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Traumatic brain injury (TBI) is the leading cause of disability and death in children and adults under 45, with approximately ten million new cases per year worldwide. Significant progress has been made in understanding the complex pathophysiological response to TBI; however, reducing the damage associated with the reactive oxygen species (ROS)-dependent secondary phase of the injury remains a substantial challenge. The development of an image-guided, Gd-conjugated, oxygen reactive polymer (ORP) to reduce ROS levels in damaged brain tissue is reported. ORP effectively sequesters ROS while remaining biocompatible even at elevated concentrations. ORP is retained in damaged brains of controlled cortical impact (CCI) mouse models of TBI for over 24 h when injected intravenously immediately and up to 3 h post-CCI. The polymer reduces neurodegeneration tenfold and gliosis twofold in these mouse models. ORP shows initial promise as an effective therapy for TBI and helps provide a better understanding of nanomaterial interaction with damaged brain.

Purpose To develop a new method of measuring quantitative regional cerebral blood volume (CBV) using epochs of hyperoxia as an intravenous contrast agent with T2*-weighted MRI. Materials and Methods Images were acquired from six subjects (four male, two female, mean age 29 ± 3.7 years) using a sequence combining pulsed arterial spin labeling interleaved with a gradient echo echo-planar imaging (EPI) blood oxygenation level-dependent (BOLD) sequence at 3T. The hyperoxia paradigm lasted 28 minutes consisting of 4 minutes of normoxia, two 6-minute blocks of hyperoxia separated by 6 minutes of normoxia. During the hyperoxic blocks the subjects were delivered a fractional oxygen concentration of 0.5. Results The mean CBV was calculated to be 3.77 ± 1.05 mL/100 g globally, 3.93 ± 0.90 mL/100 g in gray matter (GM), and 2.52 ± 0.78 mL/100 g in white matter (WM). The mean GM/WM ratio was thus found to be 1.56. These values are comparable to those obtained in other studies. Conclusion The hyperoxia technique for measuring CBV may be particularly useful for patient groups where an injected bolus of contrast agent is contraindicated. As more functional studies are employing epochs of inspired gases for calibration purposes, this method is easily incorporated into existing paradigms to produce a noninvasive, repeatable, easily tolerated, and quantitative measurement of regional CBV. J. Magn. Reson. Imaging 2007;26:894–899. © 2007 Wiley-Liss, Inc.

The study of brain function using MRI relies on acquisition techniques that are sensitive to different aspects of the hemodynamic response contiguous to areas of neuronal activity. For this purpose different contrasts such as arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional MRI techniques have been developed to investigate cerebral blood flow (CBF) and blood oxygenation, respectively. Analysis of such data typically proceeds by separate, linear modeling of the appropriate CBF or BOLD time courses. In this work an approach is developed that provides simultaneous inference on hemodynamic changes via a nonlinear physiological model of ASL data acquired at multiple echo times. Importantly, this includes a significant contribution by changes in the static magnetization, M, to the ASL signal. Inference is carried out in a Bayesian framework. This is able to extract, from dual-echo ASL data, probabilistic estimates of percentage changes of CBF, Rmath image, and the static magnetization, M. This approach provides increased sensitivity in inferring CBF changes and reduced contamination in inferring BOLD changes when compared with general linear model approaches on single-echo ASL data. We also consider how the static magnetization, M, might be related to changes in CBV by assuming the same mechanism for water exchange as in vascular space occupancy.