Although mean diffusivity and fractional anisotropy abnormalities in these patients with TBI were too subtle to be detected with the whole-brain histogram analysis, they are present in brain areas that are frequent sites of DAI. Because diffusion tensor imaging changes are present at both early and late time points following injury, they may represent an early indicator and a prognostic measure of subsequent brain damage.

Magnetization transfer imaging (MTI) was initially performed in normal guinea pigs and human volunteers. A magnetization transfer ratio (MTR) was calculated in the normal white matter and was found to be 42%-44%, with less than 2.5% variation, which indicates the high reproducibility of the measurement. MTI was then applied to an animal model of white matter disease, acute experimental allergic encephalomyelitis (EAE). In this model of EAE, pathologically proved lesions were edematous with essentially no demyelination. MTRs decreased slightly but significantly (5%-8%) compared with the MTRs of the same tissue region measured before the onset of the lesion [corrected]. Fifteen patients with multiple sclerosis (MS) also underwent MTI. In the 15 patients with MS, all lesions (209 plaques) had a significantly decreased MTR (average, 26%). The authors believe that demyelination produced the lower MTR, and, thus, lesions varied in transfer ratio on the basis of the extent of myelin loss. In patients with MS, particularly those with chronic and/or progressive MS, the MTR of the normal-appearing white matter was significantly decreased. The data suggest that calculated MTR obtained with in vivo MTI may enable differentiation of edema from demyelination, and that MTI can demonstrate white matter abnormalities that cannot be seen with standard spin-echo or gradient-echo magnetic resonance imaging.

Magnetic resonance (MR) techniques have had a major impact in the last 10-15 years in understanding and managing multiple sclerosis. This review summarizes the current uses of MR in multiple sclerosis, based on the proceedings of a recent international workshop, under four headings: (i) technical issues; (ii) role in diagnosis; (iii) natural history studies in understanding the disease; (iv) application in clinical trials. The theory and methodology of relevant technical issues is outlined, in order to provide a framework with which to understand the potential and limitations of MR in addressing biological and clinical questions in multiple sclerosis. The principles underlying signal-to-noise and contrast-to-noise ratio are discussed, along with the techniques and clinical results for conventional and fast spin echo T2-weighted imaging, fluid-attenuated inversion recovery, detection of blood-brain barrier break down and hypointense lesions on T1-weighted images, magnetization transfer, T2 decay-curve analysis, MR spectroscopy, spinal cord imaging, diffusion imaging, and quantification of lesion load and atrophy. MRI has an extremely valuable role in confirming the clinical diagnosis of multiple sclerosis. T2-weighted brain imaging remains the standard diagnostic tool, but in some instances it is usefully complemented with gadolinium enhancement and spinal imaging. The caveat that the diagnosis of multiple sclerosis remains primarily a clinical one cannot be over-emphasized. Serial MRI studies have added much to our understanding of the natural history and pathophysiology of the disease. Blood-brain barrier breakdown is a consistent early feature of new lesion development in relapsing-remitting and secondary progressive multiple, sclerosis, and this usually correlates with active inflammation and myelin breakdown. A number of the acute MR changes are reversible, but chronic persistent abnormalities in a number of MR parameters, such as reduced N-acetyl aspartate, low magnetization transfer ratios, atrophy and T1-hypointensity, suggest the presence of demyelination and/or axonal degeneration in many chronic lesions. The presence and extent of T2-weighted MRI abnormalities at first presentation with a clinically isolated syndrome suggestive of demyelination strongly predicts the risk of developing clinically definite multiple sclerosis in the next few years. In established multiple sclerosis, however, the correlations between T2 abnormalities and disability are modest. This poor relationship partly relates to the discrepancy between lesion site and function in attempting to correlate locomotor disability with brain MRI findings. However, the correlations between brain lesion load and cognitive dysfunction in multiple sclerosis, whilst more evident, are still modest. A more important limitation is the low pathological specificity of abnormalities seen on T2-weighted images. Stronger correlations have been found between disability and new putative MR markers for demyelination and/or axonal degeneration. Serial studies...

Purpose:To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging. Materials and Methods:Twenty-seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre-and postcontrast T1-weighted imaging, T2-weighted imaging, FLAIR, and SWI at 1.5 T, 3 T, and 4 T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were reevaluated for their iron content using the SWI filtered phase images. Results:There were a variety of new lesion characteristics identified by SWI, and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI, and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established. Conclusion:The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus. MULTIPLE SCLEROSIS (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (1,2). Most patients start with a relapsing-remitting course, which has a clearly defined episode of neurologic disability and recovery. The pathologic hallmark of multiple sclerosis is the demyelinated plaque, a well-demarcated hypocellular area characterized by the loss of myelin, along with axonal loss due to (3,4), and the formation of astrocytic scars. The etiologic mechanism underlying MS is generally believed to be autoimmune inflammation (5). Nevertheless, what initiates the disease and the sequence of events underlying the development of MS is not yet well established (6).Conventional magnetic resonance imaging (MRI) has been used routinely to diagnose and monitor the disease spatially and temporally. The use of conventional MRI to measure disease activity and assess effects of therapy is now standard in clinical practice and drug trials (7). T2-weighted imaging (T2WI) is highly sensitive in the detection of hyperintensities in white matter. However, hyperintensities on T2WI can correspond to a wide spectrum of pathology, ranging from edema and mild demyelination to lesions in which the neurons and supporting glial cells are replaced by glial scars or liquid necrosis (8 -14). In addition to T2WI, Gadolinium enhancement on T1-weighted imaging (T1WI) can suggest acute inflammation, which is a marker of disease It is becoming a consensus among many studies that iron is enriched within oligodendrocytes and myelin in both normal and diseased tissue (20 -23). One explanation for such findings proposes that iron is associated with the biosynthetic enzymes ...

A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans (T2 weighted, 5 mm thick) of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T2 pixel values to correct field inhomogeneities ("shading"). Average (-SD) brain volume, excluding cerebellum, was 1090.91 ml (±# 114.30; range, 822.19-1363.66), and cerebrospinal fluid (CSF) volume was 127.91 ml (±57.62; range, 34.00-297.02). Brain volume was higher (by 5 ml) in the right hemisphere (P < 0.0001). Men (n = 34) had 91 ml higher brain and 20 ml higher CSF volume than women (n = 35). Age was negatively correlated with brain volume [r(67) =-0.32, P < 0.01] and positively correlated with CSF volume (r = 0.74, P < 0.0001). The slope of the regression line with age for CSF was steeper for men than women (P = 0.03). This difference in slopes was significant for sulcal (P < 0.0001), but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas in women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions.The study of brain regulation of human behavior requires measurement of structural variables, and this has been done primarily by postmortem studies (e.g., refs. 1-6). Atrophy was inferred from reduced brain weight or volume or increased differences between brain volume and cranial capacity-i.e., cerebrospinal fluid (CSF) volume. Several studies found aging associated with atrophy (7-9). Others did not find age effects until senescence (usually defined as age >55 or 60; refs. 4, 10, and 11). Women have lower brain volume, related to body and cranial size (e.g., refs. 4, 6, and 9).In vivo measurement of brain volume became feasible with computed tomography, and more recently with magnetic resonance imaging (MRI), which is more sensitive than computed tomography for determining sulcal changes and has better tissue contrast, multiplanar imaging capabilities, absence of bone artifact, and no ionizing radiation. In addition to elucidating structural substrates of brain function, anatomic volume measures are important for interpreting metabolic data (12). Thus, decline in cerebral blood flow and metabolism with age (e.g., refs. 13-15), and higher cerebral blood flow in women (16), could be explained by structural effects (17).Several computed tomography studies investigated ageassociated changes. Takeda and Matsuzawa (18) subjects aged 21-81 studied with a 2-T magnet and a spinlattice relaxation time (T1)-weighted sequence. However, in contrast to the other studies, which yielded brain volume estimates averaging 1100-1200 ml, their estimates were >2000 ml for men and >1800 ml for women. Jernigan et al. (23) found a linear re...