Simultaneous Measurement of GABA, Glutathione, and Glutamate-Glutamine in the Thalamus using Edited MR Spectroscopy: Feasibility and Applications in Traumatic Brain Injury.

BACKGROUND: MR spectroscopy (MRS) is a noninvasive tool for evaluating biochemical alterations, such as glutamate (Glu)/gamma-aminobutyric acid (GABA) imbalance and depletion of antioxidative glutathione (GSH) after traumatic brain injury (TBI). Thalamus, a critical and vulnerable region post-TBI, is challenging for MRS acquisitions, necessitating optimization to simultaneously measure GABA/Glu and GSH. PURPOSE: To assess the feasibility and optimize acquisition and processing approaches for simultaneously measuring GABA, Glx (Glu + glutamine (Gln)), and GSH in the thalamus, employing Hadamard encoding and reconstruction of MEscher-GArwood (MEGA)-edited spectroscopy (HERMES). STUDY TYPE: Prospective. SUBJECTS: 28 control subjects (age: 35.9 ± 15.1 years), and 17 mild TBI (mTBI) patients (age: 32.4 ± 11.3 years). FIELD STRENGTH/SEQUENCE: 3T/T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE), HERMES. ASSESSMENT: We evaluated the impact of acquisition with spatial saturation bands and post-processing with spectral alignment on HERMES performance in the thalamus among controls. Within-subject variability was examined in five controls through repeated scans within a week. The HERMES spectra in the posterior cingulate cortex (PCC) of controls were used as a reference for assessing HERMES performance in a reliable target. Furthermore, we compared metabolite levels and fitting quality in the thalamus between mTBI patients and controls. STATISTICAL TESTS: Unpaired t-tests and within-subject coefficient-of-variation (CV). A P-value <0.05 was deemed significant. RESULTS: HERMES spectra, acquired with saturation bands and processed with spectral alignment, yielded reliable metabolite measurements in the thalamus. The mean within-subject CV for GABA, Glx, and GSH levels were 18%, 10%, and 16% in the thalamus (7%, 9%, and 16% in the PCC). GABA (3.20 ± 0.60 vs 2.51 ± 0.55, P < 0.01) and Glx (8.69 ± 1.23 vs 7.72 ± 1.19, P = 0.03) levels in the thalamus were significantly higher in mTBI patients than in controls, with GSH (1.27 ± 0.35 vs 1.22 ± 0.28, P = 0.65) levels showing no significant difference. DATA CONCLUSION: Simultaneous measuring GABA/Glx and GSH using HERMES is feasible in the thalamus, providing valuable insight into TBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Toward vendor-independent measurement of cerebral venous oxygenation: Comparison of TRUST MRI across three major MRI manufacturers and association with end-tidal CO2.

Cerebral venous oxygenation (Yv ) is a valuable biomarker for a variety of brain diseases. T2 relaxation under spin tagging (TRUST) MRI is a widely used method for Yv quantification. In this work, there were two main objectives. The first was to evaluate the reproducibility of TRUST Yv measurements across MRI scanners from different vendors. The second was to examine the correlation between Yv and end-tidal CO2 (EtCO2 ) in a multisite, multivendor setting and determine the usefulness of this correlation to account for variations in Yv caused by normal variations and physiological fluctuations. Standardized TRUST pulse sequences were implemented on three scanners from major MRI vendors (GE, Siemens, Philips). These scanners were located at two research institutions. Ten healthy subjects were scanned. On each scanner, the subject underwent two scan sessions, each of which included three TRUST scans, to evaluate the intrasession and intersession reproducibility of Yv . Each scanner was also equipped with a capnograph device to record the EtCO2 of the subject during the MRI scan. We found no significant bias in Yv measurements across the three scanners (P = 0.18). The measured Yv values on the three scanners were also strongly correlated with each other (intraclass correlation coefficients > 0.85, P < 0.001). The intrasession and intersession coefficients of variation of Yv were less than 4% and showed no significant difference among the scanners. In addition, our results revealed that (1) within the same subject, Yv increased with EtCO2 at a rate of 1.24 ± 0.17%/mmHg (P < 0.0001), and (2) across different subjects, individuals with a higher EtCO2 had a higher Yv , at a rate of 0.94 ± 0.36%/mmHg (P = 0.01). These results suggest that (1) the standardized TRUST sequences had similar accuracies and reproducibilities for the quantification of Yv across the scanners, and (2) recording of EtCO2 may be a useful complement to Yv measurement to account for CO2 -related physiological fluctuations in Yv in multisite, multivendor studies.

Alterations in motor functional connectivity in Neonatal Hypoxic Ischemic Encephalopathy.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is the result of global hypoxic-ischemic brain injury in neonates due to asphyxia during birth and is one of the most common causes of severe, long-term neurologic deficits in children. Methods: Resting state fMRI (rs-fMRI) was used to assess potential functional disruptions in the primary and association motor areas in HIE neonates (n = 16) compared to healthy controls (n = 11). RESULTS: Results demonstrate reduced intra-hemispheric resting state functional connectivity (rs-FC) between primary motor regions (upper extremity and facial motor regions) as well as reduced inter-hemispheric rs-FC in the HIE group. In addition, HIE neonates demonstrated increased rs-FC between motor regions and frontal, temporal and parietal cortices but decreased rs-FC with the cerebellum. DISCUSSION: These preliminary results provide initial evidence for the disruption of functional communication with the motor network in neonates with HIE. Further studies are necessary to both validate these findings in a larger dataset as well as to determine if rs-fMRI measurements collected at birth may have the potential to serve as a prognostic marker in addition to the traditional combination of clinical measurements and conventional MRI.

Prospective motion detection and re-acquisition in diffusion MRI using a phase image-based method-Application to brain and tongue imaging.

PURPOSE: To develop an image-based motion-robust diffusion MRI (dMRI) acquisition framework that is able to minimize motion artifacts caused by rigid and nonrigid motion, applicable to both brain and tongue dMRI. METHODS: We developed a novel prospective motion-correction technique in dMRI using a phase image-based real-time motion-detection method (PITA-MDD) with re-acquisition of motion-corrupted images. The prospective PITA-MDD acquisition technique was tested in the brains and tongues of volunteers. The subjects were instructed to move their heads or swallow, to induce motion. Motion-detection efficacy was validated against visual inspection as the gold standard. The effect of the PITA-MDD technique on diffusion-parameter estimates was evaluated by comparing reconstructed fiber tracts using tractography with and without re-acquisition. RESULTS: The prospective PITA-MDD technique was able to effectively and accurately detect motion-corrupted data as compared with visual inspection. Tractography results demonstrated that PITA-MDD motion detection followed by re-acquisition helps in recovering lost and misshaped fiber tracts in the brain and tongue that would otherwise be corrupted by motion and yield erroneous estimates of the diffusion tensor. CONCLUSION: A prospective PITA-MDD technique was developed for dMRI acquisition, providing improved dMRI image quality and motion-robust diffusion estimation of the brain and tongue.

Early Stage Longitudinal Subcortical Volumetric Changes following Mild Traumatic Brain Injury.

Objective: To investigate early brain volumetric changes from acute to 6 months following mild traumatic brain injury (mTBI) in deep gray matter regions and their association with patient 6-month outcome.Methods: Fifty-six patients with mTBI underwent MRI and behavioral evaluation at acute (<10 days) and approximately 1 and 6 months post injury. Regional volume changes were investigated in key gray matter regions: thalamus, hippocampus, putamen, caudate, pallidum, and amygdala, and compared with volumes from 34 healthy control subjects. In patients with mTBI, we further assessed associations between longitudinal regional volume changes with patient outcome measures at 6 months including post-concussive symptoms, cognitive performance, and overall satisfaction with life.Results: Reduction in thalamic and hippocampal volumes was observed at 1 month among patients with mTBI. Such volume reduction persisted in the thalamus until 6 months. Changes in thalamic volumes also correlated with multiple symptom and functional outcome measures in patients at 6 months.Conclusion: Our results indicate that the thalamus may be differentially affected among patients with mTBI, resulting in both structural and functional deficits with subsequent post-concussive sequelae and may serve as a biomarker for the assessment of efficacy of novel therapeutic interventions.

White Matter Alterations in Fmr1 Knockout Mice during Early Postnatal Brain Development.

Fragile X syndrome (FXS) is the most commonly inherited form of intellectual disability ascribed to the autism spectrum disorder. Studies with FXS patients have reported altered white matter volume compared to controls. The Fmr1 knockout (KO) mouse, a model for FXS, showed evidence of delayed myelination during postnatal brain development. In this study, we examined several white matter regions in the male Fmr1 KO mouse brain compared to male wild-type (WT) mice at postnatal days (PND) 18, 21, 30, and 60, which coincide with critical stages of myelination and postnatal brain development. White matter volume, T2 relaxation time, and magnetization transfer ratio (MTR) were measured using magnetic resonance imaging and myelin content was determined with histological staining of myelin. Differences in the developmental accumulation of white matter and myelin between Fmr1 KO and WT mice were observed in the corpus callosum, external and internal capsules, cerebral peduncle, and fimbria. Alterations were more predominant in the external and internal capsules and fimbria of Fmr1 KO mice, where the MTR was lower at PND 18, then elevated at PND 30, and again lower at PND 60 compared to the corresponding regions in WT mice. The pattern of changes in MTR were similar to those observed in myelin staining and could be related to the altered protein synthesis that is a hallmark of FXS. While no significant changes in white matter volumes and T2 relaxation time between the Fmr1 KO and WT mice were observed, the altered pattern of myelin staining and MTR, particularly in the external capsule, reflecting the abnormalities associated with myelin content is suggestive of a developmental delay in the white matter of Fmr1 KO mouse brain. These early differences in white matter during critical developmental stages may contribute to altered brain networks in the Fmr1 KO mice.

Association of Patient Self-Reported Shoulder Scores to Quantitative and Semiquantitative MRI Measures of Rotator Cuff Intramuscular Fatty Infiltration: A Pilot Study.

OBJECTIVE. The purpose of this study was to determine the relationship of supraspinatus fat fraction and Goutallier grade to the American Shoulder and Elbow Surgeons (ASES) score in cohorts of older adults with painful full-thickness supraspinatus tendon (SST) tear and control subjects. SUBJECTS AND METHODS. Seventeen control subjects and 15 study participants with painful full-thickness SST tear were prospectively recruited (mean age ± SD, 63.0 ± 10.1 years and 62.6 ± 9.0 years, respectively). Study participants received shoulder MRI and completed ASES questionnaires at one time. Goutallier grade was assessed on T1-weighted MRI. Fat fraction was measured on 6-point Dixon MRI. Body mass index (BMI) was determined. Descriptive, correlation, reliability, and regression analyses were performed. RESULTS. The control and painful full-thickness SST tear cohorts differed in mean supraspinatus fat fraction (3.3% ± 1.4% and 7.3 ± 5.9%, respectively; p = 0.024) and Goutallier grade (0.4 ± 0.5 and 0.9 ± 0.7, respectively; p = 0.022). Fat fraction (p = 0.014) and Goutallier grade (p = 0.017) showed a significant inverse association with ASES score only in the SST tear cohort. The association of BMI to ASES score was significant only in the control group (p = 0.036). The correlation between BMI and fat fraction were different for the two groups (control cohort, r = 0.676 and p = 0.003; SST tear cohort, r = 0.124 and p = 0.687). Fat fraction showed strong interobserver reliability (intraclass correlation coefficient, 0.903); Goutallier grade showed poor interobserver reliability (κ = 0.178). CONCLUSION. The association of ASES score and supraspinatus fat fraction or Goutallier grade differs between patients with painful full-thickness SST tear and control subjects without symptoms. Although fat fraction shows strong reliability, Goutallier grade should be regarded cautiously because of suboptimal reproducibility. Our results also suggest that painful full-thickness SST tear alters the correlation between supraspinatus fat fraction and BMI as compared with control subjects.

Quantification of shoulder muscle intramuscular fatty infiltration on T1-weighted MRI: a viable alternative to the Goutallier classification system.

BACKGROUND: Quantification of rotator cuff intramuscular fatty infiltration is important for clinical decision-making in patients with rotator cuff tear. The semi-quantitative Goutallier classification system is the most commonly used method, but has limited reliability. Therefore, we sought to test a freely available fuzzy C-means segmentation software program for reliability of the quantification of shoulder intramuscular fatty infiltration on T1-weighted MR images and for correlation with fat fraction by six-point Dixon MRI. MATERIALS AND METHODS: We performed a prospective cross-sectional study to measure visible intramuscular fat area percentage on oblique sagittal T1 MR images by fuzzy C-means segmentation and fat fraction maps by six-point Dixon MRI for 42 shoulder muscles. Intra- and inter-observer reliability were determined. Correlative analysis for fuzzy C-means and six-point Dixon intramuscular fatty infiltration measures was also performed. RESULTS: We found that inter-observer reliability for the quantification of visible intramuscular fat area percentage by fuzzy C-means segmentation and fat fraction by six-point Dixon MRI was 0.947 and 0.951 respectively. The intra-observer reliability for the quantification of visible intramuscular fat area percentage by fuzzy C-means segmentation and fat fraction by six-point Dixon MRI was 0.871 and 0.979 respectively. We found a strong correlation between fuzzy C-means segmentation and six-point Dixon techniques; r = 0.850, p < 0.001 by individual muscle; and r = 0.977, p < 0.002 by study subject. CONCLUSION: Quantification of intramuscular fatty infiltration by fuzzy C-means segmentation on T1-weighted sequences demonstrates excellent reliability and strong correlation with fat fraction by six-point Dixon MRI. Quantitative fuzzy C-means segmentation is a viable alternative to the semi-quantitative Goutallier classification system.

Carotid webs and ischemic stroke: Experiences in a comprehensive stroke center.

BACKGROUND AND PURPOSE: Carotid webs are intraluminal filling defects at the carotid bulb which are considered rare, though possibly underappreciated entities with recent studies demonstrating a likely casual association with ischemic stroke. The purpose of the study is to describe our recent experience with clinical and imaging manifestations of carotid webs. MATERIALS AND METHODS: A retrospective review of CTA neck studies in all adult patients presenting to our institution during the 19-month study interval was performed to determine the presence of carotid webs. Subsequent chart review of these patients with webs was performed to assess their clinical history and to obtain demographic detail. RESULTS: A total of 14 patients were identified with carotid webs in the study population. The mean age of patients with webs was 42.1 years (range: 28-54), consisting mostly of African Americans (86%) and females (64%). Ten (71%) of web patients had a history of ischemic stroke, each ipsilateral to the side of web, and at least four of these patients had recurrent ischemic stroke. CONCLUSION: We provide one of the largest sample sizes of webs gathered in a single study. Given its association with ischemic stroke, carotid webs should be assessed for in all patients presenting with ischemic stroke, especially younger African Americans.

Accelerated 4D quantitative single point EPR imaging using model-based reconstruction.

PURPOSE: Electron paramagnetic resonance imaging has surfaced as a promising noninvasive imaging modality that is capable of imaging tissue oxygenation. Due to extremely short spin-spin relaxation times, electron paramagnetic resonance imaging benefits from single-point imaging and inherently suffers from limited spatial and temporal resolution, preventing localization of small hypoxic tissues and differentiation of hypoxia dynamics, making accelerated imaging a crucial issue. METHODS: In this study, methods for accelerated single-point imaging were developed by combining a bilateral k-space extrapolation technique with model-based reconstruction that benefits from dense sampling in the parameter domain (measurement of the T2 (*) decay of a free induction delay). In bilateral kspace extrapolation, more k-space samples are obtained in a sparsely sampled region by bilaterally extrapolating data from temporally neighboring k-spaces. To improve the accuracy of T2 (*) estimation, a principal component analysis-based method was implemented. RESULTS: In a computer simulation and a phantom experiment, the proposed methods showed its capability for reliable T2 (*) estimation with high acceleration (8-fold, 15-fold, and 30-fold accelerations for 61×61×61, 95×95×95, and 127×127×127 matrix, respectively). CONCLUSION: By applying bilateral k-space extrapolation and model-based reconstruction, improved scan times with higher spatial resolution can be achieved in the current single-point electron paramagnetic resonance imaging modality.

A longitudinal evaluation of diffusion kurtosis imaging in patients with mild traumatic brain injury.

PRIMARY OBJECTIVE: To investigate longitudinal diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) changes in white and grey matter in patients with mild traumatic brain injury (mTBI). RESEARCH DESIGN: A prospective case-control study. METHODS AND PROCEDURES: DKI data was obtained from 24 patients with mTBI along with cognitive assessments within 10 days, 1 month and 6 months post-injury and compared with age-matched control (n» 24). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusion (l(r)), mean kurtosis (MK) and radial kurtosis (Kr) were extracted from the thalamus, internal capsule and corpus callosum. MAIN OUTCOMES AND RESULTS: Results demonstrate reduced Kr and MK in the anterior internal capsule in patients with mTBI across the three visits, and reduced MK in the posterior internal capsule during the 10 day time point. Correlations were observed between the change in MK or Kr between 1­6 months and the improvements in cognition between the 1 and 6 month visits in the thalamus, internal capsule and corpus callosum. CONCLUSIONS: These data demonstrate that DKI may be sensitive in tracking pathophysiological changes associated with mTBI and may provide additional information to conventional DTI parameters in evaluating longitudinal changes following TBI.

Diffusion kurtosis imaging: an emerging technique for evaluating the microstructural environment of the brain.

OBJECTIVE: Diffusion kurtosis imaging is an emerging technique based on the non-gaussian diffusion of water in biologic systems. The purpose of this article is to introduce and discuss the ongoing research and potential clinical applications of this technique. CONCLUSION: Diffusion kurtosis imaging provides independent and complementary information to that acquired with traditional diffusion techniques. The additional information is thought to indicate the complexity of the microstructural environment of the imaged tissue and may lead to broad-reaching applications in all aspects of neuroradiology.

Automatic Quantification of Enlarged Perivascular Space in Patients With Traumatic Brain Injury Using Super-Resolution of T2-Weighted Images.

The perivascular space (PVS) is important to brain waste clearance and brain metabolic homeostasis. Enlarged PVS (ePVS) becomes visible on magnetic resonance imaging (MRI) and is best appreciated on T2-weighted (T2w) images. However, quantification of ePVS is challenging because standard-of-care T1-weighted (T1w) and T2w images are often obtained via two-dimensional (2D) acquisition, whereas accurate quantification of ePVS normally requires high-resolution volumetric three-dimensional (3D) T1w and T2w images. The purpose of this study was to investigate the use of a deep-learning-based super-resolution (SR) technique to improve ePVS quantification from 2D T2w images for application in patients with traumatic brain injury (TBI). We prospectively recruited 26 volunteers (age: 31 ± 12 years, 12 male/14 female) where both 2D T2w and 3D T2w images were acquired along with 3D T1w images to validate the ePVS quantification using SR T2w images. We then applied the SR method to retrospectively acquired 2D T2w images in 41 patients with chronic TBI (age: 41 ± 16 years, 32 male/9 female). ePVS volumes were automatically quantified within the whole-brain white matter and major brain lobes (temporal, parietal, frontal, occipital) in all subjects. Pittsburgh Sleep Quality Index (PSQI) scores were obtained on all patients with TBI. Compared with the silver standard (3D T2w), in the validation study, the SR T2w provided similar whole-brain white matter ePVS volume (r = 0.98, p < 0.0001), and similar age-related ePVS burden increase (r = 0.80, p < 0.0001). In the patient study, patients with TBI with poor sleep showed a higher age-related ePVS burden increase than those with good sleep. Sleep status is a significant interaction factor in the whole brain (p = 0.047) and the frontal lobe (p = 0.027). We demonstrate that images produced by SR of 2D T2w images can be automatically analyzed to produce results comparable to those obtained by 3D T2 volumes. Reliable age-related ePVS burden across the whole-brain white matter was observed in all subjects. Poor sleep, affecting the glymphatic function, may contribute to the accelerated increase of ePVS burden following TBI.

Meningeal contrast enhancement in multiple sclerosis: Assessment of field strength, acquisition delay, and clinical relevance.

BACKGROUND/PURPOSE: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report an assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). METHODS: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR). RESULTS: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008). CONCLUSION: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

Meningeal contrast enhancement in multiple sclerosis: assessment of field strength, acquisition delay, and clinical relevance.

Background/Purpose: Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report a comprehensive assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). Methods: This was a cross-sectional, observational study of 95 participants with MS and 17 healthy controls (HC) subjects. Each participant underwent an MRI of the brain on both a 7 Tesla (7T) and 3 Tesla (3T) MRI scanner. 7T protocols included a FLAIR image before, soon after (Gd+ Early 7T FLAIR), and 23 minutes after gadolinium (Gd+ Delayed 7T FLAIR). 3T protocol included FLAIR before and 21 minutes after gadolinium (Gd+ Delayed 3T FLAIR). Results: LME was seen in 23.3% of participants with MS on Gd+ Delayed 3T FLAIR, 47.4% on Gd+ Early 7T FLAIR (p = 0.002) and 57.9% on Gd+ Delayed 7T FLAIR (p < 0.001 and p = 0.008, respectively). The count and volume of LME, leptomeningeal and paravascular enhancement (LMPE), and paravascular and dural enhancement (PDE) were all highest for Gd+ Delayed 7T FLAIR and lowest for Gd+ Delayed 3T FLAIR. Non-significant trends were seen for higher proportion, counts, and volumes for LME and PDE in MS compared to HCs. The rate of LMPE was different between MS and HCs on Gd+ Delayed 7T FLAIR (98.9% vs 82.4%, p = 0.003). MS participants with LME on Gd+ Delayed 7T FLAIR were older (47.6 (10.6) years) than those without (42.0 (9.7), p = 0.008). Conclusion: 7T MRI and a delay after contrast injection increased sensitivity for all forms of MCE. However, the lack of difference between groups for LME and its association with age calls into question its relevance as a biomarker of meningeal inflammation in MS.

Focused Ultrasound Central Lateral Thalamotomy for the Treatment of Refractory Neuropathic Pain: Phase I Trial.

BACKGROUND AND OBJECTIVES: Magnetic resonance-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) has not yet been validated for treating refractory neuropathic pain (NP). Our aim was to assess the safety and potential efficacy of MRgFUS CLT for refractory NP. METHODS: In this prospective, nonrandomized, single-arm, investigator-initiated phase I trial, patients with NP for more than 6 months related to phantom limb pain, spinal cord injury, or radiculopathy/radicular injury and who had undergone at least one previous failed intervention were eligible. The main outcomes were safety profile and pain as assessed using the brief pain inventory, the pain disability index, and the numeric rating scale. Medication use and the functional connectivity of the default mode network (DMN) were also assessed. RESULTS: Ten patients were enrolled, with nine achieving successful ablation. There were no serious adverse events and 12 mild/moderate severity events. The mean age was 50.9 years (SD: 12.7), and the mean symptom duration was 12.3 years (SD: 9.7). Among eight patients with a 1-year follow-up, the brief pain inventory decreased from 7.6 (SD: 1.1) to 3.8 (SD: 2.8), with a mean percent decrease of 46.3 (SD: 40.6) (paired t -test, P = .017). The mean pain disability index decreased from 43.0 (SD: 7.5) to 25.8 (SD: 16.8), with a mean percent decrease of 39.3 (SD: 41.6) ( P = .034). Numeric rating scale scores decreased from a mean of 7.2 (SD: 1.8) to 4.0 (SD: 2.8), with a mean percent decrease of 42.8 (SD: 37.8) ( P = .024). Patients with predominantly intermittent pain or with allodynia responded better than patients with continuous pain or without allodynia, respectively. Some patients decreased medication use. Resting-state functional connectivity changes were noted, from disruption of the DMN at baseline to reactivation of connectivity between DMN nodes at 3 months. CONCLUSION: MRgFUS CLT is feasible and safe for refractory NP and has potential utility in reducing symptoms as measured by validated pain scales.

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging.

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

MR imaging and differentiation of cerebral fat embolism syndrome from diffuse axonal injury: application of diffusion tensor imaging.

INTRODUCTION: Cerebral fat embolism syndrome (CFES) mimics diffuse axonal injury (DAI) on MRI with vasogenic edema, cytotoxic edema, and micro-hemorrhages, making specific diagnosis a challenge. The objective of our study is to determine and compare the diagnostic utility of the conventional MRI and DTI in differentiating cerebral fat embolism syndrome from diffuse axonal injury. METHODS: This retrospective study was performed after recruiting 11 patients with severe CFES and ten patients with severe DAI. Three trauma radiologists analyzed conventional MR images to determine the presence or absence of CFES and DAI. DTI analysis of the whole-brain white matter was performed to obtain the directional diffusivities. The results were correlated with clinical diagnosis to determine the diagnostic utility of conventional MRI and DTI. RESULTS: The sensitivity, specificity, and accuracy of conventional MRI in diagnosing CFES, obtained from the pooled data were 76, 85, and 80 %, respectively. Mean radial diffusivity (RD) was significantly higher and the mean fractional anisotropy (FA) was lower in CFES and differentiated subjects with CFES from the DAI group. Area under the receiver operating characteristic (ROC) curve for conventional MRI was 0.82, and for the differentiating DTI parameters the values were 0.75 (RD) and 0.86 (FA), respectively. CONCLUSIONS: There is no significant difference between diagnostic performance of DTI and conventional MRI in CFES, but a difference in directional diffusivities was clearly identified between CFES and DAI.

Diagnosis of traumatic optic neuropathy: application of diffusion tensor magnetic resonance imaging.

BACKGROUND: Using diffusion tensor imaging, we evaluated the directional diffusivities of the optic nerve in patients with traumatic optic neuropathy (TON). METHODS: Our study consisted of 12 patients with unilateral TON, 6 patients with severe traumatic brain injury (comparison group A), and 6 patients with normal conventional brain magnetic resonance imaging (comparison group B). The contralateral optic nerve in patients with TON also was evaluated (comparison group C). Two trauma radiologists, blinded to the clinical diagnosis, independently obtained the directional diffusivities. The intraorbital optic nerve was divided into anterior and posterior segments to evaluate intersegmental differences in directional diffusivities. RESULTS: The mean axial diffusivity (AD) in both optic nerve segments and the mean diffusivity (ADC) in the posterior segment on the affected side were significantly lower and differentiated subjects with TON from those in comparison groups A and B. Area under the receiver operating characteristic curve was 0.762, 0.746, and 0.737 for posterior AD, anterior AD, and posterior ADC, respectively. The mean AD, mean diffusivity, and radial diffusivity were lower in the affected nerves in comparison to the contralateral nerve (comparison group C), but the values did not reach statistical significance. CONCLUSION: Decreased AD and mean diffusivity in the posterior segment of the optic nerve may serve as a biomarker of axonal damage in patients with TON and merits further investigation as a predictor of initial visual acuity and potential visual recovery.

Prediction of poor outcome in cerebellar infarction by diffusion MRI.

OBJECTIVE: Identification of patients with posterior fossa infarction at risk for neurological deterioration remains a challenge. MRI-based assessments of MCA infarction can predict poor outcome. Similar quantitative imaging measures after cerebellar stroke have not been studied. We tested the hypothesis that MRI-based volumetric assessment of cerebellar infarcts can provide reliable information for the prediction of poor outcome. DESIGN: We retrospectively identified 44 consecutive subjects (age 55.2 ± 13) with cerebellar stroke who underwent MRI with diffusion-weighted imaging (DWI) (median 63.7 h). Subjects were divided into poor (n = 13) and good outcomes (n = 31). Poor outcome was defined as having at least one of the following criteria: (1) mortality, (2) decompressive craniectomy, (3) ventriculostomy, and (4) decrease level of consciousness. DWI and cerebellar volume were defined on apparent diffusion coefficient maps. The ratio of the lesion volume to the whole cerebellum volume was calculated (rVolume). MEASUREMENTS AND MAIN RESULTS: Logistic regression revealed that lesion volume and rVolume were associated with increased risk of poor outcome, even after adjusting for age and NIHSS (χ(2) = 8.2230, p < 0.0042; χ(2) = 8.3992, p < 0.0038, respectively). The receiver operating characteristic curve with age, NIHSS, and volume or rVolume achieved an AUC of 0.816 (95 % CI 0.678-0.955) and 0.831 (95 % CI 0.6989-0.9636), respectively. CONCLUSIONS: Quantitative volumetric measurement predicts poor outcome of cerebellar stroke patients, even when controlling for age and NIHSS. Quantitative analysis of diffusion MRI may assist in identification of patients with cerebellar stroke at highest risk of neurological deterioration. Prospective validation is warranted.