Early beneficial effect of matrix metalloproteinase inhibition on blood-brain barrier permeability as measured by magnetic resonance imaging countered by impaired long-term recovery after stroke in rat brain.

Proteolytic disruption of the extracellular matrix with opening of the blood-brain barrier (BBB) because of matrix metalloproteinases (MMPs) occurs in reperfusion injury after stroke. Matrix metalloproteinase inhibition blocks the early disruption of the BBB, but the long-term consequences of short-term MMP inhibition are not known. Recently, a method to quantify BBB permeability by graphical methods was described, which provides a way to study both early disruption of the BBB and long-term effects on recovery in the same animal. We used a broad-spectrum MMP inhibitor, BB1101, to determine both the usefulness of the Magnetic resonance imaging (MRI) method for treatment studies and the long-term effects on recovery. Magnetic resonance imaging studies were performed in control (N=6) and drug-treated (N=8) groups on a dedicated 4.7-T MRI scanner. Adult Wistar-Kyoto underwent a 2-h middle cerebral artery occlusion followed by an MRI study after 3 h of reperfusion, which consisted of T2- and diffusion-weighted techniques. Additionally, a rapid T1 mapping protocol was also implemented to acquire one pre-gadolinium-diethylenetriaminepentaacetic acid baseline data set followed by postinjection data sets at 3-min intervals for 45 mins. The same animal was imaged again at 48 h for lesion size estimation. Data was postprocessed pixel-wise to generate apparent diffusion coefficient and permeability coefficient maps. Treatment with BB-1101 significantly reduced BBB permeability at 3 h, but failed to reduce lesion size at 48 h. Behavioral studies showed impairment in recovery in treated rats. Magnetic resonance imaging allowed for the monitoring of multiple parameters in the same animal. Our studies showed that BB-1101 was an excellent inhibitor of the BBB damage. However, results show that BB-1101 may be responsible for significant deterioration in neurologic status of treated animals. Although these preliminary results suggest that BB-1101 is useful in reducing early BBB leakage owing to reperfusion injury in stroke, further studies will be needed to determine whether the later detrimental effects can be eliminated by shorter time course of drug delivery.

Small bowel MRI: comparison of a polyethylene glycol preparation and water as oral contrast media.

PURPOSE: To compare water and a polyethylene glycol (PEG) preparation as potential oral contrast media for magnetic resonance imaging (MRI) of the small bowel. MATERIALS AND METHODS: Twenty-two healthy volunteers underwent separate MRI examinations after drinking up to two liters of water or PEG preparation. Small bowel images were obtained every 10 minutes for at least two hours using breath-hold single shot half-Fourier imaging, including both thick section projection and thin section images. Examinations were evaluated by two radiologists in consensus, blinded to the volunteer and contrast details, for arrival at the terminal ileum, transit time, and demonstration of small bowel segments. RESULTS: The PEG preparation was significantly better than water at reaching the terminal ileum (PEG 21/22 volunteers [95.45%], water 14/22 volunteers [63.6%], P = 0.04). There was no significant difference in the mean transit time (water 51 +/- 48 minutes, PEG 37.7 +/- 22 minutes) or in the demonstration of the stomach, duodenum, and jejunum, but the PEG preparation was significantly better at demonstrating the ileum (P = 0.005) and terminal ileum (P = 0.002). CONCLUSION: A PEG preparation is significantly better than water as an oral contrast medium for demonstrating the distal small bowel during breath-hold T2-weighted MRI.