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
Radiology 2001 Sep;220(3):606-10
University of Pennsylvania Medical Center,Department of Radiology, Founders Bldg, Ground Floor, 3400 Spruce St, Philadelphia, PA 19104-4283, USA
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.
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.
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.
Pierpaoli C, Barnett A, Pajevic S, Chen R, Penix LR, Virta A, Basser P
NeuroImage 2001 Jun;13(6 Pt 1):1174-85
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5772, USA
This study investigates water Diffusion changes in Wallerian Degeneration.
We measured indices derived from the Diffusion Tensor (DT) and T2-weighted signal intensities in the Descending Motor Pathways of patients with small chronic Lacunar Infarcts of the Posterior Limb of the Internal Capsule on one side.
We compared these measurements in the healthy and lesioned sides at different levels in the BrainStem caudal to the primary lesion.
We found that secondary White Matter degeneration is revealed by a large reduction in Diffusion Anisotropy only in regions where Fibers are arranged in isolated bundles of parallel Fibers, such as in the Cerebral Peduncle.
In regions where the Degenerated Pathway crosses other Tracts, such as in the rostral Pons, paradoxically there is almost no change in Diffusion Anisotropy, but a significant change in the measured orientation of Fibers.
The trace of the Diffusion Tensor is moderately increased in all affected regions. This allows one to differentiate secondary and primary Fiber loss where the increase in trace is considerably higher.
We show that DT-MRI is more sensitive than T2-weighted MRI in detecting Wallerian Degeneration. Significant Diffusion abnormalities are observed over the entire trajectory of the affected Pathway in each patient.
This finding suggests that mapping Degenerated Pathways noninvasively with DT-MRI is feasible. However, the interpretation of water Diffusion data is complex and requires a priori information about Anatomy and architecture of the Pathway under investigation.
In particular, our study shows that in regions where Fibers cross, existing DT-MRI-based Fiber tractography algorithms may lead to erroneous conclusion about Brain connectivity.
T1 Lesion Load And Cerebral Atrophy As A Marker For Clinical Progression In Multiple Sclerosis. A Prospective 18 Months Follow-Up Study
Sailer M, Losseff NA, Wang L, Gawne-Cain ML, Thompson AJ, Miller DH
Eur J Neurol 2001 Jan;8(1):37-42
Otto-von-Guericke-University, Department of Neurology II, Magdeburg, Leipzigerstrasse 44, 39120 Magdeburg, Germany
PMID# 11509079; UI# 21400575
We investigated the relationship between local tissue destruction, diffuse Cerebral Atrophy and clinical progression in patients with established Multiple Sclerosis (MS).
Twenty-nine patients with MS (13 patients with Relapsing/Remitting and 16 with Secondary/Progressive disease) were included in a prospective serial study.
Cerebral volumes, T1 HypoIntense lesion volumes, T2 HyperIntense lesion volumes at baseline and at 18 months follow-up.
And, the volume of monthly enhancing lesions from month 0 to month 9 were assessed on Magnetic Resonance Imaging (MRI) Brain scans using highly reproducible semi-automated quantitative techniques.
The main outcome measures were the MRI parameters and disability on Kurtzkes' Expanded Disability Status Scale. There was a significant correlation between the change (increase) in T1 lesion volume and progressive Cerebral Atrophy
Whereas, no correlation between the T2 lesion volume and Atrophy was seen over the same follow-up period.
The change in T1 lesion volume correlated more strongly than did T2 lesion volume change with the change in disability.
We conclude that HypoIntense abnormalities detected in T1-weighted Brain scans and Cerebral Atrophy may be directly linked.
Although one should bear in mind some potential for reversibility due to inflammatory, Edematous lesions, these MR measures are a useful marker of progressive tissue damage and clinical progression in established MS.
Imaging Of Multiple Sclerosis: Role In NeuroTherapeutics
Bakshi R, Minagar A, Jaisani Z, Wolinsky JS
NeuroRx 2005 Apr;2(2):277-303
Brigham and Women's Hospital, Harvard Medical School, Department of Neurology and Radiology, Partners MS Center, Center for Neurological Imaging, Boston, Massachusetts 02115, USA
Magnetic Resonance Imaging (MRI) plays an ever-expanding role in the evaluation of Multiple Sclerosis (MS).
This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected Clinically Isolated Syndromes.
In addition, MRI is a key tool in providing primary therapeutic outcome measures for Phase I/II trials and secondary outcome measures in Phase III trials.
The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called Normal-Appearing Brain Tissue).
However, all current MRI methodology suffers from limited specificity for the underlying histopathology.
Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials.
In which the use of Gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation.
Advanced imaging methods including Magnetization Transfer, Fluid Attenuated Inversion Recovery, Diffusion, Magnetic Resonance Spectroscopy, Functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS.
And, may provide methods to monitor therapies more sensitively in the future.
However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on NeuroTherapeutics.