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A low-power-consumption single-arm-driven silicon (Si) Mach-Zehnder modulator (MZM) operated at C-band ( $\lambda =1550$ nm) for non-return-to-zero on-off-keying (NRZ-OOK) transmission beyond 50 Gbit/s over 10-km single-mode fiber (SMF) and dispersion-shift fiber (DSF) is demonstrated to guarantee the IEEE 802.3bs standardized 400GBASE-FR8/LR8 operation. The Si MZM exhibits asymmetric waveguide arms and 2-mm-contact-length phase shifter under carrier depletion operation in its p-n junction, which is DC biased as low as 2 V to provide a low $\text{V}_{\pi }\text{L}$ product of $0.909~\text {V}\cdot \text {cm}$ . For the error-free transmission of the NRZ-OOK data-stream, the single-arm-driven Si MZM supports the highest data rates of 53, 53 and 50 Gbit/s over optical back-to-back, 2-km SMF and 10-km DSF transmissions, respectively. The 50-Gbit/s receiving power penalties are respectively 0.2 and 0.25 dB after 2-km SMF and 10-km DSF propagation.

Fourier-domain optical coherence tomography (FD-OCT), including spectral-domain OCT (SD-OCT) and swept-source OCT (SS-OCT), allows the volumetric imaging of the tissue architecture with a faster speed and higher detection sensitivity than does time-domain OCT. Although the hardware implementations of SD-OCT and SS-OCT are different, these technologies share very similar signal processing steps for image reconstruction. In this study, we developed hardware implementations and software architectures to design a generic framework for FD-OCT. For SD-OCT systems, an external synchronization approach was used to realize a data acquisition schematic similar to that used in SS-OCT by carefully managing the timing clocks in the detection unit and for the waveform generation. In addition, by utilizing modules and factory concepts, a software engine can be developed that supports various acquisition devices and software operations or image processing functions with high operation flexibility while maintaining its robustness. Data processing and data saving were optimized using the parallel computing method with the OpenMP library and by leveraging the parallelism within the acquired data, respectively.

Background Nucleophosmin/nucleoplasmin family 1 (NPM1) has broad physiological functions, such as DNA replication, transcription, ribosome biogenesis, and centrosome replication. This study explored the clinicopathological importance of NPM1 as a prognostic marker for oral squamous cell carcinoma (OSCC). Methods We collected specimens from 96 OSCC, 45 oral epithelial dysplasia (OED), and 29 normal oral mucosa (NOM). NPM1 expression was analyzed via immunohistochemistry. Correlations between NPM1and clinical parameters were analyzed using Student t test, chi-squared test, and Kaplan-Meier product-limit method. Results The NPM1 labeling indices (LIs) were significantly higher in OSCCs than in NOM and oral OED. Higher NPM1 expression was significantly correlated with larger tumor size, nodal metastasis, and advanced clinical stage. Multivariate analysis revealed that higher NPM1 LIs were an unfavorable independent factor for survival. Conclusions Upregulated NPM1 is an independent biomarker of poor prognosis and NPM1 inhibitors may be promising in molecular targeted therapy against OSCC.

BACKGROUND Chronic radiation proctopathy (CRP) occurs as a result of pelvic radiation therapy and is associated with formation of abnormal vasculature that may lead to persistent rectal bleeding. While incidence is declining due to refinement of radiation delivery techniques, CRP remains one of the major complications of pelvic radiation therapy and significantly affects patient quality of life. Radiofrequency ablation (RFA) is an emerging treatment modality for eradicating abnormal vasculature associated with CRP. However, questions remain regarding CRP pathophysiology and optimal disease management. AIM To study feasibility of optical coherence tomography angiography (OCTA) for investigating subsurface vascular alterations in CRP and response to RFA treatment. METHODS Two patients with normal rectum and 8 patients referred for, or undergoing endoscopic RFA treatment for CRP were imaged with a prototype ultrahigh-speed optical coherence tomography (OCT) system over 15 OCT/colonoscopy visits (2 normal patients, 5 RFA-naïve patients, 8 RFA-follow-up visits). OCT and OCTA was performed by placing the OCT catheter onto the dentate line and rectum without endoscopic guidance. OCTA enabled depth-resolved microvasculature imaging using motion contrast from flowing blood, without requiring injected dyes. OCTA features of normal and abnormal microvasculature were assessed in the mucosa and submucosa. Blinded reading of OCTA images was performed to assess the association of abnormal rectal microvasculature with CRP and RFA treatment, and rectal telangiectasia density endoscopic scoring. RESULTS OCTA/OCT images are intrinsically co-registered and enabled depth-resolved visualization of microvasculature in the mucosa and submucosa. OCTA visualized normal vascular patterns with regular honeycomb patterns vs abnormal vasculature with distorted honeycomb patterns and ectatic/tortuous microvasculature in the rectal mucosa. Normal arterioles and venules < 200 μm in diameter versus abnormal heterogenous enlarged arterioles and venules > 200 μm in diameter were visualized in the rectal submucosa. Abnormal mucosal vasculature occurred in 0 of 2 normal patients and 3 of 5 RFA-naïve patients, while abnormal submucosal vasculature occurred more often, in 1 of 2 normal patients and 5 of 5 RFA-naïve patients. After RFA treatment, vascular abnormalities decreased, with abnormal mucosal vasculature observed in 0 of 8 RFA-follow-up visits and abnormal submucosal vasculature observed in only and 2 of 8 RFA-follow-up visits. CONCLUSION OCTA visualizes depth-resolved microvascular abnormalities in CRP, allowing assessment of superficial features which are endoscopically visible as well as deeper vasculature which cannot be seen endoscopically. OCTA/OCT of the rectum can be performed in conjunction with, or independently from endoscopy. Further studies are warranted to investigate if OCTA/OCT can elucidate pathophysiology of CRP or improve management.

OBJECTIVES The myeloid-derived suppressor cells (MDSCs) frequently have a high expansion in cancer patients. This research explored whether administration of β-glucan could increase anti-tumor immunity in oral squamous cell carcinoma (OSCC) patients. MATERIALS AND METHODS This study evaluated the MDSC level of circulating blood as CD33+ /CD11b+ /HLA-DR-/low by flow cytometry in 30 healthy donors (HDs, group I), in 48 oral squamous cell carcinoma (OSCC) patients before and after 14-day preoperative administration of β-glucan (group II), and in 52 OSCC patients without taking β-glucan (group III). RESULTS A significantly higher mean MDSC level was observed in 100 OSCC patients than in 30 HDs (p

Oral cancer was ranked as the fifth most common cancers in both sexes in Taiwan in 2014. For patients diagnosed with the advanced or late stage of oral SCC, the five-year survival rate is reported to be ~ 33% suggesting the importance of the early detection of oral cancer. There have been various studies of investigating the clinical utility of OCT for the early detection of oral precancerous lesions with 1300 nm OCT technology. In this study, we have developed a long-wavelength, multiscale OCT imaging system enabling multiscale imaging of the ex vivo oral precancerous tissue with an increased imaging depth. Objectives with two different magnifications are mounted to a power turret, enabling seamless change of the OCT imaging resolution via the software control. OCT imaging over a variety of oral precancer pathologies will be demonstrated with above OCT system.

This study aimed to evaluate the use of ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography (OCT) with micromotor catheters for the in vivo assessment of Barrett's esophagus and dysplasia.74 OCT datasets with correlated biopsy/endoscopic mucosal resection histology (49 nondysplastic Barrett's esophagus [NDBE], 25 neoplasia) were obtained from 14 patients with Barrett's esophagus and a history of dysplasia and 30 with NDBE. The associations between irregular mucosal patterns on en face OCT, absence of mucosal layering, surface signal subsurface, and 5 atypical glands on cross-sectional OCT vs. histology and treatment history were assessed by three blinded readers.Atypical glands under irregular mucosal patterns occurred in 75 % of neoplasia (96 % of treatment-naïve neoplasia) vs. 30 % of NDBE datasets (43 % of short- and 18 % of long-segment NDBE). Mucosal layering was absent in 35 % of neoplasia and 50 % of NDBE datasets, and surface signal subsurface occurred in 29 % of neoplasia and 30 % of NDBE datasets.Atypical glands under irregular mucosal patterns are strongly associated with neoplasia, suggesting potential markers for dysplasia and a role in pathogenesis.This study aimed to evaluate the use of ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography (OCT) with micromotor catheters for the in vivo assessment of Barrett’s esophagus and dysplasia.74 OCT datasets with correlated biopsy/endoscopic mucosal resection histology (49 nondysplastic Barrett’s esophagus [NDBE], 25 neoplasia) were obtained from 14 patients with Barrett’s esophagus and a history of dysplasia and 30 with NDBE. The associations between irregular mucosal patterns on en face OCT, absence of mucosal layering, surface signal subsurface, and 5 atypical glands on cross-sectional OCT vs. histology and treatment history were assessed by three blinded readers.Atypical glands under irregular mucosal patterns occurred in 75 % of neoplasia (96 % of treatment-naïve neoplasia) vs. 30 % of NDBE datasets (43 % of short- and 18 % of long-segment NDBE). Mucosal layering was absent in 35 % of neoplasia and 50 % of NDBE datasets, and surface signal subsurface occurred in 29 % of neoplasia and 30 % of NDBE datasets.Atypical glands under irregular mucosal patterns are strongly associated with neoplasia, suggesting potential markers for dysplasia and a role in pathogenesis.

This research looked for social determinants that shaped choices of shelter during a natural disaster. The choices consisted of hotels/rental houses, finding relatives/friends, contacting the government for help, and checking for information about public shelters online. Social determinants examined included age, disability, education, income, social network, trust in the government, and previous disaster experience. The 2013 Taiwan Social Change Survey data and logistic regression were used for analysis. The findings were as follows: (1) compared with other groups, the richest favored hotels or rental houses for sheltering. (2) Compared with other groups, people with lower levels of education had a tendency to contact the government for help regarding shelter. (3) Compared with other groups, young people (20–34 years old), people with larger social networks (informal social capital), and people with more than one previous disaster experience preferred to contact relatives or friends for shelter. (4) People with at least a senior high school education were more likely to search for sheltering information online than their counterparts. This study provides new contributions to the literature in its investigation of the influences of social networks and previous natural disaster experience on shelter choice and of education on the choice of checking sheltering information online.

Ex-ante and ex-post assessments are both essential in risk management, although ex-post assessments of engineering measures have not been widely reported. In this study, an ex-post benefit-cost assessment method was developed to enable the direct impact of remediation engineering measures for debris flows to be quantified. We propose three categories of parameters for calculating benefit and cost: (1) predicted benefits (comprising predicted benefits of saving lives, at the household level, and of infrastructure protection); (2) actual loss (of losing lives, at the household level, and of infrastructure); (3) actual cost of the engineering. Actual benefit was defined as predicted benefit minus loss after completion of the engineering measure. The engineering measures were regarded as effective when benefits outweighed costs. Government data, survey results based on past disasters, and interview results with specialists were used. This methodology was applied and tested in ten villages located in the Gaoping River Basin in southern Taiwan. The result showed that the range of the benefit and cost ratio was between 1.26 and 7.99. We recommend this ex-post assessment method for rapid screening of districts with low benefit-cost ratios.

In this study, a Q-switch pumped supercontinuum laser (QS-SCL) is used as a light source for in vivo imaging via ultrahigh-resolution optical coherence tomography and angiography (UHR-OCT/OCTA). For this purpose, an OCT system based on a spectral-domain detection scheme is constructed, and a spectrometer with a spectral range of 635 − 875 nm is designed. The effective full-width at half maximum of spectrum covers 150 nm, and the corresponding axial and transverse resolutions are 2 and 10 µm in air, respectively. The relative intensity noise of the QS-SCL and mode-locked SCL is quantitatively compared. Furthermore, a special processing algorithm is developed to eliminate the intrinsic noise of QS-SCL. This work demonstrates that QS-SCLs can effectively reduce the cost and size of UHR-OCT/OCTA instruments, making clinical applications feasible.

We developed a software architecture utilizing the MFC library, allowing OCT imaging/data acquisition in a synchronized fashion. This architecture supports both version of the Fourier-domain OCT frameworks, including the spectral-domain and the swept-source OCT.

Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes1,2, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications3-5. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort4, show greater chemical stability at high temperatures6, and do not generate biohazardous needle waste7. An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract8. We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.

Inorganic perovskite quantum dots (IPQDs) such as cesium lead halide (CsPbX3, X = Cl, Br and I) quantum dots have attracted much attention for developing cadmium-free quantum light-emitting displays (QLEDs) based on outstanding light emission properties including narrow full width at half maximum (FWHM), tunable bandgap and ultrahigh (>90%) photoluminescence quantum yield (PLQY). Nevertheless, their poor stability under ambient conditions, at high temperature or under continuous light irradiation is the main problem for practical applications. In this study, a new method is proposed to effectively stabilize CsPbBr3 IPQDs by synthesizing them with sulfate-functionalized cellulose nanocrystals (CNCs) at room temperature without using traditional quantum dot stabilizers such as oleylamine (OLA) and oleic acid (OA). The as-prepared CsPbBr3 IPQD/CNC hybrid paper-like films are highly stable and the relative photoluminescence (PL) intensity can be maintained at 92% under continuous UV light (306 nm, 15 W) illumination for 130 h, >99% at high temperature (100 °C) for 130 h, and >99% in ambient conditions for 15 d. Additionally, the PLQY and FWHM of IPQD/CNC are 45.69% and 22 nm, respectively. The ultrahigh stability and narrow FWHM characteristics proposed here for IPQD/CNC hybrid films can provide new possibilities for practical applications in the future development of IPQD-related devices.

This study examined how to effectively implement the Sendai Framework for Disaster Risk Reduction 2015–2030 by inspecting disaster governance strategies for persons with disabilities in Taiwan. We identified priorities of the Sendai Framework that especially mention persons with disabilities or related stakeholders, including Priorities 24(a), 24(g), 24(h), 27(g), 27(h), 30(j), 30(k), 33(b), and 33(i). A set of questions was designed according to these priorities and distributed to all central ministries, agencies, and local governments related to disaster governance in Taiwan. The results showed that strategies currently cover the issues of evacuation, shelter operation, facility operation for persons with disabilities, electricity backup during emergency, strategies for schools, and disaster recovery and reconstruction. We found that the present disaster governance strategies for persons with disabilities in Taiwan are focused on the preparedness and emergency response phases, and most strategies utilize a top-down approach. Based on these findings, we suggest the development of more strategies for the recovery and reconstruction phases and the incorporation of bottom-up mechanisms such as stakeholder participation, dialogue and cooperation, coordination forums, empowerment, and consultation with stakeholders, as discussed in Priorities 24(h), 27(g), 30(j), and 33(i) of the Sendai Framework.

Endoscopic optical coherence tomography (OCT) angiography enables volumetric coregistered architectural and microvasculature imaging of the human gastrointestinal tract in vivo. In this talk, we will discuss technical advances and clinical gastroenterology applications with the endoscopic OCT angiography technique.

This paper proposes a texture analysis technique that can effectively classify different types of human breast tissue imaged by Optical Coherence Microscopy (OCM). OCM is an emerging imaging modality for rapid tissue screening and has the potential to provide high resolution microscopic images that approach those of histology. OCM images, acquired without tissue staining, however, pose unique challenges to image analysis and pattern classification. We examined multiple types of texture features and found Local Binary Pattern (LBP) features to perform better in classifying tissues imaged by OCM. In order to improve classification accuracy, we propose novel variants of LBP features, namely average LBP (ALBP) and block based LBP (BLBP). Compared with the classic LBP feature, ALBP and BLBP features provide an enhanced encoding of the texture structure in a local neighborhood by looking at intensity differences among neighboring pixels and among certain blocks of pixels in the neighborhood. Fourty-six freshly excised human breast tissue samples, including 27 benign (e.g. fibroadenoma, fibrocystic disease and usual ductal hyperplasia) and 19 breast carcinoma (e.g. invasive ductal carcinoma, ductal carcinoma in situ and lobular carcinoma in situ) were imaged with large field OCM with an imaging area of 10 × 10 mm2 (10, 000 × 10, 000 pixels) for each sample. Corresponding H&E histology was obtained for each sample and used to provide ground truth diagnosis. 4310 small OCM image blocks (500 × 500 pixels) each paired with corresponding H&E histology was extracted from large-field OCM images and labeled with one of the five different classes: adipose tissue (n = 347), fibrous stroma (n = 2,065), breast lobules (n = 199), carcinomas (pooled from all sub-types, n = 1,127), and background (regions outside of the specimens, n = 572). Our experiments show that by integrating a selected set of LBP and the two new variant (ALBP and BLBP) features at multiple scales, the classification accuracy increased from 81.7% (using LBP features alone) to 93.8% using a neural network classifier. The integrated feature was also used to classify large-field OCM images for tumor detection. A receiver operating characteristic (ROC) curve was obtained with an area under the curve value of 0.959. A sensitivity level of 100% and specificity level of 85.2% was achieved to differentiate benign from malignant samples. Several other experiments also demonstrate the complementary nature of LBP and the two variants (ALBP and BLBP features) and the significance of integrating these texture features for classification. Using features from multiple scales and performing feature selection are also effective mechanisms to improve accuracy while maintaining computational efficiency.

Volumetric Mapping of Barrett’s Esophagus and Dysplasia With en face Optical Coherence Tomography Tethered Capsule

We demonstrate a micromotor balloon imaging catheter for ultrahigh speed endoscopic optical coherence tomography (OCT) which provides wide area, circumferential structural and angiographic imaging of the esophagus without contrast agents. Using a 1310 nm MEMS tunable wavelength swept VCSEL light source, the system has a 1.2 MHz A-scan rate and ~8.5 µm axial resolution in tissue. The micromotor balloon catheter enables circumferential imaging of the esophagus at 240 frames per second (fps) with a ~30 µm (FWHM) spot size. Volumetric imaging is achieved by proximal pullback of the micromotor assembly within the balloon at 1.5 mm/sec. Volumetric data consisting of 4200 circumferential images of 5,000 A-scans each over a 2.6 cm length, covering a ~13 cm2 area is acquired in

Miniaturization and cost reduction of OCT systems are important for enabling many new clinical applications as well as accelerating the development of existing applications. Silicon photonics is an important low-cost, high-volume, multi-functional platform for integrated optics because it can benefit from existing semiconductor fabrication techniques to integrate many advanced optical functions onto a single microchip. We present a miniaturized silicon photonic integrated swept source OCT receiver, measuring 3×4mm2, with advanced functionalities including dual polarization, dual balanced, in-phase and quadrature detection, essentially enabling the detection of the full vector field (amplitude, phase, and polarization) of the optical signal. With this integrated receiver, we demonstrate full-range OCT for complex conjugate artifact suppression, polarization diversity detection for removing polarization fading artifact, and polarization sensitive OCT for tissue birefringence imaging. The silicon photonic integrated receiver is a key advance towards developing a miniaturized, multi-functional swept source OCT system.

available in PMC 2012 June 04, Materials and Methods A total of 35 renal specimens from 19 patients, consisting of 12 normal tissues and 23 tumors (16 clear cell renal cell carcinomas, 5 papillary renal cell carcinomas and 2 oncocytomas) were imaged ex vivo after surgical resection. Optical coherence tomography and optical coherence microscopy images were compared to corresponding hematoxylin and eosin histology to identify characteristic features of normal and pathological renal tissues. Three pathologists blinded to histology evaluated the sensitivity and specificity of optical coherence microscopy images to differentiate normal from neoplastic renal tissues. Results Optical coherence tomography and optical coherence microscopy images of normal kidney revealed architectural features, including glomeruli, convoluted tubules, collecting tubules and loops of Henle. Each method of imaging renal tumors clearly demonstrated morphological changes and decreased imaging depth. Optical coherence tomography and microscopy features matched well with the corresponding histology. Three observers achieved 88%, 100% and 100% sensitivity, and 100%, 88% and 100% specificity, respectively, when evaluating normal vs neoplastic specimens using optical coherence microscopy images with substantial interobserver agreement (κ = 0.82, p, National Institutes of Health (U.S.) (NIH Grants R01-CA75289-14), National Institutes of Health (U.S.) (NIH R01-HL095717-02), United States. Air Force Office of Scientific Research (FA9550-10-1-0063), United States. Air Force Office of Scientific Research (FA9550-10-1-0551)

(1) Background: Barrett&rsquo, s esophagus (BE) is a complication of chronic gastroesophageal reflux disease and is a precursor to esophageal adenocarcinoma. The clinical implication of subsurface glandular structures of Barrett&rsquo, s esophagus is not well understood. Optical coherence tomography (OCT), also known as volumetric laser endomicroscopy (VLE), can assess subsurface glandular structures, which appear as subsurface hyposcattering structures (SHSs). The aim of this study is to develop a computer-aided algorithm and apply it to investigate the characteristics of SHSs in BE using clinical VLE data, (2) Methods: SHSs were identified with an initial detection followed by machine learning. Comprehensive SHS characteristics including the number, volume, depth, size and shape were quantified. Clinical VLE datasets collected from 35 patients with a history of dysplasia undergoing BE surveillance were analyzed to study the general SHS distribution and characteristics in BE. A subset of radiofrequency ablation (RFA) patient data were further analyzed to investigate the pre-RFA SHS characteristics and post-RFA treatment response, (3) Results: SHSs in the BE region were significantly shallower, more vertical, less eccentric, and more regular, as compared with squamous SHSs. SHSs in the BE region which became neosquamous epithelium after RFA were shallower than those in the regions that remained BE. Pre-ablation squamous SHSs with higher eccentricity correlated strongly with larger reduction of post-ablation BE length for less elderly patients, (4) Conclusions: The computer algorithm is potentially a valuable tool for studying the roles of SHSs in BE.

Background Combined esophageal high-resolution impedance manometry (HRIM) measures multiple pressures and bolus transit simultaneously, facilitating detailed assessment of esophageal motility. Currently, normative values for water-perfused HRIM systems for Chinese populations are lacking. Methods Healthy volunteers were enrolled for comprehensive anthropometric measures, blood biochemistry tests, and an HRIM study using 22 water-perfused pressure sensors and 12 impedance channels. Ten 5-mL liquid swallows of saline at 30-second intervals were conducted. The following parameters were calculated: distal contractile integral (DCI), distal latency (DL), lower esophageal sphincter (LES) basal pressure, 4-second integrated relaxation pressure (IRP-4s), and complete bolus transit percentage. Normal values were established based on the 5th and 95th percentiles. Key results All 66 participants (34 male, 32 female, aged 21-64 years) completed the study and tolerated the HRIM procedure well. The upper normal limit (95th percentile) of IRP-4 second was 20 mmHg. The 5th-95th percentile range for DCI, DL, and complete bolus transit was 99-2186 mmHg●s●cm, 6.2-11.3 second, and 50%-100%, respectively. Age was negatively correlated with DL. Females had significantly higher upper limits for IRP-4s and median DCI than males. Multivariate analyses confirmed that IRP-4s was higher in females, and that higher body mass index and waist circumference were associated with reduced DL and better bolus transit, respectively. Conclusions and inferences We established normative values for the water-perfused HRIM system for a Chinese population. Gender and anthropometric factors may affect various major HRIM parameters and should be taken into account when interpreting HRIM results in clinical practice.

Optical coherence tomography (OCT) is a widely used three-dimensional (3D) optical imaging method with many biomedical and non-medical applications. Miniaturization, cost reduction, and increased functionality of OCT systems will be critical for future emerging clinical applications. We present a silicon photonic integrated circuit swept-source OCT (SS-OCT) coherent receiver with dual polarization, dual balanced, in-phase and quadrature (IQ) detection. We demonstrate multiple functional capabilities of IQ polarization resolved detection including: complex-conjugate suppressed full-range OCT, polarization diversity detection, and polarization-sensitive OCT. To our knowledge, this is the first demonstration of a silicon photonic integrated receiver for OCT. The integrated coherent receiver provides a miniaturized, low-cost solution for SS-OCT, and is also a key step towards a fully integrated high speed SS-OCT system with good performance and multi-functional capabilities. With further performance improvement and cost reduction, photonic integrated technology promises to greatly increase penetration of OCT systems in existing applications and enable new applications.

This paper proposes a texture feature which is applied on human breast Optical Coherence Microscopy (OCM) images to classify different types of breast tissues. Inspired by local binary pattern (LBP) texture features, a new variant of LBP feature, block based LBP (BLBP) is proposed. Instead of representing intensity differences between neighbors and a center pixel, BLBP feature extracts the intensity differences among certain blocks of the neighborhood around a pixel. Two different ways are proposed to organize the blocks: the spokes and the rings. By integrating spoke BLBP with ring BLBP features, very high classification accuracy is achieved using a neural network classifier. In one of our experiments which classifies 4310 OCM images into five tissue types, the classification accuracy increased from 81.7% to 92.4% when new features are used instead of the traditional LBP feature. In another experiment which classifies 46 large field OCM images as either benign or containing tumor, a classification accuracy of 91.3% is reached by using multi-scale BLBP features.

Depth resolved and en face OCT visualization in vivo may have important clinical applications in endoscopy. We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Cross-sectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications.

A 30-year-old white man with established Barrett’s esophagus (BE) and continued symptoms of chronic severe heartburn, persistent cough, throat irritation, and asthma was referred for surveillance EGD at the VA Boston Healthcare System. During retraction of the endoscope, a pink circular lesion (A) was observed under white light endoscopy in the upper esophagus (spanning 20–22 cm from the incisors). Three-dimensional endoscopic optical coherence tomography (OCT) images were obtained of the region under direct visualization with white light by passing the probe through the standard accessory channel. An en face projection image (B) at 400-μm depth underneath the tissue surface showed columnar epithelium consistent with a cervical inlet patch (CIP) and surrounding normal squamous epithelium (SE). Cross-sectional OCT images along the probe pull-back direction (C) and the probe rotation direction (D and F) clearly demonstrated columnar and squamous epithelium in the CIP region and the surrounding esophagus, respectively. Biopsy specimens taken from the imaged lesion confirmed the finding of CIP. The OCT features matched representative hematoxylin and eosin histology (E and G). Both esophageal and extraesophageal symptoms responded to increased antacid therapy., United States. Veterans Administration, National Institutes of Health (U.S.) (Grant R01-CA75289-14), United States. Air Force Office of Scientific Research (Contract FA9550-10-1-0063), United States. Dept. of Defense. Medical Free Electron Laser Program (Contract FA9550-10-1-0551), MIT/Center for Integration of Medicine and Innovative Technology (Medical Engineering Fellowship), National Science Council of Taiwan (Taiwan Merit Scholarship)

Background and Aims Angiogenesis is associated with neoplastic progression of Barrett's esophagus (BE). Volumetric optical coherence tomography angiography (OCTA) visualizes subsurface microvasculature without exogenous contrast agents. We investigated the association of OCTA microvascular features with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Methods Fifty-two patients undergoing BE surveillance or endoscopic eradication therapies for dysplasia were imaged using volumetric OCTA and corresponding histologic diagnoses wre obtained to yield 97 data sets (nondysplastic BE [NDBE], 74; LGD, 10; HGD, 13). After evaluating OCTA image quality, 54 datasets (NDBE, 35; LGD, 8; HGD, 11) from 32 patients were used to develop a training and reading protocol. The association of abnormal vessel branching and heterogeneous vessel size with LGD/HGD and a regular honeycomb vessel pattern with NDBE were investigated. Results Blinded OCTA reading of 41 OCTA datasets (NDBE, 27; LGD, 7; HGD, 7) was performed by readers with various levels of OCT/OCTA experience including 3 OCT trainees, 1 gastroenterologist, and 2 gastroenterology fellows. Among the 6 readers, OCTA features of abnormal vessel branching and heterogeneous vessel size had an overall 94% sensitivity (95% CI, 89-99) and 69% specificity (95% CI, 62-76) for differentiating LGD/HGD versus NDBE with a mean reading time of 45 seconds per data set and moderate (kappa = .58) interobserver agreement. Conclusions Volumetric en face OCTA imaging enables rapid examination of depth resolved microvascular features with near-microscopic resolution. OCTA can visualize microvascular features associated with LGD/HGD with high accuracy, which motivates new technologic advances and future studies investigating the diagnostic performance of OCTA.

Endoscopic optical coherence tomography (OCT) instruments are mostly side viewing and rely on at least one proximal scan, thus limiting accuracy of volumetric imaging and en face visualization. Previous forward-viewing OCT devices had limited axial scan speeds. We report a forward-viewing fiber scanning 3D-OCT probe with 900 μm field of view and 5 μm transverse resolution, imaging at 1 MHz axial scan rate in the human gastrointestinal tract. The probe is 3.3 mm diameter and 20 mm rigid length, thus enabling passage through the endoscopic channel. The scanner has 1.8 kHz resonant frequency, and each volumetric acquisition takes 0.17 s with 2 volumes∕s display. 3D-OCT and angiography imaging of the colon was performed during surveillance colonoscopy., National Institutes of Health (U.S.) (Grant F32-CA183400), National Institutes of Health (U.S.) (Grant R01-CA075289), National Institutes of Health (U.S.) (Grant R01-CA178636), National Institutes of Health (U.S.) (Grant R01- EY011289), National Institutes of Health (U.S.) (Grant R44-CA101067), Air Force Office of Scientific Research (Grant FA9550-12-1-0499), Air Force Office of Scientific Research (Grant FA9550-15-1-0473)

We demonstrate a computationally efficient method for correcting the nonuniform rotational distortion (NURD) in catheter-based imaging systems to improve endoscopic en face optical coherence tomography (OCT) and OCT angiography. The method performs nonrigid registration using fiducial markers on the catheter to correct rotational speed variations. Algorithm performance is investigated with an ultrahigh-speed endoscopic OCT system and micromotor catheter. Scan nonuniformity is quantitatively characterized, and artifacts from rotational speed variations are significantly reduced. Furthermore, we present endoscopic en face OCT and OCT angiography images of human gastrointestinal tract in vivo to demonstrate the image quality improvement using the correction algorithm., National Institutes of Health (U.S.) (R01-EY011289-26), National Institutes of Health (U.S.) (R44-EY022864-01), National Institutes of Health (U.S.) (R01-CA075289-16), National Institutes of Health (U.S.) (R44-CA101067-05), National Institutes of Health (U.S.) (R01-CA178636-02), United States. Air Force Office of Scientific Research (Contract FA9550-10-1-0063), United States. Air Force Office of Scientific Research (Contract FA9550-12-1-0499)

We describe an ultrahigh speed endoscopic swept source optical coherence tomography (OCT) system for clinical gastroenterology using a vertical-cavity surface-emitting laser (VCSEL) and micromotor imaging catheter. The system had a 600 kHz axial scan rate and 8 µm axial resolution in tissue. Imaging was performed with a 3.2 mm diameter imaging catheter at 400 frames per second with a 12 µm spot size. Three-dimensional OCT (3D-OCT) imaging was performed in patients with a cross section of pathologies undergoing upper and lower endoscopy. The use of distally actuated imaging catheters enabled OCT imaging with more flexibility, such as volumetric imaging in the small intestine and the assessment of hiatal hernia using retroflex imaging. The high rotational scanning stability of the micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy for both en face OCT and cross-sectional imaging, as well as OCT angiography (OCTA) for 3D visualization of subsurface microvasculature. The ability to perform both structural and functional 3D OCT imaging in the GI tract with microscopic accuracy should enable a wide range of studies and enhance the sensitivity and specificity of OCT for detecting pathology.

Endoscopic imaging technologies such as confocal laser endomicroscopy and narrow band imaging (NBI) have been used to investigate vascular changes as hallmarks of early cancer in the gastrointestinal tract. However, the limited frame rate and field of view make confocal laser endomicroscopy imaging sensitive to motion artifacts, whereas NBI has limited resolution and visualizes only the surface vascular pattern. Endoscopic optical coherence tomography (OCT) enables high-speed volumetric imaging of subsurface features at near-microscopic resolution, and can image microvasculature without exogenous contrast agents, such as fluorescein, which obliterates the image in areas of bleeding, or after biopsies and resections. OCT has been used for visualizing microvasculature in small animal models and larger vasculature in swine; however, the speed, resolution, and stability of previous systems were not sufficient for 3-dimenstional visualization of microvasculature in endoscopic clinical applications. Herein, we have presented an ultra–high-speed endoscopic OCT technology that achieves >10 times faster imaging speed than commercial systems and high frame-to-frame stability, enabling OCT angiography in the human gastrointestinal tract. Endoscopic OCT angiography of normal esophagus, nondysplastic Barrett’s esophagus (BE) and normal rectoanal junction are demonstrated., National Institutes of Health (U.S.) (R01-CA75289-16), National Institutes of Health (U.S.) (R44-CA101067-06), National Institutes of Health (U.S.) (R44EY022864-01), National Institutes of Health (U.S.) (R01-EY011289-27), National Institutes of Health (U.S.) (R01-CA178636-01), National Institutes of Health (U.S.) (R01-HL095717-04), United States. Air Force Office of Scientific Research (FA9550-12-1-0499), United States. Air Force Office of Scientific Research (FA9550-10-1-0551)

We developed an ultrahigh speed endoscopic swept source optical coherence tomography (OCT) system for clinical gastroenterology using a vertical-cavity surface-emitting laser (VCSEL) and micromotor based imaging catheter, which provided an imaging speed of 600 kHz axial scan rate and 8 μm axial resolution in tissue. The micromotor catheter was 3.2 mm in diameter and could be introduced through the 3.7 mm accessory port of an endoscope. Imaging was performed at 400 frames per second with an 8 μm spot size using a pullback to generate volumetric data over 16 mm with a pixel spacing of 5 μm in the longitudinal direction. Three-dimensional OCT (3D-OCT) imaging was performed in patients with a cross section of pathologies undergoing standard upper and lower endoscopy at the Veterans Affairs Boston Healthcare System (VABHS). Patients with Barrett’s esophagus, dysplasia, and inflammatory bowel disease were imaged. The use of distally actuated imaging catheters allowed OCT imaging with more flexibility such as volumetric imaging in the terminal ileum and the assessment of the hiatal hernia using retroflex imaging. The high rotational stability of the micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy for both en face and cross-sectional imaging. The ability to perform 3D OCT imaging in the GI tract with microscopic accuracy should enable a wide range of studies to investigate the ability of OCT to detect pathology as well as assess treatment response.

We developed a compact, optical fiber scanning piezoelectric transducer (PZT) probe for endoscopic and minimally invasive optical coherence tomography (OCT). Compared with previous forward-mount fiber designs, we present a reverse-mount design that achieves a shorter rigid length. The fiber was mounted at the proximal end of a quadruple PZT tube and scanned inside the hollow PZT tube to reduce the probe length. The fiber resonant frequency was 338 Hz using a 17-mm-long fiber. A 0.9 mm fiber deflection was achieved with a driving amplitude of 35 V. Using a GRIN lens-based optical design with a 1.3× magnification, a ∼6 μm spot was scanned over a 1.2 mm diameter field. The probe was encased in a metal hypodermic tube with a ∼25 mm rigid length and covered with a 3.2 mm outer diameter (OD) plastic sheath. Imaging was performed with a swept source OCT system based on a Fourier domain modelocked laser (FDML) light source at a 240 kHz axial scan rate and 8 μm axial resolution (in air). En face OCT imaging of skin in vivo and human colon ex vivo was demonstrated.

Optical coherence tomography (OCT) is a powerful three-dimensional (3D) imaging modality with micrometer-scale axial resolution and up to multi-GigaVoxel/s imaging speed. However, the imaging range of high-speed OCT has been limited. Here, we report 3D OCT over cubic meter volumes using a long coherence length, 1310 nm vertical-cavity surface-emitting laser and silicon photonic integrated circuit dual-quadrature receiver technology combined with enhanced signal processing. We achieved 15 μm depth resolution for tomographic imaging at a 100 kHz axial scan rate over a 1.5 m range. We show 3D macroscopic imaging examples of a human mannequin, bicycle, machine shop gauge blocks, and a human skull/brain model. High-bandwidth, meter-range OCT demonstrates new capabilities that promise to enable a wide range of biomedical, scientific, industrial, and research applications., National Institutes of Health (U.S.) (R01- EY011289-30), National Institutes of Health (U.S.) (R01-CA075289-19), National Institutes of Health (U.S.) (RO1-CA178636-02), National Institutes of Health (U.S.) (R44- EY022864-03), United States. Air Force Office of Scientific Research (FA9550-12-1-0551), United States. Air Force Office of Scientific Research (FA9550-15-1-0473)

Background Radiofrequency ablation (RFA) is effective for treating Barrett's esophagus (BE) but often involves multiple endoscopy sessions over several months to achieve complete response. Objective Identify structural markers that correlate with treatment response by using 3-dimensional (3-D) optical coherence tomography (OCT; 3-D OCT). Design Cross-sectional. Setting Single teaching hospital. Patients Thirty-three patients, 32 male and 1 female, with short-segment (, Center for Integration of Medicine and Innovative Technology (Medical Engineering Fellowship), United States. Dept. of Veterans Affairs. Boston Healthcare System, National Institutes of Health (U.S.) (Grant R01-CA75289-15), National Institutes of Health (U.S.) (Grant R44CA101067-06), National Institutes of Health (U.S.) (Grant K99-EB010071-01A1), United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0063), United States. Air Force Office of Scientific Research. Medical Free Electron Laser Program (Grant FA9550-10-1-0551)

Two main nonsurgical endoscopic approaches for ablating dysplastic and early cancer lesions in the esophagus have gained popularity, namely, radiofrequency ablation (RFA) and cryospray ablation (CSA). We report a uniquely suited endoscopic and near-microscopic imaging modality, three-dimensional (3D) optical coherence tomography (OCT), to assess and compare the esophagus immediately after RFA and CSA. The maximum depths of architectural changes were measured and compared between the two treatment groups. RFA was observed to induce 230~260 𝜇 m depth of architectural changes after each set of ablations over a particular region, while CSA was observed to induce edema-like spongiform changes to ~640 μm depth within the ablated field. The ability to obtain micron-scale depth-resolved images of tissue structural changes following different ablation therapies makes 3D-OCT an ideal tool to assess treatment efficacy. Such information could be potentially used to provide real-time feedback for treatment dosing and to identify regions that need further retreatment., National Institutes of Health (U.S.) (Grant R01-CA75289-15), National Institutes of Health (U.S.) (Grant K99-EB010071-01A1), National Institutes of Health (U.S.) (Grant R44-CA101067-06), United States. Air Force Office of Scientific Research (Contract FA9550-10-1-0063), Medical Free Electron Laser Program (Contract FA9550-10-1-0551)

Background Radiofrequency ablation (RFA) is an endoscopic technique used to eradicate Barrett's esophagus (BE). However, such ablation can commonly lead to neosquamous epithelium overlying residual BE glands not visible by conventional endoscopy and may evade detection on random biopsy samples. Objective To demonstrate the capability of endoscopic 3-dimensional optical coherence tomography (3D-OCT) for the identification and characterization of buried glands before and after RFA therapy. Design Cross-sectional study. Setting Single teaching hospital. Patients Twenty-six male and 1 female white patients with BE undergoing RFA treatment. Interventions 3D-OCT was performed at the gastroesophageal junction in 18 patients before attaining complete eradication of intestinal metaplasia (pre–CE-IM group) and in 16 patients after CE-IM (post–CE-IM group). Main Outcome Measurements Prevalence, size, and location of buried glands relative to the squamocolumnar junction. Results 3D-OCT provided an approximately 30 to 60 times larger field of view compared with jumbo and standard biopsy and sufficient imaging depth for detecting buried glands. Based on 3D-OCT results, buried glands were found in 72% of patients (13/18) in the pre–CE-IM group and 63% of patients (10/16) in the post–CE-IM group. The number (mean [standard deviation]) of buried glands per patient in the post–CE-IM group (7.1 [9.3]) was significantly lower compared with the pre–CE-IM group (34.4 [44.6]; P = .02). The buried gland size (P = .69) and distribution (P = .54) were not significantly different before and after CE-IM. Limitations A single-center, cross-sectional study comparing patients at different time points in treatment. Lack of 1-to-1 coregistered histology for all OCT data sets obtained in vivo. Conclusion Buried glands were frequently detected with 3D-OCT near the gastroesophageal junction before and after radiofrequency ablation., National Institutes of Health (U.S.) (Grant R01-CA75289-15), National Institutes of Health (U.S.) (Grant R44CA101067-06), National Institutes of Health (U.S.) (Grant R01-HL095717-03), National Institutes of Health (U.S.) (Grant R01-NS057476-05), National Institutes of Health (U.S.) (Grant K99-EB010071-01A1), United States. Air Force Office of Scientific Research (Contract FA9550-10-1-0063), United States. Air Force Office of Scientific Research. Medical Free Electron Laser Program (Contract FA9550-10-1-0551), Center for Integration of Medicine and Innovative Technology

Three-dimensional (3D) tissue imaging methods are expected to improve surgical management of cancer. In this study, we examined the feasibility of two 3D imaging technologies, optical coherence tomography (OCT) and optical coherence microscopy (OCM), to view human breast specimens based on intrinsic optical contrast. Specifically, we imaged 44 ex vivo breast specimens including 34 benign and 10 malignant lesions with an integrated OCT and OCM system developed in our laboratory. The system enabled 4-μm axial resolution (OCT and OCM) with 14-μm (OCT) and 2-μm (OCM) transverse resolutions, respectively. OCT and OCM images were compared with corresponding histologic sections to identify characteristic features from benign and malignant breast lesions at multiple resolution scales. OCT and OCM provide complimentary information about tissue microstructure, thus showing distinctive patterns for adipose tissue, fibrous stroma, breast lobules and ducts, cysts and microcysts, as well as in situ and invasive carcinomas. The 3D imaging capability of OCT and OCM provided complementary information to individual 2D images, thereby allowing tracking features from different levels to identify low-contrast structures that were difficult to appreciate from single images alone. Our results lay the foundation for future in vivo optical evaluation of breast tissues, using OCT and OCM, which has the potential to guide core needle biopsies, assess surgical margins, and evaluate nodal involvement in breast cancer., National Institutes of Health (U.S.) (Grant R01-CA75289-13), Air Force Office of Scientific Research (Contract FA9550-07-1-0014)

We demonstrate photothermal optical coherence tomography (OCT) imaging in highly scattering human breast tissue ex vivo. A 120 kHz axial scan rate, swept-source phase-sensitive OCT system at 1300 nm was used to detect phase changes induced by 830 nm photothermal excitation of gold nanoshells. Localized phase modulation was observed 300–600 μm deep in scattering tissue using an excitation power of only 22 mW at modulation frequencies up to 20 kHz. This technique enables integrated structural and molecular-targeted imaging for cancer markers using nanoshells., National Institutes of Health (U.S.) (Grant Number R01- CA75289-13), United States. Air Force Office of Scientific Research (Contract Number FA9550-07-1-0014), MFELP (Contract Number FA9550-07-1-0101), Natural Sciences and Engineering Research Council of Canada (NSERC) Heritage Scholarship Fund, Center for Integration of Medicine and Innovative Technology, National Science council of Taiwan. Taiwan Merit Scholarship

Excisional biopsy is the current gold standard for disease diagnosis; however, it requires a relatively long processing time and it may also suffer from unacceptable false negative rates due to sampling errors. Optical coherence tomography (OCT) is a promising imaging technique that provide real-time, high resolution and three-dimensional (3D) images of tissue morphology. Optical coherence microscopy (OCM) is an extension of OCT, combining both the coherence gating and the confocal gating techniques. OCM imaging achieves cellular resolution with deeper imaging depth compared to confocal microscopy. An integrated OCT/OCM imaging system can provide co-registered multiscale imaging of tissue morphology. 3D-OCT provides architectural information with a large field of view and can be used to find regions of interest; while OCM provides high magnification to enable cellular imaging. The integrated OCT/OCM system has an axial resolution of