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This paper presents a combined optical coherence tomography (OCT) imaging/machine learning (ML) technique for real-time analysis of lung tissue morphology to determine the presence and level of invasiveness of idiopathic lung fibrosis (ILF). This is an important clinical problem as misdiagnosis is common, resulting in patient exposure to costly and invasive procedures and substantial use of healthcare resources. Therefore, biopsy is needed to confirm or rule out radiological findings. Videoscopic-assisted thoracoscopic wedge biopsy (VATS) under general anesthesia is typically necessary to obtain enough tissue to make an accurate diagnosis. This kind of biopsy involves the placement of several tubes through the chest wall, one of which is used to cut off a piece of lung to send for evaluation. The removed tissue is examined histopathologically by microscopy to confirm the presence and the pattern of fibrosis. However, VATS pulmonary biopsy can have multiple side effects, including inflammation, tissue morbidity, and severe bleeding, which further degrade the quality of life for the patient. Furthermore, the results are not immediately available, requiring tissue processing and analysis. Here, we report an initial attempt of using ML-assisted polarization sensitive OCT (PS-OCT) imaging for lung fibrosis assessment. This approach has been preliminarily tested on a rat model of lung fibrosis. Our preliminary results show that ML-assisted PS-OCT imaging can detect the presence of ILF with an average of 77% accuracy and 89% specificity.
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This paper presents a technique for high sensitivity measurement of singlet oxygen luminescence generated during photodynamic therapy (PDT) and ultraviolet (UV) irradiation on skin. The high measurement sensitivity is achieved by using a computational spectroscopy (CS) approach that provides improved photon detection efficiency compared to spectral filtering methodology. A solid-state InGaAs photodiode is used as the CS detector, which significantly reduces system cost and improves robustness compared to photomultiplier tubes. The spectral resolution enables high-accuracy determination and subtraction of photosensitizer fluorescence baseline without the need for time-gating. This allows for high sensitivity detection of singlet oxygen luminescence emission generated by continuous wave light sources, such as solar simulator sources and those commonly used in PDT clinics. The value of the technology is demonstrated during in vivo and ex vivo experiments that show the correlation of measured singlet oxygen with PDT treatment efficacy and the illumination intensity on the skin. These results demonstrate the potential use of the technology as a dosimeter to guide PDT treatment and as an analytical tool supporting the development of improved sunscreen products for skin cancer prevention.
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This paper presents a combined optical imaging/artificial intelligence (OI/AI) technique for the real-time analysis of tissue morphology at the tip of the biopsy needle, prior to collecting a biopsy specimen. This is an important clinical problem as up to 40% of collected biopsy cores provide low diagnostic value due to high adipose or necrotic content. Micron-scale-resolution optical coherence tomography (OCT) images can be collected with a minimally invasive needle probe and automatically analyzed using a computer neural network (CNN)-based AI software. The results can be conveyed to the clinician in real time and used to select the biopsy location more adequately. This technology was evaluated on a rabbit model of cancer. OCT images were collected with a hand-held custom-made OCT probe. Annotated OCT images were used as ground truth for AI algorithm training. The overall performance of the AI model was very close to that of the humans performing the same classification tasks. Specifically, tissue segmentation was excellent (~99% accuracy) and provided segmentation that closely mimicked the ground truth provided by the human annotations, while over 84% correlation accuracy was obtained for tumor and non-tumor classification.
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Driving is a ubiquitous activity that requires both motor skills and cognitive focus. These aspects become more problematic for some seniors, who have underlining medical conditions and tend to lose some of these capabilities. Therefore, driving can be used as a controlled environment for the frequent, non-intrusive monitoring of bio-physical and cognitive status within drivers. Such information can then be utilized for enhanced assistive vehicle controls and/or driver health monitoring. In this paper, we present a novel multi-modal smart steering sleeve (S3) system with an integrated sensing platform that can non-intrusively and continuously measure a driver's physiological signals, including electrodermal activity (EDA), electromyography (EMG), and hand pressure. The sensor suite was developed by combining low-cost interdigitated electrodes with a piezoresistive force sensor on a single, flexible polymer substrate. Comprehensive characterizations on the sensing modalities were performed with promising results demonstrated. The sweat-sensing unit (SSU) for EDA monitoring works under a 100 Hz alternative current (AC) source. The EMG signal acquired by the EMG-sensing unit (EMGSU) was amplified to within 5 V. The force-sensing unit (FSU) for hand pressure detection has a range of 25 N. This flexible sensor was mounted on an off-the-shelf steering wheel sleeve, making it an add-on system that can be installed on any existing vehicles for convenient and wide-coverage driver monitoring. A cloud-based communication scheme was developed for the ease of data collection and analysis. Sensing platform development, performance, and limitations, as well as other potential applications, are discussed in detail in this paper.
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Condução de Veículo , Condução de Veículo/psicologia , Coleta de Dados , Monitorização Fisiológica , SuorRESUMO
Noninvasive assessment of skin lesions, especially of basal cell carcinoma (BCC), has benefited more recently from the use of optical imaging techniques such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). While RCM provides submicron scale resolution and thus enables identification of skin morphological changes of the skin, with the downside of limited penetration depth, OCT imaging of the same lesion brings the benefit of better resolving its depth of invasion. OCT and RCM can be used either individually or combined within the same instrument for the noninvasive diagnosis of nonmelanoma skin cancers (NMSCs). Their combined use has shown to provide certain benefits such as better characterization of the lesion's margins, both in depth and laterally, as well as improved sensitivity and specificity, as previously demonstrated by our team. In this paper we report a new "fiber-based" implementation of the second-generation RCM-OCT hand-held probe. The fiber-based implementation of both imaging modalities enabled the construction of a smaller footprint/lower weight hand-held probe. Its preliminary evaluation on the skin of healthy volunteers is reported here, demonstrating improved capabilities for resolving sub-cellular structures and image skin morphology with micron-scale resolution to a higher depth than in the previous implementation, while also enabling the construction of angiography maps showing vascular remodeling.
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BACKGROUND: Our objective was to develop and test a combined Raman microspectroscopy (RMS) and micro-optical coherence tomography (µOCT) approach for chairside quantification of gingival collagen, DNA, epithelium, and connective tissue. We hypothesized that a high-resolution RMS/µOCT can characterize healthy and inflamed periodontal tissues for diagnosis and disease activity monitoring. METHODS: A prototype instrument was developed, tested ex vivo on gingival specimens and optimized for in vivo intraoral use. The primary outcome measures were the ratios of oral epithelium to connective tissue thickness (OE:CT) and the amount of DNA to collagen type I (DNA/Col 1), and the thickness of sulcular epithelium (SE). For ex vivo testing, eight subjects with healthy periodontal tissues or with Stage II to IV periodontitis were included in the study and underwent crown-lengthening or periodontal surgical procedures, respectively. Gingival biopsies were scanned by RMS/µOCT and histometric analyses were performed. The proof-of-concept study included OE/CT, DNA/Col 1, and SE assessed in six volunteers with or without signs of gingival inflammation (n = 3/group). RESULTS: The spatially co-registered RMS spectra revealed opposing changes in the collagen and DNA peaks of inflamed compared with healthy tissues (P <0.05). Combined RMS/µOCT analysis showed that OE/CT, DNA/Col, and SE are significantly different between healthy and inflamed sites (P <0.05). Histological assessments confirmed the differences detected by RMS/µOCT. Qualitative analysis of DNA/Col 1 ratios indicated Col I content as the main distinguishing feature for health and DNA content for periodontitis. CONCLUSION: Results suggest that combined RMS/µOCT chairside imaging may distinguish between healthy and diseased sites by evaluating marginal periodontal morphological and biochemical features.
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Periodontite , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Projetos Piloto , Gengiva/diagnóstico por imagem , Gengiva/patologia , Periodontite/patologia , Periodonto/diagnóstico por imagem , Periodonto/patologiaRESUMO
Providing surgical margin information during breast cancer surgery is crucial for the success of the procedure. The margin is defined as the distance from the tumor to the cut surface of the resection specimen. The consensus among surgeons and radiation oncologists is that there should be no tumor left within 1 to maximum 2 mm from the surface of the surgical specimen. If a positive margin remains, there is substantial risk for tumor recurrence, which may also result in potentially reduced cosmesis and eventual need for mastectomy. In this paper we report a novel multimodal optical imaging instrument based on combined high-resolution confocal microscopy-optical coherence tomography imaging for assessing the presence of potential positive margins on surgical specimens. Since rapid specimen analysis is critical during surgery, this instrument also includes a fluorescence imaging channel to enable rapid identification of the areas of the specimen that have potential positive margins. This is possible by specimen incubation with a cancer specific agent prior to imaging. In this study we used a quenched contrast agent, which is activated by cancer specific enzymes, such as urokinase plasminogen activators (uPA). Using this agent or a similar one, one may limit the use of high-resolution optical imaging to only fluorescence-highlighted areas for visualizing tissue morphology at the sub-cellular scale and confirming or ruling out cancer presence. Preliminary evaluation of this technology was performed on 20 surgical specimens and testing of the optical imaging findings was performed against histopathology. The combination of the three imaging modes allowed for high correlation between optical image analysis and histological ground-truth. The initial results are encouraging, showing instrument capability to assess margins on clinical specimens with a positive predictive value of 1.0 and a negative predictive value of 0.83.
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Neoplasias da Mama , Processamento de Imagem Assistida por Computador/métodos , Margens de Excisão , Microscopia Confocal , Imagem Óptica , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Microscopia Confocal/instrumentação , Microscopia Confocal/métodos , Imagem Óptica/instrumentação , Imagem Óptica/métodosRESUMO
The increasing rate of incidence and prevalence of basal cell carcinomas (BCCs) worldwide, combined with the morbidity associated with conventional surgical treatment has led to the development and use of alternative minimally invasive non-surgical treatments. Biopsy and pathology are used to guide BCC diagnosis and assess margins and subtypes, which then guide the decision and choice of surgical or non-surgical treatment. However, alternatively, a noninvasive optical approach based on combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) imaging may be used. Optical imaging may be used to guide diagnosis and margin assessment at the bedside, and potentially facilitate non-surgical management, along with long-term monitoring of treatment response. Noninvasive imaging may also complement minimally invasive treatments and help further reduce morbidity. In this paper, we highlight the current state of an integrated RCM/OCT imaging approach for diagnosis and triage of BCCs, as well as for assessing margins, which therefore may be ultimately used for guiding therapy.
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In this Letter, we report a low-cost, portable, two-photon excitation fluorescence microscopy imager that uses a fiber-based approach for both femtosecond supercontinuum (SC) generation and light delivery to the optical head. The SC generation is based on a tapered polarization-maintaining photonic crystal fiber that uses pre-chirped femtosecond narrowband pulses to generate a coherent SC spectrum with a bandwidth of approximately 300 nm. Using this approach, high-power, near-transform-limited, wavelength-selectable SC pulses are generated and directly delivered to the imaging optical head. Preliminary testing of this imager on brain slices is presented, demonstrating a high signal-to-noise ratio and sub-cellular imaging capabilities to a depth of approximately 200 µm. These results demonstrate the suitability of the technology for ex vivo and potentially in vivo cellular-level biomedical imaging applications.
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Luz , Microscopia de Fluorescência por Excitação Multifotônica/instrumentação , Fibras Ópticas , Fenômenos Ópticos , Desenho de Equipamento , Dinâmica não LinearRESUMO
Voice disorders affect a large number of adults in the United States, and their clinical evaluation heavily relies on laryngeal videostroboscopy, which captures the medial-lateral and anterior-posterior motion of the vocal folds using stroboscopic sampling. However, videostroboscopy does not provide direct visualization of the superior-inferior movement of the vocal folds, which yields important clinical insight. In this paper, we present a novel technology that complements videostroboscopic findings by adding the ability to image the coronal plane and visualize the superior-inferior movement of the vocal folds. The technology is based on optical coherence tomography, which is combined with videostroboscopy within the same endoscopic probe to provide spatially and temporally co-registered images of the mucosal wave motion, as well as vocal folds subsurface morphology. We demonstrate the capability of the rigid endoscopic probe, in a benchtop setting, to characterize the complex movement and subsurface structure of the aerodynamically driven excised larynx models within the 50 to 200 Hz phonation range. Our preliminary results encourage future development of this technology with the goal of its use for in vivo laryngeal imaging.
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The platform described here combines the non-invasive measurement of the retina/choroid structure and ocular blood flow based on optical coherence tomography (OCT) and wide-field semi-quantitative global flow visualization using line-scanning Doppler flowmetry (LSDF). The combination of these two imaging modalities within the same platform enables comprehensive assessment of blood flow in the retina and choroid in animals and human subjects for diagnostic purposes. Ultra-widefield vasculature visualization is demonstrated here for the first time without injecting additional contrast agents and based only on the motion of particles within the vasculature.
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Importance: The limited tissue sampling of a biopsy can lead to an incomplete assessment of basal cell carcinoma (BCC) subtypes and depth. Reflectance confocal microscopy (RCM) combined with optical coherence tomography (OCT) imaging may enable real-time, noninvasive, comprehensive three-dimensional sampling in vivo, which may improve the diagnostic accuracy and margin assessment of BCCs. Objective: To determine the accuracy of a combined RCM-OCT device for BCC detection and deep margin assessment. Design, Setting, and Participants: This pilot study was carried out on 85 lesions from 55 patients referred for physician consultation or Mohs surgery at Memorial Sloan Kettering Skin Cancer Center in Hauppauge, New York. These patients were prospectively and consecutively enrolled in the study between January 1, 2017, and December 31, 2017. Patients underwent imaging, with the combined RCM-OCT probe, for previously biopsied, histopathologically confirmed BCCs and lesions clinically or dermoscopically suggestive of BCC. Only patients with available histopathologic examination after imaging were included. Main Outcomes and Measures: Improvements in sensitivity, specificity, and diagnostic accuracy for BCC using the combined RCM-OCT probe as well as the correlation between OCT-estimated depth and histopathologically measured depth were investigated. Results: In total, 85 lesions from 55 patients (27 [49%] were female and 28 [51%] were male with a median [range] age of 59 [21-90] years) were imaged. Imaging was performed on 25 previously biopsied and histopathologically confirmed BCCs and 60 previously nonbiopsied but clinically or dermoscopically suspicious lesions. Normal skin and BCC features were correlated and validated with histopathologic examination. In previously biopsied lesions, residual tumors were detected in 12 of 25 (48%) lesions with 100% sensitivity (95% CI, 73.5%-100%) and 23.1% specificity (95% CI, 5.0%-53.8%) for combined RCM-OCT probe. In previously nonbiopsied and suspicious lesions, BCCs were diagnosed in 48 of 60 (80%) lesions with 100% sensitivity (95% CI, 92.6%-100%) and 75% specificity (95% CI, 42.8%-94.5%). Correlation was observed between depth estimated with OCT and depth measured with histopathologic examination: the coefficient of determination (R2) was 0.75 (R = 0.86; P < .001) for all lesions, 0.73 (R = 0.85; P < .001) for lesions less than 500 µm deep, and 0.65 (R = 0.43; P < .001) for lesions greater than 500 µm deep. Conclusions and Relevance: Combined RCM-OCT imaging may be prospectively used to comprehensively diagnose lesions suggestive of BCC and triage for treatment. Further validation of this device must be performed on a larger cohort.
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Carcinoma Basocelular/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Basocelular/patologia , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Imagem Multimodal , Projetos Piloto , Estudos Prospectivos , Sensibilidade e Especificidade , Pele/patologia , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
We report the development and the pre-clinical testing of a new technology based on optical coherence tomography (OCT) for investigating tissue composition at the tip of the core biopsy needle. While ultrasound, computed tomography, and magnetic resonance imaging are routinely used to guide needle placement within a tumor, they still do not provide the resolution needed to investigate tissue cellularity (ratio between viable tumor and benign stroma) at the needle tip prior to taking a biopsy core. High resolution OCT imaging, however, can be used to investigate tissue morphology at the micron scale, and thus to determine if the biopsy core would likely have the expected composition. Therefore, we implemented this capability within a custom-made biopsy gun and evaluated its capability for a correct estimation of tumor tissue cellularity. A pilot study on a rabbit model of soft tissue cancer has shown the capability of this technique to provide correct evaluation of tumor tissue cellularity in over 85% of the cases. These initial results indicate the potential benefit of the OCT-based approach for improving the success of the core biopsy procedures.
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We present a hand-held implementation and preliminary evaluation of a combined optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) probe for detecting and delineating the margins of basal cell carcinomas (BCCs) in human skin Assuntos
Carcinoma Basocelular/diagnóstico por imagem
, Microscopia Confocal
, Tomografia de Coerência Óptica
, Estudos Transversais
, Humanos
, Projetos Piloto
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We report the development of a novel otoscopy probe for assessing middle ear anatomy and function. Video imaging and phase-sensitive optical coherence tomography are combined within the same optical path. A sound stimuli channel is incorporated as well to study middle ear function. Thus, besides visualizing the morphology of the middle ear, the vibration amplitude and frequency of the eardrum and ossicles are retrieved as well. Preliminary testing on cadaveric human temporal bone models has demonstrated the capability of this instrument for retrieving middle ear anatomy with micron scale resolution, as well as the vibration of the tympanic membrane and ossicles with sub-nm resolution.
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We present a new method for generating micron-scale OCT images of interstitial tissue with a hand scanning probe and a linear optical encoder that senses probe movement relative to a fixed reference point, i.e., tissue surface. Based on this approach, we demonstrate high resolution optical imaging of biological tissues through a very long biopsy needle. Minor artifacts caused by tissue noncompliance are corrected using a software algorithm which detects the simple repetition of the adjacent A-scans. This hand-scanning OCT imaging approach offers the physician the freedom to access imaging sites of interest repeatedly.
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Retroalimentação , Tomografia de Coerência Óptica/instrumentação , Algoritmos , Animais , Processamento de Imagem Assistida por ComputadorRESUMO
The accurate determination of burn depth is critical in the clinical management of burn wounds. Polarization-sensitive optical coherence tomography (PS-OCT) has been proposed as a potentially non-invasive method for determining burn depth by measuring thermally induced changes in the structure and birefringence of skin, and has been investigated in pre-clinical burn studies with animal models and ex vivo human skin. In this study, we applied PS-OCT to the in-vivo imaging of two pediatric burn patients. Deep and superficial burned skins along with contralateral controls were imaged in 3D. The imaging size was 8 mm × 6 mm × 2 mm in width, length, and depth in the air respectively, and the imaging time was approximately 6 s per volume. Superficially burned skins exhibited the same layered structure as the contralateral controls, but more visible vasculature and reduced birefringence compared to the contralateral controls. In contrast, a deeply burned skin showed loss of the layered structure, almost absent vasculature, and smaller birefringence compared to superficial burns. This study suggested the vasculature and birefringence as parameters for characterizing burn wounds.
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Queimaduras/patologia , Microscopia de Polarização/métodos , Pele/patologia , Tomografia de Coerência Óptica/métodos , Birrefringência , Criança , Desenho de Equipamento , Humanos , Imageamento Tridimensional , Lactente , Luz , Masculino , CicatrizaçãoRESUMO
We present in-vivo 3D human vocal fold images with polarization sensitive optical coherence tomography (PS-OCT). Characterizing the extent and location of vocal fold lesions provides useful information in guiding surgeons during phonomicrosurgery. Previous studies showed that PS-OCT imaging can distinguish vocal fold lesions from normal tissue, but these studies were limited to 2D cross-sectional imaging and were susceptible to sampling error. In-vivo 3D endoscopic imaging was performed by using a recently developed 2-axis MEMS scanning catheter and a spectral domain OCT (SD-OCT), running at 18.5 frames/s. Imaging was performed in the operating room with patients under general anesthesia and 3D images were acquired either by 2D scanning of the scanner on the sites of interest or by combining 1D scanning and manual sliding to capture whole length of the vocal fold. Vocal fold scar, polyps, nodules, papilloma and malignant lesions were imaged and characteristics of individual lesions were analyzed in terms of spatial distribution and variation of tissue structure and birefringence. The 3D large sectional PS-OCT imaging showed that the spatial extent of vocal fold lesions can be found non-invasively with good contrast from normal tissue.
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Cateterismo/instrumentação , Imageamento Tridimensional/instrumentação , Imageamento Tridimensional/métodos , Sistemas Microeletromecânicos/instrumentação , Tomografia de Coerência Óptica/instrumentação , Tomografia de Coerência Óptica/métodos , Prega Vocal/patologia , Humanos , Radiografia , Prega Vocal/diagnóstico por imagemRESUMO
Progression of retinal degeneration in a mouse model was studied in vivo with high-resolution spectral-domain optical coherence tomography (SD-OCT). Imaging in 3D with high depth resolution (<3 mum), SD-OCT resolved all the major layers of the retina of control C57BL/6J mice. Images of transgenic mice having a null mutation of the rhodopsin gene revealed the anatomical consequences of retinal degeneration: thinning of the outer retina, including the outer plexiform layer (OPL), outer nuclear layer (ONL), and inner and outer segments (IS/OS). We monitored the progression of retinal degeneration in rd1 mice (C3H/HeJ) by periodically imaging the same mice from the time the pups opened their eyes on P13 to P34. SD-OCT images showed that the outer retina (OPL, ONL, IS/OS) had already thinned by 73% (100 to 27 mum) at eye opening. The retina continued to degenerate, and by P20 the outer retina was not resolvable. The thickness of entire retina decreased from 228 mum (control) to 152 mum on P13 and to 98 mum by P34, a 57% reduction with the complete loss in the outer retina. In summary, we show that SD-OCT can monitor the progression of retinal degeneration in transgenic mice.