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.
Significance: 5-Aminolevulinic acid (5-ALA)-based fluorescence guidance in conventional neurosurgical microscopes is limited to strongly fluorescent tumor tissue. Therefore, more sensitive, intrasurgical 5-ALA fluorescence visualization is needed. Aim: Macroscopic fluorescence lifetime imaging (FLIM) was performed ex vivo on 5-ALAlabeled human glioma tissue through a surgical microscope to evaluate its feasibility and to compare it to fluorescence intensity imaging. Approach: Frequency-domain FLIM was integrated into a surgical microscope, which enabled parallel wide-field white-light and fluorescence imaging. We first characterized our system and performed imaging of two samples of suspected low-grade glioma, which were compared to histopathology. Results: Our imaging system enabled macroscopic FLIM of a 6.5 × 6.5 mm 2 field of view at spatial resolutions <20 μm. A frame of 512 × 512 pixels with a lifetime accuracy <1 ns was obtained in 65 s. Compared to conventional fluorescence imaging, FLIM considerably highlighted areas with weak 5-ALA fluorescence, which was in good agreement with histopathology. Conclusions: Integration of macroscopic FLIM into a surgical microscope is feasible and a promising method for improved tumor delineation.
Intraoperative optical coherence tomography is still not overly pervasive in routine ophthalmic surgery, despite evident clinical benefits. That is because today’s spectral-domain optical coherence tomography systems lack flexibility, acquisition speed, and imaging depth. We present to the best of our knowledge the most flexible swept-source optical coherence tomography (SS-OCT) engine coupled to an ophthalmic surgical microscope that operates at MHz A-scan rates. We use a MEMS tunable VCSEL to implement application-specific imaging modes, enabling diagnostic and documentary capture scans, live B-scan visualizations, and real-time 4D-OCT renderings. The technical design and implementation of the SS-OCT engine, as well as the reconstruction and rendering platform, are presented. All imaging modes are evaluated in surgical mock maneuvers using ex vivo bovine and porcine eye models. The applicability and limitations of MHz SS-OCT as a visualization tool for ophthalmic surgery are discussed.
Fluorescence guided neurosurgery based on 5-aminolevulinic acid (5-ALA) has significantly increased maximal safe resections. Fluorescence lifetime imaging (FLIM) of 5-ALA could further boost this development by its increased sensitivity. However, neurosurgeons require real-time visual feedback which was so far limited in dual-tap CMOS camera based FLIM. By optimizing the number of phase frames required for reconstruction, we here demonstrate real-time 5-ALA FLIM of human high-and low-grade glioma with up to 12 Hz imaging rate over a wide field of view (11.0 x 11.0 mm). Compared to conventional fluorescence imaging, real-time FLIM offers enhanced contrast of weakly fluorescent tissue.
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