Cerebral blood flow in acute concussion: preliminary ASL findings from the NCAA-DoD CARE consortium
Sport-related concussion (SRC) has become a major health problem, affecting millions of athletes each year. Despite the increasing occurrence and prevalence of SRC, its underlying mechanism and recovery course have yet to be fully elucidated. The National Collegiate Athletic Association–Department of Defense Grand Alliance: Concussion Assessment, Research and Education (CARE) Consortium is a large-scale, multisite study of the natural history of concussion across multiple sports. The Advanced Research Core (ARC) of CARE is focused on the advanced biomarker assessment of a reduced subject cohort. This paper reports findings from two ARC sites to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared relative CBF maps assessed in 24 concussed contact sport athletes obtained at 24–48 h after injury to those of a control group of 24 matched contact sport players. Significantly less CBF was detected in several brain regions in concussed athletes, while clinical assessments also indicated clinical symptom and performance impairments in SRC patients. Correlations were found between decreased CBF in acute SRC and clinical assessments, including Balance Error Scoring System total score and Immediate Post-Concussion Assessment and Cognitive Test memory composite and impulse control composite scores, as well as days from injury to asymptomatic. Although using different ASL MRI sequences, our preliminary results from two sites are consistent with previous reports and suggest that advanced ASL MRI methods might be useful for detecting acute neurobiological changes in acute SRC.
KeywordsCerebral blood flow Concussion Traumatic brain injury Arterial spin labeling Contact sport MRI
This publication was made possible, in part, with support from the Grand Alliance Concussion Assessment, Research, and Education (CARE) Consortium, funded, in part by the National Collegiate Athletic Association (NCAA) and the Department of Defense (DOD). The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program under Award NO W81XWH-14-2-0151. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense (DHP funds). The authors would also like to thank Jody Harland, Janetta Matesan, Larry Riggen (Indiana University); Ashley Rettmann (University of Michigan); Melissa Koschnitzke (Medical College of Wisconsin); Michael Jarrett, Vibeke Brinck and Bianca Byrne (Quesgen); Thomas Dompier, Melissa Niceley Baker, and Sara Dalton (Datalys Center for Sports Injury Research and Prevention); and the research and medical staff at each of the participating sites.
This study was funded as part of the National Collegiate Athletic Association–Department of Defense Grand Alliance.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
Research involving human participants
This study was approved by MCW IRB.
All subjects provided written informed consent before participating in the study.
- Alsop, D. C., Detre, J. A., Golay, X., Gunther, M., Hendrikse, J., Hernandez-Garcia, L., et al. (2015). Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magnetic Resonance in Medicine, 73(1), 102–116. https://doi.org/10.1002/mrm.25197.CrossRefPubMedGoogle Scholar
- Audenaert, K., Jansen, H. M., Otte, A., Peremans, K., Vervaet, M., Crombez, R., de Ridder, L., van Heeringen, C., Thirot, J., Dierckx, R., & Korf, J. (2003). Imaging of mild traumatic brain injury using 57Co and 99mTc HMPAO SPECT as compared to other diagnostic procedures. Medical Science Monitor, 9(10), MT112–MT117.PubMedGoogle Scholar
- Barlow, K. M., Marcil, L. D., Dewey, D., Carlson, H. L., MacMaster, F. P., Brooks, B. L., & Lebel, R. M. (2017). Cerebral perfusion changes in post-concussion syndrome: A prospective controlled cohort study. Journal of Neurotrauma, 34(5), 996–1004. https://doi.org/10.1089/neu.2016.4634.CrossRefPubMedPubMedCentralGoogle Scholar
- Centers for Disease, C., & Prevention. (2007). Nonfatal traumatic brain injuries from sports and recreation activities--United States, 2001-2005. MMWR. Morbidity and Mortality Weekly Report, 56(29), 733–737.Google Scholar
- Chow, H. M., Horovitz, S. G., Carr, W. S., Picchioni, D., Coddington, N., Fukunaga, M., Xu, Y., Balkin, T. J., Duyn, J. H., & Braun, A. R. (2013). Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness. Proceedings of the National Academy of Sciences of the United States of America, 110(25), 10300–10305. https://doi.org/10.1073/pnas.1217691110.CrossRefPubMedPubMedCentralGoogle Scholar
- Gardner, A. J., Tan, C. O., Ainslie, P. N., van Donkelaar, P., Stanwell, P., Levi, C. R., & Iverson, G. L. (2015). Cerebrovascular reactivity assessed by transcranial Doppler ultrasound in sport-related concussion: A systematic review. British Journal of Sports Medicine, 49(16), 1050–1055. https://doi.org/10.1136/bjsports-2014-093901.CrossRefPubMedGoogle Scholar
- Ginsberg, M. D., Zhao, W., Alonso, O. F., Loor-Estades, J. Y., Dietrich, W. D., & Busto, R. (1997). Uncoupling of local cerebral glucose metabolism and blood flow after acute fluid-percussion injury in rats. Am J Physiol, 272(6 Pt 2), H2859–2868. https://doi.org/10.1152/ajpheart.1997.272.6.H2859.
- Gowda, N. K., Agrawal, D., Bal, C., Chandrashekar, N., Tripati, M., Bandopadhyaya, G. P., Malhotra, A., & Mahapatra, A. K. (2006). Technetium Tc-99m ethyl cysteinate dimer brain single-photon emission CT in mild traumatic brain injury: A prospective study. AJNR. American Journal of Neuroradiology, 27(2), 447–451.PubMedGoogle Scholar
- Harmon, K. G., Drezner, J. A., Gammons, M., Guskiewicz, K. M., Halstead, M., Herring, S. A., Kutcher, J. S., Pana, A., Putukian, M., & Roberts, W. O. (2013). American medical Society for Sports Medicine position statement: Concussion in sport. British Journal of Sports Medicine, 47(1), 15–26. https://doi.org/10.1136/bjsports-2012-091941.CrossRefPubMedGoogle Scholar
- Levine, B., Kovacevic, N., Nica, E. I., Cheung, G., Gao, F., Schwartz, M. L., & Black, S. E. (2008). The Toronto traumatic brain injury study: Injury severity and quantified MRI. Neurology, 70(10), 771–778. https://doi.org/10.1212/01.wnl.0000304108.32283.aa.CrossRefPubMedGoogle Scholar
- Liu, W., Wang, B., Wolfowitz, R., Yeh, P. H., Nathan, D. E., Graner, J., Tang, H., Pan, H., Harper, J., Pham, D., Oakes, T. R., French, L. M., & Riedy, G. (2013). Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI. NMR in Biomedicine, 26(6), 651–663. https://doi.org/10.1002/nbm.2910.PubMedCrossRefGoogle Scholar
- McCrea, M., Guskiewicz, K. M., Marshall, S. W., Barr, W., Randolph, C., Cantu, R. C., Onate, J. A., Yang, J., & Kelly, J. P. (2003). Acute effects and recovery time following concussion in collegiate football players: The NCAA concussion study. JAMA, 290(19), 2556–2563. https://doi.org/10.1001/jama.290.19.2556.CrossRefPubMedGoogle Scholar
- McCrea, M., Prichep, L., Powell, M. R., Chabot, R., & Barr, W. B. (2010). Acute effects and recovery after sport-related concussion: A neurocognitive and quantitative brain electrical activity study. The Journal of Head Trauma Rehabilitation, 25(4), 283–292. https://doi.org/10.1097/HTR.0b013e3181e67923.CrossRefPubMedGoogle Scholar
- McCrea, M., Guskiewicz, K., Randolph, C., Barr, W. B., Hammeke, T. A., Marshall, S. W., Powell, M. R., Woo Ahn, K., Wang, Y., & Kelly, J. P. (2013). Incidence, clinical course, and predictors of prolonged recovery time following sport-related concussion in high school and college athletes. Journal of the International Neuropsychological Society, 19(1), 22–33. https://doi.org/10.1017/S1355617712000872.CrossRefPubMedGoogle Scholar
- McCrory, P., Meeuwisse, W. H., Aubry, M., Cantu, B., Dvorak, J., Echemendia, R. J., et al. (2013). Consensus statement on concussion in sport: The 4th international conference on concussion in sport held in Zurich, November 2012. British Journal of Sports Medicine, 47(5), 250–258. https://doi.org/10.1136/bjsports-2013-092313.CrossRefPubMedGoogle Scholar
- McGoron, A. J., Capille, M., Georgiou, M. F., Sanchez, P., Solano, J., Gonzalez-Brito, M., & Kuluz, J. W. (2008). Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping. BMC Medical Imaging, 8, 4. https://doi.org/10.1186/1471-2342-8-4.CrossRefPubMedPubMedCentralGoogle Scholar
- Metting, Z., Spikman, J. M., Rodiger, L. A., & van der Naalt, J. (2014). Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury: Acute versus chronic disturbances? Brain and Cognition, 86(0), 24–31, https://doi.org/10.1016/j.bandc.2014.01.012.
- Nencka, A. S., Meier, T. B., Wang, Y., Muftuler, L. T., Wu, Y. C., Saykin, A. J., Harezlak, J., Brooks, M. A., Giza, C. C., Difiori, J., Guskiewicz, K. M., Mihalik, J. P., LaConte, S. M., Duma, S. M., Broglio, S., McAllister, T., McCrea, M. A., & Koch, K. M. (2017). Stability of MRI metrics in the advanced research core of the NCAA-DoD concussion assessment, research and education (CARE) consortium. Brain Imaging and Behavior, 12, 1121–1140. https://doi.org/10.1007/s11682-017-9775-y.CrossRefGoogle Scholar
- Okonkwo, O. C., Xu, G., Oh, J. M., Dowling, N. M., Carlsson, C. M., Gallagher, C. L., Birdsill, A. C., Palotti, M., Wharton, W., Hermann, B. P., LaRue, A., Bendlin, B. B., Rowley, H. A., Asthana, S., Sager, M. A., & Johnson, S. C. (2014). Cerebral blood flow is diminished in asymptomatic middle-aged adults with maternal history of Alzheimer's disease. Cerebral Cortex, 24(4), 978–988. https://doi.org/10.1093/cercor/bhs381.CrossRefPubMedGoogle Scholar
- Pasco, A., Lemaire, L., Franconi, F., Lefur, Y., Noury, F., Saint-Andre, J. P., et al. (2007). Perfusional deficit and the dynamics of cerebral edemas in experimental traumatic brain injury using perfusion and diffusion-weighted magnetic resonance imaging. Journal of Neurotrauma, 24(8), 1321–1330. https://doi.org/10.1089/neu.2006.0136.CrossRefPubMedPubMedCentralGoogle Scholar
- Wang, J., Alsop, D. C., Li, L., Listerud, J., Gonzalez-At, J. B., Schnall, M. D., & Detre, J. A. (2002). Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5 and 4.0 Tesla. Magnetic Resonance in Medicine, 48(2), 242–254. https://doi.org/10.1002/mrm.10211.CrossRefPubMedGoogle Scholar
- Wang, J., Licht, D. J., Jahng, G. H., Liu, C. S., Rubin, J. T., Haselgrove, J., Zimmerman, R. A., & Detre, J. A. (2003b). Pediatric perfusion imaging using pulsed arterial spin labeling. Journal of Magnetic Resonance Imaging, 18(4), 404–413. https://doi.org/10.1002/jmri.10372.CrossRefPubMedGoogle Scholar
- Wang, D. J., Alger, J. R., Qiao, J. X., Hao, Q., Hou, S., Fiaz, R., et al. (2012). The value of arterial spin-labeled perfusion imaging in acute ischemic stroke: Comparison with dynamic susceptibility contrast-enhanced MRI. Stroke, 43(4), 1018–1024. https://doi.org/10.1161/STROKEAHA.111.631929.CrossRefPubMedPubMedCentralGoogle Scholar
- Wang, Y., West, J. D., Bailey, J. N., Westfall, D. R., Xiao, H., Arnold, T. W., Kersey, P. A., Saykin, A. J., & McDonald, B. C. (2015). Decreased cerebral blood flow in chronic pediatric mild TBI: An MRI perfusion study. Developmental Neuropsychology, 40(1), 40–44. https://doi.org/10.1080/87565641.2014.979927.CrossRefPubMedPubMedCentralGoogle Scholar
- Wu, W. C., Fernandez-Seara, M., Detre, J. A., Wehrli, F. W., & Wang, J. (2007). A theoretical and experimental investigation of the tagging efficiency of pseudocontinuous arterial spin labeling. Magnetic Resonance in Medicine, 58(5), 1020–1027. https://doi.org/10.1002/mrm.21403.CrossRefPubMedGoogle Scholar
- Wu, W. C., Lin, S. C., Wang, D. J., Chen, K. L., & Li, Y. D. (2013). Measurement of cerebral white matter perfusion using pseudocontinuous arterial spin labeling 3T magnetic resonance imaging - an experimental and theoretical investigation of feasibility. PLoS One, 8(12), UNSP e82679. https://doi.org/10.1371/journal.pone.0082679.CrossRefGoogle Scholar