Citations

Increasing concerns have been raised about the long-term negative effects of subconcussive repeated head impact (RHI). To elucidate RHI injury mechanisms, many efforts have studied how head impacts affect the skull-brain biomechanics and have found that mechanical interactions at the skull-brain interface dampen and isolate brain motions by decoupling the brain from the skull. Despite intense interest, in vivo quantification of the functional state of the skull-brain interface remains difficult. This study developed a magnetic resonance elastography (MRE) based technique to non-invasively assess skull-brain mechanical interactions (i.e., motion transmission and isolation function) under dynamic loading. The full MRE displacement data were separated into rigid body motion and wave motion. The rigid body motion was used to calculate the brain-to-skull rotational motion transmission ratio ( R tr ) to quantify skull-brain motion transmissibility, and the wave motion was used to calculate the cortical normalized octahedral shear strain ( NOSS ) (calculated based on a partial derivative computing neural network) to evaluate the isolation capability of the skull-brain interface. Forty-seven healthy volunteers were recruited to investigate the effects of age/sex on R tr and cortical NOSS , and 17 of 47 volunteers received multiple scans to test the repeatability of the proposed techniques under different strain conditions. The results showed that both R tr and NOSS were robust to MRE driver variations and had good repeatability, with intraclass correlation coefficient (ICC) values between 0.68 and 0.97 (fair to excellent). No age or sex dependence were observed with R tr , whereas a significant positive correlation between age and NOSS was found in the cerebrum, frontal, temporal, and parietal lobes (all p < 0.05), but not in the occipital lobe ( p = 0.99). The greatest change in NOSS with age was found in the frontal lobe, one of the most frequent locations of traumatic brain injury (TBI). Except for the temporal lobe ( p = 0.0087), there was no significant difference in NOSS between men and women. This work provides motivation for utilizing MRE as a non-invasive tool for quantifying the biomechanics of the skull-brain interface. It evaluated the age and sex dependence and may lead to a better understanding of the protective role and mechanisms of the skull-brain interface in RHI and TBI, as well as improve the accuracy of computational models in simulating the skull-brain interface.

Background and purpose : Post-shunt MRI is usually performed at 1.5T under the general assumption that shunt-related susceptibility artifacts would be greater at higher field strengths. Purpose The purpose is to show that imaging post-shunt idiopathic normal pressure hydrocephalus (iNPH) patients at 3T is feasible and with reduced artifacts as compared to 1.5T. Methods We manually measured transverse dimensions of artifact at the levels of lateral ventricles, cerebral aqueduct, and cerebellar hemisphere. Areas/volumes of artifacts were calculated assuming an elliptic/ellipsoid shape. Relative extent of shunt-related artifact between field strengths was rated by 3 readers on a 5-point Likert scale. A Wilcoxon Signed Rank Test was used to compare artifact at 1.5T vs 3T for each sequence, with a significance level set at p < 0.05. Results Artifact areas were calculated in 22 iNPH patients; artifacts were on average smaller at 3T vs 1.5T on MPRAGE, DWI, and GRE sequences. On T2 FLAIR and T2 FSE, artifacts at 3T were larger than 1.5T. On the qualitative analysis, artifact effects were less at 3T vs 1.5T on DWI, greater at 3T on T2 FSE, and had mixed results on GRE. Conclusion Our results indicate feasibility of post-shunt imaging with the CERTAS Plus valve at 3T based on shunt-related artifact that is less than or equal in extent to that on 1.5T on most standard clinical imaging sequences. Our findings, corroborated by the qualitative image review, suggest that dedicated clinical imaging sequences for devices may allow for reduction in artifact extent at both 1.5T and 3T.

In blood-oxygen-level-dependent (BOLD)-based resting-state functional (RS-fMRI) studies, usage of multi-echo echo-planar-imaging (ME-EPI) is limited due to unacceptable late echo times when high spatial resolution is used. Equipped with high-performance gradients, the compact 3T MRI system (C3T) enables a three-echo whole-brain ME-EPI protocol with smaller than 2.5 mm isotropic voxel and shorter than 1 s repetition time, as required in landmark fMRI studies. The performance of the ME-EPI was comprehensively evaluated with signal variance reduction and region-of-interest-, seed- and independent-component-analysis-based functional connectivity analyses and compared with a counterpart of single-echo EPI with the shortest TR possible. Through the multi-echo combination, the thermal noise level is reduced. Functional connectivity, as well as signal intensity, are recovered in the medial orbital sulcus and anterior transverse collateral sulcus in ME-EPI. It is demonstrated that ME-EPI provides superior sensitivity and accuracy for detecting functional connectivity and/or brain networks in comparison with single-echo EPI. In conclusion, the high-performance gradient enabled high-spatial-temporal resolution ME-EPI would be the method of choice for RS-fMRI study on the C3T.

Abstract Objective . Interleaved reverse-gradient fMRI (RG-fMRI) with a point-spread-function (PSF) mapping-based distortion correction scheme has the potential to minimize signal loss in echo-planar-imaging (EPI). In this work, the RG-fMRI is further improved by imaging protocol optimization and application of reverse Fourier acquisition. Approach . Multi-band imaging was adapted for RG-fMRI to improve the temporal and spatial resolution. To better understand signal dropouts in forward and reverse EPIs, a simple theoretical relationship between echo shift and geometric distortion was derived and validated by the reliable measurements using PSF mapping method. After examining practical imaging protocols for RG-fMRI in three subjects on both a conventional whole-body and a high-performance compact 3 T, the results were compared and the feasibility to further improve the RG-fMRI scheme were explored. High-resolution breath-holding RG-fMRI was conducted with nine subjects on the compact 3 T and the fMRI reliability improvement in high susceptibility brain regions was demonstrated. Finally, reverse Fourier acquisition was applied to RG-fMRI, and its benefit was assessed by a simulation study based on the breath-holding RG-fMRI data. Main results . The temporal and spatial resolution of the multi-band RG-fMRI became feasible for whole-brain fMRI. Echo shift measurements from PSF mapping well estimated signal dropout effects in the EPI pair and were useful to further improve the RG-fMRI scheme. Breath-holding RG-fMRI demonstrated improved fMRI reliability in high susceptibility brain regions. Reverse partial Fourier acquisition omitting the late echoes could further improve the temporal or spatial resolution for RG-fMRI without noticeable signal degradation and spatial resolution loss. Significance . With the improved imaging scheme, RG-fMRI could reliably investigate the functional mechanisms of the human brain in the temporal and frontal areas suffering from susceptibility-induced functional sensitivity loss.

Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. Results: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (−0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus −1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (−0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). Conclusions: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01178320.

ObjectiveThis study was undertaken to explore the gene expression profile of primary central nervous system vasculitis (PCNSV).MethodsBrain specimens of 4 patients with granulomatous vasculitis (GV), 5 with lymphocytic vasculitis (LV), 4 with amyloid β‐related angiitis (ABRA), and 4 normal controls were studied. RNA‐sequencing was performed using the Illumina Hiseq‐4,000 platform and the Illumina TruSeq Total‐RNA library. Student t test and false discovery rate tests were performed for each of the differentially expressed transcripts. Ingenuity Pathway Analysis was used for the pathway expression analysis. CIBERSORT was used to estimate the abundances of different immune cell subsets in the tissues based on gene expression data.ResultsTranscripts differentially expressed between PCNSV and normal brain indicated that endosomal, mitochondrial, and ribosome dysfunction, alterations in protein synthesis, and noncoding RNAs might be involved in PCNSV. Pathway analysis revealed the activation of dendritic cell maturation and antigen processing as well as neuroinflammation in PCNSV versus normal brain, whereas oxidative phosphorylation was inhibited. CIBERSORT estimation of immune cell subsets suggested that activated NK cells, M1 macrophages, memory B cells, and follicular helper T cells were likely to be more prevalent in PCNSV samples. Naïve CD4 T cells and monocytes were mainly estimated to be present in GV and ABRA. Plasma cell and γδ T‐cell signatures were mainly found in LV and normal brain. GV showed higher levels of genes associated with macrophage activities and T cells. ABRA showed higher levels of long noncoding RNAs and miR‐616. LV showed higher levels of genes encoding immunoglobulins.InterpretationRNA sequencing confirmed PCNSV heterogeneity. ANN NEUROL 2023;93:120–130

Objective This study investigates a locally low-rank (LLR) denoising algorithm applied to source images from a clinical task-based functional MRI (fMRI) exam before post-processing for improving statistical confidence of task-based activation maps. Methods Task-based motor and language fMRI was obtained in eleven healthy volunteers under an IRB approved protocol. LLR denoising was then applied to raw complex-valued image data before fMRI processing. Activation maps generated from conventional non-denoised (control) data were compared with maps derived from LLR-denoised image data. Four board-certified neuroradiologists completed consensus assessment of activation maps; region-specific and aggregate motor and language consensus thresholds were then compared with nonparametric statistical tests. Additional evaluation included retrospective truncation of exam data without and with LLR denoising; a ROI-based analysis tracked t-statistics and temporal SNR (tSNR) as scan durations decreased. A test-retest assessment was performed; retest data were matched with initial test data and compared for one subject. Results fMRI activation maps generated from LLR-denoised data predominantly exhibited statistically significant ( p = 4.88×10 –4 to p = 0.042; one p = 0.062) increases in consensus t-statistic thresholds for motor and language activation maps. Following data truncation, LLR data showed task-specific increases in t-statistics and tSNR respectively exceeding 20 and 50% compared to control. LLR denoising enabled truncation of exam durations while preserving cluster volumes at fixed thresholds. Test-retest showed variable activation with LLR data thresholded higher in matching initial test data. Conclusion LLR denoising affords robust increases in t-statistics on fMRI activation maps compared to routine processing, and offers potential for reduced scan duration while preserving map quality.

BackgroundFocally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid‐space hydrocephalus (DESH), and should be differentiated from atrophy.PurposeTo evaluate for change in FES size and pituitary height after shunt placement in iNPH.Study typeRetrospective.SubjectsA total of 125 iNPH patients who underwent shunt surgery and 40 age‐matched controls.Field Strength/Sequence1.5 T and 3 T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w.AssessmentFES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls.Statistical testsWilcoxon signed‐rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison of cases/controls. Significance level was P < 0.05.ResultsFifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mm3 or 30.0%. Pituitary gland size significantly increased by 0.48 mm or 14.4%. FES decreased significantly by 190 mm3 or 23.1% and pituitary gland size increased significantly by 0.25 mm or 6% between the first and last postshunt MRI.Data ConclusionDecrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less‐well recognized feature of altered CSF dynamics.Evidence Level3Technical EfficacyStage 2