Computer-assisted volumetric measurement of core infarct volume in pediatric patients: feasibility for clinical use and development of quantitative metrics for outcome prediction.

BACKGROUND AND PURPOSE: Infarct volume may predict clinical outcome in acute stroke, but manual segmentation techniques limit its routine use. We hypothesized that computer-assisted volumetric analysis to quantify acute infarct volume will show no difference compared with manual segmentation but will show increased speed of performance and will correlate with outcome. MATERIALS AND METHODS: Patients with acute stroke younger than 18 years were included. Infarct volume on diffusion-weighted imaging was quantified by using computer-assisted volumetric and manual techniques. The Pediatric Stroke Outcome Measure scored clinical outcome. Computer-assisted volumetric and manual techniques were compared with correlation coefficients. Linear regression analysis compared Pediatric Stroke Outcome Measure with core infarct volume and percentage volume of brain infarction. RESULTS: Twenty-three patients were analyzed (mean age, 4.6 years). Mean infarct volume from computer-assisted volumetric and manual approaches was 65.6 and 63.7 mL, respectively (P = .56). Concordance correlation between methods was 0.980, and between users, 0.968. The mean times for segmentation between computer-assisted volumetric and manual techniques were <1 minute and 7.3 minutes (P < .001). The mean infarct volumes for good and poor outcome groups were 7.4 and 75.7 mL (P < .007). The mean percentages of infarcted brain parenchyma for good and poor outcome groups were 0.6% and 10.4% (P < .006). Volumes of 32 mL and 3% for infarcted brain were associated with poor outcome in all patients. CONCLUSIONS: Computer-assisted volumetric quantification of infarct volume is reproducible, is significantly faster than manual techniques, and may have important applications for future clinical workflow. Core infarct volumes and infarct percentage correlated with outcome severity.

Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells: respective roles of Vav and Bcr-Abl GEFs.

The chimeric oncogene Bcr-Abl is known to induce autonomous motility of leukemic cells. We show here that p210(bcr-abl) responsible for chronic myelogenous leukemia induces an amoeboid type of motility while p190(bcr-abl), associated with acute lymphoid leukemia, induces a rolling type of motility. We previously reported that p210(bcr-abl) activates RhoA and Rac1, while p190(bcr-abl) although devoid of a Dbl-homology (DH) domain activates Rac1, but not RhoA. We investigated the regulation of GDP/GTP exchange factor (GEF) activities in the Bcr-Abl complex. For that purpose, different GEF activity mutants of Vav and of Bcr-Abl were constructed and stably transfected in Ba/F3 cells. Using these mutants, we demonstrate that RhoA is exclusively activated by the DH domain of p210(bcr-abl), while Rac1 activation is mostly due to Vav. Inhibition of Rac1 by Vav GEF mutant leads to immobilization of cells. Vav depletion using shRNA also induces immobilization of cells and suppression of GTP-bound Rac1. RhoA inactivation induces the specific loss of amoeboid movements. These results suggest that Rac1 activation by Vav triggers the motility of Bcr-Abl-expressing Ba/F3 cells, while the specific amoeboid mode of motility induced by p210(bcr-abl) is a consequence of RhoA activation.