Background: Coronavirus disease 2019 (COVID-19) induces myocardial injury, either direct myocarditis or indirect injury due to systemic in ammatory response. Myocardial involvement has been proved to be one of the primary manifestations of COVID-19 infection, according to laboratory test, autopsy, and cardiac magnetic resonance imaging (CMRI). However, the middle-term outcome of cardiac involvement after the patients were discharged from the hospital is yet unknown. The present study aimed to evaluate mid-term cardiac sequelae in recovered COVID-19 patients by CMRI Methods: A total of 47 recovered COVID-19 patients were prospectively recruited and underwent CMRI examination in this study. The CMRI protocol consisted of black blood fat-suppressed T2 weighted imaging (BB-T2WI), T2 star mapping, left ventricle cine imaging, pre-and post-contrast T1 mapping, and late gadolinium enhancement (LGE). Myocardium edema and LGE were assessed in recovered COVID-19 patients. The left ventricle (LV) and right ventricle (RV) function and LV mass were assessed and compared with normal controls. Results: Finally, 44 recovered COVID-19 patients and 31 normal controls were included in this study. No edema was observed in any patient. LGE was found in 13 patients. All LGE lesions were located in the middle myocardium and/or sub-epicardium with a scattered distribution. Further analysis showed that LGE-positive patients had signi cantly decreased left ventricle peak global circumferential strain (LVpGCS), right ventricle peak global circumferential strain (RVpGCS), right ventricle peak global longitudinal strain (RVpGLS) as compared to non-LGE patients (p 0.05), while no difference was detected between the non-LGE patients and normal controls. Conclusion: Myocardium injury existed in about 30% of COVID-19 patients. These patients had peak right ventricle strain that decreased at the 3-month follow-up. Cardiac MRI can monitor the COVID-19-induced myocarditis progression, and CMR strain analysis is a sensitive tool to evaluate the recovery of left ventricle circumferential contraction dysfunction and right ventricular dysfunction.

Systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. Previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. We compared the efficiency of multiple adeno-associated virus (AAV) vectors after a single injection via intraperitoneal or intravenous routes without additional intervention. We show that AAV8 is the most efficient vector for crossing the blood vessel barrier to attain systemic gene transfer in both skeletal and cardiac muscles of mice and hamsters. Serotypes such as AAV1 and AAV6, which demonstrate robust infection in skeletal muscle cells, were less effective in crossing the blood vessel barrier. Gene expression persisted in muscle and heart, but diminished in tissues undergoing rapid cell division, such as neonatal liver. This technology should prove useful for muscle-directed systemic gene therapy.

The goal of the current investigation was to detect clinically important axonal damage in cerebral white matter after mild traumatic brain injury (TBI) using diffusion tensor imaging (DTI). To this end, we evaluated a prospective, pilot study of six subjects with isolated mild TBI and six matched orthopedic controls. All subjects underwent DTI scanning, post-concussive symptom (PCS) assessment, and neurobehavioral testing within 72 h of injury. Fractional anisotropy (FA) and trace values in white matter voxels of whole brain and five preselected regions of interest (ROI) were compared in mild TBI and control subjects using a quantile approach. In addition, whole brain images were analyzed using voxel-based morphometry. All subjects underwent quality of life and repeat PCS assessment at 1 month. Whole brain images revealed significantly lower 1(st) percentile trace values (mean 0.465 vs. 0.488, p = 0.049) among mild TBI subjects. These trace values correlated with PCS scores at both 72 h (r = -0.57, p = 0.05) and 1 month (r = -0.61, p = 0.04). Analysis of ROIs showed mild TBI subjects to have significantly lower mean trace in the left anterior internal capsule (0.536 vs. 0.574, p = 0.007) and higher maximum ROI-specific median FA values (mean 0.801 vs. 0.756, p = 0.035) in the posterior corpus callosum. These FA values correlated with 72-h PCS score (r = -0.63, p = 0.03), and two neurobehavioral tests (visual motor speed [r = 0.63, p = 0.03] and impulse control [r = 0.59, p = 0.04]). Collectively, DTI detected significantly lower trace and elevated FA values in mild TBI subjects compared to controls. These abnormalities correlated to poor clinical outcome. We believe these findings represent axonal swelling, an early step in the process of axonal injury.

IntroductionRepetitive head impacts (RHI) sustained in contact sports are thought to be necessary for the long-term development of chronic traumatic encephalopathy (CTE). Our objectives were to: 1) characterize the magnitude and persistence of RHI-induced white matter (WM) changes; 2) determine their relationship to kinematic measures of RHI; and 3) explore their clinical relevance.MethodsProspective, observational study of 10 Division III college football players and 5 non-athlete controls during the 2011-12 season. All subjects underwent diffusion tensor imaging (DTI), physiologic, cognitive, and balance testing at pre-season (Time 1), post-season (Time 2), and after 6-months of no-contact rest (Time 3). Head impact measures were recorded using helmet-mounted accelerometers. The percentage of whole-brain WM voxels with significant changes in fractional anisotropy (FA) and mean diffusivity (MD) from Time 1 to 2, and Time 1 to 3 was determined for each subject and correlated to head impacts and clinical measures.ResultsTotal head impacts for the season ranged from 431–1,850. No athlete suffered a clinically evident concussion. Compared to controls, athletes experienced greater changes in FA and MD from Time 1 to 2 as well as Time 1 to 3; most differences at Time 2 persisted to Time 3. Among athletes, the percentage of voxels with decreased FA from Time 1 to 2 was positively correlated with several helmet impact measures. The persistence of WM changes from Time 1 to 3 was also associated with changes in serum ApoA1 and S100B autoantibodies. WM changes were not consistently associated with cognition or balance.ConclusionsA single football season of RHIs without clinically-evident concussion resulted in WM changes that correlated with multiple helmet impact measures and persisted following 6 months of no-contact rest. This lack of WM recovery could potentially contribute to cumulative WM changes with subsequent RHI exposures.

The acknowledgement of risks for traumatic brain injury in American football players has prompted studies for sideline concussion diagnosis and testing for neurological deficits. While concussions are recognized etiological factors for a spectrum of neurological sequelae, the consequences of sub-concussive events are unclear. We tested the hypothesis that blood-brain barrier disruption (BBBD) and the accompanying surge of the astrocytic protein S100B in blood may cause an immune response associated with production of auto-antibodies. We also wished to determine whether these events result in disrupted white matter on diffusion tensor imaging (DT) scans. Players from three college football teams were enrolled (total of 67 volunteers). None of the players experienced a concussion. Blood samples were collected before and after games (n = 57); the number of head hits in all players was monitored by movie review and post-game interviews. S100B serum levels and auto-antibodies against S100B were measured and correlated by direct and reverse immunoassays (n = 15 players; 5 games). A subset of players underwent DTI scans pre- and post-season and after a 6-month interval (n = 10). Cognitive and functional assessments were also performed. After a game, transient BBB damage measured by serum S100B was detected only in players experiencing the greatest number of sub-concussive head hits. Elevated levels of auto-antibodies against S100B were elevated only after repeated sub-concussive events characterized by BBBD. Serum levels of S100B auto-antibodies also predicted persistence of MRI-DTI abnormalities which in turn correlated with cognitive changes. Even in the absence of concussion, football players may experience repeated BBBD and serum surges of the potential auto-antigen S100B. The correlation of serum S100B, auto-antibodies and DTI changes support a link between repeated BBBD and future risk for cognitive changes.

Background and Purpose Current approaches to diffusion tensor imaging (DTI) analysis do not permit identification of individual-level changes in DTI indices. We investigated the ability of wild bootstrapping analysis to detect subject-specific changes in brain white matter (WM) before and after sports-related concussion. Materials and Methods A prospective cohort study was performed in 9 high school athletes engaged in hockey or football, and 6 controls. Subjects underwent DTI pre- and post-season within a 3-month interval. One athlete was diagnosed with concussion (scanned within 72 hours) and 8 suffered between 26 and 399 sub-concussive head blows. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in each white matter voxel. Bootstrap samples were generated and a permuted t test used to compare voxel-wise FA/MD changes in each subject pre- vs. post-season. Results The percentage of WM voxels with significant (p<0.05) pre-post FA changes was highest for the concussion subject (3.2%), intermediary for those with sub-concussive head blows (mean 1.05±.15%) and lowest for controls (mean 0.28±.01%). Similarly, the percentage of WM voxels with significant MD changes was highest for the concussion subject (3.44%), intermediary for those with sub-concussive head blows (mean 1.48±.17%) and lowest for controls (mean 0.48±.05%). Significantly changed FA and MD voxels co-localized in the concussion subject to the right corona radiata and right inferior longitudinal fasciculus. Conclusions Wild bootstrap analysis detected significantly changed WM in a single concussed athlete. Athletes with multiple sub-concussive head blows had significant changes in a percentage of their WM that was over 3 times higher than controls. Efforts to understand the significance of these WM changes, and their relationship to head impact forces appear warranted.

Importance Severe early life neglect is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in white matter pathways that underlie emotional and cognitive development are unknown. Objective To examine associations between early life neglect, early intervention, and microstructural integrity of white matter pathways in middle childhood. Design, setting, and participants The Bucharest Early Intervention Project is a randomized clinical trial of high quality foster care as an intervention for institutionally reared children in Bucharest, Romania. During infancy, children were randomly selected to remain in an institution or to be placed into foster care. Developmental trajectories of these children were compared to a group of socio-demographically matched children reared in biological families at baseline and several points throughout development. At around eight years of age, 69 of the original 136 children underwent structural MRI scans. Intervention(s) for Clinical Trials Institutionally reared children were randomized into high quality foster homes in Bucharest, Romania. Main Outcome Measure(s) Four estimates of white matter integrity (Fractional Anisotropy, and Mean, Radial, and Axial Diffusivity) for 48 white matter tracts throughout the brain were obtained through Diffusion Tensor Imaging. Results Significant associations emerged between early life neglect and microstructural integrity of the body of the corpus callosum and tracts involved in limbic circuitry (fornix crus, cingulum), fronto-striatal circuitry (anterior and superior corona radiata, external capsule) and sensory processing (medial lemniscus, retrolenticular internal capsule). Follow up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care. Conclusions and Relevance Results suggest that removal from conditions of severe early life neglect and entry into a high quality family environment can support more normative trajectories of white matter growth. Findings have implications for public health and policy efforts designed to promote normative brain development among vulnerable children. Trial Registration clinicaltrials.gov Identifier: NCT00747396

BACKGROUND AND PURPOSE: Differentiation of enhancing malignant lesions on conventional MR imaging can be difficult and various newer imaging techniques have been suggested. Our aim was to evaluate the role of PSR obtained from DSC perfusion measurements in differentiating lymphoma, GBM, and metastases. The effectiveness of PSR was compared with that of rCBV. We hypothesized that the newly defined parameter of PSR is more sensitive and specific in differentiating these lesions.