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18
result(s) for
"Mitchell, Lex A."
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Longitudinal alteration of cortical thickness and volume in high-impact sports
2020
Collegiate football athletes are subject to repeated head impacts. The purpose of this study was to determine whether this exposure can lead to changes in brain structure. This prospective cohort study was conducted with up to 4 years of follow-up on 63 football (high-impact) and 34 volleyball (control) male collegiate athletes with a total of 315 MRI scans (after exclusions: football n = 50, volleyball n = 24, total scans = 273) using high-resolution structural imaging. Volumetric and cortical thickness estimates were derived using FreeSurfer 5.3’s longitudinal pipeline. A linear mixed-effects model assessed the effect of group (football vs. volleyball), time from baseline MRI, and the interaction between group and time. We confirmed an expected developmental decrement in cortical thickness and volume in our cohort (p < .001). Superimposed on this, total cortical gray matter volume (p = .03) and cortical thickness within the left hemisphere (p = .04) showed a group by time interaction, indicating less age-related volume reduction and thinning in football compared to volleyball athletes. At the regional level, sport by time interactions on thickness and volume were identified in the left orbitofrontal (p = .001), superior temporal (p = .001), and postcentral regions (p < .001). Additional cortical thickness interactions were found in the left temporal pole (p = .003) and cuneus (p = .005). At the regional level, we also found main effects of sport in football athletes characterized by reduced volume in the right hippocampus (p = .003), right superior parietal cortical gray (p < .001) and white matter (p < .001), and increased volume of the left pallidum (p = .002). Within football, cortical thickness was higher with greater years of prior play (left hemisphere p = .013, right hemisphere p = .005), and any history of concussion was associated with less cortical thinning (left hemisphere p = .010, right hemisphere p = .011). Additionally, both position-associated concussion risk (p = .002) and SCAT scores (p = .023) were associated with less of the expected volume decrement of deep gray structures. This prospective longitudinal study comparing football and volleyball athletes shows divergent age-related trajectories of cortical thinning, possibly reflecting an impact-related alteration of normal cortical development. This warrants future research into the underlying mechanisms of impacts to the head on cortical maturation.
•This longitudinal study compares changes in brain structure between athletes playing high impact and low impact sports (collegiate tackle football vs. volleyball).•Football athletes show a decreased rate of age-related cortical thinning compared to volleyball athletes.•Changes in brain structure were related to the years of prior football exposure, concussion history, concussion risk, and cognitive performance.
Journal Article
Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section
by
Mitchell, Lex A
,
Singh, Inder Paul
,
Do, Huy M
in
Catheters
,
Cesarean Section - adverse effects
,
Childbirth & labor
2014
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.
Journal Article
Longitudinal Changes in Hippocampal Subfield Volume Associated with Collegiate Football
by
Grant, Gerald
,
Wolman, Dylan
,
Parivash, Sherveen N.
in
Alzheimer's disease
,
Athletes
,
Brain Concussion - diagnostic imaging
2019
Collegiate football athletes are subject to repeated traumatic brain injuriesthat may cause brain injury. The hippocampus is composed of several distinct subfields with possible differential susceptibility to injury. The aim of this study is to determine whether there are longitudinal changes in hippocampal subfield volume in collegiate football. A prospective cohort study was conducted over a 5-year period tracking 63 football and 34 volleyball male collegiate athletes. Athletes underwent high-resolution structural magnetic resonance imaging, and automated segmentation provided hippocampal subfield volumes. At baseline, football (n = 59) athletes demonstrated a smaller subiculum volume than volleyball (n = 32) athletes (−67.77 mm3; p = 0.012). A regression analysis performed within football athletes similarly demonstrated a smaller subiculum volume among those at increased concussion risk based on athlete position (p = 0.001). For the longitudinal analysis, a linear mixed-effects model assessed the interaction between sport and time, revealing a significant decrease in cornu ammonis area 1 (CA1) volume in football (n = 36) athletes without an in-study concussion compared to volleyball (n = 23) athletes (volume difference per year = −35.22 mm3; p = 0.005). This decrease in CA1 volume over time was significant when football athletes were examined in isolation from volleyball athletes (p = 0.011). Thus, this prospective, longitudinal study showed a decrease in CA1 volume over time in football athletes, in addition to baseline differences that were identified in the downstream subiculum. Hippocampal changes may be important to study in high-contact sports.
Journal Article
123 Quantitative Volumetric Magnetic Resonance Perfusion Identifies a Distinct Vasculogenic Molecular Subtype of Human Glioblastoma Associated With Worse Clinical Outcomes
by
Mitchell, Lex A.
,
Liu, Tiffany
,
Achrol, Achal Singh
in
Blood
,
Brain cancer
,
Clinical outcomes
2015
Abstract
INTRODUCTION:
Glioblastoma is the most common and aggressive primary human brain cancer. Noninvasive characterization of intratumor blood flow parameters may help guide clinical decision making. Beyond risk stratification and prognostication, tumor perfusion may inform treatment selection and serial monitoring of newer antiangiogenic targeted therapies. In this study, intra- and intertumor variations in blood volume were quantified by using a novel 3-D volumetric, dynamic-susceptibility contrast-enhanced (DSCE), T2*-weighted perfusion magnetic resonance (MR) analysis to determine associations with molecular features and clinical outcomes.
METHODS:
A total of n = 150 patients underwent preoperative DSCE T2* MR perfusion analysis, including an internal test cohort and external validation cohort. Volumetric quantitative voxel-based data on relative cerebral blood volume (rCBV) were assessed, including mean, median, kurtosis, skewness, and percentage of elevated rCBV (ie, elevated rCBV). Intra- and intertumor heterogeneity in each parameter was characterized by mosaic analysis. Hierarchical clustering was performed to identify subsets of patients with correlated perfusion patterns. Resulting perfusion-based clusters were assessed against molecular features by using integrated PARADIGM genomic pathway-level elastic net logistic regression analyses. Perfusion-based clusters were assessed in univariate Kaplan-Meier (log-rank) and multivariate Cox proportional hazards models for association with overall clinical survival outcomes. Validated MR perfusion parameters discovered in the test cohort were externally validated in the independent validation cohort.
RESULTS:
Intra- and intertumor heterogeneity was observed in mosaic analyses of quantitative voxel-based MR perfusion data of mean, median, kurtosis, skewness, and elevated rCBV. Hierarchical clustering and random forest analyses identified an elevated rCBV cluster of patients with correlated MR perfusion patterns that demonstrated distinct molecular features of vasculogenesis, gap junction assembly, and endothelial permeability in integrated PARADIGM genomic pathway-level analysis. This elevated rCBV subgroup of patients demonstrated worse overall survival in univariate and multivariate survival analyses (HR 2.9, P = .02), and these findings externally validated in an independent cohort.
CONCLUSION:
A distinct vasculogenic subtype of glioblastoma identified by quantitative MR perfusion voxel-based analysis was associated with unique molecular features and worse overall survival. Quantitative volumetric MR perfusion holds potential in characterizing intra- and intertumoral heterogeneity, and identifying biologically distinct, clinically relevant subsets of patients for risk stratification and treatment selection.
Journal Article
Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section
2013
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.
Journal Article
Microstructural alterations in tract development in college football: a longitudinal diffusion MRI study
by
Zeineh, Michael
,
Rosenberg, Jarrett
,
Georgiadis, Marios
in
Anisotropy
,
Chronic effects
,
Cingulum
2022
Background and Objectives: Repeated concussive and sub-concussive impacts in high-contact sports can affect microstructure of the brain, which can be studied using diffusion MRI. Most prior imaging studies, however, employ a cross-sectional design, do not include low-contact players as controls, or use traditional diffusion tensor imaging without investigating novel tract-specific microstructural metrics. Methods: We examined brain microstructure in 63 high-contact (American football) and 34 low-contact (volleyball) collegiate athletes with up to 4 years of follow-up (315 total scans) using advanced diffusion MRI, a comprehensive set of multi-compartment models, and automated fiber quantification tools. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of sub-concussive and concussive impacts, as well as associations between diffusion changes with clinical, behavioral, and sports-related measures. Results: Significant longitudinal increases in fractional anisotropy and axonal water fraction were detected in volleyball players, but not in football players, along with decreases in radial and mean diffusivity as well as orientation dispersion index (all findings absolute T-statistic > 3.5, p < .0001). This pattern was present in the callosum forceps minor, left superior longitudinal fasciculus, left thalamic radiation, and right cingulum hippocampus. Longitudinal group differences were more prominent and observed in a larger number of tracts in concussed (previously or in-study) football players (p < .0001), while smaller effects were noted in un-concussed players. An analysis of immediate-post concussion scans in football players demonstrated a transient localized increase in axial diffusivity, mean and radial kurtosis in the left uncinate and right cingulum hippocampus (p < .0001). Finally, football players with high position-based sub-concussive risk demonstrated increased orientation dispersion index over time (p < .0001). Discussion: The observed longitudinal changes in our volleyball cohort likely reflect normal development in this age range, while the relative attenuation of these effects seen in football, and especially concussed athletes, could possibly reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, non-decreasing axonal dispersion. This prospective longitudinal study demonstrates significantly divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and/or repeated sub-concussive impact-related alteration of normal white matter development in football athletes. Competing Interest Statement The authors have declared no competing interest.
Linoleic acid metabolites act to increase contractility in isolated rat heart
by
Grant, David F.
,
Melchert, Russell B.
,
Mitchell, Lex A.
in
Animals
,
Blood Pressure - drug effects
,
Blood Pressure - physiology
2002
Previous in vivo studies in dogs suggest that the 9,10-monoepoxide of linoleic acid (9,10-cis-epoxyoctadecenoic acid [9,10-EOA]) has toxic cardiovascular effects that result in death at higher doses. More recent work with rabbit renal proximal tubule cells suggests that the 12,13-metabolites of linoleic acid are more toxic than the 9,10-isomers. Thus, in the current study, we tested the hypothesis that 12,13-EOA and 12,13-dihydroxyoctadecadienoic acid (12,13-DHOA) have direct adverse effects on the heart. Langendorff-perfused rat hearts were exposed to 30 microM linoleic acid, 30 microM 12,13-EOA, or 30 microM 12,13-DHOA for 60 min followed by a 30-min recovery period. As indicated by peak left intraventricular pressure and/or +dP/dt(max), all three of the agents elicited moderate increases in contractile function that peaked within 10 20 min. The effects of linoleic acid and 12,13-EOA returned to control values during the remainder of the 60-min exposure, whereas the positive inotropic response to 12,13-DHOA was maintained until washout. Sustained arrhythmias and negative inotropic actions were not observed with any of the three compounds. Subsequently, the monoepoxides were infused into conscious rats (35 mg/kg/h) while blood pressure, heart rate, and EKG were monitored for 24 h using biotelemetry techniques. The only effect observed was a slight decline in blood pressure. Thus, current data suggest that linoleic acid and its oxidative metabolites do not have direct cardiotoxic effects during acute exposure.
Journal Article
Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section
2013
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.
Report
Fracture Hunting in Ruby-Throated Hummingbirds (Archilochus colubris): A Comparative Study of General Radiography, Dental Radiography, Micro-CT, and 3D Reconstructed Imaging
2026
Diagnosing fractures in hummingbirds is challenging because of their small size. This study evaluated the diagnostic performance and inter-reviewer agreement of four imaging modalities—conventional radiography, dental radiography, micro-computed tomography (micro-CT), and three-dimensional (3D)-reconstructed images from micro-CT scans—for identifying fractures in 16 ruby-throated hummingbirds (Archilochus colubris) admitted to a wildlife hospital. Six independent reviewers, with or in training for a specialty in veterinary radiology or wildlife medicine, assessed randomized image sets. Gross dissection of the carcasses using dermestid beetle larvae established the gold standard. Diagnostic performance metrics—sensitivity, specificity, predictive values, and likelihood ratios—were calculated for each modality. Inter-reviewer agreement was assessed using Fleiss’ kappa. Our results demonstrated that advanced imaging techniques improved diagnostic performance and inter-reviewer agreement compared to traditional radiography. While specificity (>88%) was comparable to other small animal studies, the sensitivity did not exceed 50% across all modalities. This low sensitivity reflects the challenges posed by minimal fracture displacement and hummingbirds’ extremely small size. Only 3D images achieved high positive likelihood ratios and superior inter-reviewer agreement, highlighting the unique value of 3D visualization in complex anatomical evaluations. Overall, the minute structures of hummingbirds present inherent diagnostic limitations, underscoring that negative radiographic results must be interpreted cautiously, and the possibility of false negatives should prompt consideration of advanced or follow-up imaging when clinical suspicion persists.
Journal Article
Characterizing the Roles of Life Stage and Season on the Prevalence of Select Viral Pathogens in Acheta domesticus Crickets on a Commercial Cricket Farm in the United States
by
Lex, Zoey N.
,
Bitter, Amy
,
Tuminello, John
in
Acheta domesticus
,
Acheta domesticus densovirus
,
Acheta domesticus volvovirus
2025
Commercial cricket production has been plagued by viral disease outbreaks that have decimated their potential outputs and profit margins. To date, no epidemiological studies have been performed to estimate the prevalence of major viruses affecting crickets raised in commercial settings. A cross-sectional study was performed to estimate the prevalence of three important viruses (Acheta domesticus densovirus [AdDV], Acheta domesticus volvovirus [AdVVV], and invertebrate iridovirus 6 [CrIV]). Samples were collected across age groups (2-, 4-, and 6-week-olds) and seasons (January, May, August, and October) to determine the effect that these variables had on the prevalence rates. Quantitative real-time PCR was performed and revealed the following high overall prevalence rates: 46.7, 100, and 100% for AdDV, AdVVV, and CrIV, respectively. Viral loads varied from 101–5 for AdDV, 102–7 for AdVVV, and 102–9 for CrIV. AdDV prevalence rates were statistically significant across age and season (age: χ2 = 8.3, p = 0.015; season: χ2 = 59.7, p < 0.001), with crickets more likely to be infected as they aged and during the colder winter months. CrIV followed similar trends when looking at changes in viral loads between ages and seasons. AdVVV experienced a spike in viral loads across all ages during the month of August. Understanding the epidemiology of these viruses is instrumental in determining best management practices for commercially raised crickets.
Journal Article