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

Abstract

The optical properties of human brain tumor tissues, including glioblastoma, meningioma, oligodendroglioma, and metastasis, that were classified into "strong," "vague," and "unobservable" fluorescence by a neurosurgeon were measured and compared. The optical properties of the tissues were measured with a double integrating sphere and the inverse Monte Carlo technique from 350 to 1000 nm. Using reasons of ex-vivo measurement, the optical properties at around 420 nm were potentially affected by the hemoglobin content in tissues. Significant differences were not observed between the optical properties of the glioblastoma regions with "strong" and "unobservable" fluorescence. Sections of human brain tumor tissue with "strong" and "unobservable" fluorescence were stained with hematoxylin and eosin. The cell densities [mean ± standard deviation (S.D.)] in regions with "strong" and "unobservable" fluorescence were 31 ± 9 × 102 per mm2 and 12 ± 4 × 102 per mm2, respectively, which is a statistically significant difference. The higher fluorescence intensity is associated with higher cell density. The difference in cell density modified the scattering coefficient yet it does not lead to significant differences in the reduced scattering coefficient and thus does not affect the propagation of the diffuse fluorescent light. Hence, the false negatives, which mean a brain tumor only shows "unobservable" fluorescence and is hence classified incorrectly as nontumor, in using 5-ALA for detection of human glioblastoma do not result from the differences in optical properties of human brain glioblastoma tissues. Our results suggest that the primary cause of false negatives may be a lack of PpIX or a low accumulation of PpIX.

Comparison of optically‐derived biomarkers in healthy and brain tumor tissue under one‐ and two‐photon excitation

“…This is particularly true for gliomas as they are known to have different histological properties (degree of necrosis, endothelial proliferation and genetic atypia) even within the same tumor grade . The limited capability of discriminating between tumor types based solely on tissue optical properties has also been reported elsewhere , where in vivo, frozen and fixed brain tissue samples were examined. Our absorption and scattering coefficients of GBM, meningioma and cortical tissue are similar to those reported by Honda et al , where integrating sphere measurements were performed on freshly excised samples and are generally higher than the in vivo results reported by Bevilacqua et al Additionally, they are higher than those obtained by Gebhart et al on frozen tissue due to the change in hemodynamics upon snap freezing .…”

“…The limited capability of discriminating between tumor types based solely on tissue optical properties has also been reported elsewhere , where in vivo, frozen and fixed brain tissue samples were examined. Our absorption and scattering coefficients of GBM, meningioma and cortical tissue are similar to those reported by Honda et al , where integrating sphere measurements were performed on freshly excised samples and are generally higher than the in vivo results reported by Bevilacqua et al Additionally, they are higher than those obtained by Gebhart et al on frozen tissue due to the change in hemodynamics upon snap freezing . The varying techniques in preserving tissue directly affect the optical properties and thus explain the discrepancies .…”

Singlet oxygen model evaluation of interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor

“…The absorption coefficient, μ a (cm −1 ), scattering coefficient, μ s (cm −1 ), and anisotropy factor of scattering, g, were set as 1.7 cm −1 , 365 cm −1 , and 0.9, respectively, for the tumor regions and 0.7 cm −1 , 951 cm −1 , and 0.9, respectively, for the white matter regions at the wavelength of 635 nm. 35 For iPDT outcome estimations, each voxel was divided into thirds in a direction perpendicular to the slice plane to give an isotropic voxel size of 468 × 468 × 417 μm 3 .…”

“…The μ a , μ s , and g were set as 1.7 cm −1 , 365 cm −1 , and 0.9, respectively, for the wavelength of 635 nm. 35 The photobleaching coefficient and initial PpIX concentration values were varied in evaluation.…”

Identifying different types of tumors in human brain, breast, and uterus according to their optical properties in the red to near-infrared region

“…Tissue diffuse reflectance and transmittance are the main measurements required to determine the optical parameters of any type of biological tissue, they can be experimentally measured by either integrating spheres [20] or distant photo-detectors [21]. Based on the reflection and transmission collected data, tissue absorption coefficient µa, scattering coefficient µs and anisotropy factor g can be estimated using various analytical approaches referred as indirect or inverse methods such as Kubelka-Munk mathematical model [22], inverse Monte-Carlo [23] and inverse adding-doubling iterative method [24]. Other techniques referred as forward or direct methods that use the known optical parameters values to obtain the diffuse reflectance and transmission profiles of the studied tissue based on the radiative transport theory of light propagation [25].…”