Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study.

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .

Differential vulnerability of thalamic nuclei in multiple sclerosis.

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.

Thalamic nuclei atrophy at high and heterogenous rates during cognitively unimpaired human aging.

The thalamus is a central integration structure in the brain, receiving and distributing information among the cerebral cortex, subcortical structures, and the peripheral nervous system. Prior studies clearly show that the thalamus atrophies in cognitively unimpaired aging. However, the thalamus is comprised of multiple nuclei involved in a wide range of functions, and the age-related atrophy of individual thalamic nuclei remains unknown. Using a recently developed automated method of identifying thalamic nuclei (3T or 7T MRI with white-matter-nulled MPRAGE contrast and THOMAS segmentation) and a cross-sectional design, we evaluated the age-related atrophy rate for 10 thalamic nuclei (AV, CM, VA, VLA, VLP, VPL, pulvinar, LGN, MGN, MD) and an epithalamic nucleus (habenula). We also used T1-weighted images with the FreeSurfer SAMSEG segmentation method to identify and measure age-related atrophy for 11 extra-thalamic structures (cerebral cortex, cerebral white matter, cerebellar cortex, cerebellar white matter, amygdala, hippocampus, caudate, putamen, nucleus accumbens, pallidum, and lateral ventricle). In 198 cognitively unimpaired participants with ages spanning 20-88 years, we found that the whole thalamus atrophied at a rate of 0.45% per year, and that thalamic nuclei had widely varying age-related atrophy rates, ranging from 0.06% to 1.18% per year. A functional grouping analysis revealed that the thalamic nuclei involved in cognitive (AV, MD; 0.53% atrophy per year), visual (LGN, pulvinar; 0.62% atrophy per year), and auditory/vestibular (MGN; 0.64% atrophy per year) functions atrophied at significantly higher rates than those involved in motor (VA, VLA, VLP, and CM; 0.37% atrophy per year) and somatosensory (VPL; 0.32% atrophy per year) functions. A proximity-to-CSF analysis showed that the group of thalamic nuclei situated immediately adjacent to CSF atrophied at a significantly greater atrophy rate (0.59% atrophy per year) than that of the group of nuclei located farther from CSF (0.36% atrophy per year), supporting a growing hypothesis that CSF-mediated factors contribute to neurodegeneration. We did not find any significant hemispheric differences in these rates of change for thalamic nuclei. Only the CM thalamic nucleus showed a sex-specific difference in atrophy rates, atrophying at a greater rate in male versus female participants. Roughly half of the thalamic nuclei showed greater atrophy than all extra-thalamic structures examined (0% to 0.54% per year). These results show the value of white-matter-nulled MPRAGE imaging and THOMAS segmentation for measuring distinct thalamic nuclei and for characterizing the high and heterogeneous atrophy rates of the thalamus and its nuclei across the adult lifespan. Collectively, these methods and results advance our understanding of the role of thalamic substructures in neurocognitive and disease-related changes that occur with aging.

Comparison between 7 Tesla and 3 Tesla MRI for characterizing orbital lesions.

PURPOSE: Characterizing orbital lesions remains challenging with imaging. The purpose of this study was to compare 3 Tesla (T) to 7 T magnetic resonance imaging (MRI) for characterizing orbital lesions. MATERIALS AND METHODS: This prospective single-center study enrolled participants presenting with orbital lesions from May to October 2019, who underwent both 7 T and 3 T MRI examinations. Two neuroradiologists, blinded to all data, read both datasets independently and randomly. They assessed general characteristics of each orbital lesion as well as image quality and presence of artifacts. Comparison between both datasets was made using Fisher exact test. RESULTS: Seven patients (4 women, 3 men) with a median age of 52 years were enrolled. Orbital lesion conspicuity was better scored at 7 T compared to 3 T MRI, with 3/7 lesions (43%) scored as very conspicuous at 7 T compared to 0/7 lesion (0%) at 3 T, although the difference was not significant (P = 0.16). Delineation of lesion margins was better scored at 7 T compared to 3 T with 3/7 lesions (43%) scored as very well delineated on 7 T compared to 0/7 lesions (0%) at 3 T, although the difference was not significant (P = 0.34). Details of internal structure were better assessed at 7 T compared to 3 T, with 4/7 lesions (57%) displaying numerous internal details compared to 0/7 lesions (0%) at 3 T (P = 0.10). Internal microvessels were visible in 3/7 lesions (43%) at 7 T compared to 0/7 lesions (0%) at 3 T (P = 0.19). CONCLUSION: Although no significant differences were found between 7 T and 3 T MRI, assumably due to a limited number of patients, our study suggests that 7 Tesla MRI might help improve the characterization of orbital lesions. However, further studies with more patients are needed.

In vivo high-resolution structural MRI-based atlas of human thalamic nuclei.

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.

Electric field calculation and peripheral nerve stimulation prediction for head and body gradient coils.

PURPOSE: To demonstrate and validate electric field (E-field) calculation and peripheral nerve stimulation (PNS) prediction methods that are accurate, computationally efficient, and that could be used to inform regulatory standards. METHODS: We describe a simplified method for calculating the spatial distribution of induced E-field over the volume of a body model given a gradient coil vector potential field. The method is easily programmed without finite element or finite difference software, allowing for straightforward and computationally efficient E-field evaluation. Using these E-field calculations and a range of body models, population-weighted PNS thresholds are determined using established methods and compared against published experimental PNS data for two head gradient coils and one body gradient coil. RESULTS: A head-gradient-appropriate chronaxie value of 669 µs was determined by meta-analysis. Prediction errors between our calculated PNS parameters and the corresponding experimentally measured values were ~5% for the body gradient and ~20% for the symmetric head gradient. Our calculated PNS parameters matched experimental measurements to within experimental uncertainty for 73% of ∆Gmin estimates and 80% of SRmin estimates. Computation time is seconds for initial E-field maps and milliseconds for E-field updates for different gradient designs, allowing for highly efficient iterative optimization of gradient designs and enabling new dimensions in PNS-optimal gradient design. CONCLUSIONS: We have developed accurate and computationally efficient methods for prospectively determining PNS limits, with specific application to head gradient coils.

Minimum electric-field gradient coil design: Theoretical limits and practical guidelines.

PURPOSE: To develop new concepts for minimum electric-field (E-field) gradient design, and to define the extents to which E-field can be reduced in gradient design while maintaining a desired imaging performance. METHODS: Efficient calculation of induced electric field in simplified patient models was integrated into gradient design software, allowing constraints to be placed on the peak E-field. Gradient coils confined to various build envelopes were designed with minimum E-fields subject to standard magnetic field constraints. We examined the characteristics of E-field-constrained gradients designed for imaging the head and body and the importance of asymmetry and concomitant fields in achieving these solutions. RESULTS: For transverse gradients, symmetric solutions create high levels of E-fields in the shoulder region, while fully asymmetric solutions create high E-fields on the top of the head. Partially asymmetric solutions result in the lowest E-fields, balanced between shoulders and head and resulting in factors of 1.8 to 2.8 reduction in E-field for x-gradient and y-gradient coils, respectively, when compared with the symmetric designs of identical gradient distortion. CONCLUSIONS: We introduce a generalized method for minimum E-field gradient design and define the theoretical limits of magnetic energy and peak E-field for gradient coils of arbitrary cylindrical geometry.

Effect of radiofrequency shield diameter on signal-to-noise ratio at ultra-high field MRI.

PURPOSE: In this work, we investigated how the position of the radiofrequency (RF) shield can affect the signal-to-noise ratio (SNR) of a receive RF coil. Our aim was to obtain physical insight for the design of a 10.5T 32-channel head coil, subject to the constraints on the diameter of the RF shield imposed by the head gradient coil geometry. METHOD: We used full-wave numerical simulations to investigate how the SNR of an RF receive coil depends on the diameter of the RF shield at ultra-high magnetic field (UHF) strengths (≥7T). RESULTS: Our simulations showed that there is an SNR-optimal RF shield size at UHF strength, whereas at low field the SNR monotonically increases with the shield diameter. For a 32-channel head coil at 10.5T, an optimally sized RF shield could act as a cylindrical waveguide and increase the SNR in the brain by 27% compared to moving the shield as far as possible from the coil. Our results also showed that a separate transmit array between the RF shield and the receive array could considerably reduce SNR even if they are decoupled. CONCLUSION: At sufficiently high magnetic field strength, the design of local RF coils should be optimized together with the design of the RF shield to benefit from both near field and resonant modes.

Association of CSF Biomarkers With Hippocampal-Dependent Memory in Preclinical Alzheimer Disease.

OBJECTIVE: To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF ß-amyloid (Aß)42/Aß40 and phosopho-tau181 (p-tau181) in cognitively unimpaired older adults (CU). METHODS: CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aß42, Aß40, and p-tau181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied "target" objects, novel "foil" objects, and perceptually similar "lure" objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education. RESULTS: Age and lower Aß42/Aß40 were independently associated with elevated p-tau181. Age, Aß42/Aß40, and p-tau181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aß42/Aß40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aß42 was not significantly associated with p-tau181 or memory. CONCLUSIONS: Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.

Automated thalamic nuclei segmentation using multi-planar cascaded convolutional neural networks.

PURPOSE: To develop a fast and accurate convolutional neural network based method for segmentation of thalamic nuclei. METHODS: A cascaded multi-planar scheme with a modified residual U-Net architecture was used to segment thalamic nuclei on conventional and white-matter-nulled (WMn) magnetization prepared rapid gradient echo (MPRAGE) data. A single network was optimized to work with images from healthy controls and patients with multiple sclerosis (MS) and essential tremor (ET), acquired at both 3 T and 7 T field strengths. WMn-MPRAGE images were manually delineated by a trained neuroradiologist using the Morel histological atlas as a guide to generate reference ground truth labels. Dice similarity coefficient and volume similarity index (VSI) were used to evaluate performance. Clinical utility was demonstrated by applying this method to study the effect of MS on thalamic nuclei atrophy. RESULTS: Segmentation of each thalamus into twelve nuclei was achieved in under a minute. For 7 T WMn-MPRAGE, the proposed method outperforms current state-of-the-art on patients with ET with statistically significant improvements in Dice for five nuclei (increase in the range of 0.05-0.18) and VSI for four nuclei (increase in the range of 0.05-0.19), while performing comparably for healthy and MS subjects. Dice and VSI achieved using 7 T WMn-MPRAGE data are comparable to those using 3 T WMn-MPRAGE data. For conventional MPRAGE, the proposed method shows a statistically significant Dice improvement in the range of 0.14-0.63 over FreeSurfer for all nuclei and disease types. Effect of noise on network performance shows robustness to images with SNR as low as half the baseline SNR. Atrophy of four thalamic nuclei and whole thalamus was observed for MS patients compared to healthy control subjects, after controlling for the effect of parallel imaging, intracranial volume, gender, and age (p < 0.004). CONCLUSION: The proposed segmentation method is fast, accurate, performs well across disease types and field strengths, and shows great potential for improving our understanding of thalamic nuclei involvement in neurological diseases.

Improved Vim targeting for focused ultrasound ablation treatment of essential tremor: A probabilistic and patient-specific approach.

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.

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults.

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson's Disease: A 7 Tesla Imaging Study.

BACKGROUND: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor. OBJECTIVE: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI. METHODS: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty). RESULTS: We found that smaller SN correlated with longer disease duration (r = -0.49, p = 0.004), more severe MDS-UPDRS motor score (r = -0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r = -0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume. CONCLUSIONS: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and laterality-dependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

A within-coil optical prospective motion-correction system for brain imaging at 7T.

PURPOSE: Motion artifact limits the clinical translation of high-field MR. We present an optical prospective motion correction system for 7 Tesla MRI using a custom-built, within-coil camera to track an optical marker mounted on a subject. METHODS: The camera was constructed to fit between the transmit-receive coils with direct line of sight to a forehead-mounted marker, improving upon prior mouthpiece work at 7 Tesla MRI. We validated the system by acquiring a 3D-IR-FSPGR on a phantom with deliberate motion applied. The same 3D-IR-FSPGR and a 2D gradient echo were then acquired on 7 volunteers, with/without deliberate motion and with/without motion correction. Three neuroradiologists blindly assessed image quality. In 1 subject, an ultrahigh-resolution 2D gradient echo with 4 averages was acquired with motion correction. Four single-average acquisitions were then acquired serially, with the subject allowed to move between acquisitions. A fifth single-average 2D gradient echo was acquired following subject removal and reentry. RESULTS: In both the phantom and human subjects, deliberate and involuntary motion were well corrected. Despite marked levels of motion, high-quality images were produced without spurious artifacts. The quantitative ratings confirmed significant improvements in image quality in the absence and presence of deliberate motion across both acquisitions (P < .001). The system enabled ultrahigh-resolution visualization of the hippocampus during a long scan and robust alignment of serially acquired scans with interspersed movement. CONCLUSION: We demonstrate the use of a within-coil camera to perform optical prospective motion correction and ultrahigh-resolution imaging at 7 Tesla MRI. The setup does not require a mouthpiece, which could improve accessibility of motion correction during 7 Tesla MRI exams.

Correlative Microscopy to Localize and Characterize Iron Deposition in Alzheimer's Disease.

BACKGROUND: Recent evidence suggests that the accumulation of iron, specifically ferrous Fe2+, may play a role in the development and progression of neurodegeneration in Alzheimer's disease (AD) through the production of oxidative stress. OBJECTIVE: To localize and characterize iron deposition and oxidation state in AD, we analyzed human hippocampal autopsy samples from four subjects with advanced AD that have been previously characterized with correlative MRI-histology. METHODS: We perform scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron energy loss spectroscopy (EELS) in the higher resolution transmission electron microscope on the surface and cross-sections of specific iron-rich regions of interest. RESULTS: Specific previously analyzed regions were visualized using SEM and confirmed to be iron-rich deposits using EDS. Subsequent analysis using focused ion beam cross-sectioning and SEM characterized the iron deposition throughout the 3-D volumes, confirming the presence of iron throughout the deposits, and in two out of four specimens demonstrating colocalization with zinc. Analysis of traditional histology slides showed the analyzed deposits overlapped both with amyloid and tau deposition. Following higher resolution analysis of a single iron deposit using scanning transmission electron microscope (STEM), we demonstrated the potential of monochromated STEM-EELS to discern the relative oxidation state of iron within a deposit. CONCLUSION: These findings suggest that iron is present in the AD hippocampus and can be visualized and characterized using combined MRI and EM techniques. An altered relative oxidation state may suggest a direct link between iron and oxidative stress in AD. These methods thus could potentially measure an altered relative oxidation state that could suggest a direct link between iron and oxidative stress in AD. Furthermore, we have demonstrated the ability to analyze metal deposition alongside commonly used histological markers of AD pathology, paving the way for future insights into the molecular interactions between Aß, tau, iron, and other putative metals, such as zinc.

SMS MUSSELS: A navigator-free reconstruction for simultaneous multi-slice-accelerated multi-shot diffusion weighted imaging.

PURPOSE: To introduce a novel reconstruction method for simultaneous multi-slice (SMS)-accelerated multi-shot diffusion weighted imaging (ms-DWI). METHODS: SMS acceleration using blipped-CAIPI schemes have been proposed to speed up the acquisition of ms-DWIs. The reconstruction of the data requires (a) phase compensation to combine data from different shots and (b) slice unfolding to separate the data of different slices. The traditional approaches first estimate the phase maps corresponding to each shot and slice which are then employed to iteratively recover the slice unfolded DWIs without phase artifacts. In contrast, the proposed reconstruction directly recovers the slice-unfolded k-space data of the multiple shots for each slice in a single-step recovery scheme. The proposed method is enabled by the low-rank property inherent in the k-space samples of ms-DW acquisition. This enabled to formulate a joint recovery scheme that simultaneously (a) unfolds the k-space data of each slice using a SENSE-based scheme and (b) recover the missing k-space samples in each slice of the multi-shot acquisition employing a structured low-rank matrix completion. Additional smoothness regularization is also utilized for higher acceleration factors. The proposed joint recovery is tested on simulated and in vivo data and compared to similar un-navigated methods. RESULTS: Our experiments show effective slice unfolding and successful recovery of DWIs with minimal phase artifacts using the proposed method. The performance is comparable to existing methods at low acceleration factors and better than existing methods for higher acceleration factors. CONCLUSIONS: For the slice accelerations considered in this study, the proposed method can successfully recover DWIs from SMS-accelerated ms-DWI acquisitions.

White-matter-nulled MPRAGE at 7T reveals thalamic lesions and atrophy of specific thalamic nuclei in multiple sclerosis.

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.

MR susceptibility contrast imaging using a 2D simultaneous multi-slice gradient-echo sequence at 7T.

PURPOSE: To develop a 7T simultaneous multi-slice (SMS) 2D gradient-echo sequence for susceptibility contrast imaging, and to compare its quality to 3D imaging. METHODS: A frequency modulated and phase cycled RF pulse was designed to simultaneously excite multiple slices in multi-echo 2D gradient-echo imaging. The imaging parameters were chosen to generate images with susceptibility contrast, including T2*-weighted magnitude/phase images, susceptibility-weighted images and quantitative susceptibility/R2* maps. To compare their image quality with 3D gradient-echo imaging, both 2D and 3D imaging were performed on 11 healthy volunteers and 4 patients with multiple sclerosis (MS). The signal to noise ratio (SNR) in gray and white matter and their contrast to noise ratio (CNR) was simulated for the 2D and 3D magnitude images using parameters from the imaging. The experimental SNRs and CNRs were measured in gray/white matter and deep gray matter structures on magnitude, phase, R2* and QSM images from volunteers and the visibility of MS lesions on these images from patients was visually rated. All SNRs and CNRs were compared between the 2D and 3D imaging using a paired t-test. RESULTS: Although the 3D magnitude images still had significantly higher SNRs (by 13.0~17.6%), the 2D magnitude and QSM images generated significantly higher gray/white matter or globus pallidus/putamen contrast (by 13.3~87.5%) and significantly higher MS lesion contrast (by 5.9~17.3%). CONCLUSION: 2D SMS gradient-echo imaging can serve as an alternative to often used 3D imaging to obtain susceptibility-contrast-weighted images, with an advantage of providing better image contrast and MS lesion sensitivity.

Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life. METHODS: We studied 29 participants with PD (age 65.5 ±â€¯7.8 years; disease duration 4.5 ±â€¯3.0 years) and 8 matched-healthy controls (age 67.9 ±â€¯6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD. RESULTS: In our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05). CONCLUSIONS: In PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.

Thalamus Optimized Multi Atlas Segmentation (THOMAS): fast, fully automated segmentation of thalamic nuclei from structural MRI.

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.