Cognitive impairment is a common symptom in individuals with Multiple Sclerosis (MS), but meaningful, reliable biomarkers relating to cognitive decline have been elusive, making evaluation of the ...impact of therapeutics on cognitive function difficult. Here, we combine pathway-based MRI measures of structural and functional connectivity to construct a metric of functional decline in MS. The Structural and Functional Connectivity Index (SFCI) is proposed as a simple, z-scored metric of structural and functional connectivity, where changes in the metric have a simple statistical interpretation and may be suitable for use in clinical trials. Using data collected at six time points from a 2-year longitudinal study of 20 participants with MS and 9 age- and sex-matched healthy controls, we probe two common symptomatic domains, motor and cognitive function, by measuring structural and functional connectivity in the transcallosal motor pathway and posterior cingulum bundle. The SFCI is significantly lower in participants with MS compared to controls (p = 0.009) and shows a significant decrease over time in MS (p = 0.012). The change in SFCI over two years performed favorably compared to measures of brain parenchymal fraction and lesion volume, relating to follow-up measures of processing speed (r = 0.60, p = 0.005), verbal fluency (r = 0.57, p = 0.009), and score on the Multiple Sclerosis Functional Composite (r = 0.67, p = 0.003). These initial results show that the SFCI is a suitable metric for longitudinal evaluation of functional decline in MS.
Resting state fMRI has become widely accepted as a viable technique for investigating functional connectivity of the human brain. I review from a personal perspective the events of the first ...8–10years after the initial report of resting state functional connectivity, focusing on the events that led to eventual acceptance of the method. During this time there were important studies, both in MRI and other modalities, that were critical to the eventual acceptance of the resting state as a viable research tool in fMRI.
Ultra-high spatial resolution imaging of whole, ex vivo brains provides new opportunities to understand neurological disease. Recent work has demonstrated that 100 μm isotropic resolution can reveal ...anatomical details that are otherwise difficult to appreciate, but relied on fabrication facilities, fabrication expertise and programming expertise that is not available at clinical imaging sites that lack a dedicated research staff and resources. The purpose of this work is to describe a whole-brain, ultra-high spatial resolution imaging procedure for ex vivo specimens using equipment that can be purchased, assembled and implemented by most clinical sites. We provide enough detail so that other groups can readily reproduce the approach.
A container and hardware for holding the brain fixed for long scan times was developed, along with a procedure for removing bubbles, which can cause artifact. Imaging was performed on a standard knee coil on a whole-body 7 T MRI at 170 μm isotropic spatial resolution. Five specimens were examined in Fomblin or formalin to evaluate consistency of image quality.
High quality images were acquired on all specimens. Anatomical features that are not readily observed at standard resolution, such as subthalamic nuclei, are readily observed. Disease-related features such as microscopic infarcts are also readily observed.
Ultra-high spatial resolution, whole-brain images can be readily achieved without specialized hardware and software development. The approach is expected to be valuable as a complement to histology and to discover relationships among pathology located at different places throughout the brain.
•Whole-brain ultra-high spatial resolution imaging provides spectacular images.•Methods to date have relied on specialized equipment.•We describe an approach that can be readily reproduced.
Introduction
Identifying drivers in persistent atrial fibrillation (AF) remains challenging. We sought to validate an automated system for detection of focal activation using basket and PentaRay ...catheters in AF.
Methods
Patients having ablation for atrial tachycardia (AT) and persistent AF were mapped. Thirty‐second unipolar basket and PentaRay recordings were analyzed using CARTOFINDER. Focal activation or “region of interest” (ROI) was defined as more than or equal to 2 consecutive focal activations with one electrode leading relative to its neighbors with QS morphology on the unipolar electrogram. ROI was validated in AT. AF patients were mapped to (1) look for evidence of focal activations on wavefront maps, (2) evaluate whether these were detected as ROI on basket recordings, and (3) whether these sites could be identified on sequential PentaRay recordings.
Results
ROIs were identified in five focal ATs but none of 16 reentrant ATs. Twenty‐eight AF patients had 35 focal drivers identified from basket wavefront maps with an ablation response in all (16 cycle length slowing and 19 AF termination). Thirty focal activations were detected on basket ROI maps (86%). Twenty‐three of 28 patients had sequential PentaRay mapping and 22 of 30 focal drivers in these patients (73%) were identified as ROI. These drivers had greater temporal stability (3.6 ± 0.6 vs 2.7 ± 0.6; P < 0.001), higher recurrence rate (12.4 ± 2.7 vs 7.2 ± 0.9;
P < 0.001), and more frequently were associated with AF termination (
P < 0.001) compared with those not identified as ROI.
Conclusions
Focal activations can be detected in AF using sequential recordings. The ablation response at focal sources suggests they may be viable therapeutic targets.
In echo-planar imaging (EPI), such as commonly used for functional MRI (fMRI) and diffusion-tensor imaging (DTI), compressed distortion is a more difficult challenge than local stretching as spatial ...information can be lost in strongly compressed areas. In addition, the effects are more severe at ultra-high field (UHF) such as 7T due to increased field inhomogeneity. To resolve this problem, two EPIs with opposite phase-encoding (PE) polarity were acquired and combined after distortion correction. For distortion correction, a point spread function (PSF) mapping method was chosen due to its high correction accuracy and extended to perform distortion correction of both EPIs with opposite PE polarity thus reducing the PSF reference scan time. Because the amount of spatial information differs between the opposite PE datasets, the method was further extended to incorporate a weighted combination of the two distortion-corrected images to maximize the spatial information content of a final corrected image. The correction accuracy of the proposed method was evaluated in distortion-corrected data using both forward and reverse phase-encoded PSF reference data and compared with the reversed gradient approaches suggested previously. Further we demonstrate that the extended PSF method with an improved weighted combination can recover local distortions and spatial information loss and be applied successfully not only to spin-echo EPI, but also to gradient-echo EPIs acquired with both PE directions to perform geometrically accurate image reconstruction.
Intimate partner violence (IPV) survivors frequently report face, head, and neck as their injury site. Many mild traumatic brain injuries (TBIs) are undiagnosed or underreported among IPV survivors ...while these injuries may be linked to changes in brain function or pathology. TBI sustained due to IPV often occurs over time and ranges in severity. The aim of this case-series study was to explore risk factors, symptoms, and brain changes unique to survivors of intimate partner violence with suspicion of TBI. This case-series exploratory study examines the potential relationships among IPV, mental health issues, and TBI. Participants of this study included six women: 3 women with a history of IPV without any experience of concussive blunt force to the head, and 3 women with a history of IPV with concussive head trauma. Participants completed 7T MRI of the brain, self-report psychological questionnaires regarding their mental health, relationships, and IPV, and the Structured Clinical Interview. MRI scans were analyzed for cerebral hemorrhage, white matter disturbance, and cortical thinning. Results indicated significant differences in resting-state connectivity among survivors of partner violence as well as differences in relationship dynamics and mental health symptoms. White matter hyperintensities are also observed among the survivors. Developing guidelines and recommendations for TBI-risk screening, referrals, and appropriate service provision is crucial for the effective treatment of TBI-associated IPV. Early and accurate characterization of TBI in survivors of IPV may relieve certain neuropsychological consequences.
It has been hypothesized that one of the effects of antidepressants is to increase functional connectivity between the cortical mood-regulating and the limbic mood-generating regions. One consequence ...of this antidepressant effect is thought to be decreased limbic activation in response to negative emotional stimuli. Twelve unmedicated unipolar depressed patients and 11 closely matched healthy comparison subjects completed two magnetic resonance imaging (MRI) scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each MRI session, subjects completed a resting state functional connectivity scan and a conventional block-design negative vs. neutral pictures regional brain activation scan. After 6 weeks of sertraline treatment resting state, functional connectivity between the ACC and limbic regions increased while limbic activation in response to negative versus neutral pictures decreased. The results of this study are consistent with the hypothesis that antidepressant treatment has reciprocal effects on corticolimbic functional connectivity and limbic activation in response to emotional stimuli.
Well‐defined copolymers containing luminescent iridium and hybrid iridium/rhenium fragments are prepared utilizing parent poly(n‐butyl acrylamide‐co‐N‐(1H‐tetrazol‐5‐yl) acrylamide) as macromolecular ...chelating species. The parent (co)polymers are prepared via the modification of a precursor poly(pentafluorophenyl acrylate) (polyPFPA) homopolymer, prepared by reversible addition‐fragmentation chain transfer polymerization, with n‐butylamine and 5‐aminotetrazole. Reaction of the parent copolymers with Ir2(ppy)4(μ−Cl2) (ppy = 2‐phenylpyridine) yields modified copolymers containing the Ir(ppy)2 fragment as a pendent group. Attachment of the Ir species is confirmed by a combination of photophysical studies, UV–Vis spectroscopy, and visually under irradiation with UV light. Importantly, it is demonstrated that the chelation of the Ir(ppy)2 fragment to a polymeric scaffold does not impact the fundamental photophysical properties of the Ir species. Attachment of a second luminescent metal species, Re(CO)3(phen) (phen = 1,10‐phenanthroline), gives hybrid materials containing Re(I) and Ir(III). The photophysical properties of these hybrid materials are consistent with the presence of both metal species and indicate the occurrence of energy transfer phenomena from the polymer‐bound Ir to Re metal centers. Finally, it is demonstrated that the Ir modified polymers and the Ir/Re hybrid materials offer potential in tissue imaging applications with scope to tune both luminescent properties and biological specificity as evidenced from preliminary brain tissue staining experiments.
Reversible addition‐fragmentation chain transfer‐prepared, tetrazole‐functionalized copolymers are employed as macromolecular ligands for attachment of luminescent iridium(III) and rhenium(I) fragments. Detailed photophysical studies indicate that chelation to a polymeric scaffold does not affect the fundamental properties of the iridium and rhenium species. In the case of copolymers containing both metal species, there is evidence on internal energy transfer phenomena. The iridium‐based materials are shown to have potential as bioimaging agents.
Research during the past decade has seen significant progress in the understanding of the genetic architecture of autism spectrum disorders (ASDs), with gene discovery accelerating as the ...characterization of genomic variation has become increasingly comprehensive. At the same time, this research has highlighted ongoing challenges. Here we address the enormous impact of high-throughput sequencing (HTS) on ASD gene discovery, outline a consensus view for leveraging this technology, and describe a large multisite collaboration developed to accomplish these goals. Similar approaches could prove effective for severe neurodevelopmental disorders more broadly.
To assess intrascanner repeatability and cross-scanner comparability for diffusion tensor imaging (DTI) metrics in a multicenter clinical trial.
DTI metrics (including longitudinal diffusivity LD, ...fractional anisotropy FA, mean diffusivity MD, and transverse diffusivity TD) from pyramidal tracts for healthy controls were calculated from images acquired on twenty-seven 3T MR scanners (Siemens and GE) with 6 different scanner models and 7 different software versions as part of the NN102/SPRINT-MS clinical trial. Each volunteer underwent two scanning sessions on the same scanner. Signal-to-noise ratio (SNR) and signal-to-noise floor ratio (SNFR) were also assessed.
DTI metrics showed good scan-rescan repeatability. There were no significant differences between scans and rescans in LD, FA, MD, or TD values. Although the cross-scanner coefficient of variation (CV) values for all DTI metrics were <5.7%, significant differences were observed for LD (p < 3.3e-5) and FA (p < 0.0024) when GE scanners were compared with Siemens scanners. Significant differences were also observed for SNR when comparing GE scanners and Siemens Skyra scanners (p < 1.4e-7) and when comparing Siemens Skyra scanners and TIM Trio scanners (p < 1.0e-10). Analysis of background signal also demonstrated differences between GE and Siemens scanners in terms of signal statistics. The measured signal intensity from a background noise region of interest was significantly higher for GE scanners than for Siemens scanners (p < 1.2e-12). Significant differences were also observed for SNFR when comparing GE scanners and Siemens Skyra scanners (p < 2.5e-11), GE scanners and Siemens Trio scanners (p < 7.5e-11), and Siemens Skyra scanners and TIM Trio scanners (p < 2.5e-9).
The good repeatability of the DTI metrics among the 27 scanners used in this study confirms the feasibility of combining DTI data from multiple centers using high angular resolution sequences. Our observations support the feasibility of longitudinal multicenter clinical trials using DTI outcome measures. The noise floor level and SNFR are important parameters that must be assessed when comparing studies that used different scanner models.
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