Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1alpha, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.

Previous research in non-human primates has shown that the superior longitudinal fascicle (SLF), a major intrahemispheric fiber tract, is actually composed of four separate components. In humans, only post-mortem investigations have been available to examine the trajectory of this tract. This study evaluates the hypothesis that the four subcomponents observed in non-human primates can also be found in the human brain using in vivo diffusion tensor magnetic resonance imaging (DT-MRI). The results of our study demonstrated that the four subdivisions could indeed be identified and segmented in humans. SLF I is located in the white matter of the superior parietal and superior frontal lobes and extends to the dorsal premotor and dorsolateral prefrontal regions. SLF II occupies the central core of the white matter above the insula. It extends from the angular gyrus to the caudal-lateral prefrontal regions. SLF III is situated in the white matter of the parietal and frontal opercula and extends from the supramarginal gyrus to the ventral premotor and prefrontal regions. The fourth subdivision of the SLF, the arcuate fascicle, stems from the caudal part of the superior temporal gyrus arches around the caudal end of the Sylvian fissure and extends to the lateral prefrontal cortex along with the SLF II fibers. Since DT-MRI allows the precise definition of only the stem portion of each fiber pathway, the origin and termination of the subdivisions of SLF are extrapolated from the available data in experimental material from non-human primates.