Faculty Bibliography

PURPOSE: To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects. MATERIALS AND METHODS: Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups' EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age. RESULTS: Analyses indicated three subgroups of WBNAA dynamics: Ten patients' conditions were 'stable,' exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P =.54); 27 patients showed 'moderate' decline, -2.8% (-0.34/12.18) per year (P <.01); and 12 patients experienced 'rapid' decline, -27.9% (-3.39/12.14) per year (P <.01). No correlation was found between WBNAA deficit, EDSS score, and age. CONCLUSION: Ascertaining an individual's NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status

Conventional MRI (cMRI) is limited in its ability to provide specific information about pathology in MS. Measures commonly derived from cMRI include T2 lesions, T1-enhanced lesions, atrophy, and possibly T1-hypointense lesions, which have been extensively investigated in many clinical trials. Better MRI measures are needed to advance our understanding of MS and design ideal clinical trials. This article reviews the strengths and weaknesses of the major MRI-based methods used to monitor MS evolution and submits that 1) metrics derived from magnetization transfer MRI, diffusion-weighted MRI, and proton MRS should be implemented to achieve reliable specific in vivo quantification of MS pathology; 2) targeted multiparametric MRI protocols rather than generic application of cMRI should be used in all possible clinical circumstances and trials; and 3) reproducible quantitative MR measures should ideally be used for the assessment of patients but are essential for clinical trials

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

BACKGROUND AND PURPOSE: Although mild or moderate traumatic brain injury (TBI) is known to cause persistent neurologic sequelae, the underlying structural changes remain elusive. Our purpose was to assess decreases in the volume of brain parenchyma (VBP) in patients with TBI and to determine if clinical parameters are predictors of the extent of atrophy. METHODS: We retrospectively assessed the total VBP in 14 patients with mild or moderate TBI at more than 3 months after injury and in seven patients at two time points more than 3 months apart. VBP was calculated from whole-brain MR images and then normalized by calculating the percent VBP (%VBP) to correct for intraindividual variations in cranial size. Clinical parameters at the time of trauma were evaluated for potential predictors of atrophy. Findings were compared with those of control subjects of similar ages. RESULTS: In the single time-point analysis, brain volumes, CSF volumes, and %VBP were not significantly different between patients and control subjects. In the longitudinal analysis, the rate of decline in %VBP (0.02 versus 0.0064 U/day, P =.05) and the change in %VBP between the first and second time points (-4.16 +/- 1.68 versus -1.49 +/- 1.7, P =.022 [mean +/-SD]) were significantly greater in patients. Change in %VBP was significantly greater in patients with loss of consciousness (LOC) than in those without LOC (P =.023). CONCLUSION: Whole-brain atrophy occurs after mild or moderate TBI and is evident at an average of 11 months after trauma. Injury that produces LOC leads to more atrophy. These findings may help elucidate an etiology for the persistent or new neurologic deficits that occur months after injury

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

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

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

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