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.

The radiofrequency (RF) transmit field is severely inhomogeneous at ultrahigh field due to both RF penetration and RF coil design issues. This particularly impairs image quality for sequences that use inversion pulses such as magnetization prepared rapid acquisition gradient echo and limits the use of quantitative arterial spin labeling sequences such as flow-attenuated inversion recovery. Here we have used a search algorithm to produce inversion pulses tailored to take into account the heterogeneity of the RF transmit field at 7 T. This created a slice selective inversion pulse that worked well (good slice profile and uniform inversion) over the range of RF amplitudes typically obtained in the head at 7 T while still maintaining an experimentally achievable pulse length and pulse amplitude in the brain at 7 T. The pulses used were based on the frequency offset correction inversion technique, as well as time dilation of functions, but the RF amplitude, frequency sweep, and gradient functions were all generated using a genetic algorithm with an evaluation function that took into account both the desired inversion profile and the transmit field inhomogeneity. The radiofrequency (RF) transmit field is severely inhomogeneous at ultrahigh field due to both RF penetration and RF coil design issues. This is a particular problem for techniques that use inversion pulses such as magnetization prepared rapid acquisition gradient echo (MPRAGE) (1) and arterial spin labeling sequences such as flow attenuated inversion recovery (2). A number of approaches to solving this problem are being investigated, generally requiring additional hardware. Here we have taken a simpler approach, using a search algorithm to produce inversion pulses tailored to take into account the heterogeneity of the RF transmit field at 7 T. The goal was to create a slice selective inversion pulse that worked well (good slice profile and low sensitivity to RF inhomogeneity) over the range of RF amplitudes typically obtained in vivo while still maintaining an experimentally achievable pulse length and pulse amplitude in the brain at 7 T.The standard inversion pulse used in MRI is the hyperbolic secant inversion pulse (3), which has previously been subject to reshaping (frequency offset corrected inversion [FOCI] pulses) to provide improved slice profile over a wide range of pulse powers (4) and to time resampling/dilation (variable rate selective excitation) to reduce the pulse power or improve inversion at low RF amplitudes (5,6). In this work, the RF amplitude, frequency sweep, and gradient functions were optimized using a genetic algorithm (7) with an evaluation function that took into account both the desired inversion slice profile and sensitivity to transmit field inhomogeneity, within the constraints of maximum RF field amplitude (B 1 ) and fixed pulse length. We used this to optimize two similar pulses. The first pulse is the C-shape FOCI (C-FOCI) pulse, which is defined by three variables ( , ␤, and A max ), with no time resampling. The second pul...

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 T 1 -weighted magnetization prepared rapid acquisition gradient echo [MP-RAGE] sequences) and 7T (T 1 -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. GRAY MATTER BRAIN pathology was recognized in early neuropathological descriptions of multiple sclerosis (MS) but until recently it has received scant attention. Histology reveals cortical demyelinating lesions, a third of which simultaneously involve subcortical white matter. The finding of neuroaxonal injury within cortical lesions (1-3), along with the high frequency of cortical demyelination in the brains of patients with advanced disability (4), suggests that cortical demyelination could account for some chronic features of MS. The ability to address this hypothesis in vivo has been hindered so far by the low sensitivity of MRI to cortical demyelination.Postmortem MR imaging in MS patients has shown a 1.5 Tesla (T) fluid attenuated inversion recovery (FLAIR) sequence to detect 41% of mixed cortical/subcortical (C/SC) lesions and only 5% of intracortical (IC) lesions (5). The double inversion recovery (DIR) sequence uses two inversion pulses which null signal from both the normal-appearing white matter and the cerebrospinal fluid (CSF). DIR has been shown to increase the detection rate of intra-cortical lesions by 150% when compared with FLAIR in vivo (6-8), still predicting a sensitivity of only $12.5%. In vivo studies comparing FLAIR and DIR in patients with MS have analyzed total lesion number rather than investigating the agreement between sequences for individual cortical lesions (6,8).Factors precluding MRI visualization of cortical demyelination are likely to include the small volum...

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.

SummaryAimsThis 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.MethodsTen 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.ResultsThe 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.ConclusionThe used protocol was safe and feasible with possible efficacy. The addition of MSC‐CM could be related to the magnitude of EDSS improvement observed.

Diverse pathological changes occur in the white matter (WM) of patients with schizophrenia. Various microstructural alterations including a reduction in axonal number or diameter, reduced myelination, or poor coherence of fibers could account for these changes. Abnormal integrity of macromolecules such as myelin ('dysmyelination') can be studied by applying multiple modalities of WM imaging such as diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) in parallel. Using ultra-high field (7 Tesla) MTI in 17 clinically stable patients with schizophrenia and 20 controls, we evaluated the voxelwise distribution of macromolecular WM abnormalities. Patients had a significant reduction in magnetization transfer ratio (MTR) in WM adjacent to visual processing regions and inferior temporal cortex (Cohen's d=1.54). Among the regions showing MTR reduction, a concurrent reduction in fractional anisotropy (FA) occurs proximal to the lingual gyrus. Multiple regression analysis revealed that the degree of FA reduction in the putatively 'dysmyelinated' regions in patients predicted impaired processing speed (PS; β=0.74; P=0.003), a core cognitive dysfunction in schizophrenia. In controls, MTR/FA in the occipito-temporal regions were not associated with PS. Our findings suggest that dysmyelination in visual processing regions is present in patients with schizophrenia with greatest cognitive and functional impairment. Combined DTI/MTI deficits in the occipito-temporal region may be an important variable when considering potential treatment targets for improving cognitive function in schizophrenia.

Objective The aim of this study was to compare the use of high-resolution phase and QSM images acquired at ultra-high field in the investigation of multiple sclerosis (MS) lesions with peripheral rings, and to discuss their usefulness for drawing inferences about underlying tissue composition.Materials and methodsThirty-nine Subjects were scanned at 7 T, using 3D T2*-weighted and T1-weighted sequences. Phase images were then unwrapped and filtered, and quantitative susceptibility maps were generated using a thresholded k-space division method. Lesions were compared visually and using a 1D profiling algorithm.ResultsLesions displaying peripheral rings in the phase images were identified in 10 of the 39 subjects. Dipolar projections were apparent in the phase images outside of the extent of several of these lesions; however, QSM images showed peripheral rings without such projections. These projections appeared ring-like in a small number of phase images where no ring was observed in QSM. 1D profiles of six well-isolated example lesions showed that QSM contrast corresponds more closely to the magnitude images than phase contrast.ConclusionsPhase images contain dipolar projections, which confounds their use in the investigation of tissue composition in MS lesions. Quantitative susceptibility maps correct these projections, providing insight into the composition of MS lesions showing peripheral rings.

MR changes consistent with iron accumulation occurring in the SN and RN of CIS patients can be identified using susceptibility mapping; this may provide an additional method of monitoring early MS development.