Tsang-Wei Tu¹, Wael Ibrahim¹, Neekita Jikaria¹, William Reid¹, George Z. Papadakis¹, Dima Hammoud ¹, and Joseph A. Frank^1
1Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, United States

The present glucose measurements from the brain are still insufficient to provide the essential spatial-temporal information. This study presents longitudinal glucose chemical exchange saturation transfer (glucoCEST) MRI to noninvasively detect the glucose metabolism in a rat model of mild traumatic brain injury (mTBI) and compares to the gold-standard 2-deoxyglucose (2DG) autoradiography. The current glucoCEST results parallel with 2DG-autoradiography results showing glucose uptake largely decreased after mTBI, that persisted over time. GlucoCEST is capable of delivering better image quality, higher image resolution and sensitivity to identify the potential window for effective treatments to increase the survival of injured brain.

Kavita Singh¹, Seenu Haridas², Kailash Manda², Richa Trivedi¹, and Subash Khushu^1
1NMR, INMAS, DRDO, Delhi, Delhi, India, ²Neurobehavioral lab, INMAS, DRDO, Delhi, Delhi, India

Mild traumatic brain injury (mTBI), (70-90% of all TBI) shows consequences of anxiety-like behavioral alterations in approximately 23% of cases. The present study assesses acute anxiety-like behavior and its neurometabolic basis in a rodent model of mTBI using 1H-MRS and neurobehavioral analysis. At day5 reduced Tau/tCr levels in cortex was observed in mTBI group as compared to control. Neurobehavioral analysis showed increased anxiety-like behavior with normal cognition at day5. This study provides a putative neurometabolic basis of anxiety-like behavior in mTBI model which closely mimics human concussion injury. 

Clarisse Ildiko Mark¹, Alex Bhogal², Douglas J Cook³, and Ingrid Johnsrude^4
1Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada, ²Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ³Department of Surgery, Division of Neurosurgery, Queen’s University, Kingston, ON, Canada, ⁴Brain and Mind Institute, Department of Psychology, University of Western Ontario, London, ON, Canada

Concussion can result in disability related to covert symptoms and deficits that persist long after the initial injury. A possible explanation for these observed phenomena is sustained impairment of cerebrovascular autoregulation. Here, we complement BOLD acquisition with simultaneous cerebral blood flow (CBF) measurements during targeted hypercapnic breathing challenges in varsity athletes during the acute, early and late stages following injury. Changes in basal CBF and cerebrovascular reactivity (CVR) were observed over the first 2 weeks following injury compared to matched un-concussed athletes. These biomarkers represent promising tools to gauge the extent of brain injury and monitor recovery.

Lesley May Foley¹, Emin Fidan², Henry L Alexander², Lee Ann New², Patrick M Kochanek^2,3, T Kevin Hitchens^1,4, and Hulya Bayir^2,3
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States, ²Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States,³Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Animal Imaging Center, University of Pittsburgh, Pittsburgh, PA, United States

Recently we developed a closed-skull repeated mild (rm) TBI model in postnatal day (PND) 18 rats. We hypothesized that MRS and DTI can detect early microstructural changes of brain and metabolite changes in the hippocampus. Alterations in NAA and Ins after mTBI and rmTBI likely reflect neuro­axonal damage and glial pro­liferation, respectively. Reduced FA and increased AD in the white matter may reflect a loss of integrity a possible indication of damage to myelin/axonal membranes or demyelination. ¹H-MRS and DTI can identify subtle metabolic and structural alterations in the hippocampus which appears normal on histological analysis and conventional MR images.

Ivan Kirov^1,2, Matthew S. Davitz^1,2, Assaf Tal³, James S. Babb^1,2, Robert I Grossman^1,2, Yvonne W Lui^1,4, and Oded Gonen^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, New York University School of Medicine, New York, NY, United States, ³Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, ⁴Bernard and Irene Schwartz Center for Biomedical Imaging, New York, NY, United States

Since axonal injury is a primary outcome of traumatic brain injury, our goal was to characterize its regional distribution from a metabolic perspective. We set out to identify regions prone to disproportionate injury, hence, candidate targets in potential clinical applications of proton MR spectroscopy (¹H-MRS). We found that metabolic axonal injury is diffusely distributed among commonly injured tracts, but multivoxel ¹H-MRS may lack sensitivity for its detection on a regional basis. These results motivate the use of ¹H-MRS approaches with higher sensitivity, such as global averaging, or large "single voxels" in areas of white matter, irrespective of placement location.

Ivan Kirov^1,2, Matthew S. Davitz^1,2, Assaf Tal³, James S. Babb^1,2, Robert I Grossman^1,2, Yvonne W Lui^1,4, and Oded Gonen^1,2
1Center for Advanced Imaging Innovation and Research (CAI2R), New York University School of Medicine, New York, NY, United States, ²Bernard and Irene Schwartz Center for Biomedical Imaging, New York University School of Medicine, New York, NY, United States, ³Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, ⁴Bernard and Irene Schwartz Center for Biomedical Imaging, New York, NY, United States

Basic science studies have posited that the mechanical force associated with a traumatic brain injury disproportionately affects the interface between the brain’s gray and white matter (GM, WM); however, this has not yet been demonstrated in vivo. In this study we used multivoxel proton MR spectroscopy to compare metabolite levels of patients and controls in voxels with different GM and WM partial volume, on a continuum from “pure” GM to “pure” WM. The results indicate that the largest amount of damage lies within voxels representative of interface tissue.

Samuel Barnes¹, Brenda Bartnik-Olson¹, Barbara Holshouser¹, and Stephen Ashwal^2
1Radiology, Loma Linda University, Loma Linda, CA, United States, ²Pediatric Neurology, Loma Linda University, Loma Linda, CA, United States

Several studies have shown regions of hypoperfusion in symptomatic patients in the chronic phase of mild TBI. In this study we used whole-brain spatial mapping and a voxel-wise statistical approach to investigate the extent and anatomical distribution of cerebral hypoperfusion in chronic symptomatic pediatric concussion subjects. Our findings identified multiple areas of reduced CBF, incorporating both the cerebral cortex and subcortical regions. Compared to our previous results using region of interest analysis, we detected a greater number of areas of hypoperfusion suggesting that the use of whole-brain spatial mapping and voxel-wise analysis improved detection of CBF abnormalities. We speculate that hypoperfusion in these regions may be implicated in cognitive deficits in these subjects.

Caroline Guglielmetti^1,2, Austin Chou¹, Annemie Van der Linden², Susanna Rosi¹, and Myriam M Chaumeil^1
1University of California San Francisco, San Francisco, CA, United States, ²University of Antwerp, Antwerp, Belgium

This study demonstrates that ¹³C MRS of hyperpolarized pyruvate can be used to detect increased lactate production from pro-inflammatory macrophages in a preclinical model of Traumatic Brain Injury, hence providing a novel tool for in vivo detection of neuroinflammation.

Gregory Simchick^1,2, Martha Betancur^3,4, Lohitash Karumbaiah^3,4, and Qun Zhao^1,2
1Physics, University of Georgia, Athens, GA, United States, ²Bio-Imaging Research Center, Athens, GA, United States, ³Animal and Dairy Science, University of Georgia, Athens, GA, United States, ⁴Regenerative Bioscience Center, Athens, GA, United States

Due to both short-term and long-term effects, traumatic brain injuries (TBIs) have been a growing topic of interest over the last several years; therefore, research related to the development of new methods to treat and monitor these types of injuries has also gained interest. Presented here is a non-invasive method using magnetic resonance (MR) phase gradient mapping (PGM) to characterize TBI treatment in relation to regional cerebral blood flow (rCBF) in angiogenesis and tissue loss. In a rat moderate-to-severe TBI model, increases between 16-29% in rCBF were seen in the treatment group twenty weeks post TBI, while decreases between 9-27% in rCBF were seen in the non-treatment group.

Kavita Singh¹, Richa Trivedi¹, Maria M D'souza², and Subash Khushu^1
1NMR, INMAS, DRDO, Delhi, Delhi, India, ²Molecular imaging, INMAS, DRDO, Delhi, Delhi, India

Hippocampal atrophy is seen in traumatic brain injury even when it is remote to the site of injury. Present study assess acute microstructural and inflammatory changes affecting hippocampal damage using diffusion tensor imaging and Iba-1, GFAP immunostaining at D0, 4H, D1 and D5 in rodent model of moderate TBI. Significantly reduced mean diffusivity and radial diffusivity alongwith increased fractional anisotropy at 4H, D1 and D5. Iba-1+ cells significantly increased at D1 and D5 with GFAP+ cells peaking at D5. Study provides temporal evaluation of diffusion changes which may be due to underlying inflammatory changes.