Interrelation between Spectral Online Monitoring and Postoperative T1-Weighted MRI in Interstitial Photodynamic Therapy of Malignant Gliomas

CANCERS(2022)

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摘要
Simple Summary Treatment monitoring is highly important for the delivery and control of brain tumor therapy. For interstitial photodynamic therapy (iPDT), an intraoperative spectral online monitoring (SOM) setup was established in former studies to monitor photosensitizer fluorescence and treatment light transmission during therapy. In this work, data from patients treated with iPDT as the initial treatment for newly diagnosed glioblastoma (n = 11) were retrospectively analyzed. Observed changes in treatment light transmission were assessed, and changes in optical tissue absorption were calculated out of these. In addition, magnetic resonance imaging (MRI) data were recorded within 48 h after therapy and showed intrinsic T1 hyperintensity in the treated area in non-contrast-enhanced T1-weighted sequences. A 3D co-registration of intrinsic T1 hyperintensity lesions and the light transmission zones between cylindrical diffuser fiber pairs showed that reduction in treatment light transmission corresponding to increased light absorption had a spatial correlation with post-therapeutic intrinsic T1 hyperintensity (p <= 0.003). In a former study, interstitial photodynamic therapy (iPDT) was performed on patients suffering from newly diagnosed glioblastoma (n = 11; 8/3 male/female; median age: 68, range: 40-76). The procedure includes the application of 5-ALA to selectively metabolize protoporphyrin IX (PpIX) in tumor cells and illumination utilizing interstitially positioned optical cylindrical diffuser fibers (CDF) (2-10 CDFs, 2-3 cm diffusor length, 200 mW/cm, 635 nm, 60 min irradiation). Intraoperative spectral online monitoring (SOM) was employed to monitor treatment light transmission and PpIX fluorescence during iPDT. MRI was used for treatment planning and outcome assessment. Case-dependent observations included intraoperative reduction of treatment light transmission and local intrinsic T1 hyperintensity in non-contrast-enhanced T1-weighted MRI acquired within one day after iPDT. Intrinsic T1 hyperintensity was observed and found to be associated with the treatment volume, which indicates the presence of methemoglobin, possibly induced by iPDT. Based on SOM data, the optical absorption coefficient and its change during iPDT were estimated for the target tissue volumes interjacent between evaluable CDF-pairs at the treatment wavelength of 635 nm. By spatial comparison and statistical analysis, it was found that observed increases of the absorption coefficient during iPDT were larger in or near regions of intrinsic T1 hyperintensity (p = 0.003). In cases where PpIX-fluorescence was undetectable before iPDT, the increase in optical absorption and intrinsic T1 hyperintensity tended to be less. The observations are consistent with in vitro experiments and indicate PDT-induced deoxygenation of hemoglobin and methemoglobin formation. Further investigations are needed to provide more data on the time course of the observed changes, thus paving the way for optimized iPDT irradiation protocols.
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malignant glioma, glioblastoma, photodynamic therapy, interstitial photodynamic therapy, 5-ALA, protoporphyrin IX, online monitoring, fluorescence, T1 hyperintensity, methemoglobin
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