Yulin Ge

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Yulin Ge, M.D.

Associate Professor;
Department of Radiology (CBI)

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660 First Ave
Floor 4th
660 First Avenue
New York, NY 10016

212-263-3784
Yulin.Ge@nyumc.org

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Research Summary

Magnetic resonance imaging (MRI) provides a highly efficacious means for observing brain anatomy, locating and identifying brain abnormalities, and making diagnosis of brain disorders. Recent advances in state-of-the-art high-field human MR systems have provided ever-advancing imaging capabilities for both clinical diagnosis and basic science research.

Research interests are directed toward developing and applying the quantitative measures at high field MRI in various brain diseases including multiple sclerosis (MS), traumatic brain injury (TBI), brain tumors, and other neurodegenerative diseases. The implementation of these advanced MRI techniques in these diseases has greatly improved our understanding of the dynamics of disease evolution, clinicoradiological correlation, and efficacy of experimental treatments. These advanced techniques include:

1. Volumetric and histographical analysis: objective assessment of lesion load, tissue atrophy, and disease activity.
2. Diffusion tensor imaging (DTI) and fiber tractography (Fig 1): measuring the diffusion characteristics of tissue water can provide information about white matter integrity, connectivity, and pathological substrate of brain lesions.
3. Susceptibility weighted imaging (Fig 2): a 3D high resolution imaging (SWI) that provides high quality of MR venography and susceptibility sensitive technique especially at higher field-strength MR.
4. MR perfusion and functional MR imaging: mapping cerebral blood flow and volume in tissues to evaluate the critical components of blood supply and hemodynamic conditions in the brain. With event-associated fMRI and resting-state fMRI, brain activity related to a specific task or sensory process as well as functional network can be imaged.

It is believed that at higher field strengths of MR such as 7 Tesla, new areas of research are opening up in microscopic and molecular imaging, biomedical imaging, and functional brain imaging and these ultra-high-field systems will evolve into a new standard for clinical care and scientific discovery.

Research Documents

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All data from NYU Health Sciences Library Faculty Bibliography — -

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Thalamus and cognitive impairment in Mild Traumatic Brain Injury: A Diffusional Kurtosis Imaging Study
Grossman EJ; Ge Y; Jensen JH; Babb JS; Miles L; Reaume J; Silver JM; Grossman RI; Inglese M
2011 Jun 3;:?-? #, Journal of neurotrauma
Conventional imaging is unable to detect damage that accounts for permanent cognitive impairment in patients with mild traumatic brain injury (MTBI). While diffusion tensor imaging (DTI) can help to detect diffuse axonal injury (DAI), it is a limited indicator of tissue complexity. It has also been suggested that the thalamus may play an important role in the development of clinical sequelae in MTBI. The purpose of this study was to determine if diffusional kurtosis imaging (DKI), a novel quantitative magnetic resonance imaging (MRI) technique, can provide early detection of damage in the thalamus and white matter (WM) of MTBI patients and if thalamic injury is associated with cognitive impairment. Twenty-two MTBI patients and 14 controls underwent MRI and neuropsychological testing. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) were measured in the thalamus and several WM regions classically identified with DAI. Compared to controls, patients examined within one year after injury exhibited variously altered DTI and DKI derived measures in the thalamus and the internal capsule while, in addition to these regions, patients examined more than one year after injury also showed similar differences in the splenium of the corpus callosum and the centrum semiovale. Cognitive impairment was correlated to MK in the thalamus and the internal capsule. These findings suggest that combined use of DTI and DKI provides a more sensitive tool for identifying brain injury. In addition, MK in the thalamus might be useful for early prediction of permanent brain damage and cognitive outcome
— id: 135641, year: 2011, vol: , page: ?, stat: Journal Article,

Brain iron quantification in mild traumatic brain injury: a magnetic field correlation study
Raz, E; Jensen, J H; Ge, Y; Babb, J S; Miles, L; Reaume, J; Grossman, R I; Inglese, M
2011 Nov;32(10):1851-1856, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Experimental studies have suggested a role for iron accumulation in the pathology of TBI. Magnetic field correlation MR imaging is sensitive to the presence of non-heme iron. The aims of this study are to 1) assess the presence, if any, and the extent of iron deposition in the deep gray matter and regional white matter of patients with mTBI by using MFC MR imaging; and 2) investigate the association of regional brain iron deposition with cognitive and behavioral performance of patients with mTBI. MATERIALS AND METHODS: We prospectively enrolled 28 patients with mTBI. Eighteen healthy subjects served as controls. The subjects were administered the Stroop color word test, the Verbal Fluency Task, and the Post-Concussion Symptoms Scale. The MR imaging protocol (on a 3T imager) consisted of conventional brain imaging and MFC sequences. After the calculation of parametric maps, MFC was measured by using a region of interest approach. MFC values across groups were compared by using analysis of covariance, and the relationship of MFC values and neuropsychological tests were evaluated by using Spearman correlations. RESULTS: Compared with controls, patients with mTBI demonstrated significant higher MFC values in the globus pallidus (P = .002) and in the thalamus (P = .036). In patients with mTBI, Stroop test scores were associated with the MFC value in frontal white matter (r = -0.38, P = .043). CONCLUSIONS: MFC values were significantly elevated in the thalamus and globus pallidus of patients with mTBI, suggesting increased accumulation of iron. This supports the hypothesis that deep gray matter is a site of injury in mTBI and suggests a possible role for iron accumulation in the pathophysiological events after mTBI
— id: 141487, year: 2011, vol: 32, page: 1851, stat: Journal Article,

Thalamic resting-state functional networks: disruption in patients with mild traumatic brain injury
Tang, Lin; Ge, Yulin; Sodickson, Daniel K; Miles, Laura; Zhou, Yongxia; Reaume, Joseph; Grossman, Robert I
2011 Sep;260(3):831-840, Radiology
Purpose: To explore the neural correlates of the thalamus by using resting-state functional magnetic resonance (MR) imaging and to investigate whether thalamic resting-state networks (RSNs) are disrupted in patients with mild traumatic brain injury (MTBI). Materials and Methods: This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained from 24 patients with MTBI and 17 healthy control subjects. The patients had varying degrees of symptoms, with a mean disease duration of 22 days. The resting-state functional MR imaging data were analyzed by using a standard seed-based whole-brain correlation method to characterize thalamic RSNs. Student t tests were used to perform comparisons. The association between thalamic RSNs and performance on neuropsychologic and neurobehavioral measures was also investigated in patients with MTBI by using Spearman rank correlation. Results: A normal pattern of thalamic RSNs was demonstrated in healthy subjects. This pattern was characterized as representing relatively symmetric and restrictive functional thalamocortical connectivity, suggesting an inhibitory property of the thalamic neurons during the resting state. This pattern was disrupted, with significantly increased thalamic RSNs (P </= .005) and decreased symmetry (P = .03) in patients with MTBI compared with healthy control subjects. Increased functional thalamocortical redistributive connectivity was correlated with diminished neurocognitive functions and clinical symptoms in patients with MTBI. Conclusion: These findings of abnormal thalamic RSNs lend further support to the presumed subtle thalamic injury in patients with MTBI. Resting-state functional MR imaging can be used as an additional imaging modality for detection of thalamocortical connectivity abnormalities and for better understanding of the complex persistent postconcussive syndrome. (c) RSNA, 2011
— id: 136638, year: 2011, vol: 260, page: 831, stat: Journal Article,

Smallworld network properties changes in mild cognitive impairment and earlyalzheimer's disease
Zhou Y.; Ge Y.; Dougherty J.
2011 ;7(4 SUPPL 1):S729-S729, Alzheimer's & Dementia
Background: Small-world network is a relatively new concept, characterized by a class of regional hubs with short communication length and high clustering coefficient. It consists of well-balanced networks with local specialization and global integration.We hypothesize that the degree and topographic pattern of cortical adaptive changes are different in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and can be detected with small-world properties based on cortical thickness. Methods: 13 normal controls, 10 individuals with MCI and 10 with early AD were enrolled. The MRI scans were conducted using the 1.5T scanner. We used the 3D high resolution anatomical MPRAGE data to obtain structural small world networks based on cortical thickness measurements using Freesurfer (http:// surfer.nmr.mgh.harvard.edu/) software. The thickness of total of 156 brain structures (78 ROIs on each hemisphere of brain from Freesurfer standardized landmarks) was computed to derive the correlation matrix, which is used to generate small world graphic topology with a threshold of p < 0.0001 to maintain sparseness (Fig1). Small world properties were then computed and analyzed with in-house matlab scripts and programs from matlab-bgl (http://www.stanford.edu/~dgleich/programs/matlab-bgl/) in all subjects. Results: We found significant disruption of small-world properties in patients compared to controls. These include significantly decreased mean relative betweeness centrality (BC, a measure of path length) and highest cluster coefficient (CC) in patients with MCI and AD compared to controls. The core number was reduced in AD (29) compared to NC (23) and was increased in MCI (48). The number of edges (number of undirected connections) was also reduced in AD compared to NC (from 4842 to 3948) and was increased MCI (9584). Conclusions: Both MCI and AD showed disrupted small world properties compared to controls with higher degree in AD. However, the findings of increased core number in the superior and inferior temporal parts in patients with MCI may reflect a compensative mechanism for reduced BC and CC in the posterior cingulate and precuneus regions. Further follow-up studies of different stages of MCI are warranted. (Figure presented)
— id: 136957, year: 2011, vol: 7, page: S729, stat: Journal Article,

Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T
Ge, Yulin; Patel, Mayur B; Chen, Qun; Grossman, Elan J; Zhang, Ke; Miles, Laura; Babb, James S; Reaume, Joseph; Grossman, Robert I
2009 Jul;23(7):666-674, Brain injury
OBJECTIVE: To assess cerebral blood flow (CBF) changes in patients with mild traumatic brain injury (MTBI) using an arterial spin labelling (ASL) perfusion MRI and to investigate the severity of neuropsychological functional impairment with respect to haemodynamic changes. MATERIALS AND METHODS: Twenty-one patients with MTBI and 20 healthy controls were studied at 3T MR. The median time since the onset of brain injury in patients was 24.6 months. Both patients and controls underwent a traditional consensus battery of neurocognitive tests. ASL was performed using true fast imaging with steady state precession and a flow-sensitive alternating inversion recovery preparation. Regional CBF were measured in both deep and cortical gray matter as well as white matter at the level of basal ganglia. RESULTS: The mean regional CBF was significantly lower in patients with MTBI (45.9 +/- 9.8 ml/100 g min(-1)) as compared to normal controls (57.1 +/- 8.1 ml/100 g min(-1); p = 0.002) in both sides of thalamus. The decrease of thalamic CBF was significantly correlated with several neurocognitive measures including processing and response speed, memory/learning, verbal fluency and executive function in patients. CONCLUSIONS: Haemodynamic impairment can occur and persist in patients with MTBI, the extent of which is more severe in thalamic regions and correlate with neurocognitive dysfunction during the extended course of disease
— id: 100616, year: 2009, vol: 23, page: 666, stat: Journal Article,

Diminished visibility of cerebral venous vasculature in multiple sclerosis by susceptibility-weighted imaging at 3.0 Tesla
Ge, Yulin; Zohrabian, Vahe M; Osa, Etin-Osa; Xu, Jian; Jaggi, Hina; Herbert, Joseph; Haacke, E Mark; Grossman, Robert I
2009 May;29(5):1190-1194, Journal of magnetic resonance imaging
Multiple sclerosis (MS) is a disease of the central nervous system characterized by widespread demyelination, axonal loss and gliosis, and neurodegeneration; susceptibility-weighted imaging (SWI), through the use of phase information to enhance local susceptibility or T2* contrast, is a relatively new and simple MRI application that can directly image cerebral veins by exploiting venous blood oxygenation. Here, we use high-field SWI at 3.0 Tesla to image 15 patients with clinically definite relapsing-remitting MS and to assess cerebral venous oxygen level changes. We demonstrate significantly reduced visibility of periventricular white matter venous vasculature in patients as compared to control subjects, supporting the concept of a widespread hypometabolic MS disease process. SWI may afford a noninvasive and relatively simple method to assess venous oxygen saturation so as to closely monitor disease severity, progression, and response to therapy
— id: 98007, year: 2009, vol: 29, page: 1190, stat: Journal Article,

Measurement of deep gray matter perfusion using a segmented true-fast imaging with steady-state precession (True-FISP) arterial spin-labeling (ASL) method at 3T
Grossman, Elan J; Zhang, Ke; An, Jing; Voorhees, Abram; Inglese, Matilda; Ge, Yulin; Oesingmann, Niels; Xu, Jian; McGorty, Kelly A; Chen, Qun
2009 Jun;29(6):1425-1431, Journal of magnetic resonance imaging
PURPOSE: To study the feasibility of using the MRI technique of segmented true-fast imaging with steady-state precession arterial spin-labeling (True-FISP ASL) for the noninvasive measurement and quantification of local perfusion in cerebral deep gray matter at 3T. MATERIALS AND METHODS: A flow-sensitive alternating inversion-recovery (FAIR) ASL perfusion preparation was used in which the echo-planar imaging (EPI) readout was replaced with a segmented True-FISP data acquisition strategy. The absolute perfusion for six selected regions of deep gray matter (left and right thalamus, putamen, and caudate) were calculated in 11 healthy human subjects (six male, five female; mean age = 35.5 years +/- 9.9). RESULTS: Preliminary measurements of the average absolute perfusion values at the six selected regions of deep gray matter are in agreement with published values for mean absolute cerebral blood flow (CBF) baselines acquired from healthy volunteers using positron emission tomography (PET). CONCLUSION: Segmented True-FISP ASL is a practical and quantitative technique suitable to measure local tissue perfusion in cerebral deep gray matter at a high spatial resolution without the susceptibility artifacts commonly associated with EPI-based methods of ASL. J. Magn. Reson. Imaging 2009;29:1425-1431. (c) 2009 Wiley-Liss, Inc
— id: 99238, year: 2009, vol: 29, page: 1425, stat: Journal Article,

Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging
Haacke, E Mark; Makki, Malek; Ge, Yulin; Maheshwari, Megha; Sehgal, Vivek; Hu, Jiani; Selvan, Madeswaran; Wu, Zhen; Latif, Zahid; Xuan, Yang; Khan, Omar; Garbern, James; Grossman, Robert I
2009 Mar;29(3):537-544, Journal of magnetic resonance imaging
PURPOSE: To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging. MATERIALS AND METHODS: Twenty-seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre- and postcontrast T1-weighted imaging, T2-weighted imaging, FLAIR, and SWI at 1.5 T, 3 T, and 4 T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were reevaluated for their iron content using the SWI filtered phase images. RESULTS: There were a variety of new lesion characteristics identified by SWI, and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI, and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established. CONCLUSION: The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus
— id: 142010, year: 2009, vol: 29, page: 537, stat: Journal Article,

Noninvasive Quantification of Whole-Brain Cerebral Metabolic Rate of Oxygen (CMRO2) by MRI
Xu, F; Ge, YL; Lu, HZ
2009 JUL ;62(1):141-148, Magnetic resonance in medicine
Cerebral metabolic rate of oxygen (CMRO2) is an important marker for brain function and brain health. Existing techniques for quantification of CMRO2 with positron emission tomography (PEI) or MRI involve special equipment and/or exogenous agents, and may not be suitable for routine clinical studies. In the present study, a noninvasive method is developed to estimate whole-brain CMRO2 in humans. This method applies phase-contrast MRI for quantitative blood flow measurement and T-2-relaxation-under-spin-tagging (TRUST) MRI for venous oxygenation estimation, and uses the Fick principle of arteriovenous difference for the calculation of CMRO2. Whole-brain averaged CMRO2 values in young, healthy subjects were 132.1 +/- 20.0 mu mol/100 g/min, in good agreement with literature reports using PET. Various acquisition strategies for phasecontrast and TRUST MRI were compared, and it was found that nongated phase-contrast and sagittal sinus (SS) TRUST MRI were able to provide the most efficient and accurate estimation of CMRO2. In addition, blood flow and venous oxygenation were found to be positively correlated across subjects. Owing to the noninvasive nature of this method, it may be a convenient and useful approach for assessment of brain metabolism in brain disorders as well as under various physiologic conditions. Magn Reson Med 62:141-148, 2009. (C) 2009 Wiley-Liss, Inc
— id: 100633, year: 2009, vol: 62, page: 141, stat: Journal Article,

Seven-Tesla magnetic resonance imaging: new vision of microvascular abnormalities in multiple sclerosis
Ge, Yulin; Zohrabian, Vahe M; Grossman, Robert I
2008 Jun;65(6):812-816, Archives of neurology
BACKGROUND: Although the role of vascular pathology in multiple sclerosis (MS) lesions was suggested long ago, the derivation of these lesions from the vasculature has been difficult to assess in vivo. Ultrahigh-field (eg, 7-T) magnetic resonance imaging (MRI) has become a tool for assessing vascular involvement in MS lesions owing to markedly increased image resolution and susceptibility contrast of venous blood. OBJECTIVE: To describe the perivenous association of MS lesions on high-resolution and high-contrast 7-T susceptibility-sensitive MRI. DESIGN: Case study. SETTING: University hospital. PATIENTS: Two women with clinically definite relapsing-remitting MS. RESULTS: We demonstrated markedly enhanced detection of unique microvascular involvement associated with most of the visualized MS lesions with abnormal signals on and around the venous wall on 7-T compared with 3-T MRI. CONCLUSIONS: These findings, which have never been shown on conventional fields of MRI, not only allow for direct evidence of vascular pathogenesis in MS in vivo but also have important implications for monitoring lesion activity and therapeutic response
— id: 79389, year: 2008, vol: 65, page: 812, stat: Journal Article,

Quantitative evaluation of oxygenation in venous vessels using T2-Relaxation-Under-Spin-Tagging MRI
Lu, Hanzhang; Ge, Yulin
2008 Aug;60(2):357-363, Magnetic resonance in medicine
Noninvasive measurement of cerebral venous oxygenation can serve as a tool for better understanding fMRI signals and for clinical evaluation of brain oxygen homeostasis. In this study a novel technique, T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, is developed to estimate oxygenation in venous vessels. This method uses the spin labeling principle to automatically isolate pure blood signals from which T2 relaxation times are determined using flow-insensitive T2-preparation pulses. The blood T2 is then converted to blood oxygenation using a calibration plot. In vivo experiments gave a baseline venous oxygenation of 64.8 +/- 6.3% in sagittal sinus in healthy volunteers (n = 24). Reproducibility studies demonstrated that the standard deviation across trials was 2.0 +/- 1.1%. The effects of repetition time and inversion time selections were investigated. The TRUST technique was further tested using various physiologic challenges. Hypercapnia induced an increase in venous oxygenation by 13.8 +/- 1.1%. On the other hand, caffeine ingestion resulted in a decrease in oxygenation by 7.0 +/- 1.8%. Contrast agent infusion (Gd-DTPA, 0.1 mmol/kg) reduced venous blood T2 by 11.2 ms. The results of this study show that TRUST MRI is a useful technique for quantitative assessment of blood oxygenation in the brain
— id: 86624, year: 2008, vol: 60, page: 357, stat: Journal Article,

Quantitative measurement of spinal cord blood volume in humans using vascular-space-occupancy MRI
Lu, Hanzhang; Law, Meng; Ge, Yulin; Hesseltine, Stephen M; Rapalino, Otto; Jensen, Jens H; Helpern, Joseph A
2008 Mar;21(3):226-232, NMR in biomedicine
Although perfusion is of major interest for many spinal cord disorders, there is no established, reproducible technique for evaluating blood flow or blood volume of the spinal cord in humans. Here the first report of in vivo measurement of human spinal cord blood volume (scBV) is presented. An FDA-approved contrast agent, Gd-DTPA, was used as an intravascular agent for the cord parenchyma, and pre-/post-contrast vascular-space-occupancy (VASO) MRI experiments were performed to obtain a quantitative estimation of scBV in mL blood/100 mL tissue. VASO MRI was used because it does not rely on knowledge of an arterial input function, it avoids the imaging artifacts of single-shot echo planar imaging approaches, and it requires only relatively simple and direct calculations for scBV quantification. Preliminary tests at 1.5 T and 3 T gave mean +/- SD scBV values of 4.3 +/- 0.7 ml/100 mL tissue (n = 6) and 4.4 +/- 0.7 ml/100 mL tissue (n = 4), respectively, consistent with the expectation that the scBV values would not be field-dependent
— id: 79451, year: 2008, vol: 21, page: 226, stat: Journal Article,

Baseline blood oxygenation modulates response amplitude: Physiologic basis for intersubject variations in functional MRI signals
Lu, Hanzhang; Zhao, Chenguang; Ge, Yulin; Lewis-Amezcua, Kelly
2008 Aug;60(2):364-372, Magnetic resonance in medicine
Although BOLD functional MRI (fMRI) provides a useful tool for probing neuronal activities, large intersubject variations in signal amplitude are commonly observed. Understanding the physiologic basis for these variations will have a significant impact on many fMRI studies. First, the physiologic modulator can be used as a regressor to reduce variations across subjects, thereby improving statistical power for detecting group differences. Second, if a pathologic condition or a drug treatment is shown to change fMRI responses, monitoring this modulatory parameter is useful in correctly interpreting the fMRI changes to neuronal deficits/recruitments. Here we present evidence that the task-evoked fMRI signals are modulated by baseline blood oxygenation. To measure global blood oxygenation, we used a recently developed technique, T(2) relaxation under spin-tagging (TRUST) MRI, which yielded baseline oxygenation of 63.7% +/- 7.2% in the sagittal sinus with an estimation error of 1.3%. It was found that individuals with higher baseline oxygenation tend to have a smaller fMRI signal, and vice versa. For every 10% difference in baseline oxygenation across subjects, BOLD and cerebral blood flow (CBF) signals differ by -0.4% and -30.0%, respectively, when using visual stimulation. TRUST MRI is a useful measurement for fMRI studies to control for the modulatory effects of baseline oxygenation that are unique to each subject
— id: 86625, year: 2008, vol: 60, page: 364, stat: Journal Article,

Quantitative assessment of iron accumulation in the deep gray matter of multiple sclerosis by magnetic field correlation imaging
Ge, Y; Jensen, J H; Lu, H; Helpern, J A; Miles, L; Inglese, M; Babb, J S; Herbert, J; Grossman, R I
2007 Oct;28(9):1639-1644, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Deposition of iron has been recognized recently as an important factor of pathophysiologic change including neurodegenerative processes in multiple sclerosis (MS). We propose that there is an excess accumulation of iron in the deep gray matter in patients with MS that can be measured with a newly developed quantitative MR technique--magnetic field correlation (MFC) imaging. MATERIALS AND METHODS: With a 3T MR system, we studied 17 patients with relapsing-remitting MS and 14 age-matched healthy control subjects. We acquired MFC imaging using an asymmetric single-shot echo-planar imaging sequence. Regions of interest were selected in both deep gray matter and white matter regions, and the mean MFC values were compared between patients and controls. We also correlated the MFC data with lesion load and neuropsychologic tests in the patients. RESULTS: MFC measured in the deep gray matter in patients with MS was significantly higher than that in the healthy controls (P < or = .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. The increased iron deposition measured with MFC in the deep gray matter in the patients correlated positively with the total number of MS lesions (thalamus: r = 0.61, P = .01; globus pallidus: r = 0.52, P = .02). A moderate but significant correlation between the MFC value in the deep gray matter and the neuropsychologic tests was also found. CONCLUSION: Quantitative measurements of iron content with MFC demonstrate increased accumulation of iron in the deep gray matter in patients with MS, which may be associated with the disrupted iron outflow pathway by lesions. Such abnormal accumulation of iron may contribute to neuropsychologic impairment and have implications for neurodegenerative processes in MS
— id: 75382, year: 2007, vol: 28, page: 1639, stat: Journal Article,

A Holm-type procedure controlling the false discovery rate
Ge, Y; Sealfon, SC; Tseng, CH; Speed, TP
2007 DEC ;77(18):1756-1762, Statistics & probability letters
Benjamini and Hochberg [1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. Roy. Statist. Soc. Ser. B 57, 289-300] proposed a step-up procedure controlling the false discovery rate (FDR) under the assumption that test statistics are independent. Benjamini and Yekutieli [2001. The control of false discovery rate in multiple hypothesis testing under dependency. Ann. Statist. 29 (4) 1165-1188] further developed a conservative procedure without this assumption. This paper proposes a Holm-type procedure controlling the FDR. This simple step-down procedure can be more powerful than the Benjamini and Yekutieli (2001) procedure when the number of rejected hypotheses is smaller than In(m), where m is the total number of hypotheses. (C) 2007 Elsevier B.V. All rights reserved
— id: 75463, year: 2007, vol: 77, page: 1756, 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,

Multiple sclerosis: the role of MR imaging
Ge, Y
2006 Jun-Jul;27(6):1165-1176, AJNR. American journal of neuroradiology
MR offers by far the most sensitive technique for detecting multiple sclerosis (MS) lesions and has proved to be an important paraclinical tool for diagnosing MS and monitoring therapeutic trials. Technologic advances of MR in recent years have dramatically improved our understanding of MS disease. This review will focus on the contribution of MR imaging in MS and provide a discussion of conventional and advanced nonconventional MR techniques with regard to current findings, clinical correlations, and future directions
— id: 67532, year: 2006, vol: 27, page: 1165, stat: Journal Article,

Seeing is believing: in vivo evolution of multiple sclerosis pathology with magnetic resonance
Ge, Yulin
2006 Aug;17(4):295-306, Topics in magnetic resonance imaging
Multiple sclerosis (MS) is considered a prototypical inflammatory autoimmune disease of the central nervous system that affects both myelin and axon. One of the most challenging aspects of MS is understanding the nature and mechanism of tissue injury because inflammation, demyelination, axonal degeneration, microvascular injury, and atrophy are all identified in histopathologic studies. Magnetic resonance (MR) imaging provides an in vivo examination of the brain that directly defines the extent of the pathology. In recent years, extensive MR studies have had a major impact on MS not only in making an early diagnosis but also in understanding of the disease. By exploiting the natural history and histopathologic correlation, conventional and various novel quantitative MR techniques have demonstrated the ability to image underlying pathological processes in MS. This review examines the role of different MR techniques in going beyond anatomical imaging and produces a more comprehensive overview of the pathophysiological changes which occur and evolve in MS.
— id: 72814, year: 2006, vol: 17, page: 295, 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,

Applications of Diffusion Tensor MR Imaging in Multiple Sclerosis
Ge, Yulin; Law, Meng; Grossman, Robert I
2005 Dec;1064:202-219, Annals of the New York Academy of Sciences
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that is the most common cause of nontraumatic disability in young adults in the United States. In recent years, magnetic resonance imaging (MRI) has been established as an important paraclinical tool in MS for the assessment of clinical diagnosis, natural history, and treatment effects. In MS studies, there are many advantages to having a sensitive and reliable in vivo method for investigating the specific pathological changes of white matter and its integrity during the disease process. As a consequence, in the past decade, the application of MRI to the study of MS has been explored from conventional MRI to new advanced quantitative techniques with greater pathological specificity and sensitivity. Diffusion tensor imaging (DTI) is one of the most promising techniques with regard to MS. It quantifies the amount of nonrandom water diffusion within tissues and provides unique in vivo information about the pathological processes that affect water diffusion as a result of brain microstructural damage. This review outlines the current state of the art and future direction of DTI and fiber tractography in the study of MS disease
— id: 61244, year: 2005, vol: 1064, page: 202, stat: Journal Article,

Applications of Diffusion Tensor MR Imaging in Multiple Sclerosis
Ge, Yulin; Law, Meng; Grossman, Robert I
White matter in cognitive neuroscience: Advances in diffusion tensor imaging and its applications New York, NY, US: New York Academy of Sciences, 2005,
(from the chapter) Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that is the most common cause of nontraumatic disability in young adults in the United States. In recent years, magnetic resonance imaging (MRI) has been established as an important paraclinical tool in MS for the assessment of clinical diagnosis, natural history, and treatment effects. In MS studies, there are many advantages to having a sensitive and reliable in vivo method for investigating the specific pathological changes of white matter and its integrity during the disease process. As a consequence, in the past decade, the application of MRI to the study of MS has been explored from conventional MRI to new advanced quantitative techniques with greater pathological specificity and sensitivity. Diffusion tensor imaging (DTI) is one of the most promising techniques with regard to MS. It quantifies the amount of nonrandom water diffusion within tissues and provides unique in vivo information about the pathological processes that affect water diffusion as a result of brain microstructural damage. This review outlines the current state of the art and future direction of DTI and fiber tractography in the study of MS disease.
— id: 4106, year: 2005, vol: , page: 202, stat: Chapter,

Prominent perivenular spaces in multiple sclerosis as a sign of perivascular inflammation in primary demyelination
Ge, Yulin; Law, Meng; Herbert, Joseph; Grossman, Robert I
2005 Oct;26(9):2316-2319, AJNR. American journal of neuroradiology
In this study, we describe prominent perivenular spaces as a sign that is seen on high-resolution (512 x 512) transverse T2-weighted MR images in patients with multiple sclerosis. The observed widening of perivenular space is depicted as a stringlike hyperintensity projecting radially and aligned with multiple sclerosis lesions (usually small), following the course and configuration of deep venular structures. This widening may be an important sign in differentiating primary (ie, in multiple sclerosis) from secondary causes of demyelination
— id: 61247, year: 2005, vol: 26, page: 2316, 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,

Neuronal cell injury precedes brain atrophy in multiple sclerosis - Reply
Gonen, O; Ge, YL; Inglese, M; Grossman, RI
2005 JAN 11 ;64(1):176-176, Neurology
— id: 105100, year: 2005, vol: 64, page: 176, 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,

Neuronal cell injury precedes brain atrophy in multiple sclerosis
Ge, Y; Gonen, O; Inglese, M; Babb, J S; Markowitz, C E; Grossman, R I
2004 Feb 24;62(4):624-627, Neurology
Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity)
— id: 43785, year: 2004, vol: 62, page: 624, 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,

Quantitative MRI: hidden age-related changes in brain tissue
Inglese, Matilde; Ge, Yulin
2004 Dec;15(6):355-363, Topics in magnetic resonance imaging
The advent of MRI has made a remarkable progress in the understanding of age-related brain changes providing a noninvasive tool to study in vivo the normally aging individuals at multiple time points. However, conventional MRI techniques are unable to detect and quantify age-related microstructural changes that have been documented at the post-mortem examination of brain tissues. More sophisticated, quantitative MR techniques such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy have been shown to be sensitive to microstructural and metabolic changes that occur in gray and white matter over the course of life span. This review highlights some of these innovative, quantitative MR techniques that are particularly relevant for the study of occult age-related brain tissue changes. Characterization of the in vivo patterns of molecular and cellular changes that occur in the normal aging brain is of crucial importance to understand the pathophysiology of normal cognitive decline and to interpret observed changes in neurodegenerative diseases
— id: 58896, year: 2004, vol: 15, page: 355, stat: Journal Article,

Indirect evidence for early widespread gray matter involvement in relapsing-remitting multiple sclerosis
Inglese, Matilde; Ge, Yulin; Filippi, Massimo; Falini, Andrea; Grossman, Robert I; Gonen, Oded
2004 Apr;21(4):1825-1829, Neuroimage
Multiple sclerosis (MS) has traditionally been viewed as an inflammatory demyelinating white matter (WM) disease of the central nervous system. However, recent pathology and MRI studies have shown lesions in the gray matter (GM) as well. To ascertain the extent of GM involvement, we obtained with nonlocalizing proton MR spectroscopy the concentration of N-acetylaspartate (NAA), a metabolite found almost exclusively in neuronal cells, T2-lesion loads, and GM and WM fractions in the entire brain of 71 relapsing-remitting (RR) MS patients (51 women, 20 men, 25-55 years old) and 41 healthy controls (27 women, 14 men, 23-55 years old). The average whole-brain NAA (WBNAA) difference between the patients and the controls was -2.9 mM (-22%, P < 0.0001); range: +1.2 to -7.8 mM (+8% to -63%). The patients' median T2 lesion volume was 5.5 (range: 0.140-28) cm(3). GM and WM comprised 50.4 +/- 3.8% and 30.4 +/- 5.0% (mean +/- standard deviation), respectively, of the total brain volume in the patients; 53.8 +/- 3.7% and 35.4 +/- 4.7% in the controls. Because WM and GM constitute approximately 40% and 60% of the brain parenchyma, respectively, and the NAA concentration in the former is 2/3 of the latter, WBNAA loss greater than 40% x 2/3 = 27% cannot be explained in terms of WM (axonal) pathology alone and must include widespread GM (neuronal) deficits. Therefore, the concept of MS, even at its earlier stages, as a WM disease might need to be reexamined
— id: 42809, year: 2004, vol: 21, page: 1825, 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,

Standardized calculation of brain parenchymal fraction: An approach to objective assessment of cerebral atrophy - Reply
Ge, YL
2003 AUG ;24(7):1493-1493, AJNR. American journal of neuroradiology
— id: 98232, year: 2003, vol: 24, page: 1493, stat: Journal Article,

Dirty-appearing white matter in multiple sclerosis: volumetric MR imaging and magnetization transfer ratio histogram analysis
Ge, Yulin; Grossman, Robert I; Babb, James S; He, Juan; Mannon, Lois J
2003 Nov-Dec;24(10):1935-1940, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: In contrast to 'normal-appearing' white matter (NAWM) in patients with multiple sclerosis (MS), there are subtle, abnormal and diffuse signal intensity changes often seen on T2-weighted MR images, which we have referred to as 'dirty-appearing' white matter (DAWM). These areas of DAWM have slightly higher signal intensity than that of NAWM, but lower than that of lesion plaques. Our study was designed to determine the volumetric and magnetization transfer ratio (MTR) features of DAWM in patients with MS. METHODS: Dual-echo fast spin-echo MR imaging and magnetization transfer imaging were performed in 22 patients with relapsing-remitting MS. Slightly hyperintense DAWM areas were manually outlined on the basis of T2-weighted imaging findings. The volume and MTR of DAWM were calculated and compared with the volume and MTR of NAWM and T2 lesion plaques. RESULTS: The average volume of DAWM (18.3 mL) was greater than the average volume of T2 lesion plaques (11.0 mL, P =.04), and the mean MTR in DAWM (38.7%) differed significantly (P <.0001) from that in NAWM (40.7%) and plaques (33.3%). There was a modest negative correlation between either mean MTR (r = -0.60; P =.003) of DAWM or peak height (r = -0.50; P =.02) of DAWM with T2 lesion load. Neither DAWM volume nor total T2 abnormality (DAWM + plaques) volume correlates with the Expanded Disability Status Scale. CONCLUSION: The results of this study indicate that MTR is able to differentiate DAWM from lesion plaques and NAWM and that DAWM might be a different pathologic process of the disease. The notion and quantification of these subtle imaging findings of DAWM areas may improve our understanding of certain stages of disease progression and disease burden in patients with relapsing-remitting MS
— id: 43786, year: 2003, vol: 24, page: 1935, stat: Journal Article,

Whole brain imaging of HIV-infected patients: quantitative analysis of magnetization transfer ratio histogram and fractional brain volume
Ge, Yulin; Kolson, Dennis L; Babb, James S; Mannon, Lois J; Grossman, Robert I
2003 Jan;24(1):82-87, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) histogram analysis and volumetric MR imaging are sensitive tools with which to quantify the tissue destructive effects in patients with white matter or neurodegenerative disease. Our purpose was to determine whether whole brain MTR and fractional brain parenchyma volume measurements are altered in HIV-1-infected patients who are neurologically symptomatic and in those who are asymptomatic. METHODS: We performed MR imaging and MTR studies of 15 neurologically symptomatic (seven patients) and asymptomatic (eight patients) HIV-1-seropositive patients and compared their findings with those of 10 seronegative normal control participants. MTR was computed on the basis of whole brain parenchyma segmented by using thin section dual echo MR images. RESULTS: The loss of brain tissue, indicated by fractional brain parenchyma volume, was more pronounced in neurologically symptomatic patients (P =.003) but not in asymptomatic patients (P =.23) when compared with control participants. As for whole brain MTR histogram analysis, both patient groups showed significant decrease in mean (P =.02) and median (P < or =.009) values, compared with normal control participants. There was a trend toward positive correlation (r > or = 0.56) between MTR histogram statistics and fractional brain parenchyma volume. CONCLUSION: Our results suggest that MTR histogram analysis is sensitive in detecting early involvement in neurologically asymptomatic patients with HIV and may, therefore, be used as a combined tool with volumetric measurement, which showed significant tissue loss only in symptomatic patients, to assess various stages of brain damage induced by HIV
— id: 39325, year: 2003, vol: 24, page: 82, stat: Journal Article,

Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis
Ge, Yulin; Grossman, Robert I; Babb, James S; Rabin, Marcie L; Mannon, Lois J; Kolson, Dennis L
2002 Sep;23(8):1327-1333, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and total white matter (WM) in human brain is now available. We investigated the effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM) volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four healthy volunteers (22 men, 32 women) aged 20-86 years underwent dual-echo fast spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were segmented by using MR image-based computerized semiautomated software. Volumes were normalized as a percentage of intracranial volume (%GM and %WM) to adjust for variations in head size. Age and sex effects were then assessed. RESULTS: Both %GM and %WM in the intracranial space were significantly less in older subjects (> or =50 years) than in younger subjects (<50 years) (P <.0001 and P =.02, respectively). Consistently, %GM decreased linearly with age, beginning in the youngest subjects. %WM decreased in a quadratic fashion, with a greater rate beginning only in adult midlife. Although larger GM volumes were observed in men before adjustments for cranium size, no significant differences in %GM or %WM were observed between the sexes. CONCLUSION: GM volume loss appears to be a constant, linear function of age throughout adult life, whereas WM volume loss seems to be delayed until middle adult life. Both appear to be independent of sex. Quantitative analysis of %GM and %WM volumes can improve our understanding of brain atrophy due to normal aging; this knowledge may be valuable in distinguishing atrophy of disease patterns from characteristics of the normal aging process
— id: 43788, year: 2002, vol: 23, page: 1327, stat: Journal Article,

Age-related total gray matter and white matter changes in normal adult brain. Part II: quantitative magnetization transfer ratio histogram analysis
Ge, Yulin; Grossman, Robert I; Babb, James S; Rabin, Marcie L; Mannon, Lois J; Kolson, Dennis L
2002 Sep;23(8):1334-1341, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: The magnetization transfer ratio (MTR) is a sensitive and quantitative identifier of underlying structural changes in the brain. We quantitatively evaluated age- and sex-related MTR changes in global gray matter (GM) and global white matter (WM) in healthy adults. METHODS: Fifty-two healthy volunteers (21 men, 31 women) aged 20-86 years underwent dual-echo fast spin-echo and magnetization transfer imaging performed with and then without a saturation pulse. GM and WM were distinguished by using a computer-assisted semiautomated segmentation technique. MTR histograms were generated for each segmented tissue in each subject and compared among age and sex groups. RESULTS: The mean, median, first quartile, and peak height of the MTR histogram were significantly lower in the older group (> or =50 years) than those in the younger group (<50 years) for both GM and WM. The age dependency of these values can be expressed in a quadratic fashion over the entire span of adulthood. The MTRs started to decline only after the age of approximately 40 years in both tissues. No statistically significant differences in MTR histogram measurements between the sexes were observed. CONCLUSION: The different MTR values for both GM and WM in the two age groups suggest that notable microscopic changes occur in GM and WM with advancing age, yet no significant sex-related variations in MTR measurements were found in these neurologically healthy adults. Such normative data based on the inherent contrast in MTRs are essential in studies of specific disorders of aging, and they may have implications for our understanding of the gross structural changes in both GM and WM in the aging brain
— id: 43787, year: 2002, vol: 23, page: 1334, stat: Journal Article,

Magnetization transfer ratio histogram analysis of normal-appearing gray matter and normal-appearing white matter in multiple sclerosis
Ge, Yulin; Grossman, Robert I; Udupa, Jayaram K; Babb, James S; Mannon, Lois J; McGowan, Joseph C
2002 Jan-Feb;26(1):62-68, Journal of computer assisted tomography
PURPOSE: The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis. METHOD: Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group. RESULTS: Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p </= 0.0015). SP MS patients had a significantly lower first quartile and MTR histogram peak height for NAGM only (p </= 0.004) when compared with both RR MS patients and healthy subjects. The T2 lesion load had a modest negative correlation with MTR values in both RR and SP MS, but only in NAGM. CONCLUSION: Separate analysis of GM and WM MTR histograms may allow better detection of subtle damage and better understanding of the natural history of MS disease and ultimately the response to therapeutics
— id: 39727, year: 2002, vol: 26, page: 62, stat: Journal Article,

Proton magnetic resonance spectroscopy evidence for early gray matter involvement in relapsing remitting MS
Inglese, M; Ge, Y; Filippi, M; Falini, A; Grossman, RI; Gonen, O
2002 NOV ;225(1):429-429, Radiology
— id: 105103, year: 2002, vol: 225, page: 429, stat: Journal Article,

Evidence for early widespread gray matter involvement in relapsing remitting multiple sclerosis
Inglese, M; Ge, YL; Filippi, M; Falini, A; Grossman, RI; Gonen, O
2002 SEP ;52(3):S40-S40, Annals of neurology
— id: 105107, year: 2002, vol: 52, page: S40, stat: Journal Article,

Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV-infected patients
Patel, Sohil H; Kolson, Dennis L; Glosser, Guila; Matozzo, Isabel; Ge, Yulin; Babb, James S; Mannon, Lois J; Grossman, Robert I
2002 Apr;23(4):543-549, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: This study was designed to determine whether neuropsychological function in HIV-infected persons is correlated with loss of brain volume (as measured by percentage of brain parenchymal volume [PBV]). We hypothesized that whole-brain parenchymal volume might correlate with neuropsychologic performance, even before overt clinical dysfunction is apparent. METHODS: A computer-assisted segmentation technique with thin section MR imaging was used for 15 patients with HIV infection (seven symptomatic, eight asymptomatic) and for five HIV-negative control participants to quantify whole brain and CSF volumes. To determine the degree of brain atrophy, the PBV relative to that of intracranial content was calculated. Neuropsychological performance was assessed by using a standard battery of eight tests (NPZ-8 test battery). RESULTS: HIV-infected patients had significantly lower NPZ-8 scores (t[18] = 2.26, P <.05) and lower PBV (t[18] = 1.79, P <.01) than those of healthy control participants. With the Spearman rank order correlation coefficients, data analyzed for all 20 study participants (15 HIV-infected patients and five noninfected control participants) showed a significant (r = -0.50, P <.05) negative correlation between PBV and NPZ-8 test battery score. In addition, there was a significant negative correlation between subtest score of motor impairment and PBV (r = -0.69, P <.01) and between AIDS dementia complex score (r = -0.64) and PBV (P <.01). CONCLUSION: These correlations suggest that quantitation of PBV may offer an objective, easily acquired surrogate predictor of neuropsychological impairment and clinically apparent cognitive/motor dysfunction among HIV-infected persons
— id: 43789, year: 2002, vol: 23, page: 543, stat: Journal Article,

Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis
Ge Y; Grossman RI; Udupa JK; Babb JS; Kolson DL; McGowan JC
2001 Mar;22(3):470-475, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Gray matter may be affected by multiple sclerosis (MS), a white matter disease. Magnetization transfer ratio (MTR) is a sensitive and quantitative marker for structural abnormalities, and has been used frequently in the imaging of MS. In this study, we evaluated the amount of MTR of gray matter among patients with relapsing-remitting MS and healthy control subjects as well as the correlation between gray matter MTR abnormality and neurologic disability associated with relapsing-remitting MS. METHODS: We obtained fast spin-echo dual-echo and magnetization transfer (with and without MT saturation pulses) images from eighteen patients with relapsing-remitting MS and 18 age-matched healthy control subjects. Gray matter was segmented using a semiautomated system. Gray matter MTR histogram parameters, Kurtzke Expanded Disability Status Scale (EDSS), total T2 lesion volume, and gray matter volumes were obtained for statistical analysis. RESULTS: A significant difference was found in gray matter MTR between patients with relapsing-remitting MS and healthy subjects (mean and median). Gray matter MTR histogram normalized peak heights in patients inversely correlated with EDSS (r = -0.65, P =.01). There was also an inverse correlation between mean MTR of gray matter and total T2 lesion volume. CONCLUSION: The MTR of gray matter significantly differed between patients with relapsing-remitting MS and healthy control subjects, suggesting that MS is a more diffuse disease affecting the whole brain, and neuronal damage accumulates in step with T2 lesion volume. Our finding of the relationship between gray matter MTR and EDSS indicates that measurement of gray matter abnormality may be a potentially useful tool for assessing clinical disability in MS
— id: 24400, year: 2001, vol: 22, page: 470, stat: Journal Article,

Brain atrophy in relapsing-remitting multiple sclerosis: fractional volumetric analysis of gray matter and white matter
Ge Y; Grossman RI; Udupa JK; Babb JS; Nyul LG; Kolson DL
2001 Sep;220(3):606-610, Radiology
PURPOSE: To determine the fractional brain tissue volume changes in the gray matter and white matter of patients with relapsing-remitting multiple sclerosis (MS) and to correlate these measurements with clinical disability and total lesion load. MATERIALS AND METHODS: Thirty patients with relapsing-remitting MS and 25 healthy control subjects underwent magnetic resonance imaging. Fractional brain tissue volumes (tissue volume relative to total intracranial volume) were obtained from the total segmented gray matter and white matter in each group and were analyzed. RESULTS: The fractional volume of white matter versus that of gray matter was significantly lower (-6.4%) in patients with MS (P <.0001) than in control subjects. Neither gray matter nor white matter fractional volume measurements correlated with clinical disability in the patients with MS. CONCLUSION: Loss of brain parenchymal volume in patients with relapsing-remitting MS is predominantly confined to white matter. Analysis of fractional brain tissue volumes provides additional information useful in characterizing MS and may have potential in evaluating treatment strategies
— id: 24396, year: 2001, vol: 220, page: 606, stat: Journal Article,

Comparison between EPI and HASTE for ultra-fast MR imaging of the human brain
Ge, Y; Korogi, Y; Sugahara, T; Shigematsu, Y; Hirai, T; Kitajima, M; Liang, L; Dai, J; Takahashi, M
2001 Dec;43(12):1046-1055, Neuroradiology
Our purpose was to evaluate and compare the performance of ultra-fast single-shot T2-weighted sequences: echo-planar imaging (EPI) versus half-Fourier single-shot turbo spin-echo (HASTE) and to assess the usefulness of their combined reading. Comparative experiments on a phantom as well as a prospective clinical study in 47 patients were done. Axial images acquired with the following methods were compared: (a) HASTE; (b) segmented HASTE (s-HASTE); (c) single-shot spin-echo EPI (SE-EPI); and (d) gradient-echo EPI (GREEPI). Quantitative and qualitative criteria as well as lesion detectability were analyzed against the 'gold standard' fast spin-echo (FSE) sequence. For contrast and contrast-to-noise ratio (CNR) between gray and white matter, GRE-EPI was best. The visibility of small markedly hyperintense lesion was best with HASTE and s-HASTE in the clinical study. Small hyperintense lesions were detected equally well with all four sequences, although all performed significantly worse than FSE. The two HASTE variants were better than the EPIs for the extraaxial lesions. The combination of the GRE-EPI and s-HASTE was judged best, and sometimes superior to the FSE image. HASTE or EPI alone cannot substitute for FSE in the screening evaluation of the brain. However, together, EPI and HASTE could provide comparable diagnostic information to that of FSE because their combination compensates for their individual limitations
— id: 86626, year: 2001, vol: 43, page: 1046, stat: Journal Article,

Enhancing patterns in multiple sclerosis: evolution and persistence
He J; Grossman RI; Ge Y; Mannon LJ
2001 Apr;22(4):664-669, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Contrast enhancement on MR images of patients with multiple sclerosis (MS) is known to be associated with abnormalities of the blood-brain barrier (BBB). However, little is known about diagnostic patterns and common features of enhanced MS lesions. This study was designed to evaluate initial enhancement patterns, changes in these enhancing patterns, and duration of enhancement in a cohort of patients with MS. METHODS: Twenty-five patients with clinically definite MS were studied retrospectively. The appearance of enhancing lesions and sequential changes in the appearance on axial contrast-enhanced spin-echo images were evaluated. The enhancing lesions were classified as nodular, ringlike, or 'other' (eg, arclike). RESULTS: Of 301 new enhancing lesions, 205 (68%) showed nodular enhancement, 70 (23%) a ring pattern, and 26 (9%) a pattern neither nodular nor ringlike (eg, arclike). Two hundred eighty (93%) of 301 enhancing lesions disappeared within 6 months, and seven (2%) lesions showed persistent enhancement longer than 6 months. The other 14 (5%) lesions, which disappeared by the time of the next scan, were excluded, because the course between two examinations was longer than 6 months. Of nine persisting nodular enhancing lesions on the follow-up images, seven were decreased in size, whereas all of two persisting ringlike enhancing lesions on the follow-up images were larger than before. CONCLUSION: Nodular enhancement is the predominant enhancement pattern for new MS lesions, and the temporal course of enhancement is usually shorter than 6 months. The appreciation of the evolution of MS-enhanced lesions aids in both identifying new MS lesions and distinguishing these lesions from other pathologic entities. This may be helpful in clinically evaluating the stage of MS lesions
— id: 24397, year: 2001, vol: 22, page: 664, stat: Journal Article,

Investigation of global absolute N-acetyl aspartate levels in Alzheimer's disease
McGowan, JC; Clark, CC; Ge, Y; Udupa, J; Grossman, RI; Gonen, O
2001 MAR-APR ;22(2):33-33, Neurobiology of aging
— id: 105111, year: 2001, vol: 22, page: 33, stat: Journal Article,

Electron capture dissociation of gaseous multiply charged ions by Fourier-transform ion cyclotron resonance
McLafferty FW; Horn DM; Breuker K; Ge Y; Lewis MA; Cerda B; Zubarev RA; Carpenter BK
2001 Mar;12(3):245-249, Journal of the American Society for Mass Spectrometry
Fourier-transform ion cyclotron resonance instrumentation is uniquely applicable to an unusual new ion chemistry, electron capture dissociation (ECD). This causes nonergodic dissociation of far larger molecules (42 kDa) than previously observed (<1 kDa), with the resulting unimolecular ion chemistry also unique because it involves radical site reactions for similarly larger ions. ECD is highly complementary to the well known energetic methods for multiply charged ion dissociation, providing much more extensive protein sequence information, including the direct identification of N- versus C-terminal fragment ions. Because ECD only excites the molecule near the cleavage site, accompanying rearrangements are minimized. Counterintuitively, cleavage of backbone covalent bonds of protein ions is favored over that of noncovalent bonds; larger (>10 kDa) ions give far more extensive ECD if they are first thermally activated. This high specificity for covalent bond cleavage also makes ECD promising for studying the secondary and tertiary structure of gaseous protein ions caused by noncovalent bonding
— id: 24398, year: 2001, vol: 12, page: 245, stat: Journal Article,

Multiprotocol MR image segmentation in multiple sclerosis: experience with over 1,000 studies
Udupa JK; Nyul LG; Ge Y; Grossman RI
2001 Nov;8(11):1116-1126, Academic radiology
RATIONALE AND OBJECTIVES: Multiple sclerosis (MS) is an acquired disease of the central nervous system. Several clinical measures are commonly used to express the severity of the disease, including the Expanded Disability Status Scale and the ambulation index. These measures are subjective and may be difficult to reproduce. The aim of this research is to investigate the possibility of developing more objective measures derived from MR imaging. MATERIALS AND METHODS: Various magnetic resonance (MR) imaging protocols are being investigated for the study of MS. Seeking to replace the Expanded Disability Status Scale and ambulation index with an objective means to assess the natural course of the disease and its response to therapy, the authors have developed multiprotocol MR image segmentation methods based on fuzzy connectedness to quantify both macrosopic features of the disease (lesions, gray matter, white matter, cerebrospinal fluid, and brain parenchyma) and the microscopic appearance of diseased white matter. Over 1,000 studies have been processed to date. RESULTS: By far the strongest correlations with the clinical measures were demonstrated by the magnetization transfer ratio histogram parameters obtained for the various segmented tissue regions. These findings emphasize the importance of considering the microscopic and diffuse nature of the disease in the individual tissue regions. Brain parenchymal volume also demonstrated a strong correlation with clinical measures, which suggests that brain atrophy is an important disease indicator. CONCLUSION: Fuzzy connectedness is a viable, highly reproducible segmentation method for studying MS
— id: 24395, year: 2001, vol: 8, page: 1116, stat: Journal Article,

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment
Ge Y; Grossman RI; Udupa JK; Fulton J; Constantinescu CS; Gonzales-Scarano F; Babb JS; Mannon LJ; Kolson DL; Cohen JA
2000 Feb 22;54(4):813-817, Neurology
OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS
— id: 43792, year: 2000, vol: 54, page: 813, stat: Journal Article,

Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis
Ge Y; Grossman RI; Udupa JK; Wei L; Mannon LJ; Polansky M; Kolson DL
2000 Mar;214(3):665-670, Radiology
PURPOSE: To determine annual rates of volumetric changes in the whole-brain parenchyma of patients with relapsing-remitting and secondary progressive multiple sclerosis (MS) and test the hypothesis that these changes correlate with clinical disability. MATERIALS AND METHODS: A computer-assisted segmentation technique with thin-section magnetic resonance (MR) imaging was used in 36 patients with MS (27 relapsing-remitting, nine secondary progressive) and in 20 control subjects to quantify brain and cerebrospinal fluid volumes. To determine the degree of brain atrophy, the percentage brain parenchyma volume (PBV) relative to that of intracranial contents was calculated. RESULTS: At the beginning of the study, the PBV was smaller in the MS group than in the control group (P = .007); brain parenchyma volumes were similar. The median rate of brain volume loss was 17.3 mL per year in patients with relapsing-remitting MS and 23.6 mL per year in those with secondary progressive MS. There was a negative correlation between brain atrophy and Expanded Disability Status Scale (EDSS) score in patients with secondary progressive MS (r = -0.69, P = .004) and no correlation in patients with relapsing-remitting MS. T2 lesion volume did not correlate with brain atrophy in either group. CONCLUSION: The correlation between brain atrophy and EDSS score was better in patients with secondary progressive MS than in those with relapsing-remitting MS
— id: 43791, year: 2000, vol: 214, page: 665, stat: Journal Article,

Numerical tissue characterization in MS via standardization of the MR image intensity scale
Ge Y; Udupa JK; Nyul LG; Wei L; Grossman RI
2000 Nov;12(5):715-721, Journal of magnetic resonance imaging
Image intensity standardization is a recently developed postprocessing method that is capable of correcting the signal intensity variations in MR images. We evaluated signal intensity of healthy and diseased tissues in 10 multiple sclerosis (MS) patients based on standardized dual fast spin-echo MR images using a numerical postprocessing technique. The main idea of this technique is to deform the volume image histogram of each study to match a standard histogram and to utilize the resulting transformation to map the image intensities into standard scale. Upon standardization, the coefficients of variation of signal intensities for each segmented tissue (gray matter, white matter, lesion plaques, and diffuse abnormal white matter) in all patients were significantly smaller (2.3-9.2 times) than in the original images, and the same tissues from different patients looked alike, with similar intensity characteristics. Numerical tissue characterizability of different tissues in MS achieved by standardization offers a fixed tissue-specific meaning for the numerical values and can significantly facilitate image segmentation and analysis
— id: 24403, year: 2000, vol: 12, page: 715, stat: Journal Article,

Total brain N-acetylaspartate: a new measure of disease load in MS
Gonen O; Catalaa I; Babb JS; Ge Y; Mannon LJ; Kolson DL; Grossman RI
2000 Jan 11;54(1):15-19, Neurology
OBJECTIVE: To quantitate the extent of neuronal cell loss in MS via the whole brain's N-acetylaspartate (NAA) concentration (WBNAA). METHODS: Because NAA is assumed to be present only in neuronal cell bodies and their axons, we measured WBNAA as a marker for viable neurons in 12 patients (9 women and 3 men, 26 to 53 years of age) suffering from relapsing-remitting (RR) MS for at least 5 years and compared them with 13 age- and sex-matched normal controls. Total brain NAA was determined with proton MR spectroscopy, and WBNAA was obtained by dividing it by the total brain volume, calculated from high resolution MRI. RESULTS: The WBNAA of the RR MS patients was lower than their matched controls (p<0.005). This difference was greater among older than younger subjects. The linear prediction equations of WBNAA with age indicate a faster, x10, decline in the patients, approximately 0.8% per year of age (p = 0.022). CONCLUSION: The age-dependent decrease of whole brain N-acetylaspartate (WBNAA) in the patients suggests that progressive neuronal cell loss is a cardinal feature of this disease. WBNAA offers a quick, highly reproducible measure of disease progression and may be an important marker of treatment efficacy in MS as well as other neurodegenerative diseases
— id: 27737, year: 2000, vol: 54, page: 15, stat: Journal Article,

The effect of gadolinium-enhancing lesions on whole brain atrophy in relapsing-remitting MS
Saindane AM; Ge Y; Udupa JK; Babb JS; Mannon LJ; Grossman RI
2000 Jul 12;55(1):61-65, Neurology
OBJECTIVE: To determine the relationship between gadolinium-enhancing lesions and changes in whole brain parenchymal volume in patients with relapsing-remitting MS, and to test the hypothesis that gadolinium enhancement is a predictor of whole brain atrophy. METHODS: Twenty-four patients with clinically definite MS were imaged over 2 years. A computer-assisted segmentation technique based on high-resolution MRI was used to quantify gadolinium-enhancing T1 lesion volume and brain parenchyma and CSF volumes. Percent brain parenchymal volume (PBV) relative to the total intracranial volume was calculated, and changes in PBV were used to represent the degree of whole brain atrophy over 2 years. RESULTS: PBV at baseline was dependent on duration of MS, and a significant decrease in PBV was observed over the course of the study. Changes in enhanced T1 lesion load failed to correlate with changes in PBV, and multiple regression analyses determined that enhanced T1 lesion load at baseline was not a significant predictor of subsequent change in PBV. CONCLUSIONS: MR visible inflammation as demonstrated by enhanced T1 lesions is not a significant factor in the pathogenesis of whole brain atrophy in relapsing-remitting MS, suggesting that a more global pathologic process is responsible for the loss of brain parenchymal volume
— id: 43790, year: 2000, vol: 55, page: 61, stat: Journal Article,

Contrast enhancement of intracranial lesions: conventional T1-weighted spin-echo versus fast spin-echo MR imaging techniques
Sugahara, T; Korogi, Y; Ge, Y; Shigematsu, Y; Liang, L; Yoshizumi, K; Kitajima, M; Takahashi, M
1999 Sep;20(8):1554-1559, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: The T1-weighted fast spin-echo (T1-FSE) MR imaging sequence is not used routinely, since the speed advantage is not as dramatic as it is in T2-weighted imaging. We evaluated the T1-FSE sequence to determine whether this technique can replace the conventional T1-weighted spin-echo (T1-SE) sequence for routine contrast-enhanced imaging. METHODS: Sixty-nine patients with intracranial enhancing lesions underwent both T1-SE and T1-FSE sequences in a random order after administration of contrast agent. Acquisition time was 55 seconds for the T1-FSE sequence and 2 minutes 38 seconds for the SE sequence. The conspicuity of enhancing lesions, peritumoral edema, and gray-to-white matter contrast as well as motion and flow artifacts were analyzed. Signal-to-noise ratios of enhancing lesions, gray matter, and white matter as well as contrast-to-noise ratios (CNRs) of enhancing lesions, with gray matter with white matter as the standard, were calculated. RESULTS: The conspicuity of enhancing lesions was better on T1-FSE sequences than on T1-SE sequences, although the difference in the CNRs of enhancing lesions did not reach significance. Images obtained with the T1-FSE sequence showed less flow and motion artifacts than did those obtained with the T1-SE sequence. The conspicuity of peritumoral edema and gray-to-white matter contrast was lower on the T1-FSE images than on the T1-SE images. CONCLUSION: The T1-FSE sequence reduces imaging time and has the potential to replace the conventional T1-SE sequence for the evaluation of enhancing lesions in the brain when time is a consideration
— id: 86627, year: 1999, vol: 20, page: 1554, stat: Journal Article,

Usefulness of diffusion-weighted MRI with echo-planar technique in the evaluation of cellularity in gliomas
Sugahara, T; Korogi, Y; Kochi, M; Ikushima, I; Shigematu, Y; Hirai, T; Okuda, T; Liang, L; Ge, Y; Komohara, Y; Ushio, Y; Takahashi, M
1999 Jan;9(1):53-60, Journal of magnetic resonance imaging
The purpose of this study was to evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) with echo-planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2-weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2-weighted images. The minimum ADC of the high-grade gliomas was significantly higher than that of the low-grade gliomas. Diffusion-weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas
— id: 86628, year: 1999, vol: 9, page: 53, stat: Journal Article,

Virtual MRI endoscopy of the intracranial cerebrospinal fluid spaces
Shigematsu, Y; Korogi, Y; Hirai, T; Okuda, T; Ikushima, I; Sugahara, T; Liang, L; Ge, Y; Takahashi, M
1998 Oct;40(10):644-650, Neuroradiology
We used constructive interference in steady state (CISS) 3D Fourier transform (3DFT) MRI data sets to obtain three-dimensional (3D) virtual MRI endoscopic views of the intracranial cerebrospinal fluid (CSF) spaces, processing them with a commercially available perspective endoscopic algorithm. We investigated the potential of the intracranial virtual MRI endoscopy applied to visualisation of the pathology in 13 patients with surgically confirmed trigeminal neuralgia (3), hemifacial spasm (3), acoustic neuroma (3), suprasellar germinoma (1), Langerhans cell histiocytosis (1), lateral ventricle nodules (1) and pituitary dwarfism (1). All images were acquired using a 1.5-T imager employing a circular polarised head coil. The CISS-3DFT data sets were transferred to a workstation for processing with the perspective endoscopic algorithm. Postprocessing for virtual MRI endoscopy was possible for all data sets. The lesions in 12 patients, and their complex anatomical relationships with the surrounding structures, were well seen on the 3D images. A small acoustic neuroma in the internal auditory meatus was not seen using virtual endoscopy. Although virtual MRI endoscopy has limitations, it provides 3D images which cannot be acquired using any other procedure
— id: 86630, year: 1998, vol: 40, page: 644, stat: Journal Article,

III. New developments: 2. Virtual MR endoscopy in the central nervous system
Shigematsu, Y; Korogi, Y; Hirai, T; Okuda, T; Sugahara, T; Liang, L; Ge, Y; Takahashi, M
1998 Mar-Apr;8(2):289-296, Journal of magnetic resonance imaging
Recent advances in three-dimensional (3D) data acquisition and postprocessing technologies have been playing a important role in widening the potential applications of 3D display. The authors described new applications of a virtual endoscopic algorithm for 3D display of high resolution MR images: (a) intracranial intravascular virtual MR endoscopy using the 3D fast imaging with steady state precession (FISP) sequence, and (b) virtual MR endoscopy of the cerebrospinal fluid (CSF) spaces using the constructive interference in steady state (CISS) three-dimensional Fourier transform (3DFT) sequence. The virtual endoscopic images were displayed with use of a commercially available perspective volume-rendering algorithm. Our initial experience showed that virtual MR endoscopy can be performed to observe the intracranial arteries and CSF spaces from the viewpoints within themselves. Although the clinical use of the intracranial virtual MR endoscopy has not been established yet, the images obtained are very attractive and further investigations in this field will be expected
— id: 86631, year: 1998, vol: 8, page: 289, stat: Journal Article,

Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas
Sugahara, T; Korogi, Y; Kochi, M; Ikushima, I; Hirai, T; Okuda, T; Shigematsu, Y; Liang, L; Ge, Y; Ushio, Y; Takahashi, M
1998 Dec;171(6):1479-1486, American journal of roentgenology
OBJECTIVE: Our purpose was to evaluate the relationships between the ratio of maximum relative cerebral blood volume (rCBV) (rCBV ratio = rCBV[tumor]/rCBV[contralateral white matter]) and histologic and angiographic vascularities of gliomas using the gradient-echo echoplanar MR imaging technique. We also evaluated the usefulness of rCBV maps for grading gliomas. SUBJECTS AND METHODS: We examined 30 patients with histologically verified gliomas. Gliomas were classified as glioblastoma, anaplastic glioma with enhancement, anaplastic glioma without enhancement, and low-grade glioma. The maximum rCBV ratio of each glioma was compared with both histologic and angiographic vascularities, and the relationship between the maximum rCBV ratios and each type of glioma was established. RESULTS: The maximum rCBV ratios of the gliomas significantly correlated with both histologic and angiographic vascularities (p < .001). Mean values and SDs of maximum rCBV ratios of each type of tumor were 7.32+/-4.39 for glioblastomas, 5.84+/-1.82 for anaplastic gliomas with enhancement, 1.53+/-0.75 for anaplastic gliomas without enhancement, and 1.26+/-0.55 for low-grade gliomas. The maximum rCBV ratios of the glioblastomas were significantly higher than those of the anaplastic gliomas without enhancement (p = .002) and the low-grade gliomas (p < .001). The maximum rCBV ratios of the anaplastic gliomas with enhancement were higher than those of the anaplastic gliomas without enhancement and the low-grade gliomas, but the differences were not statistically significant (p = .08 and p = .03, respectively). CONCLUSION: The results of perfusion-sensitive MR imaging with gradient-echo echoplanar technique correlated with both histologic and angiographic vascularities
— id: 86629, year: 1998, vol: 171, page: 1479, stat: Journal Article,