Abstract
Achieving a maximal safe extent of resection during brain tumor surgery is the goal for improved patient prognosis. Fluorescence‐guided neurosurgery using 5‐aminolevulinic acid (5‐ALA) induced protoporphyrin IX has thereby become a valuable tool enabling a high frequency of complete resections and a prolonged progression‐free survival in glioblastoma patients. We present a widefield fluorescence lifetime imaging device with 250 mm working distance, working under similar conditions such as surgical microscopes based on a time‐of‐flight dual tap CMOS camera. In contrast to intensity‐based fluorescence imaging, our method is invariant to light scattering and absorption while being sensitive to the molecular composition of the tissue. We evaluate the feasibility of lifetime imaging of protoporphyrin IX using our system to analyze brain tumor phantoms and fresh 5‐ALA‐labeled human tissue samples. The results demonstrate the potential of our lifetime sensing device to go beyond the limitation of current intensity‐based fluorescence‐guided neurosurgery.
Highlights
The discrimination between tumorous and healthy tissue in brain tumor surgery is of fundamental importance to achieve a maximal safe extent of resection and better patient outcome [1]
As the phantoms are homogeneous the average and SD were computed over the whole field of view (FOV)
We first discarded the possibility of photon-reabsorption of protoporphyrin IX (PpIX) which would artificially increase the lifetime at higher PpIX concentrations as we did not expect an influence by absorption
Summary
The discrimination between tumorous and healthy tissue in brain tumor surgery is of fundamental importance to achieve a maximal safe extent of resection and better patient outcome [1]. Owing to rapid technological development of time-of-flight (TOF) sensors and cameras [18] as well as the requirements mentioned above, we developed a FLIM system for PpIX imaging in brain tumor tissue around a modulated dual tap complementary metal-oxide semiconductor (CMOS) camera [19, 20]. Specifications such as working distance, imaging rate and sensitivity were chosen to match the requirements for current neurosurgical microscopes. We show the feasibility of PpIX lifetime imaging using our TOF camera–based approach on brain tissue phantoms as well as on ex vivo human tumor samples and discuss the potential transfer of this technology into a surgical environment
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