Abstracts from The 34(th) Annual National Neurotrauma Symposium June 26-29, 2016 Lexington, Kentucky.

Abstract

Journal of NeurotraumaVol. 33, No. 13 AbstractsFree AccessAbstracts from The 34th Annual National Neurotrauma SymposiumJune 26–29, 2016 Lexington, KentuckyPublished Online:21 Jun 2016https://doi.org/10.1089/neu.2016.29008.abstractsAboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail AANS/CNS SessionsAANS01-02 TREATMENT OF THE DIFFICULT THORACOLUMBAR FRACTURESMiller CatherineUniversity of Minnesota, Neurosurgery, Minneapolis, USAThe thoracolumbar junction, from T11 to L2, is the most commonly injured portion of the spinal column. Over 15,000 major thoracolumbar spine injuries occur per year in the United States, with over 5,000 resulting in neurological deficits. Identifying these injuries is paramount to prevent secondary neurologic injury and assist in clinical decision-making. Several classification schemes are in use to describe these fractures, determine their overall stability, and help predict which fractures will require operative versus non-operative management. Some types of fractures are conventionally treated with or without surgery, but there still remains controversy regarding how to best manage certain fractures.During this session, there will be a brief overview of the different fracture types which occur in the thoracolumbar spine and the classifications systems in use today. The management for each of these fractures will be discussed with respect to their fracture morphology, neurologic injury, and spinal stability. It will conclude with a review of the current literature regarding treatment of the difficult and controversial fractures.Keywords: thoracolumbar fracture, spinal stability, managementAANS02-01 BRAIN TISSUE OXYGENATION–WHAT HAVE WE LEARNED FROM BOOST-2?Diaz-Arrastia RamonCenter for Neuroscience and Regenerative Medicine, Department of Neurology, Rockville, USAICU management of patients with severe TBI has focused on intracranial pressure (ICP) and cerebral perfusion pressure (CPP), but this approach was never validated in a randomized clinical trial, and recent studies have questioned the benefit of ICP-directed therapies. These studies indicate that a strategy focused on ICP may be overly simplistic. Some have suggested that monitoring the partial pressure of oxygen in brain tissue (PbtO2) provides a useful marker of tissue metabolism, and that interventions based on PbtO2 may improve patient's outcome. However, existing studies using non-randomized designs have conflicting results. We recently completed a Phase II randomized clinical trial of Brain Oxygen Optimization in Severe TBI (BOOST-2). The primary hypothesis was that a neurocritical care management strategy informed by PbtO2 values as well as ICP values would reduce the total burden on hypoxia. Secondary hypotheses related to safety, feasibility, and non-futility.122 participants were enrolled in the study. There was a substantial and highly statistically significant reduction in total hypoxia burden (p < 0.0001). No patients in the PbtO2 + ICP treatment group experience a hypoxia burden >400 hrs*mm Hg, while more than 20% of ICP only treated patients experienced a similar hypoxia burden. There were no significant differences in the rate of serious adverse events (SAEs) between the two groups. Functional outcome was assessed using the GOS-E 6 months after injury. There was a trend towards reduced mortality (GOS-E 1) and increased good outcome (GOS-E 7–8) in the PbtO2 + ICP treatment group, compared to the ICP-only treatment group. The mean (SD) GOS-E was 3.4 (2.2) in the ICP-only group and 4.2 (2.5) in the PbtO2 + ICP group (p = 0.111). In the pre-specified analysis dichotomizing the GOS-E at 4, the Odds Ratio favoring good recovery in the PbtO2 + ICP treatment group was 1.8 (p = 0.221, Fisher's exact test). These findings were supportive of the pre-determined non-futility hypothesis. A Phase III study designed to obtain definitive evidence of clinical benefit is currently under review.Keywords: PbtO2, randomized clinical trial, Glasgow Outcome Scale-ExtendedAANS02-02withdrawnAANS02-03 LOW-LEVEL LIGHT THERAPY FOR TRAUMATIC BRAIN INJURY (TBI)Gupta Rajiv1,2, Ahmadi Emad1,2, Namati Jacqueline1,2, Blair Parry1, Padole Atul1,2, Chico-Calero Isabel1,2, Lev Michael1,2, Lee Jarone1,2, Hamblin Michael1,2, Vakoc Benjamin1,21Massachusetts General Hospital, Neuroradiology, Boston, USA2Harvard Medical School, Radiology, Boston, USAPurpose: We have developed a helmet for trans-calvarial delivery of low-level, NIR light to the brain to assess the feasibility and effectiveness of low-level light therapy after moderate TBI.Methods: In this ongoing randomized controlled trial, we are enrolling adult subjects with in 72 hours of moderate TBI (GCS = 9–12 or GCS = 13–15 + abnormal CT). Subjects are randomized to treatment group (20 minutes of light therapy on 3 consecutive days immediately after enrollment) or control group (Sham treatment with the helmet without the light). All subjects undergo clinical assessments at baseline and after 2 weeks, 3 months, 6 months, and one year. Subjects also undergo MRI at baseline and after 2 weeks and 3 months. We obtain structural (T1, FLAIR, SWI, and Angiography), high-resolution DTI, resting-state functional MRI, cerebrovascular reactivity (CVR) imaging using hypercapnia BOLD MRI, and perfusion imaging using arterial spin labeling (ASL).Results: Of the 10 enrolled patients so far, 4 are still in the study while the rest were lost to follow-up. Light therapy did not lead to any adverse effects in any patient. The most common abnormalities were edema (3 subjects) and microhemorrhages (3 subjects). Angiography was normal in all subjects. There was abnormal CVR around left lentiform nucleus in one subject, with concordant abnormal perfusion in the same area. The Disability Rating Scale improved in one subject, while it did not change in any other subject. There was no change in the structural MRI findings from baseline to week 2 in any of the subjects.Conclusion: Our preliminary results, while the study population is still blinded, suggest that low-level light therapy is safe in patients with moderate traumatic brain injury. Assessment of the efficacy of low-level light therapy is pending further data collection and un-blinded analysis of the data.Keywords: low-level light therapy, advanced MRI imaging, diffusion tensor imaging, resting-state fMRI, hypercapnia, cerbrovascular reserveAANS03-01 NERVE TRANSFERS FOR CERVICAL SPINAL CORD INJURYRay WilsonWashington University, Neurosurgery, St. Louis, USASpinal cord injury (SCI) is a significant public health problem with approximately 12,000 new cases each year. More than 50% SCI occur in the cervical spine (i.e., tetraplegia), resulting in some loss of arm and/or hand function. Hand function is consistently rated as the most desired function for persons with tetraplegia above bowel and bladder function, sexual function, standing and pain control.Nerve transfers to treat brachial plexus and peripheral nerve injuries have gained significant momentum over last decade. The central principle of nerve transfers is the conversion of a high level injury, to a low injury, placing regenerating axons in close proximity to the target end-organ. Increased experience with nerve transfer procedures has markedly improved the functional outcomes obtained in comparison with traditional graft techniques for peripheral nerve injuries and changed the treatment algorithm in patients with nerve injuries. While tendon transfers have an established role in the management of patients with tetraplegia, only recently have nerve transfers been considered as a potential treatment option.Utilizing donor nerves above the SCI, nerve transfers can be done either acutely into the zone of the injury (upper and lower motor neuron dysfunction) or in a delayed fashion below the zone of injury. Motor neurons in the zone of injury are subject to lower motor degeneration, with a similar degeneration pattern seen in peripheral nerve injuries. Injuries in the zone of injury should be treated aggressively, to prevent progressive motor endplate fibrosis and contractures. Motor neurons below the level of injury are still in continuity with distal motor endplates, these nerves do not undergo typical Wallerian degeneration as observed in the zone with injury. This provides two distinct windows of opportunity for acute treatment (<6 months) after injury and chronic treatment (years) after injury.We have treated several tetraplegic patients with nerve transfers following a cervical spinal cord injury. Nerve transfers can reliably provide improved function below the level of injury reanimating muscles 1–3 myotomes below the level of injury, this treatment can be considered in the long-term management of cervical SCI patients.Keywords: spinal cord injury, Nerve transfer, tetraplegia, hand functionAANS03-02 PAIRED MAGNETIC AND ELECTRICAL STIMULATION FOR CERVICAL SCIHarel Noam1,2, Yung Lok1, Romero Angelica1, Santiago Tiffany1, Guber Kenneth1, Kastuar Shivani2, Nguyen Nhuquynh1, Wu Yu-Kuang1, Carmel Jason3, Spungen Ann1,2, Bauman William1,21James J. Peters VA Medical Center, Neurology, Spinal Cord Injury, Bronx, USA2Icahn School of Medicine at Mount Sinai, Neurology, Rehabilitation Medicine, New York, USA3Burke Medical Research Institute, Neurology, White Plains, USAObjective: We are using a novel combination of non-invasive cervical and transcranial stimulation to target residual motor synapses after cervical SCI.Methods: Individuals with incomplete cervical SCI, definite or probable ALS, and able-bodied volunteers participate in this ongoing pilot study. Stimulation modalities include transcranial magnetic stimulation (TMS), median nerve electrical stimulation, and a novel form of transcutaneous cervical electrical stimulation (CES). We developed CES to flexibly target either dorsal or ventral nerve roots on both sides of the lower cervical cord. Baseline testing evaluates CES safety and acute interactions between CES and TMS. Subsequent sessions test different combinations of repetitive paired or unpaired stimulation modalities. Paired stimulation is timed for TMS pulse arrival at cervical motor neurons either several milliseconds before or after electrical pulse arrival. Electrophysiological and clinical outcomes are measured for up to 90 minutes after 20 minutes of stimulation at 0.1 Hz.Results: To date, eight subjects have undergone >50 CES sessions without any safety or tolerability issues. CES induces action potentials across multiple muscles in both arms. At peri-threshold intensity, CES activates cervical motor neurons trans-synaptically via sensory afferents. At higher intensity, CES directly (non-synaptically) activates motor efferents. Preliminary results of CES-TMS interactions and effects on corticospinal transmission to hand muscles will be presented.Conclusions: Cervical electrical stimulation is non-invasive, activates multiple upper extremity muscles on both sides simultaneously, and has the ability to target novel interaction sites for convergent peripheral and corticospinal input onto cervical motor neurons. These features offer the potential to strengthen cortical control over arm and hand muscles. Support: VA RR&D B0881-W and B9212-C; and New York State SCIRB DOH01-CARTID-2015-00037.Keywords: non-invasive brain stimulation, TMS, cervical electrical stimulation, spike timing-dependent plasticityAANS03-03 REVIEW OF CELL TRANSPLANTATION FOR SPINAL CORD INJURYParr AnnUniversity of Minnesota, Neurosurgery, Minneapolis, USAThis presentation will review the current status of cellular therapeutics for spinal cord injury. Spinal cord injury currently has no effective therapies and cell transplantation therapy has been suggested to be of benefit. There are 4 major categories of cells being transplanted: schwann cells, olfactory ensheathing cells, mesenchymal stromal cells and related cells, and neural stem/progenitor cells, each with different proposed mechanisms of action. Review of the website “clinicaltrials.gov” reveals 31 studies currently active around the world. Of these listed trials, there are 4 relevant groups currently active in the United States. These four groups and their trials will be discussed. Three of these groups are utilizing allogeneic neural stem cells or their progenitors. It has been suggested that autologous cells would provide a superior source due to concerns of immune rejection. We have developed an efficient, reproducible, clinically compatible protocol for generating neural stem cells and their oligodendrocytic and neuronal progenitors from an autologous source. We believe that this type of personalized medicine represents the future in this field.Keywords: Cell Transplantation for Spinal Cord InjuryAANS04-01 ARE WE EVER GOING TO HAVE A TBI CLINICAL TRIAL THAT SUCCEEDS?Samadani UzmaHennepin County Medical Center/Univ of Minnesota, Neurosurgery, Minneapolis, USAEurotherm 3235 enrolled 387 out of a planned 600 patients, prior to early termination for identification of worse outcomes in the test group. PROTECT III enrolled 882 out of a planned 1140 patients before early termination for futility. SYNAPSE enrolled 1195 patients. ROC was terminated after enrolling 1331 of a planned 2500 patients. And these are only the latest of more than 33 failed consecutive trials demonstrating lack of efficacy for treatment of traumatic brain injury. All of these massively funded, well conducted multicenter prospective randomized trials were built on a foundation of preclinical evidence supporting efficacy. For progesterone alone, more than 200 papers demonstrated potential utility for treatment of TBI. Clearly, the failure of these trials suggests fundamental problems in our understanding of brain injury, and the limitations of translating animal research to humans. Consider this: would a hospital conduct a clinical trial of a treatment (eg anticoagulation) for “chest pain” in the emergency department, classifying patients on the basis of severity (mild/moderate/severe), and using an 8-point outcome measure (ranging from normal to disabled)? Given that chest pain in the emergency department has more than 20 common myriad causes, some of which might improve with the treatment (myocardial infarction, pulmonary embolism) and others of which might be exacerbated (hemothorax, cardiac tamponade), the idea is preposterous. Yet we attempt to treat brain injury in clinical trials without first classifying its pathophysiology. Improved multimodal classification of brain injury, based on eye tracking, serum biomarkers and imaging modalities is a prerequisite for testing and development of effective therapeutics. Given the complex and heterogeneous nature of both brain function and injury, better outcome measures that accurately capture treatment effects are also needed. Until these goals are obtained, effective therapeutics for brain injury will remain elusive.Keywords: brain injury, clinical trialsAANS04-03 CAN TECHNOLOGY SAVE US? THE BIOMECHANICS OF CONCUSSION PREVENTIONArbogast Kristy1,21Children's Hospital of Philadelphia, Center for Injury Research and Prevention, Philadelphia, USA2University of Pennsylvania School of Medicine, Pediatrics, Philadelphia, USANearly 90% of pediatric traumatic brain injuries (TBIs) are considered “mild” (mTBI and concussion), and they can lead to poor neurological outcomes and functional disabilities that adversely affect academic, behavioral and emotional aspects of quality of life, and produce deficits in multiple domains (memory, concentration, sleep, processing speed, sleep, and eye and motor function). The best strategy for mitigating these long term consequences is to prevent the injury from occurring. Development of effective prevention approaches requires consideration of two fundamental questions: what is the clinical entity that is mTBI and what is the mechanical event that leads to the injury occurring? Current research is advancing on both of these fronts including 1) the development of objective, age-specific metrics for diagnosis and monitoring of recovery and 2) understanding of injury mechanisms and injury risk curves to guide the development of preventative equipment and policies. Animal studies and human studies are both being utilized to advance the fundamental knowledge. In both of these efforts, the promise of technology is great – technology for prevention, technology for injury monitoring and technology for diagnosis. Science and evidence should guide the utilization of all types of technology. Four fundamental questions should be asked: 1) what is the technology designed to do, 2) does it measure what it intends to measure and does it do that accurately, 3) is there high quality evidence of its effectiveness and reliability, and 4) for what scenarios (i.e. age, sport, stage of recovery) does it apply? By understanding the answers to these questions, we gain insight into the role that technology can play in mitigating the long-term consequences of mTBI on children and adolescents.Keywords: prevention, technology, protective equipmentNNS 2016 Trainee Competition FinalistsT01-01 AGING WITH TRAUMATIC BRAIN INJURY:AGE-AT-INJURY EFFECTS ON BEHAVIORAL OUTCOME FOLLOWING DIFFUSE BRAIN INJURY IN RATSRowe Rachel1, Ziebell Jenna2, Harrison Jordan3, Law Matthew1, Adelson David1, Lifshitz Jonathan11Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, USA2University of Tasmania, Hobart, Australia3Arizona State University, Tempe, USADevelopment and aging are influenced by external factors with potential to impact health throughout the lifespan. While there is ongoing research of experimental pediatric and adult TBI, few studies have incorporated animal models of pediatric, adolescent, and adult TBI to understand the role of age-at-injury across the lifespan. Our aim was to follow neurological morbidities across the rodent lifespan, with respect to age-at-injury. A single cohort of rats (n = 69) was received at post-natal day (PND)10. Subgroups (n = 11–12/group) were subjected to midline fluid percussion injury at age PND17, PND35, 2 mo, 4 mo, or 6 mo or were naïve (n = 12). Rats were assessed for motor function, anxiety-like behavior, cognitive performance and depression-like behavior across their lifespan. TBI resulted in deficits on a beam walk. Brain-injured rats committed significantly more foot-faults compared to naive at 1.5 mo, 3 mo, and 5 mo. TBI resulted in anxiety-like-behaviors at 8 mo assessed by the open field task. Rats injured at 2 mo, 4 mo, and 6 mo spent significantly less time in the center of the arena compared to naïve. TBI also resulted in memory deficits assessed using novel location task. There was an overall effect on average duration of visits to the novel location at 8 mo and 9 mo and rats injured at PND17 and PND35 had significantly shorter visits to the novel location compared to naïve. Lastly, TBI did not result in depressive-like behavior at 9 mo assessed by forced swim task measured as the amount of time spent trying to escape or total number of escape attempts. These data support TBI can negatively impact neurological function during discrete stages of development and aging. The interplay of age-at-injury and aging with an injury are translationally important factors that influence behavioral performance as a quality of life metric. More complete understanding of these factors can direct rehabilitative efforts and personalized medicine for TBI survivors.Support:Science-Foundation-Arizona, Arizona-Alzheimer-ConsortiumKeywords: age-at-injury, aging, development, TBI, behaviorT01-02 THE ROLE OF MTOR IN EXERCISE DEPENDENT AXON REGENERATION THROUGH A PERIPHERAL NERVE GRAFT FOLLOWING SPINAL CORD INJURYRecker Matthew, Kulich Danielle, Austin Scarlett, Kranz Victoria, Houle JohnDrexel University College of Medicine, Philadelphia, USAMammalian target of rapamycin (mTOR) – a signaling molecule involved in protein synthesis, cell growth, and cell proliferation – is linked to neural plasticity and regeneration in the CNS. The aim of this study is twofold: to determine whether mTOR signaling is a necessary component of axonal regeneration in the injured spinal cord and to determine whether mTOR signaling is involved in the increase in regeneration that occurs with forced exercise. This is accomplished using rapamycin, which blocks mTOR signaling. Axons damaged during spinal cord transection will regenerate through a peripheral nerve graft if apposed to the lesion. Neurons whose axon regenerated through the graft can then be labeled, and subsequently quantified, by applying the retrograde fluorescent tracer True Blue to the distal end of the graft. A complete T12 spinal cord transection was performed on adult Sprague-Dawley rats and a tibial nerve graft was apposed to the injured spinal cord. The rats were divided into four groups: no exercise and no rapamycin; no exercise plus rapamycin; exercise and no rapamycin; exercise plus rapamycin. Five weeks after grafting, True Blue was applied to the distal end of the graft. One week later, the number of neurons that regenerated an axon through the graft was quantified and compared between the four groups. Among the non-exercised animals, those not given rapamycin demonstrated an almost three-fold (p < 0.05) increase in number of neurons that regenerate over those that received rapamycin injections. Among the exercised animals, the same result was found, with the rats not given rapamycin showing three times (p > 0.05) the regeneration as those given rapamycin. Our results demonstrate that blocking mTOR signaling with rapamycin significantly reduces the regenerative potential of the injured spinal cord. The pro-regenerative effects of exercise are impaired by blocking mTOR signaling, potentially pointing to the mTOR pathway as a mechanism by which exercise enhances regeneration. Supported by the Alpha Omega Alpha Carolyn Kuckein Student Research Fellowship.Keywords: SCI, peripheral nerve graft, rapamycinT01-03 EPIGENETIC, TRANSCRIPTOMIC, AND SLEEP ALTERATIONS FOLLOWING PENETRATING BALLISTIC BRAIN INJURY (PBBI)Umali Michelle1, Mountney Andrea2, Mendelev Natalia1, Ge Yongchao1, Shear Deborah2, Haghighi Fatemeh11Icahn School of Medicine at Mount Sinai, Neuroscience/Neurology, New York, USA2Walter Reed Army Institute of Research, Silver Spring, USATraumatic brain injury (TBI) affects 1.7 million Americans each year according to the Centers for Disease Control and Prevention. Long-term consequences of TBI significantly impact quality of life and one of the most commonly reported symptoms is sleep disturbance. Reduction in the quality and amount of sleep can affect a wide range of behavioral and physiological symptoms, such as impaired cognition, mood and anxiety disorders, and cardiovascular effects. In an established model of PBBI, we investigated the epigenetic and transcriptional alterations associated with sleep changes following PBBI. Rats were randomly assigned to injury cohorts, implanted with bilateral electrodes, and subjected to unilateral frontal PBBI. Continuous electroencepholographic recordings were collected from baseline through 7 days post-injury and assessed for changes in sleep-wake architecture. PBBI-injured animals showed significant deviations in sleep-wake architecture compared to baseline recordings. Animals demonstrated irregular sleep patterns with increased daytime and nighttime sleepiness, reduced REM sleep, and greater time to REM onset. The most salient effects were detected within 24 h post-injury. To examine epigenetic alterations associated with these sleep disturbances, we performed DNA methylation profiling via expanded reduced representation bisulfite sequencing on genomic DNA extracted from brain cortical tissue and leukocytes. To determine whether PBBI related methylation alterations confer changes in gene expression, we performed genome-wide gene expression profiling of whole brain tissue and blood samples using RNA sequencing on the Illumina HiSeq2500. Data showed DNA methylation and transcriptional perturbations associated with sleep disturbances following PBBI. These findings highlight the importance of the role of sleep in TBI symptomatology and may identify genetic targets for future translational studies of TBI and associated sleep disturbance.Keywords: epigenetic, methylation, gene expression, blast, sleepT01-04 EARLY NEUROVASCULAR CHANGES PRECEDE LONG-LASTING BEHAVIORAL DEFICITS AFTER JUVENILE MILD TRAUMATIC BRAIN INJURYRodriguez-Grande Beatriz, Ichkova Aleksandra, Bessy Thomas, Bertrand Sandrine, Badaut JeromeCNRS-INCIA-Universite de Bordeaux, Bordeaux, FranceTraumatic brain injury (TBI) is the leading cause of death and disability amongst children and adolescents. Moreover, mild/moderate TBI (mTBI) is frequently under-diagnosed, with patients being soon discharged from the hospital. However, growing evidence shows that behavioral impairments endure or even arise months after injury, without a full knowledge of their pathophysiology. We aimed to characterize these deficits and identify the cellular mechanisms underlying juvenile mTBI (jmTBI).We developed a new model of closed-head jmTBI on postnatal day 17 mice using an electromagnetic impactor on non-fixed head, allowing rotation, with 2 severity grades with no skull fracture: mild (1 mm impact depth, 2 m/s speed) and moderate (3 mm impact depth, 3 m/s speed). Mice were evaluated with a battery of behavioral tests followed by morpho-functional neurovascular unit assessment.Increasing severity caused a significant increase in the time to resume exploratory behavior after impact. Over 60% of mice from the moderate group and none in the mild group exhibited subdural/ intraparenchymal hemorrhages 24 h after injury. An impairment in vascular reactivity (ex vivo contraction of cortical vessels in response to thromboxane agonist applied to acute brain slices) was observed in the moderate group 24 h post-jmTBI. Both grades of jmTBI induced significant blood-brain barrier dysfunction (assessed byIgG infiltration) and significant astrogliosis (assessed by GFAP staining) in the ipsilateral hemisphere 3 days after injury. IgG infiltration and astrogliosis were also observed in the contralateral corpus callosum, suggesting that fibers were especially sensitive to rotation. As in clinical mild TBI, there was no major neurological deficit at 1 and 3 days post-jmTBI. However, our longitudinal analysis up to 1 month post-jmTBI showed significant anxiety (open field test) and a trend for cognitive decline (novel object location test) in the moderate group 1 month post-jmTBI.In summary, early significant vascular and astrocytic changes may contribute to longterm behavioral impairments. Our results strongly suggest that the neurovascular unit represents a promising target for pediatric mTBI patients.Keywords: concussion / mTBI, pediatric / juvenile, neurovascular unit, long-term damage, behaviorT01-05 DOUBLE DIFFUSION ENCODING FOR RAPID IN VIVO EVALUATION OF RAT SPINAL CORD INJURYSkinner Nathan1,2, Kurpad Shekar1, Schmit Brian3, Muftuler L. Tugan1, Budde Matthew11Medical College of Wisconsin, Neurosurgery, Milwaukee, USA2Medical College of Wisconsin, MSTP, Milwaukee, USA3Marquette University, Biomedical Engineering, Milwaukee, USANoninvasive assessment of spinal cord injury (SCI) severity and functional outcome are important challenges in acute SCI care. A promising magnetic resonance imaging (MRI) technique known as Diffusion Tensor Imaging (DTI) has been extensively studied for SCI evaluation by quantifying microstructural tissue changes following injury. However, in-vivo DTI application is complicated as its specificity to the important functional status marker of axonal integrity is reduced by confounding diffusion changes from edema. Furthermore, technical difficulties and involved post-processing requirements reduce clinical feasibility. To overcome these challenges, we developed a double diffusion encoding (DDE) MRI application to improve specificity to axonal integrity, reduce scan time, and minimize data processing. This is accomplished with a strong diffusion “filter” that attenuates edema and non-neuronal tissue signal before preferentially sampling axonal diffusion in a spectroscopic acquisition. In-vivo testing and comparison to DTI was performed in a rat contusion SCI model with severe, moderate, mild, and sham severities at the T10 vertebral level. At 48 hours post-injury, diffusion MRI data were collected at the lesion epicenter with acquisition times of 3 minutes for DDE and 65 minutes for DTI. Standard DTI analysis used manual region of interest drawing for whole-cord measurements while DDE signal analysis was automated. Regression of diffusion measurements against spinal cord compression during injury showed significance with multiple DDE parameters, including fraction of restricted diffusion (R2 = 0.67, p < 0.001), while only fractional anisotropy from DTI showed significance (R2 = 0.31, p = 0.02). Similar results were seen for regression against functional scores at 24 hours and 30 days post-injury, indicating significant association with functional status and potential prognostic value. Thus, DDE provides a sensitive measurement of injury severity and functional status while significantly reducing acquisition and analysis demands. These improvements over DTI show promise for DDE in future preclinical and clinical applications for rapid, sensitive SCI assessment.Keywords: spinal cord injury, double diffusion encoding, diffusion tensor imaging, magnetic resonance imagingT01-06 EXPOSURE TO BLAST OVERPRESSURE ALTERS CEREBROVASCULAR REACTIVITY IN RATSAbutarboush Rania1, Mullah Saad1, Lashof-Sullivan Margaret1, Mehalick Melissa1, Shaughness Michael1, Mccarron Richard1,2, Ahlers Stephe