Histologic examination of multiple sclerosis (MS) brain lesions reveals heterogeneity including the presence or absence of a central blood vessel. Recent work has shown that T2* weighted magnetic resonance imaging at 7T allows the identification of small parenchymal veins within MS lesions. The aims of this study were (1) to compare whether a comparable sequence at 3T was also capable of demonstrating parenchymal veins within MS brain lesions, and (2) to investigate the potential of 7T T2* weighted imaging to differentiate between MS white matter lesions and age-related vascular lesions seen in controls. Seven patients with demyelinating brain disease and 7 healthy volunteers were scanned at 3T and 7T. Fluid attenuated inversion recovery (FLAIR) images acquired at 3T were used to identify each brain lesion in each patient. A comparison of images from both field strengths was then made to determine whether white matter lesions seen in 3T FLAIR images could be identified in T2*-weighted images, and whether a central vein could be detected. A total of 358 brain lesions were identified in the brains of the 7 patients using 3T FLAIR images. The 3T T2* sequence detected 89% of FLAIR lesions compared with 94% using the 7T T2* sequence (P = 0.0002). A central vessel could be identified in 45% of visible lesions using 3T T2* and 87% of visible lesions using 7T T2* (P < 0.0001). Using 7T T2* imaging, a central vein was evident in only 8% of the discrete white matter lesions found in the brains of healthy volunteers. This study suggests that ultra high field imaging is advantageous in demonstrating detailed structural anatomy of MS lesions. 7T T2* imaging can be used in the future to investigate the pathogenesis of MS lesions. The potential for ultra high field imaging to discriminate between MS white matter lesions and microangiopathic lesions warrants further investigation as this would represent a clinically useful application.

Summary: Aims: This open‐label prospective phase I/IIa clinical study used autologous bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) followed by mesenchymal stromal cells conditioned media (MSC‐CM) for the first time to treat multiple sclerosis (MS) patients. The primary goal was to assess the safety and feasibility and the secondary was efficacy. The correlation between the MSC‐CM content and treatment outcome was investigated.Methods: Ten MS patients who failed conventional therapy were enrolled. Adverse events were recorded to assess safety. The Expanded Disability Status Scale (EDSS) was the primary efficacy measurement, the secondary included clinical (25WFT, 9‐PHT), cognitive (MMS), ophthalmology (OCT, VEP), and radiological (MRI lesion and volume) tests. The MSCs‐CM concentration of 27 inflammatory biomarkers was investigated.Results: The treatment protocol was well tolerated by patients. There was an overall trend of improvement in all the tests, except the lesion volume which increased significantly. A decrease of 4 and 3.5 points on the EDSS was achieved in two patients. We report a correlation between a decreased lesion number at baseline and higher IL‐6, IL‐8, and VEGF MSC‐CM content.Conclusion: The used protocol was safe and feasible with possible efficacy. The addition of MSC‐CM could be related to the magnitude of EDSS improvement observed.

Cortical lesions are prevalent in multiple sclerosis but are poorly detected using MRI. The double inversion recovery (DIR) sequence is increasingly used to explore the clinical relevance of cortical demyelination. Here we evaluate the agreement between imaging sequences at 3 Tesla (T) and 7T for the presence and appearance of individual multiple sclerosis cortical lesions. Eleven patients with demyelinating disease and eight healthy volunteers underwent MR imaging at 3T (fluid attenuated inversion recovery [FLAIR], DIR, and T₁‐weighted magnetization prepared rapid acquisition gradient echo [MP‐RAGE] sequences) and 7T (T₁‐weighted MP‐RAGE). There was good agreement between images for the presence of mixed cortical lesions (involving both gray and white matter). However, agreement between imaging sequences was less good for purely intracortical lesions. Even after retrospective analysis, 25% of cortical lesions could only be visualized on a single MRI sequence. Several DIR hyperintensities thought to represent cortical lesions were found to correspond to signal arising from extracortical blood vessels. High‐resolution 7T imaging appeared useful for confidently classifying the location of lesions in relation to the cortical/subcortical boundary. We conclude that DIR, FLAIR, and MP‐RAGE imaging sequences appear to provide complementary information during the detection of multiple sclerosis cortical lesions. High resolution 7T imaging may facilitate anatomical localization of lesions in relation to the cortical boundary. J. Magn. Reson. Imaging 2010;32:971–977.

Objective: To determine, using ultra-high field magnetic resonance imaging (MRI), whether changes in iron content occur in the earliest phases of demyelinating disease, by quantifying the magnetic susceptibility of deep grey matter structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive of multiple sclerosis (MS), as compared with age-matched healthy subjects. Methods: We compared 19 CIS patients to 20 age-matched, healthy controls. Scanning of the study subjects was performed on a 7T Philips Achieva system, using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were first high-pass filtered, using a dipole fitting method, and then inverted to produce magnetic susceptibility maps. Region of interest (ROI) analysis was used to estimate magnetic susceptibility values for deep grey matter structures (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar). Results: Significantly increased relative susceptibilities were found in the CIS group, compared with controls, for the caudate nucleus ( p = < 0.01), putamen ( p < 0.01), globus pallidus ( p < 0.01) and pulvinar ( p < 0.05). We found no significant nor consistent trends in the relationship between susceptibility and age for either the study controls or CIS patients, in any ROI ( r² < 0.5; p > 0.05). In CIS patients, the time elapsed since the clinical event and the Expanded Disability Status Scale (EDSS) scores were not correlated with iron levels in any ROI ( r² < 0.5; p > 0.05); however, a moderate correlation ( r² = 0.3; p < 0.01) was found between the T1 lesion load and the mean susceptibility of the caudate nucleus. Conclusion: CIS patients showed an increased iron accumulation, as measured using susceptibility mapping of the deep grey matter, suggesting that iron changes did occur at the earlier stages of CIS disease.