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Christine MacDonald, PhD

Dr. Mac Donald is a Research Assistant Professor in the Department of Neurology and Director of the Advanced MRI and Blast-Related TBI research study, as well as Director of the Radiological-Pathological Correlations Study through funding from the Department of Defense and PI David Brody. Her research is focused on advanced MR methods for the evaluation of traumatic brain injury both in the civilian and military population. Diffuse axonal injury is thought to be a major contributor to cognitive dysfunction in patients following traumatic brain injury (TBI). However, it is difficult to diagnose anti-mortem, and new diagnostic methods are needed. Current clinical imaging modalities have been optimized to assess haemorrhage and ischemia but are inadequate for the direct assessment of axonal injury. Diffusion tensor imaging (DTI) has shown promise but it has yet to be fully validated for its potential role as a diagnostic tool in the evaluation of brain injury. Resting-state functional MRI (fMRI) correlation analysis has also been proposed as a useful tool in the evaluation of brain functional connectivity (fcMRI). The basis of this method is that anatomically connected regions in the brain show correlated fluctuations in the blood oxygen level dependent (BOLD) signal. Our initial studies indicate that these methods have high clinical utility and could be easily implemented as part of the standard imaging protocol for trauma. This work has given further insight into the structural and functional changes occurring following injury and added additional information not previously apparent from conventional MR imaging. In the future, these techniques may be able to better assist with diagnosis and prognosis, as well as stratify patients for therapeutic intervention.

Medical Training

Christine received her B.S. cum laude from Santa Clara University in 2002 with a major in mechanical engineering. Throughout her undergraduate education, she worked for NASA Ames research center in the Thermo-Physics facilities branch under the direction of Mark Hightower on the Enthalpy by Energy Balance (EB2) Project. She then entered a graduate program at Washington University where she obtained her M.S. and Ph.D. in Biomedical Engineering with her mentor Dr. Philip Bayly. Her thesis explored the relationship between histologically verified axonal injury and diffusion tensor imaging (DTI) following an experimental model of TBI. With this model, she investigated the correlation between white matter injury pathology as evidenced by histological markers along with electron microscopy and the corresponding DTI signal change. In 2007 she was recruited by Dr. David Brody to gain further training in traumatic brain injury research and began conducting clinical research studies evaluating DTI and resting-state fMRI signal changes in patients following brain injury. Between 2008-2010 she lived for months at a time and worked at Landstuhl Regional Medical Center (LRMC) in Landstuhl, Germany to conduct clinical research with wounded US military personnel medically evacuated from theatre in collaboration with the Departments of Trauma Surgery and Radiology at LRMC. Following a successful clinical research fellowship, she accepted a faculty position in 2010 with the Department of Neurology at Washington University School of Medicine. In 2011, she began working directly with LCDR Octavian Adam, a neurologist stationed at Kandahar Air Field, then Camp Leatherneck, in Afghanistan. Through a combined effort with CDR Dennis Rivet, a neurosurgeon also stationed at Kandahar, she began supporting all image processing and analysis of DTI data collected from MR scanners deployed to theatre.

To date, she maintains Directorships of two Department of Defense research studies in collaboration with PI David Brody. While her primary position is in St. Louis, Dr. MacDonald still travels regularly to Landstuhl, Germany as well as Milan, Italy where she supports research efforts at Ospedale Maggiore Policlinico through collaboration with Dr. Sandra Magnoni, investigating the relationship between neuroimaging and microdialysis in severely brain-injured patients.

Selected Publications

C. L. Mac Donald, A. Johnson, D. Cooper, T. Malone, J. Sorrell, J. Shimony, M. Parsons, A. Snyder, M. Raichle, R. Fang, S. Flaherty, M. Russell, D. Brody. “Cerebellar White Matter Abnormalities Following Primary Blast Injury in US Military Personnel” PLOS One (accepted January 2013)

Bennett RE, Mac Donald CL, Brody DL. “Diffusion tensor imaging detects axonal injury in a mouse model of repetitive closed-skull traumatic brain injury” Neurosci Lett. 2012 Feb 17

Mac Donald CL, Johnson AM, Cooper D, Nelson EC, Werner NJ, Shimony JS, Snyder AZ, Raichle ME, Witherow JR, Fang R, Flaherty SF, Brody DL. “Detection of blast-related traumatic brain injury in US military personnel” New England Journal of Medicine 2011 Jun 2;364(22):2091-100

Schwetye KE, Cirrito JR, Esparza TJ, Mac Donald CL, Holtzman DM, Brody DL. Traumatic brain injury reduces soluble extracellular amyloid-beta in mice: A methodologically novel combined microdialysis-controlled cortical impact study. Neurobiol Dis. 2010 Aug 1

Wrathall, J., Benzinger, T., Brody, D., .. MacDonald, C., et al. Blast-Related Brain Injury: Imaging for Clinical and Research Applications, Report of the 2008 St. Louis Workshop. Journal of Neurotrauma, Volume 26, Number 6 (June 2009)

C. L. Mac Donald, N. Schwarze, S. N. Vaishnavi, A. A. Epstein, A. Z. Snyder, M. E. Raichle, J. S. Shimony, and D. L. Brody. Verbal Memory Deficit Following Traumatic Brain Injury: Assessment using Advanced MRI Methods. Neurology 71 Oct 7, 2008

Dikranian, K., Cohen, R., Mac Donald, C., Pan, Y., Brakefield, P., Bayly, P., Parsadian, A. Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic neuronal cell death. Exp Neurol. 2008 Jun;211(2):551-60.

Mac Donald, C.L., Dikranian, K., Bayly, P.V., Holtzman, D.M., Brody, D.L. Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci. 2007 Oct 31;27(44):11869-76.

Mac Donald, C.L., Dikranian, K., Song, S.K., Bayly, P.V., Holtzman, D.M., Brody, D.L. Detection of Traumatic Axonal Injury with Diffusion Tensor Imaging in a Mouse Model of Traumatic Brain Injury. Experimental Neurology 205 (2007) 116–131.

Brody, D; Mac Donald, C; Kessons, C; Yuede, C; Parsadanian, M; Spinner, M; Schwetye, K; Holtzman, D; Bayly, P; “An Electromagnetic Controlled Cortical Impact Device for Precise, Graded Experimental Traumatic Brain Injury” Journal of Neurotrauma, Volume 24, Number 4 (2007) 657-673

Hightower, M; Mac Donald, C. Enthalpy by Energy Balance For Aerodynamic Heating Facility at NASA Ames Research Center Arc Jet Complex. Journal of Instrumentation Systems and Automation Society. Volume 420, 5 May 2002