In vivo polarisation sensitive optical coherence tomography for fibrosis assessment in interstitial lung disease: a prospective, exploratory, observational study.

INTRODUCTION: Endobronchial polarisation sensitive optical coherence tomography (EB-PS-OCT) is a bronchoscopic imaging technique exceeding resolution of high-resolution CT (HRCT) by 50-fold. It detects collagen birefringence, enabling identification and quantification of fibrosis. STUDY AIM: To assess pulmonary fibrosis in interstitial lung diseases (ILD) patients with in vivo EB-PS-OCT using histology as reference standard. PRIMARY OBJECTIVE: Visualisation and quantification of pulmonary fibrosis by EB-PS-OCT. SECONDARY OBJECTIVES: Comparison of EB-PS-OCT and HRCT detected fibrosis with histology, identification of ILD histological features in EB-PS-OCT images and comparison of ex vivo PS-OCT results with histology. METHODS: Observational prospective exploratory study. Patients with ILD scheduled for transbronchial cryobiopsy or surgical lung biopsy underwent in vivo EB-PS-OCT imaging prior to tissue acquisition. Asthma patients were included as non-fibrotic controls. Per imaged lung segment, fibrosis was automatically quantified assessing the birefringent area in EB-PS-OCT images. Fibrotic extent in corresponding HRCT areas and biopsies were compared with EB-PS-OCT detected fibrosis. Microscopic ILD features were identified on EB-PS-OCT images and matched with biopsies from the same segment. RESULTS: 19 patients were included (16 ILD; 3 asthma). In 49 in vivo imaged airway segments the parenchymal birefringent area was successfully quantified and ranged from 2.54% (no to minimal fibrosis) to 21.01% (extensive fibrosis). Increased EB-PS-OCT detected birefringent area corresponded to increased histologically confirmed fibrosis, with better predictive value than HRCT. Microscopic ILD features were identified on both in vivo and ex vivo PS-OCT images. CONCLUSIONS: EB-PS-OCT enables pulmonary fibrosis quantification, thereby has potential to serve as an add-on bronchoscopic imaging technique to diagnose and detect (early) fibrosis in ILD.

Polarization-sensitive optical coherence tomography in end-stage lung diseases: an ex vivo pilot study.

A non-invasive diagnostic tool to assess remodeling of the lung airways caused by disease is currently missing in the clinic. Measuring key features such as airway smooth muscle (ASM) thickness would increase the ability to improve diagnosis and enable treatment evaluation. In this research, polarization-sensitive optical coherence tomography (PS-OCT) has been used to image a total of 24 airways from two healthy lungs and four end-stage diseased lungs ex vivo, including fibrotic sarcoidosis, chronic obstructive pulmonary disease (COPD), fibrotic hypersensitivity pneumonitis, and cystic fibrosis. In the diseased lungs, except COPD, the amount of measured airway smooth muscle was increased. In COPD, airway smooth muscle could not be distinguished from surrounding collagen. COPD lungs showed increased alveolar size. 3D pullbacks in the same lumen provided reproducible assessment of airway smooth muscle (ASM). Image features such as thickened ASM and size/presence of alveoli were recognized in histology. The results of this study are preliminary and must be confirmed with further ex vivo and in vivo studies. PS-OCT is applicable for in vivo assessment of peribronchial and peribronchiolar lung structures and may become a valuable tool for diagnosis in pulmonology.

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer's disease human brain tissue.

Alzheimer's disease (AD) neuropathology is characterized by hyperphosphorylated tau containing neurofibrillary tangles and amyloid-beta (Aß) plaques. Normally these hallmarks are studied by (immuno-) histological techniques requiring chemical pretreatment and indirect labelling. Label-free imaging enables one to visualize normal tissue and pathology in its native form. Therefore, these techniques could contribute to a better understanding of the disease. Here, we present a comprehensive study of high-resolution fluorescence imaging (before and after staining) and spectroscopic modalities (Raman mapping under pre-resonance conditions and stimulated Raman scattering (SRS)) of amyloid deposits in snap-frozen AD human brain tissue. We performed fluorescence and spectroscopic imaging and subsequent thioflavin-S staining of the same tissue slices to provide direct confirmation of plaque location and correlation of spectroscopic biomarkers with plaque morphology; differences were observed between cored and fibrillar plaques. The SRS results showed a protein peak shift towards the ß-sheet structure in cored amyloid deposits. In the Raman maps recorded with 532 nm excitation we identified the presence of carotenoids as a unique marker to differentiate between a cored amyloid plaque area versus a non-plaque area without prior knowledge of their location. The observed presence of carotenoids suggests a distinct neuroinflammatory response to misfolded protein accumulations.

Detailed optical coherence tomography angiographic short-term response of type 3 neovascularization to combined treatment with photodynamic therapy and intravitreal bevacizumab.

PURPOSE: To explore the short-term vascular and structural changes of type 3 neovascularization using optical coherence tomography angiography (OCT-A) when treated with a combination of photodynamic therapy (PDT) and intravitreal bevacizumab (IVB), and to evaluate the course of different sequences of the combined therapies. METHODS: Thirty eyes of 29 treatment-naïve patients with a type 3 neovascularization were included in this prospective observational cohort study. They were all treated with PDT and IVB 2 weeks apart, starting either with PDT (PDT-first group) or IVB (IVB-first group). Optical coherence tomography angiography (OCT-A) imaging was performed at week 0, 2, 4 and 18, and best corrected visual acuity (BCVA) at week 0 and 18. Vascular, structural and functional features were graded and analysed over time. RESULTS: In all patients, at all follow-up visits, vascular and structural features were significantly more often decreased or resolved than unchanged or increased. Best corrected visual acuity (BCVA) significantly improved at 18 weeks. Vascular, structural and functional outcomes were all slightly better in the PDT-first group compared to the IVB-first group, although not statistically significant. CONCLUSION: Combined treatment of PDT and IVB is effective in short-term for type 3 neovascularization based on vascular and structural features. Initial treatment with PDT tended to be more effective than with IVB.

Label-free stimulated Raman scattering imaging reveals silicone breast implant material in tissue.

Millions of women worldwide have silicone breast implants. It has been reported that implant failure occurs in approximately a tenth of patients within 10 years, and the consequences of dissemination of silicone debris are poorly understood. Currently, silicone detection in histopathological slides is based on morphological features as no specific immunohistochemical technique is available. Here, we show the feasibility and sensitivity of stimulated Raman scattering (SRS) imaging to specifically detect silicone material in stained histopathological slides, without additional sample treatment. Histology slides of four periprosthetic capsules from different implant types were obtained after explantation, as well as an enlarged axillary lymph node from a patient with a ruptured implant. SRS images coregistered with bright-field images revealed the distribution and quantity of silicone material in the tissue. Fast and high-resolution imaging of histology slides with molecular specificity using SRS provides an opportunity to investigate the role of silicone debris in the pathophysiology of implant-linked diseases.

Optical coherence tomography (OCT) to image active and inactive retinoblastomas as well as retinomas.

PURPOSE: To illustrate Optical Coherence Tomography (OCT) images of active and inactive retinoblastoma (Rb) tumours. METHODS: Current observational study included patients diagnosed with retinoblastoma and retinoma who were presented at Amsterdam UMC and Jules-Gonin Eye Hospital, between November 2010 and October 2017. Patients aged between 0 and 4 years were imaged under general anaesthesia with handheld OCT in supine position. Patients older than 4 years were imaged with the conventional OCT (Heidelberg Engineering, Heidelberg Spectralis, Germany). All patients included were divided into two groups: active and inactive tumours (retinoma and regression patterns). Patients' medical records and OCT images were analysed during meetings via discussions by ophthalmologists and physicists. RESULTS: Twelve Dutch and 8 Swiss patients were divided into two groups: 2 patients with active tumour versus 18 patients with inactive tumour. Subsequently, inactive group could be divided in two groups, which consisted of 10 patients with retinoma and 8 patients with different regression pattern types. Of all included patients, 15 were male (75%). Median age at diagnosis was 18.0 months (range 0.19-715.2 months). A total of 12 retinoblastoma (active and inactive) and 8 retinoma foci were investigated by OCT. No distinction could be made between active and inactive tumours using only OCT. CONCLUSION: Optical coherence tomography alone cannot distinguish between active and inactive Rbs. However, handheld OCT adds useful information to the established imaging techniques in the monitoring and follow-up of retinoblastoma patients. With this study, we provide an overview of OCT images of active and inactive Rbs.

Classification and treatment follow-up of a juxtapapillary retinal hemangioblastoma with optical coherence tomography angiography.

PURPOSE: Only an endophytic growth pattern in juxtapapillary retinal hemangioblastoma (JRH) is an indication for surgical treatment, but classification of growth types is difficult using conventional imaging techniques. This case report describes the use of optical coherence tomography angiography (OCT-A) features for classification and treatment follow-up in a case with JRH. OBSERVATIONS: The JRH of this patient was easily detected with two different OCT-A methods in both en-face and cross-sectional B-scan images, and was classified as a sessile growth type. This growth type excluded the treatment option of vitreoretinal surgery with excision of the lesion or ligation of the feeder vessels. The patient was treated multiple times with intravitreal bevacizumab. Treatment follow-up with OCT-A initially revealed a stable extent of the JRH, with some slight flow deviations in en-face visualization, followed by a period of progressive growth of the lesion. CONCLUSIONS: OCT-A revealed the depth localization of the JRH and seems to be a valuable tool for JRH classification. Detailed classification may be useful when surgery is considered as a treatment strategy. Furthermore, treatment follow-up is possible with OCT-A, although imaging artifacts should be taken into account.

Optical coherence tomography to detect acute esophageal radiation-induced damage in mice: A validation study.

Radiation therapy for patients with non-small-cell lung cancer is hampered by acute radiation-induced toxicity in the esophagus. This study aims to validate that optical coherence tomography (OCT), a minimally invasive imaging technique with high resolution (~10 µm), is able to visualize and monitor acute radiation-induced esophageal damage (ARIED) in mice. We compare our findings with histopathology as the gold standard. Irradiated mice receive a single dose of 40 Gy at proximal and distal spots of the esophagus of 10.0 mm in diameter. We scan mice using OCT at two, three, and seven days post-irradiation. In OCT analysis, we define ARIED as a presence of distorted esophageal layering, change in backscattering signal properties, or change in the esophageal wall thickness. The average esophageal wall thickness is 0.53 mm larger on OCT when ARIED is present based on histopathology. The overall sensitivity and specificity of OCT to detect ARIED compared to histopathology are 94% and 47%, respectively. However, the overall sensitivity of OCT to assess ARIED is 100% seven days post-irradiation. We validate the capability of OCT to detect ARIED induced by high doses in mice. Nevertheless, clinical studies are required to assess the potential role of OCT to visualize ARIED in humans.

Phase-based OCT angiography in diagnostic imaging of pediatric retinoblastoma patients: abnormal blood vessels in post-treatment regression patterns.

Phase-based OCT angiography of retinoblastoma regression patterns with a novel handheld 1050 nm clinical imaging system is demonstrated for the first time in children between 0 and 4 years old under general anesthesia. Angiography is mapped at OCT resolution by flow detection at every pixel with en-face projection from the volume between nerve fiber layer and retinal pigment epithelium. We show a striking difference between blood vasculature of healthy retina, and retinoblastoma regression patterns after chemotherapy, as well as varying complexity of abnormal vasculature in regression patterns types 2, 3, and 4. We demonstrate abnormal, tortuous and prominent vasculature in type 3 regression patterns having the highest risk of tumor recurrences and a lower probability to reduction into flat scars. The ability to visualize 3-D angiography might offer new insights in understanding of retinoblastoma development and its response to therapy.

Treatment Effects in Retinal Angiomatous Proliferation Imaged with OCT Angiography.

PURPOSE: This prospective case series is aimed at exploring optical coherence tomographic angiography (OCT-A) as a treatment monitoring tool in patients treated for retinal angiomatous proliferation (RAP). METHODS: Twelve treatment-naïve RAP patients were included, with a median age of 79 years (range 65-90). Patients were imaged with an experimental 1,040-nm swept-source phase-resolved OCT-A instrument before and after treatment. Treatment consisted of either intravitreal bevacizumab or triamcinolone injections with or without photodynamic therapy (PDT). Abnormal blood flow after treatment was graded as increased, unchanged, decreased, or resolved. RESULTS: OCT-A images before and after treatment could be obtained in 9 patients. The median follow-up period was 10 weeks (range 5-19). After various treatments, the RAP lesion resolved in 7 patients, in 1 patient the OCT-A depicted decreased flow in the lesion, and 1 patient showed unchanged abnormal blood flow. Monotherapy with intravitreal bevacizumab injections resolved RAP in 1 out of 2 patients. Combined therapy of bevacizumab with PDT resolved RAP in 6 out of 7 patients. CONCLUSIONS: OCT-A visualized resolution of abnormal blood flow in 7 out of 9 RAP patients after various short-term treatment sequences. OCT-A may become an important noninvasive monitoring tool for optimizing treatment strategies in RAP patients.

Feasibility of using optical coherence tomography to detect acute radiation-induced esophageal damage in small animal models.

Lung cancer survival is poor, and radiation therapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to acute radiation-induced esophageal damage (ARIED). We investigated the feasibility of optical coherence tomography (OCT) for minimally invasive imaging of the esophagus with high resolution (10 µm) to detect ARIED in mice. Thirty mice underwent cone-beam computed tomography imaging for initial setup assessment and dose planning followed by a single-dose delivery of 4.0, 10.0, 16.0, and 20.0 Gy on 5.0-mm spots, spaced 10.0 mm apart in the esophagus. They were repeatedly imaged using OCT up to three months postirradiation. We compared OCT findings with histopathology obtained three months postirradiation qualitatively and quantitatively using the contrast-to-background-noise ratio (CNR). Histopathology mostly showed inflammatory infiltration and edema at higher doses; OCT findings were in agreement with most of the histopathological reports. We were able to identify the ARIED on OCT as a change in tissue scattering and layer thickness. Our statistical analysis showed significant difference between the CNR values of healthy tissue, edema, and inflammatory infiltration. Overall, the average CNR for inflammatory infiltration and edema damages was 1.6-fold higher and 1.6-fold lower than for the healthy esophageal wall, respectively. Our results showed the potential role of OCT to detect and monitor the ARIED in mice, which may translate to humans.

Feasibility of using optical coherence tomography to detect radiation-induced fibrosis and residual cancer extent after neoadjuvant chemo-radiation therapy: an ex vivo study.

Treatment of resectable esophageal cancer includes neoadjuvant chemo-radiation therapy (nCRT) followed by esophagectomy in operable patients. High-risk surgery may have been avoided in patients with a pathological complete response (pCR). We investigated the feasibility of optical coherence tomography (OCT) to detect residual cancer and radiation-induced fibrosis in 10 esophageal cancer patients that underwent nCRT followed by esophagectomy. We compared our OCT findings with histopathology. Overall, OCT was able to differentiate between healthy tissue, fibrotic tissue, and residual cancer with a sensitivity and specificity of 79% and 67%, respectively. Hence, OCT has the potential to add to the assessment of a pCR.

High resolution combined molecular and structural optical imaging of colorectal cancer in a xenograft mouse model.

With the emergence of immunotherapies for cancer treatment, there is a rising clinical need to visualize the tumor microenvironment (TME) non-invasively in detail, which could be crucial to predict the efficacy of therapy. Nuclear imaging techniques enable whole-body imaging but lack the required spatial resolution. Conversely, near-infrared immunofluorescence (immuno-NIRF) is able to reveal tumor cells and/or other cell subsets in the TME by targeting the expression of a specific membrane receptor with fluorescently labeled monoclonal antibodies (mAb). Optical coherence tomography (OCT) provides three-dimensional morphological imaging of tissues without exogenous contrast agents. The combination of the two allows molecular and structural contrast at a resolution of ~15 µm, allowing for the specific location of a cell-type target with immuno-NIRF as well as revealing the three-dimensional architectural context with OCT. For the first time, combined immuno-NIRF and OCT of a tumor is demonstrated in situ in a xenograft mouse model of human colorectal cancer, targeted by a clinically-safe fluorescent mAb, revealing unprecedented details of the TME. A handheld scanner for ex vivo examination and an endoscope designed for imaging bronchioles in vivo are presented. This technique promises to complement nuclear imaging for diagnosing cancer invasiveness, precisely determining tumor margins, and studying the biodistribution of newly developed antibodies in high detail.

Visibility of fiducial markers used for image-guided radiation therapy on optical coherence tomography for registration with CT: An esophageal phantom study.

PURPOSE: Optical coherence tomography (OCT) is of interest to visualize microscopic esophageal tumor extensions to improve tumor delineation for radiation therapy (RT) planning. Fiducial marker placement is a common method to ensure target localization during planning and treatment. Visualization of these fiducial markers on OCT permits integrating OCT and computed tomography (CT) images used for RT planning via image registration. We studied the visibility of 13 (eight types) commercially available solid and liquid fiducial markers in OCT images at different depths using dedicated esophageal phantoms and evaluated marker placement depth in clinical practice. MATERIALS AND METHODS: We designed and fabricated dedicated esophageal phantoms, in which three layers mimic the anatomical wall structures of a healthy human esophagus. We successfully implanted 13 commercially available fiducial markers that varied in diameter and material property at depths between 0.5 and 3.0 mm. The resulting esophageal phantoms were imaged with OCT, and marker visibility was assessed qualitatively and quantitatively using the contrast-to-background-noise ratio (CNR). The CNR was defined as the difference between the mean intensity of the fiducial markers and the mean intensity of the background divided by the standard deviation of the background intensity. To determine whether, in current clinical practice, the implanted fiducial markers are within the OCT visualization range (up to 3.0 mm depth), we retrospectively measured the distance of 19 fiducial markers to the esophageal lumen on CT scans of 16 esophageal cancer patients. RESULTS: In the esophageal phantoms, all the included fiducial markers were visible on OCT at all investigated depths. Solid fiducial markers were better visible on OCT than liquid fiducial markers with a 1.74-fold higher CNR. Although fiducial marker identification per type and size was slightly easier for superficially implanted fiducial markers, we observed no difference in the ability of OCT to visualize the markers over the investigated depth range. Retrospective distance measurements of 19 fiducial markers on the CT scan of esophageal cancer patients showed that 84% (distance from the closest border of the marker to the lumen) and 53% (distance from the center of the marker to the lumen) of the fiducial markers were located within the OCT visualization range of up to 3.0 mm. CONCLUSIONS: We studied the visibility of eight types of commercially available fiducial markers at different depths on OCT using dedicated esophageal phantoms. All tested fiducial markers were visible at depths ≤3.0 mm and most, but not all, clinically implanted markers were at a depth accessible to OCT. Consequently, the use of fiducial markers as a reference for OCT to CT registration is feasible.

Phase-Resolved Doppler Optical Coherence Tomographic Features in Retinal Angiomatous Proliferation.

PURPOSE: To study patients diagnosed with retinal angiomatous proliferation (RAP) based on conventional imaging techniques with phase-resolved Doppler optical coherence tomography (OCT) to detect and localize blood flow in RAP lesions; and to compare these findings to conventional imaging, which are mostly invasive and give limited information concerning intra- and transretinal blood flow. DESIGN: Single-center, consecutive observational case series. METHODS: Twelve treatment-naïve patients diagnosed with RAP based on fundus examination, fluorescein angiography, and indocyanine green angiography were included. Median age was 79 years (range 65-90). Patients were imaged with an experimental 1040 nm swept-source phase-resolved Doppler OCT instrument. Abnormal flow was defined as intraretinal neovascularization or retinal choroidal anastomosis. RESULTS: In 11 patients adequate phase-resolved Doppler OCT images were obtained showing abnormal blood flow in the RAP lesion. In 4 patients a retinal choroidal anastomosis was found, 3 patients showed intraretinal neovascularization connected with a pigment epithelial detachment, 2 patients showed only intraretinal neovascularization, and in 2 patients flow was limited to the subretinal or sub-retinal pigment epithelial space. CONCLUSIONS: Phase-resolved Doppler OCT is able to detect and localize abnormal blood flow within RAP lesions. Blood flow was mostly confined to the intraretinal structures with or without a connecting pigment epithelial detachment; in one-third of patients a retinal choroidal anastomosis was detected. The potential of angiography with phase-resolved Doppler OCT to accurately distinguish between normal and pathologic blood flow in addition to structural OCT data without invasive procedures will help to further elucidate both retinal and choroidal vascular pathologies like RAP.

Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node.

PURPOSE: At present, the only approved fluorescent tracer for clinical near-infrared fluorescence-guided sentinel node (SN) detection is indocyanine green (ICG), but the use of this tracer is limited due to its poor retention in the SN resulting in the detection of higher tier nodes. We describe the development and characterization of a next-generation fluorescent tracer, nanocolloidal albumin-IRDye 800CW that has optimal properties for clinical SN detection. METHODS: The fluorescent dye IRDye 800CW was covalently coupled to colloidal human serum albumin (HSA) particles present in the labelling kit Nanocoll in a manner compliant with current Good Manufacturing Practice. Characterization of nanocolloidal albumin-IRDye 800CW included determination of conjugation efficiency, purity, stability and particle size. Quantum yield was determined in serum and compared to that of ICG. For in vivo evaluation a lymphogenic metastatic tumour model in rabbits was used. Fluorescence imaging was performed directly after peritumoral injection of nanocolloidal albumin-IRDye 800CW or the reference ICG/HSA (i.e. ICG mixed with HSA), and was repeated after 24 h, after which fluorescent lymph nodes were excised. RESULTS: Conjugation of IRDye 800CW to nanocolloidal albumin was always about 50% efficient and resulted in a stable and pure product without affecting the particle size of the nanocolloidal albumin. The quantum yield of nanocolloidal albumin-IRDye 800CW was similar to that of ICG. In vivo evaluation revealed noninvasive detection of the SN within 5 min of injection of either nanocolloidal albumin-IRDye 800CW or ICG/HSA. No decrease in the fluorescence signal from SN was observed 24 h after injection of the nanocolloidal albumin-IRDye 800CW, while a strong decrease or complete disappearance of the fluorescence signal was seen 24 h after injection of ICG/HSA. Fluorescence-guided SN biopsy was very easy. CONCLUSION: Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection.

Phase-stabilized optical frequency domain imaging at 1-µm for the measurement of blood flow in the human choroid.

In optical frequency domain imaging (OFDI) the measurement of interference fringes is not exactly reproducible due to small instabilities in the swept-source laser, the interferometer and the data-acquisition hardware. The resulting variation in wavenumber sampling makes phase-resolved detection and the removal of fixed-pattern noise challenging in OFDI. In this paper this problem is solved by a new post-processing method in which interference fringes are resampled to the exact same wavenumber space using a simultaneously recorded calibration signal. This method is implemented in a high-speed (100 kHz) high-resolution (6.5 µm) OFDI system at 1-µm and is used for the removal of fixed-pattern noise artifacts and for phase-resolved blood flow measurements in the human choroid. The system performed close to the shot-noise limit (<1dB) with a sensitivity of 99.1 dB for a 1.7 mW sample arm power. Suppression of fixed-pattern noise artifacts is shown up to 39.0 dB which effectively removes all artifacts from the OFDI-images. The clinical potential of the system is shown by the detection of choroidal blood flow in a healthy volunteer and the detection of tissue reperfusion in a patient after a retinal pigment epithelium and choroid transplantation.

Polarization-sensitive optical frequency domain imaging based on unpolarized light.

Polarization-sensitive optical coherence tomography (PS-OCT) is an augmented form of OCT, providing 3D images of both tissue structure and polarization properties. We developed a new method of polarization-sensitive optical frequency domain imaging (PS-OFDI), which is based on a wavelength-swept source. In this method the sample was illuminated with unpolarized light, which was composed of two orthogonal polarization states (i.e., separated by 180° in the Poincaré sphere) that are uncorrelated to each other. Reflection of these polarization states from within the sample was detected simultaneously and independently using a frequency multiplexing scheme. This simultaneous sample probing with two polarization states enabled determination of the depth-resolved Jones matrices of the sample. Polarization properties of the sample were obtained by analyzing the sample Jones matrices through eigenvector decomposition. The new PS-OFDI system ran at 31K wavelength-scans/s with 3072 pixels per wavelength-scan, and was tested by imaging a polarizer and several birefringent tissues such as chicken muscle and human skin. Lastly the new PS-OFDI was applied to imaging two cancer animal models: a mouse model by injecting cancer cells and a hamster cheek pouch model. These animal model studies demonstrated the significant differences in tissue polarization properties between cancer and normal tissues in vivo.

In vivo 3D human vocal fold imaging with polarization sensitive optical coherence tomography and a MEMS scanning catheter.

We present in-vivo 3D human vocal fold images with polarization sensitive optical coherence tomography (PS-OCT). Characterizing the extent and location of vocal fold lesions provides useful information in guiding surgeons during phonomicrosurgery. Previous studies showed that PS-OCT imaging can distinguish vocal fold lesions from normal tissue, but these studies were limited to 2D cross-sectional imaging and were susceptible to sampling error. In-vivo 3D endoscopic imaging was performed by using a recently developed 2-axis MEMS scanning catheter and a spectral domain OCT (SD-OCT), running at 18.5 frames/s. Imaging was performed in the operating room with patients under general anesthesia and 3D images were acquired either by 2D scanning of the scanner on the sites of interest or by combining 1D scanning and manual sliding to capture whole length of the vocal fold. Vocal fold scar, polyps, nodules, papilloma and malignant lesions were imaged and characteristics of individual lesions were analyzed in terms of spatial distribution and variation of tissue structure and birefringence. The 3D large sectional PS-OCT imaging showed that the spatial extent of vocal fold lesions can be found non-invasively with good contrast from normal tissue.