Endoscopic fluorescence visualization of 5-ALA photosensitized central nervous system tumors in the neural tissue transparency spectral range

Abstract

Background:Fluorescence endoscopy systems for photosensitizer visualization have proved to be powerful tools for highlighting malignant tumor boundaries as well as detecting small, visually non-detectable, residual parts during photodynamic therapy. Most of these devices use excitation wavelengths in the blue visual spectrum range (405 nm) which limits the penetration depth in the tissue.Objective:In the study being presented in this article an apparatus and a method were developed for performing endoscopic fluorescence diagnostics of photosensitizer accumulation using excitation light in the red part of visual spectrum, i.e., 635 nm, which allows not only a deeper penetration of light into the tissue but also better scanning abilities and a higher diagnostic quality. Additionally, 635-nm radiation can penetrate thin layers of blood which appear during surgery.Material and methods:In order to use 635-nm excitation, a specially designed video endoscopy system was developed. The key feature of the video system is a dual camera video receiver where one sensitive B/W camera receives the fluorescence signal and a color camera receives the real-time image in natural colors during navigation. The software developed for the apparatus allows overlaying of the video output of fluorescence image on top of the conventional color image in real-time. The experimental setup and method were tested on Intralipid-based phantoms with protoporphyrin IX (PpIX) concentrations of 0.5–5 mg/kg, and then on two patients during surgery. The patients were administered 20 mg/kg 5-ALA photosensitizer 3 h before surgery according to standard practice of 5-ALA in neurosurgery.Results:The experiments demonstrate that the designed setup is sensitive enough for clear visualization of biological concentrations of PpIX in both phantoms with 0.5 mg/kg PpIX and previously photosensitized tissues of patients.Conclusion:Further prospective validation is needed to translate the results to clinical practice.

405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence‐guided stereotactic biopsy of brain tumors

“…Based on the bulk-tumor detection limit of 200 nM•mW for λexc = 633 nm (see Section 3.1.1), vital GBM tissue, which typically exhibits PpIX concentrations of a few µM after 5-ALA administration at 20 mg per kg body weight [24,33,51], should well be detectable with a 200 µm diameter fiber (NA = 0.22) in contact with the tissue. As shown in Section 3.1.2, the detection limit for smaller tumor parts that are still big enough to be sampled during stereotactic biopsy is only slightly increased.…”

“…During open brain surgery, the blood often but not always can be removed by rinsing the probe or the surgical site; yet, even small amounts of blood will affect proper interpretation of the signals. [32][33][34] During stereotactic biopsy, however, rinsing appears to be even more challenging because the (diluted) blood cannot drain off and suctioning through the needle would draw even more blood towards the probe tip, at least for conventional needle designs. Even if no blood vessel disruption occurs, the micro-vessels in the tissue right next to the probe do sometimes obstruct the fluorescence signals.…”

“…Light in this spectral range, however, is highly absorbed by blood, hence blood-covered tumor tissue may easily be missed. During open brain surgery, the blood often but not always can be removed by rinsing the probe or the surgical site; yet, even small amounts of blood will affect proper interpretation of the signals [32][33][34]. During stereotactic biopsy, however, rinsing appears to be even more challenging because the (diluted) blood cannot drain off and suctioning through the needle would draw even more blood towards the probe tip, at least for conventional needle designs.…”

Optical spectroscopy for stereotactic biopsy of brain tumors

“…Regarding the detection limit of 200 nM·mW for λ exc = 633 nm, vital glioblastoma tissue, which typically exhibits PpIX concentrations of a few µM after 5-ALA administration 11,22,23 , should well be detectable with a 200 µm fiber (NA = 0.22) in contact with the tissue. Finally, 633 nm excitation is unambiguously superior in case of blood-covered tumor structures.…”

Laser interstitial thermal therapy (LITT) of the brain – Experiences and new indications

“…Different modalities of neuronavigation [1,2], intraoperative imaging ("open MR" system) and intraoperative fluoroscopy with 5-ALA [3] have proved to be important technical achievements to support this aim.…”