Upgrading Structural Conjugation in Three-Dimensional Ni-Based Metal-Organic Frameworks for Promoting Electrical Conductivity and Specific Capacitance.

Metal-organic frameworks (MOFs) have emerged as promising candidates for electrochemical energy storage and conversion due to their high specific surface areas, abundant active sites, and excellent chemical and structural tunability. However, the direct utilization of MOFs as electrochemical materials is a challenge because of the poor electroconductivity induced by the insulating nature of most organic linkers. Herein, a conjugated three-dimensional Ni-MOF {Ni(HBTC)(BPE)}n (Ni-BPE) with a 2-fold interpenetrating structure was developed via the coordination polymerization of Ni2+, a H3BTC ligand (1,3,5-benzenetricarboxylic acid), and a vinyl-functionalized bipyridine linker (1,2-di(4-pyridyl)ethylene, BPE). Ni-BPE displayed an enhanced conjugation system compared to analogous and insulated Ni-BPY that is constructed by the Ni-BTC layer and ordinary bipyridine linker (4,4'-bipyridine, BPY). Notably, upgrading structural conjugation promoted a dramatical ∼204 times increase in the electroconductivity of Ni-BPE compared to Ni-BPY. More importantly, Ni-BPE displayed a higher specific capacitance of 633.2 F g-1 (316.6 C g-1) at 1 A g-1, which exhibited a significant ∼1.5-fold enhancement than Ni-BPY. Furthermore, the asymmetric supercapacitor can reach a good energy density of 25.2 Wh kg-1 with a reasonable cycle stability of 71.0% over 5000 cycles. This work provides an effective method for optimizing the structure of insulating MOFs to enhance the electroconductivity and specific capacitance.

Copper-Catalyzed, N-Directed Distal C(sp3)-H Functionalization toward Azepanes.

We herein report a copper-catalyzed formal [5 + 2] aza-annulation of N-fluorosulfonamides and 1,3-dienes/1,3-enynes for synthesis of structurally diverse alkene/alkyne-containing azepanes. The reaction features selective functionalization of distal unactivated C(sp3)-H bonds and a broad substrate scope, thus allowing the late-stage modification of pharmaceuticals and natural products. A radical mechanism involving 1,5-hydrogen atom transfer of N-radicals, facile coupling of alkyl radicals with 1,3-dienes/1,3-enynes, and the construction of azepane motifs via C-N bond formation is proposed.

Effects of Different Pedaling Positions on Muscle Usage and Energy Expenditure in Amateur Cyclists.

BACKGROUND: Inappropriate cycling positions may affect muscle usage strategy and raise the level of fatigue or risk of sport injury. Dynamic bike fitting is a growing trend meant to help cyclists select proper bikes and adjust them to fit their ergometry. The purpose of this study is to investigate how the "knee forward of foot" (KFOF) distance, an important dynamic bike fitting variable, influences the muscle activation, muscle usage strategy, and rate of energy expenditure during cycling. METHODS: Six amateur cyclists were recruited to perform the short-distance ride test (SRT) and the graded exercise tests (GXT) with pedaling positions at four different KFOF distances (+20, 0, -20, and -40 mm). The surface electromyographic (EMG) and portable energy metabolism systems were used to monitor the muscle activation and energy expenditure. The outcome measures included the EMG root-mean-square (RMS) amplitudes of eight muscles in the lower extremity during the SRT, the regression line of the changes in the EMG RMS amplitude and median frequency (MF), and the heart rate and oxygen consumption during the GXT. RESULTS: Our results revealed significant differences in the muscle activation of vastus lateralis, vastus medialis, and semitendinosus among four different pedaling positions during the SRT. During GXT, no statistically significant differences in muscle usage strategy and energy expenditure were found among different KFOF. However, most cyclists had the highest rate of energy expenditure with either KFOF at -40 mm or 20 mm. CONCLUSIONS: The KFOF distance altered muscle activation in the SRT; however, no significant influence on the muscle usage strategy was found in the GXT. A higher rate of energy expenditure in the extreme pedaling positions of KFOF was observed in most amateur cyclists, so professional assistance for proper bike fitting was recommended.

Reshaping the Tumor Immune Microenvironment Based on a Light-Activated Nanoplatform for Efficient Cancer Therapy.

The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO3 /Bi2 WO6 (BFO/BWO) with a p-n type heterojunction is constructed for reshaping the immunosuppressive TME. Reactive oxygen species can be generated under light activation by the well-separated hole (h+ )-electron (e- ) pairs owing to the heterojunction in BFO/BWO-PVP NPs. Interestingly, h+ can trigger the decomposition of H2 O2 to generate O2 for alleviating tumor hypoxia, which not only sensitizes photodynamic therapy (PDT) and radiotherapy (RT), but also promotes tumor-associated macrophages (TAMs) polarization from M2 to M1 phenotype, which is beneficial to decrease the expression of HIF-1α. Importantly, such a light-activated nanoplatform, combining with RT can efficiently activate and recruit cytotoxic T lymphocytes to infiltrate in tumor tissues, as well as stimulate TAMs to M1 phenotype, dramatically reverse the immunosuppressive TME into an immunoactive one, and further boost immune memory responses. Moreover, BFO/BWO-PVP NPs also present high performance for computed tomography imaging contrast. Taken together, this work offers a novel paradigm for achieving O2 self-supply of inorganic nanoagents and reshaping of the tumor immune microenvironment for effective inhibition of cancer as well as metastasis and recurrence.

Multi-MHz MEMS-VCSEL swept-source optical coherence tomography for endoscopic structural and angiographic imaging with miniaturized brushless motor probes.

Swept source optical coherence tomography (SS-OCT) enables volumetric imaging of subsurface structure. However, applications requiring wide fields of view (FOV), rapid imaging, and higher resolutions have been challenging because multi-MHz axial scan (A-scan) rates are needed. We describe a microelectromechanical systems vertical cavity surface-emitting laser (MEMS-VCSEL) SS-OCT technology for A-scan rates of 2.4 and 3.0 MHz. Sweep to sweep calibration and resampling are performed using dual channel acquisition of the OCT signal and a Mach Zehnder interferometer signal, overcoming inherent optical clock limitations and enabling higher performance. We demonstrate ultrahigh speed structural SS-OCT and OCT angiography (OCTA) imaging of the swine gastrointestinal tract using a suite of miniaturized brushless motor probes, including a 3.2 mm diameter micromotor OCT catheter, a 12 mm diameter tethered OCT capsule, and a 12 mm diameter widefield OCTA probe. MEMS-VCSELs promise to enable ultrahigh speed SS-OCT with a scalable, low cost, and manufacturable technology, suitable for a diverse range of imaging applications.

Correction of circumferential and longitudinal motion distortion in high-speed catheter/endoscope-based optical coherence tomography.

Catheter/endoscope-based optical coherence tomography (OCT) is a powerful modality that visualizes structural information in luminal organs. Increases in OCT speed have reduced motion artifacts by enabling acquisition faster than or comparable to the time scales of physiological motion. However motion distortion remains a challenge because catheter/endoscope OCT imaging involves both circumferential and longitudinal scanning of tissue. This paper presents a novel image processing method to estimate and correct motion distortion in both the circumferential and longitudinal directions using a single en face image from a volumetric data set. The circumferential motion distortion is estimated and corrected using the en face image. Then longitudinal motion distortion is estimated and corrected using diversity of image features along the catheter pullback direction. Finally, the OCT volume is resampled and motion corrected. Results are presented on synthetic images and clinical OCT images of the human esophagus.

Design, synthesis, and biological evaluation of hederagenin derivatives with improved aqueous solubility and tumor resistance reversal activity.

Multidrug resistance (MDR) has become a major obstacle to malignancies treatment by chemotherapeutic drugs, therefore, it is important to develop MDR reversal agents with high activity. We have previously found that the hederagenin (HD) derivative HBQ showed good tumor MDR reversal activity in vitro and in vivo but had poor solubility. In this study, to enhance the aqueous solubility and tumor MDR reversal activity of HBQ, three series of HD derivatives were designed and synthesized. Nitrogen-containing heterocyclic-substituted, PEGylated, and ring-A substituted derivatives significantly reversed the MDR phenotype of KBV (multidrug-resistant oral epidermoid carcinoma) cells toward paclitaxel at a concentration of 10 µM in MTT assays. The PEGylated derivatives 10c-10e had increased aqueous solubility compared with HBQ by 18-657 fold, while maintaining tumor MDR reversal activity. The most in vitro active compound 10c possessed good chemical stability to an esterase over 24 h and enhanced the sensitivity of KBV cells to paclitaxel and vincristine with IC50 values of 4.58 and 0.79 nM, respectively. Mechanism studies indicated that compound 10c increased the accumulation of P-glycoprotein (P-gp) substrates rhodamine 123 and Flutax1 in KBV cells and MCF-7T (paclitaxel-resistant breast carcinoma) cells, that is to say, compound 10c exerted the reversal effect of tumor MDR by inhibiting the efflux function of P-gp. Finally, the structure-activity relationships were further investigated by analyzing the relationship between structure and tumor MDR reversal activity of HD derivatives. This study highlights the potential of PEGylated HD derivatives such as compound 10c for the development of tumor MDR reversal agents and provides information for the further improvement of the aqueous solubility and tumor MDR reversal activity of HD derivatives in the future.

Tethered capsule en face optical coherence tomography for imaging Barrett's oesophagus in unsedated patients.

OBJECTIVE: Barrett's oesophagus (BE) screening outside the endoscopy suite can identify patients for surveillance and reduce mortality. Tethered capsule optical coherence tomography (OCT) can volumetrically image oesophageal mucosa in unsedated patients and detect features of BE. We investigated ultrahigh-speed tethered capsule swept-source OCT (SS-OCT), improved device design, developed procedural techniques and measured capsule contact, longitudinal pullback non-uniformity and patient toleration. DESIGN: OCT was performed in 16 patients prior to endoscopic surveillance/treatment. Unsedated patients swallowed the capsule with sips of water and the tether was pulled back to image the oesophagus. SS-OCT at 1 000 000 A-scans/s enabled imaging 10 cm oesophageal lengths in 10 s with 30 µm transverse and 8 µm axial resolution. Capsule contact, longitudinal image coverage and patient toleration were assessed. RESULTS: Nine patients had non-dysplastic BE, three had ablative treatment-naïve neoplasia and four had prior ablation for dysplasia. Dry swallows facilitated capsule transit through the lower oesophageal sphincter (LES), and waiting 10 s before pullback reduced swallow induced LES relaxation. Slow nasal inhalation facilitated capsule retrieval and minimised gag reflex. The procedure was well tolerated. Ultrahigh-speed SS-OCT generated cross-sectional and subsurface en face images showing BE features, while subsurface en face images were required to assess the gastro-oesophageal junction. Candidate features of dysplasia were also identified which could inform follow-up endoscopy/biopsy. BE features were seen in all patients with histologically confirmed BE. Mean capsule contact over BE was 75%±27% for all patients and better in short segment BE. Mean longitudinal image coverage over BE was 59%±34% and better for long segment BE. CONCLUSIONS: Ultrahigh-speed tethered capsule SS-OCT can image en face and cross-sectional mucosal features over wide areas. Device and procedure optimisation improved performance. BE features could be identified in all patients, but limited capsule contact and longitudinal coverage could cause sampling errors for focal pathologies.

Construction of microneedle-assisted co-delivery platform and its combining photodynamic/immunotherapy.

Despite advances in photodynamic therapy (PDT) for treating superficial tumor, the prospect of this monotherapy remains challenges in the context of systemic phototoxicity and poor efficacy. In this work, a physiologically self-degradable microneedle (MN)-assisted platform is developed for combining PDT and immunotherapy via controlled co-delivery of photosensitizer (PS) and checkpoint inhibitor anti-CTLA4 antibody (aCTLA4), which generates synergistic reinforcement outcome while reducing side effects. MN is composed of biocompatible hyaluronic acid integrated with the pH-sensitive dextran nanoparticles, which is fabricated to simultaneously encapsulate hydrophobic (Zinc Phthalocyanine) and hydrophilic agents (aCTLA4) via a double emulsion method. This co-loading carrier can aggregate effectively around topical tumor by microneedle-assisted transdermal delivery. In vivo studies using 4T1 mouse models, PDT firstly exerts its effect to killing tumor and triggers the immune responses, subsequently, facilitating the immunotherapy with immune checkpoint inhibitor (aCTLA4). The possible mechanism and systemic effects of the combined therapy are investigated, which demonstrate that this co-administration platform can be a promising tool for focal cancer treatment.

Synthesis, antifungal activity and potential mechanism of fusidic acid derivatives possessing amino-terminal groups.

Aim: Fusidic acid (FA) is a narrow-spectrum bacteriostatic antibiotic. We inadvertently discovered that a FA derivative modified by an amino-terminal group at the 3-OH position, namely 2, inhibited the growth of Cryptococcus neoformans. Methods & results: Multiscale molecular modeling approaches were used to analyze the binding modes of 2 with eEF2. FA derivatives modified at the 3-OH position were designed based on in silico models; seven derivatives possessing different amino-terminal groups were synthesized and tested in vitro for antifungal activity against C. neoformans. Conclusion: Compound 7 had the strongest minimum inhibitory concentration. Two protonated nitrogen atoms of 7 interacted with a negative electrostatic pocket of eEF2 likely explain the superiority of 7-2.

Intelligent Nanocomposites with Intrinsic Blood-Brain-Barrier Crossing Ability Designed for Highly Specific MR Imaging and Sonodynamic Therapy of Glioblastoma.

The blood-brain barrier (BBB) is the most important obstacle to improving the clinical outcomes of diagnosis and therapy of glioblastoma. Thus, the development of a novel nanoplatform that can efficiently traverse the BBB and achieve both precise diagnosis and therapy is of great importance. Herein, an intelligent nanoplatform based on holo-transferrin (holo-Tf) with in situ growth of MnO2 nanocrystals is constructed via a reformative mild biomineralization process. Furthermore, protoporphyrin (ppIX), acting as a sonosensitizer, is then conjugated into holo-Tf to obtain MnO2 @Tf-ppIX nanoparticles (TMP). Because of the functional inheritance of holo-Tf during fabrication, TMP can effectively traverse the BBB for highly specific magnetic resonance (MR) imaging of orthotopic glioblastoma. Clear suppression of tumor growth in a C6 tumor xenograft model is achieved via sonodynamic therapy. Importantly, the experiments also indicate that the TMP nanoplatform has satisfactory biocompatibility and biosafety, which favors potential clinical translation.

Protein-based nanoplatforms for tumor imaging and therapy.

Cancer is one of the leading causes of death all over the world. The development of nanoplatform provides a promising strategy for the diagnosis and treatment of cancer. As the foundation of the nanoplatform, the composition of nanocarrier decides the basic properties. Protein exists in all kinds of life and participates in any life activities, having great potentials to serve as a nanocarrier because of its excellent biocompatibility, abundance of functional groups, and inherent biological activity. As a result, protein-based nanoplatforms have evoked extensive interests for tumor imaging and therapy. This review presents the latest progresses on the advancement of protein-based nanoplatforms, introducing the most common protein nanocarriers (such as human/bovine serum albumin, ferritin, human transferrin) thoroughly including their physiochemical properties and specific applications. Also, other kinds of protein are briefly involved. Finally, the prospects and challenges of the development of protein-based nanoplatforms are summarized. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Automated grading of acne vulgaris by deep learning with convolutional neural networks.

BACKGROUND: The visual assessment and severity grading of acne vulgaris by physicians can be subjective, resulting in inter- and intra-observer variability. OBJECTIVE: To develop and validate an algorithm for the automated calculation of the Investigator's Global Assessment (IGA) scale, to standardize acne severity and outcome measurements. MATERIALS AND METHODS: A total of 472 photographs (retrieved 01/01/2004-04/08/2017) in the frontal view from 416 acne patients were used for training and testing. Photographs were labeled according to the IGA scale in three groups of IGA clear/almost clear (0-1), IGA mild (2), and IGA moderate to severe (3-4). The classification model used a convolutional neural network, and models were separately trained on three image sizes. The photographs were then subjected to analysis by the algorithm, and the generated automated IGA scores were compared to clinical scoring. The prediction accuracy of each IGA grade label and the agreement (Pearson correlation) of the two scores were computed. RESULTS: The best classification accuracy was 67%. Pearson correlation between machine-predicted score and human labels (clinical scoring and researcher scoring) for each model and various image input sizes was 0.77. Correlation of predictions with clinical scores was highest when using Inception v4 on the largest image size of 1200 × 1600. Two sets of human labels showed a high correlation of 0.77, verifying the repeatability of the ground truth labels. Confusion matrices show that the models performed sub-optimally on the IGA 2 label. CONCLUSION: Deep learning techniques harnessing high-resolution images and large datasets will continue to improve, demonstrating growing potential for automated clinical image analysis and grading.

Resolution enhancement and realistic speckle recovery with generative adversarial modeling of micro-optical coherence tomography.

A resolution enhancement technique for optical coherence tomography (OCT), based on Generative Adversarial Networks (GANs), was developed and investigated. GANs have been previously used for resolution enhancement of photography and optical microscopy images. We have adapted and improved this technique for OCT image generation. Conditional GANs (cGANs) were trained on a novel set of ultrahigh resolution spectral domain OCT volumes, termed micro-OCT, as the high-resolution ground truth (∼1 µm isotropic resolution). The ground truth was paired with a low-resolution image obtained by synthetically degrading resolution 4x in one of (1-D) or both axial and lateral axes (2-D). Cross-sectional image (B-scan) volumes obtained from in vivo imaging of human labial (lip) tissue and mouse skin were used in separate feasibility experiments. Accuracy of resolution enhancement compared to ground truth was quantified with human perceptual accuracy tests performed by an OCT expert. The GAN loss in the optimization objective, noise injection in both the generator and discriminator models, and multi-scale discrimination were found to be important for achieving realistic speckle appearance in the generated OCT images. The utility of high-resolution speckle recovery was illustrated by an example of micro-OCT imaging of blood vessels in lip tissue. Qualitative examples applying the models to image data from outside of the training data distribution, namely human retina and mouse bladder, were also demonstrated, suggesting potential for cross-domain transferability. This preliminary study suggests that deep learning generative models trained on OCT images from high-performance prototype systems may have potential in enhancing lower resolution data from mainstream/commercial systems, thereby bringing cutting-edge technology to the masses at low cost.

Inlaying Radiosensitizer onto the Polypeptide Shell of Drug-Loaded Ferritin for Imaging and Combinational Chemo-Radiotherapy.

Rationale: Ferritin with unique hollow cavity is an emerging protein-based nanoplatform for anticancer-drug delivery, but the in vivo chemotherapeutic effectiveness is still unsatisfactory with such a monotherapy modality, which is urgently in need of improvement. Methods: Here a novel ferritin nanotheranostic with anticancer-drug doxorubicin encapsulated into its hollow interior and nanoradiosensitizer bismuth sulfide nanocrystals inlayed onto its polypeptide shell was synthesized for combinational therapeutic benefits. The formation mechanism of bismuth sulfide nanocrystals based on ferritin has been analyzed. The in vitro and in vivo treatment effects were carried out on HeLa cancer cells and tumor-bearing mice, respectively. The biocompatibility and excretion of the ferritin nanotheranostic have also been evaluated to guarantee their biosafety. Results: The polypeptide shell of ferritin provides nucleation sites for the bismuth sulfide nanocrystals through coordination interaction, and simultaneously inhibits the further growth of bismuth sulfide nanocrystals, rendering the bismuth sulfide nanocrystals like rivets inlaying onto the polypeptide firmly, which can not only strengthen the architectural stability of ferritin to prevent drug burst leakage during systemic circulation, but also act as excellent computed tomography contrast agents and nanoradiosensitizers for in vivo imaging-guided cancer combinational treatments. Conclusions: The design concept of inlaying bismuth sulfide nanocrystals onto the polypeptide shell of doxorubicin-encapsulated ferritin significantly inhibits the tumor growth and simultaneously further broadens the application of ferritin in nanomedicine.

Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study.

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.

Assessment of Barrett's esophagus and dysplasia with ultrahigh-speed volumetric en face and cross-sectional optical coherence tomography.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Atypical glands under irregular mucosal patterns are strongly associated with neoplasia, suggesting potential markers for dysplasia and a role in pathogenesis.

Cycloid scanning for wide field optical coherence tomography endomicroscopy and angiography in vivo.

Devices that perform wide field-of-view (FOV) precision optical scanning are important for endoscopic assessment and diagnosis of luminal organ disease such as in gastroenterology. Optical scanning for in vivo endoscopic imaging has traditionally relied on one or more proximal mechanical actuators, limiting scan accuracy and imaging speed. There is a need for rapid and precise two-dimensional (2D) microscanning technologies to enable the translation of benchtop scanning microscopies to in vivo endoscopic imaging. We demonstrate a new cycloid scanner in a tethered capsule for ultrahigh speed, side-viewing optical coherence tomography (OCT) endomicroscopy in vivo. The cycloid capsule incorporates two scanners: a piezoelectrically actuated resonant fiber scanner to perform a precision, small FOV, fast scan and a micromotor scanner to perform a wide FOV, slow scan. Together these scanners distally scan the beam circumferentially in a 2D cycloid pattern, generating an unwrapped 1 mm × 38 mm strip FOV. Sequential strip volumes can be acquired with proximal pullback to image centimeter-long regions. Using ultrahigh speed 1.3 µm wavelength swept-source OCT at a 1.17 MHz axial scan rate, we imaged the human rectum at 3 volumes/s. Each OCT strip volume had 166 × 2322 axial scans with 8.5 µm axial and 30 µm transverse resolution. We further demonstrate OCT angiography at 0.5 volumes/s, producing volumetric images of vasculature. In addition to OCT applications, cycloid scanning promises to enable precision 2D optical scanning for other imaging modalities, including fluorescence confocal and nonlinear microscopy.

Endoscopic forward-viewing optical coherence tomography and angiography with MHz swept source.

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.