Optical biopsy: noninvasive tissue evaluation utilizing optical coherence tomography

Abstract

The accurate noninvasive assessment of traumatic wound depth and serial evaluation of wound healing is an active and ongoing research goal. A large number of noninvasive modalities have been evaluated including the use of vital dyes, indocyanine green dye fluorescence, fluorescein fluorometry, laser Doppler flowmetry (LDF), thermography, ultrasound, nuclear magnetic resonance imaging, and spectral analysis of light reflectance. Due to various limiting factors, none of these technologies has greatly improved the clinician's ability to assess tissue viability beyond simple observation. Biopsy and histopathology remain the gold standard for tissue evaluation. Histologic assessment is invasive and has a slow turn‐around time, even when frozen section techniques are utilized. Polarization‐sensitive optical coherence tomography (PS‐OCT) and optical coherence tomography/optical Doppler tomography (OCT/ODT) devices have recently been developed that have the potential to assess traumatic injury noninvasively at the bedside in a real‐time mode. The technology is analogous to ultrasound except that the images are created with echoes of light rather than sound. Polarization‐sensitive optical coherence tomography uses coherence gating to image tissue birefringence with a high degree of spatial resolution. Skin contains collagen, a weakly birefringent material. When collagen is subjected to temperatures between 56 and 65°C, the collagen denatures and loses its birefringence. When the polarization state of light reflects from various depths in a tissue, PS‐OCT can determine depth based on condition of the collagen. The OCT/ODT technology has the ability to noninvasively image in vivo blood flow with high spatial resolution. Optical Doppler tomography essentially combines LDF with OCT to produce high‐resolution tomographic images of static and moving constituents in biologic tissues. By using a Michelson interferometer with a low coherence light source, ODT can measure amplitude and frequency of the interference fringe intensity generated between the reference and target arm to form a combined structural and velocity image. Using skin in a rodent model, we compared the results of this instrument to standard histopathology and frozen section techniques. We compared four different histology staining techniques, H&E, Masson's trichrome, Movat's pentachrome, and nitroblue tetrazolium (a vital stain), to the PS‐OCT and OCT/ODT device results. The OCT measurement contained less variability site‐to‐site when compared with standard histology techniques. We also found the PS‐OCT technique provided an accurate assessment of wound depth when compared with 366 histology specimens (r2 = 0.86). Further studies are planned with OCT/ODT technology in skin and other tissues. Preliminary work with this device in the airway, gastrointestinal tract, and muscle appears promising. Utilization of these combined noninvasive imaging technologies has the potential to improve assessment of traumatically‐ and thermally‐injured patients in real time, thereby improving overall wound care. Funding: United States Department of Defense.