Concurrent Reflectance Confocal Microscopy and Laser Doppler Flowmetry to Improve Skin Cancer Imaging: A Monte Carlo Model and Experimental Validation

Abstract

Optical interrogation of suspicious skin lesions is standard care in the management of skin cancer worldwide. Morphological and functional markers of malignancy are often combined to improve expert human diagnostic power. We propose the evaluation of the combination of two independent optical biomarkers of skin tumours concurrently. The morphological modality of reflectance confocal microscopy (RCM) is combined with the functional modality of laser Doppler flowmetry, which is capable of quantifying tissue perfusion. To realize the idea, we propose laser feedback interferometry as an implementation of RCM, which is able to detect the Doppler signal in addition to the confocal reflectance signal. Based on the proposed technique, we study numerical models of skin tissue incorporating two optical biomarkers of malignancy: (i) abnormal red blood cell velocities and concentrations and (ii) anomalous optical properties manifested through tissue confocal reflectance, using Monte Carlo simulation. We also conduct a laboratory experiment on a microfluidic channel containing a dynamic turbid medium, to validate the efficacy of the technique. We quantify the performance of the technique by examining a signal to background ratio (SBR) in both the numerical and experimental models, and it is shown that both simulated and experimental SBRs improve consistently using this technique. This work indicates the feasibility of an optical instrument, which may have a role in enhanced imaging of skin malignancies.

In�vivo confocal laser scanning microscopy imaging of skin inflammation: Clinical applications and research directions (Review)

“…An alternative to RCM is two-photon excitation microscopy that provides advantages for 3D and deep tissue imaging. A widespread application of this tool is to evaluate the blood flow via blood cell velocity and brightness, these measurements being very useful in setting different experimental models such as stroke, embryo development (57) or different skin cancers (basal cell carcinoma, squamous cell carcinoma) where morphological and functional assessments of skin layers are primarily made by combining techniques as laser Doppler flowmetry and RCM (58).…”

Advances in Monte Carlo Simulation for Light Propagation in Tissue

“…(6) Photoacoustic imaging was used for early detection of prostate cancer for which MC was used to design light delivery [38]. (7) Optical properties were varied over time in a time-gated MC for modelling of Doppler flow [109][110][111]. (8) Photoacoustic wave was modelled from the absorbance obtained from vMC simulations [112].…”

Confocal Laser Scanning Microscope Imaging of Custom-Made Multi-Cylinder Phantoms: Theory and Experiment

“…From a theoretical point of view, Monte Carlo (MC) methods have become the gold standard for describing light propagation in turbid media [ 9 ]. It is therefore not surprising to find that MC simulations are also applied in the study of confocal imaging [ 10 , 11 , 12 , 13 , 14 ]. In particular, Schmitt et al [ 10 ] investigated the performance of a confocal microscope for probing a mirror embedded in scattering media.…”