We present a modified colonoscope that allows for precise control over the illumination coherence, direction, and color. By capturing and processing images under different illumination conditions, this colonoscope generates maps of superficial blood flow, high spatial frequency 3D topography, reflectance, and chromophore concentrations. In this presentation, we describe the system design and characterize its contrast in benchtop experiments with various tissue phantoms. Finally, we will summarize our findings from using this multimodal imaging system on human participants undergoing colonoscopy screening.
Endogenous chromophore mapping has been applied for distinguishing healthy and malignant tissue, but challenges with adapting these techniques for use with flexible endoscopes have limited exploration in gastrointestinal imaging. To enable investigative imaging in-vivo, a clinical colonoscope was retrofitted with custom fiber optics for coupling with both standard-of-care and external light sources. A multispectral illumination source with eight narrowband channels was constructed from multimode laser diodes for measuring tissue reflectance. Following benchtop validation with calibration targets, the system and correction methods were applied to human screening colonoscopies to estimate oxygen saturation of lesions and surrounding healthy tissue.
Screening colonoscopy is used to detect and remove lesions prior to progressing to colorectal cancer, but some lesions go undetected due to poor visual contrast in white light endoscopy. We present a retrofit clinical colonoscope capable of multispectral, topographic, and blood flow imaging for improving lesion contrast. We develop a custom fiber bundle to enable simultaneous illumination with commercial and research light sources. The research light source consists of nine wavelengths (405nm-659nm) for multispectral imaging and a high-coherence source for speckle-flow imaging. Point sources circling the image sensor are individually toggled to generate topographic maps with photometric stereo.
Oblique back-illumination capillaroscopy (OBC) has recently demonstrated clear images of unlabeled human blood cells in vivo. Combined with deep learning-based algorithms, this technology may enable non-invasive blood cell counting and analysis as flowing red blood cells, platelets, and white blood cells can be observed in their native environment. To harness the full potential of OBC, new techniques and methods must be developed that provide ground truth data using human blood cells. Here we present such a model, where human blood cells with paired ground truth information are imaged flowing in a custom tissue-mimicking micro fluidic device. This model enables the acquisition of OBC datasets that will help with both training and validating machine learning models for applications including the complete blood count, specific blood cell classification, and the study of hematologic disorders such as anemia.
Spatial Frequency Domain Imaging (SFDI) is a powerful technique for non-contact tissue optical property and chromophore mapping over a large field of view. However, a major challenge that limits the clinical adoption of SFDI is that it requires carefully-controlled imaging geometry and the projection of known spatial frequencies. We present speckle-illumination SFDI (si-SFDI), a projector-free technique that measures tissue optical properties from structured illumination formed by randomized speckle patterns. We compute the local power spectral density of images under speckle illumination, from which a high-frequency and a low-frequency tissueresponse parameter can be characterized for each pixel. A lookup table generated by Monte-Carlo simulations is subsequently used to accurately determine optical absorption and reduced scattering coefficients. Compared to conventional SFDI, si-SFDI may be particularly useful for endoscopic applications due to its utilization of simple coherent illumination, which makes it more easily incorporated into existing endoscopic systems. Moreover, speckle illumination offers a large depth of focus compared to projector-based illumination. In this study, we explore wide-field optical property mapping with an endoscope camera and fiber-coupled laser speckle illumination. We apply this technique to tissue-mimicking silicone phantoms and biological tissues. The accuracy of si-SFDI is evaluated by comparing to optical properties measured by conventional SFDI. Future work could accelerate si-SFDI reconstruction by using parallel computing or machine learning algorithms.
Capillaroscopy is a simple microscopy technique able to measure important clinical biomarkers non-invasively. For example, optical absorption gaps between red blood cells in capillary vessels of the nailfold have been shown to correlate with severity of neutropenia. The direct visualization of individual white blood cells with capillaroscopic techniques is elusive because it is challenging to generate epiillumination phase contrast in thick turbid media. Here, we evaluate white blood cell visibility with graded-field capillaroscopy in a flow phantom. We fabricate capillary phantoms with soft photolithography using PDMS doped with TiO2 and India ink to emulate skin optical properties. These glass-free phantoms feature channels embedded in scattering media at controlled depths (70-470 μm), as narrow as 15 x 15 μm, and permit blood flow up to 6 mm/s. We optimize the contrast of the graded-field capillaroscope in these tissue-realistic phantoms and demonstrate high speed imaging (200 Hz) of blood cells flowing through scattering media.
Endoscope size is a major design constraint that must be managed with the clinical demand for high-quality illumination and imaging. Existing commercial endoscopes most often use an arc lamp to produce bright, incoherent white light, requiring large-area fiber bundles to deliver sufficient illumination power to the sample. Moreover, the power instability of these light sources creates challenges for computer vision applications. We demonstrate an alternative illumination technique using red-green-blue laser light and a data-driven approach to combat the speckle noise that is a byproduct of coherent illumination. We frame the speckle artifact problem as an image-to-image translation task solved using conditional Generative Adversarial Networks (cGANs). To train the network, we acquire images illuminated with a coherent laser diode, with a laser diode source made partially- coherent using a laser speckle reducer, and with an incoherent LED light source as the target domain. We train networks using laser-illuminated endoscopic images of ex-vivo, porcine gastrointestinal tissues, augmented by images of laser-illuminated household and laboratory objects. The network is then benchmarked against state of-the-art optical and image processing speckle reduction methods, achieving an increased peak signal-to-noise ratio (PSNR) of 4.1 db, compared to 0.7 dB using optical speckle reduction, 0.6 dB using median filtering, and 0.5 dB using non-local means. This approach not only allows for endoscopes with smaller, more efficient light sources with extremely short triggering times, but it also enables imaging modalities that require both coherent and incoherent sources, such as combined widefield and speckle ow contrast imaging in a single image frame.
Colorectal cancer accounts for an estimated 8% of cancer deaths in the United States with a five-year survival rate of 55-75%. The early detection and removal of precancerous lesions is critical for reducing mortality, but subtle neoplastic growths, such as non-polypoid lesions, often go undetected during routine colonoscopy. Current approaches to flat or depressed lesion detection are ineffective due to the poor contrast of subtle features in white light endoscopy. Towards improving colorectal lesion contrast, we present an endoscopic light source with custom laser channels for multimodal color, topographic, and speckle contrast flow imaging. Three red-green-blue laser units, paired with laser speckle reducers, are coupled into endoscopic fiber optic light guides in a benchtop endoscope. Tissue phantom topography is reconstructed using alternating illumination of the laser units and a photometric stereo endoscopy algorithm. The contrast of flow regions is enhanced in an optical flow phantom using laser speckle contrast imaging. Further, the system retains the ability to offer white light and narrow band illumination modes with improved power efficiency, a reduced size, and longer lifetimes compared to conventional endoscopic arc lamp sources. This novel endoscopic light source design shows promise for increasing the detection of subtle lesions in routine colonoscopy screening.
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