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The extant literature supports the involvement of the thalamus in the cognitive and motor impairment associated with chronic alcohol consumption, but clear structure/function relationships remain elusive. Alcohol effects on specific nuclei rather than the entire thalamus may provide the basis for differential cognitive and motor decline in Alcohol Use Disorder (AUD). This functional MRI (fMRI) study was conducted in 23 abstinent individuals with AUD and 27 healthy controls to test the hypothesis that functional connectivity between anterior thalamus and hippocampus would be compromised in those with an AUD diagnosis and related to mnemonic deficits. Functional connectivity between 7 thalamic structures [5 thalamic nuclei: anterior ventral (AV), mediodorsal (MD), pulvinar (Pul), ventral lateral posterior (VLP), and ventral posterior lateral (VPL); ventral thalamus; the entire thalamus] and 14 "functional regions" was evaluated. Relative to controls, the AUD group exhibited different VPL-based functional connectivity: an anticorrelation between VPL and a bilateral middle temporal lobe region observed in controls became a positive correlation in the AUD group; an anticorrelation between the VPL and the cerebellum was stronger in the AUD than control group. AUD-associated altered connectivity between anterior thalamus and hippocampus as a substrate of memory compromise was not supported; instead, connectivity differences from controls selective to VPL and cerebellum demonstrated a relationship with impaired balance. These preliminary findings support substructure-level evaluation in future studies focused on discerning the role of the thalamus in AUD-associated cognitive and motor deficits., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The thalamus consists of several histologically and functionally distinct nuclei increasingly implicated in brain pathology and important for treatment, motivating the need for development of fast and accurate thalamic parcellation. The contrast between thalamic nuclei as well as between the thalamus and surrounding tissues is poor in T1- and T2-weighted magnetic resonance imaging (MRI), inhibiting efforts to date to segment the thalamus using standard clinical MRI. Automatic parcellation techniques have been developed to leverage thalamic features better captured by advanced MRI methods, including magnetization prepared rapid acquisition gradient echo (MP-RAGE), diffusion tensor imaging (DTI), and resting-state functional MRI (fMRI). Despite operating on fundamentally different image contrasts, these methods claim a high degree of agreement with the Morel stereotactic atlas of the thalamus. However, no comparison has been undertaken to compare the results of these disparate parcellation methods. We have implemented state-of-the-art structural-, diffusion-, and functional imaging-based thalamus parcellation techniques and used them on a single set of subjects. We present the first systematic qualitative and quantitative comparison of these methods. The results show that DTI parcellation agrees more with structural parcellation in the larger thalamic nuclei, while rsfMRI parcellation agrees more with structural parcellation in the smaller nuclei. Structural parcellation is the most accurate in the delineation of small structures such as the habenular, antero-ventral, and medial geniculate nuclei.

Direct targeting methods for stereotactic neurosurgery in the treatment of essential tremor have been the subject of active research over the past decade but have not yet been systematically reviewed. We present a clinically oriented topic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses Group guidelines. Our focus is studies using advanced magnetic resonance imaging (MRI) techniques (ultrahigh-field structural MRI, diffusion-weighted imaging, diffusion-tensor tractography, and functional MRI) for patient specific, in vivo identification of the ventral intermediate nucleus and the dentato-rubro-thalamic tract., (© 2020 S. Karger AG, Basel.)

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]

Specific thalamic nuclei are implicated in healthy aging and age‐related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age‐related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi‐Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white‐matter‐nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20–86 years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV‐adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye‐hand coordination task. These results support the use of THOMAS for standard T1‐weighted data as adequately robust for thalamic nuclear parcellation. [ABSTRACT FROM AUTHOR]

• We examined subregional metrics of thalamus and hippocampus in MS using 7T MRI. • Smaller bilateral anterior thalamic volume correlated with worse gait function. • Most thalamic nuclei correlated with visual and cognitive processing speed. • Volumes correlated with T1 relaxation time in a subset of thalamic nuclei. • Ultrahigh field MRI detects structural changes informative of MS outcomes. 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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer's disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum.Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS).Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA.Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects.Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes. [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]

Magnetic resonance‐guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET). The standard initial targeting method uses an approximate, atlas‐based stereotactic approach. We developed a new patient‐specific targeting method to identify an individual's Vim and the optimal MRgFUS target region therein for suppression of tremor. In this retrospective study of 14 ET patients treated with MRgFUS, we investigated the ability of WMnMPRAGE, a highly sensitive and robust sequence for imaging gray matter‐white matter contrast, to identify the Vim, FUS ablation, and a clinically efficacious region within the Vim in individual patients. We found that WMnMPRAGE can directly visualize the Vim in ET patients, segmenting this nucleus using manual or automated segmentation capabilities developed by our group. WMnMPRAGE also delineated the ablation's core and penumbra, and showed that all patients' ablation cores lay primarily within their Vim segmentations. We found no significant correlations between standard ablation features (e.g., ablation volume, Vim‐ablation overlap) and 1‐month post‐treatment clinical outcome. We then defined a group‐based probabilistic target, which was nonlinearly warped to individual brains; this target was located within the Vim for all patients. The overlaps between this target and patient ablation cores correlated significantly with 1‐month clinical outcome (r = −.57, p =.03), in contrast to the standard target (r = −.23, p =.44). We conclude that WMnMPRAGE is a highly sensitive sequence for segmenting Vim and ablation boundaries in individual patients, allowing us to find a novel tremor‐associated center within Vim and potentially improving MRgFUS treatment for ET. [ABSTRACT FROM AUTHOR]

Abstract: Novel MR image acquisition strategies have been investigated to elicit contrast within the thalamus, but direct visualization of individual thalamic nuclei remains a challenge because of their small size and the low intrinsic contrast between adjacent nuclei. We present a step-by-step specific optimization of the 3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first measured T1 values within different sub-regions of the thalamus at 7T in 5 individuals. We used these to perform simulations and sequential experimental measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal set of parameters was used to collect high-quality data in 6 additional volunteers. Delineation of thalamic nuclei was performed twice by one rater and MR-defined nuclei were compared to the classic Morel histological atlas. T1 values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei. Using these values for theoretical evaluations combined with in vivo measurements, we showed that a short inversion time (TI) close to the white matter null regime (TI=670ms) enhanced the contrast between the thalamus and the surrounding tissues, and best revealed intra-thalamic contrast. At this particular nulling regime, lengthening the time between successive inversion pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the α pulse train time (N*TR) further increased the thalamic signal. Finally, a low flip angle during the gradient echo acquisition (α=4°) was observed to mitigate the blur induced by the evolution of the magnetization along the α pulse train. This optimized set of parameters enabled the 3D delineation of 15 substructures in all 6 individuals; these substructures corresponded well with the known anatomical structures of the thalamus based on the classic Morel atlas. The mean Euclidean distance between the centers of mass of MR- and Morel atlas-defined nuclei was 2.67mm (±1.02mm). The reproducibility of the MR-defined nuclei was excellent with intraclass correlation coefficient measured at 0.997 and a mean Euclidean distance between corresponding centers of mass found at first versus second readings of 0.69mm (±0.38mm). This 7T strategy paves the way to better identification of thalamic nuclei for neurosurgical planning and investigation of regional changes in neurological disorders. [Copyright &y& Elsevier]

The thalamus and its nuclei are largely indistinguishable on standard T1 or T2 weighted MRI. While diffusion tensor imaging based methods have been proposed to segment the thalamic nuclei based on the angular orientation of the principal diffusion tensor, these are based on echo planar imaging which is inherently limited in spatial resolution and suffers from distortion. We present a multi-atlas segmentation technique based on white-matter-nulled MP-RAGE imaging that segments the thalamus into 12 nuclei with computation times on the order of 10 min on a desktop PC; we call this method THOMAS (THalamus Optimized Multi Atlas Segmentation). THOMAS was rigorously evaluated on 7T MRI data acquired from healthy volunteers and patients with multiple sclerosis by comparing against manual segmentations delineated by a neuroradiologist, guided by the Morel atlas. Segmentation accuracy was very high, with uniformly high Dice indices: at least 0.85 for large nuclei like the pulvinar and mediodorsal nuclei and at least 0.7 even for small structures such as the habenular, centromedian, and lateral and medial geniculate nuclei. Volume similarity indices ranged from 0.82 for the smaller nuclei to 0.97 for the larger nuclei. Volumetry revealed that the volumes of the right anteroventral, right ventral posterior lateral, and both right and left pulvinar nuclei were significantly lower in MS patients compared to controls, after adjusting for age, sex and intracranial volume. Lastly, we evaluated the potential of this method for targeting the Vim nucleus for deep brain surgery and focused ultrasound thalamotomy by overlaying the Vim nucleus segmented from pre-operative data on post-operative data. The locations of the ablated region and active DBS contact corresponded well with the segmented Vim nucleus. Our fast, direct structural MRI based segmentation method opens the door for MRI guided intra-operative procedures like thalamotomy and asleep DBS electrode placement as well as for accurate quantification of thalamic nuclear volumes to follow progression of neurological disorders. • White-matter nulled MP-RAGE sequence provides improved intra-thalamic contrast. • THOMAS exploits this improved contrast to segment 12 thalamic nuclei with excellent accuracy as measured by Dice against manual segmentation. • Volumetry results using THOMAS revealed atrophy of select nuclei in multiple sclerosis patients. • THOMAS can also be used to accurately predict the ventralis intermedius nucleus for deep brain stimulation targeting. [ABSTRACT FROM AUTHOR]