Automated quantitative assessment of bone contusions and overlying articular cartilage following anterior cruciate ligament injury.

Quantitative methods to characterize bone contusions and associated cartilage injury remain limited. We combined standardized voxelwise normalization and 3D mapping to automate bone contusion segmentation post-anterior cruciate ligament (ACL) injury and evaluate anomalies in articular cartilage overlying bone contusions. Forty-five patients (54% female, 26.4 ± 11.8 days post-injury) with an ACL tear underwent 3T magnetic resonance imaging of their involved and uninvolved knees. A novel method for voxelwise normalization and 3D anatomical mapping was used to automate segmentation, labeling, and localization of bone contusions in the involved knee. The same mapping system was used to identify the associated articular cartilage overlying bone lesions. Mean regional T1ρ was extracted from articular cartilage regions in both the involved and uninvolved knees for quantitative paired analysis against ipsilateral cartilage within the same compartment outside of the localized bone contusion. At least one bone contusion lesion was detected in the involved knee within the femur and/or tibia following ACL injury in 42 participants. Elevated T1ρ (p = 0.033) signal were documented within the articular cartilage overlying the bone contusions resulting from ACL injury. In contrast, the same cartilaginous regions deprojected onto the uninvolved knees showed no ipsilateral differences (p = 0.795). Automated bone contusion segmentation using standardized voxelwise normalization and 3D mapping deprojection identified altered cartilage overlying bone contusions in the setting of knee ACL injury.

There is high variability in quantitative measurement techniques in glenohumeral capsular measurements for shoulder instability: A systematic review.

PURPOSE: Instability of the glenohumeral joint remains a complex clinical issue with high rates of surgical failure and significant morbidity. Advances in specific radiologic measurements involving the glenoid and the humerus have provided insight into glenohumeral pathology, which can be corrected surgically towards improving patient outcomes. The contributions of capsular pathology to ongoing instability remain unclear. The purpose of this study is to provide a systematic review of existing glenohumeral capsular measurement techniques published in the last 15 years. METHODS: A systematic review of multiple databases was performed following PRISMA guidelines for all primary research articles between 2008 and 2023 with quantitative measurements of the glenohumeral capsule in patients with instability, including anterior, posterior and multi-directional instability. RESULTS: There were a total of 14 articles meeting the inclusion criteria. High variability in measurement methodology across studies was observed, including variable amounts of intra-articular contrast, heterogeneity among magnetic resonance sequence acquisitions, differences in measurements performed and the specific approach taken to compute each measurement. CONCLUSION: There is a need for standardization of methods in the measurement of glenohumeral capsular pathology in the setting of glenohumeral instability to allow for cross-study analysis. LEVEL OF EVIDENCE: Level III.

Brain atrophy, reduced cerebral perfusion, arterial stiffening, and wall thickening with aging coincide with stimulus-specific changes in fMRI-BOLD responses.

The aim of this study was to investigate how aging affects blood flow and structure of the brain. It was hypothesized older individuals would have lower gray matter volume (GMV), resting cerebral blood flow (CBF0), and depressed responses to isometabolic and neurometabolic stimuli. In addition, increased carotid-femoral pulse-wave velocity (PWV), carotid intima-media thickness (IMT), and decreased brachial flow-mediated dilation (FMD) would be associated with lower CBF0, cerebrovascular reactivity (CVR), and GMV. Brain scans (magnetic resonance imaging) and cardiovascular examinations were conducted in young (age = 24 ± 3 yr, range = 22-28 yr; n = 13) and old (age = 71 ± 4 yr; range = 67-82 yr, n = 14) participants, and CBF0, CVR [isometabolic % blood oxygen level-dependent (BOLD) in response to a breath hold (BH)], brain activation patterns during a working memory task (neurometabolic %BOLD response to N-back trial), GMV, PWV, IMT, and FMD were measured. CBF0 and to a lesser extent CVRBH were lower in the old group (P ≤ 0.050); however, the increase in the %BOLD response to the memory task was not blunted (P ≥ 0.2867). Age-related differential activation patterns during the working memory task were characterized by disinhibition of the default mode network in the old group (P < 0.0001). Linear regression analyses revealed PWV, and IMT were negatively correlated with CBF0, CVRBH, and GMV across age groups, but within the old group alone only the relationships between PWV-CVRBH and IMT-GMV remained significant (P ≤ 0.0183). These findings suggest the impacts of age on cerebral %BOLD responses are stimulus specific, brain aging involves alterations in cerebrovascular and possibly neurocognitive control, and arterial stiffening and wall thickening may serve a role in cerebrovascular aging.NEW & NOTEWORTHY Cerebral perfusion was lower in old versus young adults. %Blood oxygen level-dependent (BOLD) responses to an isometabolic stimulus and gray matter volume were decreased in old versus young adults and associated with arterial stiffening and wall thickening. The increased %BOLD response to a neurometabolic stimulus appeared unaffected by age; however, the old group displayed disinhibition of the default mode network during the stimulus. Thus, age-related alterations in cerebral %BOLD responses were stimulus specific and related to arterial remodeling.

Blood-Brain Barrier Dysfunction and Exposure to Head Impacts in University Football Players.

OBJECTIVE: To investigate the link between dysfunction of the blood-brain barrier (BBB) and exposure to head impacts in concussed football athletes. DESIGN: This was a prospective, observational pilot study. SETTING: Canadian university football. PARTICIPANTS: The study population consisted of 60 university football players, aged 18 to 25. Athletes who sustained a clinically diagnosed concussion over the course of a single football season were invited to undergo an assessment of BBB leakage. INDEPENDENT VARIABLES: Head impacts detected using impact-sensing helmets were the measured variables. MAIN OUTCOME MEASURES: Clinical diagnosis of concussion and BBB leakage assessed using dynamic contrast-enhanced MRI (DCE-MRI) within 1 week of concussion were the outcome measures. RESULTS: Eight athletes were diagnosed with a concussion throughout the season. These athletes sustained a significantly higher number of head impacts than nonconcussed athletes. Athletes playing in the defensive back position were significantly more likely to sustain a concussion than remain concussion free. Five of the concussed athletes underwent an assessment of BBB leakage. Logistic regression analysis indicated that region-specific BBB leakage in these 5 athletes was best predicted by impacts sustained in all games and practices leading up to the concussion-as opposed to the last preconcussion impact or the impacts sustained during the game when concussion occurred. CONCLUSIONS: These preliminary findings raise the potential for the hypothesis that repeated exposure to head impacts may contribute to the development of BBB pathology. Further research is needed to validate this hypothesis and to test whether BBB pathology plays a role in the sequela of repeated head trauma.

Suture Augmentation of a Four-Strand Semitendinosus Graft Improves Time-Zero Biomechanical Properties.

PURPOSE: To compare the time-zero biomechanical properties of hamstring graft preparations with or without suture augmentation for anterior cruciate ligament reconstruction (ACLR) in a full-construct cadaveric model. METHODS: Hamstring grafts were harvested from 24 fresh frozen human cadavers and prepared in 1 of 3 ways: quadrupled SemiTendinosus (SemiT), and quadrupled SemiT with suture augmentation (SemiT+2.0-mm tape or SemiT+1.3-mm tape; n = 8 per group). Adjustable loop suspensory implants and cortical buttons were used for fixation on a porcine tibia and acrylic block. Testing included force-controlled cyclic loading at 250 N and 400 N followed by load to failure. RESULTS: The 2 suture augmentation groups had less total elongation and increased stiffness compared to the nonsuture-augmented group (P = .025). The SemiT+2.0-mm tape group had 36% less total elongation and 34% increased stiffness compared to SemiT+1.3mm tape (P < .001). CONCLUSIONS: Suture augmentation improves construct biomechanics at time zero following hamstring tendon ACLR. Augmentation with 2.0-mm tape suture improves construct biomechanics compared to 1.3-mm tape suture. CLINICAL RELEVANCE: Independent suture augmentation of a quadrupled SemiT graft improves ACLR construct biomechanics. Outcomes were improved with augmentation using 2.0-mm tape suture compared to 1.3-mm tape suture.

Spontaneous Behavioural Recovery Following Stroke Relates to the Integrity of Parietal and Temporal Regions.

Stroke is a devastating disease that results in neurological deficits and represents a leading cause of death and disability worldwide. Following a stroke, there is a degree of spontaneous recovery of function, the neural basis of which is of great interest among clinicians in their efforts to reduce disability following stroke and enhance rehabilitation. Conventionally, work on spontaneous recovery has tended to focus on the neural reorganization of motor cortical regions, with comparably little attention being paid to changes in non-motor regions and how these relate to recovery. Here we show, using structural neuroimaging in a macaque stroke model (N = 31) and by exploiting individual differences in spontaneous behavioural recovery, that the preservation of regions in the parietal and temporal cortices predict animal recovery. To characterize recovery, we performed a clustering analysis using Non-Human Primate Stroke Scale (NHPSS) scores and identified a good versus poor recovery group. By comparing the preservation of brain volumes in the two groups, we found that brain areas in integrity of brain areas in parietal, temporal and somatosensory cortex were associated with better recovery. In addition, a decoding approach performed across all subjects revealed that the preservation of specific brain regions in the parietal, somatosensory and medial frontal cortex predicted recovery. Together, these findings highlight the importance of parietal and temporal regions in spontaneous behavioural recovery.

The physiological basis underlying functional connectivity differences in older adults: A multi-modal analysis of resting-state fMRI.

The purpose of this study was to determine if differences in functional connectivity strength (FCS) with age were confounded by vascular parameters including resting cerebral blood flow (CBF0), cerebrovascular reactivity (CVR), and BOLD-CBF coupling. Neuroimaging data were collected from 13 younger adults (24 ± 2 years) and 14 older adults (71 ± 4 years). A dual-echo resting state pseudo-continuous arterial spin labeling sequence was performed, as well as a BOLD breath-hold protocol. A group independent component analysis was used to identify networks, which were amalgamated into a region of interest (ROI). Within the ROI, FC strength (FCS) was computed for all voxels and compared across the groups. CBF0, CVR and BOLD-CBF coupling were examined within voxels where FCS was different between young and older adults. FCS was greater in old compared to young (P = 0.001). When the effect of CBF0, CVR and BOLD-CBF coupling on FCS was examined, BOLD-CBF coupling had a significant effect (P = 0.003) and group differences in FCS were not present once all vascular parameters were considered in the statistical model (P = 0.07). These findings indicate that future studies of FCS should consider vascular physiological markers in order to improve our understanding of aging processes on brain connectivity.

Quantitative Susceptibility Mapping for Staging Acute Cerebral Hemorrhages: Comparing the Conventional and Multiecho Complex Total Field Inversion magnetic resonance imaging MR Methods.

BACKGROUND: The perceived acuity of intracerebral hemorrhage (ICH) impacts the management of patients, both within emergent and outpatient/urgent settings. Morphology enabled dipole inversion (MEDI) quantitative susceptibility imaging (QSM) has improved characterization of ICH acuity, despite outstanding limitations in distinguishing blood products. PURPOSE/HYPOTHESIS: Using improved susceptibility quantification, novel postprocessing QSM method from multiecho complex total field inversion (mcTFI) may better discriminate between acute and subacute ICH, compared to MEDI. STUDY TYPE: Retrospective cohort study. SUBJECTS: A total of 121 subjects enrolled following positive computerized tomography (CT) findings for ICH. Subjects were grouped based on time between admission and MR imaging: hyperacute (<24 hours), acute (1-3 days), early subacute (3-7 days), and late subacute (7-18 days). FIELD STRENGTH/SEQUENCE: A multiecho gradient echo sequence at 3.0 T was paired with clinical noncontrast CT imaging. ASSESSMENT: A quantitative index (CTindex ) was derived based on relative intensities of blood on noncontrast CT. All images were co-registered, from which QSM parameters within the ICH area were assessed across groups, as well as the correlation with CTindex . STATISTICAL TESTS: Group differences were assessed using ANOVAs. Linear regressions between the CTindex , MEDI, and mcTFI measurements were used to assess their relationships. Statistical significance was set at P < 0.05. RESULTS: A total of 21 hyperacute, 72 acute, 21 early subacute, and 7 late-subacute patients were included in this analysis. Significant changes in blood susceptibility were found over time for the MEDI and mcTFI, although mcTFI better differentiated the hyperacute/acute from subacute stages. CTindex values within the ICH were more strongly correlated with mcTFI QSM (r = 0.727) than MEDI (r = 0.412) QSM. DATA CONCLUSION: McTFI susceptibility estimation demonstrated better correlation with ICH acuity as suggested by CT, providing an improved method to assess acuity of intracranial blood products in clinical settings to identify cases that may require acute intervention. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

3D amplified MRI (aMRI).

PURPOSE: Amplified MRI (aMRI) has been introduced as a new method of detecting and visualizing pulsatile brain motion in 2D. Here, we improve aMRI by introducing a novel 3D aMRI approach. METHODS: 3D aMRI was developed and tested for its ability to amplify sub-voxel motion in all three directions. In addition, 3D aMRI was qualitatively compared to 2D aMRI on multi-slice and 3D (volumetric) balanced steady-state free precession cine data and phase contrast (PC-MRI) acquired on healthy volunteers at 3T. Optical flow maps and 4D animations were produced from volumetric 3D aMRI data. RESULTS: 3D aMRI exhibits better image quality and fewer motion artifacts compared to 2D aMRI. The tissue motion was seen to match that of PC-MRI, with the predominant brain tissue displacement occurring in the cranial-caudal direction. Optical flow maps capture the brain tissue motion and display the physical change in shape of the ventricles by the relative movement of the surrounding tissues. The 4D animations show the complete brain tissue and cerebrospinal fluid (CSF) motion, helping to highlight the "piston-like" motion of the ventricles. CONCLUSIONS: Here, we introduce a novel 3D aMRI approach that enables one to visualize amplified cardiac- and CSF-induced brain motion in striking detail. 3D aMRI captures brain motion with better image quality than 2D aMRI and supports a larger amplification factor. The optical flow maps and 4D animations of 3D aMRI may open up exciting applications for neurological diseases that affect the biomechanics of the brain and brain fluids.

Characterizing changes in network connectivity following chronic head trauma in special forces military personnel: a combined resting-fMRI and DTI study.

BACKGROUND: Soldiers are exposed to significant repetitive head trauma, which may disrupt functional and structural brain connectivity patterns. PURPOSE/HYPOTHESIS: Integrate resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) to characterize changes in connectivity biomarkers within Canadian Special Operations Forces (CANSOF), hypothesizing that alterations in architectural organization of cortical hubs may follow chronic repetitive head trauma. METHODS: Fifteen CANSOFs with a history of chronic exposure to sub-concussive head trauma and concussive injuries (1.9 ± 2.0 concussions (range: [0-6])), as well as an equal age-matched cohort of controls (CTLs) were recruited. BOLD-based rs-fMRI was combined with DTI to reconstruct functional and structural networks using independent component analyses and probabilistic tractography. Connectivity markers were computed based on the distance between functional seeds to assess for possible differences in injury susceptibility of short- and long-range connections. RESULTS/DISCUSSION: Significant hyper- and hypo-connectivity differences in cortical connections were observed suggesting that chronic head trauma may predispose soldiers to changes in the functional organization of brain networks. Significant structural alterations in axonal fibers directly connecting disrupted functional nodes were specific to hyper-connected long-range connections, suggesting a potential relationship between axonal injury and increases in neural recruitment following repetitive head trauma from high-exposure military duties.

The role of diffusion tensor imaging in characterizing injury patterns on athletes with concussion and subconcussive injury: a systematic review.

Traumatic brain injury (TBI) is a major public health problem. The majority of TBIs are in the form of mild TBI (also known as concussion) with sports-related concussion (SRC) receiving public attention in recent years.Here we have performed a systematic review of the literature on the use of Diffusion Tensor Imaging (DTI) on sports-related concussion and subconcussive injuries. Our review found different patterns of change in DTI parameters between concussed and subconcussed groups. The Fractional Anisotropy (FA) was either unchanged or increased for the concussion group, while the subconcussed group generally experienced a decrease in FA. A reverse pattern was observed for Mean Diffusivity (MD) - where the concussed group experienced a decrease in MD while the subconcussed group showed an increase in MD. However, in general, discrepancies were observed in the results reported in the literature - likely due to the huge variations in DTI acquisition parameters, and image processing and analysis methods used in these studies. This calls for more comprehensive and well-controlled studies in this field, including those that combine the advanced brain imaging with biomechancial modeling and kinematic sensors - to shed light on the underlying mechanisms behind the structural changes observed from the imaging studies.

The Hammer and the Nail: Biomechanics of Striking and Struck Canadian University Football Players.

This study sought to evaluate head accelerations in both players involved in a football collision. Players on two opposing Canadian university teams were equipped with helmet mounted sensors during one game per season, for two consecutive seasons. A total of 276 collisions between 58 instrumented players were identified via video and cross-referenced with sensor timestamps. Player involvement (striking and struck), impact type (block or tackle), head impact location (front, back, left and right), and play type were recorded from video footage. While struck players did not experience significantly different linear or rotational accelerations between any play types, striking players had the highest linear and rotational head accelerations during kickoff plays (p ≤ .03). Striking players also experienced greater linear and rotational head accelerations than struck players during kickoff plays (p = .001). However, struck players experienced greater linear and rotational accelerations than striking players during kick return plays (p ≤ .008). Other studies have established that the more severe the head impact, the greater risk for injury to the brain. This paper's results highlight that kickoff play rule changes, as implemented in American college football, would decrease head impact exposure of Canadian university football athletes and make the game safer.

Insights Into Cerebral Tissue-Specific Response to Respiratory Challenges at 7T: Evidence for Combined Blood Flow and CO2-Mediated Effects.

Cerebrovascular reactivity (CVR) mapping is finding increasing clinical applications as a non-invasive probe for vascular health. Further analysis extracting temporal delay information from the CVR response provide additional insight that reflect arterial transit time, blood redistribution, and vascular response speed. Untangling these factors can help better understand the (patho)physiology and improve diagnosis/prognosis associated with vascular impairments. Here, we use hypercapnic (HC) and hyperoxic (HO) challenges to gather insight about factors driving temporal delays between gray-matter (GM) and white-matter (WM). Blood Oxygen Level Dependent (BOLD) datasets were acquired at 7T in nine healthy subjects throughout BLOCK- and RAMP-HC paradigms. In a subset of seven participants, a combined HC+HO block, referred as the "BOOST" protocol, was also acquired. Tissue-based differences in Rapid Interpolation at Progressive Time Delays (RIPTiDe) were compared across stimulus to explore dynamic (BLOCK-HC) versus progressive (RAMP-HC) changes in CO2, as well as the effect of bolus arrival time on CVR delays (BLOCK-HC versus BOOST). While GM delays were similar between the BLOCK- (21.80 ± 10.17 s) and RAMP-HC (24.29 ± 14.64 s), longer WM lag times were observed during the RAMP-HC (42.66 ± 17.79 s), compared to the BLOCK-HC (34.15 ± 10.72 s), suggesting that the progressive stimulus may predispose WM vasculature to longer delays due to the smaller arterial content of CO2 delivered to WM tissues, which in turn, decreases intravascular CO2 gradients modulating CO2 diffusion into WM tissues. This was supported by a maintained ∼10 s offset in GM (11.66 ± 9.54 s) versus WM (21.40 ± 11.17 s) BOOST-delays with respect to the BLOCK-HC, suggesting that the vasoactive effect of CO2 remains constant and that shortening of BOOST delays was be driven by blood arrival reflected through the non-vasodilatory HO contrast. These findings support that differences in temporal and magnitude aspects of CVR between vascular networks reflect a component of CO2 sensitivity, in addition to redistribution and steal blood flow effects. Moreover, these results emphasize that the addition of a BOOST paradigm may provide clinical insights into whether vascular diseases causing changes in CVR do so by way of severe blood flow redistribution effects, alterations in vascular properties associated with CO2 diffusion, or changes in blood arrival time.

Robotic Assessment of Upper Limb Function in a Nonhuman Primate Model of Chronic Stroke.

Stroke is a leading cause of death and disability worldwide and survivors are frequently left with long-term disabilities that diminish their autonomy and result in the need for chronic care. There is an urgent need for the development of therapies that improve stroke recovery, as well as accurate and quantitative tools to measure function. Nonhuman primates closely resemble humans in neuroanatomy and upper limb function and may be crucial in randomized pre-clinical trials for testing the efficacy of stroke therapies. To test the feasibility of robotic assessment of motor function in a NHP model of stroke, two cynomolgus macaques were trained to perform a visually guided reaching task and were also assessed in a passive stretch task using the Kinarm robot. Strokes were then induced in these animals by transiently occluding the middle cerebral artery, and their motor performance on the same tasks was assessed after recovery. Relative to pre-stroke performance, post-stroke hand movements of the affected limb became slower and less accurate. Regression analyses revealed both recovered and compensatory movements to complete movements in different spatial directions. Lastly, we noted decreased range of motion in the elbow joint of the affected limb post-stroke associated with spasticity during passive stretch. Taken together, these studies highlight that sensorimotor deficits in reaching movements following stroke in cynomolgus macaques resemble those in human patients and validate the use of robotic assessment tools in a nonhuman primate model of stroke for identifying and characterizing such deficits.

Compromised resting cerebral metabolism after sport-related concussion: A calibrated MRI study.

Altered resting cerebral blood flow (CBF0) in the acute phase post-concussion may contribute to neurobehavioral deficiencies, often reported weeks after the injury. However, in addition to changes in CBF0, little is known about other physiological mechanisms that may be disturbed within the cerebrovasculature. The aim of this study was to assess whether changes in baseline perfusion following sport-related concussion (SRC) were co-localized with changes in cerebral metabolic demand. Forty-two subjects (15 SRC patients 8.0 ± 4.6 days post-injury and 27 age-matched healthy control athletes) were studied cross-sectionally. CBF0, cerebrovascular reactivity (CVR), resting oxygen extraction (OEF0) and cerebral metabolic rate of oxygen consumption (CMRO2|0) were measured using a combination of hypercapnic and hyperoxic breathing protocols, and the biophysical model developed in calibrated MRI. Blood oxygenation level dependent and perfusion data were acquired simultaneously using a dual-echo arterial spin labelling sequence. SRC patients showed significant decreases in CBF0 spread across the grey-matter (P < 0.05, corrected), and these differences were also confounded by the effects of baseline end-tidal CO2 (P < 0.0001). Lower perfusion was co-localized with reductions in regional CMRO2|0 (P = 0.006) post-SRC, despite finding no group-differences in OEF0 (P = 0.800). Higher CVR within voxels showing differences in CBF was also observed in the SRC group (P = 0.001), compared to controls. Reductions in metabolic demand despite no significant changes in OEF0 suggests that hypoperfusion post-SRC may reflect compromised metabolic function after the injury. These results provide novel insight about the possible pathophysiological mechanisms underlying concussion that may affect the clinical recovery of athletes after sport-related head injuries.

Multi-modal normalization of resting-state using local physiology reduces changes in functional connectivity patterns observed in mTBI patients.

Blood oxygenation level dependent (BOLD) resting-state functional magnetic resonance imaging (rs-fMRI) may serve as a sensitive marker to identify possible changes in the architecture of large-scale networks following mild traumatic brain injury (mTBI). Differences in functional connectivity (FC) measurements derived from BOLD rs-fMRI may however be confounded by changes in local cerebrovascular physiology and neurovascular coupling mechanisms, without changes in the underlying neuronally driven connectivity of networks. In this study, multi-modal neuroimaging data including BOLD rs-fMRI, baseline cerebral blood flow (CBF0) and cerebrovascular reactivity (CVR; acquired using a hypercapnic gas breathing challenge) were collected in 23 subjects with reported mTBI (14.6±14.9 months post-injury) and 27 age-matched healthy controls. Despite no group differences in CVR within the networks of interest (P > 0.05, corrected), significantly higher CBF0 was documented in the mTBI subjects (P < 0.05, corrected), relative to the controls. A normalization method designed to account for differences in CBF0 post-mTBI was introduced to evaluate the effects of such an approach on reported group differences in network connectivity. Inclusion of regional perfusion measurements in the computation of correlation coefficients within and across large-scale networks narrowed the differences in FC between the groups, suggesting that this approach may elucidate unique changes in connectivity post-mTBI while accounting for shared variance with CBF0. Altogether, our results provide a strong paradigm supporting the need to account for changes in physiological modulators of BOLD in order to expand our understanding of the effects of brain injury on large-scale FC of cortical networks.

Co-localized impaired regional cerebrovascular reactivity in chronic concussion is associated with BOLD activation differences during a working memory task.

The purpose of this study was to quantify differences in blood oxygen level dependent (BOLD) activation on a working memory task, baseline cerebral blood flow (CBF0), and cerebrovascular reactivity (CVR) between participants with and without a history of concussion. A dual-echo pseudo-continuous arterial spin labelling (pCASL) sequence was performed on a group of 10 subjects with a previous concussion (126 ± 15 days prior) and on a control group (n = 10) during a visual working memory protocol. A separate dual-echo pCASL sequence was used to derive CVR and CBF0 measurements from a boxcar hypercapnic breathing protocol. Brain areas with significant activation differences on the working memory task between groups were identified and combined as an aggregate region of interest for CBF and CVR analyses. Areas of reduced BOLD activation during the working memory task in the concussed group included the ventral anterior cingulate cortex (ACC), the medial temporal gyrus (MTG), and the lateral occipital cortex in two loci. A single area of increased activation was located in the parietal operculum. Further analyses of CBF0 and CVR in these regions revealed reduced CVR in the concussed group in the MTG and ACC, while CBF0 did not differ. The differences in CVR between the two groups in these regions suggest that concussive injury may result in microvascular dysfunction. In turn, the decreased BOLD response during the task could be due to altered neurovascular coupling, rather than an impairment in neural activation alone. However, in other regions associated with working memory, unchanged CBF0 and CVR suggests that neural injury also persists after concussion. In the future, BOLD results should be normalized to CVR in order achieve a clearer understanding of the neural and vascular contributions to the differences in the signal.

Changes in volumetric and metabolic parameters relate to differences in exposure to sub-concussive head impacts.

Structural and calibrated magnetic resonance imaging data were acquired on 44 collegiate football players prior to the season (PRE), following the first four weeks in-season (PTC) and one month after the last game (POST). Exposure data collected from g-Force accelerometers mounted to the helmet of each player were used to split participants into HIGH (N = 22) and LOW (N = 22) exposure groups, based on the frequency of impacts sustained by each athlete. Significant decreases in grey-matter volume specific to the HIGH group were documented at POST (P = 0.009), compared to baseline. Changes in resting cerebral blood flow (CBF0), corrected for partial volume effects, were observed within the HIGH group, throughout the season (P < 0.0001), suggesting that alterations in perfusion may follow exposure to sub-concussive collisions. Co-localized significant increases in cerebral metabolic rate of oxygen consumption (CMRO2|0) mid-season were also documented in the HIGH group, with respect to both PRE- and POST values. No physiological changes were observed in the LOW group. Therefore, cerebral metabolic demand may be elevated in players with greater exposure to head impacts. These results provide novel insight into the effects of sub-concussive collisions on brain structure and cerebrovascular physiology and emphasize the importance of multi-modal imaging for a complete characterization of cerebral health.

Multi-parametric analysis reveals metabolic and vascular effects driving differences in BOLD-based cerebrovascular reactivity associated with a history of sport concussion.

Objective: Identify alterations in cerebrovascular reactivity (CVR) based on the history of sport-related concussion (SRC). Further explore possible mechanisms underlying differences in vascular physiology using hemodynamic parameters modeled using calibrated magnetic resonance imaging (MRI). Method: End-tidal targeting and dual-echo MRI were combined to probe hypercapnic and hyperoxic challenges in athletes with (n = 32) and without (n = 31) a history of SRC. Concurrent blood oxygenation level dependent (BOLD) and arterial spin labeling (ASL) data were used to compute BOLD-CVR, ASL-CVR, and other physiological parameters including resting oxygen extraction fraction (OEF0) and cerebral blood volume (CBV0). Multiple linear and logistic regressions were then used to identify dominant parameters driving group-differences in BOLD-CVR. Results: Robust evidence for elevated BOLD-CVR were found in athletes with SRC history spreading over parts of the cortical hemispheres. Follow-up analyses showed co-localized differences in ASL-CVR (representing modulation of cerebral blood flow) and hemodynamic factors representing static vascular (i.e., CBV0) and metabolic (i.e., OEF0) effects suggesting that group-based differences in BOLD-CVR may be driven by a mixed effect from factors with vascular and metabolic origins. Conclusion: These results emphasize that while BOLD-CVR offers promises as a surrogate non-specific biomarker for cerebrovascular health following SRC, multiple hemodynamic parameters can affect its relative measurements. Abbreviations: [dHb]: concentration of deoxyhemoglobin; AFNI: Analysis of Functional NeuroImages ( https://afni.nimh.nih.gov ); ASL: arterial spin labeling; BIG: position group: defensive and offensive linemen; BIG-SKILL: position group: full backs, linebackers, running backs, tight-ends; BOLD: blood oxygen level dependent; CBF: cerebral blood flow; CMRO2: cerebral metabolic rate of oxygen consumption; CTL: group of control subjects; CVR: cerebrovascular reactivity; fMRI: functional magnetic resonance imaging; FSL: FMRIB software library ( https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/ ); HC: hypercapnia; HO: hyperoxia; HX: group with history of concussion; M: maximal theoretical BOLD signal upon complete removal of venous dHb; pCASL: pseudo-continuous arterial spin labeling; PETCO2: end-tidal carbon dioxide; PETO2: end-tidal oxygen; SCAT: sport-concussion assessment tool; SKILL: position group: defensive backs, kickers, quarterbacks, safeties, wide-receivers; SRC: sport-related concussion.