Diffusion-weighted MR finds new niche in stroke therapy

MR imaging is chipping away at time restrictions for treating acute stroke while also building a reputation for evaluating neurological disorders.

For example, results from a landmark study have found diffusion-weighted MR useful in triaging patients likely to benefit from tissue plasminogen activator thrombolysis three to six hours after stroke onset. Findings from the Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study were released in February.

Since 1996, FDA policy has limited tPA administration to a three-hour poststroke window because of increased risk of fatal intracranial hemorrhage. The DEFUSE trial demonstrated that diffusion-perfusion MRI can identify patients who will probably recover from stroke because of thrombolysis without a high risk of a fatal intracranial hemorrhage, according to principal investigator Dr. Michael Marks, director of neuroradiology at the Stanford University Stroke Center.

The prospective pilot study involved baseline imaging performed before thrombolysis three to six hours after ictus and again three to six hours after thrombolysis for evidence of reperfusion. Results were compared with patient outcomes at three months.

Early in the trial, six patients incurred cerebral hemorrhage, and three died, leading investigators to reconsider assumptions about the benefits of mismatch alone for selecting candidates most likely to benefit from reperfusion in the three to six- hour period. The study results confirmed their revised hypothesis that patients benefiting most were those with a baseline mismatch (a volumetric perfusion deficit 20% larger than the volumetric diffusion deficit) and no evidence of malignant pattern involving volumetric diffusion deficits of more than 100 cc of brain tissue or more than an eight-second delay in the appearance of the Tmax hemodynamic parameter in the diffusion volume, Marks said.

The probability of a good clinical outcome was far better for patients whose brains were successfully reperfused following thrombolyis. Sixty-six percent with DWI/PWI mismatch and early reperfusion had a modified Rankin score of 3 or less 30 days after stroke. But only 24% of patients who could not be reperfused had a modified Rankin score of 3 or less.

"We were encouraged that the target mismatch pattern identified patients who appear to benefit substantially from early reperfusion as well as a separate set of patients with a malignant pattern who do not appear to benefit," Marks said.

The application of imaging as a triage tool in the DEFUSE study should not be overlooked, according to Dr. Michael Lev, director of emergency neuroradiology at Massachusetts General Hospital. Imaging may transcend the clock for identifying candidates for recanalization treatment.

"It has long been said that time is brain," he said. "We are trying to coin a new phase, 'mismatch is brain.'"

ADVANCED INTERVENTIONS

While stroke imaging re-search has been dominant in 2006, advances in other areas are also notable. Interventional neurology and vertebroplasty were major themes at the American Society of Neuroradiology meeting in San Diego in April. A retrospective study examining the clinical impact of 1000 vertebroplasty procedures at the Mayo Clinic in Rochester, MN, confirmed the procedure's ability to dramatically alleviate pain from compression spinal fractures. The review found measurable relief in most cases two hours after intervention and sustained pain relief two years later, according to Dr. Kenneth F. Layton, an interventional neuroradiology fellow.

The growing appeal of diffusion tensor imaging became apparent at the International Society for Magnetic Resonance in Medicine meeting in May. Preliminary clinical trials explored the ability of DTI to characterize brain-based neoplasms and neurological disorders. Results from pilot studies suggest a role for DTI in assessing white matter integrity and predicting disease progression among amyotrophic lateral sclerosis patients, and for monitoring the remodeling of language centers in the brain in response to therapy following stroke.

Other research suggests that DTI fractional anisotropy can detect the degradation of cingulum fibers in the hippocampi of patients with mild cognitive impairment and additional deterioration that possibly correlates with Alzheimer's disease.

A preliminary study from St. George's University of London found that DTI tractography can noninvasively discriminate among the presence of glioblastoma, meningioma, and metastasis. The technique could reduce the need for invasive biopsy to make these determinations in future. A separate study from the University of Cambridge suggests that DTI may predict recurrence of gliomas.

A study from the Medical College of Wisconsin in Milwaukee employed regional cerebral blood flow measures to achieve 90% accuracy in grading brain tumors. At New York University, researchers found a possible role for vascular space occupancy (VASO) MRI for grading cerebral gliomas.