Edmond A Knopp, M.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,

Magnetic resonance dynamic susceptibility-weighted contrast-enhanced perfusion imaging in the diagnosis of posterior fossa hemangioblastomas and pilocytic astrocytomas: initial results
Kumar, Vinodh A; Knopp, Edmond A; Zagzag, David
2010 Nov-Dec;34(6):825-829, Journal of computer assisted tomography
OBJECTIVE:: The purpose of this study was to compare the dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance (MR) perfusion and MR imaging findings between hemangioblastomas and pilocytic astrocytoma (PA). METHODS:: We retrospectively identified 6 patients with hemangioblastomas and 8 patients with PAs who underwent MR imaging before resection. Using fluid-attenuated inversion-recovery imaging, we graded peritumoral edema as absent, minimal, mild, moderate, or severe. In addition, 3 patients with hemangioblastomas and 4 patients with PAs underwent DSC-MR imaging before resection. RESULTS:: We observed moderate to severe peritumoral edema in 6 patients with hemangioblastomas and none or minimal peritumoral edema in 8 patients with PAs. The mean relative cerebral blood volume was 7.7 (SD, 1.0) in patients with hemangioblastomas and 1.8 (SD, 1.8) in patients with PAs. CONCLUSIONS:: Our preliminary findings demonstrate significantly higher DSC-MR imaging relative cerebral blood volumes in patients with hemangioblastomas when compared with patients with PAs. In addition, moderate to severe peritumoral edema was associated with hemangioblastomas
— id: 114593, year: 2010, vol: 34, page: 825, stat: Journal Article,

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma
Narayana A; Kunnakkat SD; Medabalmi P; Golfinos J; Parker E; Knopp E; Zagzag D; Eagan P; Gruber D; Gruber ML
2010 Jan 1;82(1):77-82, International journal of radiation oncology biology physics
PURPOSE: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. METHODS AND MATERIALS: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. RESULTS: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R(2) = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). CONCLUSION: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials
— id: 138155, year: 2010, vol: 82, page: 77, stat: Journal Article,

INVASION AS A DOMINANT FEATURE OF FAILURE PATTERN IN HIGH-GRADE GLIOMAS FOLLOWING BEVACIZUMAB THERAPY
Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Gruber, Deborah; Gruber, Michael L.
2010 NOV ;12(2):3-3, Neuro-oncology
— id: 122727, year: 2010, vol: 12, page: 3, stat: Journal Article,

Magnetic field correlation as a measure of iron-generated magnetic field inhomogeneities in the brain
Jensen, Jens H; Szulc, Kamila; Hu, Caixia; Ramani, Anita; Lu, Hanzhang; Xuan, Liang; Falangola, Maria F; Chandra, Ramesh; Knopp, Edmond A; Schenck, John; Zimmerman, Earl A; Helpern, Joseph A
2009 Feb;61(2):481-485, Magnetic resonance in medicine
The magnetic field correlation (MFC) at an applied field level of 3 Tesla was estimated by means of MRI in several brain regions for 21 healthy human adults and 1 subject with aceruloplasminemia. For healthy subjects, highly elevated MFC values compared with surrounding tissues were found within the basal ganglia. These are argued as being primarily the result of microscopic magnetic field inhomogeneities generated by nonheme brain iron. The MFC in the aceruloplasminemia subject was significantly higher than for healthy adults in the globus pallidus, thalamus and frontal white matter, consistent with the known increased brain iron concentration associated with this disease
— id: 95730, year: 2009, vol: 61, page: 481, 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,

High-grade glioma before and after treatment with radiation and Avastin: initial observations
Fischer, Ingeborg; Cunliffe, Clare H; Bollo, Robert J; Raza, Shahzad; Monoky, David; Chiriboga, Luis; Parker, Erik C; Golfinos, John G; Kelly, Patrick J; Knopp, Edmond A; Gruber, Michael L; Zagzag, David; Narayana, Ashwatha
2008 Oct;10(5):700-708, Neuro-oncology
We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent 'normalization' after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers
— id: 91374, year: 2008, vol: 10, page: 700, stat: Journal Article,

Change in pattern of relapse following anti-angiogenic therapy in high grade glioma
Narayana, A; Golfinos, JG; Raza, S; Knopp, E; Medabalmi, P; Parker, E; Kelly, P; Zagzag, D; Gruber, M
2008 AUG ;72(1):S11-S11, International journal of radiation oncology biology physics
— id: 86794, year: 2008, vol: 72, page: S11, stat: Journal Article,

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma
Narayana, Ashwatha; Golfinos, John G; Fischer, Ingeborg; Raza, Shahzad; Kelly, Patrick; Parker, Erik; Knopp, Edmond A; Medabalmi, Praveen; Zagzag, David; Eagan, Patricia; Gruber, Michael L
2008 Oct 1;72(2):383-389, International journal of radiation oncology biology physics
INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely
— id: 91373, year: 2008, vol: 72, page: 383, 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,

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,

Comparing real-world advantages for the clinical neuroradiologist between a high field (3 T), a phased array (1.5 T) vs. a single-channel 1.5-T MR system
Orbach, Darren B; Wu, Chris; Law, Meng; Babb, James S; Lee, Ray; Padua, Abraham; Knopp, Edmond A
2006 Jul;24(1):16-24, Journal of magnetic resonance imaging
PURPOSE: To evaluate signal-to-noise ratio (SNR) and neuroradiologists' subjective assessments of image quality in 3-Tesla (3-T) or phased-array MR systems that are now available for clinical neuroimaging. MATERIALS AND METHODS: Brain MR images of six normal volunteers were obtained on each of three scanners: a 1.5-T single-channel system, a 12-channel, phased-array system, and a 3-T single-channel system. Additionally, clinically optimized images acquired from 28 patients who underwent imaging in more than one of these systems were analyzed. SNRs were measured and image quality and artifact conspicuity were graded by two blinded readers. RESULTS: The phased-array system produced higher SNR than either the 1.5-T or the 3-T single-channel systems, and in no instance was it outperformed. Both blinded readers judged the phased-array images to be of higher quality than those produced by the single-channel systems, with significantly less artifact. The 3-T magnet produced images with high SNR, but with increased artifact conspicuity. The phased-array system markedly decreased acquisition times without introduction of artifacts. CONCLUSION: Both quantitatively and qualitatively, the phased-array system provided image quality superior to that of the 1.5-T and 3-T single-channel systems
— id: 68591, year: 2006, vol: 24, page: 16, stat: Journal Article,

Results of surgical resection for progression of brain metastases previously treated by gamma knife radiosurgery
Truong, Minh T; St Clair, Eric G; Donahue, Bernadine R; Rush, Stephen C; Miller, Douglas C; Formenti, Silvia C; Knopp, Edmond A; Han, Kerry; Golfinos, John G
2006 Jul;59(1):86-97, Neurosurgery
OBJECTIVE: To determine treatment outcome after surgical resection for progressive brain metastases after gamma knife radiosurgery (GKR) and to explore the role of dynamic contrast agent-enhanced perfusion magnetic resonance imaging (MRI) and proton spectroscopic MRI studies (MRS/P) in predicting pathological findings. METHODS: Between 1997 and 2002, 32 patients underwent surgical resection for suspected progression of brain metastases from a cohort of 245 patients with brain metastases treated with GKR. Postradiosurgery MRI surveillance was performed at 6 and 12 weeks, and then every 12 weeks after GKR. In some cases, additional MRI scanning with spectroscopy or perfusion (MRS/P) was used to aid differentiation of radiation change from tumor progression. The decision to perform neurosurgical resection was based on MRI or clinical evidence of lesion progression among patients with a Karnofsky performance score of 60 or more and absent or stable systemic disease. RESULTS: Thirteen percent (32 out of 245) of patients and 6% (38 out of 611) of lesions required surgical resection after GKR. The median time from GKR to surgical resection was 8.6 months (range, 1.7-27.1 mo). The 6-, 12-, and 24-month actuarial survival from time of GKR was 97, 78, and 47% for the resected patients and 65, 40, and 19% for the nonresected patients (P < 0.0001). The two-year survival rate of patients requiring two resections after GKR was 100% compared with 39% for patients undergoing one resection (P = 0.02). The median survival of resected patients was 27.2 months (range, 7.0-72.5 mo) from the diagnosis of brain metastases, 19.9 months (range, 5.0-60.7 mo) from GKR, and 8.9 months (range, 0.2-53.1 mo) from surgical resection. Tumor was found in 90% of resected specimens and necrosis alone in 10%. MRS/P studies were performed in 15 resected patients. Overall, MRS/P predicted tumor in 11 lesions, confirmed pathologically in nine lesions, and necrosis alone was found in two. The MRS/P predicted necrosis alone in three, whereas pathology revealed viable tumor in two and necrosis in one lesion. CONCLUSION: Surgical intervention of progressive brain metastases after GKR in selected patients leads to a meaningful improvement in survival rates. Further studies are necessary to determine the role of MRS/P in the postradiosurgery surveillance of brain metastases
— id: 67932, year: 2006, vol: 59, page: 86, stat: Journal Article,

Brain MRI: tumor evaluation
Young, Robert J; Knopp, Edmond A
2006 Oct;24(4):709-724, Journal of magnetic resonance imaging
The designation 'brain tumors' is commonly applied to a wide variety of intracranial mass lesions that are distinct in their location, biology, treatment, and prognosis. Since many of these lesions do not arise from brain parenchyma, the more appropriate term would be 'intracranial tumors.' The term 'tumor' is used to include both neoplastic and non-neoplastic mass lesions, and should be considered in its broadest sense to simply indicate a space-occupying mass. This review describes an imaging-based approach for evaluating intracranial tumors. Conventional MRI is discussed in the setting of a regional classification system. This system provides a framework for analysis, and imaging clues can then be applied to narrow the differential possibilities. Emphasis is placed on advanced MRI techniques and their utility for deciphering common diagnostic problems
— id: 68892, year: 2006, vol: 24, page: 709, stat: Journal Article,

Assessing global invasion of newly diagnosed glial tumors with whole-brain proton MR spectroscopy
Cohen, Benjamin A; Knopp, Edmond A; Rusinek, Henry; Babb, James S; Zagzag, David; Gonen, Oded
2005 Oct;26(9):2170-2177, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Because of their invasive nature, high-grade glial tumors are uniformly fatal. The purpose of this study was to quantify MR imaging-occult, glial tumor infiltration beyond its radiologic margin through its consequent neuronal cell damage, assessed by the global concentration decline of the neuronal marker N-acetylaspartate (NAA). METHODS: Seventeen patients (10 men; median age, 39 years; age range, 23-79 years) with radiologically suspected (later pathologically confirmed) supratentorial glial neoplasms, and 17 age- and sex-matched controls were studied. Their whole-brain NAA (WBNAA) amounts were obtained with proton MR spectroscopy: for patients on the day of surgery (n = 17), 1 day postsurgery (n = 15), and once for each control. To convert into concentrations, suitable for intersubject comparison, patients' global NAA amounts were divided by their brain volumes segmented from MR imaging. Least squares regression was used to analyze the data. RESULTS: Pre- and postoperative WBNAA (mean +/- SD) of 9.2 +/- 2.1 and 9.7 +/- 1.8 mmol/L, respectively, in patients were indistinguishable (P = .369) but significantly lower than in controls (12.5 +/- 1.4 mmol/L). Mean resected tumor size (n = 15) was approximately 3% of total brain volume. CONCLUSION: The average 26% WBNAA deficit in the patients, which persisted following surgical resection, cannot be explained merely by depletion within the approximately 3% MR imaging-visible tumor volume or an age-dependent effect. Although there could be several possible causes of such widespread decline--perineuronal satellitosis, neuronal deafferentation, Wallerian and retrograde degeneration, vasogenic edema, functional diaschisis, secondary vascular changes--most are a direct or indirect reflection of extensive, MR imaging-occult, microscopic tumor cell infiltration, diffusely throughout the otherwise 'normal-appearing' brain
— id: 61241, year: 2005, vol: 26, page: 2170, stat: Journal Article,

Brain compression without global neuronal loss in meningiomas: whole-brain proton MR spectroscopy report of 2 cases
Cohen, Benjamin A; Knopp, Edmond A; Rusinek, Henry; Liu, Songtao; Gonen, Oded
2005 Oct;26(9):2178-2182, AJNR. American journal of neuroradiology
We report the findings from whole-brain proton MR spectroscopy, quantifying the neuronal marker N-acetylaspartate (NAA), for 2 presurgical meningioma patients and 10 healthy controls. The patients' whole-brain NAA (WBNAA) concentrations were considerably elevated (3+ SDs) compared with healthy controls when excluding the tumors from brain volume; WBNAA levels normalized following correction to approximate 'preneoplastic' brain size. These results suggest global neuronal preservation in these 2 patients while their brains were compressed by large, slowly growing, extra-axial masses
— id: 61240, year: 2005, vol: 26, page: 2178, stat: Journal Article,

Neuroimaging of metastatic brain disease
Young, Robert J; Sills, Allen K; Brem, Steven; Knopp, Edmond A
2005 Nov;57(5 Suppl):S10-S23, Neurosurgery
This review discusses imaging techniques for the diagnosis, treatment, and monitoring of brain metastases. It assesses the various modalities on the basis of their respective advantages and limitations. Recent advances in imaging technologies provide evaluation that is more accurate for tumor localization, morphology, physiology, and biology. When used in combination, these technologies provide clinicians with a powerful diagnostic and prognostic tool for managing metastatic brain disease
— id: 62740, year: 2005, vol: 57, page: S10, stat: Journal Article,

Newly diagnosed high-risk malignant brain tumors with leptomeningeal dissemination in young children: Response to "head start" induction chemotherapy intensified with high-dose methotrexate
Chi, SN; Gardner, S; Levy, AS; Knopp, EA; Miller, DC; Wisoff, JH; Weiner, HL; Finlay, JL
2004 OCT ;6(4):451-451, Neuro-oncology
— id: 48920, year: 2004, vol: 6, page: 451, stat: Journal Article,

Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma
Chi, Susan N; Gardner, Sharon L; Levy, Adam S; Knopp, Edmond A; Miller, Douglas C; Wisoff, Jeffrey H; Weiner, Howard L; Finlay, Jonathan L
2004 Dec 15;22(24):4881-4887, Journal of clinical oncology
PURPOSE: To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas. PATIENTS AND METHODS: From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk x three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d x 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue. RESULTS: Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively. CONCLUSION: This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies
— id: 47907, year: 2004, vol: 22, page: 4881, stat: Journal Article,

Brain tumor M
Knopp EA
2004 ;15(5):277-277, Topics in magnetic resonance imaging
— id: 47910, year: 2004, vol: 15, page: 277, 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,

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,

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,

Importance of MR technique for stereotactic radiosurgery
Donahue, Bernadine R; Goldberg, Judith D; Golfinos, John G; Knopp, Edmond A; Comiskey, Jessica; Rush, Stephen C; Han, Kerry; Mukhi, Vandana; Cooper, Jay S
2003 Oct;5(4):268-274, Neuro-oncology
We investigated how frequently the imaging procedure we use immediately prior to radiosurgery--triple-dose gadolinium-enhanced MR performed with the patient immobilized in a nonrelocatable head frame and 1-mm-thick MPRAGE (magnetization-prepared rapid gradient echo) images (SRS3xGado)-identifies previously unrecognized cerebral metastases in patients initially imaged by conventional MR with single-dose gadolinium (1xGado). Between July 1998 and July 2000, the diagnoses established for 47 patients who underwent radio-surgical procedures for treatment of cerebral metastases at The Gamma Knife Center of New York University were based initially on the 1xGado protocol. In July 1998, we began using SRS3xGado as our routine imaging protocol in preparation for targeting lesions for radio-surgery, using triple-dose gadolinium and acquisition of contiguous 1-mm Tl-weighted axial images. Because our SRS3xGado scans sometimes unexpectedly revealed additional metastases, we sought to learn how frequently the initial 1xGado scans would underestimate the number of metastases. We therefore reviewed the number of brain metastases identified on the SRS3xGado studies and compared the results to the number found by the 1xGado protocol, which had initially identified the brain metastases. Additional metastases, ranging from 1 to 23 lesions per patient, were identified on the SRS3xGado scan in 23 of 47 patients (49%). In 57% of the 23 patients, only one additional lesion was identified. The mean time interval between the 1xGado and the SRS3xGado scans was 20.6 days (range, 4-83 days), and the number of additional lesions detected and the time interval between two scans were negatively correlated (-0.11). The number of lesions detected on the SRS3xGado was associated only with the number of lesions on the 1xGado and not with any other patient or tumor pretreatment characteristics such as age, gender, largest tumor volume on the 1xGado, or number of days between the 1xGado and the SRS3xGado or prior surgery. The identification of additional lesions with SRS3xGado MR may have implications for patients who are treated with stereotactic radiosurgery alone (without whole-brain irradiation) with single-dose gadolinium imaging, in that unidentified lesions may go untreated. As a result of these findings we continue to use and advocate SRS3xGado scans for radiosurgery
— id: 42023, year: 2003, vol: 5, page: 268, stat: Journal Article,

Temozolomide is active in childhood, progressive, unresectable, low-grade gliomas
Kuo, Dennis J; Weiner, Howard L; Wisoff, Jeffrey; Miller, Douglas C; Knopp, Edmond A; Finlay, Jonathan L
2003 May;25(5):372-378, Journal of pediatric hematology/oncology
PURPOSE: To assess the activity and tolerability of temozolomide in children with progressive low-grade gliomas (LGGs). PATIENTS AND METHODS: The authors reviewed the records of 13 children (6 months to 19 years old) with progressive LGGs and magnetic resonance imaging evidence of unresectable tumors who were treated with temozolomide at the authors' institution since 1999. RESULTS: Four patients received a 5-day regimen of temozolomide (150 mg/m2 per day) repeated every 28 days, and nine patients received a 42-day regimen (75 mg/m2 per day) repeated every 56 days. Three patients demonstrated partial responses to temozolomide, with a median time to maximal response of 5 months (range 4-12 months), and one had a minor response at 9 months. Four patients developed progression while on temozolomide, with a median time to progression of 7 months (range 1-12 months). Five patients had disease stabilization. Among the five patients with prior chemotherapy and/or radiation therapy, temozolomide was associated with disease stabilization in three and tumor response in one. In the three patients with neurofibromatosis type 1, two patients experienced tumor responses and one disease stabilization. Thrombocytopenia, nausea, emesis, and fatigue were the most common toxicities. Four patients discontinued therapy because of the side effects. CONCLUSIONS: Temozolomide is active in children with LGGs. It is effective in previously treated patients and in patients with neurofibromatosis type 1. The 42-day regimen appears less toxic than the 5-day regimen. Any impact on survival for these patients remains to be demonstrated
— id: 44852, year: 2003, vol: 25, page: 372, 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,

Dynamic contrast enhanced perfusion MRI in mycosis fungoides
Law, Meng; Teicher, Noah; Zagzag, David; Knopp, Edmond A
2003 Sep;18(3):364-367, Journal of magnetic resonance imaging
Mycosis fungoides is a malignant, cutaneous lymphoma of T-helper (TH or CD4+) cells. At presentation, the disease is usually limited to the skin, with lesions that resemble eczema or psoriasis. Neurologic involvement is uncommon. This case demonstrates the conventional MRI and dynamic contrast enhanced perfusion MRI findings in intracerebral mycosis fungoides. T1-weighted spin echo imaging demonstrated a lesion with slightly decreased signal within the body of the corpus callosum. The lesion was isointense with grey matter on axial T2-weighted imaging. Following administration of contrast, there was patchy heterogeneous enhancement. Multiple relative cerebral blood volume (rCBV) measurements were made and the minimum rCBV was 0.30 with the maximum rCBV being 1.61. The mean rCBV was 0.81 +/- 0.49 (average of 10 measurements and standard deviation)
— id: 44786, year: 2003, vol: 18, page: 364, 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,

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,

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,

Proton MR spectroscopy of tumefactive demyelinating lesions
Saindane, Amit M; Cha, Soonmee; Law, Meng; Xue, Xiaonan; Knopp, Edmond A; Zagzag, David
2002 Sep;23(8):1378-1386, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Tumefactive demyelinating lesions (TDLs) can simulate intracranial neoplasms in clinical presentation and MR imaging appearance, and surgical biopsy is often performed in suspected tumors. Proton MR spectroscopy has been applied in assessing various intracranial diseases and is increasingly used in diagnosis and clinical management. Our purpose was to determine if multivoxel proton MR spectroscopy can be used to differentiate TDLs and high-grade gliomas. METHODS: Conventional MR images, proton MR spectra, and medical records were retrospectively reviewed in six patients with TDLs diagnosed by means of biopsy or by documented clinical improvement, with or without supporting laboratory testing and follow-up imaging. Proton MR spectra of 10 high-grade gliomas with similar conventional MR imaging appearances were used for comparison. In contrast-enhancing, central, and perilesional areas of each lesion, peak heights of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were measured and the lactate peak noted. Cho/Cr and NAA/Cr ratios of corresponding regions in TDLs and gliomas were compared. RESULTS: No significant differences in mean Cho/Cr ratios were found in the corresponding contrast-enhancing, central, or perilesional areas of TDLs and gliomas. The mean central-region NAA/Cr ratio in gliomas was significantly lower than that of TDLs, but mean NAA/Cr ratios in other regions were not significantly different. A lactate peak was identified in four of six TDLs and three of 10 gliomas. CONCLUSION: In the cases examined, the NAA/Cr ratio in the central region of TDLs and high-grade gliomas differed significantly. However, overall metabolite profiles of both lesions were similar; this finding emphasizes the need for the cautious interpretation of spectroscopic findings
— id: 34738, year: 2002, vol: 23, page: 1378, 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,

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,

Primitive neuroectodermal tumors of the brainstem: investigation of seven cases
Zagzag D; Miller DC; Knopp E; Farmer JP; Lee M; Biria S; Pellicer A; Epstein FJ; Allen JC
2000 Nov;106(5):1045-1053, Pediatrics
OBJECTIVE: We discuss the clinical aspects, pathology, and molecular genetics of 7 patients with primitive neuroectodermal tumors (PNETs) arising in the brainstem that were treated at our institution from 1986 through 1995. Most neuro-oncologists avoid performing biopsies in children with pontine tumors. This article raises the question as to whether biopsies should be performed, because treatment recommendations might differ if a PNET was diagnosed rather than a pontine glioma. PATIENTS AND METHODS: We reviewed the clinical neuro-oncology database and the files of the Division of Neuropathology at New York University Medical Center from 1986 through 1995 and identified 7 histologically confirmed PNETs arising in the brainstem among 146 pediatric brainstem tumors. The clinical, neuroradiological, and neuropathological data were reviewed. Postmortem examinations were performed in 2 cases. Formalin-fixed, paraffin-embedded tumor tissues were also available in 6 of 7 patients that were tested for p53 gene mutations using single-strand conformation polymorphism analysis. We also tested 9 cerebellar PNETs, 9 brainstem gliomas, and 3 normal brains for p53 gene mutations as controls. RESULTS: All 7 patients presented with focal cranial nerve deficits, and 2 were also hemiparetic. The median age at diagnosis was 2.7 (1-8 years). Magnetic resonance imaging (MRI) characteristics included a focal intrinsic exophytic nonenhancing brainstem lesion that had low T1-weighted and high T2-weighted signals. Hydrocephalus was present in 5 patients at diagnosis, 3 of whom had leptomeningeal dissemination. Meningeal dissemination occurred later in the course of the disease in 3 other patients. Five children required shunts at diagnosis and another 2 at recurrence. Despite therapy, all 7 PNET patients died within 17 months of diagnosis with a mean survival of 8 (4-17) months. No mutation in the p53 gene was detected. CONCLUSIONS: Brainstem PNETs tend to arise at a younger age than brainstem gliomas and medulloblastomas. The MRI pattern suggests a localized rather than a diffuse intrinsic nonenhancing brainstem tumor. Like other PNETs, brainstem PNETs have a high predilection to disseminate within the central nervous system. The absence of p53 mutations is similar to other PNETs. Despite their origin close to the cerebellum, brainstem PNETs exhibit a more aggressive behavior and result in worse clinical outcomes than do cerebellar PNETs
— id: 26837, year: 2000, vol: 106, page: 1045, 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,

Mycosis fungoides metastasizing to the brain parenchyma: case report
Zonenshayn M; Sharma S; Hymes K; Knopp EA; Golfinos JG; Zagzag D
1998 Apr;42(4):933-937, Neurosurgery
OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. CLINICAL PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis
— id: 57297, year: 1998, vol: 42, page: 933, stat: Journal Article,

The role of magnetic resonance angiography in the assessment of intracranial vascular disease
Knopp EA
1996 Aug;6(3):769-780, Neuroimaging clinics of North America
Magnetic resonance techniques have a significant role in the evaluation of intracranial vascular diseases; however, to achieve an appropriate diagnosis, a combination of both magnetic resonance imaging and angiography are needed. It is extremely important for the interpreting physician to be aware of the potential limitations of the techniques being used. With this knowledge, magnetic resonance techniques can eliminate the need for more invasive procedures. An overview of the current methods and their applications and limitations is provided
— id: 12561, year: 1996, vol: 6, page: 769, stat: Journal Article,

Water excitation MPRAGE MRI of VII and VIII cranial nerves
Litt AW; Licata P; Knopp EA; Thomasson DM
1996 Mar-Apr;20(2):194-200, Journal of computer assisted tomography
OBJECTIVE: Our goal was to compare magnetization prepared rapid gradient echo--water excitation (MRPRAGE-WE) with conventional spin echo (CSE) in the evaluation of the VII and VIII cranial nerves. METHODS: One hundred three consecutive patients with symptoms referable to the VII/VIII nerves were studied with CSE T1 and MPRAGE-WE following intravenous gadolinium contrast agent. Each right and left nerve pair was independently evaluated for the presence of an enhancing mass and for visualization of the nerves. RESULTS: On the CSE images, 26 definite and 2 possible lesions were identified, whereas 28 definite and 2 possible abnormalities were seen on the MPRAGE-WE. Four cases were better identified on the MPRAGE-WE and one better seen on the CSE. This difference was not statistically significant (p = 0.19). CSE demonstrated the nerves partially in 23 instances and completely in 6; MPRAGE-WE showed the nerves partially in 35 and completely in 73. This was highly significant (p<0.001). CONCLUSION: With equivalent or slightly improved lesion detection and better visualization of the nerves, MPRAGE-WE may replace CSE in studying the VII/VIII nerves
— id: 6930, year: 1996, vol: 20, page: 194, stat: Journal Article,

Contrast-enhancing progressive multifocal leukoencephalopathy: radiological and pathological correlations: case report
Woo HH; Rezai AR; Knopp EA; Weiner HL; Miller DC; Kelly PJ
1996 Nov;39(5):1031-1034, Neurosurgery
OBJECTIVE AND IMPORTANCE: Progressive multifocal leukoencephalopathy (PML), a demyelinating disease caused by the JC papovavirus, is an opportunistic infection afflicting patients with impaired cellular immunity. Although initially described in patients with hematological malignancies, PML has become associated with several other immunocompromised states, particularly human immunodeficiency virus (HIV) infection. There are numerous central nervous system manifestations in patients with acquired immunodeficiency syndrome. A major characteristic that distinguishes PML from other more common lesions, such as toxoplasmosis or non-Hodgkin's lymphoma, is the lack of contrast enhancement. We describe a case of PML that exhibits contrast enhancement, and we conclude that the diagnosis of PML must be considered in patients with HIV who have contrast-enhancing lesions. CLINICAL PRESENTATION: A 40-year-old woman presented with progressive hemiparesis, blurred vision, and ataxia. Magnetic resonance imaging revealed a contrast-enhancing lesion involving the left middle cerebellar peduncle, causing mild compression of the fourth ventricle. INTERVENTION: The patient underwent a stereotactic serial biopsy with the presumptive diagnosis of moderate- to high-grade glioma. Histological examination of the biopsy specimen revealed early PML. Subsequently, a test for HIV was obtained and the results were positive. CONCLUSION: We have reported another atypical radiographic characteristic of PML associated with HIV. We conclude that PML lesions can enhance after the administration of gadolinium. Therefore, the diagnosis of PML must be entertained in patients whose test results were positive for HIV with contrast-enhancing lesions and that a stereotactic serial biopsy may be necessary to provide a definitive diagnosis
— id: 12504, year: 1996, vol: 39, page: 1031, stat: Journal Article,

Venous disease and tumors
Knopp EA
1995 Aug;3(3):509-528, Magnetic resonance imaging clinics of North America
MR imaging of the venous system of the brain plays an important role in the diagnosis and follow up of intracranial venous vascular diseases. This article serves to acquaint the reader with the currently available methods to study the venous vascular system in addition to covering specific instances in which these methods should be used
— id: 12745, year: 1995, vol: 3, page: 509, stat: Journal Article,

Presumed vestibular hemorrhage secondary to warfarin
Kothari M; Knopp E; Jonas S; Levine D
1995 May;37(4):324-325, Neuroradiology
Hemorrhage secondary to anticoagulant therapy is well documented. We report a patient who presented with acute vertigo and unilateral deafness while on warfarin and was found to have a probable hemorrhage in the labyrinth, identified on MRI
— id: 56769, year: 1995, vol: 37, page: 324, stat: Journal Article,

MP-RAGE subtraction venography: a new technique
Stevenson J; Knopp EA; Litt AW
1995 Mar-Apr;5(2):239-241, Journal of magnetic resonance imaging
Preliminary evaluation of a new magnetic resonance (MR) venography technique was performed with data sets from five patients undergoing MR imaging of the brain before and after intravenous administration of gadopentetate dimeglumine. Before contrast agent injection, the patients were imaged with MP-RAGE (magnetization-prepared rapid gradient-echo) and axial turbo T2-weighted sequences. After contrast agent injection, the MP-RAGE sequence was repeated. Images were post-processed with an algorithm that calculates, on a pixel-by-pixel basis, the absolute value of signal intensity of each postcontrast MP-RAGE partition minus that of each precontrast MP-RAGE partition. These subtracted partitions were then subjected to a standard maximum-intensity-projection algorithm to obtain the venogram. In all cases, the new method afforded a high-resolution venogram with clear depiction of venous sinus anatomy. Cortical venous anatomy was also clearly depicted
— id: 12800, year: 1995, vol: 5, page: 239, stat: Journal Article,

Primary lymphoma of the cauda equina: myelographic, CT myelographic, and MR appearance
Knopp, E A; Chynn, K Y; Hughes, J
1994 Jun;15(6):1187-1189, AJNR. American journal of neuroradiology
This case demonstrates the myelographic, CT myelographic, and MR appearance of primary lymphoma of the cauda equina. It also illustrates the utility of high-resolution CT myelography in certain lesions of the cauda equina. The authors feel that CT myelography, with its inherent ability to depict individual nerve roots and therefore any pathologic involvement as well, should be considered an adjunct to MR in imaging the cauda equina
— id: 133243, year: 1994, vol: 15, page: 1187, stat: Journal Article,

Preservation of myocardial ATP during cardioplegia: comparison of techniques
Catinella, F P; Knopp, E A; Cunningham, J N Jr
1984 Jul-Aug;25(4):296-303, Journal of cardiovascular surgery
Preservation of myocardial ATP enhances the heart's ability to resume normal function following aortic crossclamping (AXC). Preservation of this high energy substrate during 4 cardioplegia delivery techniques was evaluated and compared with changes occurring during 4 hours of continuous coronary perfusion. Dogs (31) were placed on cardiopulmonary bypass and transmural left ventricular biopsies obtained for control ATP measurements. Animals were then divided into five groups: Group I (n = 6): 4 hrs. of continuous coronary perfusion (CCP); Group II (n = 6): 3 hrs. continuous AXC, multidose blood cardioplegia (MBC); Group III (n = 6): 3 hrs. continuous AXC, multidose crystalloid cardioplegia (MCC); Group IV (n = 6): 2 hrs. intermittent AXC, single dose BC (SBC); Group V (n = 7): 2 hrs. continuous AXC, continuous perfusion BC (CBC). In each group, where applicable, myocardial biopsies were taken at 30 minute intervals during AXC, before and after cardioplegia injection, and 30 minutes following final unclamping and rewarming. Hearts in Group II (MBC) and V (CBC) showed greatest preservation of ATP stores (increases 1.1 +/- 1.2%, increases 1.8 +/- 0.9% respectively; p greater than .05) ATP levels rose as high as 23 +/- 2% (p less than .005) above control immediately following cardioplegia injection in Group II (MBC). Group IV showed poorest preservation of ATP (decreases 26 +/- 5%, p less than .01) with levels falling as much as 37 +/- 10% (p less than .01) during the period of AXC. Hearts in Group I (CCP) demonstrated a 15.6 +/- 7.5% decrease in ATP from control (p less than .05). Group III (MCC) also showed a steady decline in ATP declining 18 +/- 3% (p less than .005) from control. These data indicate that multidose blood and continuous-blood cardioplegia techniques will maintain normal myocardial ATP stores throughout the period of AXC. These groups actually show a slight rise in ATP as compared to 4 hrs. of continuous coronary perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 126735, year: 1984, vol: 25, page: 296, stat: Journal Article,

Demonstration of sustained increases in myocardial ATP following preischemic enhancement
Laschinger JC; Cunningham JN Jr; Krieger K; Knopp E; Culliford AT; Colvin S; Spencer FC
1984 Mar-Apr;41(2):104-106, Current surgery
— id: 28931, year: 1984, vol: 41, page: 104, stat: Journal Article,

Preservation of myocardial ATP. Comparison of blood vs crystalloid cardioplegia
Catinella, F P; Cunningham, J N Jr; Knopp, E A; Laschinger, J C; Spencer, F C
1983 Apr;83(4):650-654, Chest
Preservation of myocardial high-energy phosphates correlates with the heart's ability to resume normal function following aortic crossclamping (AXC). The ability of the canine myocardium to synthesize and maintain ATP during 180 minutes of AXC was evaluated in 12 hearts subjected to either blood or crystalloid cardioplegic arrest. Group 1 hearts were arrested by infusion of 750 ml of blood potassium cardioplegia (BKC) solution into the aortic root initially and every 30 minutes, as were group 2 (six) hearts but with a crystalloid cardioplegia (CC) solution. Transmural left ventricular biopsy specimens were obtained for ATP analysis prior to AXC (control), before and after cardioplegia injections 2, 4, and 6, prior to unclamping (180 minutes of AXC), and 30 minutes following reperfusion. ATP levels increased significantly above control (p less than 0.005) during the 180 minutes of AXC immediately following infusion of BKC. At the end of 180 minutes of AXC and following 30 minutes of reperfusion, ATP was noted to be normal in this group (p = NS). In contrast, ATP levels fell significantly (p less than 0.005) during the period of aortic cross-clamping in the crystalloid cardioplegia group and did not return to normal even after 30 minutes of reperfusion (p less than 0.005). We concluded that BKC, by presenting the arrested myocyte with adequate oxygen and substrate, allows for synthesis and preservation of myocardial ATP during periods of AXC as long as three hours. In this respect, it should be regarded as superior to CC, which permits a statistically significant depletion of ATP (p less than 0.005) uncorrected, even after 30 minutes of reperfusion in the beating, nonworking state
— id: 107080, year: 1983, vol: 83, page: 650, stat: Journal Article,

Myocardial protection with cold blood potassium cardioplegia during prolonged aortic cross-clamping. Laboratory evaluation
Catinella, F P; Cunningham, J N Jr; Knopp, E A; Srungaram, R K; Nathan, I M
1983 Apr;83(5):721-726, New York state journal of medicine
— id: 126738, year: 1983, vol: 83, page: 721, stat: Journal Article,

PRESERVATION OF MYOCARDIAL ATP - COMPARISON OF BLOOD VS CRYSTALLOID CARDIOPLEGIA
Catinella, FP; Cunningham, JN; Knopp, EA; Laschinger, JC; Spencer, FC
1983 ;83(4):650-654, Chest
— id: 30662, year: 1983, vol: 83, page: 650, stat: Journal Article,

CLINICAL USE OF PREISCHEMIC ENHANCEMENT - REPLENISHMENT OF MYOCARDIAL ADENOSINE-TRIPHOSPHATE STORES IN HYPERTROPHIED RIGHT VENTRICLES
CUNNINGHAM, JN; LASCHINGER, JC; KRIEGER, KH; KNOPP, EA; ISOM, OW; SPENCER, FC
1983 ;34(12):279-282, Surgical forum
— id: 41123, year: 1983, vol: 34, page: 279, stat: Journal Article,

'Pulsatile' left atrial-femoral artery bypass. A new method of preventing extension of myocardial infarction
Laschinger, J C; Cunningham, J N Jr; Catinella, F P; Knopp, E A; Glassman, E; Spencer, F C
1983 Aug;118(8):965-969, Archives of Surgery (Chicago)
A left atrial-femoral artery (LA-FA) bypass system was designed to deliver synchronous pulsatile blood flow. We compared it with nonpulsatile LA-FA bypass in its effectiveness to limit infarct extension after ligation of the left anterior descending coronary artery at its origin in 35 dogs. Nonpulsatile LA-FA bypass resulted in a 70% reduction in the size of infarct. The addition of synchronous diastolic counterpulsation (P-LA-FA) further reduced the size of infarct, when compared with that in controls (95%) or animals that underwent LA-FA bypass (83%). Both LA-FA and P-LA-FA bypasses limited infarct extension and reduced mortality after acute coronary occlusion through effective unloading of the left ventricle. The addition of diastolic counterpulsation to LA-FA bypass led to further significant infarct reduction, when compared with LA-FA bypass alone. These effects were most likely secondary to improvements in myocardial blood flow distribution
— id: 107078, year: 1983, vol: 118, page: 965, stat: Journal Article,

Experimental and clinical assessment of the adequacy of partial bypass in maintenance of spinal cord blood flow during operations on the thoracic aorta
Laschinger, J C; Cunningham, J N Jr; Nathan, I M; Knopp, E A; Cooper, M M; Spencer, F C
1983 Oct;36(4):417-426, Annals of thoracic surgery
We studied both experimentally and clinically the efficacy of partial bypass techniques in maintaining spinal cord blood flow and physiological function during surgical procedures on the thoracoabdominal aorta. We attempted to define the level of distal aortic pressure required to safely ensure normal neurological function in the absence of critical intercostal occlusion. Six dogs underwent left thoracotomy with baseline measurements of spinal cord blood flow and spinal cord impulse conduction (somatosensory evoked potentials). Following exclusion of the entire descending thoracic aorta from the left subclavian artery to the T-13 level, partial left atrium-femoral artery bypass was instituted, and baseline levels of proximal and distal aortic pressure were maintained during a 30-minute stabilization period. Mean distal aortic pressure then was progressively altered at 30-minute intervals to 100, 70, and 40 mm Hg. Measurements of spinal cord blood flow and somatosensory evoked potential were repeated at the end of each interval for comparison with baseline. No significant changes in spinal cord blood flow or somatosensory evoked potential were observed in any animal with a distal aortic pressure greater than or equal to 70 mm Hg. With a pressure of 40 mm Hg, normal flow and somatosensory evoked potentials were maintained in 5 of the 6 dogs. Loss of somatosensory evoked potential, with simultaneous loss of spinal cord blood flow at the T-6 level, occurred in 1 dog. Restoration of distal aortic pressure to 70 mm Hg in all animals resulted in immediate return of somatosensory evoked potential. Loss of somatosensory evoked potential routinely occurred in animals with a distal aortic pressure less than 40 mm Hg. Clinically, 9 patients have undergone operation for lesions of the thoracoabdominal aorta using shunt or bypass techniques. Normal somatosensory evoked potentials were preserved in 7 patients with maintenance of adequate distal aortic pressure (greater than or equal to 60 mm Hg) without evidence of postoperative neurological deficit. Two patients showed hypotensive somatosensory evoked potential loss (distal aortic pressure less than 40 mm Hg). Prolonged distal hypotension (85 minutes of aortic cross-clamping) in the latter resulted in paraplegia. We conclude that maintenance of a distal aortic pressure greater than 60 to 70 mm Hg will uniformly preserve spinal cord blood flow in the absence of critical intercostal exclusion. Should distal aortic pressure be inadequate, early reversible changes in the somatosensory evoked potential will alert the surgeon. Failure to institute measures to reverse these changes may result in paraplegia
— id: 107076, year: 1983, vol: 36, page: 417, stat: Journal Article,

EXPERIMENTAL AND CLINICAL-ASSESSMENT OF THE ADEQUACY OF PARTIAL BYPASS IN MAINTENANCE OF SPINAL-CORD BLOOD-FLOW DURING OPERATIONS ON THE THORACIC AORTA
Laschinger, JC; Cunningham, JN; Nathan, IM; Knopp, EA; Cooper, MM; Spencer, FC
1983 ;36(4):417-426, Annals of thoracic surgery
— id: 30606, year: 1983, vol: 36, page: 417, stat: Journal Article,

The factors influencing early patency of coronary artery bypass vein grafts: correlation of angiographic and ultrastructural findings
Catinella, F P; Cunningham, J N Jr; Srungaram, R K; Baumann, F G; Nathan, I M; Glassman, E A; Knopp, E A; Spencer, F C
1982 May;83(5):686-700, Journal of thoracic & cardiovascular surgery
To test the hypothesis that suboptimal preparation of saphenous veins may adversely affect early patency of aorta-coronary artery bypass grafts, a nonrandomized prospective study was undertaken comparing two methods of saphenous vein preparation prior to grafting. Forty recatheterizations were performed during the postoperative hospital stay (approximately 10 days) in two groups of asymptomatic patients who had undergone isolated coronary artery bypass grafting. Veins from patients in Group I were bathed in autologous, heparinized blood at 20 degrees C and distended to 80 mm Hg, prior to grafting. The veins from Group II patients were prepared in an identical manner, except that the bathing solution consisted of heparinized electrolyte solution with added papaverine (0.6 mg/lg). Segments of vein from each group were obtained prior to grafting and preserved in 3% glutaraldehyde for subsequent electron microscopic studies. Operative technique in both groups of patients was identical and all procedures were performed by the same surgeons. Comparison of patients in Group I and II revealed no significant difference in the number of diseased vessels per patient (3.1 versus 3.4), number of grafts per patient (2.9 versus 2.9), native vessel diameter (1.9 versus 1.7 mm), and postoperative graft flows (65 versus 68 cc/min). However, early postoperative graft patency in Group II patients was 93% versus 80% in patients in Group I (p less thn 0.01). Electron microscopic analysis revealed severe spasm of venous smooth muscle in the blood-stored veins causing intraluminal smooth muscle cell cytoplasmic protrusions with resultant endothelial separation and desquamation. Formation of fibrin-platelet microaggregates was common. These findings were not present in the solution-treated veins. In view of these ultrastructural findings, and the highly significant difference in patency rates, we have abandoned all blood storage techniques and now prepare saphenous veins by soaking them in a clear bathing medium with added heparin and papaverine. Long-term follow-up of these patients is currently in progress and may reveal even more dramatic results than we have heretofore observed
— id: 106536, year: 1982, vol: 83, page: 686, stat: Journal Article,

A simplified method for delivery of cold blood cardioplegia and aortic root venting during coronary artery bypass
Catinella, F P; Knopp, E A; Cunningham, J N Jr; Adams, P X
1982 Mar-Apr;23(2):163-165, Journal of cardiovascular surgery
We present a simplified method for delivery of cold blood cardioplegia and left ventricular decompression during coronary artery bypass surgery when aortic occlusion is utilized. The system provides immediate delivery of the cardioplegic solution followed by continuous sump suction on the aortic root to decompress the left ventricle and to aspirate non-coronary collateral flow. This system has been utilized in over 200 consecutive cases of coronary revascularization without complication and is a safe, effective and inexpensive method of both delivery of the cardioplegic agent and maintenance of a dry quiet operative field
— id: 126743, year: 1982, vol: 23, page: 163, stat: Journal Article,

Release of particulate matter from extracorporeal tubing: ineffectiveness of standard arterial line filters during bypass
Knopp, E A; Baumann, F G; Pratt, D; Faden, R; Catinella, F P; Nathan, I M; Adams, P X; Cunningham, J N Jr; Spencer, F C
1982 Nov-Dec;23(6):470-476, Journal of cardiovascular surgery
Microemboli resulting from extracorporeal circulation have been considered to be a cause of organ dysfunction after cardiopulmonary bypass. A scanning electron microscopic study was carried out to quantitate the number of nonbiological particles which escape capture by the arterial line filter in a standard extracorporeal circulation circuit. Five different lots of polyvinylchloride (PVC) tubing from the same manufacturer were used in closed circuit extracorporeal pump set-ups consisting of a typical length of PVC tubing, a cardiotomy reservoir, and an arterial line filter (Pall 40 microns (mu)). A liter of Plasmalyte was circulated through this set-up for 15 minutes at 2 liters/minute with the pump head set at almost total occlusion. The circulated Plasmalyte from each pump line was then collected and passed through a 0.22 mu Millipore filter. Numerous particles ranging from 5-40 mu in diameter were observed on the surface of the filters. A mean of 51.2 particles/mm2 of filter was found after the first recirculation period. By extrapolation the mean total number of particles contained in the Plasmalyte was calculated to be 70,943. A second similar 15 minute rinse on the same pump set-ups revealed the release of a mean of 51.0 particles/mm2, or a mean total number of 70,665 particles. Analysis of variance showed no significant difference in the number of particles produced by the first compared with the second recirculation period but there were significant differences (P less than .05) between the numbers of particles produced by the different lots of tubing. This study demonstrates that commonly employed tubing packs and standard roller pump designs for extracorporeal circulation are associated with continuous release of particulate matter (5-40 mu) which is not removed by the arterial line filters most often employed. These particles seem to be released at a constant rate which makes an initial pre-bypass filtration run ineffective. Such particles can only be removed by continuous use of lower porosity filters in the pump circuit. The clinical significance of these large numbers of small particles is unknown, but they may contribute to the multi-organ failure often seen in prolonged (greater than 2 hour) periods of cardiopulmonary bypass
— id: 106533, year: 1982, vol: 23, page: 470, stat: Journal Article,

Myocardial cooling: beneficial effects of topical hypothermia
Laschinger, J C; Catinella, F P; Cunningham, J N Jr; Knopp, E A; Nathan, I M; Spencer, F C
1982 Dec;84(6):807-814, Journal of thoracic & cardiovascular surgery
— id: 107084, year: 1982, vol: 84, page: 807, stat: Journal Article,

Detection and prevention of intraoperative spinal cord ischemia after cross-clamping of the thoracic aorta: use of somatosensory evoked potentials
Laschinger, J C; Cunningham, J N Jr; Catinella, F P; Nathan, I M; Knopp, E A; Spencer, F C
1982 Dec;92(6):1109-1117, Surgery
— id: 107082, year: 1982, vol: 92, page: 1109, stat: Journal Article,

DETECTION AND PREVENTION OF INTRA-OPERATIVE SPINAL-CORD ISCHEMIA AFTER CROSS-CLAMPING OF THE THORACIC AORTA - USE OF SOMATOSENSORY EVOKED-POTENTIALS
LASCHINGER, JC; CUNNINGHAM, JN; CATINELLA, FP; NATHAN, IM; KNOPP, EA; SPENCER, FC
1982 ;92(6):1109-1117, Surgery
— id: 40367, year: 1982, vol: 92, page: 1109, stat: Journal Article,

Blood potassium cardioplegia preserves ATP and ventricular function for three hours of aortic crossclamping
Catinella, F P; Cunningham, J N Jr; Paone, G; Knopp, E A; Nathan, I M; Spencer, F C
1981 Nov-Dec;38(6):387-391, Current surgery
— id: 107087, year: 1981, vol: 38, page: 387, stat: Journal Article,

Blood potassium cardioplegia administration. Comparison of myocardial protection offered by three techniques
Catinella, F P; Cunningham, J N Jr; Srungaram, R K; Nathan, I M; Knopp, E A; Paone, G; Baumann, F G; Adams, P X; Spencer, F C
1981 Dec;116(12):1509-1516, Archives of Surgery (Chicago)
To investigate the best method of administration of blood potassium cardioplegia, 19 dogs were studied while undergoing 120 minutes each of aortic crossclamping (myocardial temperature, less than 15 degrees C). Group 1 (six dogs) underwent a single 120-minute period of aortic crossclamping with the heart protected by multiple reinjections (1,000 mL every 30 minutes) of blood potassium cardioplegia solution (potassium chloride, 30 mEq/L; pH, 8; temperature, less than 15 degrees C). Group 2 (six dogs) underwent four separate 30-minute periods of aortic crossclamping, but allowing hearts to beat in a nonworking state for 20 minutes at 35 degrees C between each arrest interval. Hearts in group 3 (seven dogs) were initially arrested as described above, following which a continuous infusion (75 mL/min; KCl, 10 mEq/L) of blood potassium cardioplegia solution was maintained throughout the arrest period. Measurements of myocardial metabolism, ventricular function, regional blood flow, and ultrastructure were carried out before arrest and 30 minutes after final unclamping. Analysis of the data revealed no significant benefit of one method over another, with the exception that adenosine triphosphate level was least preserved with intermittent unclamping and reperfusion. Because continuous perfusion techniques are more cumbersome than multidose reinjection, and intermittent aortic crossclamping lengthens total cardiopulmonary bypass time, we favor the simplest approach, multidose reinjection during a single uninterrupted period of aortic crossclamping
— id: 106539, year: 1981, vol: 116, page: 1509, stat: Journal Article,

SYNTHESIS AND PRESERVATION OF MYOCARDIAL ATP - BLOOD CARDIOPLEGIA IS SUPERIOR TO CRYSTALLOID CARDIOPLEGIA
CATINELLA, FP; CUNNINGHAM, JN; SRUNGARAM, R; NATHAN, IM; KNOPP, EA; SPENCER, FC
1981 ;80(3):368-368, Chest
— id: 40192, year: 1981, vol: 80, page: 368, stat: Journal Article,

BLOOD VERSUS CRYSTALLOID CARDIOPLEGIA - WHICH IS SUPERIOR FOR PROLONGED AORTIC CROSS-CLAMPING
Srungaram, RK; Cunningham, JN; Catinella, FP; Knopp, EA; Nathan, IM; Spencer, FC
1981 ;32(1):288-290, Surgical forum
— id: 30336, year: 1981, vol: 32, page: 288, stat: Journal Article,

IMPORTANCE OF IONIZED CALCIUM CONCENTRATIONS IN SECONDARY BLOOD CARDIOPLEGIA SOLUTIONS
STRAUSS, ED; CUNNINGHAM, JN; SCHNEINERMAN, SJ; CATINELLA, FP; KNOPP, EA; ADAMS, PX; SPENCER, FC
1981 ;80(3):368-368, Chest
— id: 40193, year: 1981, vol: 80, page: 368, stat: Journal Article,

Preservation of ATP, ultrastructure, and ventricular function after aortic cross-clamping and reperfusion. Clinical use of blood potassium cardioplegia
Cunningham, J N Jr; Adams, P X; Knopp, E A; Baumann, F G; Snively, S L; Gross, R I; Nathan, I M; Spencer, F C
1979 Nov;78(5):708-720, Journal of thoracic & cardiovascular surgery
— id: 106541, year: 1979, vol: 78, page: 708, stat: Journal Article,

CLINICAL USE OF POTASSIUM BLOOD CARDIOPLEGIA - PRESERVATION OF ADENOSINE-TRIPHOSPHATE, ULTRASTRUCTURE, AND VENTRICULAR-FUNCTION FOLLOWING AORTIC CROSSCLAMPING AND REPERFUSION
CUNNINGHAM, JN; ADAMS, PX; ISOM, OW; KNOPP, EA; BAUMANN, FG; CULLIFORD, AC; COLBIN, S; SPENCER, FC
1979 ;79(13):2042-2042, New York state journal of medicine
— id: 50126, year: 1979, vol: 79, page: 2042, stat: Journal Article,