statistically significant (P =.001). CONCLUSION: Although conventional MR imaging characteristics of solitary metastases and primary high-grade gliomas may sometimes be similar, perfusion-weighted and spectroscopic MR imaging enable distinction between the two
— id: 66604, year: 2002, vol: 222, page: 715, stat: Journal Article,

Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study
Wetzel, Stephan G; Cha, Soonmee; Johnson, Glyn; Lee, Peter; Law, Meng; Kasow, David L; Pierce, Sean D; Xue, Xiaonan
2002 Sep;224(3):797-803, Radiology
PURPOSE: To assess inter- and intraobserver reproducibility for different techniques of measuring relative cerebral blood volume (rCBV) in patients with intracranial mass lesions. MATERIALS AND METHODS: Three independent observers (neuroradiology fellows) who were blinded to the histopathologic diagnosis performed rCBV measurements in 50 patients with various intracranial mass lesions. Three different methods were compared. With method 1, placement of a single region of interest was guided by a color overlay map. With methods 2 and 3, the highest rCBV value and the mean of repeated rCBV measurements, respectively, were recorded. Calculations of the intraclass correlation coefficient, coefficient of variation (CV), and descriptive statistics were used to determine the levels of reproducibility. A multiple linear regression model was used to evaluate for possible explanatory factors for interobserver variance. RESULTS: Method 2 had, overall, the best reproducibility of all techniques, with an intraclass interobserver correlation coefficient of 0.71 (indicating good agreement), interobserver CV of 30%, and intraobserver CV in the range of 32%-41%. Measurement variations between observers correlated significantly (P <.001) with increasing rCBV values. CONCLUSION: In this study, interobserver and intraobserver reproducibility of rCBV measurements were clinically acceptable
— id: 39600, year: 2002, vol: 224, page: 797, stat: Journal Article,

Preoperative assessment of intracranial tumors with perfusion MR and a volumetric interpolated examination: a comparative study with DSA
Wetzel, Stephan G; Cha, Soonmee; Law, Meng; Johnson, Glyn; Golfinos, John; Lee, Peter; Nelson, Peter Kim
2002 Nov-Dec;23(10):1767-1774, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: In evaluating intracranial tumors, a safe low-cost alternative that provides information similar to that of digital subtraction angiography (DSA) may be of interest. Our purpose was to determine the utility and limitations of a combined MR protocol in assessing (neo-) vascularity in intracranial tumors and their relation to adjacent vessels and to compare the results with those of DSA. METHODS: Twenty-two consecutive patients with an intracranial tumor who underwent preoperative stereoscopic DSA were examined with contrast-enhanced dynamic T2*-weighted perfusion MR imaging followed by a T1-weighted three-dimensional (3D) MR study (volumetric interpolated brain examination [VIBE]). The maximum relative cerebral blood volume (rCBV) of the tumor was compared with tumor vascularity at DSA. Critical vessel structures were defined in each patient, and VIBE images of these structures were compared with DSA findings. For full exploitation of the 3D data sets, maximum-intensity projection algorithms reconstructed in real time with any desired volume and orientation were used. RESULTS: Tumor blush scores at DSA were significantly correlated with the rCBV measurements (r = 0.75; P <.01, Spearman rank correlation coefficient). In 17 (77%) patients, VIBE provided all relevant information about the venous system, whereas information about critical arteries were partial in 50% of the cases and not relevant in the other 50%. CONCLUSION: A fast imaging protocol consisting of perfusion MR imaging and a volumetric MR acquisition provides some of the information about tumor (neo-) vascularity and adjacent vascular anatomy that can be obtained with conventional angiography. However, the MR protocol provides insufficient visualization of distal cerebral arteries
— id: 43233, year: 2002, vol: 23, page: 1767, stat: Journal Article,

Three-dimensional, T1-weighted gradient-echo imaging of the brain with a volumetric interpolated examination
Wetzel, Stephan G; Johnson, Glyn; Tan, Andrew G S; Cha, Soonmee; Knopp, Edmond A; Lee, Vivian S; Thomasson, David; Rofsky, Neil M
2002 Jun-Jul;23(6):995-1002, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: T1-weighted, 3D gradient-echo MR sequences can be optimized for rapid acquisition and improved resolution through asymmetric k-space sampling and interpolation. We compared a volumetric interpolated brain examination (VIBE) sequence with a magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence and a 2D T1-weighted spin-echo (SE) sequence. METHODS: Thirty consecutive patients known or suspected to have focal brain lesions underwent postcontrast studies (20 mL of gadopentetate dimeglumine) with VIBE, MP RAGE, and 2D T1-weighted SE imaging. Source and 5-mm VIBE and MP RAGE reformations, and 5-mm T1-weighted SE images were compared qualitatively and by using signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). SNRs in a gadolinium-doped water phantom were also measured for all three sequences. RESULTS: On the source images, SNRs for gray matter (GM) and white matter (WM), and CNRs for WM-to-GM and contrast-enhancing lesion-to-GM were slightly, but significantly higher for the VIBE sequence than for the MP RAGE sequence (P <.05). On 5-mm reformations, WM-to-GM CNR was significantly higher on VIBE and MP RAGE images than on T1-weighted SE images (P <.001), but contrast-enhancing lesion-to-GM CNRs were higher on SE images compared with both gradient-echo sequences (P <.001). Qualitatively, VIBE images showed fewer flow artifacts than did SE and MP RAGE images (P <.05). In the phantom, VIBE SNR was higher than MP RAGE SNR for short T1 relaxation times. CONCLUSION: VIBE provides an effective, alternative approach to MP RAGE for fast 3D T1-weighted imaging of the brain
— id: 32127, year: 2002, vol: 23, page: 995, stat: Journal Article,

Dynamic contrast-enhanced t2*-weighted mr imaging of tumefactive demyelinating lesions
Cha S; Pierce S; Knopp EA; Johnson G; Yang C; Ton A; Litt AW; Zagzag D
2001 Jun;22(6):1109-1116, AJNR. American journal of neuroradiology
PURPOSE: Dynamic contrast-enhanced T2*-weighted MR imaging has been helpful in characterizing intracranial mass lesions by providing information on vascularity. Tumefactive demyelinating lesions (TDLs) can mimic intracranial neoplasms on conventional MR images, can be difficult to diagnose, and often result in surgical biopsy for suspected tumor. The purpose of this study was to determine whether dynamic contrast-enhanced T2*-weighted MR imaging can be used to distinguish between TDLs and intracranial neoplasms that share common features on conventional MR images. METHODS: We retrospectively reviewed the conventional and dynamic contrast-enhanced T2*-weighted MR images and medical records of 10 patients with tumefactive demyelinating disease that was diagnosed by either biopsy or strong clinical suspicion supported by laboratory evaluation that included CSF analysis and evoked potential tests. Twelve TDLs in 10 patients and 11 brain tumors that appeared similar on conventional MR images were studied. Relative cerebral blood volume (rCBV) was calculated from dynamic MR data and was expressed as a ratio to contralateral normal white matter. rCBV values from 11 patients with intracranial neoplasms with very similar conventional MR imaging features were used for comparison. RESULTS: The rCBV values of TDLs ranged from 0.22 to 1.79 (n = 12), with a mean of 0.88 +/- 0.46 (SD). The rCBV values of intracranial neoplasms ranged from 1.55 to 19.20 (n = 11), with a mean of 6.47 +/- 6.52. The difference in rCBV values between the two groups was statistically significant (P =.009). The difference in rCBV values between TDLs and primary cerebral lymphomas (n = 4) was less pronounced but was statistically significant (P =.005). CONCLUSION: Dynamic contrast-enhanced T2*-weighted MR imaging is a useful diagnostic tool in differentiating TDLs from intracranial neoplasms and may therefore obviate unnecessary surgical biopsy
— id: 21176, year: 2001, vol: 22, page: 1109, stat: Journal Article,

MR renography with low-dose gadopentetate dimeglumine: feasibility
Lee VS; Rusinek H; Johnson G; Rofsky NM; Krinsky GA; Weinreb JC
2001 Nov;221(2):371-379, Radiology
PURPOSE: To develop a low-dose magnetic resonance (MR) renographic method performed with and without an angiotensin converting enzyme (ACE) inhibitor and in conjunction with gadolinium-enhanced MR angiography in patients with suspected renovascular disease. MATERIALS AND METHODS: Thirty-two patients underwent MR renography (turbo fast low-angle shot sequence: repetition time, 5 msec; echo time, 2.3 msec; flip angle, 15 degrees; one coronal image acquired every 2 seconds for 4 minutes) following intravenous injection of 2 mL of gadopentetate dimeglumine, which was repeated following intravenous injection of an ACE inhibitor. Contrast material-enhanced MR angiography was also performed. On the basis of renographic findings, renal cortex and renal medulla enhancement curves and normalized enhancement ratios were analyzed. RESULTS: The cortex and medulla showed an early transient period of enhancement within 20 seconds (vascular phase). During 1-2 minutes, a second, gradual increase in medullary enhancement, reflecting transit of filtered contrast material, was observed that was significantly greater in patients with a serum creatinine level less than 2 mg/dL (177 micromol/L) than in those with a level of 2 mg/dL or greater (P < .01). After injection of the ACE inhibitor, patients with elevated creatinine levels showed low renal medullary enhancement regardless of the presence of renal artery stenosis (RAS). However, in patients with creatinine less than 2 mg/dL, medullary enhancement ratios after injection of the ACE inhibitor were consistently lower in patients with RAS of 50% or greater than in those without stenosis (P = .02 to .08). CONCLUSION: Low-dose MR renography can be performed in the clinical setting before and after injection of an ACE inhibitor, and its potential use for evaluating decreased renal function as a consequence of RAS is promising
— id: 26587, year: 2001, vol: 221, page: 371, stat: Journal Article,

White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study
Pomara N; Crandall DT; Choi SJ; Johnson G; Lim KO
2001 Feb 28;106(1):15-24, Psychiatry research
Diffuse white matter pallor is the most frequent neuropathological feature of HIV-1 infection and has been found to be particularly prominent in the advanced stages of the disease. The purpose of this study was to determine whether subtle white matter abnormalities can be detected in medically stable, ambulatory HIV-1 patients, in vivo, using diffusion tensor imaging (DTI). DTI is a magnetic resonance imaging (MRI) technique that is uniquely suited for the study of subtle white matter abnormalities. DTI was performed in six HIV-1 patients and nine controls. The two groups were similar in age. Abnormal fractional anisotropy was found in the white matter of the frontal lobes and internal capsules of the HIV-1 patients, in the absence of group differences in mean diffusivity, computed proton density, and computed T2. DTI may be more sensitive than conventional MRI methods for detecting subtle white matter disruptions in HIV-1 disease
— id: 23681, year: 2001, vol: 106, page: 15, stat: Journal Article,

Optimal dose of Gd-DTPA in dynamic MR studies
Rusinek H; Lee VS; Johnson G
2001 Aug;46(2):312-316, Magnetic resonance in medicine
The relationship between the administered dose d of Gd-DTPA and the accuracy of measurements of the glomerular filtration rate G and the cardiac output O was investigated. For a wide range of values the concentration of Gd-DTPA can be uniquely derived from MR signals and precontrast longitudinal relaxation time. Fixed and random errors in these measured variables were analyzed. Depending on noise level and the level of renal function, errors in G reach a minimum for d = 1.4-2.8 mmol. Random errors in G are relatively insensitive to d as long as d > 1.5 mmol. These results establish the feasibility of dynamic MR measurements using doses of Gd-DTPA that are several times lower than current standards
— id: 26716, year: 2001, vol: 46, page: 312, stat: Journal Article,

Sensitivity and performance time in MRI dephasing artifact reduction methods
Wadghiri YZ; Johnson G; Turnbull DH
2001 Mar;45(3):470-476, Magnetic resonance in medicine
Although shimming can improve static field inhomogeneity, local field imperfections induced by tissue susceptibility differences cannot be completely corrected and can cause substantial signal loss in gradient echo images through intravoxel dephasing. Dephasing increases with voxel size so that one simple method of reducing the effect is to use thin slices. Signal-to-noise ratio (SNR) can then be increased by averaging over the subslices to form the final, thick slice. We call this method subslice averaging or SSAVE. Alternatively, a range of different amplitude slice select rephase gradients can be used to compensate for different susceptibility induced gradient offsets. The final image can then be formed by combining individual images in a variety of ways: summation, summation of the squares of the images, forming the maximum intensity projection of the image set, and Fourier transformation followed by summation. We show here that, contrary to previous claims, the theoretical sensitivity (i.e., SNR divided by the square root of the imaging time) of all these alternative methods is very similar. However, performance time (i.e., minimum-imaging time) of the simplest method, SSAVE, is much shorter than that of alternatives. This is confirmed experimentally on phantoms and anesthetized mice. Magn Reson Med 45:470-476, 2001.
— id: 21239, year: 2001, vol: 45, page: 470, stat: Journal Article,

Real-time interactive duplex MR measurements: application in neurovascular imaging
Wetzel SG; Lee VS; Tan AG; Heid O; Cha S; Johnson G; Rofsky NM
2001 Sep;177(3):703-707, American journal of roentgenology
OBJECTIVE: Real-time interactive duplex MR imaging is a new phase-contrast MR imaging technique that enables the quantification and display of flow velocities in real time without the need for cardiac gating. We investigated the feasibility and reliability of the technique to assess hemodynamic information both in vitro and in vivo in the carotid arteries and in the venous sinuses. SUBJECTS AND METHODS: Real-time interactive duplex MR measurements (TR/TE, 53/27; flip angle, 90 degrees; encoding velocity, 100 or 150 cm/sec) were performed in vitro with a steady-flow phantom and in 10 healthy volunteers in whom common and internal carotid artery velocities were measured. In eight volunteers, velocity measurements were also performed in the superior sagittal sinus during both normal breathing and hyperventilation. Time-velocity plots were analyzed qualitatively and quantitatively and compared with findings from conventional segmented k-space phase-contrast MR imaging and Doppler sonography. RESULTS: Velocity determinations for real-time duplex MR and conventional phase-contrast MR imaging showed an in vitro correlation of 0.99 and an in vivo correlation of 0.83 (carotid arteries) and 0.76 (venous sinus). Velocity measurements in the carotid arteries with real-time MR imaging were significantly lower than those obtained with conventional phase-contrast MR (averaged, 7.8%; p = 0.003) or sonography (23.7%, p < 0.001), likely because of volume averaging. Small but significant velocity changes occurring in the venous sinus during hyperventilation were reliably identified with both MR techniques. CONCLUSION: Real-time interactive duplex MR imaging can be effectively applied in neurovascular imaging to obtain hemodynamic information
— id: 26698, year: 2001, vol: 177, page: 703, stat: Journal Article,

Dynamic contrast-enhanced T2-weighted MR imaging of recurrent malignant gliomas treated with thalidomide and carboplatin
Cha S; Knopp EA; Johnson G; Litt A; Glass J; Gruber ML; Lu S; Zagzag D
2000 May;21(5):881-890, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Dynamic, contrast-enhanced MR imaging has allowed quantitative assessment of cerebral blood volume (CBV) in brain tumors. The purpose of our study was to compare postcontrast T1-weighted imaging with dynamic, contrast-enhanced T2*-weighted echo-planar imaging in the evaluation of the response of recurrent malignant gliomas to thalidomide and carboplatin. METHODS: Serial MR imaging was performed in 18 consecutive patients with recurrent malignant gliomas receiving both thalidomide and carboplatin for 12-month periods. Six patients undergoing carboplatin therapy alone were chosen as control subjects. Conventional postcontrast T1-weighted images were compared with relative CBV (rCBV) maps calculated on a pixel-by-pixel basis from dynamic echo-planar imaging data. Tumor progression was evaluated clinically using established criteria for malignant gliomas. Studies were performed at 2- to 3-month intervals, and imaging and clinical findings were compared. RESULTS: Tumor response to treatment, based on clinical findings, did not correlate well with conventional imaging findings. The rCBV values decreased significantly in all patients between the start of therapy and the first follow-up in the study group, but not in the control group. The difference in rCBV values between the clinically stable and the progressive group at 12-month follow-up was statistically significant, with the progressive group having higher values. CONCLUSION: Dynamic, contrast-enhanced MR imaging is a valuable adjunct to conventional imaging in assessing tumor activity during antiangiogenic therapy, and correlates better than conventional studies with clinical status and response to therapy
— id: 9344, year: 2000, vol: 21, page: 881, stat: Journal Article,

Dynamic susceptibility contrast MR imaging: correlation of signal intensity changes with cerebral blood volume measurements
Cha S; Lu S; Johnson G; Knopp EA
2000 Feb;11(2):114-119, Journal of magnetic resonance imaging
Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging provide valuable information regarding intracranial micro-hemodynamics and have been helpful in characterizing primary brain tumors and guiding stereotactic biopsy. Another parameter, the maximum signal drop (MSD) during the first pass of intravascular contrast bolus due to T2* effect, can also be measured directly without extensive post-processing and data manipulation. The purpose of our study is to determine whether MSD maps provide information similar to CBV maps in patients presenting with intracranial mass lesions. Twenty-nine patients with various intracranial mass lesions were studied with DSC MR imaging prior to stereotactic biopsy or volumetric resection. Maps of both CBV and MSD are calculated on a pixel-by-pixel basis and displayed as color overlays over the raw images. Relative CBV (rCBV) and MSD (rMSD) values were measured in regions of interest (ROIs) within areas of abnormality and compared. In addition, computer-generated noise was added to the data to estimate the sensitivity of each measurement to noise. The rMSD values were strongly correlated with rCBV values (r = 0.87, P = 0.0001). CBV values were much more sensitive to added noise than MSD values (P < 0.01). MSD maps derived from DSC MR imaging provide information similar to CBV maps in patients with intracranial mass lesions. MSD maps are a simple and reliable indicator of vascularity that can easily be incorporated into routine MR imaging
— id: 11804, year: 2000, vol: 11, page: 114, stat: Journal Article,

Angiotensin-converting enzyme inhibitor-enhanced phase-contrast MR imaging to measure renal artery velocity waveforms in patients with suspected renovascular hypertension
Lee VS; Rofsky NM; Ton AT; Johnson G; Krinsky GA; Weinreb JC
2000 Feb;174(2):499-508, American journal of roentgenology
OBJECTIVE: We investigated the usefulness of phase-contrast MR imaging to measure renal artery velocity waveforms as an adjunct to renal MR angiography. We also examined whether an angiotensin-converting enzyme (ACE) inhibitor improves the diagnostic accuracy of waveform analysis. SUBJECTS AND METHODS: Thirty-five patients referred for MR angiography of renal arteries underwent non-breath-hold oblique sagittal velocity-encoded phase-contrast MR imaging through both renal hila (TR/TE, 24/5; flip angle, 30 degrees; signal averages, two; encoding velocity, 75 cm/sec) before and after i.v. administration of an ACE inhibitor (enalaprilat). We analyzed velocity waveforms using established Doppler sonographic criteria. A timing examination with a test bolus of gadolinium contrast material was performed to ensure optimal arterial enhancement during breath-hold gadolinium-enhanced three-dimensional gradient-echo MR angiography. RESULTS: MR phase-contrast waveform pattern analysis was 50% (9/18) sensitive and 78% (40/51) specific for the detection of renal artery stenosis equal to or greater than 60% as shown on MR angiography. Sensitivity (67%, 12/18) and specificity (84%, 42/50) increased slightly, but not significantly, after i.v. administration of an ACE inhibitor. Also, the accuracy of quantitative criteria such as acceleration time and acceleration index did not improve after the administration of ACE inhibitor. CONCLUSION: Renal hilar velocity waveforms, measured using non-breath-hold MR phase-contrast techniques with or without an ACE inhibitor, are insufficiently accurate to use in predicting renal artery stenosis
— id: 8570, year: 2000, vol: 174, page: 499, stat: Journal Article,

2D multislice and 3D MRI sequences are often equally sensitive
Johnson G; Wadghiri YZ; Turnbull DH
1999 Apr;41(4):824-828, Magnetic resonance in medicine
A simple theoretical model was developed to compare the sensitivities (i.e., signal-to-noise ratios per unit imaging time) of two-dimensional (2D) multislice and 3D imaging sequences. The model shows that the sensitivities of 3D and 2D multislice MRI sequences are usually similar. Sensitivities are identical in T2-weighted sequences when the T(R)s of the two sequences are the same. In T1-weighted gradient-echo sequences, sensitivities are very similar when Ernst angle excitation is used and the T(R) of the 2D sequence is less than T1. The predictions of the model are confirmed in phantom and animal experiments
— id: 6119, year: 1999, vol: 41, page: 824, stat: Journal Article,

Glial neoplasms: dynamic contrast-enhanced T2*-weighted MR imaging
Knopp EA; Cha S; Johnson G; Mazumdar A; Golfinos JG; Zagzag D; Miller DC; Kelly PJ; Kricheff II
1999 Jun;211(3):791-798, Radiology
PURPOSE: To evaluate the role of T2*-weighted echo-planar perfusion imaging by using a first-pass gadopentetate dimeglumine technique to determine the association of magnetic resonance (MR) imaging-derived cerebral blood volume (CBV) maps with histopathologic grading of astrocytomas and to improve the accuracy of targeting of stereotactic biopsy. MATERIALS AND METHODS: MR imaging was performed in 29 patients by using a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence followed by conventional imaging. The perfusion data were processed to obtain a color map of relative regional CBV. This information formed the basis for targeting the stereotactic biopsy. Relative CBV values were computed with a nondiffusible tracer model. The relative CBV of lesions was expressed as a percentage of the relative CBV of normal white matter. The maximum relative CBV of each lesion was correlated with the histopathologic grading of astrocytomas obtained from samples from stereotactic biopsy or volumetric resection. RESULTS: The maximum relative CBV in high-grade astrocytomas (n = 26) varied from 1.73 to 13.7, with a mean of 5.07 +/- 2.79 (+/- SD), and in the low-grade cohort (n = 3) varied from 0.92 to 2.19, with a mean of 1.44 +/- 0.68. This difference in relative CBV was statistically significant (P < .001; Student t test). CONCLUSION: Echo-planar perfusion imaging is useful in the preoperative assessment of tumor grade and in providing diagnostic information not available with conventional MR imaging. The areas of perfusion abnormality are invaluable in the precise targeting of the stereotactic biopsy
— id: 6128, year: 1999, vol: 211, page: 791, stat: Journal Article,

ACE-inhibitor-enhanced ultra-low dose Gd-DTPA MR renography performed in conjunction with breath-hold Gd-M
Lee, VS; Rusinek, H; Johnson, G; Yoon, S; Kim, R; Krinsky, GA
1999 NOV ;213P(3):217-217, Radiology
— id: 73270, year: 1999, vol: 213P, page: 217, stat: Journal Article,

Thoracic aorta: rapid black-blood MR imaging with half-Fourier rapid acquisition with relaxation enhancement with or without electrocardiographic triggering
Stemerman DH; Krinsky GA; Lee VS; Johnson G; Yang BM; Rofsky NM
1999 Oct;213(1):185-191, Radiology
PURPOSE: To evaluate and compare findings for thoracic aortic disease with three black-blood magnetic resonance (MR) pulse sequences: half-Fourier rapid acquisition with relaxation enhancement (RARE), with and without electrocardiographic (ECG) triggering, and ECG-triggered turbo spin echo (SE). MATERIALS AND METHODS: Axial black-blood MR images of the chest acquired at 1.5 T with a phased-array coil were obtained in 38 consecutive patients referred for evaluation of thoracic aortic disease. ECG-triggered and nontriggered half-Fourier RARE images were compared with T1-weighted ECG-triggered turbo SE images. Two readers independently scored images for each of the following parameters: ghosting artifacts; clarity of the mediastinum, cardiac chambers, and aortic wall; conspicuity of abnormality; intraluminal signal void uniformity; and overall image quality. RESULTS: Both half-Fourier RARE sequences outperformed the turbo SE sequence for all measured parameters. Scores for the ECG-triggered half-Fourier RARE sequence were significantly (P < .05) higher than those for the nontriggered version for clarity of the mediastinum and aortic wall, conspicuity of any abnormality other than aortic dissection, and overall image quality. Mean acquisition times for the ECG-triggered (48 seconds) and nontriggered (30 seconds) sequences were significantly shorter than that for the turbo SE sequence (2 minutes 20 seconds). CONCLUSION: Rapid black-blood half-Fourier RARE sequences, with or without ECG triggering, can replace ECG-triggered turbo SE sequences for evaluation of thoracic aortic disease
— id: 8479, year: 1999, vol: 213, page: 185, stat: Journal Article,

MR perfusion imaging in human brain using the UNFAIR technique. Un-inverted flow-sensitive alternating inversion recovery
Tanabe JL; Yongbi M; Branch C; Hrabe J; Johnson G; Helpern JA
1999 Jun;9(6):761-767, Journal of magnetic resonance imaging
Pulsed arterial spin labeling magnetic resonance techniques have been developed recently to estimate cerebral blood flow (CBF). Flow-sensitive alternating inversion recovery (FAIR) is one such technique that has been implemented successfully in humans. Un-inverted FAIR (UNFAIR) is an alternative technique in which the flow-sensitive image is acquired following inversion of all spins outside the slice of interest, and the control image is acquired without any spin labeling. This approach is potentially more efficient than FAIR since the UNFAIR control image is entirely flow independent and need only be acquired once. Here, we describe implementation of the sequence on a clinical 1.5 T magnetic resonance system. Both FAIR and UNFAIR perfusion-weighted images were obtained from six normal volunteers. Wash-in/wash-out curves measured in cortical gray and white matter were practically identical for the two techniques, as predicted by our model
— id: 67104, year: 1999, vol: 9, page: 761, stat: Journal Article,

Segmentation analysis in functional MRI: activation sensitivity and gray-matter specificity of RARE and FLASH
Hutchinson M; Rusinek H; Nenov VI; Feinberg DA; Johnson G
1997 Mar-Apr;7(2):361-364, Journal of magnetic resonance imaging
Brain activation is accompanied by local decreases in vascular deoxyhemoglobin. Theoretically, gradient-echo and spin-echo sequences show similar sensitivity to capillary deoxyhemoglobin, but spin-echo sequences should be less sensitive to venous deoxyhemoglobin. This is an important distinction in the context of cortical localization. We report herein a direct experimental comparison of a gradient-echo sequence (fast low-angle shot [FLASH]) with a spin-echo sequence (rapid acquisition with relaxation enhancement [RARE]) for functional MRI (fMRI) in seven subjects undergoing visual stimulation. A Student t test analysis was used to locate areas of significant activation, and then computerized image segmentation was performed to determine the type of activated tissue. Contrary to previous reports, both sequences proved equally sensitive to overall activation. RARE activation, however, was more specific for gray matter, as suggested by prior theoretical models
— id: 7167, year: 1997, vol: 7, page: 361, stat: Journal Article,

Venous aneurysms: MR diagnosis with the "layered gadolinium" sign
Krinsky G; Johnson G; Rofsky N; Shapiro R; Yang B; Weinreb J
1997 Jul-Aug;21(4):623-627, Journal of computer assisted tomography
OBJECTIVE: Our goal was to present MR findings in venous aneurysms and introduce the 'layered gadolinium' sign as an ancillary diagnostic finding. METHOD: Gadolinium-enhanced MR images of three patients with retroperitoneal venous aneurysms were retrospectively reviewed. Prior to MRI, venous aneurysm had been suspected clinically in only one patient. Surgical correlation was available in one patient. A phantom was constructed and imaged to investigate the cause of the layered gadolinium sign. RESULTS: A gradation of signal intensity, the layered gadolinium sign, was observed in three patients with venous aneurysms on postcontrast T1-weighted images. The anterior portion of the aneurysms demonstrated high signal intensity separated by a sharp interface from the low signal intensity posterior region. Unenhanced time-of-flight MR venography, color Doppler, and duplex sonography failed to demonstrate flow in the patient with surgical proof. CONCLUSION: The layered gadolinium sign may be helpful in the diagnosis of venous aneurysm and in differentiating these masses from solid neoplasms
— id: 7188, year: 1997, vol: 21, page: 623, stat: Journal Article,

Peripheral vascular disease evaluated with reduced-dose gadolinium-enhanced MR angiography
Rofsky NM; Johnson G; Adelman MA; Rosen RJ; Krinsky GA; Weinreb JC
1997 Oct;205(1):163-169, Radiology
PURPOSE: To demonstrate the utility of low-dose gadolinium-enhanced magnetic resonance (MR) angiography of two consecutive anatomic areas for assessment of peripheral vascular disease. MATERIALS AND METHODS: Fifteen patients underwent gadolinium-enhanced MR angiography for evaluation of lower extremity peripheral vascular disease after conventional digital subtraction angiography (DSA). MR angiography was performed with three-dimensional coronal gradient-echo acquisitions before and during administration of gadopentetate dimeglumine. Two separate, contiguous areas were studied with separate doses of 0.075 and 0.1 mmol/kg gadopentetate dimeglumine. MR angiography findings were compared with DSA findings; DSA was the standard of reference. Treatment options were determined first with MR angiograms and then with DSA images. RESULTS: For distinguishing greater than 50% stenosis from 50% or less stenosis, gadolinium-enhanced MR angiography yielded a sensitivity of 97%, a specificity of 96%, and an accuracy of 97%. In 146 (97%) of 150 anatomic segments, there was essential or total agreement on treatments determined with MR angiography and DSA. In two cases (one case of vascular stent placement and one case of surgical anastomosis), extent of disease was overestimated with MR angiography. The MR study of one infrapopliteal area was insufficient for evaluation. CONCLUSION: Accurate gadolinium-enhanced MR angiography of multiple peripheral vascular areas of the lower extremities can be performed in most patients with less than 0.2 mmol/kg contrast material
— id: 7249, year: 1997, vol: 205, page: 163, stat: Journal Article,

Suppression of venous signal in time-of-flight MR angiography of the lower extremities after administration of gadopentetate dimeglumine
Rofsky NM; Purdy DE; Johnson G; DeCorato DR; Earls JP; Krinsky G; Weinreb JC
1997 Jan;202(1):177-182, Radiology
PURPOSE: To evaluate a magnetic resonance (MR) angiography time-of-flight technique that can effectively suppress venous signal after gadopentetate dimeglumine administration. MATERIALS AND METHODS: Twelve adult patients underwent MR angiography for the evaluation of peripheral vascular disease. Gradient-echo sequences were performed after the administration of 0.2 mmol/kg gadopentetate dimeglumine. Three sequences were compared: a nontriggered sequence; a gap sequence, an electrocardiographically triggered, segmented sequence with a 7-mm gap between saturation and imaging sections; and a no-gap sequence, a similar sequence as gap but with partially overlapping imaging and saturation sections. For each sequence, identical regions of interest were generated for arterial, venous, and background muscle tissue and noise. A paired Student t test was used to compare the signal-to-noise and contrast-to-noise ratios (C/Ns) among the sequences. In seven patients, the no-gap sequence was used to acquire MR angiograms of the distal lower extremities. RESULTS: The mean artery-muscle C/N was similar for the triggered sequences; both were statistically significantly greater than the ratios for the nontriggered sequence. Venous suppression was much better with the no-gap sequence. Overall, the best artery-vein C/N was also obtained with the no-gap sequence. MR angiograms with effective venous suppression could be obtained only with the no-gap sequence. CONCLUSION: Time-of-flight MR angiograms can be obtained with effective venous suppression after the administration of 0.2 mmol/kg gadopentetate dimeglumine
— id: 12436, year: 1997, vol: 202, page: 177, stat: Journal Article,

A comparison of phase encoding ordering schemes in T2-weighted GRASE imaging
Johnson G; Feinberg DA; Venkataraman V
1996 Sep;36(3):427-435, Magnetic resonance in medicine
Gradient and spin echo (GRASE) imaging is an echo train imaging sequence that combines gradient and RF refocusing. This combination introduces phase modulations into the echo train. If the phase encoding order is linear with echo time, these modulations cause severe ghosting artifacts. Changing the order of phase encoding can greatly reduce these artifacts. Several phase encoding orders for T2-weighted sequences are compared in this paper, linear, partially randomized, standard GRASE ordering, and k-banded (kb) GRASE ordering. Different possible implementations of GRASE and kbGRASE are also considered. Computer simulation is used to compare resolution and artifact levels. Phantom and volunteer images are presented. The linear order is most sensitive to ghosting artifacts associated with chemical shift, susceptibility differences and static field inhomogeneities. The standard GRASE order is least sensitive to these but most vulnerable to artifacts associated with short T2 signals, kb-GRASE is a good intermediate between linear and standard GRASE and generally shows the lowest artifact levels. The partially randomized order gives the most diffuse artifacts. Computer simulations show that spatial resolution and contrast with all phase encoding orders are similar
— id: 7007, year: 1996, vol: 36, page: 427, stat: Journal Article,

Single-shot GRASE imaging with short effective TEs
Johnson G; Feinberg DA; Venkataraman V
1996 Nov-Dec;6(6):944-947, Journal of magnetic resonance imaging
A new phase-encoding scheme for gradient- and spin-echo (GRASE) imaging giving a short effective TE is described. Unlike previous orders, phase encoding is centric rather than sequential. The sequence is a development of k-banded GRASE that uses different time segments of the echo train to encode different bands of k space. This phase-encoding order has been implemented in single-shot sequences on an imager with high performance gradients. Approximately 144 phase-encoding lines can be acquired in an echo train time of 390 ms. With centric phase encoding, the effective TE is 8 ms, compared with 75 ms for sequential encoding, and signal-to-noise ratios (SNRs) in brain tissue are 50 to 70% higher. The sequence can be employed in, for example, diffusion and velocity imaging
— id: 12485, year: 1996, vol: 6, page: 944, stat: Journal Article,

Multiple-window spectrum estimation applied to in vivo NMR spectroscopy
Johnson, G; Thomson, DJ; Wu, EX; Williams, SCR
1996 FEB ;110(2):138-149, Journal of magnetic resonance. Series B.
Multiple-window spectrum estimation (MWSE) is a method of deriving frequency spectra from time series, A set of apodizing windows is applied to the time data and each windowed data set is Fourier transformed, The windows are prolate spheroidal sequences, These form the orthonormal set of functions that is maximally concentrated in both time and frequency domains, An iterative algorithm is then applied to the data set to find a least-squares estimate of the power spectrum, In addition, statistical tests may be applied to determine the existence of periodic components at particular frequencies, their amplitudes, phases, and positions, The method is quantitative and makes no lineshape assumptions, Computer simulations were used to compare MWSE performance with that of conventional Fourier-transform processing with quantification by curve fitting. Signal-to-noise ratio, spectral resolution, linearity, and susceptibility to artifacts were compared, MWSE gives similar signal-to-noise ratio and spectral resolution to Fourier-transform data and is linear over three orders of magnitude but is much more robust with respect to artifacts, In particular, data truncation introduces no baseline distortion, broad baseline humps are removed automatically, and large solvent peaks may be easily removed without affecting adjacent lines, No separate phase correction is required, MWSE gives more accurate quantitative spectra, particularly when the time data are imperfect, The method is, therefore, particularly appropriate for processing in vivo data, The utility of the MWSE method is demonstrated on in vivo H-1, (31)p, and C-13 NMR spectroscopy data. (C) 1996 Academic Press, Inc
— id: 53052, year: 1996, vol: 110, page: 138, stat: Journal Article,

A methodology for co-registering abdominal MR images over multiple breath-holds
Feinberg DA; Johnson G
1995 Nov;34(5):770-774, Magnetic resonance in medicine
Previous studies have demonstrated that the SNR of abdominal MR images can be increased by averaging images obtained in different breath-hold acquisitions. In this note, the authors present a simple new methodology for ensuring that images acquired in multiple breath-hold periods are accurately co-registered. Within each breath-hold, a quick coronal scout scan is followed by a longer axial scan. The scout is used to position the axial slices in a fixed position relative to the organ under examination. This MR technique can, in principle, be automated so as to add less than 1 s to the imaging time of the axial scan. The method can be used to increase SNR by signal averaging or to co-register images acquired during, for example, uptake of contrast agents. SNR improvement with negligible blurring is demonstrated in liver images acquired by this method from healthy volunteers
— id: 7935, year: 1995, vol: 34, page: 770, stat: Journal Article,

Increased flexibility in GRASE imaging by k space-banded phase encoding
Feinberg DA; Johnson G; Kiefer B
1995 Aug;34(2):149-155, Magnetic resonance in medicine
GRASE (GRadient and spin Echo) is an echo train imaging technique that combines gradient and RF refocusing. Although overall signal decay is with T2 and field inhomogeneity phase errors do not accumulate, the small residual phase errors are periodic with echo number. The echo order described previously eliminates the phase error periodicity in k space but instead creates periodicity in the T2 modulation function that can also cause artifacts. In addition, with this order, the effective TE must be half the echo train time, and asymmetric Fourier sampling is difficult to implement. A new method is described that greatly reduces artifacts due to T2 decay, permits greater control of T2 contrast, and lends itself to asymmetric Fourier sampling. Different time segments of the echo train are encoded with different bands of spatial frequency in k space (hence 'k banding'). Both computer simulations and experimental results demonstrate improvements in GRASE images acquired by this method
— id: 6824, year: 1995, vol: 34, page: 149, stat: Journal Article,

GRASE improves spatial resolution in single shot imaging
Feinberg DA; Kiefer B; Johnson G
1995 Apr;33(4):529-533, Magnetic resonance in medicine
In single shot echo train imaging all the data required for a two dimensional image is acquired from a series of echoes generated following a single RF excitation pulse. Spatial resolution is limited because all samples must be acquired before the signal decays. In this paper we show theoretically that more echoes and hence better spatial resolution can be obtained with single shot GRASE imaging than with either echo planar imaging or single shot RARE imaging. This conclusion holds for both conventional imaging hardware and specialized gradient hardware designed for EPI. High quality single shot GRASE images support the theoretical conclusions
— id: 6613, year: 1995, vol: 33, page: 529, stat: Journal Article,

Multiple breath-hold averaging (MBA) method for increased SNR in abdominal MRI
Feinberg DA; Rofsky NM; Johnson G
1995 Dec;34(6):905-909, Magnetic resonance in medicine
Breath-holding during MR imaging eliminates respiratory motion artifacts but places a major time constraint on data acquisition. This constraint limits image signal-to-noise ratio and hence spatial resolution. A new method, multiple breath-hold averaging, is presented that overcomes these time limitations. Several images are acquired in sequential breath-hold periods, separated by periods of normal breathing, and averaged. This averaged image shows the expected increase in SNR with surprisingly little blurring due to misregistration. SNR improvements can be traded for increased spatial resolution. The MBA methodology can also be applied to 3D data acquisitions, dynamic contrast acquisitions, and image subtractions
— id: 6906, year: 1995, vol: 34, page: 905, stat: Journal Article,

Sensitivity optimization of echo times and data sampling times for spin-echo spectroscopy
Johnson G; Wu EX
1994 Nov;105(3):238-241, Journal of magnetic resonance. Series B.
— id: 8248, year: 1994, vol: 105, page: 238, stat: Journal Article,

Optimized phase scrambling for RF phase encoding
Johnson G; Wu EX; Hilal SK
1994 Jan;103(1):59-63, Journal of magnetic resonance. Series B.
— id: 8247, year: 1994, vol: 103, page: 59, stat: Journal Article,

SOLVENT SUPPRESSION BY SELECTIVE SIGNAL SUBTRACTION, A TIME-DOMAIN NEGATIVE-FEEDBACK DYNAMIC-RANGE-COMPRESSION METHOD FOR PROTON NMR-SPECTROSCOPY
GONEN, O; JOHNSON, G
1993 AUG ;102(1):98-102, Journal of magnetic resonance. Series B.
— id: 105122, year: 1993, vol: 102, page: 98, stat: Journal Article,