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

Abstract

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.

Photodynamic therapy for malignant brain tumors in children and young adolescents

“…Aumiller et al. noted the changes in hyperintensity on T1-weighted images after PDT irradiation, which suggested the possibility of PDT-induced deoxygenation of hemoglobin and methemoglobin formation ( 16 ). In the future, it will be necessary to clarify whether this feature represents recurrence/dissemination or a benign inflammatory change and identify ways to differentiate these pathologies from each other ( 14 ).…”

“…This will allow visual confirmation of the position and laser irradiation with pinpoint accuracy, even in areas where the brain parenchyma covers and obscures the resection cavity. In addition, as described previously, a new methodological concept of interstitial PDT was recently introduced, and the development of methods or devices for more effective PD irradiation is expected to continue in the future ( 16 , 17 ). The third unresolved issue is that PDT irradiation takes additional time; one shot of PDT takes 3 min.…”

“…Conversely, the disadvantage of PDT, particularly that utilized in the present study, is that the depth of the light is limited to 2.0 to 4.0 mm; therefore, maximum surgical resection is mandatory to achieve optimal effects ( 6 , 10 , 13 ). Recently, the methodological concept of interstitial PDT was introduced, and it is expected that various new methods will be developed to enable the delivery of the PD laser to the target location with equal or better efficacy in the future ( 16 , 17 ). This will also allow the expansion of the indications of PDT treatment for children and young adolescents, a new age group.…”

Interstitial photodynamic therapy for malignant gliomas: the Munich experience

“…Analysis of MRI after every iPDT showed a circumscribed volume in T1-and T2-weighted images as well as T1-hyperintensity in the treated tumor area. The T1-hyperintensity might indicate a silent hemorrhage and seems locally correlated with a decrease of treatment light transmission as measured with the spectral online monitoring between the fibers (p<0.001) [4].…”

“…The ROS are created by the interaction of light-activated 5-ALA mediated protoporphyrin IX (PpIX) and intracellular oxygen or other molecules, using cylindrical diffuser fibers stereotactically inserted into the brain as light -guides for irradiation and excitation of the accumulated PpIX. Apart from the therapeutic tumor irradiation, spectral online monitoring measurements are performed between the fibers to monitor treatment light transmission as well as PpIX accumulation and photobleaching via the measured PpIX fluorescence [3,4]. In this work, results from retrospectively analyzed 5-ALA iPDT treatments on patients suffering from newly diagnosed and recurrent gliomas are shown.…”