The large liver transplant waitlists and increasing of marginal donor organs call for a rapid, non-destructive method of evaluating organ quality for transplantation. We demonstrate a diffuse optical non-destructive organ risk (DONOR) indexing method for identifying significant liver pathology, in particular unacceptable fibrosis and necrosis. Measurements were acquired from 27 human livers not meeting the clinical criteria for transplantation (OUHSC IRB #8155). A portable lab-on-a-crate diffuse optical spectroscopy (DOS) device with a hands-free probe of 3mm source-detector separation was used for measurements on liver surface and cross-section. The DOS measurements were obtained from a total of five sites, including the right anterior, right posterior, and left anterior liver surfaces and the right and left cut sections, and corresponding tissue sections were obtained for formalin-fixed paraffin embedded (FFPE) H&E controls of 8 types of liver pathology. Due to the difficulty of obtaining a control liver, a clinically inconspicuous and histologically unremarkable liver number 24 was used as the baseline for DONOR index processing. For the measurements at the cross-sectional parenchyma of the right lobe alone, a single threshold of the DONOR index at 1.5 identified all six livers with fibrosis stage ≥2 and one liver with necrosis=5, in the presence of mixed pathologies. A prime pattern of altering the DOS profile by the fibrosis alone is identified. The surface measurements differ from the parenchyma measurements at various levels, due to the shielding effect of the thin collagen-rich capsule. DONOR indexing of liver pathology is promising, but requiring unsheilding the capsular effect.
We hypothesize that the capsular optical properties and thickness combined affect how accurate the diffuse reflectance on the surface of a capsular solid organ represents that on the subcapsular parenchyma. Monte Carlo simulations on two-layer geometries evaluated how a thin superficial layer with the thickness from 10 to 1000 μm affected the surface diffuse reflectance over a source–detector separation spanning 0.01 to 10 mm. The simulations represented the superficial layer presenting various contrasts concerning refractive index, anisotropy factor, absorption coefficient, and reduced scattering coefficient, versus those of the subsurface main medium. An analytical approach modeled the effects of the superficial layer of various thicknesses and optical properties on diffuse reflectance. Diffuse reflectance spectroscopy was performed ex vivo on 10 fresh human livers and 9 fresh human kidneys using a surface probe with a 3-mm source–detector separation. The difference of the device-specific diffuse reflectance on the organ between with the capsule and without the capsule has significantly greater spectral variation in the kidney than in the liver. The significantly greater spectral deviation of surface diffuse reflectance between with and without the capsule in the kidney than in the liver was analytically accountable by considering the much thicker capsule of the kidney than of the liver.
Surface diffuse reflectance spectroscopy (DRS) has the potential for real-time, bed-side evaluation of solid donor organs including liver and kidney for transplant. Nilsson et al used an applicator-probe with multiple source-detector paired with a 2.5mm source-detector separation to show that DRS of liver through the capsule represents the DRS of cross-sectional liver; however, a small but consistent difference over 600nm—850nm between DRS with capsule and without capsule was observed. Understanding the effect of the capsule on surface DRS of solid capsular organs is important to accurately resolving subcapsular tissue properties for the evaluation of organ quality. We have developed a portable lab-on-a-crater DRS system with an applicator-probe with 3mm source-detector separation for evaluating human liver and kidney specimens routinely in a pathology lab. The DRS performed on liver with capsule is consistently lower in the spectral intensity between 600-850nm when compared to DRS performed on the cross-section of liver, regardless of the pathology of subcapsular parenchyma. To model the effect of capsule on surface DRS of capsular solid organs like liver, we have implemented an analytical approach based on a master-slave dual-source configuration model (Piao and Patel, App. Opt, 56(5) 1447-1452, 2017). Under the assumption of the capsular layer having lower oxygenated hemoglobin and potentially increased elastin content and by making the location and intensity of the slave-source dependent upon the properties of the capsular layer, the surface DRS predicted by this master-slave dual-source model reveals the measured pattern over 600-850nm between with the capsule and without the capsule.
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