Optical spectroscopy detects
histological hallmarks of pancreatic cancer

Abstract

An empirical model was developed to interpret differences in the experimentally measured reflectance and fluorescence spectra of freshly excised human pancreatic tissues: normal, adenocarcinoma, and pancreatitis (inflammation). The model provided the first quantitative links between spectroscopic measurements and histological characteristics in the human pancreas. The reflectance model enabled the first (to our knowledge) extraction of wavelength resolved absorption and reduced scattering coefficients for normal and diseased human pancreatic tissues. The fluorescence model employed reflectance information to extract attenuation free "intrinsic" endogenous fluorescence spectra from normal pancreatic tissue, pancreatic adenocarcinoma, and pancreatitis. The method developed is simple, intuitive, and potentially useful for a range of applications in optical tissue diagnostics. This approach is potentially applicable to in vivo studies, because it can account for the absorptive effects of blood in tissues.

Characterizing human pancreatic cancer precursor using quantitative tissue optical spectroscopy

“…For one IPMN patient, fluorescence spectra were not recorded due to misalignment. Among 18 measured IPMN reflectance spectra from 9 sites, two spectra from one site were excluded by the exclusion criteria R 550 nm /R 650 nm < 0.1 [12,14] due to excessive blood absorption.…”

“…A PTI model for reflectance and fluorescence spectra was reported [12,13]. The model employed a semi-empirical reflectance equation to extract absorption-and scattering-related tissue parameters from measured reflectance spectra.…”

“…Here, a Direct Fit PTI (DF-PTI) model was developed and employed with seven main modifications to the previous model [12]: 1) to improve fit quality at all wavelengths, the semi-empirical model was fit directly to the measured data without a "canonical normal" spectrum, 2) the wavelength range for fitting was expanded from 700 nm to 750 nm to more accurately account for the effect of cellular nuclear size and refractive index on spectrum shape [17], 3) the cost function was minimized with a nonlinear least-squares iterative algorithm, 4) bilirubin [Bilirubin] was added as an absorber [11], 5) collagen concentration [Collagen] and cellular density [Cell] were freely varied, 6) nuclear refractive index was freely varied, as the refractive index is related to tissue malignancy [18], and 7) the mean vessel radius R v was freely varied [19]. In the original PTI model, mean vessel radius was fixed at 7 µm and the absorption coefficient of whole blood was employed for the vessel packaging correction factor.…”

“…The ranges of varied tissue parameters employed in the DF-PTI model are shown in Table 2. For each tissue measurement, the scattering coefficient calculated via the best DF-PTI reflectance fit was employed to correct the corresponding fluorescence spectrum for attenuation [12]. As measurements were ex vivo and local blood content could vary over time, only the extracted scattering, and not absorption, coefficient was employed to calculate intrinsic fluorescence, while hemoglobin and bilirubin concentrations were varied when calculating intrinsic fluorescence.…”

“…Advantages of optical spectroscopy compared to current imaging modalities (listed above) include quantifying tissue morphological and biochemical alterations occurring at the molecular and cellular levels during neoplastic progression [10] and clinical compatibility with EUS-FNA procedures [11]. Previously, our group successfully distinguished human pancreatic diseases, including pancreatic adenocarcinoma (AC) and chronic pancreatitis, from normal tissues with multimodal optical spectroscopy and a mathematical photon-tissue interaction (PTI) model [12][13][14][15].…”