MRI assessment of treatment delivery for interstitial photodynamic therapy of high‐grade glioma in a preclinical model

Abstract

Ethical approval: This article contains studies using animals. All applicable institutional and national guidelines for the care and use of animals were followed. The experimental design was declared to the French National Ethics Committee under reference number 04870.01. Acknowledgments ObjectivesPrevious studies have reported the outcomes of PDT for glioblastoma via immunohistological data.Our study aimed to evaluate MRI findings, including diffusion and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation. Materials and MethodsTwenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers. ResultsElevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (p < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (p = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm 3 vs. 2.67 mm 3 , p < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (p < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (p = 0.01). ConclusionDiffusion and perfusion MRI revealed histological lesions. Interstitial PDT induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT.

Improved MR thermometry for laser interstitial thermotherapy

“…Laser interstitial thermal therapy (LITT) has been used to treat a wide variety of diseases and disorders, such as epilepsy and tumors in the brain, breast, prostate, liver, and bone . Ablations using LITT can be used on its own, but also in, for example, conjunction with radiotherapy or after injection of light‐activated photosensitizer in photodynamic therapy . LITT is especially well suited for magnetic resonance imaging (MRI) guidance since the thin fiberoptic applicator and the catheter used for cooling fluid do not create large susceptibility artifacts in the MR images.…”

Oxygen saturation imaging as a useful tool for visualizing the mode of action of photodynamic therapy for esophageal cancer

“…PDT can directly affect cancer cells by inducing necrosis and/or apoptosis in the tumoral vasculature. 8 Some investigators have demonstrated the mode of action of PDT using functional magnetic resonance imaging 9 or optoacoustic imaging 10 in animal models. We would have clinically demonstrated the mode of action of PDT through the decreasing StO₂ levels after treatment in OS imaging.…”

The role of medical imaging in the context of photodynamic therapy

“…Primary effects of PDT are necrosis and apoptosis of tumor cells and the reduction of tumor vascularization. Our previous preclinical studies allowed us to compare MRI volumes with histological samples [24][25][26]. Using these results, we demonstrated that diffusion MRI is a marker of cell death, perfusion MRI indicates the level of necrosis and T2 sequences enhance strongly the peritumoral edema of tumors.…”