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Background: Previous studies have shown that thalamic and hippocampal neurodegeneration is associated with clinical decline in Multiple Sclerosis (MS). However, contributions of the specific thalamic nuclei and hippocampal subfields require further examination., Objective: Using 7 Tesla (7T) magnetic resonance imaging (MRI), we investigated the cross-sectional associations between functionally grouped thalamic nuclei and hippocampal subfields volumes and T1 relaxation times (T1-RT) and subsequent clinical outcomes in MS., Methods: High-resolution T1-weighted and T2-weighted images were acquired at 7T (n=31), preprocessed, and segmented using the Thalamus Optimized Multi Atlas Segmentation (THOMAS, for thalamic nuclei) and the Automatic Segmentation of Hippocampal Subfields (ASHS, for hippocampal subfields) packages. We calculated Pearson correlations between hippocampal subfields and thalamic nuclei volumes and T1-RT and subsequent multi-modal rater-determined and patient-reported clinical outcomes (∼2.5 years after imaging acquisition), correcting for confounders and multiple tests., Results: Smaller volume bilaterally in the anterior thalamus region correlated with worse performance in gait function, as measured by the Patient Determined Disease Steps (PDDS). Additionally, larger volume in most functional groups of thalamic nuclei correlated with better visual information processing and cognitive function, as measured by the Symbol Digit Modalities Test (SDMT). In bilateral medial and left posterior thalamic regions, there was an inverse association between volumes and T1-RT, potentially indicating higher tissue degeneration in these regions. We also observed marginal associations between the right hippocampal subfields (both volumes and T1-RT) and subsequent clinical outcomes, though they did not survive correction for multiple testing., Conclusion: Ultrahigh field MRI identified markers of structural damage in the thalamic nuclei associated with subsequently worse clinical outcomes in individuals with MS. Longitudinal studies will enable better understanding of the role of microstructural integrity in these brain regions in influencing MS outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tamer S. Ibrahim reports financial support was provided by National Institutes of Health. Zongqi Xia reports financial support was provided by National Institutes of Health. Tales Santini reports financial support was provided by Coordination of Higher Education Personnel Improvement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Thalamic atrophy can be used as a proxy for neurodegeneration in multiple sclerosis (MS). Some data point toward thalamic nuclei that could be affected more than others. However, the dynamic of their changes during MS evolution and the mechanisms driving their differential alterations are still uncertain., Methods: We paired a large cohort of 1,123 patients with MS with the same number of healthy controls, all scanned with conventional 3D-T1 MRI. To highlight the main atrophic regions at the thalamic nuclei level, we validated a segmentation strategy consisting of deep learning-based synthesis of sequences, which were used for automatic multiatlas segmentation. Then, through a lifespan-based approach, we could model the dynamics of the 4 main thalamic nuclei groups., Results: All analyses converged toward a higher rate of atrophy for the posterior and medial groups compared with the anterior and lateral groups. We also demonstrated that focal MS white matter lesions were associated with atrophy of groups of nuclei when specifically located within the associated thalamocortical projections. The volumes of the most affected posterior group, but also of the anterior group, were better associated with clinical disability than the volume of the whole thalamus., Discussion: These findings point toward the thalamic nuclei adjacent to the third ventricle as more susceptible to neurodegeneration during the entire course of MS through potentiation of disconnection effects by regional factors. Because this information can be obtained even from standard T1-weighted MRI, this paves the way toward such an approach for future monitoring of patients with MS.

Objectives: Investigating differential vulnerability of thalamic nuclei in multiple sclerosis (MS)., Methods: In a secondary analysis of prospectively collected datasets, we pooled 136 patients with MS or clinically isolated syndrome and 71 healthy controls all scanned with conventional 3D-T1 and white-matter-nulled magnetization-prepared rapid gradient echo (WMn-MPRAGE) and tested for cognitive performance. T1-based thalamic segmentation was compared with the reference WMn-MPRAGE method. Volumes of thalamic nuclei were compared according to clinical phenotypes and cognitive profile., Results: T1- and WMn-MPRAGE provided comparable segmentations (0.84 ± 0.13 < volume-similarity-index < 0.95 ± 0.03). Medial and posterior thalamic groups were significantly more affected than anterior and lateral groups. Cognitive impairment related to volume loss of the anterior group., Conclusion: Thalamic nuclei closest to the third ventricle are more affected, with cognitive consequences.

Background: Investigating the degeneration of specific thalamic nuclei in multiple sclerosis (MS) remains challenging., Methods: White-matter-nulled (WMn) MPRAGE, MP-FLAIR, and standard T1-weighted magnetic resonance imaging (MRI) were performed on MS patients ( n  = 15) and matched controls ( n  = 12). Thalamic lesions were counted in individual sequences and lesion contrast-to-noise ratio (CNR) was measured. Volumes of 12 thalamic nuclei were measured using an automatic segmentation pipeline specifically developed for WMn-MPRAGE., Results: WMn-MPRAGE showed more thalamic MS lesions ( n  = 35 in 9 out of 15 patients) than MP-FLAIR ( n  = 25) and standard T1 ( n  = 23), which was associated with significant improvement of CNR ( p  < 0.0001). MS patients had whole thalamus atrophy ( p  = 0.003) with lower volumes found for the anteroventral ( p  < 0.001), the pulvinar ( p  < 0.0001), and the habenular ( p  = 0.004) nuclei., Conclusion: WMn-MPRAGE and automatic thalamic segmentation can highlight thalamic MS lesions and measure patterns of focal thalamic atrophy.

Purpose: The aim of this study was to optimize the 3-dimensional (3D) fluid attenuated inversion recovery (FLAIR) pulse sequence for isotropic high-spatial-resolution imaging of white matter (WM) and cortical lesions at 7 T., Materials and Methods: We added a magnetization-prepared (MP) FLAIR module to a Cube 3D fast spin echo sequence and optimized the refocusing flip angle train using extended phase graph simulations, taking into account image contrast, specific absorption rate (SAR), and signal-to-noise ratio (SNR) as well as T1/T2 values of the different species of interest (WM, grey matter, lesions) at 7 T. We also effected improved preparation homogeneity at 7 T by redesigning the refocusing pulse used in the MP segments. Two sets of refocusing flip angle trains-(a) an SNR-optimal and (b) a contrast-optimal set-were derived and used to scan 7 patients with Alzheimer disease/cognitive impairment and 7 patients with multiple sclerosis. Conventional constant refocusing flip MP-FLAIR images were also acquired for comparison. Lesion SNR, contrast, and lesion count were compared between the 2 optimized and the standard FLAIR sequences., Results: Whole brain coverage with 0.8 mm isotropic spatial resolution in ∼5-minute scan times was achieved using the optimized 3D FLAIR sequences at clinically acceptable SAR levels. The SNR efficiency of the SNR-optimal sequence was significantly better than that of conventional constant refocusing flip MP-FLAIR sequence, whereas the scan time was reduced more than 2-fold (∼5 vs >10 minutes). The contrast efficiency of the contrast-optimal sequence was comparable with that of the constant refocusing flip sequence. Lesion load ascertained by lesion counting was not significantly different among the sequences., Conclusion: Magnetization-prepared FLAIR-Cube with refocusing flip angle trains optimized for SNR and contrast can be used to characterize WM and cortical lesions at 7 T with 0.8 mm isotropic resolution in short scan times and without SAR penalty.

Objectives: Investigating differential vulnerability of thalamic nuclei in multiple sclerosis (MS). Methods: In a secondary analysis of prospectively collected datasets, we pooled 136 patients with MS or clinically isolated syndrome and 71 healthy controls all scanned with conventional 3D-T1 and white-matter-nulled magnetization-prepared rapid gradient echo (WMn-MPRAGE) and tested for cognitive performance. T1-based thalamic segmentation was compared with the reference WMn-MPRAGE method. Volumes of thalamic nuclei were compared according to clinical phenotypes and cognitive profile. Results: T1- and WMn-MPRAGE provided comparable segmentations (0.84 ± 0.13 < volume-similarity-index < 0.95 ± 0.03). Medial and posterior thalamic groups were significantly more affected than anterior and lateral groups. Cognitive impairment related to volume loss of the anterior group. Conclusion: Thalamic nuclei closest to the third ventricle are more affected, with cognitive consequences. [ABSTRACT FROM AUTHOR]

Thalamic nuclei play critical roles in regulation of neurological functions like sleep and wakefulness. They are increasingly implicated in neurodegenerative and neurological diseases such as multiple sclerosis and essential tremor. However, segmentation of thalamic nuclei is difficult due to their poor visibility in conventional MRI scans. Sophisticated methods have been proposed which require specialized MRI acquisitions and complex post processing. There are few high spatial resolution (1 mm3 or higher) in vivo MRI thalamic atlases available currently. The goal of this work is the development of an in vivo MRI-based structural thalamic atlas at 0.7 × 0.7 × 0.5 mm resolution based on manual segmentation of 9 healthy subjects using the Morel atlas as a guide. Using data analysis from healthy subjects as well as patients with multiple-sclerosis and essential tremor and at 3T and 7T MRI, we demonstrate the utility of this atlas to provide fast and accurate segmentation of thalamic nuclei when only conventional T1 weighted images are available. Measurement(s) thalamic nuclei Technology Type(s) multi-atlas segmentation Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16601045 [ABSTRACT FROM AUTHOR]

Purpose: Thalamic nuclei are largely invisible in conventional MRI due to poor contrast. Thalamus Optimized Multi‐Atlas Segmentation (THOMAS) provides automatic segmentation of 12 thalamic nuclei using white‐matter‐nulled (WMn) Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence at 7T, but increases overall scan duration. Routinely acquired, bias‐corrected Magnetization Prepared 2 Rapid Gradient Echo (MP2RAGE) sequence yields superior tissue contrast and quantitative T1 maps. Application of THOMAS to MP2RAGE has been investigated in this study. Methods: Eight healthy volunteers and five pediatric‐onset multiple sclerosis patients were recruited at Children's Hospital of Philadelphia and scanned at Siemens 7T with WMn‐MPRAGE and multi‐echo‐MP2RAGE (ME‐MP2RAGE) sequences. White‐matter‐nulled contrast was synthesized (MP2‐SYN) from T1 maps from ME‐MP2RAGE sequence. Thalamic nuclei were segmented using THOMAS joint label fusion algorithm from WMn‐MPRAGE and MP2‐SYN datasets. THOMAS pipeline was modified to use majority voting to segment bias corrected T1‐weighted uniform (MP2‐UNI) images. Thalamic nuclei from MP2‐SYN and MP2‐UNI images were evaluated against corresponding nuclei obtained from WMn‐MPRAGE images using dice coefficients, volume similarity indices (VSIs) and distance between centroids. Results: For MP2‐SYN, dice > 0.85 and VSI > 0.95 was achieved for five larger nuclei and dice > 0.6 and VSI > 0.7 was achieved for seven smaller nuclei. The dice and VSI were slightly higher, whereas the distance between centroids were smaller for MP2‐SYN compared to MP2‐UNI, indicating improved performance using the MP2‐SYN image. Conclusions: THOMAS algorithm can successfully segment thalamic nuclei in MP2RAGE images with essentially equivalent quality as WMn‐MPRAGE, widening its applicability in studies focused on thalamic involvement in aging and disease. [ABSTRACT FROM AUTHOR]

Background: Investigating the degeneration of specific thalamic nuclei in multiple sclerosis (MS) remains challenging. Methods: White-matter-nulled (WMn) MPRAGE, MP-FLAIR, and standard T1-weighted magnetic resonance imaging (MRI) were performed on MS patients (n = 15) and matched controls (n = 12). Thalamic lesions were counted in individual sequences and lesion contrast-to-noise ratio (CNR) was measured. Volumes of 12 thalamic nuclei were measured using an automatic segmentation pipeline specifically developed for WMn-MPRAGE. Results: WMn-MPRAGE showed more thalamic MS lesions (n = 35 in 9 out of 15 patients) than MP-FLAIR (n = 25) and standard T1 (n = 23), which was associated with significant improvement of CNR (p < 0.0001). MS patients had whole thalamus atrophy (p = 0.003) with lower volumes found for the anteroventral (p < 0.001), the pulvinar (p < 0.0001), and the habenular (p = 0.004) nuclei. Conclusion: WMn-MPRAGE and automatic thalamic segmentation can highlight thalamic MS lesions and measure patterns of focal thalamic atrophy. [ABSTRACT FROM AUTHOR]