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Purpose: Validation of quantitative MR measures for myelin imaging in the postmortem multiple sclerosis spinal cord., Methods: Four fixed spinal cord samples were imaged first with a 3T clinical MR scanner to identify areas of interest for scanning, and then with a 7T small bore scanner using a multicomponent-driven equilibrium single-pulse observation of T 1 and T 2 protocol to produce apparent proton density, T 1 , T 2 , myelin water, intracellular water, and free-water fraction maps. After imaging, the cords were sectioned and stained with histological markers (hematoxylin and eosin, myelin basic protein, and neurofilament protein), which were quantitatively compared with the MR maps., Results: Excellent correspondence was found between high-resolution MR parameter maps and histology, particularly for apparent proton density MRI and myelin basic protein staining., Conclusion: High-resolution quantitative MRI of the spinal cord provides biologically meaningful measures, and could be beneficial to diagnose and track multiple sclerosis lesions in the spinal cord., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Clinical trials are probably the most informative experiments to help an understanding of multiple sclerosis (MS) biology. Recent successes with CD20-depleting antibodies have focused attention towards B cell subsets as important mediators in MS. The trial of tabalumab (NTC00882999), which inhibits B cell activation factor (BAFF), is reported and reviewed and this trial is contrasted with the trial on the inhibition of a proliferation-inducing ligand (APRIL) and BAFF using atacicept (NCT00642902). Both tabalumab and atacicept induce depletion of mature B cells and inhibit antibody formation, but they fail to deplete memory B cells and do not inhibit relapsing MS. Atacicept is reported to augment memory B cell responses and may precipitate relapse, suggesting the importance of APRIL. However, BAFF inhibition can enhance peripheral blood memory B cell responses, which was not associated with augmented relapse. Although other interpretations are possible, these data further support the hypothesis that memory B cells may be of central importance in relapsing MS, as they are the major CD20+ B cell subset expressing APRIL receptors. They also suggest that quantitative and/or qualitative differences in B cell responses or other factors, such as an immune-regulatory effect associated with APRIL, may be important in determining whether MS reactivates following neutralization of peripheral B cell maturation and survival factors., (© 2019 European Academy of Neurology.)

Purpose: Current MRI techniques cannot reliably assess iron content in white matter due to the confounding diamagnetic effect of myelin. The purpose of this study was to validate with histology a novel iron mapping technique that uses the temperature dependency of the paramagnetic susceptibility in multiple sclerosis (MS) brains, where white matter has been reported to show significant variations in iron content., Methods: We investigated post mortem brain tissue from three MS patients and one control subject. Temperature-dependent R2* relaxometry was performed between 4°C and 37°C. The resulting temperature coefficient ( TcR2*) maps were compared with immunohistochemical stains for ferritin light chain., Results: Good agreement between TcR2* maps and ferritin staining was found by way of visual comparison and quantitative analysis. The highest iron concentrations were detected at the edge of MS lesions and in the basal ganglia. For all regions, except the subcortical U-fibers, there was a significant negative correlation between the TcR2* values and the ferritin count., Conclusion: This study provides further evidence that TcR2* may be a reliable measure of white matter iron content due to the elimination of myelin-induced susceptibility changes and is well suited for further research into neurological diseases with distortions of the iron homeostasis. Magn Reson Med 79:1609-1615, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background and Purpose: Lumbar puncture (LP) is a key diagnostic procedure in medicine. Post lumbar puncture headache (PLPHA) is a well recognized complication of LP. Evidence suggests that using atraumatic needles for diagnostic LP (ATNLP) reduces risk of PLPHA. However, clinicians in Europe and the USA routinely use traumatic needles for diagnostic LP (TNLP). The occurrence of PLPHA following ATNLP and TNLP was compared in a clinical setting. Further, a survey was performed exploring use of ATNLP amongst UK neurologists., Methods: Service development study. Patients were followed up 2 and 7 days after LP using blinded telephone assessment. A questionnaire was developed to assess use of ATNLP amongst UK neurologists. Frequency, onset, duration and severity of PLPHA were recorded as were use of analgesia, general practitioner consultations, hospital readmissions, days off work due to PLPHA and cost. Neurologists were asked about their familiarity with, and use of, ATNLP., Results: One hundred and nine participants attending the Royal London Hospital were included, and 74 attendees of the Association of British Neurologists 2012 conference completed an on-site questionnaire. ATNLP reduced the rate of PLPHA (27.1% vs. 60.4%; P < 0.01). In those participants who developed PLPHA symptoms were short lived (mean 50 h vs. 94 h, P = 0.02) and less severe after ATNLP. Use of ATNLP led to significant cost savings. Only one in five UK neurologists regularly use ATNLP stating lack of training and availability of atraumatic needles as main reasons., Conclusions: ATNLP significantly reduces the risk of PLPHA. Training is required 3 to facilitate a change from TNLP to ATNLP amongst clinicians., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Unfixed and fixed postmortem multiple sclerosis (MS) brain is being used to probe pathology underlying quantitative MR (qMR) changes. Effects of fixation on qMR indices in MS brain are unknown. In 15 postmortem MS brain slices T(1), T(2), MT ratio (MTR), macromolecular proton fraction (f(B)), fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, D(ax), and D(rad)) were assessed in white matter (WM) lesions (WML) and normal appearing WM (NAWM) before and after fixation in formalin. Myelin content, axonal count, and gliosis were quantified histologically. Student's t-test and regression were used for analysis. T(1), T(2), MTR, and f(B) obtained in unfixed MS brain were similar to published values obtained in patients with MS in vivo. Following fixation T(1), T(2) (NAWM, WML) and MTR (NAWM) dropped, whereas f(B) (NAWM, WML) increased. Compared to published in vivo data all diffusivity measures were lower in unfixed MS brain, and dropped further following fixation (except for FA). MTR was the best predictor of T(myelin) (inversely related to myelin) in unfixed MS brain (r = -0.83; P < 0.01) whereas postfixation T(2) (r = 0.92; P < 0.01), T(1) (r = 0.89; P < 0.01), and f(B) (r = -0.86; P < 0.01) were superior. All diffusivity measures (except for D(ax) in unfixed tissue) were predictors of myelin content., ((c) 2008 Wiley-Liss, Inc.)

There is increasing interest in imaging cadavers for noninvasive autopsies for research purposes. However, the temperature is well below that of in vivo imaging, and a variety of interesting 'cold brain' effects are observed. At lower temperatures conventional FLAIR sequences no longer produce dark cerebrospinal fluid (CSF); T(1) is reduced from about 4.0 sec in vivo to 1.7 sec at 1 degrees C. The diffusion coefficient (DC) of CSF is much reduced (from 3.1 10(-9) m(2)s(-1) in vivo to 1.1 at 1 degrees C). DC values therefore provide a noninvasive thermometer to measure brain core temperature to within 1.0 degrees C. In three cadavers DC values were 1.1-1.5 10(-9) m(2)s(-1), indicating brain core temperatures of 1-10 degrees C, consistent with external thermocouple measurements. An improved inversion time (TI(0)) can then be found for FLAIR. At 10 degrees C this Cold FLAIR sequence (TI(0) = 1.5 sec) gave black CSF. Expressions for CSF DC and T(1) as a function of temperature were produced. A measurement of CSF DC could be converted directly to temperature and the required TI(0) found. In vitro values of CSF DC were about 1% lower than that of water. Thus, FLAIR imaging can be optimized for cadaveric brains at low and unknown temperatures, thereby improving value for autopsy purposes and facilitating comparisons with in vivo imaging., (2007 Wiley-Liss, Inc)