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.

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.

White matter alterations over the course of two consecutive high-school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study.

The cumulative effects of repetitive subclinical head impacts during sports may result in chronic white matter (WM) changes and possibly, neurodegenerative sequelae. In this pilot study, we investigated the longitudinal WM changes over the course of two consecutive high-school football seasons and explored the long-term effects of a jugular vein compression collar on these WM alterations. Diffusion tensor imaging data were prospectively collected both pre- and postseason in the two consecutive seasons. Participants were assigned into either collar or noncollar groups. Tract-based spatial statistics (TBSS) approach and region of interest-based approach were used to quantify changes in WM diffusion properties. Despite comparable exposure to repetitive head impacts, significant reductions in mean, axial, and/or radial diffusivity were identified in Season 1 in multiple WM regions in the noncollar group but not in the collar group. After an 8- to 9-month long off-season, these changes observed in the noncollar group partially and significantly reversed but also remained significantly different from the baseline. In Season 2, trend level WM alterations in the noncollar group were found but located in spatially different regions than Season 1. Last, the WM integrity in the collar group remained unchanged throughout the four time points. In conclusion, we quantitatively assessed the WM structural changes and partial reversal over the course of two consecutive high-school football seasons. In addition, the mitigated WM alterations in athletes in the collar group might indicate potential effect of the collar in ameliorating the changes against repetitive head impacts. Hum Brain Mapp 39:491-508, 2018. © 2017 Wiley Periodicals, Inc.

Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury.

Studies using traditional treatment strategies for mild traumatic brain injury (TBI) have produced limited clinical success. Interest in treatment for mild TBI is at an all time high due to its association with the development of chronic traumatic encephalopathy and other neurodegenerative diseases, yet therapeutic options remain limited. Traditional pharmaceutical interventions have failed to transition to the clinic for the treatment of mild TBI. As such, many pre-clinical studies are now implementing non-pharmaceutical therapies for TBI. These studies have demonstrated promise, particularly those that modulate secondary injury cascades activated after injury. Because no TBI therapy has been discovered for mild injury, researchers now look to pharmaceutical supplementation in an attempt to foster success in human clinical trials. Non-traditional therapies, such as acupuncture and even music therapy are being considered to combat the neuropsychiatric symptoms of TBI. In this review, we highlight alternative approaches that have been studied in clinical and pre-clinical studies of TBI, and other related forms of neural injury. The purpose of this review is to stimulate further investigation into novel and innovative approaches that can be used to treat the mechanisms and symptoms of mild TBI.

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-ß] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.

National Football League Head, Neck and Spine Committee's Concussion Diagnosis and Management Protocol: 2017-18 season.

One of the National Football League's (NFL) Head, Neck and Spine Committee's principal goals is to create a 'best practice' protocol for concussion diagnosis and management for its players. The science related to concussion diagnosis and management continues to evolve, thus the protocol has evolved contemporaneously. The Fifth International Conference on Concussion in Sport was held in Berlin in 2016, and guidelines for sports concussion diagnosis and management were revised and refined. The NFL Head, Neck and Spine Committee has synthesised the most recent empirical evidence for sports concussion diagnosis and management including the Berlin consensus statement and tailored it to the game played in the NFL. One of the goals of the Committee is to provide a standardised, reliable, efficient and evidence-based protocol for concussion diagnosis and management that can be applied in this professional sport during practice and game day. In this article, the end-of-season version of the 2017-18 NFL Concussion Diagnosis and Management Protocol is described along with its clinical rationale. Immediate actions for concussion programme enhancement and research are reviewed. It is the Committee's expectation that the protocol will undergo refinement and revision over time as the science and clinical practice related to concussion in sports crystallise.

A systematic review of potential long-term effects of sport-related concussion.

OBJECTIVE: Systematic review of possible long-term effects of sports-related concussion in retired athletes. DATA SOURCES: Ten electronic databases. STUDY SELECTION: Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury. DATA EXTRACTION: Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. RESULTS: Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. CONCLUSION: Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports.

Brainstem Monitoring in the Neurocritical Care Unit: A Rationale for Real-Time, Automated Neurophysiological Monitoring.

Patients with severe traumatic brain injury or large intracranial space-occupying lesions (spontaneous cerebral hemorrhage, infarction, or tumor) commonly present to the neurocritical care unit with an altered mental status. Many experience progressive stupor and coma from mass effects and transtentorial brain herniation compromising the ascending arousal (reticular activating) system. Yet, little progress has been made in the practicality of bedside, noninvasive, real-time, automated, neurophysiological brainstem, or cerebral hemispheric monitoring. In this critical review, we discuss the ascending arousal system, brain herniation, and shortcomings of our current management including the neurological exam, intracranial pressure monitoring, and neuroimaging. We present a rationale for the development of nurse-friendly-continuous, automated, and alarmed-evoked potential monitoring, based upon the clinical and experimental literature, advances in the prognostication of cerebral anoxia, and intraoperative neurophysiological monitoring.

Use of Head Guards in AIBA Boxing Tournaments-A Cross-Sectional Observational Study.

OBJECTIVE: This study looks at the changes in injuries after the implementation of a new rule by the International Boxing Association (AIBA) to remove head guards from its competitions. DESIGN: A cross-sectional observational study performed prospectively. This brief report examines the removal of head guards in 2 different ways. The first was to examine the stoppages due to blows to the head by comparing World Series Boxing (WSB), without head guards, to other AIBA competitions with head guards. Secondly, we examined the last 3 world championships: 2009 and 2011 (with head guards) and 2013 (without head guards). SETTING: World Series Boxing and AIBA world championship boxing. PARTICIPANTS: Boxers from WSB and AIBA world championships. INTERVENTIONS: The information was recorded by ringside medical physicians. MAIN OUTCOME MEASURES: Stoppages per 10 000 rounds; stoppages per 1000 hours. RESULTS: Both studies show that the number of stoppages due to head blows was significantly decreased without head guards. The studies also showed that there was a notable increase in cuts. CONCLUSIONS: Removing head guards may reduce the already small risk of acute brain injury in amateur boxing.

The Impact of Traumatic Brain Injury on the Aging Brain.

Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident.

Sports-related concussions: diagnosis, complications, and current management strategies.

Sports-related concussions (SRCs) are traumatic events that affect up to 3.8 million athletes per year. The initial diagnosis and management is often instituted on the field of play by coaches, athletic trainers, and team physicians. SRCs are usually transient episodes of neurological dysfunction following a traumatic impact, with most symptoms resolving in 7-10 days; however, a small percentage of patients will suffer protracted symptoms for years after the event and may develop chronic neurodegenerative disease. Rarely, SRCs are associated with complications, such as skull fractures, epidural or subdural hematomas, and edema requiring neurosurgical evaluation. Current standards of care are based on a paradigm of rest and gradual return to play, with decisions driven by subjective and objective information gleaned from a detailed history and physical examination. Advanced imaging techniques such as functional MRI, and detailed understanding of the complex pathophysiological process underlying SRCs and how they affect the athletes acutely and long-term, may change the way physicians treat athletes who suffer a concussion. It is hoped that these advances will allow a more accurate assessment of when an athlete is truly safe to return to play, decreasing the risk of secondary impact injuries, and provide avenues for therapeutic strategies targeting the complex biochemical cascade that results from a traumatic injury to the brain.

The science and questions surrounding chronic traumatic encephalopathy.

Recently, the pathobiology, causes, associated factors, incidence and prevalence, and natural history of chronic traumatic encephalopathy (CTE) have been debated. Data from retrospective case series and high-profile media reports have fueled public fear and affected the medical community's understanding of the role of sports-related traumatic brain injury (TBI) in the development of CTE. There are a number of limitations posed by the current evidence that can lead to confusion within the public and scientific community. In this paper, the authors address common questions surrounding the science of CTE and propose future research directions.

Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities.

BACKGROUND: Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE) have long been recognized as sharing some similar neuropathological features, mainly the presence of neurofibrilary tangles and hyperphosphorylated tau, but have generally been described as distinct entities. Evidence indicates that neurotrauma increases the risk of developing dementia and accelerates the progression of disease. Findings are emerging that CTE and AD may be present in the same patients. CLINICAL PRESENTATION: This study presents a series of previously unpublished cases, with one case demonstrating possible neurotrauma-related AD, one pure CTE, and an example of a case exhibiting features of both AD and CTE. The future significance of this work lies not only in the confirmation of AD-CTE co-existence, but, more importantly, ways of generating a hypothesis about the possibility that CTE may accelerate AD development. Understanding the relationship between neurotrauma and neurodegenerative disease will help elucidate how distinct disease entities can co-exist in the same patient. It will ultimately require the use of pre-clinical animal models and repeat injury paradigms to investigate clinically relevant injury mechanisms. These models should produce a CTE-like phenotype that must be both neuropathologically and behaviourally similar to human disease. CONCLUSION: This case series and review of the literature presents a discussion of AD and CTE in the context of neurotrauma. It highlights recent work from repetitive neurotrauma models with an emphasis on those exhibiting a CTE-like phenotype. Potential mechanisms of interest shared amongst AD and CTE are briefly addressed and future experiments are advocated for to enhance understanding of CTE pathophysiology and the relationship between CTE and AD.

Thrombolysis for intraventricular hemorrhage.

Intraventricular hemorrhage is a frequent complication of intracerebral hemorrhage and is independently associated with significant morbidity and mortality. Intraventricular fibrinolytic therapy is used with increasing frequency to accelerate clot clearance. We review the recent evidence and discuss the therapeutic benefits as well as the current concerns and limitations of fibrinolytic use in this setting.

PET scanning of brain tau in retired national football league players: preliminary findings.

OBJECTIVE: Mild traumatic brain injury due to contact sports may cause chronic behavioral, mood, and cognitive disturbances associated with pathological deposition of tau protein found at brain autopsy. To explore whether brain tau deposits can be detected in living retired players, we used positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP). METHODS: Five retired National Football League players (age range: 45 to 73 years) with histories of mood and cognitive symptoms received neuropsychiatric evaluations and FDDNP-PET. PET signals in subcortical (caudate, putamen, thalamus, subthalamus, midbrain, cerebellar white matter) and cortical (amygdala, frontal, parietal, posterior cingulate, medial and lateral temporal) regions were compared with those of five male controls of comparable age, education, and body mass index. RESULTS: FDDNP signals were higher in players compared with controls in all subcortical regions and the amygdala, areas that produce tau deposits following trauma. CONCLUSIONS: The small sample size and lack of autopsy confirmation warrant larger, more definitive studies, but if future research confirms these initial findings, FDDNP-PET may offer a means for premorbid identification of neurodegeneration in contact-sports athletes.

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.

An overview of the basic science of concussion and subconcussion: where we are and where we are going.

There has been a growing interest in the diagnosis and management of mild traumatic brain injury (TBI), or concussion. Repetitive concussion and subconcussion have been linked to a spectrum of neurological sequelae, including postconcussion syndrome, chronic traumatic encephalopathy, mild cognitive impairment, and dementia pugilistica. A more common risk than chronic traumatic encephalopathy is the season-ending or career-ending effects of concussion or its mismanagement. To effectively prevent and treat the sequelae of concussion, it will be important to understand the basic processes involved. Reviewed in this paper are the forces behind the primary phase of injury in mild TBI, as well as the immediate and delayed cellular events responsible for the secondary phase of injury leading to neuronal dysfunction and possible cell death. Advanced neuroimaging sequences have recently been developed that have the potential to increase the sensitivity of standard MRI to detect both structural and functional abnormalities associated with concussion, and have provided further insight into the potential underlying pathophysiology. Also discussed are the potential long-term effects of repetitive mild TBI, particularly chronic traumatic encephalopathy. Much of the data regarding this syndrome is limited to postmortem analyses, and at present there is no animal model of chronic traumatic encephalopathy described in the literature. As this arena of TBI research continues to evolve, it will be imperative to appropriately model concussive and even subconcussive injuries in an attempt to understand, prevent, and treat the associated chronic neurodegenerative sequelae.