Magnetic Resonance Imaging: Application to the Investigation of Experimental Traumatic Brain Injury in Rats
Patrick M. Kochanek, P.I.

Through a collaboration with Dr. Chien Ho and his investigative team at the Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, we are using conventional and novel magnetic resonance imaging methods to facilitate investigation in our study of experimental traumatic brain injury in rats. A variety of magnetic resonance imaging techniques are being applied to our brain trauma models including: T1- and T2-weighted imaging, perfusion imaging using the arterial spin labeling method, assessment of cerebral swelling using maps of T1obs, and assessment of calcium accumulation using activity-induced-manganese-dependent (AIM) contrast, among other techniques. The non-invasive nature of magnetic resonance imaging and the menu of techniques that it affords provide the unique opportunity to perform longitudinal studies of multiple parameters. This collaboration has resulted in several novel studies including the first report of serial maps of cerebral blood flow after traumatic brain injury in rat, the first report of the assessment of CO2 reactivity after experimental brain injury in rats, and the first application of magnetic resonance imaging to a model of traumatic brain injury in immature rats (see Figure below). This method has also allowed us to test the effect of novel pharmacologic agents in our injury models in a unique variety of ways (Figure 2).

Figure 1. Perfusion percent change maps from immature rats (post-natal day 17) studied by the non-invasive arterial spin labeling method at either ~5 hours or ~29 hours after focal cerebral contusion produced by controlled cortical impact. This exciting method affords the opportunity for serial assessment of cerebral blood flow in tiny (~35 gram) immature rats after traumatic brain injury.

Figure 2. Maps of cerebral blood flow in normal adult rats injected into hippocampus with varying doses of the adenosine analog 2-chloroandnosine. This powerful, dose-dependent cerebral vasodilator produces marked increases in cerebral blood flow that are readily defined by this novel perfusion magnetic resonance imaging method.

Selected publications resulting from this work include:

1. Forbes ML, Hendrich KS, Kochanek PM, et al: Assessment of Cerebral Blood Flow and CO2 Reactivity After Controlled Cortical Impact By Perfusion Magnetic Resonance Imaging Using Arterial Spin Labeling in Rats. J Cereb Blood Flow Metab 17:865-874, 1997.

2. Hendrich K, Schiding J, Kochanek P, et al: Early Perfusion After Controlled Cortical Impact in Rats: Quantification by Arterial Spin-Labeled MRI and the Influence of Spin-Lattice Relaxation Time Heterogeneity. Magn Reson Med 42:673-681, 1999.

3. Zhang W, Kochanek P, Styren S, et al:. Differentiation Between Tissue Edema and Infarct after Traumatic Brain Injury in Rats Using T2 and Perfusion MRI. Proc Soc Magnetic Resonance Imaging, Second Annual Meeting, San Francisco, California, p 1384, 1994.

4. Hendrich K, Schiding J, Kochanek P, et al:: Sequential MRI Assessment of Cerebral Blood Flow and Blood-Brain Barrier Permeability Early After Traumatic Brain Injury in Rats. Proc Internat Soc Magn Reson Med Fifth Scientific Meeting and Exhibition, Vancouver, B.C., Canada, April 12-18, p 620, 1997.

5. Hendrich K, Schiding J, Kochanek P, et al: Sequential MRI Assessment of Cerebral Blood Flow and Blood-Brain Barrier Permeability Early After Traumatic Brain Injury in Rats. J Cereb Blood Flow Metab 17: S76, 1997.

6. Kochanek PM, Hendrich KS, Dixon CE, et al: Perfusion Magnetic Resonance Imaging at One Year After Controlled Cortical Impact in Rats. J Neurotrauma 14:783, 1997.

7. Adelson PD, Hendrich K, Robichaud P, et al: Magnetic Resonance Imaging (MRI) Assessment of Traumatic Brain Injury (TBI) in Immature Rats: A Preliminary Report. J Neurotrauma 15:853, 1998.

8. Hendrich KS, Kochanek PM, Williams DS, et al: Effects of Anesthetic Agents on Cerebral Perfusion in Rats Studied by Arterial Spin-Labeled MRI. Proc Intl Soc Magn Reson Med 7:874, 1999.

9. Robertson CL, Hendrich KS, Kochanek PM, et al: Assessment of 2-Chloroadenosine Treatment after Experimental Traumatic Brain Injury in the Rat using Arterial Spin-Labeled MRI. Proc Intl Soc Magn Reson Med 7:896, 1999.

10. Hendrich KS, Robertson CL, Kochanek PM, et al:: Effect of 2-chloroadenosine after experimental traumatic brain injury in rats. J Neurotrauma 16:974, 1999.

11. Hendrich KS, Kochanek PM, Melick JA, et al:: Characterization of cerebral blood flow during anesthesia with fentanyl, isoflurane, or pentobarbital in normal rats. Int Soc Magn Reson Med (in press).

Collaborators (alphabetical order):

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