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Background and Hypothesis Although the thalamus has a central role in schizophrenia pathophysiology, contributing to sensory, cognitive, and sleep alterations, the nature and dynamics of the alterations occurring within this structure remain largely elusive. Using a multimodal magnetic resonance imaging (MRI) approach, we examined whether anomalies: (1) differ across thalamic subregions/nuclei, (2) are already present in the early phase of psychosis (EP), and (3) worsen in chronic schizophrenia (SCHZ). Study Design T1-weighted and diffusion-weighted images were analyzed to estimate gray matter concentration (GMC) and microstructural parameters obtained from the spherical mean technique (intra-neurite volume fraction [VFINTRA)], intra-neurite diffusivity [DIFFINTRA], extra-neurite mean diffusivity [MDEXTRA], extra-neurite transversal diffusivity [TDEXTRA]) within 7 thalamic subregions. Results Compared to age-matched controls, the thalamus of EP patients displays previously unreported widespread microstructural alterations (VFINTRA decrease, TDEXTRA increase) that are associated with similar alterations in the whole brain white matter, suggesting altered integrity of white matter fiber tracts in the thalamus. In both patient groups, we also observed more localized and heterogenous changes (either GMC decrease, MDEXTRA increase, or DIFFINTRA decrease) in mediodorsal, posterior, and ventral anterior parts of the thalamus in both patient groups, suggesting that the nature of the alterations varies across subregions. GMC and DIFFINTRA in the whole thalamus correlate with global functioning, while DIFFINTRA in the subregion encompassing the medial pulvinar is significantly associated with negative symptoms in SCHZ. Conclusion Our data reveals both widespread and more localized thalamic anomalies that are already present in the early phase of psychosis.

Objective Cortical lesions are common in multiple sclerosis (MS), but their visualization is challenging on conventional magnetic resonance imaging. The uniform image derived from magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE(uni)) detects cortical lesions with a similar rate as the criterion standard sequence, double inversion recovery. Fluid and white matter suppression (FLAWS) provides multiple reconstructed contrasts acquired during a single acquisition. These contrasts include FLAWS minimum image (FLAWS(min)), which provides an exquisite sensitivity to the gray matter signal and therefore may facilitate cortical lesion identification, as well as high contrast FLAWS (FLAWS(hco)), which gives a contrast that is similar to one of MP2RAGE(uni). In this study, we compared the manual detection rate of cortical lesions on MP2RAGE(uni), FLAWS(min), and FLAWS(hco) in MS patients. Furthermore, we assessed whether the combined detection rate on FLAWS(min) and FLAWS(hco) was superior to MP2RAGE(uni) for cortical lesions identification. Last, we compared quantitative T1 maps (qT1) provided by both MP2RAGE and FLAWS in MS lesions. Materials and Methods We included 30 relapsing-remitting MS patients who underwent MP2RAGE and FLAWS magnetic resonance imaging with isotropic spatial resolution of 1 mm at 3 T. Cortical lesions were manually segmented by consensus of 3 trained raters and classified as intracortical or leukocortical lesions on (1) MP2RAGE uniform/flat images, (2) FLAWS(min), and (3) FLAWS(hco). In addition, segmented lesions on FLAWS(min) and FLAWS(hco) were merged to produce a union lesion map (FLAWS(min + hco)). Number and volume of all cortical, intracortical, and leukocortical lesions were compared among MP2RAGE(uni), FLAWS(min), and FLAWS(hco) using Friedman test and between MP2RAGE(uni) and FLAWS(min + hco) using Wilcoxon signed rank test. The FLAWS T1 maps were then compared with the reference MP2RAGE T1 maps using relative differences in percentage. In an exploratory analysis, individual cortical lesion counts of the 3 raters were compared, and interrater variability was quantified using Fleiss K. Results In total, 633 segmentations were made on the 3 contrasts, corresponding to 355 cortical lesions. The median number and volume of single cortical, intracortical, and leukocortical lesions were comparable among MP2RAGE(uni), FLAWS(min), and FLAWS(hco). In patients with cortical lesions (22/30), median cumulative lesion volume was larger on FLAWS(min) (587 mu L; IQR, 1405 mu L) than on MP2RAGE(uni) (490 mu L; IQR, 990 mu L; P = 0.04), whereas there was no difference between FLAWS(min) and FLAWS(hco), or FLAWS(hco) and MP2RAGE(uni). FLAWS(min + hco) showed significantly greater numbers of cortical (median, 4.5; IQR, 15) and leukocortical (median, 3.5; IQR, 12) lesions than MP2RAGE(uni) (median, 3; IQR, 10; median, 2.5; IQR, 7; both P < 0.001). Interrater agreement was moderate on MP2RAGE(uni) (K = 0.582) and FLAWS(hco) (K = 0.584), but substantial on FLAWS(min) (K = 0.614). qT1 in lesions was similar between MP2RAGE and FLAWS. Conclusions Cortical lesions identification in FLAWS(min) and FLAWS(hco) was comparable to MP2RAGE(uni)., The combination of FLAWS(min) and FLAWS(hco) allowed to identify a higher number of cortical lesions than MP2RAGE(uni), whereas qT1 maps did not differ between the 2 acquisition schemes.

Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging., We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage. Ninety-one multiple sclerosis patients (62 relapsing-remitting, 29 progressive) and 72 healthy controls were enrolled in the study., Differences in myelin water fraction and neurite density index were substantial when lesions were compared to healthy control subjects and normal-appearing multiple sclerosis tissue: both white matter and cortical lesions exhibited a decreased myelin water fraction and neurite density index compared with healthy (P < 0.0001) and peri-plaque white matter (P < 0.0001). Periventricular lesions showed decreased myelin water fraction and neurite density index compared with lesions in the juxtacortical region ( P < 0.0001 and P < 0.05). Similarly, lesions with paramagnetic rims showed decreased myelin water fraction and neurite density index relative to lesions without a rim (P < 0.0001). Also, in 75% of white matter lesions, the reduction in neurite density index was higher than the reduction in the myelin water fraction. Besides, normal-appearing white and grey matter revealed diffuse reduction of myelin water fraction and neurite density index in multiple sclerosis compared to healthy controls (P < 0.01). Further, a more extensive reduction in myelin water fraction and neurite density index in normalappearing cortex was observed in progressive versus relapsing-remitting participants. Neurite density index in white matter lesions correlated with disability in patients with clinical deficits (P < 0.01, beta = -10.00); and neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patient cohort (P < 0.01, beta = -3.60 and P < 0.01, beta = 0.13, respectively)., These findings suggest that (i) myelin and axon pathology in multiple sclerosis is extensive in both lesions and normal-appearing tissue; (ii) particular types of lesions exhibit more damage to myelin and axons than others; (iii) progressive patients differ from relapsing-remitting patients because of more extensive axon/myelin damage in the cortex; and (iv) myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage.

Magnetic resonance imaging of the eye and orbit (MReye) is a cross-domain research field, combining (bio)physics, (bio)engineering, physiology, data sciences and ophthalmology. A growing number of reports document technical innovations of MReye and promote their application in preclinical research and clinical science. Realizing the progress and promises, this review outlines current trends in MReye. Examples of MReye strategies and their clinical relevance are demonstrated. Frontier applications in ocular oncology, refractive surgery, ocular muscle disorders and orbital inflammation are presented and their implications for explorations into ophthalmic diseases are provided. Substantial progress in anatomically detailed, high-spatial resolution MReye of the eye, orbit and optic nerve is demonstrated. Recent developments in MReye of ocular tumors are explored, and its value for personalized eye models derived from machine learning in the treatment planning of uveal melanoma and evaluation of retinoblastoma is highlighted. The potential of MReye for monitoring drug distribution and for improving treatment management and the assessment of individual responses is discussed. To open a window into the eye and into (patho)physiological processes that in the past have been largely inaccessible, advances in MReye at ultrahigh magnetic field strengths are discussed. A concluding section ventures a glance beyond the horizon and explores future directions of MReye across multiple scales, including in vivo electrolyte mapping of sodium and other nuclei. This review underscores the need for the (bio)medical imaging and ophthalmic communities to expand efforts to find solutions to the remaining unsolved problems and technical obstacles of MReye, with the objective to transfer methodological advancements driven by MR physics into genuine clinical value.

Manually segmenting multiple sclerosis (MS) cortical lesions (CL) is extremely time-consuming, and past studies have shown only moderate inter-rater reliability. To accelerate this task, we developed a deep learning-based framework (CLAIMS: Cortical Lesion Artificial Intelligence-based assessment in Multiple Sclerosis) for the automated detection and classification of MS CL with 7T MRI.Two 7T datasets, acquired at different sites, were considered. The first consisted of 60 scans that include 0.5mm isotropic MP2RAGE acquired 4 times (MP2RAGEx4), 0.7mm MP2RAGE, 0.5mm T2*-weighted GRE, and 0.5mm T2*-weighted EPI. The second dataset consisted of 20 scans including only 0.75×0.75×0.9 mm MP2RAGE. CLAIMS was first evaluated using 6-fold cross-validation with single and multi-contrast 0.5mm MRI input. Second, performance of the model was tested on 0.7mm MP2RAGE images after training with either 0.5mm MP2RAGEx4, 0.7mm MP2RAGE, or alternating the two. Third, its generalizability was evaluated on the second external dataset and compared with a state-of-the-art technique based on partial volume estimation and topological constraints (MSLAST). CLAIMS trained only with MP2RAGEx4 achieved comparable results to the multi-contrast model, reaching a CL true positive rate of 74% with a false positive rate of 30%. Detection rate was excellent for leukocortical and subpial lesions (83%, and 70%, respectively), whereas it reached 53% for intracortical lesions. The correlation between disability measures and CL count was similar for manual and CLAIMS lesion counts. Applying a domain-scanner adaptation approach and testing CLAIMS on the second dataset, the performance was superior to MSLAST when considering a minimum lesion volume of 6μL (lesion-wise detection rate of 71% vs 48%).The proposed framework outperforms previous state-of-the-art methods for automated CL detection across scanners and protocols. In the future, CLAIMS may be useful to support clinical decisions at 7T MRI, especially in the field of diagnosis and differential diagnosis of multiple sclerosis patients.

Neuropathological studies have shown that multiple sclerosis (MS) lesions are heterogeneous in terms of myelin/axon damage and repair as well as iron content. However, it remains a challenge to identify specific chronic lesion types, especially remyelinated lesions, in vivo in patients with MS.We performed 3 studies: (1) a cross-sectional study in a prospective cohort of 115 patients with MS and 76 healthy controls, who underwent 3 T magnetic resonance imaging (MRI) for quantitative susceptibility mapping (QSM), myelin water fraction (MWF), and neurite density index (NDI) maps. White matter (WM) lesions in QSM were classified into 5 QSM lesion types (iso-intense, hypo-intense, hyperintense, lesions with hypo-intense rims, and lesions with paramagnetic rim legions [PRLs]); (2) a longitudinal study of 40 patients with MS to study the evolution of lesions over 2 years; (3) a postmortem histopathology-QSM validation study in 3 brains of patients with MS to assess the accuracy of QSM classification to identify neuropathological lesion types in 63 WM lesions.At baseline, hypo- and isointense lesions showed higher mean MWF and NDI values compared to other QSM lesion types (p 0.0001). Further, at 2-year follow-up, hypo-/iso-intense lesions showed an increase in MWF. Postmortem analyses revealed that QSM highly accurately identifies (1) fully remyelinated areas as hypo-/iso-intense (sensitivity = 88.89% and specificity = 100%), (2) chronic inactive lesions as hyperintense (sensitivity = 71.43% and specificity = 92.00%), and (3) chronic active/smoldering lesions as PRLs (sensitivity = 92.86% and specificity = 86.36%).These results provide the first evidence that it is possible to distinguish chronic MS lesions in a clinical setting, hereby supporting with new biomarkers to develop and assess remyelinating treatments. ANN NEUROL 2022;92:486-502.