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R I Grossman

Publications and source records attributed to R I Grossman.

At least 19 recordsLinked to original sources

Reproducibility of the whole-brain N-acetylaspartate level across institutions, MR scanners, and field strengths.

BACKGROUND AND PURPOSE: Radiologic markers in multicenter trials are often confounded by different instrumentation used. Our goal was to estimate the variance of the global concentration of the neuronal cell marker N-acetylaspartate (NAA) among research centers using MR imaging scanners of different models, from different manufacturers, and of different magnetic field strength. MATERIALS AND METHODS: Absolute millimolar amounts of whole-brain NAA (WBNAA) were quantified with nonlocalizing proton MR spectroscopy in the brains of 101 healthy subjects (53 women, 48 men) aged 16-59 years (mean, 34.2 years). Twenty-three were scanned at 1 institute in a 1.5T Siemens Vision; 31 from another institute were studied with a 1.5T Siemens SP63; 36 were scanned at a third institute (24 with a 1.5T Vision, 12 with a 3T Siemens Trio); and 11 were obtained at a fourth institute using a 4T GE Signa 5.x. The NAA amounts were quantified with phantom-replacement and divided by the brain volume, segmented from MR imaging, to yield the concentration, a metric independent of brain size suitable for cross-sectional comparison. RESULTS: The average WBNAA concentration among institutions was 12.2 +/- 1.2 mmol/L. The subjects' WBNAA distributions did not differ significantly (p > .237) among the 4 centers, regardless of scanner manufacturer, model, or field strength and irrespective of whether adjustments were made for age or sex. CONCLUSION: Absolute quantification against a standard makes the WBNAA concentration insensitive to the MR hardware used to acquire it. This important attribute renders it a robust surrogate marker for multicenter neurologic trials.

Adolescent↗

Three-dimensional proton spectroscopy of deep gray matter nuclei in relapsing-remitting MS.

The metabolic changes in the deep gray matter (GM) nuclei, thalamus, and basal ganglia of patients with relapsing-remitting multiple sclerosis were investigated with quantitative, multivoxel, three-dimensional proton MR spectroscopy. This technique facilitated the study of several bilateral structures in a single session at sub-cubic centimeter spatial resolution. Compared with 9 matched control subjects, the deep GM nuclei of 11 patients showed 7% lower N-acetylaspartate and 14% higher choline levels (p = 0.02 for both).

Adult↗

Neuronal cell injury precedes brain atrophy in multiple sclerosis.

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity).

Adult↗

The utility of MRI in suspected MS [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Advancements in imaging technologies and newly evolving treatments offer the promise of more effective management strategies for MS. Until recently, confirmation of the diagnosis of MS has generally required the demonstration of clinical activity that is disseminated in both time and space. Nevertheless, with the advent of MRI techniques, occult disease activity can be demonstrated in 50 to 80% of patients at the time of the first clinical presentation. Prospective studies have shown that the presence of such lesions predicts future conversion to clinically definite (CD) MS. Indeed, in a young to middle-aged adult with a clinically isolated syndrome (CIS), once alternative diagnoses are excluded at baseline, the finding of three or more white matter lesions on a T2-weighted MRI scan (especially if one of these lesions is located in the periventricular region) is a very sensitive predictor (>80%) of the subsequent development of CDMS within the next 7 to 10 years. Moreover, the presence of two or more gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new Gd enhancement on follow-up scans are also highly predictive of the subsequent development of CDMS in the near term. By contrast, normal results on MRI at the time of clinical presentation makes the future development of CDMS considerably less likely.

Adult↗

Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis.

Although axonal pathology is recognized as one of the major pathological features of multiple sclerosis, it is less clear how early in its course it occurs and how it correlates with MRI-visible lesion loads. To assess this early axonal pathology, we quantified the concentration of whole-brain N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical stage of the disease and compared the results with those from healthy controls. Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance spectroscopy were obtained from 31 patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis and paraclinical evidence of dissemination in space, and from 16 matched controls. An additional conventional MRI scan was obtained in all patients 4-6 months later to detect dissemination of lesions in time. The mean WBNAA concentration was significantly lower in patients compared with the controls (P < 0.0001). It was not significantly different between patients with and without enhancing lesions at the baseline MRI or between patients with and without lesion dissemination in time. No correlation was found between WBNAA concentrations and lesion volumes. Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis. This finding lessens the validity of the current concept that the axonal pathology of multiple sclerosis is the end-stage result of repeated inflammatory events, and argues strongly in favour of early neuroprotective intervention.

Adult↗

Development of a posterior cerebral artery aneurysm subsequent to occlusion of the contralateral internal carotid artery for giant cavernous aneurysm.

We report a case of a patient who developed a left posterior cerebral artery aneurysm 5 years after balloon occlusion of the right internal carotid artery for a giant cavernous aneurysm. The location of the new aneurysm was outside of the primary collateral pathways to the contralateral, proximally occluded, anterior circulation, illustrating the complexity of hemodynamic factors contributing to the development of intracranial saccular aneurysms. The appearance of an aneurysm in this setting supports the hypothesis that degenerative factors and hemodynamic stresses are important in the etiology of intracranial aneurysms.

Balloon Occlusion↗

Role of magnetic resonance imaging in the diagnosis and monitoring of multiple sclerosis: consensus report of the White Matter Study Group.

On June 24-26, 2001, the first meeting of the White Matter Study Group (WMSG) of the International Society for Magnetic Resonance in Medicine (ISMRM) was held in Bordeaux, France. This paper is the report of the consensus reached among the delegates of the meeting on how to use magnetic resonance imaging (MRI) to make an early diagnosis of multiple sclerosis (MS), to measure MS activity accurately and reliably, and to monitor the effect of treatment on disease evolution.

Brain↗

Future applications of DWI in MS.

Diffusion imaging is a noninvasive technique for measuring the movement of water molecules. Although it has had its greatest impact thus far in the area of stroke imaging, the information garnered from diffusion experiments can provide an indication of myelin injury and perhaps axonal integrity. In this paper, we describe some current and potential future applications of diffusion imaging in multiple sclerosis. These include the use of global indices such as diffusion trace and anisotropy, as well as implementation of axonal fiber tracking methodologies for assessment of axonal integrity and connectivity between cortical regions.

Diffusion↗

Multiprotocol MR image segmentation in multiple sclerosis: experience with over 1,000 studies.

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

Humans↗

Brain atrophy in relapsing-remitting multiple sclerosis: fractional volumetric analysis of gray matter and white matter.

PURPOSE: To determine the fractional brain tissue volume changes in the gray matter and white matter of patients with relapsing-remitting multiple sclerosis (MS) and to correlate these measurements with clinical disability and total lesion load. MATERIALS AND METHODS: Thirty patients with relapsing-remitting MS and 25 healthy control subjects underwent magnetic resonance imaging. Fractional brain tissue volumes (tissue volume relative to total intracranial volume) were obtained from the total segmented gray matter and white matter in each group and were analyzed. RESULTS: The fractional volume of white matter versus that of gray matter was significantly lower (-6.4%) in patients with MS (P <.0001) than in control subjects. Neither gray matter nor white matter fractional volume measurements correlated with clinical disability in the patients with MS. CONCLUSION: Loss of brain parenchymal volume in patients with relapsing-remitting MS is predominantly confined to white matter. Analysis of fractional brain tissue volumes provides additional information useful in characterizing MS and may have potential in evaluating treatment strategies.

Adult↗

Magnetization transfer imaging and proton MR spectroscopy in the evaluation of axonal injury: correlation with clinical outcome after traumatic brain injury.

BACKGROUND AND PURPOSE: Current imaging does not permit quantification of neural injury after traumatic brain injury (TBI) and therefore limits both the development of new treatments and the appropriate counseling of patients concerning prognosis. We evaluated the utility of magnetization transfer ratio (MTR) and proton MR spectroscopy in identifying patients with neuronal injury after TBI. METHODS: Thirty patients with TBI (21-77 years old; mean age, 42 years; admission Glasgow Coma Scale (GOS) scores 3-15; mean score, 11) were studied on a 1.5-T system with magnetization transfer imaging and MR spectroscopy of the splenium. Magnetization transfer imaging was also performed in the brain stem in all patients, and other areas of the brain were sampled in one patient. The splenium of the corpus callosum and brain stem were studied because these are often affected by diffuse axonal injury. Scans were obtained 2 to 1129 days after injury (median, 41 days). MTR was considered abnormal if it was more than 2 SD below normal. Proton MR spectroscopy was used to calculate the N-acetylaspartate (NAA)/creatine (Cr) ratio. GOS was determined at least 3 months after injury. RESULTS: In 10 patients with a GOS of 1 to 4, the mean NAA/Cr was 1.24 +/- 0.28; two of these patients had abnormal MTR in normal-appearing white matter (NAWM). In 20 patients with a GOS of 5, the mean NAA/Cr was 1.53 +/- 0.37 (P < .05); four of these patients had abnormal MTR in NAWM. MTR abnormalities in NAWM were identified in six patients, but these changes did not correlate with GOS or MR spectroscopy changes. CONCLUSION: MTR and MR spectroscopy can quantify damage after TBI, and NAA levels may be a sensitive indicator of the neuronal damage that results in a worse clinical outcome.

Aspartic Acid↗

Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis.

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

Adult↗

Enhancing patterns in multiple sclerosis: evolution and persistence.

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

Adult↗

The effect of gadolinium-enhancing lesions on whole brain atrophy in relapsing-remitting MS.

OBJECTIVE: To determine the relationship between gadolinium-enhancing lesions and changes in whole brain parenchymal volume in patients with relapsing-remitting MS, and to test the hypothesis that gadolinium enhancement is a predictor of whole brain atrophy. METHODS: Twenty-four patients with clinically definite MS were imaged over 2 years. A computer-assisted segmentation technique based on high-resolution MRI was used to quantify gadolinium-enhancing T1 lesion volume and brain parenchyma and CSF volumes. Percent brain parenchymal volume (PBV) relative to the total intracranial volume was calculated, and changes in PBV were used to represent the degree of whole brain atrophy over 2 years. RESULTS: PBV at baseline was dependent on duration of MS, and a significant decrease in PBV was observed over the course of the study. Changes in enhanced T1 lesion load failed to correlate with changes in PBV, and multiple regression analyses determined that enhanced T1 lesion load at baseline was not a significant predictor of subsequent change in PBV. CONCLUSIONS: MR visible inflammation as demonstrated by enhanced T1 lesions is not a significant factor in the pathogenesis of whole brain atrophy in relapsing-remitting MS, suggesting that a more global pathologic process is responsible for the loss of brain parenchymal volume.

Adult↗

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.

OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS.

Adult↗

Assessment of spinal cord damage in MS using MRI.

Spinal cord imaging is important in the evaluation of patients with MS. There are several techniques available which provide satisfactory images of lesions in the spinal cord. Conventional measures used in the assessment of damage to the spinal cord include quantification of: (1) high intensity on T2 weighted images; (2) spinal cord enhancement; and (3) spinal cord atrophy. Although not presently implemented, newer methods including magnetization transfer, diffusion, and proton spectroscopy offer the potential for more specific classification of spinal cord MS. Assessment of spinal cord damage using MR still remains behind the development of brain methodology and represents both a challenge and an opportunity.

Humans↗