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Supplementary Video 3 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 4 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Figure 1, Legends for Figure 1 and Videos 1-4 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 1 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 2 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

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.

Optical coherence tomography angiography (OCTA) can provide rapid, volumetric, and noninvasive imaging of tissue microvasculature without the requirement of exogenous contrast agents. To investigate how A-scan rate and interscan time affected the contrast and dynamic range of OCTA, we developed a 1.06-µm swept-source OCT system enabling 100-kHz or 200-kHz OCT using two light sources. After system settings were carefully adjusted, almost the same detection sensitivity was achieved between the 100-kHz and 200-kHz modalities. OCTA of ear skin was performed on five mice. We used the variable interscan time analysis algorithm (VISTA) and the designated scanning protocol with OCTA images reconstructed through the correlation mapping method. With a relatively long interscan time (e.g., 12.5 ms vs. 6.25 ms for 200-kHz OCT), OCTA can identify more intricate microvascular networks. OCTA image sets with the same interscan time (e.g., 12.5 ms) were compared. OCTA images acquired with a 100-kHz A-scan rate showed finer microvasculature than did other imaging modalities. We performed quantitative analysis on the contrast from OCTA images reconstructed with different A-scan rates and interscan time intervals in terms of vessel area, total vessel length, and junction density.

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.

Recently, the functional extension of optical coherence tomography (OCT) with OCT angiography (OCTA) allows volumetric imaging of the subsurface microvasculature without requiring exogenous contrast agents like conventional angiography techniques. However, performing OCTA requires intensive computation to extract the changes of OCT signal due to moving red blood cells in the microvascular network. In this study, we have developed a graphic processing unit (GPU)-accelerated framework to realize high speed OCTA imaging and the visualization of the microvascular network after the data acquisition. In addition, we investigate the feasibility of providing real-time microvascular imaging leveraging dynamic scattering OCT and GPU.

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.

This study investigated the effects of social determinants and resource distribution on trust in government after a disaster. This involved an analysis of four waves of the Social Impact an...

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

Currently, the cochlear implantation procedure mainly relies on using a hand lens or surgical microscope, where the success rate and surgery time strongly depend on the surgeon’s experience. Therefore, a real-time image guidance tool may facilitate the implantation procedure. In this study, we performed a systematic and quantitative analysis on the optical characterization of ex vivo mouse cochlear samples using two swept-source optical coherence tomography (OCT) systems operating at the 1.06-µm and 1.3-µm wavelengths. The analysis results demonstrated that the 1.06-µm OCT imaging system performed better than the 1.3-µm OCT imaging system in terms of the image contrast between the cochlear conduits and the neighboring cochlear bony wall structure. However, the 1.3-µm OCT imaging system allowed for greater imaging depth of the cochlear samples because of decreased tissue scattering. In addition, we have investigated the feasibility of identifying the electrode of the cochlear implant within the ex vivo cochlear sample with the 1.06-µm OCT imaging. The study results demonstrated the potential of developing an image guidance tool for the cochlea implantation procedure as well as other otorhinolaryngology applications.

Manipulation and precise delivery of optical energies in the regions of interest within specimens require different strategies. Hence, proper control of input beam parameters is a prerequisite. One of the prominent methods is metasurface optics, capable of crafting properties of light at nanoscales. Here, the generation of an abrupt autofocusing (AAF) beam by a nanophotonic metasurface for biomedical applications is demonstrated. Fluorescence guided laser microprofiling of mouse cardiac samples is experimentally investigated, using the AAF beam to deliver optical energy selectively to specific locations. In addition, photocoagulation of ex vivo swine skin tissue is performed and observed through optical coherence tomography. The results show great potentials for integrating metasurface optics to realize miniature laser surgery instruments for wide applications in biomedicine.

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.

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.

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.

A technique using Linnik-based optical coherence microscopy (OCM), with built-in fluorescence microscopy (FM), is demonstrated here to describe cellular-level morphology for fresh porcine and biobank tissue specimens. The proposed method utilizes color-coding to generate digital pseudo-H&E (p-H&E) images. Using the same camera, colocalized FM images are merged with corresponding morphological OCM images using a 24-bit RGB composition process to generate position-matched p-H&E images. From receipt of dissected fresh tissue piece to generation of stitched images, the total processing time is 2 specimen, which is on average two times faster than frozen-section H&E process for fatty or water-rich fresh tissue specimens. This technique was successfully used to scan human and animal fresh tissue pieces, demonstrating its applicability for both biobank and veterinary purposes. We provide an in-depth comparison between p-H&E and human frozen-section H&E images acquired from the same metastatic sentinel lymph node slice (∼10 µm thick), and show the differences, like elastic fibers of a tiny blood vessel and cytoplasm of tumor cells. This optical sectioning technique provides histopathologists with a convenient assessment method that outputs large-field H&E-like images of fresh tissue pieces without requiring any physical embedment.

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.

The theoretical relationships between resilience and vulnerability have long been debated, but limited research has been done to test their relationships from an empirical perspective. This study presents an important case to demonstrate the empirical verification of the relationships. After reviewing relevant theories, we propose revisions of two widely adopted disaster risk and vulnerability formulas and apply them in a Taiwanese case of Typhoon Morakot. The data incorporate four natural hazard data sets, a Taiwan Social Change Survey of nonvictims as the reference group, and a longitudinal data set of Social Impact and Recovery Survey for Typhoon Morakot victims (2010–2012). With those data, two sets of models were constructed based on the two revised formulas. The first set of models estimates a disaster risk, defined as the probability and expected value of victimization determined by the typhoon hazard, household’s exposure, and contextual vulnerability composed of social class, ethnicity, education, and family status. The second set of models estimates an affected household’s outcome vulnerability, defined as the continuous trajectory of household living condition consisted of exposure, contextual vulnerability, and resilience. In the second set, outcome vulnerability is measured through household income pre- and post-disaster to depict the impact and dynamism; resilience is measured through social capital variables. Logit, ordinal linear regression (OLS), and fixed-effect regression were applied to statistically estimate the models. The results highlight that contextual vulnerability deteriorates the disaster risk of typhoon. Resilience has an impact on outcome vulnerability, but its effect is uncertain, likely to be restricted in the disaster recovery.

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.

Enamel is the outermost layer of the tooth that protects it from invasion. In general, an acidic environment accelerates tooth demineralization, leading to the formation of cavities. Scanning electron microscopy (SEM) is conventionally used as an in vitro tool for the observation of tooth morphology changes with acid attacks. Yet, SEM has intrinsic limitations for the potential application of in vivo detection in the early demineralization process. In this study, a high-resolution optical coherence tomography (OCT) system with the axial and transverse resolutions of 2.0 and 2.7 μm in teeth has been utilized for characterizing the effect of the acidic environment (simulated by phosphoric acid) on the enamel topology. The scattering coefficient and the surface roughness of enamel can be directly derived from the OCT results, enabling a quantitative evaluation of the topology changes with demineralization. The dynamic process induced by the acid application is also recorded and analyzed with OCT, depicting the evolution of the demineralization process on enamel. Notably, the estimated enamel scattering coefficient and surface roughness significantly increase with the application time of acid and the results illustrate that the values of both parameters after demineralization are significantly larger than those obtained before the demineralization, illustrating both parameters could be effective to differentiate the healthy and demineralized teeth and determine the severity. The obtained results unambiguously illustrate that demineralization of the tooth surface can be successfully detected by OCT and further used as an indicator of early-stage cavity formation.

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.