Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
References
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.
Aslan, S., & Lu, H. (2010). On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow. Magnetic Resonance Imaging, 28(7), 928–935. https://doi.org/10.1016/j.mri.2010.03.037.
Asllani, I., Borogovac, A., & Brown, T. R. (2008). Regression algorithm correcting for partial volume effects in arterial spin labeling MRI. Magnetic Resonance in Medicine, 60(6), 1362–1371. https://doi.org/10.1002/mrm.21670.
Asllani, I., Habeck, C., Borogovac, A., Brown, T. R., Brickman, A. M., & Stern, Y. (2009). Separating function from structure in perfusion imaging of the aging brain. Human Brain Mapping, 30(9), 2927–2935. https://doi.org/10.1002/hbm.20719.
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.
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.
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.
Chen, Y., Wang, D. J., & Detre, J. A. (2011). Test-retest reliability of arterial spin labeling with common labeling strategies. Journal of Magnetic Resonance Imaging, 33(4), 940–949. https://doi.org/10.1002/jmri.22345.
Chen, G., Saad, Z. S., Nath, A. R., Beauchamp, M. S., & Cox, R. W. (2012). FMRI group analysis combining effect estimates and their variances. Neuroimage, 60(1), 747–765. https://doi.org/10.1016/j.neuroimage.2011.12.060.
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.
Cox, R. W., Chen, G., Glen, D. R., Reynolds, R. C., & Taylor, P. A. (2017). FMRI clustering in AFNI: False-positive rates redux. Brain Connectivity, 7(3), 152–171. https://doi.org/10.1089/brain.2016.0475.
Dashnaw, M. L., Petraglia, A. L., & Bailes, J. E. (2012). An overview of the basic science of concussion and subconcussion: Where we are and where we are going. Neurosurgical Focus, 33(6), E5: 1–9. https://doi.org/10.3171/2012.10.FOCUS12284.
Detre, J. A., Wang, J., Wang, Z., & Rao, H. (2009). Arterial spin-labeled perfusion MRI in basic and clinical neuroscience. Current Opinion in Neurology, 22(4), 348–355. https://doi.org/10.1097/WCO.0b013e32832d9505.
Dijkhuizen, R. M. (2011). Advances in MRI-based detection of cerebrovascular changes after experimental traumatic brain injury. Translational Stroke Research, 2(4), 524–532. https://doi.org/10.1007/s12975-011-0130-0.
Donahue, M. J., Lu, H., Jones, C. K., Pekar, J. J., & van Zijl, P. C. (2006). An account of the discrepancy between MRI and PET cerebral blood flow measures. A high-field MRI investigation. NMR in Biomedicine, 19(8), 1043–1054. https://doi.org/10.1002/nbm.1075.
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.
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.
Giza, C. C., & Hovda, D. A. (2014). The new neurometabolic cascade of concussion. Neurosurgery, 75(Suppl 4), S24–S33. https://doi.org/10.1227/NEU.0000000000000505.
Goldstein, B., Toweill, D., Lai, S., Sonnenthal, K., & Kimberly, B. (1998). Uncoupling of the autonomic and cardiovascular systems in acute brain injury. The American Journal of Physiology, 275(4 Pt 2), R1287–R1292.
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.
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.
Iadecola, C., & Nedergaard, M. (2007). Glial regulation of the cerebral microvasculature. Nature Neuroscience, 10(11), 1369–1376. https://doi.org/10.1038/nn2003.
Iverson, G. L., Brooks, B. L., Collins, M. W., & Lovell, M. R. (2006). Tracking neuropsychological recovery following concussion in sport. Brain Injury, 20(3), 245–252. https://doi.org/10.1080/02699050500487910.
Jordan, B. D. (2013). The clinical spectrum of sport-related traumatic brain injury. Nature Reviews. Neurology, 9(4), 222–230. https://doi.org/10.1038/nrneurol.2013.33.
Junger, E. C., Newell, D. W., Grant, G. A., Avellino, A. M., Ghatan, S., Douville, C. M., et al. (1997). Cerebral autoregulation following minor head injury. Journal of Neurosurgery, 86(3), 425–432. https://doi.org/10.3171/jns.1997.86.3.0425.
Len, T. K., & Neary, J. P. (2011). Cerebrovascular pathophysiology following mild traumatic brain injury. Clinical Physiology and Functional Imaging, 31(2), 85–93. https://doi.org/10.1111/j.1475-097X.2010.00990.x.
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.
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.
Manley, G. T., & Maas, A. I. (2013). Traumatic brain injury: An international knowledge-based approach. JAMA, 310(5), 473–474. https://doi.org/10.1001/jama.2013.169158.
McCrea, M., & Guskiewicz, K. (2014). Evidence-based management of sport-related concussion. Progress in Neurological Surgery, 28, 112–127. https://doi.org/10.1159/000358769.
McCrea, M., Kelly, J. P., Kluge, J., Ackley, B., & Randolph, C. (1997). Standardized assessment of concussion in football players. Neurology, 48(3), 586–588.
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.
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.
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.
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.
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.
Meier, T. B., Bellgowan, P. S., Singh, R., Kuplicki, R., Polanski, D. W., & Mayer, A. R. (2015). Recovery of cerebral blood flow following sports-related concussion. JAMA Neurology, 72(5), 530–538. https://doi.org/10.1001/jamaneurol.2014.4778.
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.
Muir, J. K., Boerschel, M., & Ellis, E. F. (1992). Continuous monitoring of posttraumatic cerebral blood flow using laser-Doppler flowmetry. Journal of Neurotrauma, 9(4), 355–362. https://doi.org/10.1089/neu.1992.9.355.
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.
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.
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.
Pop, V., & Badaut, J. (2011). A neurovascular perspective for long-term changes after brain trauma. Translational Stroke Research, 2(4), 533–545. https://doi.org/10.1007/s12975-011-0126-9.
Rangel-Castilla, L., Gasco, J., Nauta, H. J., Okonkwo, D. O., & Robertson, C. S. (2008). Cerebral pressure autoregulation in traumatic brain injury. Neurosurgical Focus, 25(4), E7. https://doi.org/10.3171/FOC.2008.25.10.E7.
Riemann, B. L., & Guskiewicz, K. M. (2000). Effects of mild head injury on postural stability as measured through clinical balance testing. Journal of Athletic Training, 35(1), 19–25.
Schatz, P., & Maerlender, A. (2013). A two-factor theory for concussion assessment using ImPACT: Memory and speed. Archives of Clinical Neuropsychology, 28(8), 791–797. https://doi.org/10.1093/arclin/act077.
Slobounov, S., Gay, M., Johnson, B., & Zhang, K. (2012). Concussion in athletics: Ongoing clinical and brain imaging research controversies. Brain Imaging and Behavior, 6(2), 224–243. https://doi.org/10.1007/s11682-012-9167-2.
Strebel, S., Lam, A. M., Matta, B. F., & Newell, D. W. (1997). Impaired cerebral autoregulation after mild brain injury. Surgical Neurology, 47(2), 128–131.
Tan, C. O., Meehan 3rd, W. P., Iverson, G. L., & Taylor, J. A. (2014). Cerebrovascular regulation, exercise, and mild traumatic brain injury. Neurology, 83(18), 1665–1672. https://doi.org/10.1212/WNL.0000000000000944.
Vidorreta, M., Wang, Z., Rodriguez, I., Pastor, M. A., Detre, J. A., & Fernandez-Seara, M. A. (2013). Comparison of 2D and 3D single-shot ASL perfusion fMRI sequences. Neuroimage, 66, 662–671. https://doi.org/10.1016/j.neuroimage.2012.10.087.
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.
Wang, J., Aguirre, G. K., Kimberg, D. Y., Roc, A. C., Li, L., & Detre, J. A. (2003a). Arterial spin labeling perfusion fMRI with very low task frequency. Magnetic Resonance in Medicine, 49(5), 796–802. https://doi.org/10.1002/mrm.10437.
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.
Wang, Y., Saykin, A. J., Pfeuffer, J., Lin, C., Mosier, K. M., Shen, L., Kim, S., & Hutchins, G. D. (2011). Regional reproducibility of pulsed arterial spin labeling perfusion imaging at 3T. Neuroimage, 54(2), 1188–1195. https://doi.org/10.1016/j.neuroimage.2010.08.043.
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.
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.
Wang, Y., Nelson, L. D., LaRoche, A. A., Pfaller, A. Y., Nencka, A. S., Koch, K. M., & McCrea, M. A. (2016). Cerebral blood flow alterations in acute sport-related concussion. Journal of Neurotrauma, 33(13), 1227–1236. https://doi.org/10.1089/neu.2015.4072.
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.
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.
Yamakami, I., & McIntosh, T. K. (1989). Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres. Journal of Cerebral Blood Flow and Metabolism, 9(1), 117–124. https://doi.org/10.1038/jcbfm.1989.16.
Zhang, R., Zuckerman, J. H., Iwasaki, K., Wilson, T. E., Crandall, C. G., & Levine, B. D. (2002). Autonomic neural control of dynamic cerebral autoregulation in humans. Circulation, 106(14), 1814–1820.
Acknowledgements
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.
Funding
This study was funded as part of the National Collegiate Athletic Association–Department of Defense Grand Alliance.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare that they have no conflicts of interest.
Research involving human participants
This study was approved by MCW IRB.
Informed consent
All subjects provided written informed consent before participating in the study.
Rights and permissions
About this article
Cite this article
Wang, Y., Nencka, A.S., Meier, T.B. et al. Cerebral blood flow in acute concussion: preliminary ASL findings from the NCAA-DoD CARE consortium. Brain Imaging and Behavior 13, 1375–1385 (2019). https://doi.org/10.1007/s11682-018-9946-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11682-018-9946-5