Faculty Bibliography

Although perfusion is of major interest for many spinal cord disorders, there is no established, reproducible technique for evaluating blood flow or blood volume of the spinal cord in humans. Here the first report of in vivo measurement of human spinal cord blood volume (scBV) is presented. An FDA-approved contrast agent, Gd-DTPA, was used as an intravascular agent for the cord parenchyma, and pre-/post-contrast vascular-space-occupancy (VASO) MRI experiments were performed to obtain a quantitative estimation of scBV in mL blood/100 mL tissue. VASO MRI was used because it does not rely on knowledge of an arterial input function, it avoids the imaging artifacts of single-shot echo planar imaging approaches, and it requires only relatively simple and direct calculations for scBV quantification. Preliminary tests at 1.5 T and 3 T gave mean +/- SD scBV values of 4.3 +/- 0.7 ml/100 mL tissue (n = 6) and 4.4 +/- 0.7 ml/100 mL tissue (n = 4), respectively, consistent with the expectation that the scBV values would not be field-dependent

BACKGROUND AND PURPOSE: Deposition of iron has been recognized recently as an important factor of pathophysiologic change including neurodegenerative processes in multiple sclerosis (MS). We propose that there is an excess accumulation of iron in the deep gray matter in patients with MS that can be measured with a newly developed quantitative MR technique--magnetic field correlation (MFC) imaging. MATERIALS AND METHODS: With a 3T MR system, we studied 17 patients with relapsing-remitting MS and 14 age-matched healthy control subjects. We acquired MFC imaging using an asymmetric single-shot echo-planar imaging sequence. Regions of interest were selected in both deep gray matter and white matter regions, and the mean MFC values were compared between patients and controls. We also correlated the MFC data with lesion load and neuropsychologic tests in the patients. RESULTS: MFC measured in the deep gray matter in patients with MS was significantly higher than that in the healthy controls (P < or = .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. The increased iron deposition measured with MFC in the deep gray matter in the patients correlated positively with the total number of MS lesions (thalamus: r = 0.61, P = .01; globus pallidus: r = 0.52, P = .02). A moderate but significant correlation between the MFC value in the deep gray matter and the neuropsychologic tests was also found. CONCLUSION: Quantitative measurements of iron content with MFC demonstrate increased accumulation of iron in the deep gray matter in patients with MS, which may be associated with the disrupted iron outflow pathway by lesions. Such abnormal accumulation of iron may contribute to neuropsychologic impairment and have implications for neurodegenerative processes in MS

BACKGROUND AND PURPOSE: Hypoperfusion of the normal-appearing white matter in multiple sclerosis (MS) may be related to ischemia or secondary to hypometabolism from wallerian degeneration (WD). This study evaluated whether correlating perfusion and diffusion tensor imaging (DTI) metrics in normal-appearing corpus callosum could provide support for an ischemic mechanism for hypoperfusion. MATERIALS AND METHODS: Fourteen patients with relapsing-remitting MS (RRMS) and 17 control subjects underwent perfusion MR imaging and DTI. Absolute measures of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated. Mean diffusivity (MD) and fractional anisotropy (FA) maps were computed from DTI data. After visual coregistration of perfusion and DTI images, regions of interest were placed in the genu, central body, and splenium of normal-appearing corpus callosum. Pearson product-moment correlation coefficients were calculated using mean DTI and perfusion measures in each region. RESULTS: In the RRMS group, CBF and CBV were significantly correlated with MD in the splenium (r = 0.83 and r = 0.63, respectively; both P < .001) and in the central body (r = 0.86 and r = 0.65, respectively; both P < .001), but not in the genu (r = 0.23 and 0.25, respectively; both P is nonsignificant). No significant correlations were found between MTT and DTI measures or between FA and any perfusion measure in the RRMS group. No significant correlations between diffusion and perfusion metrics were found in control subjects. CONCLUSION: In the normal-appearing corpus callosum of patients with RRMS, decreasing perfusion is correlated with decreasing MD. These findings are more consistent with what would be expected in primary ischemia than in secondary hypoperfusion from WD.

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