Lauri Juhani Lehto¹, Alejandra Sierra¹, Asla Pitkänen^1,2, and Olli Gröhn^1
1Neurobiology, University of Eastern Finland, Kuopio, Eastern Finland, Finland, ²Neurology, Kuopio University Hospital, Kuopio, Eastern Finland, Finland

Magnetization transfer (MT) weighted imaging and diffusion tensor imaging (DTI) were performed in rats with experimental traumatic brain injury (TBI) at six months post-TBI. Results were validated by analyzing histological sections. MT ratio (MTR) followed consistently the severity of myelin loss whereas fractional anisotropy gave seemingly mixed results. In line with histology, MTR revealed cortical and white matter damage ipsilateral to injury, particularly in the myelinated thalamocortical pathway. MTR appears be a more sensitive tool than DTI for assessing changes in the myelin integrity after TBI.

Wanyong Shin¹, Blessy Mathew¹, Banks Sarah², Mark J Lowe¹, Michael Phillips¹, Modic T Michael³, and Charles Bernick^2
1Imaging Institute, Cleveland Clinic Foundatoin, Cleveland, Ohio, United States, ²Lou Ruvo Center for Brain Health, Cleveland Clinic Foundation, Las Vegas, Nervada, United States, ³Neurological Institute, Cleveland Clinic Founcatoin, Cleveland, Ohio, United States

The Professional Fighters’ Brain Health Study (PFBHS) is a longitudinal cohort study that is following active professional fighters annually over 4 years. From the initial data including 74 boxers and 84 mixed martial art (MMA) fighters, ROI based DTI results have been published that show that the number of times a fighter has been knocked out (NKO) predicts DTI changes mainly in posterior corpus callosum. [1]. In this study, we included all the baseline visits of the male fighters in PFBHS (N=305) and performed a voxelwise DTI group analysis using non-linear registration method to investigate if fight exposure history predicts DTI measures of white matter integrity in whole brain. We found that NKO predicts DTI changes mainly in corpus callosum and splenium of corpus callosum after controlling age and education effects.

Justin Alexander Long¹, Lora Talley Watts^1,2, Wei Li¹, Qiang Shen¹, Shiliang Huang¹, and Timothy Q. Duong^1,3
1Research Imaging Institute, UTHSCSA, San Antonio, Texas, United States, ²Department of Cellular and Structural Biology, UTHSCSA, San Antonio, Texas, United States, ³Department of Ophthamology and Radiology, UTHSCSA, San Antonio, Texas, United States

We previously reported T2 and diffusion following mild TBI in a rat model. However, it is unclear how the widespread hemodynamic disruption affects perilesional tissue outcome. This study evaluated the effects of CBF and cerebrovascular reactivity deficits on diffusion, T2 and fractional anisotropy by analyzing tissue in the impact area and its surrounding. Multimodal MRI measurements were made longitudinally from 1 hour and up to 14 days post TBI. Comparisons were also made with behavioral assessments.

Lora Talley Watts¹, Justin Alexander Long¹, Qiang Shen¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Methylene blue (MB) has energy-enhancing and antioxidant properties. We previously showed that MB given one-hour post TBI had neuroprotective effects in rats. This study investigated the neuroprotective effect of delayed MB treatment (24 hrs) as measured by lesion volume and functional outcome. Comparisons were made with vehicle and acute (1 hr) treatment. We found that delayed MB treatment minimized lesion volume and functional deficits compared to vehicle-treated animals. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored.

Wenzhu Wang¹, Dong-Hoon Lee², Hong Zhang², Jinyuan Zhou², and Jian Wang^1
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States, ²Department of Radiology, Johns Hopkins University, Baltimore, Maryland, United States

We applied several MRI modalities, T2-weighted, T2*-weighted, T2, isotropic apparent diffusion coefficient (ADC), arterial spin labeling-based cerebral blood flow (CBF), and amide proton transfer (APT)-weighted (APTw) sequences to several rats with traumatic brain injury (TBI) that were treated with pinocembrin (5 or 10 mg/kg). Our results show that flavonoid pinocembrin is neuroprotective in the TBI model in rats. The multiple MRI (particularly APTw) could have potential clinical applications as a unique, sensitive biomarker for identification and assessment of neuroinflammation in the TBI model.

Tsang-Wei Tu¹, Rashida Williams², Neekita Jikaria³, L. Christine Turtzo³, and Joseph Frank^2
1Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD - Maryland, United States, ²Radiology and Imaging Sciences, National Institutes of Health, Maryland, United States, ³National Institutes of Health, Maryland, United States

Tramatic brain injury(TBI) results in an instant increase in cerebral metabolic rates to fulfill the cellular energy requirements to maintain transmembrane potential. Glucose is the main energy souce of brain but after traumatic insult levels decrease dramatically. The energy substrate supply and consumption is crucial for the survival of traumatized brain tissue after TBI. In this study, we conducted the asymmetry analysis of non-chemical exchange saturation transfer (CEST) MRI experiments on 9.4T scaner to study the glucose distribution after mild TBI. Our results indicate that the CEST asymmetry analysis could be a sensitive marker to measure glucose distribution non-invasively after TBI.

Alexander Peter Lin^1,2, Marc Muehlmann^2,3, Sai Merugumala¹, Huijun Vicky Liao¹, Tyler Starr¹, David Kaufmann³, Michael Mayinger^2,3, Denise Steffinger³, Barbara Fisch³, Susanne Karch³, Florian Heinen³, Birgit Ertl-Wagner³, Maximilian Reiser³, Robert A. Stern⁴, Ross Zafonte⁵, Martha Shenton^2,6, and Inga K Koerte^2,3
1Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States, ²Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Boston, MA, United States, ³Ludwig-Maximilian-University, Munich, Germany, ⁴Boston University Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA, United States, ⁵Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Boston, MA, United States, ⁶VA Boston Healthcare System, Boston, MA, United States

Repeatedly heading the ball may place soccer players at high risk for repetitive subconcussive head impacts (RSHI). This study evaluates the long-term effects of RSHI on neurochemistry in former professional soccer players in comparison to gender-matched former non-contact sport athletes. In the soccer players, a significant increase was observed in both, choline, a membrane marker, and myo-inositol, a marker of glial activation, compared to control athletes. Myo-inositol and glutathione were significantly correlated with lifetime estimate of RSHI. Results suggest an association between RSHI in soccer players and MRS markers of neuroinflammation and the consequences of subconcussive head impacts.

Bhanu Prakash KN¹, Sanjay Kumar Verma¹, Yevgen Marchenko¹, Suresh Anand Sadananthan², Yang Ming³, Sein Lwin³, Charmaine Childs⁴, Yeo Tseng Tsai³, Lu Jia⁵, Andrew Maudsley⁶, and Sendhil Velan S^1,2
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, A*STAR, Singapore, ²Singapore Institute for Clinical Sciences, A*STAR, Singapore,³Division of Neurosurgery, National University Health Sciences, Singapore, ⁴Centre for Health and Social Care Research, Faculty of Health and Wellbeing, Sheffield Hallam University, United Kingdom, ⁵Combat Protection and Performance Lab, Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, ⁶Miller School of Medicine, University of Miami, Miami, Florida, United States

Measurement of whole brain temperature is of relevance in traumatic brain injuries including survival outcome of patients. Whole brain 3D MRSI approach with interleaved water acquisition and larger spatial coverage is highly desirable for assessing changes in cerebral metabolism and investigation of hot spots. In this study, we have implemented 3D EPSI on a clinical Siemens 3T Tim Trio scanner to evaluate the brain temperature changes in control and mild traumatic brain injuries (TBI). Brain temperature across the brain was investigated in Control and mild TBI subjects. Reduction in acquisition time along with high spatial resolution allows translation of this technology to a clinical setting.

Roman Fleysher¹, Susan Sotardi¹, Michael Stockman¹, Namhee Kim¹, David Gutman¹, Jeremy Smith¹, Craig A. Branch¹, and Michael L. Lipton^1
1Gruss Magnetic Resonance Research Center, Department of Radiology, Albert Einstein College of Medicine, Bronx, New York, United States

Linking evidence of structural damage to functional consequences in brain disorders remains essential for advancing the diagnostic utility of DTI. Many successful investigations into their role employed diffusion measures of structural white matter integrity and BOLD fMRI measures of functional connectivity. This approach is inherently limited by the essentially separate and parallel nature of its structural and functional methodologies. We propose a method enhancing ability to establish structural-to-functional consequences link by eliminating the need for predefined ROIs and by directly coupling functional to structural arms of the analysis. We illustrate this method in a cohort of mTBI patients.

Xiang He¹, Serter Gumus², Hoi-Chung Leung³, Parsey Ramin⁴, Mark Schweitzer¹, Marion Hughes², Lea Alhilali², and Saeed Fakhran^2
1Department of Radiology, Stony Brook University, Stony Brook, New York, United States, ²Department of Radiology, University of Pittsburgh Medical Center, pennsylvania, United States, ³Department of Psychology, Stony Brook University, New York, United States, ⁴Department of Psychiatry, Stony Brook University, New York, United States

Abnormal cerebral oxidative metabolism (CMRO2) plays a significant role to the pathophysiology of concussion. This study constitutes one of the first MRI-based approaches to investigate the regional cerebral oxidative metabolism and oxidative stress in post-concussion patients. By combining MR-qBOLD and pCASL techniques, depressed gray matter CMRO2 and CBF has been observed in concussion patient, consistent with the findings using FDG-PET on glucose metabolism. Hence, the proposed technique provides a potential tool to non-invasively monitor the brain metabolic response in mTBI without radiation, which is especially important to study sports-related concussion in adolescent and young patients.