Assessment of brain tumor angiogenesis inhibitors using perfusion magnetic resonance imaging: quality and analysis results of a phase I trial.
OBJECTIVE
To determine thresholds of quality for a T2*-weighted perfusion magnetic resonance imaging (MRI) study and evaluate the effects of an angiogenesis inhibitor on relative blood flow and volume changes in brain tumor patients in a multi-institution setting.


METHODS
A total of 36 volunteers from four participating institutions with clinically diagnosed malignant gliomas were studied using perfusion MRI protocols. These included a baseline study and follow-up studies every eight weeks to evaluate the effect of an anti-angiogenic agent on tumor perfusion. Quality tests were performed on the perfusion imaging data by defining statistical thresholds of acceptance. Region of interest (ROI) analysis was performed on tumors and kinetic parameters were normalized with respect to normal tissue.


RESULTS
Statistical thresholds for goodness of the gamma variate fit, T2* recovery, and mean signal full-width half-minimum (FWHMin) were computed for our data sets with a 99% one-sided confidence interval; these were 6.91%, 79.48%, and 23.35 seconds, respectively. Decreases in-blood volume and flow measurements were observed in patients with documented clinical response.


CONCLUSIONS
Malignant brain tumors have altered perfusion parameters that may be used to understand and monitor neovascularization. This permits non-invasive assessment of the efficacy of angiogenesis inhibiting drugs.
Akella
N Shastry
NS
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Twieg
Donald B
DB
Mikkelsen
Tom
T
Hochberg
Fred H
FH
Grossman
Stuart
S
Cloud
Gretchen A
GA
Nabors
L Burt
LB
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001783:Blood Flow Velocity; D001810:Blood Volume; D001932:Brain Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000188:drug therapy; D018450:Disease Progression; D017352:Echo-Planar Imaging; D005909:Glioblastoma / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy; D005910:Glioma / Q000098:blood supply* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D018810:Magnetic Resonance Angiography; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D010456:Peptides, Cyclic / Q000627:therapeutic use; D012910:Snake Venoms
D020533:Angiogenesis Inhibitors; D010456:Peptides, Cyclic; D012910:Snake Venoms; C422910:Cilengitide