Hyperspectral data processing improves PpIX contrast during fluorescence guided surgery of human brain tumors

Abstract

Fluorescence guided surgery (FGS) using aminolevulinic-acid (ALA) induced protoporphyrin IX (PpIX) provides intraoperative visual contrast between normal and malignant tissue during resection of high grade gliomas. However, maps of the PpIX biodistribution within the surgical field based on either visual perception or the raw fluorescence emissions can be masked by background signals or distorted by variations in tissue optical properties. This study evaluates the impact of algorithmic processing of hyperspectral imaging acquisitions on the sensitivity and contrast of PpIX maps. Measurements in tissue-simulating phantoms showed that (I) spectral fitting enhanced PpIX sensitivity compared with visible or integrated fluorescence, (II) confidence-filtering automatically determined the lower limit of detection based on the strength of the PpIX spectral signature in the collected emission spectrum (0.014–0.041 μg/ml in phantoms), and (III) optical-property corrected PpIX estimates were more highly correlated with independent probe measurements (r = 0.98) than with spectral fitting alone (r = 0.91) or integrated fluorescence (r = 0.82). Application to in vivo case examples from clinical neurosurgeries revealed changes to the localization and contrast of PpIX maps, making concentrations accessible that were not visually apparent. Adoption of these methods has the potential to maintain sensitive and accurate visualization of PpIX contrast over the course of surgery.

Spectral complexity of 5-ALA induced PpIX fluorescence in guided surgery: a clinical study towards the discrimination of healthy tissue and margin boundaries in high and low grade gliomas

“…The contribution of State 634 is constant in healthy tissues and in LGG, and increases of only 37% in low density margin of HGG. This is consistent with the actual sensitivity issues of the 5-ALA induced PpIX fluorescence surgical microscopy in HGG and LGG [21][22][23]. However, the contribution of State 620 is 80% higher in LGG and 95% higher in low density margins of HGG than in healthy tissues.…”

“…Then, a decrease in fluorescence intensity might not only reveal a decrease in PpIX concentration but also a change of PpIX aggregate, in favor of State 620 [37]. Our results suggest that the decrease of PpIX fluorescence intensity in low-density tumor cells regions [21][22][23] attributed mainly to low PpIX concentrations could also be linked to a different aggregation of PpIX in these regions, due to a microenvironment favoring the PpIX State 620. The similarities in the PpIX fluorescence behaviors in LGG and HGG low density margins could be explained by biological processes rather close from each other: presence of infiltrative but not joined tumor cells without blood brain barrier breakage around.…”

“…The contribution of state 634 is 10 to 100 times higher in high-density tumor cells regions as compared to healthy or low density tumor cells regions. This should be related to the actual sensitivity issues of the 5-ALA induced PpIX fluorescence surgical microscopy in the low density margin of HGG [21,22] and in LGG [23]. Surgical microscopy fluorescence intensity was also assessed in this study.…”

“…It is also investigated for intracranial stereotactic biopsies [19,20]. However, its sensitivity is still limited when applied to low density infiltrative parts of HGG [21,22] or to LGG [23]. Some studies also emphasize that the link between the subjective fluorescence intensity scale chosen by the surgeon and the pathological status of tissues is still to be clarified [24,25].…”

Determination of optical properties of human brain tumor tissues from 350 to 1000 nm to investigate the cause of false negatives in fluorescence-guided resection with 5-aminolevulinic acid

“…32,33 The correction of optical properties for the detection of PpIX validated with a phantom was found to be suitable for quantitative fluorescence spectroscopy and imaging. 28,34 If there is a region with high δ in brain Table 2 Comparison of (a) mean absorption coefficients, (b) mean reduced scattering coefficients, and (c) optical penetration depths of meningioma and brain tumor. Differences to the means of two measurements are calculated.…”