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

Ge Y; Grossman RI; Udupa JK; Babb JS; Nyul LG; Kolson DL
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
PMID: 11526256
ISSN: 0033-8419
CID: 24396

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

Ge Y; Grossman RI; Udupa JK; Babb JS; Kolson DL; McGowan JC
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
PMID: 11237968
ISSN: 0195-6108
CID: 24400

Enhancing patterns in multiple sclerosis: evolution and persistence

He J; Grossman RI; Ge Y; Mannon LJ
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
PMID: 11290475
ISSN: 0195-6108
CID: 24397

New magnetic resonance spectroscopy strategies

Chapter by: Gonen O; Grossman RI
in: Magnetic resonance spectroscopy in multiple sclerosis by Filippi M; Arnold DL; Comi G [Eds]
Milano ; New York : Springer, 2001
pp. 97-112
ISBN: 8847001234
CID: 3795

Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study

Gottlieb, A B; Lebwohl, M; Shirin, S; Sherr, A; Gilleaudeau, P; Singer, G; Solodkina, G; Grossman, R; Gisoldi, E; Phillips, S; Neisler, H M; Krueger, J G
BACKGROUND:OKTcdr4a (IMUCLONE) is a humanized anti-CD4 IgG4 monoclonal antibody that retains the binding and in vitro immunosuppressive properties of the parent murine antibody. Psoriasis is a chronic disease for which treatment with multiple doses of monoclonal antibodies is likely to be required for adequate control. OBJECTIVE:This study was performed to test the efficacy and safety of OKTcdr4a, given in sequential courses over a period of several weeks, in the treatment of moderate to severe psoriasis vulgaris. METHODS:Twenty-eight patients (45.6 +/- 10.1 years of age) were studied, with a mean pretreatment Psoriasis Area and Severity Index (PASI) score of 18.3. In the first double-blind phase of the study, patients were randomized to receive OKTcdr4a as a 225 mg/course (low dose), 750 mg/course (high dose), or placebo divided into 3 identical infusions over a 5-day period. After 42 days, patients who met the criteria for re-treatment with OKTcdr4a were re-treated with the 750 mg/course in an open phase of the study. RESULTS:After the double-blind course of treatment, the mean PASI decreased by 11% in the placebo group, by 4% in the low-dose group, and by 17% in the high-dose group at 15 days. Twenty patients met the criteria for re-treatment (ie, did not experience a decrease in PASI score of 50% at 42 days). They were re-treated with OKTcdr4a at 43 days with the 750 mg/course in the open phase of the study. By day 99, the mean PASI score decreased from 19.9 at baseline to 17 in those patients who had received either placebo or low-dose OKTcdr4a followed by high-dose OKTcdr4a. In contrast, the mean PASI score decreased from 17.4 at baseline to only 7.7 in those patients who had received high-dose OKTcdr4a for both courses. Sustained CD4 saturation was not necessary for sustained clinical response. No patients had significant changes in circulating CD4(+) T-cell counts. The infusions were well tolerated. CONCLUSION/CONCLUSIONS:Targeting CD4 using sequential treatments with a humanized monoclonal antibody (OKTcdr4a) may offer another therapeutic option for the treatment of moderate to severe psoriasis.
PMID: 11004613
ISSN: 0190-9622
CID: 3866642

Multiple sclerosis: magnetization transfer histogram analysis of segmented normal-appearing white matter

Catalaa I; Grossman RI; Kolson DL; Udupa JK; Nyul LG; Wei L; Zhang X; Polansky M; Mannon LJ; McGowan JC
PURPOSE: To investigate and characterize the global distribution of magnetization transfer (MT) ratio values of normal-appearing white matter (NAWM) in patients with relapsing-remitting multiple sclerosis (MS) and test the hypothesis that the MT histogram for NAWM reflects disease progression. MATERIALS AND METHODS: Conventional and MT magnetic resonance (MR) images were obtained in 23 patients and 25 healthy volunteers. Clinical tests for comparison with the MT histogram parameters included the Extended Disability Status Scale and the ambulation index. Lesion load calculated with T2-weighted MR images and whole-brain and white matter volumes were measured. RESULTS: The location of the MT histogram peak and the mean MT ratio for NAWM were significantly lower in patients with MS than in control subjects. In longitudinal studies, the histogram peak location and mean MT ratio shifted in the direction of normal values as the duration of disease increased. A mean of 26.5% of the volume of new lesions identified on the later studies were demonstrated to have originated in NAWM corresponding to 'lost' pixels on the histogram. CONCLUSION: MT histogram analysis of NAWM, including longitudinal analysis, may provide new prognostic information regarding lesion formation and increase understanding of the course of the disease
PMID: 10924552
ISSN: 0033-8419
CID: 24405

Numerical tissue characterization in MS via standardization of the MR image intensity scale

Ge Y; Udupa JK; Nyul LG; Wei L; Grossman RI
Image intensity standardization is a recently developed postprocessing method that is capable of correcting the signal intensity variations in MR images. We evaluated signal intensity of healthy and diseased tissues in 10 multiple sclerosis (MS) patients based on standardized dual fast spin-echo MR images using a numerical postprocessing technique. The main idea of this technique is to deform the volume image histogram of each study to match a standard histogram and to utilize the resulting transformation to map the image intensities into standard scale. Upon standardization, the coefficients of variation of signal intensities for each segmented tissue (gray matter, white matter, lesion plaques, and diffuse abnormal white matter) in all patients were significantly smaller (2.3-9.2 times) than in the original images, and the same tissues from different patients looked alike, with similar intensity characteristics. Numerical tissue characterizability of different tissues in MS achieved by standardization offers a fixed tissue-specific meaning for the numerical values and can significantly facilitate image segmentation and analysis
PMID: 11050641
ISSN: 1053-1807
CID: 24403

The costs of CT procedures in an academic radiology department determined by an activity-based costing (ABC) method

Nisenbaum HL; Birnbaum BA; Myers MM; Grossman RI; Gefter WB; Langlotz CP
PURPOSE: The purpose of this work was to determine the costs of computed tomography (CT) procedures in a large academic radiology department, including both professional (PC) and technical (TC) components, by analyzing actual resource consumption using an activity-based costing (ABC) method and comparing them with Medicare payments. METHOD: Over a 12 month period from July 1, 1996, to June 30, 1997, 1,011 CT procedures, representing 16 Physicians' Current Procedural Terminology (CPT) codes and 98.3% of CT studies performed, were carefully observed by a research assistant trained in ABC methodology. Information collected during these time and motion studies included personnel/machine time and direct materials used. Actual resource units used during the different activities in each CT procedure were valued using appropriate cost drivers. Unit values for both direct and overhead costs were calculated: the cost of an individual procedure equaled the sum of component costs. Costs were compared with PC and TC payments according to the 1997 Medicare Fee Schedule. RESULTS: Total costs of CPT codes 70450 (CT Head unenhanced), 71260 (CT Chest enhanced), and 74160 (CT Abdomen enhanced), which represented 71.2% of CT studies performed, were $189.19, $273.53, and $343.20, respectively. For all 16 nonmodified CPT codes analyzed, Medicare's professional reimbursement was less than the professional cost, whereas its technical reimbursement exceeded respective cost in 14 of the 16 codes. CONCLUSION: In the setting and time period studied, Medicare underreimbursed professional costs while overreimbursing technical costs
PMID: 11045708
ISSN: 0363-8715
CID: 24404

Assessment of spinal cord damage in MS using MRI

Grossman RI; Barkhof F; Filippi M
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
PMID: 10606804
ISSN: 0022-510x
CID: 43963

Magnetic resonance imaging in patients with central nervous system pathology: a comparison of OptiMARK (Gd-DTPA-BMEA) and Magnevist (Gd-DTPA)

Grossman RI; Rubin DL; Hunter G; Haughton VM; Lee D; Sze G; Kuhn MJ; Maravilla K; Tu R; Heindel W; Wippold FJ 2nd; Leeds N; Zelch J; Jinkins JR; Grodd W; Truwit C; Kanal E; Provenzale JM; Ramsey R; Simon J; Brunberg JA; Stevens GR; Kristy RM
RATIONALE AND OBJECTIVES: The objective of the two pivotal phase 3 studies was to evaluate the safety and efficacy of OptiMARK (Gd-DTPA-bis(methoxyethylamide) [Gd-DTPA-BMEA]) compared with Magnevist (Gd-DTPA) in magnetic resonance imaging of the central nervous system. METHODS: Two multicenter, randomized, double-blind, parallel group studies were conducted in 395 patients with known or suspected central nervous system pathology. Subjects were randomized to receive a single 0.1 mmol/kg intravenous injection of either Gd-DTPA-BMEA or Gd-DTPA. The safety of Gd-DTPA-BMEA and Gd-DTPA was monitored for up to 72 hours after study drug administration. Precontrast and postcontrast administration magnetic resonance scans were acquired using identical imaging planes and techniques. RESULTS: No deaths or unexpected adverse events were reported in either group. A comparison of adverse events by intensity and relation demonstrated no statistically significant differences between the two groups. Gd-DTPA-BMEA and Gd-DTPA were equivalent with respect to confidence in diagnosis, conspicuity, and border delineation. CONCLUSIONS: Gd-DTPA-BMEA and Gd-DTPA demonstrated comparable efficacy profiles, and the safety profiles were considered similar
PMID: 10901102
ISSN: 0020-9996
CID: 24406