Dark Blood Contrast-Enhanced Brain MRI Using Echo-uT1 RESS.

BACKGROUND: The widely used magnetization-prepared rapid gradient-echo (MPRAGE) sequence makes enhancing lesions and blood vessels appear bright after gadolinium administration. However, dark blood imaging using T1-weighted Sampling Perfection with Application optimized Contrast using different flip angle Evolution (T1 SPACE) can be advantageous since it improves the conspicuity of small metastases and leptomeningeal disease. As a potential alternative to T1 SPACE, we evaluated a new dark blood sequence called echo-uT1 RESS (unbalanced T1 Relaxation-Enhanced Steady-State). PURPOSE: We compared the performance of echo-uT1 RESS with Dixon fid-uT1 RESS, MPRAGE, and T1 SPACE. STUDY TYPE: Retrospective, IRB approved. SUBJECTS/PHANTOM: Phantom to assess flow properties of echo-uT1 RESS. Twenty-one patients (14 female, age range 35-82 years) with primary and secondary brain tumors. FIELD STRENGTH/SEQUENCES: 3 Tesla/MPRAGE, T1 SPACE, Dixon fid-uT1 RESS, echo-uT1 RESS. ASSESSMENT: Flow phantom signal vs. velocity as a function of flip angle and sequence. Qualitative image assessment on 4-point scale. Quantitative evaluation of tumor-to-brain contrast, apparent contrast-to-noise ratio (aCNR), and vessel-to-brain aCNR. STATISTICAL TESTS: Friedman and Mann-Whitney U tests. A P value <0.05 was considered statistically significant. RESULTS: In the phantom, echo-uT1 RESS showed greater flow-dependent signal loss than fid-uT1 RESS. In patients, blood vessels appeared bright with MPRAGE, gray with fid-uT1 RESS, and dark with T1 SPACE and echo-uT1 RESS. For MPRAGE, Dixon fid-uT1 RESS, echo-uT1 RESS, and T1 SPACE, respective tumor-to-brain contrast values were 0.6 ± 0.3, 1.3 ± 0.5, 1.0 ± 0.4, and 0.6 ± 0.4, while normalized aCNR values were 68.9 ± 50.9, 128.4 ± 59.2, 74.2 ± 42.1, and 99.4 ± 73.9. DATA CONCLUSION: Volumetric dark blood contrast-enhanced brain MRI is feasible using echo-uT1 RESS. The dark blood effect was improved vs. fid-uT1 RESS, while both uT1 RESS versions provided better tumor-to-brain contrast than MPRAGE. Whereas T1 SPACE provided better tumor aSNR, echo-uT1 RESS provided better Weber contrast, lesion sharpness and a more consistent dark blood effect. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Examining later-in-life health risks associated with sport-related concussion and repetitive head impacts: a systematic review of case-control and cohort studies.

OBJECTIVE: Concern exists about possible problems with later-in-life brain health, such as cognitive impairment, mental health problems and neurological diseases, in former athletes. We examined the future risk for adverse health effects associated with sport-related concussion, or exposure to repetitive head impacts, in former athletes. DESIGN: Systematic review. DATA SOURCES: Search of MEDLINE, Embase, Cochrane, CINAHL Plus and SPORTDiscus in October 2019 and updated in March 2022. ELIGIBILITY CRITERIA: Studies measuring future risk (cohort studies) or approximating that risk (case-control studies). RESULTS: Ten studies of former amateur athletes and 18 studies of former professional athletes were included. No postmortem neuropathology studies or neuroimaging studies met criteria for inclusion. Depression was examined in five studies in former amateur athletes, none identifying an increased risk. Nine studies examined suicidality or suicide as a manner of death, and none found an association with increased risk. Some studies comparing professional athletes with the general population reported associations between sports participation and dementia or amyotrophic lateral sclerosis (ALS) as a cause of death. Most did not control for potential confounding factors (eg, genetic, demographic, health-related or environmental), were ecological in design and had high risk of bias. CONCLUSION: Evidence does not support an increased risk of mental health or neurological diseases in former amateur athletes with exposure to repetitive head impacts. Some studies in former professional athletes suggest an increased risk of neurological disorders such as ALS and dementia; these findings need to be confirmed in higher quality studies with better control of confounding factors. PROSPERO REGISTRATION NUMBER: CRD42022159486.

Improved Brain Tumor Conspicuity at 3 T Using Dark Blood, Fat-Suppressed, Dixon Unbalanced T1 Relaxation-Enhanced Steady-State MRI.

OBJECTIVES: Contrast-enhanced magnetic resonance imaging (MRI) is the cornerstone for brain tumor diagnosis and treatment planning. We have developed a novel dual-echo volumetric dark blood pulse sequence called Dixon unbalanced T1 relaxation-enhanced steady-state (uT 1 RESS) that improves the visibility of contrast-enhancing lesions while suppressing the tissue signals from blood vessels and fat. The purpose of this study was to test the hypothesis that Dixon uT 1 RESS would significantly improve the conspicuity of brain tumors compared with magnetization-prepared rapid gradient echo (MPRAGE), as well as to determine potential limitations of the technique. MATERIALS AND METHODS: This retrospective study was approved by the hospital institutional review board. Forty-seven adult patients undergoing an MRI scan for a brain tumor indication were included. Contrast-enhanced MRI of the brain was performed at 3 T using both MPRAGE and Dixon uT 1 RESS. To control for any impact of contrast agent washout during the scan procedure, Dixon uT 1 RESS was acquired in approximately half the subjects immediately after MPRAGE, and in the other half immediately before MPRAGE. Image quality, artifacts, and lesion detection were scored by 3 readers, whereas lesion apparent signal-to-noise ratio and lesion-to-background Weber contrast were calculated from region-of-interest measurements. RESULTS: Image quality was not rated significantly different between MPRAGE and Dixon uT 1 RESS, whereas motion artifacts were slightly worse with Dixon uT 1 RESS. Comparing Dixon uT 1 RESS with MPRAGE, the respective values for mean lesion apparent signal-to-noise ratio were not significantly different (199.31 ± 99.05 vs 203.81 ± 110.23). Compared with MPRAGE, Dixon uT 1 RESS significantly increased the tumor-to-brain contrast (1.60 ± 1.18 vs 0.61 ± 0.47 when Dixon uT1RESS was acquired before MPRAGE and 1.94 ± 0.97 vs 0.82 ± 0.55 when Dixon uT 1 RESS was acquired after MPRAGE). In patients with metastatic disease, Dixon uT 1 RESS detected at least 1 enhancing brain lesion that was missed by MPRAGE on average in 24.7% of patients, whereas Dixon uT 1 RESS did not miss any lesions that were demonstrated by MPRAGE. Dixon uT 1 RESS better detected vascular and dural invasion in a small number of patients. CONCLUSIONS: In conclusion, brain tumors were significantly more conspicuous at 3 T using Dixon uT 1 RESS compared with MPRAGE, with an approximately 2.5-fold improvement in lesion-to-background contrast irrespective of sequence order. It outperformed MPRAGE for the detection of brain metastases, dural or vascular involvement. These results suggest that Dixon uT 1 RESS could prove to be a useful adjunct or alternative to existing neuroimaging techniques for the postcontrast evaluation of intracranial tumors.

National Athletic Trainers' Association Position Statement: Reducing Intentional Head-First Contact Behavior in American Football Players.

OBJECTIVE: To provide evidence-based recommendations for reducing the prevalence of head-first contact behavior in American football players with the aim of reducing the risk of head and neck injuries. BACKGROUND: In American football, using the head as the point of contact is a persistent, well-documented, and direct cause of catastrophic head and cervical spine injury. Equally concerning is that repeated head-impact exposures are likely to result from head-first contact behavior and may be associated with long-term neurocognitive conditions such as dementia, depression, and chronic traumatic encephalopathy. CONCLUSIONS: The National Athletic Trainers' Association proposes 14 recommendations to help the certified athletic trainer, allied health care provider, coach, player, parent, and broader community implement strategies for reducing the prevalence of head-first contact in American football.

Return to Play Guidelines After Cervical Spine Injuries in American Football Athletes: A Literature-Based Review.

STUDY DESIGN: Literature-based review. OBJECTIVE: We sought to evaluate clinical and case studies related to return to play (RTP) after cervical spine injuries in elite American football athletes and to formulate guidelines to help health care practitioners manage these conditions. SUMMARY OF BACKGROUND DATA: American football athletes are at unique risk of cervical spine injury and appropriate case-by-case management of cervical spine injuries is necessary for these athletes. Despite this need, no standardized guidelines exist for RTP after cervical spine injury. METHODS: Observational or case-based articles relating to RTP after cervical spine injury in American football athletes were curated from PubMed/EMBASE databases. Primary literature published before December 1, 2019 involving National Football League (NFL) or National Collegiate Athletic Association (NCAA) athletes met inclusion criteria. RESULTS: The data acquisition process yielded 28 studies addressing cervical spine injuries and RTP in American football athletes. Stingers/burners were the most common injury and placed athletes at higher risk of a more severe re-injury. Transient quadriplegia, cervical stenosis, cervical disc herniation (CDH), and cervical fractures have a more significant impact on the long-term health and career longevity of the American football athlete. As such, the literature offers some guidance for management of these athletes, including average time for RTP in patients treated nonoperatively, thresholds involving cervical stenosis, and postoperative recommendations after spinal decompression and/or fusion surgery. CONCLUSION: Elite American football athletes are at high risk for cervical spine injury due to the nature of their sport. The decision to allow these athletes to return to play should involve an understanding of the average RTP time, the potential risks of recurrence or re-injury, and individual characteristics such as position played and pathology on imaging.Level of Evidence: 3.

Sport-Related Structural Brain Injury and Return to Play: Systematic Review and Expert Insight.

BACKGROUND: Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI. OBJECTIVE: To provide key insight for operative management and RTP following SRSBI using a (1) focused systematic review and (2) survey of expert opinions. METHODS: A systematic literature review of SRSBI from 2012 to present in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a cross-sectional survey of RTP in SRSBI by 31 international neurosurgeons was conducted. RESULTS: Of 27 included articles out of 241 systematically reviewed, 9 (33.0%) case reports provided RTP information for 12 athletes. To assess expert opinion, 31 of 32 neurosurgeons (96.9%) provided survey responses. For acute, asymptomatic SRSBI, 12 (38.7%) would not operate. Of the 19 (61.3%) who would operate, midline shift (63.2%) and hemorrhage size > 10 mm (52.6%) were the most common indications. Following SRSBI with resolved hemorrhage, with or without burr holes, the majority of experts (>75%) allowed RTP to high-contact/collision sports at 6 to 12 mo. Approximately 80% of experts did not endorse RTP to high-contact/collision sports for athletes with persistent hemorrhage. Following craniotomy for SRSBI, 40% to 50% of experts considered RTP at 6 to 12 mo. Linear regression revealed that experts allowed earlier RTP at higher levels of play (ß = -0.58, 95% CI -0.111, -0.005, P = .033). CONCLUSION: RTP decisions following structural brain injury in athletes are markedly heterogeneous. While individualized RTP decisions are critical, aggregated expert opinions from 31 international sports neurosurgeons provide key insight. Level of play was found to be an important consideration in RTP determinations.

The effect of dietary supplementation with high- or low-dose omega-3 fatty acid on inflammatory pathology after traumatic brain injury in rats.

This study investigated dietary supplementation as a prophylactic for neuroinflammation following traumatic brain injury (TBI) in a preclinical model. Adult male Sprague-Dawley rats received 30 days of supplementation with either water or two dietary supplements. The first consisted of high-dose omega-3 fatty acid (O3FA) (supplement A) along with vitamin D3 and vitamin E. The second had the same ingredients at different doses with an addition of cannabidiol (supplement B). Rats were subjected to an impact TBI and then euthanized 7 days post-injury and neuroinflammation quantified by histological detection of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and CD68, a marker of microglial activity. There was a trend toward increased GFAP staining in injured, unsupplemented animals as compared to sham, unsupplemented animals, consistent with increased activation of astrocytes in response to trauma which was reversed by supplement A but not by supplement B. The pattern of CD68 staining across groups was similar to that of GFAP staining. There was a trend toward an increase in the injured unsupplemented group, relative to sham which was reversed by supplement A but not by supplement B. CD68 staining in injured animals was concentrated in the perivascular domain. The consistency between trends across different measures of neuroinflammation showing benefits of high-dose O3FA supplementation following TBI suggests that the observed effects are real. These findings are preliminary, but they justify further study to determine the functional benefits associated with improvements in histological outcomes and understand associated dose-response curves.

Insulin-Like Growth Factor-1 (IGF-1) and Its Monitoring in Medical Diagnostic and in Sports.

Insulin-like growth factor-1 (IGF-1) is the principal mediator of growth hormone (GH), plays a crucial role in promoting cell growth and differentiation in childhood and continues to have an anabolic effect in adults. IGF-1 is part of a wide network of growth factors, receptors and binding proteins involved in mediating cellular proliferation, differentiation and apoptosis. Bioavailability of IGF-1 is affected by insulin-like growth factor binding proteins (IGFBPs) which bind IGF-1 in circulation with an affinity equal to or greater than that of the IGF-1 receptor (IGF-1R). The six IGFBPs serve as carrier proteins and bind approximately 98% of all circulating IGF-1. Other proteins known to bind IGF-1 include ten IGFBP-related proteins (IGFBP-rPs), albeit with lower affinities than the IGFBPs. IGF-1 expression levels vary in a number of clinical conditions suggesting it has the potential to provide crucial information as to the state of an individual's health. IGF-1 is also a popular doping agent in sport and has featured in many high-profile doping cases in recent years. However, the existence of IGFBPs significantly reduces the levels of immunoreactive IGF-1 in samples, requiring multiple pre-treatment steps that reduce reproducibility and complicates interpretation of IGF-1 assay results. Here we provide an overview of the IGF network of growth factors, their receptors and the entirety of the extended family of IGFBPs, IGFBP-rPs, E peptides as well as recombinant IGF-1 and their derivatives. We also discuss issues related to the detection and quantification of bioavailable IGF-1.

Consensus Recommendations on the Prehospital Care of the Injured Athlete With a Suspected Catastrophic Cervical Spine Injury.

INTRODUCTION: Sports participation is among the leading causes of catastrophic cervical spine injury (CSI) in the United States. Appropriate prehospital care for athletes with suspected CSIs should be available at all levels of sport. The goal of this project was to develop a set of best-practice recommendations appropriate for athletic trainers, emergency responders, sports medicine and emergency physicians, and others engaged in caring for athletes with suspected CSIs. METHODS: A consensus-driven approach (RAND/UCLA method) in combination with a systematic review of the available literature was used to identify key research questions and develop conclusions and recommendations on the prehospital care of the spine-injured athlete. A diverse panel of experts, including members of the National Athletic Trainers' Association, the National Collegiate Athletic Association, and the Sports Institute at UW Medicine participated in 4 Delphi rounds and a 2-day nominal group technique (NGT) meeting. The systematic review involved 2 independent reviewers and 4 rounds of blinded review. RESULTS: The Delphi process identified 8 key questions to be answered by the systematic review. The systematic review comprised 1544 studies, 49 of which were included in the final full-text review. Using the results of the systematic review as a shared evidence base, the NGT meeting created and refined conclusions and recommendations until consensus was achieved. CONCLUSIONS: These conclusions and recommendations represent a pragmatic approach, balancing expert experiences and the available scientific evidence.

Consensus Recommendations on the Prehospital Care of the Injured Athlete With a Suspected Catastrophic Cervical Spine Injury.

INTRODUCTION: Sports participation is among the leading causes of catastrophic cervical spine injury (CSI) in the United States. Appropriate prehospital care for athletes with suspected CSIs should be available at all levels of sport. The goal of this project was to develop a set of best-practice recommendations appropriate for athletic trainers, emergency responders, sports medicine and emergency physicians, and others engaged in caring for athletes with suspected CSIs. METHODS: A consensus-driven approach (RAND/UCLA method) in combination with a systematic review of the available literature was used to identify key research questions and develop conclusions and recommendations on the prehospital care of the spine-injured athlete. A diverse panel of experts, including members of the National Athletic Trainers' Association, the National Collegiate Athletic Association, and the Sports Institute at UW Medicine participated in 4 Delphi rounds and a 2-day nominal group technique meeting. The systematic review involved 2 independent reviewers and 4 rounds of blinded review. RESULTS: The Delphi process identified 8 key questions to be answered by the systematic review. The systematic review comprised 1544 studies, 49 of which were included in the final full-text review. Using the results of the systematic review as a shared evidence base, the nominal group technique meeting created and refined conclusions and recommendations until consensus was achieved. CONCLUSIONS: These conclusions and recommendations represent a pragmatic approach, balancing expert experiences and the available scientific evidence.

Diffusion Tensor Imaging Detects Acute and Subacute Changes in Corpus Callosum in Blast-Induced Traumatic Brain Injury.

There is a critical need for understanding the progression of neuropathology in blast-induced traumatic brain injury using valid animal models to develop diagnostic approaches. In the present study, we used diffusion imaging and magnetic resonance (MR) morphometry to characterize axonal injury in white matter structures of the rat brain following a blast applied via blast tube to one side of the brain. Diffusion tensor imaging was performed on acute and subacute phases of pathology from which fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated for corpus callosum (CC), cingulum bundle, and fimbria. Ventricular volume and CC thickness were measured. Blast-injured rats showed temporally varying bilateral changes in diffusion metrics indicating persistent axonal pathology. Diffusion changes in the CC suggested vasogenic edema secondary to axonal injury in the acute phase. Axonal pathology persisted in the subacute phase marked by cytotoxic edema and demyelination which was confirmed by ultrastructural analysis. The evolution of pathology followed a different pattern in the cingulum bundle: axonal injury and demyelination in the acute phase followed by cytotoxic edema in the subacute phase. Spatially, structures close to midline were most affected. Changes in the genu were greater than in the body and splenium; the caudal cingulum bundle was more affected than the rostral cingulum. Thinning of CC and ventriculomegaly were greater only in the acute phase. Our results reveal the persistent nature of blast-induced axonal pathology and suggest that diffusion imaging may have potential for detecting the temporal evolution of blast injury.

Photostability of Semiconductor Quantum Dots in Response to UV Exposure.

The interest in quantum dots (QDs) and their popularity in life science applications stems from their high photostability and unique optical properties such as superior light absorption. Photostability of semiconductor QDs is reportedly higher than that of organic dyes, but QDs may also be affected by light exposure. The outcome of such exposure may depend on many experimental factors, can lead to either an increase or decrease in the photoluminescent efficiency of QDs and is difficult to predict. QDs may therefore require experimental testing for their photostability especially prior to quantitative applications. A simple QD testing procedure described here showed a substantial degree of photobleaching when exposed to UV; nevertheless, the rate of change was noticeably lower than that measured for traditional organic dyes, as expected. The procedure reported is also applicable to traditional organic dyes and allows for quantitative comparisons to be conducted.

Navigable Channel-Based Trans-Sulcal Resection of Third Ventricular Colloid Cysts: A Multicenter Retrospective Case Series and Review of the Literature.

BACKGROUND: Developments in frameless neuronavigation and tubular retractors hold the potential for minimizing iatrogenic injury to the overlying cortex and subcortical tracts, with improved access to the ventricular system. The objective of the present study was to evaluate the surgical outcomes after resection of third ventricular colloid cysts using an integrated neuronavigation and channel-based approach. METHODS: We performed a multicenter retrospective analysis of surgical Outcomes after surgical resection of third ventricular colloid cysts via a transtubular trans-sulcal approach. RESULTS: A total of 16 patients were included, with a mean age of 42 years (range, 23-62 years). The mean maximum diameter of cysts was 14 mm (range, 7-28 mm), and preoperative hydrocephalous was present in 12 patients (75%). Gross total resection was achieved in all 16 cases. Of the 12 patients, 4 (25%) had undergone septum pellucidotomy, in addition to cyst resection. No case had required conversion to open craniotomy. No perioperative mortalities occurred. Three patients (18.8%) had developed transient memory deficits, 1 of whom had also developed a pulmonary thromboembolism. The median length of hospital stay was 4 days (range, 2-18 days). All the patients reported resolution of preoperative symptoms at the 1-month follow-up examination. Only 1 patient (6.25%) had required insertion of a ventriculoperitoneal shunt. The median follow-up duration was 6.5 months (range, 3-24 months), and no recurrences were observed. CONCLUSION: Use of a channel-based navigable retractor provided a minimal trans-sulcal approach to third ventricular colloid cysts with the benefit of bimanual surgical control in an air medium for definitive resection of third ventricular colloid cysts.

Multicenter Investigation of Channel-Based Subcortical Trans-Sulcal Exoscopic Resection of Metastatic Brain Tumors: A Retrospective Case Series.

BACKGROUND: Recent advancements have aimed to optimize visualization and minimize insult to healthy cortical and subcortical tissue through the use of tubular-based retractors. OBJECTIVE: To investigate outcomes following resection of cerebral metastases using an integrated tubular retraction system with an exoscope and neuronavigation. METHODS: A multicenter retrospective analysis of surgical outcomes in consecutive patients who underwent resection of a brain metastasis using a tubular retraction system and exoscope was performed. RESULTS: Twenty-five patients were included, with a mean age of 61 yr (24-81 yr). Primary sources included lung (n = 13), breast (n = 3), renal cell (n = 3), and other (n = 6). Locations were frontal (n = 5), parietal (n = 8), cerebellar (n = 8), occipital (n = 3), and splenium (n = 1). Most lesions had a maximum diameter > 3.0 cm (n = 20) and a tumor depth > 4 cm (n = 14). Conversion to open (microscopic) craniotomy was not required in any case. Gross total resection was achieved in 20 cases (80.0%) and subtotal resection in 5 cases (20.0%). Median hospital stay was 2 d (1-12 d). All patients underwent postoperative radiation therapy. Perioperative complications developed in 1 patient (4.0%; hemiparesis and subsequent deep vein thrombosis). At 3-mo follow-up, no mortalities were observed, 19 patients (76.0%) demonstrated neurological improvements, 5 patients (20.0%) had a stable neurological exam, and 1 patient (4.0%) had a neurological decline. CONCLUSION: Utilization of a channel-based, navigable retractor and exoscope is a feasible option for surgical resection of metastatic brain lesions.

Elevations in MicroRNA Biomarkers in Serum Are Associated with Measures of Concussion, Neurocognitive Function, and Subconcussive Trauma over a Single National Collegiate Athletic Association Division I Season in Collegiate Football Players.

This prospective controlled observational cohort study assessed the performance of a novel panel of serum microRNA (miRNA) biomarkers on indicators of concussion, subconcussive impacts, and neurocognitive function in collegiate football players over the playing season. Male collegiate student football athletes participating in a Division I Football Bowl Subdivision of the National Collegiate Athletic Association (NCAA) were enrolled. There were a total of 53 participants included in the study, 30 non-athlete control subjects and 23 male collegiate student football athletes. Neurocognitive assessments and blood samples were taken within the week before the athletic season began and within the week after the last game of the season and measured for a panel of pre-selected miRNA biomarkers. All the athletes had elevated levels of circulating miRNAs at the beginning of the season compared with control subjects (p < 0.001). Athletes with the lowest standard assessment of concussion (SAC) scores at the beginning of the season had the highest levels of miRNAs. The area under the curve (AUC) for predicting pre-season SAC scores were miR-195 (0.90), miR-20a (0.89), miR-151-5p (0.86), miR-505* (0.85), miR-9-3p (0.77), and miR-362-3p (0.76). In athletes with declining neurocognitive function over the season, concentrations of miRNAs increased over same period. There were significant negative correlations with miR-505* (p = 0.011), miR-30d (p = 0.007), miR-92 (p = 0.033), and (p = 0.008). The miRNAs correlating with balance problems were miR-505* (p = 0.007), miR-30d (p = 0.028), and miR-151-5p (p = 0.023). Those correlating with poor reaction times were miR-20a (0.043), miR-505* (p = 0.049), miR-30d (p = 0.031), miR-92 (p = 0.015), and miR-151-5p (p = 0.044). Select miRNAs were associated with baseline concussion assessments at the beginning of the season and with neurocognitive changes from pre to post-season in collegiate football players. Should these findings be replicated in a larger cohort of athletes, these markers could potentially serve as measures of neurocognitive status in athletes at risk for concussion and subconcussive injuries.