MRI phase imaging in multiple sclerosis (MS) patients and in autopsy tissue have demonstrated the presence of iron depositions in white matter lesions.The accumulation of iron in some but not all lesions suggests a specific, potentially disease-relevant process, however; its pathophysiological significance remains unknown.Here, we explore the role of lesional iron in multiple sclerosis using multiple approaches: immunohistochemical examination of autoptic MS tissue, an in vitro model of iron-uptake in human cultured macrophages and ultra-highfield phase imaging of highly active and of secondary progressive MS patients.Using Perls' stain and immunohistochemistry, iron was detected in MS tissue sections predominantly in non-phagocytosing macrophages/microglia at the edge of established, demyelinated lesions. Moreover, iron-containing macrophages but not myelin-laden macrophages expressed markers of proinflammatory (M1) polarization.Similarly, in human macrophage cultures, iron was preferentially taken up by non-phagocytosing, M1-polarized macrophages and induced M1 (super) polarization. Iron uptake was minimal in myelin-laden macrophages and active myelin phagocytosis led to depletion of intracellular iron.Finally, we demonstrated in MS patients using GRE phase imaging with ultra-highfield MRI that phase hypointense lesions were significantly more prevalent in patients with active relapsing than with secondary progressive MS.Taken together, our data provide a basis to interpret iron-sensitive GRE phase imaging in MS patients: iron is present in non-phagocytosing, M1-polarized microglia/macrophages at the rim of chronic active white matter demyelinating lesions. Phase imaging may therefore visualize specific, chronic proinflammatory activity in established MS lesions and thus provide important clinical information on disease status and treatment efficacy in MS patients.

The μFA maps can be measured using DDE in a clinical setting and may provide new opportunities for characterizing multiple sclerosis lesions and other types of tissue degeneration. Magn Reson Med 80:507-520, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

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PurposeTo resolve the motion‐induced phase variations in multi‐shot multi‐direction diffusion‐weighted imaging (DWI) by applying regularization to magnitude images.Theory and MethodsA nonlinear model was developed to estimate phase and magnitude images separately. A locally low‐rank regularization (LLR) term was applied to the magnitude images from all diffusion‐encoding directions to exploit the spatial and angular correlation. In vivo experiments with different resolutions and b‐values were performed to validate the proposed method.ResultsThe proposed method significantly reduces the noise level compared to the conventional reconstruction method and achieves submillimeter (0.8mm and 0.9mm isotropic resolutions) DWI with a b‐value of 1,000  and 1‐mm isotropic DWI with a b‐value of 2,000  without modification of the sequence.ConclusionsA joint reconstruction method with spatial‐angular LLR regularization on magnitude images substantially improves multi‐direction DWI reconstruction, simultaneously removes motion‐induced phase artifacts, and denoises images.

Demetalation of Fe(III) microperoxidase-8 (MP8) by anhydrous HF gives metal-free MP8, a convenient starting material for a wide variety of metal-substituted MP8 derivatives, including Mn(III)MP8. Mn(III)MP8 was produced by treatment of metal-free MP8 with manganous acetate in aerated aqueous solution; it was characterized by mass spectrometry and UV−visible absorption spectroscopy. Resonance Raman spectra suggest that Mn(III)MP8 contains histidine and water axial ligands at neutral pH. The Mn(IV)O derivative is readily prepared by oxidation of Mn(III)MP8 with hydrogen peroxide or Ru(bpy)3 3+ (bpy = 2,2‘-bipyridine).