Assessment of the morphological and functional effects of the anti-angiogenic agent SU11657 on 9L gliosarcoma vasculature using dynamic susceptibility contrast MRI

To investigate the influence of anti-angiogenic agents on tumor perfusion, we employed a dynamic susceptibility contrast (DSC)-MRI method that utilizes a simultaneous gradient-echo (GE) and spin-echo (SE) imaging sequence to derive perfusion parameters (blood flow, blood volume, and mean transit time (MTT)). These parameters are sensitive to both the total vasculature (from the GE data) and the microvasculature (from the SE data), and can also provide a measure of the mean vessel diameter (mVD). This approach was used to evaluate the response of a 9L rat brain tumor model to 20 mg/kg and 40 mg/kg of the anti-angiogenic agent SU11657. The 20-mg/kg dose significantly decreased mVD by 29.9% (P=0.02). The 40-mg/kg dose significantly decreased mVD by 30.4% (P=0.0007), SE blood volume by 31.8% (P=0.03), GE and SE MTT by 46.9% (P=0.03) and 62.0% (P=0.0005), and increased GE and SE blood flow by 36.6% (P=0.04) and 52.6% (P=0.02). These findings demonstrate that DSC-MRI perfusion methods can play a key role in the noninvasive evaluation of morphological and functional changes in tumor vasculature in response to therapy.