Assessing effects of pressure on tumor and normal tissue physiology using an automated self-calibrated, pressure-sensing probe for diffuse reflectance spectroscopy

Abstract

Diffuse reflectance spectroscopy (DRS) represents a quantitative, noninvasive, nondestructive means of assessing vascular oxygenation, vascularity, and structural properties. However, it is known that such measurements can be influenced by the effects of pressure, which is a major concern for reproducible and operator-independent assessment of tissues. Second, regular calibration is a necessary component of quantitative DRS to account for factors such as lamp decay and fiber bending. Without a means of reliably controlling for these factors, the accuracy of any such assessments will be reduced, and potentially biased. To address these issues, a self-calibrating, pressure-controlled DRS system is described and applied to both a patient-derived xenograft glioma model, as well as a set of healthy volunteers for assessments of oral mucosal tissues. It was shown that pressure had a significant effect on the derived optical parameters, and that the effects on the optical parameters were magnified with increasing time and pressure levels. These findings indicate that not only is it critical to integrate a pressure sensor into a DRS device, but that it is also important to do so in an automated way to trigger a measurement as soon as possible after probe contact is made to minimize the perturbation to the tissue site.

A Clinical Study to Assess Diffuse Reflectance Spectroscopy with an Auto-Calibrated, Pressure-Sensing Optical Probe in Head and Neck Cancer

“…This tool requires (1) rapid feedback, (2) non-invasiveness, (3) portability, (4) a quantitative approach and (5) minimal operator bias. An instrument that meets these requirements could significantly decrease the emotional and physical toll of patients with suspicious lesions and prioritize patients with a high likelihood of malignancy by increasing clinical efficiency [ 5 ].…”

“…For applications in HNSCC, however, a smaller probe is better suited to obtaining functional measurements as long as it can be rigorously optimized as DRS is generally not used in combination with ultrasound, MRI or x-ray diagnostic imaging. Prior studies using DRS have found that reproducibility is improved with real-time assessment of probe pressure and system throughput calibration [ 5 ], which must be addressed before widespread clinical testing.…”

“…More recently, we have shown that pressure control and self-calibration can significantly reduce systematic errors in the measurement of THb and μ s ′, respectively [ 5 ]. This was demonstrated in a pilot study with healthy volunteers.…”

“…This was demonstrated in a pilot study with healthy volunteers. We evaluated the influence of pressure and found that by controlling and minimizing the probe pressure, it is possible to minimize pressure-induced changes that occur in the tissue being measured [ 5 ].…”

“…With improved self-calibration and pressure-sensing capabilities, we expect that robust, precise, accurate and quantitative measurements of tumor physiology will lead to significantly reduced errors in the extracted parameters [ 5 ]. Our goal was to measure tissue absorption and scattering difference between a “tumor” site and distant “normal” site in a pilot cohort of HNSCC patients and to correlate our results with gold-standard pathological results.…”