Faculty Bibliography

Multiple sclerosis (MS) is considered a prototypical inflammatory autoimmune disease of the central nervous system that affects both myelin and axon. One of the most challenging aspects of MS is understanding the nature and mechanism of tissue injury because inflammation, demyelination, axonal degeneration, microvascular injury, and atrophy are all identified in histopathologic studies. Magnetic resonance (MR) imaging provides an in vivo examination of the brain that directly defines the extent of the pathology. In recent years, extensive MR studies have had a major impact on MS not only in making an early diagnosis but also in understanding of the disease. By exploiting the natural history and histopathologic correlation, conventional and various novel quantitative MR techniques have demonstrated the ability to image underlying pathological processes in MS. This review examines the role of different MR techniques in going beyond anatomical imaging and produces a more comprehensive overview of the pathophysiological changes which occur and evolve in MS.

MR offers by far the most sensitive technique for detecting multiple sclerosis (MS) lesions and has proved to be an important paraclinical tool for diagnosing MS and monitoring therapeutic trials. Technologic advances of MR in recent years have dramatically improved our understanding of MS disease. This review will focus on the contribution of MR imaging in MS and provide a discussion of conventional and advanced nonconventional MR techniques with regard to current findings, clinical correlations, and future directions

BACKGROUND AND PURPOSE: Evaluation of the spinal cord is important in the diagnosis and follow-up of patients with multiple sclerosis. Our purpose was to investigate diffusion tensor imaging (DTI) changes in different regions of normal-appearing spinal cord (NASC) in relapsing-remitting multiple sclerosis (RRMS). METHODS: Axial DTI of the cervical spinal cord was performed in 24 patients with RRMS and 24 age- and sex-matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated in separate regions of interest (ROIs) in the anterior, lateral, and posterior spinal cord, bilaterally, and the central spinal cord, at the C2-C3 level. Patients and control subjects were compared with respect to FA and MD with the use of an exact Mann-Whitney test. Logistic regression and receiver operating characteristic (ROC) curve analysis assessed the utility of each measure for the diagnosis of RRMS. RESULTS: DTI metrics in areas of NASC in MS were significantly different in patients compared with control subjects; FA was lower in the lateral (mean +/- SD of 0.56 +/- 0.10 versus 0.69 +/- 0.09 in control subjects, P < .0001), posterior (0.52 +/- 0.11 versus 0.63 +/- 0.10, P < .0001), and central (0.53 +/- 0.10 versus 0.58 +/- 0.10, P = .049) NASC ROIs. Assessing DTI metrics in the diagnosis of MS, a sensitivity of 87.0% (95% confidence interval [CI], 66.4 to 97.1) and a specificity of 91.7% (95% CI, 73.0 to 98.7) were demonstrated. CONCLUSION: The NASC in RRMS demonstrates DTI changes. This may prove useful in detecting occult spinal cord pathology, predicting clinical course, and monitoring disease progression and therapeutic effect in MS

Quantitative determination of cerebral blood volume (CBV) is important for understanding brain physiology and pathophysiology. In this work, a novel approach is presented for accurate measurement of absolute CBV (aCBV) using vascular-space-occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T(1) shortening property of Gd-DTPA. Two VASO images with identical imaging parameters are acquired before and after contrast agent injection, resulting in a subtracted image that reflects the amount of blood present in the brain, i.e., CBV. With an additional normalizing factor, aCBV in units of milliliters of blood per 100 mL of brain can be estimated. Experimental results at 1.5 and 3 T systems showed that aCBV maps with high spatial resolution can be obtained with high reproducibility. The averaged aCBV values in gray and white matter were 5.5 +/- 0.2 and 1.4 +/- 0.1 mL of blood/100 mL of brain, respectively. Compared to dynamic susceptibility contrast techniques, VASO MRI is based upon a relatively straightforward theory and the calculation of CBV does not require measurement of an arterial input function. In comparison with previous pre/postcontrast difference approaches, VASO MRI provides maximal signal difference between pre- and postcontrast situation and does not require the use of whole blood for signal normalization

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that is the most common cause of nontraumatic disability in young adults in the United States. In recent years, magnetic resonance imaging (MRI) has been established as an important paraclinical tool in MS for the assessment of clinical diagnosis, natural history, and treatment effects. In MS studies, there are many advantages to having a sensitive and reliable in vivo method for investigating the specific pathological changes of white matter and its integrity during the disease process. As a consequence, in the past decade, the application of MRI to the study of MS has been explored from conventional MRI to new advanced quantitative techniques with greater pathological specificity and sensitivity. Diffusion tensor imaging (DTI) is one of the most promising techniques with regard to MS. It quantifies the amount of nonrandom water diffusion within tissues and provides unique in vivo information about the pathological processes that affect water diffusion as a result of brain microstructural damage. This review outlines the current state of the art and future direction of DTI and fiber tractography in the study of MS disease

In this study, we describe prominent perivenular spaces as a sign that is seen on high-resolution (512 x 512) transverse T2-weighted MR images in patients with multiple sclerosis. The observed widening of perivenular space is depicted as a stringlike hyperintensity projecting radially and aligned with multiple sclerosis lesions (usually small), following the course and configuration of deep venular structures. This widening may be an important sign in differentiating primary (ie, in multiple sclerosis) from secondary causes of demyelination

BACKGROUND AND PURPOSE: Perfusion measurement in multiple sclerosis (MS) may cast light on the disease pathogenesis and lesion development since vascular pathology is frequently demonstrated in the disease. This study was performed to investigate the perfusion characteristics in MS lesions using dynamic susceptibility contrast MR imaging (DSC-MRI) to better understand the hemodynamic changes in MS. METHODS: Seventeen patients with relapsing-remitting MS were studied with DSC-MRI. Perfusion measurements included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), were obtained in enhancing, non-enhancing lesions covered by DSC-MRI and contralateral normal appearing white matter (NAWM) in patients as well as normal white matter in seventeen control subjects. RESULTS: DSC-MRI data demonstrated reduced perfusion with significantly prolonged MTT (P < 0.001) in lesions and NAWM in patients compared with normal white matter in controls. Compared to contralateral NAWM, enhancing lesions demonstrate increased CBF (P = 0.007) and CBV (P < 0.0001), indicating inflammation-mediated vasodilatation. A K means cluster analysis was performed and identifies approximately 63.8% of non-enhancing lesions (Class 1) with significantly decreased perfusion (P < or = 0.0001) when compared with contralateral NAWM. In contrast, the remainder 36.2% non-enhancing lesions (Class 2) show increased CBV (P = 0.02) in a similar fashion to enhancing lesions and can be observed on quantitative color-coded maps even without blood-brain barrier breakdown. CONCLUSION: DSC-MRI measurements demonstrate potential for investigating hemodynamic abnormalities that are associated with inflammatory activity, lesion reactivity and vascular compromise in MS lesions. Non-enhancing lesions showed both low and high perfusion suggesting microvascular abnormalities with hemodynamic impairment and inflammatory reactivity that cannot be seen on conventional MRI

The advent of MRI has made a remarkable progress in the understanding of age-related brain changes providing a noninvasive tool to study in vivo the normally aging individuals at multiple time points. However, conventional MRI techniques are unable to detect and quantify age-related microstructural changes that have been documented at the post-mortem examination of brain tissues. More sophisticated, quantitative MR techniques such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy have been shown to be sensitive to microstructural and metabolic changes that occur in gray and white matter over the course of life span. This review highlights some of these innovative, quantitative MR techniques that are particularly relevant for the study of occult age-related brain tissue changes. Characterization of the in vivo patterns of molecular and cellular changes that occur in the normal aging brain is of crucial importance to understand the pathophysiology of normal cognitive decline and to interpret observed changes in neurodegenerative diseases

PURPOSE: To investigate the feasibility of diffusion tensor imaging (DTI) assessment of microscopic fiber tract injury in the corpus callosum (CC) and other normal-appearing white matter (NAWM) in patients with early multiple sclerosis (MS). MATERIALS AND METHODS: DTI was performed in 12 healthy volunteers and 15 patients who have relatively short disease duration (mean = 2.7 years). Both fractional anisotropy (FA) and mean diffusivity (MD) were obtained in different regions of normal-appearing CC (NACC) and NAWM in frontal and occipital regions. RESULTS: The data showed significantly lower FA (P < 0.001) and higher MD (P < 0.04) for NACC regions, but not for frontal and occipital NAWM regions, in patients than in those in healthy volunteers after Bonferroni adjustment. The increase of MD in the entire NACC regions was correlated with the total cerebral lesion volume (r = 0.75, P = 0.001) in patients. CONCLUSION: The water diffusion changes indicate that in the early phase of disease there is a preferential occult injury of CC, which is likely due to the Wallerian degeneration from distant lesions