Noninvasive in vivo optical coherence tomography tracking of chronic otitis media in pediatric subjects after surgical intervention.

In an institutional review board-approved study, 25 pediatric subjects diagnosed with chronic or recurrent otitis media were observed over a period of six months with optical coherence tomography (OCT). Subjects were followed throughout their treatment at the initial patient evaluation and preoperative consultation, surgery (intraoperative imaging), and postoperative follow-up, followed by an additional six months of records-based observation. At each time point, the tympanic membrane (at the light reflex region) and directly adjacent middle-ear cavity were observed in vivo with a handheld OCT probe and portable system. Imaging results were compared with clinical outcomes to correlate the clearance of symptoms in relation to changes in the image-based features of infection. OCT images of most all participants showed the presence of additional infection-related biofilm structures during their initial consultation visit and similarly for subjects imaged intraoperatively before myringotomy. Subjects with successful treatment (no recurrence of infectious symptoms) had no additional structures visible in OCT images during the postoperative visit. OCT image findings suggest surgical intervention consisting of myringotomy and tympanostomy tube placement provides a means to clear the middle ear of infection-related components, including middle-ear fluid and biofilms. Furthermore, OCT was demonstrated as a rapid diagnostic tool to prospectively monitor patients in both outpatient and surgical settings.

Real-time Imaging of the Resection Bed Using a Handheld Probe to Reduce Incidence of Microscopic Positive Margins in Cancer Surgery.

Wide local excision (WLE) is a common surgical intervention for solid tumors such as those in melanoma, breast, pancreatic, and gastrointestinal cancer. However, adequate margin assessment during WLE remains a significant challenge, resulting in surgical reinterventions to achieve adequate local control. Currently, no label-free imaging method is available for surgeons to examine the resection bed in vivo for microscopic residual cancer. Optical coherence tomography (OCT) enables real-time high-resolution imaging of tissue microstructure. Previous studies have demonstrated that OCT analysis of excised tissue specimens can distinguish between normal and cancerous tissues by identifying the heterogeneous and disorganized microscopic tissue structures indicative of malignancy. In this translational study involving 35 patients, a handheld surgical OCT imaging probe was developed for in vivo use to assess margins both in the resection bed and on excised specimens for the microscopic presence of cancer. The image results from OCT showed structural differences between normal and cancerous tissue within the resection bed following WLE of the human breast. The ex vivo images were compared with standard postoperative histopathology to yield sensitivity of 91.7% [95% confidence interval (CI), 62.5%-100%] and specificity of 92.1% (95% CI, 78.4%-98%). This study demonstrates in vivo OCT imaging of the resection bed during WLE with the potential for real-time microscopic image-guided surgery.

Multimodal nonlinear endo-microscopy probe design for high resolution, label-free intraoperative imaging.

We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery.

Noninvasive depth-resolved optical measurements of the tympanic membrane and middle ear for differentiating otitis media.

OBJECTIVE/HYPOTHESIS: In this study, optical coherence tomography (OCT) is used to noninvasively and quantitatively determine tympanic membrane (TM) thickness and the presence and thickness of any middle-ear biofilm located behind the TM. These new metrics offer the potential to differentiate normal, acute, and chronic otitis media (OM) infections in pediatric subjects. STUDY DESIGN: Case series with comparison group. METHODS: The TM thickness of 34 pediatric subjects was acquired using a custom-built, handheld OCT system following a traditional otoscopic ear exam. RESULTS: Overall thickness (TM and any associated biofilm) was shown to be statistically different for normal, acute, and chronic infection groups (normal-acute and normal-chronic: P value < 0.001; acute-chronic: P value = 0.0016). Almost all observed scans from the chronic group had an accompanying biofilm structure. When the thickness of the TM and biofilm were considered separately in chronic OM, the chronic TM thickness correlated with the normal group (P value = 0.68) yet was still distinct from the acute OM group (P value < 0.001), indicating that the TM in chronic OM returns to relatively normal thickness levels. CONCLUSION: Identifying these physical changes in vivo provides new metrics for noninvasively and quantitatively differentiating normal, acute, and chronic OM. This new diagnostic information has the potential to assist physicians to more effectively and efficiently screen, manage, and refer patients based on quantitative data. LEVEL OF EVIDENCE: 4.

Comparison of a MEMS-Based Handheld OCT Scanner With a Commercial Desktop OCT System for Retinal Evaluation.

PURPOSE: The goal of this study was to evaluate the ability of our handheld optical coherence tomography (OCT) scanner to image the posterior and anterior structures of the human eye, and especially the individual layers of the retina, and to compare its diagnostic performance with that of a fixed desktop commercial ophthalmic OCT system. METHODS: We compared the clinical imaging results of our handheld OCT with a leading commercial desktop ophthalmic system (RTVue) used in specialist offices. Six patients exhibiting diabetes-related retinal pathology had both eyes imaged with each OCT system. RESULTS: In both sets of images, the structural irregularities of the retinal layers could be identified such as retinal edema and vitreomacular traction. CONCLUSIONS: Our handheld OCT system can be used to identify relevant anatomical structures and pathologies in the eye, potentially enabling earlier screening, disease detection, and treatment. Images can be acquired quickly, with sufficient resolution and negligible motion artifacts that would normally limit its diagnostic use. TRANSLATIONAL RELEVANCE: Following screening and early disease detection in primary care via our optimized handheld OCT system, patients can be referred to a specialist for treatment, preventing further disease progression. While many primary care physicians are adept at using the ophthalmoscope, they can definitely take advantage of more advanced technologies.

Optical coherence tomography for advanced screening in the primary care office.

Optical coherence tomography (OCT) has long been used as a diagnostic tool in the field of ophthalmology. The ability to observe microstructural changes in the tissues of the eye has proved very effective in diagnosing ocular disease. However, this technology has yet to be introduced into the primary care office, where indications of disease are first encountered. We have developed a portable, handheld imaging probe for use in the primary care setting and evaluated its tissue site accessibility, ability to observe diseased tissue, and screening capabilities in in vivo human patients, particularly for pathologies related to the eye, ear and skin. Various stages of diabetic retinopathy were investigated using the handheld probe and early-stage diabetic retinopathy was flagged as abnormal from the OCT images. At such early stages of disease, it is difficult to observe abnormalities with the limited tools that are currently available to primary care physicians. These results indicate that OCT shows promise to transform from being a diagnostic technology in the medical and surgical specialities to a screening technology in the primary care office and at the front-line of healthcare.

In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror.

A biopsy is a well-known medical test used to evaluate tissue abnormality. Biopsy specimens are invasively taken from part of a lesion and visualized by microscope after chemical treatment. However, diagnosis by means of biopsy is not only variable due to depth and location of specimen but may also damage the specimen. In addition, only a limited number of specimens can be obtained, thus, the entire tissue morphology cannot be observed. We introduce a three-dimensional (3-D) endoscopic optical biopsy via optical coherence tomography employing a dual-axis microelectromechanical system scanning mirror. Since this technique provides high-resolution, noninvasive, direct, and multiple visualization of tissue, it could function as a clinical biopsy with advanced performance. The device was integrated with a conventional endoscope and utilized to generate in vivo 3-D clinical images in humans and animals.