Huston, John

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.

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.

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.

Introduction: Mortality in patients with unruptured intracranial aneurysm (UIA) is significantly higher than the general population. However a minority of the deaths are due to subarachnoid hemorrhage. Hypothesis: There are differential characteristics of patients that might predict specific causes of death that would be informative in counseling patients about aneurysm risk. Methods: 4059 patients with UIA who were enrolled prospectively between 1991 and 1998 were followed by 61 medical centers in North America, Canada, and Europe. Patients have at least one UIA, which may or may not be symptomatic. Patients were Rankin grade 1 or 2 at enrollment. Patients were followed annually from enrollment to 2007. For patients who died a death certificate search was done and information was requested from local physicians and other contacts. A National Death Index search in 2008 determined cases who died and cause of death. Foreign centers also did a national search where possible. Patients who died before 30 days post treatment or lost to follow up before 30 days post enrollment were excluded. Results: Twenty-five percent of patients died during follow-up. The life expectancy was significantly less than age-, sex-, and country-matched expected estimates. Among the total of 4004 patients with UIA who survived 30 days after enrollment, 2331 were treated and 1673 were not. There were 965 deaths after 30 days after treatment, of which 320 died from vascular disease (252 died from non-SAH vascular disease), 114 died from respiratory tract disease, 255 died from cancer, and the rest died of other or unknown reasons. Predictors of SAH death were aneurysm size, site, age and convulsive disorders at enrollment. Factors related to vascular death were UIA treatment, age, gender, race, hypertension, Rankin at discharge and diminishing influence of aneurysm characteristics over time. Respiratory deaths were related to treatment, race, smoking, age, initial Rankin and presentation with convulsive disorder. Cancer deaths were related to gender, race, smoking and age. Conclusions: In patients with UIA, an assessment of risk for death underscores the importance of age, race and gender and several modifiable risk factors. Patient management should include not only aneurysm rupture prevention but also modification of smoking and hypertension.

Introduction: Quality of life changes can occur following procedural interventions and subarachnoid hemorrhage in unruptured intracranial aneurysms (UIA). The International Study of Unruptured Intracranial Aneurysms conducted quality of life assessment using the Mini-Mental State Exam, Rankin Score, and Barthel Index at baseline and the Telephone Interview Cognitive Status Exam (TICS), Rankin Score, and Barthel Index at follow-up. Hypothesis: The purpose of this analysis was to compare the 1 year and 5 year outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treated and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort and 2388 in the treated cohort. The cohorts were followed annually with measures of neurological status, Rankin Scale, Barthel Index and cognition (TICS). Outcomes were determined prospectively. Comparison of outcomes was done using continuous and categorical data. Covariate adjustment was done using general linear models. Stratified analysis was done by Rankin Score at the time of follow-up. Results: The percent of patients with a Barthel Index score of less than 60 at 1 year in the cohort was 9.4% (treated patients, 9.7%; untreated patients, 9.2%). The percent of patients at year 1 with a score of greater than 90 was 87.6%, 87.4% for treated patients and 87.8% for untreated patients. The percent of patients with a Barthel Index score of less than 60 at 5 years in the cohort was 41.4% (treated patients, 41.4%; untreated patients, 41.4%). The percent of patients at year 5 with a score of greater than 90 was 56.3%, 56.1% for treated patients and 56.5% for untreated patients. TICS and Barthel Index scores were significantly associated with each other for patients with Rankin Scores 0-2 (P<0.0001). This was seen at both year 1 and year 5 follow-up, but not for patients with Rankin Score 3-5. At both 1 year and 5 year follow-up, after controlling for Rankin Score, the distribution of Barthel Index scores of untreated patients and treated patients did not significantly differ. At both the 1 year follow-up, baseline Rankin Score, TICS and follow-up Rankin Score were significant predictors of Barthel Score (P<0.0001). At 5 years, only the follow-up Rankin Score was associated with Barthel Score (P<0.0001). Conclusions: Barthel Index Score decreased over time, but does not differ with treatment. The Rankin Score was the main predictor at follow-up of Barthel Index Score distribution.

BackgroundLocalized regions of left–right image intensity asymmetry (LRIA) were incidentally observed on T2‐weighted (T2‐w) and T1‐weighted (T1‐w) diagnostic magnetic resonance imaging (MRI) images. Suspicion of herpes encephalitis resulted in unnecessary follow‐up imaging. A nonbiological imaging artifact that can lead to diagnostic uncertainty was identified.PurposeTo investigate whether systematic LRIA exist for a range of scanner models and to determine if LRIA can introduce diagnostic uncertainty.Study TypeA retrospective study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) data base.SubjectsOne thousand seven hundred fifty‐three (median age: 72, males/females: 878/875) unique participants with longitudinal data were included.Field Strength3T.SequencesT1‐w three‐dimensional inversion‐recovery spoiled gradient‐echo (IR‐SPGR) or magnetization‐prepared rapid gradient‐echo (MP‐RAGE) and T2‐w fluid‐attenuated inversion recovery (FLAIR) long tau fast spin echo inversion recovery (LT‐FSE‐IR). Only General Electric, Philips, and Siemens' product sequences were used.AssessmentLRIA was calculated as the left–right percent difference with respect to the mean intensity from automated anatomical atlas segmented regions. Three neuroradiologists with 37 (**), 32 (**), and 3 (**) years of experience rated the clinical impact of 30 T2‐w three‐dimensional FLAIR exams with LRIA to determine the diagnostic uncertainty. Statistical comparisons between retrospective intensity normalized T1m and original T1‐w images were made.Statistical TestsFor each image type, a linear mixed effects model was fit using LRIA scores from all scanners, regions, and participants as the outcome and age and sex as predictors. Statistical significance was defined as having a P‐value <0.05.ResultsLRIA scores were significantly different from zero on most scanners. All clinicians were uncertain or recommended definite diagnostic follow‐up in 62.5% of cases with LRIA >10%. Individuals with acute brain pathology or focal neurologic deficits are not enrolled in ADNI; therefore, focal signal abnormalities were considered false positives.Data ConclusionLRIA is system specific, systematic, creates diagnostic uncertainty, and impacts IR‐SPGR, MP‐RAGE, and LT‐FSE‐IR product sequences.Level of Evidence: 2Technical Efficacy Stage: 3

INTRODUCTION: Cognitive changes can occur following procedural interventions and subarachnoid hemorrhage in unruptured intracranial aneurysms (UIA). The International Study of Unruptured Intracranial Aneurysms conducted cognitive assessment using the Mini-Mental State Exam at baseline and the Telephone Interview Cognitive Status Exam (TICS) at follow-up. Hypothesis: The purpose of this analysis was to compare the 1 year and 5 year outcome in the treatment cohorts (surgery and endovascular) with those of the untreated subgroup. Methods: Patients were subdivided into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort and 2388 in the treated cohort. The cohorts were followed annually with measures of neurological status, Rankin Scale and cognition (TICS). Outcomes were determined prospectively. Comparison of outcomes was done using continuous data and by categories. Covariate adjustment was done using general linear models. Stratified analysis was done by Rankin Score at the time of follow-up. Results: The mean TICS score at 1 year in the cohort was 33.4 with a median of 34 (maximum is 40). In the treated patients the mean was 33.5 and in the untreated patients it was 33.3 (P=0.644). However, Rankin Score at 1 year was significant with a higher percentage of 3-5 scores in the treated group (P=0.003) Categorical analysis of the TICS Score when stratified by Rankin Score at 1 year showed small but significant differences, P=0.03 for Rankin 0-2, and P=0.07 for Rankin 3-5. However after adjustment for baseline variables treatment TICS Score was no longer significant.. The 5 year results showed that the untreated patients did worse than the treated group in TICS. However after adjustment no differences were apparent. Conclusions: Cognitive changes associated with treatment may be minor source of disability post-treatment compared to observation and patient outcomes may be worse in the observation group over time. Differences in outcome also were better explained through the Rankin Score at follow-up than by cognitive deficits.

Introduction: There is ongoing debate regarding the rupture risk of an unruptured intracranial aneurysm (UIA), and the predictors of rupture. Hypothesis: There are aneurysm morphology characteristics which predict rupture in patients with an UIA. The purpose of this analysis was to assess for such characteristics utilizing the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort. Methods: Patients were entered prospectively at 61 centers. Patients must have had at least one UIA, which may or may not have been symptomatic. Patients were followed for a median of 9 years and all potential hemorrhages were carefully adjudicated. A case-control design was used. The cases were 57 patients with aneurysmal rupture during followup for whom detailed radiology data were available from arteriography. Controls were 198 size- (+/- 2 mm maximum diameter) and location- (parent artery) matched patients without rupture during followup. Numerous aneurysm morphology characteristics were assessed on arteriogram review. Multivariable condition logistic regression modeling was performed. Results: A total of 57 cases and 198 controls were included. Most (76%) of the 255 cases were women, and 20% had a prior history of SAH from some other aneurysm. There were no differences between cases and controls in aneurysm maximum diameter, aneurysm location, patient age, gender, reason for presentation, or prior medical history. Multivariate analysis identified that only perpendicular height of the aneurysm--the measurement of the aneurysm height at a perpendicular to the center of the aneurysm neck to the aneurysm dome-was an independent predictor of aneurysm rupture. Aspect ratio, size ratio, parent vessel diameter, presence of daughter sac, and aneurysm angle were not independent predictors of rupture. Conclusions: After controlling for aneurysm size and location, the aneurysm perpendicular height remained a predictor of UIA rupture during long-term followup. The assessment of perpendicular height may be helpful in clinical practice, in addition to the other key predictors of UIA rupture, aneurysm maximum diameter and location. Further investigation into the use of perpendicular height as a predictor of rupture in patients with UIA is indicated.