Improved Detection of 5-Aminolevulinic Acid-Induced Fluorescence in Gliomas Using a Novel Handheld Device

Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid enables improved intraoperative visualization of gliomas but is currently limited by the long distance between the light source and tissue of interest. We introduce a novel handheld device (NHD) with a light source at the tip that enables in situ delivery of light to the surgical field; we hypothesized that this close-proximity light source would improve visualization of gliomas. We investigated the feasibility of the NHD for FGS and compared the quality of fluorescence with an existing microscope or exoscope (collectively termed "scope") in Vivo (within the surgical field) and ex Vivo (outside the surgical field).

We performed a prospective clinical study of 18 glioma patients who underwent FGS. During each surgery, 3 areas of tumor were inspected in Vivo and ex Vivo using the scope alone or the scope and the NHD. Fluorescence intensity was scored as none, weak, or strong, and fluorescence character was scored as none, patchy, or uniform. These qualitative descriptions were converted to ordinal scores and compared using Mann-Whitney tests. Fluorescence was further quantified in ImageJ and compared using paired t tests. A neuropathologist performed histopathology studies to verify tumor cell presence and quantify tumor cellularity. Relationships between fluorescence and cellularity were analyzed using Kruskal-Willis tests.

The NHD increased rates of positive fluorescence detection compared with the scope in Vivo and ex Vivo. The NHD significantly improved fluorescence intensity and character in Vivo and ex Vivo, with a mean 2.8-fold increase in fluorescence intensity in Vivo. There was a trend toward increasing tumor cellularity with increasing fluorescence intensity and character.

The NHD was feasible to use and provided clinically meaningful improvements in fluorescence visualization compared with existing intraoperative technology.