Protoporphyrin IX Fluorescence Contrast in Invasive Glioblastomas is Linearly Correlated with Gd Enhanced Magnetic Resonance Image Contrast but has Higher Diagnostic Accuracy

The sensitivity and specificity of in vivo magnetic resonance (MR) imaging is compared with production of protoporphyrin IX (PpIX), determined ex vivo, in a diffusely infiltrating glioma. A human glioma transfected with green fluorescent protein, displaying diffuse, infiltrative growth, was implanted intracranially in athymic nude mice. Image contrast from corresponding regions of interest (ROIs) in in vivo MR and ex vivo fluorescence images was quantified. It was found that all tumor groups had statistically significant PpIX fluorescence contrast and that PpIX contrast demonstrated the best predictive power for tumor presence. Contrast from gadolinium enhanced T1-weighted (T1W+Gd) and absolute T2 images positively predicted the presence of a tumor, confirmed by the GFP positive (GFP+) and hematoxylin and eosin positive (H&E+) ROIs. However, only the absolute T2 images had predictive power from controls in ROIs that were GFP+ but H&E negative. Additionally, PpIX fluorescence and T1W+Gd image contrast were linearly correlated in both the GFP+ (r = 0.79, p\u3c1×10−8) and H&E+ (r = 0.74, p\u3c0.003) ROIs. The trace diffusion images did not have predictive power or significance from controls. This study indicates that gadolinium contrast enhanced MR images can predict the presence of diffuse tumors, but PpIX fluorescence is a better predictor regardless of tumor vascularity

Blood oxygenation level dependent, blood volume, and blood flow responses to carbogen and hypoxic hypoxia in 9L rat gliomas as measured by MRI

PURPOSE: To study vascular responsiveness to hypoxia and hypercarbia together with vessel size index (VSI) in a 9L rat glioma (n = 11) using multimodal MRI. MATERIALS AND METHODS: VSI was determined using T2 and T 2* MRI following AMI-227 contrast agent. Blood oxygenation level dependent (BOLD) signal response was determined using T2 EPI MRI, blood volume changes using AMI-227 and blood flow by means of continuous arterial spin labeling. RESULTS: VSI in the cortex, tumor rim, and core of 2.2 ± 1.0, 18.2 ± 5.4, and 23.9 ± 14.7 μm, respectively, showing a larger average vessel size in glioma than in the brain parenchyma. BOLD and blood volume signal changes to hypoxia and hypercapnia were much more profound in the tumor rim than the core. Hypoxia led to rim BOLD signal change that was larger in amplitude and it attained the low value much faster than either core or brain cortex. The vasculature in the rim appears more responsive to respiratory challenges in terms of volume adaptation than the core. Blood flow values within the gliomas were much lower than in the contralateral brain. Neither hypercarbia nor hypoxia had an effect on the tumor blood flow. CONCLUSION: Vascular responses of 9L gliomas to respiratory challenge, in particular hypoxia, are heterogeneous between the core and rim zones, potentially offering a means to classify and separate intratumor tissues with differing hemodynamic characteristics. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc

Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing:a multisite EPR oximetry with implantable resonators

INTRODUCTION: Several techniques currently exist for measuring tissue oxygen; however technical difficulties have limited their usefulness and general application. We report a recently developed electron paramagnetic resonance (EPR) oximetry approach with multiple probe implantable resonators (IRs) that allow repeated measurements of oxygen in tissue at depths of greater than 10 mm. METHODS: The EPR signal to noise (S/N) ratio of two probe IRs was compared with that of LiPc deposits. The feasibility of intracranial tissue pO(2) measurements by EPR oximetry using IRs was tested in normal rats and rats bearing intracerebral F98 tumors. The dynamic changes in the tissue pO(2) were assessed during repeated hyperoxia with carbogen breathing. RESULTS: A 6–10 times increase in the S/N ratio was observed with IRs as compared to LiPc deposits. The mean brain pO(2) of normal rats was stable and increased significantly during carbogen inhalation in experiments repeated for 3 months. The pO(2) of F98 glioma declined gradually, while the pO(2) of contralateral brain essentially remained the same. Although a significant increase in the glioma pO(2) was observed during carbogen inhalation, this effect declined in experiments repeated over days. CONCLUSION: EPR oximetry with IRs provides a significant increase in S/N ratio. The ability to repeatedly assess orthotopic glioma pO(2) is likely to play a vital role in understanding the dynamics of tissue pO(2) during tumor growth and therapies designed to modulate tumor hypoxia. This information could then be used to optimize chemoradiation by scheduling treatments at times of increased glioma oxygenation

Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy

The sensitivity and specificity of in vivo magnetic resonance (MR) imaging is compared with production of protoporphyrin IX (PpIX), determined ex vivo, in a diffusely infiltrating glioma. A human glioma transfected with green fluorescent protein, displaying diffuse, infiltrative growth, was implanted intracranially in athymic nude mice. Image contrast from corresponding regions of interest (ROIs) in in vivo MR and ex vivo fluorescence images was quantified. It was found that all tumor groups had statistically significant PpIX fluorescence contrast and that PpIX contrast demonstrated the best predictive power for tumor presence. Contrast from gadolinium enhanced T1-weighted (T1W+Gd) and absolute T2 images positively predicted the presence of a tumor, confirmed by the GFP positive (GFP+) and hematoxylin and eosin positive (H&E+) ROIs. However, only the absolute T2 images had predictive power from controls in ROIs that were GFP+ but H&E negative. Additionally, PpIX fluorescence and T1W+Gd image contrast were linearly correlated in both the GFP+ (r = 0.79, p<1×10(−8)) and H&E+ (r = 0.74, p<0.003) ROIs. The trace diffusion images did not have predictive power or significance from controls. This study indicates that gadolinium contrast enhanced MR images can predict the presence of diffuse tumors, but PpIX fluorescence is a better predictor regardless of tumor vascularity