Distinguishing Tumor from Associated Fibrosis to Increase Diagnostic Biopsy Yield with Polarization-Sensitive Optical Coherence Tomography

Abstract

Purpose: With recent advancements in personalized medicine, biopsies must contain sufficient tumor for histologic diagnosis and molecular testing. However, inadvertent biopsy of tumor-associated fibrosis compromises tumor yield, resulting in delayed diagnoses and/or repeat procedures when additional tumor is needed. The ability to differentiate tumor from fibrosis intraprocedurally during biopsy could significantly increase tumor yield. Polarization-sensitive optical coherence tomography (PS-OCT) is an imaging modality that is endoscope-and/or needle-compatible, and provides large volumetric views of tissue microstructure with high resolution ($10 mm) while simultaneously measuring birefringence of organized tissues such as collagen. We aim to determine whether PS-OCT can accurately detect and distinguish tumor-associated fibrosis from tumor. Experimental Design: PS-OCT was obtained ex vivo in 64 lung nodule samples. PS-OCT birefringence was measured and correlated to collagen content in precisely matched histology, quantified on picrosirius red (PSR) staining. Results: There was a strong positive correlation between PS-OCT measurement of birefringent fibrosis and total collagen content by PSR (r ¼ 0.793; P < 0.001). In addition, PS-OCT was able to accurately classify tumor regions with >20% fibrosis from those with low fibrosis (20%) that would likely yield higher tumor content (P < 0.0001). Conclusions: PS-OCT enables accurate fibrosis detection and can distinguish tumor regions with low fibrosis. PS-OCT has significant potential for clinical impact, as the ability to differentiate tumor from fibrosis could be used to guide intraprocedural tissue sampling in vivo, or for rapid biopsy adequacy assessment ex vivo, to increase diagnostic tumor yield essential for patient care and research.

Optical Imaging Technology for Real-time Tumor Monitoring

“…23 Polarization-sensitive (PS) OCT is an imaging modality that provides large volumetric views of tissue microstructure with high resolution while simultaneously measuring birefringence of organized tissues such as collagen. 24 PS-OCT clearly shows a distinction between solid carcinoma and surrounding fibrosis compared to structural OCT (Fig. 6A, B).…”

Enhanced medical diagnosis for dOCTors: a perspective of optical coherence tomography

“…Catheter, endoscopy, and needle-based PS-OCT might, in the near future, turn out to be an extremely interesting clinical application for this contrast enhancing OCT extension. [228][229][230] Before OCTA, Doppler optical coherence tomography (DOCT) was the first [231][232][233] and most extensively used functional OCT extension determining the speed of moving particles in the tissue by measuring the frequency shift imparted on light scattered by the particles and already setting out to produce three-dimensional maps of tissue perfusion. 1,234 The classic example of Doppler shifts is the increase in frequency of an approaching train whistle followed by the decrease in frequency as it passes and departs.…”

Therapeutic and diagnostic targeting of fibrosis in metabolic, proliferative and viral disorders

“…Such guiding techniques (e.g., endobronchial ultrasound (EBUS), however, do not allow for discrimination between cancer and desmoplasia. To resolve, in order to differentiate tumor from fibrosis during needle biopsies, polarization-sensitive OCT (PS-OCT; i.e., functional OCT) has been utilized as a guidance tool [305]. PS OCT detects birefringent tissue component, e.g., collagen, while simultaneously generating structural OCT images, thus providing a reliable tool to quantify and characterize fibrosis [306].…”