Abstract
•Co-registered in-vivo magnetic resonance (MR) perfusion and ex-vivo spatial frequency domain imaging (SFDI) images of brain tumors.•Negative correlation of brain blood flow with tumor size in rats.•No strong correlation of perfusion parameters with photosensitizer uptake.•Tumor rim has higher blood flow and photosensitizer than tumor core; outer rim edge shows low photosensitizer uptake.•Findings emphasize importance of spatial photosensitizer heterogeneity in PDT planning.
The efficacy of photodynamic therapy (PDT) can be impacted by heterogeneous Photosensitizer (PS) accumulation. Our previous study indicated that neglecting spatial variations in photosensitizer (PS) accumulation during treatment planning can result in morbidity and treatment failure. Knowledge and incorporation of the PS distribution at the 1 mm³ scale in the treatment planning process can compensate for heterogeneous PS efficacy losses. Effects of vascular perfusion parameters in the brain and local PS concentration are investigated.
Correlations between MRI-derived blood flow (BF), blood volume (BV), mean transit time (MTT), and quantitative Spatial Frequency Domain imaging (qSFDI) of the photosensitizer concentration [PS] in the tumour rim, core, and normal brain are investigated.
In-vivo MRI with continuous arterial spin labeling (CASL) and intravoxel incoherent motion (IVIM) provided BF, BV, and MTT in a rat glioma model for the tumour regions, normal brain, and spatially resolved within 1.5 mm of the tumour rim. Two photosensitizers were used: a small-molecule agent (Ce6) and a nanoparticle-based formulation (Porphysome). qSFDI provided spatially resolved [PS], which was co-registered with the MRI data to enable evaluation of the perfusion and [PS] correlation strength.
The imaging techniques showed elevated BF and [PS] in the tumour rim and reduced BF and [PS] in the tumour core, but BV did not differ between the core and rim. No strong correlations between any perfusion parameter and ex-vivo [PS] were observed. A strong positive [PS] gradient was noted from the tumour’s outer rim towards its centre. This spatial uptake trend was observed for both photosensitizers, with Porphysome showing a steeper gradient and higher overall accumulation.
These findings highlight that MR perfusion metrics alone are insufficient to predict spatial [PS] in solid brain tumours for PDT pre-treatment planning.
Photodynamic Therapy’s efficacy depends on the extravasation of systemically administered cellular-acting photosensitizers from the vasculature. Hence, knowledge of the blood vessels’ integrity, density, and flow can be important parameters in the treatment planning process.
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