DISCOVER: 2-D multiview summarization of Optical Coherence Tomography Angiography for automatic diabetic retinopathy diagnosis.

Diabetic Retinopathy (DR), an ocular complication of diabetes, is a leading cause of blindness worldwide. Traditionally, DR is monitored using Color Fundus Photography (CFP), a widespread 2-D imaging modality. However, DR classifications based on CFP have poor predictive power, resulting in suboptimal DR management. Optical Coherence Tomography Angiography (OCTA) is a recent 3-D imaging modality offering enhanced structural and functional information (blood flow) with a wider field of view. This paper investigates automatic DR severity assessment using 3-D OCTA. A straightforward solution to this task is a 3-D neural network classifier. However, 3-D architectures have numerous parameters and typically require many training samples. A lighter solution consists in using 2-D neural network classifiers processing 2-D en-face (or frontal) projections and/or 2-D cross-sectional slices. Such an approach mimics the way ophthalmologists analyze OCTA acquisitions: (1) en-face flow maps are often used to detect avascular zones and neovascularization, and (2) cross-sectional slices are commonly analyzed to detect macular edemas, for instance. However, arbitrary data reduction or selection might result in information loss. Two complementary strategies are thus proposed to optimally summarize OCTA volumes with 2-D images: (1) a parametric en-face projection optimized through deep learning and (2) a cross-sectional slice selection process controlled through gradient-based attribution. The full summarization and DR classification pipeline is trained from end to end. The automatic 2-D summary can be displayed in a viewer or printed in a report to support the decision. We show that the proposed 2-D summarization and classification pipeline outperforms direct 3-D classification with the advantage of improved interpretability.

Quantitative imaging of red blood cell velocity invivo using optical coherence Doppler tomography.

We present particle counting ultrahigh-resolution optical Doppler tomography (pc-µODT) that enables accurate imaging of red blood cell velocities (ν(RBC)) of cerebrovascular networks by detecting the Doppler phase transients induced by the passage of a RBC through a capillary. We apply pc-µODT to image the response of capillary ν(RBC) to mild hypercapnia in mouse cortex. The results show that ν(RBC) in normocapnia (ν(N) = 0.72 ± 0.15 mm/s) increased 36.1% ± 5.3% (ν(H) = 0.98 ± 0.29 mm/s) in response to hypercapnia. Due to uncorrected angle effect and low hematocrit (e.g., ∼10%), ν(RBC) directly measured by µODT were markedly underestimated (ν(N) ≈ 0.27 ± 0.03 mm/s, ν(H) ≈ 0.37± 0.05 mm/s). Nevertheless, the measured ν(RBC) increase (35.3%) matched that (36.1% ± 5.3%) by pc-µODT.

Cerebral blood flow imaged with ultrahigh-resolution optical coherence angiography and Doppler tomography.

Speckle contrast based optical coherence angiography (OCA) and optical coherence Doppler tomography (ODT) have been applied to image cerebral blood flow previously. However, the contrast mechanisms of these two methods are not fully studied. Here, we present both flow phantom and in vivo animal experiments using ultrahigh-resolution OCA (µOCA) and ODT (µODT) to investigate the flow sensitivity differences between these two methods. Our results show that the high sensitivity of µOCA for visualizing minute vasculature (e.g., slow capillary beds) is due to the enhancement by random Brownian motion of scatterers (e.g., red and white blood cells) within the vessels; whereas, µODT permits detection of directional flow below the Brownian motion regime (e.g., laser-induced microischemia) and is, therefore, more suitable for brain functional imaging.

Early detection of carcinoma in situ of the bladder: a comparative study of white light cystoscopy, narrow band imaging, 5-ALA fluorescence cystoscopy and 3-dimensional optical coherence tomography.

PURPOSE: We compared the efficacy and potential limitations of white light cystoscopy, narrow band imaging, 5-ALA fluorescence cystoscopy and 3-dimensional optical coherence tomography for early diagnosis of bladder carcinoma in situ. MATERIALS AND METHODS: By expressing simian virus 40T antigen in the urothelium carcinoma in situ typically develops in SV40T transgenic mice in about 8 to 20 weeks and then frank high grade papillary urothelial carcinoma starts to emerge. A total of 18 control and 29 SV40T mice were examined during weeks 8 to 22 by white light cystoscopy, fluorescence cystoscopy, narrow band imaging and 3-dimensional optical coherence tomography. Results were validated by histology. Newly improved algorithms for computer aided detection were applied to acquired 3-dimensional optical coherence tomography images to enhance the quantitative diagnosis of carcinoma in situ in near real time. RESULTS: Of 29 carcinoma in situ samples 27 were detected by 3-dimensional optical coherence tomography, 1 by white light cystoscopy, 26 by narrow band imaging and 13 by fluorescence cystoscopy. Of the 18 histologically confirmed benign cases 17 were detected by 3-dimensional optical coherence tomography, 14 by white light cystoscopy, 5 by narrow band imaging and 18 by fluorescence cystoscopy. The diagnostic sensitivity of white light cystoscopy (3.4%) and fluorescence cystoscopy (44.8%), and the specificity of narrow band imaging (27.8%) were significantly enhanced by 3-dimensional optical coherence tomography to 93.1% and 94.4%, respectively (p <0.01). CONCLUSIONS: Three-dimensional optical coherence tomography with quantitative computer aided detection can significantly enhance the sensitivity of white light cystoscopy and fluorescence cystoscopy, and the specificity of narrow band imaging for early diagnosis of carcinoma in situ. This suggests the potential of narrow band imaging guided 3-dimensional optical coherence tomography for future clinical detection of carcinoma in situ when effective image guidance is desirable.

High-resolution imaging diagnosis of human fetal membrane by three-dimensional optical coherence tomography.

Microscopic chorionic pseudocyst (MCP) arising in the chorion leave of the human fetal membrane (FM) is a clinical precursor for preeclampsia which may progress to fatal medical conditions (e.g., abortion) if left untreated. To examine the utility of three-dimensional (3D) optical coherence tomography (OCT) for noninvasive delineation of the morphology of human fetal membranes and early clinical detection of MCP, 60 human FM specimens were acquired from 10 different subjects undergoing term cesarean delivery for an ex vivo feasibility study. Our results showed that OCT was able to identify the four-layer architectures of human FMs consisting of high-scattering decidua vera (DV, average thickness d(DV) ≈ 92±38 µm), low-scattering chorion and trophoblast (CT, d(CT) ≈ 150±67 µm), high-scattering subepithelial amnion (A, d(A) ≈ 95±36 µm), and low-scattering epithelium (E, d(E) ≈ 29±8 µm). Importantly, 3D OCT was able to instantaneously detect MCPs (low scattering due to edema, fluid buildup, vasodilatation) and track (staging) their thicknesses d(MCP) ranging from 24 to 615 µm. It was also shown that high-frequency ultrasound was able to compliment OCT for detecting more advanced thicker MCPs (e.g., d(MCP)>615 µm) because of its increased imaging depth.

Enhancing detection of bladder carcinoma in situ by 3-dimensional optical coherence tomography.

PURPOSE: We examined the usefulness of 3-dimensional optical coherence tomography to enhance the diagnosis of urothelial carcinoma in situ. MATERIALS AND METHODS: By expressing SV40T antigen with uroplakin II promoter, carcinoma in situ readily develops in SV40T transgenic mice at about ages 8 to 20 weeks and then frank high grade papillary carcinoma develops in bladder epithelium. We examined 10 control and 40 SV40T mice during weeks 8 to 20 after birth by parallel en face white light imaging and 3-dimensional optical coherence tomography, and compared results with histology findings. We applied quantitative analysis of computer aided detection to 3-dimensional tomography images to enhance the diagnosis of carcinoma in situ, including 3-dimensional segmentation, speckle reduction, fast Fourier transform analysis, and standard deviation and histogram evaluation. RESULTS: We identified carcinoma in situ in 23 SV40T mice by histology. Most carcinoma could not be detected by en face imaging and 2-dimensional optical coherence tomography but was well differentiated by 3-dimensional optical coherence tomography. The 56.5% sensitivity and 61.5% specificity of 2-dimensional optical coherence tomography for carcinoma in situ diagnosis were significantly enhanced by 3-dimensional optical coherence tomography to 95.7% and 92.3%, respectively (p ≤0.031). CONCLUSIONS: On quantitative analysis of increased urothelial heterogeneity induced by carcinogenesis we noted that 3-dimensional optical coherence tomography enabled accurate differentiation of carcinoma in situ from normal bladder and benign lesions. Results reveal the potential of cystoscopic 3-dimensional optical coherence tomography to significantly enhance the clinical diagnosis of nonmuscle invasive bladder cancer, particularly carcinoma in situ.

Noninvasive and high-resolution optical monitoring of healing of diabetic dermal excisional wounds implanted with biodegradable in situ gelable hydrogels.

Closure of diabetic dermal chronic wounds remains a clinical challenge. Implant-assisted healing is emerging as a potential class of therapy for dermal wound closure; this advancement has not been paralleled by the development in complementary diagnostic techniques to objectively monitor the wound-healing process in conjunction with assessing/monitoring of implant efficacy. Biopsies provide the most objective morphological assessments of wound healing; however, they not only perpetuate the wound presence but also increase the risk of infection. A noninvasive and high-resolution imaging technique is highly desirable to provide objective longitudinal diagnosis of implant-assisted wound healing. We investigated the feasibility of deploying optical coherence tomography (OCT) for noninvasive monitoring of the healing of full-thickness excisional dermal wounds implanted with a novel in situ gelable hydrogel composed of N-carboxyethyl chitosan, oxidized dextran, and hyaluronan, in both normal and db/db mice. The results showed that OCT was able to differentiate the morphological differences (e.g., thickness of dermis) between normal and diabetic mice as validated by their corresponding histological evaluations (p < 0.05). OCT could detect essential morphological changes during wound healing, including re-epithelization, inflammatory response, and granulation tissue formation as well as impaired wound repair in diabetic mice. Importantly, by tracking specific morphological changes in hydrogel-assisted wound healing (e.g., implants' degradation and resorption, cell-mediated hydrogel degradation, and accelerated re-epithelization), OCT could also be deployed to monitor and evaluate the transformation of implanted biomaterials, thus holding the promise for noninvasive and objective monitoring of wound healing longitudinally and for objective efficacy assessment of implantable therapeutics in tissue engineering.

On the possibility of time-lapse ultrahigh-resolution optical coherence tomography for bladder cancer grading.

It has been recently demonstrated that the cellular details of bladder epithelium embedded in speckle noise can be uncovered with time-lapse ultrahigh-resolution optical coherence tomography (TL-uOCT) by proper time-lapse frame averaging that takes advantage of cellular micromotion in fresh biological tissue ex vivo. Here, spectral-domain 3-D TL-uOCT is reported to further improve the image fidelity, and new experimental evidence is presented to differentiate normal and cancerous nuclei of rodent bladder epithelia. Results of animal cancer study reveal that despite a slight overestimation (e.g., <10%) of nuclear size (D(N)) to histological evaluation, TL-uOCT is capable of distinguishing normal (D(N) approximately 7 microm) and cancerous (e.g., high-grade D(N(") ) approximately 13 microm) urothelia, which may potentially be very useful for enhancing the diagnosis of nonpapillary bladder cancer. More animal study is being conducted to examine the utility to differentiate hyperplasia, dysplasia, and carcinoma in situ.

Diagnosis of bladder cancer with microelectromechanical systems-based cystoscopic optical coherence tomography.

OBJECTIVES: To examine the utility and potential limitations of microelectromechanical systems-based spectral-domain cystoscopic optical coherence tomography (COCT) so as to improve the diagnosis of early bladder cancer. METHODS: An optical coherence tomography catheter was integrated into the single instrument channel of a 22F cystoscope to permit white-light-guided COCT over a large field of view (4.6 mm wide and 2.1 mm deep per scan at 8 frames/s) and 10-microm resolution. Intraoperative COCT diagnosis was performed in 56 patients, with a total of 110 lesions examined and compared with biopsied histology. RESULTS: The overall sensitivity of COCT (94%) was significantly higher than cystoscopy (75%, P = .02) and voided cytology (59%, P = .005); the major enhancement over cystoscopy was for low-grade pTa-1 cancer and carcinoma in situ (P < .018). The overall specificity of COCT (81%) was comparable to voided cytology (88.9%, P = .49), but significantly higher than cystoscopy (62.5%, P = .02). CONCLUSIONS: The microelectromechanical systems-based COCT, owing to its high resolution and detection sensitivity and large field of view, offers great potential for "optical biopsy" to enhance the diagnosis of nonpapillary bladder tumors and their recurrences and to guide bladder tumor resection.