INTRODUCTION: Precise and accurate quantification of the volume, and the change in volume across time, of the lateral ventricles (LV) based on MRI data is an important goal in understanding the natural progression of neurodegenerative disorders such as Alzheimer’s disease (AD) (e.g., Nestor et al., Brain. 2008;131:2443-54) and multiple sclerosis (MS) (e.g., Dalton et al., Neurology. 2006;66:693-8). Development of precise and accurate automated-segmentation techniques (e.g., Schnack et al., NeuroImage. 2001;14:95-104) is important in order to increase the efficiency, objectivity, and reliability of such quantifications of the LVs. In the present study, we addressed two issues related to such a goal. First, we examined the accuracy of a novel technique for the automated segmentation of the LVs in 270 patients with AD. Second, in a preliminary, representative subset of 33 of these patients, we assessed the concurrent validity, face validity, and precision of two novel techniques that we have developed for the automated quantification of longitudinal changes in the LV volumes of patients with AD.

There were two aims to this study. First, to explore how the reduction in the volume of abnormal T2-signal intensity associated with white matter (WM) lesions in multiple sclerosis (MS) relates to tissue loss resulting from focal pathology inside lesions. Second, to demonstrate that this volume of abnormal T2-signal intensity underestimates the actual size of the region to which the direct effects of lesion activity extend. For these purposes, we used deformation field analysis to quantify the evolution of local atrophy associated with a chronic peri-ventricular lesion in a patient with secondary progressive MS. This subject had particular features that may not necessarily co-exist in a group of unselected patients, which enabled interesting observations to be made. We show, quantitatively, that the focal WM lesion was associated with adjacent regional WM volume loss, which was disproportionate to concurrent diffuse atrophy in the rest of the normal appearing brain tissue, and that the loss of volume associated with the lesion was partially reciprocated by local ventricular expansion. Our observations re-emphasise the complex relationship between the change in the volume of abnormal signal intensity on magnetic resonance images and the tissue volume change directly related to lesion pathology. Multiple Sclerosis 2007; 13: 809-813. http:// msj.sagepub.com

We present a new method for advanced image processing to separately quantify significant decreases and increases in the magnetization transfer ratio (MTR) of individual voxels of MS lesions as markers of demyelination and remyelination. We used this method to analyze the evolution of MTR in individual voxels of an acute, Gadolinium (Gd)-enhancing lesion that was available for pathology. Over 6.5 months following enhancement, MTR was low and stable in the lesion center (81% of the initially Gd-enhancing lesion volume (GdLV)) and MTR increased at the lesion border with normal-appearing white matter (14%GdLV). The estimated error of these measurements was less than 1.8%GdLV based on scan/rescan analysis. Histopathological analysis confirmed a demyelinated lesion centre with diffuse presence of macrophages/microglia and marked loss of oligodendrocytes and a partially remyelinated lesion border with diffuse presence of macrophages/microglia and relatively more oligodendrocytes compared to the lesion centre. The correlation of imaging and histopathological findings support the validity and sensitivity of our method of voxel-based MTR image processing for monitoring demyelination and remyelination in vivo.

At a conference held in October 2005, participants presented studies on high dose immunosuppression with hematopoietic cell transplant (HCT) for multiple sclerosis (MS), including neuroimmunological and magnetic resonance imaging (MRI) mechanistic approaches, clinical registry reports, and ongoing or newly-designed protocols. A discussion panel considered questions on how to define success, timing of controlled clinical trials, difficulty in patient recruitment, and future direction of high dose therapy.

The authors measured brain atrophy in nine patients undergoing immunoablation and autologous hematopoietic stem cell transplantation for multiple sclerosis. From baseline to 1 month after treatment, atrophy was 10 times faster than before treatment. A patient with non-CNS lymphoma showed comparable acute brain atrophy after analogous therapy. These observations suggest that brain atrophy after immunoablation may not be due entirely to the resolution of edema but may be related to chemotoxicity.

Multiple sclerosis (MS) lesions show differing degrees of demyelination and remyelination. Changes in myelin content are associated with changes in magnetization transfer on MRI. Since acute inflammation and demyelination are spatially and temporally inhomogeneous, we hypothesized that local magnetic transfer ratio (MTR) heterogeneity might be predictive of subsequent changes in MTR. To test this hypothesis, we analyzed MTR images obtained in 14 subjects, at baseline and after 2 months follow-up. We segmented lesions and normal-appearing white-matter (NAWM), calculated MTR signal inhomogeneity maps at baseline and MTR lesion difference maps between baseline and follow-up. We found that regions with low MTR inhomogeneity at baseline experienced little further change in MTR on follow-up. The mean change in lesion MTR between baseline and follow-up was 0.10 ± 3.70; in NAWM it was −0.09 ± 2.02. We found that regions with high MTR inhomogeneity at baseline would change MTR on follow-up: (1) voxels with significantly high MTR in regions of high MTR inhomogeneity at baseline showed a mean decrease in MTR between baseline and follow-up of −2.51 ± 4.68 in lesions and −1.41 ± 3.00 in NAWM; (2) voxels with low MTR in regions of high MTR inhomogeneity at baseline showed a mean increase in MTR between baseline and follow-up of 2.61 ± 6.07 in lesions. These changes in MTR were significantly different (P < 0.001). These results suggest that calculation of MTR signal inhomogeneity may provide a method for quantifying the potential for remyelination and demyelination, and thus could provide an important MRI biomarker for assessing the efficacy of therapies targeting remyelination.

Cortical grey matter (cGM) develops a substantial burden of pathology in multiple sclerosis (MS). Previous cross-sectional studies have suggested a relationship between measures of cortical atrophy and disability. Our objective was to develop a method for automatically measuring the apparent cGM thickness as well as the integrity of the interface between cGM and subcortical white matter (GM/WM) both globally and regionally on T-1-weighted MRI, and use this method in a longitudinal investigation of how these measures differed between patients with stable MS and patients with progressing disability. Measurements were made over the whole brain and for anatomically specified cortical regions, both cross-sectionally at baseline and longitudinally on two MRI scans performed on average I year apart. We found a higher average rate of apparent loss of cGM thickness across the whole brain in the group that progressed over the intersean interval compared to the group that remained stable (progressing = -3.13 +/- 2.88%/year, stable = 0.06 +/- 2.31%/year, P = 0.002). This difference was detected with regional measures in parietal and precentral cortex. In contrast, change in the GM/WM interface integrity did not show detectable regional differences, although the group of MS patients whose disability progressed showed a significant decrease in GM/WM interface integrity compared to the stable group (P = 0.003). Regional measures of apparent loss of cGM thickness enhance sensitivity to cortical pathological changes. A measure of integrity offers a new index of disease-associated cortical changes at the GM/WM interface. The results suggest that progression of disability in MS is associated with the progression of MRI-detectable cortical pathology. (C) 2004 Elsevier Inc. All rights reserved.

Post-exercise recovery of intracellular pH (pH(i)) assessed using phosphorus magnetic resonance spectroscopy has not been previously evaluated in its entirety due to its complex time-course and missing data points resulting from a transient loss of inorganic phosphate signal. By considering the transition from exercise to recovery as a step function input, pH(i) recovery was modeled based on the creatine-kinase equilibrium, and the entire pH(i) recovery was characterized by calculating the time required for pH(i) recovery (t(pHrec)). Applying this methodology, normal subjects showed a strong linear correlation between phosphocreatine (PCr) half-time and t(pHrec) (r = 0.90, P < 0.001). In mitochondrial myopathy (MM) patients with weakness in the limb examined, 9/10 had faster pH(i) recovery relative to PCr recovery; wide normal ranges from a control group which included deconditioned subjects resulted in 7 of those 10 patients having otherwise normal recovery indices. Therefore, modeling pH(i) recovery allows characterization of the entire pH(i) recovery and detects altered proton handling in MM patients, including those with otherwise normal recovery indices.

The purpose of this study was to assess the effect of physical deconditioning on skeletal muscle's oxidative metabolism as evaluated by phosphorus-31 magnetic resonance spectroscopy ((31)P MRS). Twenty-seven subjects without muscle disease, representing a wide range of fitness levels, were evaluated with (31)P MRS. Spectra were obtained at rest and during recovery from in-magnet exercise. The data show a significant correlation between maximum resting metabolic equivalent (MET) score and the following (31)P MRS recovery indices: adenosine diphosphate and phosphocreatine recovery half-time; initial phosphocreatine resynthesis rate; calculated estimation of mitochondrial capacity; pH at end of exercise; and phosphocreatine depletion. In addition, significant differences between the deconditioned and conditioned group were found for all of the aforementioned recovery indices. At rest, only the inorganic phosphate concentration was significantly different between the two groups. These data indicate that physical activity level should be taken into account when assessing patients' oxidative metabolism with (31)P MRS.

Phosphorus magnetic resonance (MR) spectroscopy was used to measure the recovery kinetics of calculated cytoplasmic metabolically active adenosine diphosphate (ADP) after exercise in normal subjects and patients with mitochondrial myopathies. These kinetics have previously been fitted with a single exponential function, despite a complex time-dependent undershoot in many subjects. By considering the transition from ischemic-exercise to perfused-recovery as a step function input, a second-order linear system was developed yielding a step response function to fit the ADP recovery. Using this method, an average improvement in fit of 23% resulted in a significant improvement in the characterization of ADP recovery for all normal subjects with substantial undershoot. The patient group had a comparable improvement in fit of 11%. Fitting the ADP recovery with a second-order step response function can provide significantly better characterization of muscle oxidative metabolism in vivo.