Showing papers by "Brett E. Bouma published in 2021"

Retinal Imaging in Alzheimer's and Neurodegenerative Diseases

Abstract: In the last 20 years, research focused on developing retinal imaging as a source of potential biomarkers for Alzheimer's disease and other neurodegenerative diseases, has increased significantly. The Alzheimer's Association and the Alzheimer's & Dementia: Diagnosis, Assessment, Disease Monitoring editorial team (companion journal to Alzheimer's & Dementia) convened an interdisciplinary discussion in 2019 to identify a path to expedite the development of retinal biomarkers capable of identifying biological changes associated with AD, and for tracking progression of disease severity over time. As different retinal imaging modalities provide different types of structural and/or functional information, the discussion reflected on these modalities and their respective strengths and weaknesses. Discussion further focused on the importance of defining the context of use to help guide the development of retinal biomarkers. Moving from research to context of use, and ultimately to clinical evaluation, this article outlines ongoing retinal imaging research today in Alzheimer's and other brain diseases, including a discussion of future directions for this area of study.

Spectral- and Polarization-Dependent Scattering of Gold Nanobipyramids for Exogenous Contrast in Optical Coherence Tomography.

Abstract: Polarization-sensitive optical coherence tomography (PS-OCT) reveals the subsurface microstructure of biological tissue and provides information regarding the polarization state of light backscattered from tissue. Complementing OCT's structural signal with molecular imaging requires strategies to simultaneously detect multiple exogenous contrast agents with high specificity in tissue. Specific detection of molecular probes enables the parallel visualization of physiological, cellular, and molecular processes. Here we demonstrate that, by combining PS-OCT and spectral contrast (SC)-OCT measurements, we can distinguish signatures of different gold nanobipyramids (GNBPs) in lymphatic vessels from the surrounding tissue and blood vessels in live mouse models. This technique could well be extended to other anisotropic nanoparticle-based OCT contrast agents and presents significant progress toward enabling OCT molecular imaging.

Expert assessment on volumetric laser endomicroscopy full scans in Barrett's esophagus patients with or without high grade dysplasia or early cancer.

Abstract: Background Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett’s esophagus (BE). Interpretation of a 6-cm long, circumferential VLE “full scan” may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE). Methods 29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as “neoplastic” or “NDBE.” If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence. Results VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % – 79 %) of neoplastic VLE videos. In 54 % (range 27 % – 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % – 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %). Conclusions Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.

Layer-based, depth-resolved computation of attenuation coefficients and backscattering fractions in tissue using optical coherence tomography

Abstract: Structural optical coherence tomography (OCT) images of tissue stand to benefit from greater functionalization and quantitative interpretation. The OCT attenuation coefficient µ, an analogue of the imaged sample’s scattering coefficient, offers potential functional contrast based on the relationship of µ to sub-resolution physical properties of the sample. Attenuation coefficients are computed either by fitting a representative µ over several depth-wise pixels of a sample’s intensity decay, or by using previously-developed depth-resolved attenuation algorithms by Girard et al. [Invest. Ophthalmol. Vis. Sci.52, 7738 (2011). 10.1167/iovs.10-6925] and Vermeer et al. [Biomed. Opt. Express5, 322 (2014). 10.1364/BOE.5.000322]. However, the former method sacrifices axial information in the tomogram, while the latter relies on the stringent assumption that the sample’s backscattering fraction, another optical property, does not vary along depth. This assumption may be violated by layered tissues commonly observed in clinical imaging applications. Our approach preserves the full depth resolution of the attenuation map but removes its dependence on backscattering fraction by performing signal analysis inside individual discrete layers over which the scattering properties (e.g., attenuation and backscattering fraction) vary minimally. Although this approach necessitates the detection of these layers, it removes the constant-backscattering-fraction assumption that has constrained quantitative attenuation coefficient analysis in the past, and additionally yields a layer-resolved backscattering fraction, providing complementary scattering information to the attenuation coefficient. We validate our approach using automated layer detection in layered phantoms, for which the measured optical properties were in good agreement with theoretical values calculated with Mie theory, and show preliminary results in tissue alongside corresponding histological analysis. Together, accurate backscattering fraction and attenuation coefficient measurements enable the estimation of both particle density and size, which is not possible from attenuation measurements alone. We hope that this improvement to depth-resolved attenuation coefficient measurement, augmented by a layer-resolved backscattering fraction, will increase the diagnostic power of quantitative OCT imaging.

Computational refocusing in polarization-sensitive optical coherence tomography with phase unstable systems

Abstract: We present computational refocusing in polarization-sensitive optical coherence tomography (PS-OCT) to improve spatial resolution in the calculated polarimetric parameters and extending the depth-of-field in PS-OCT. To achieve this, we successfully integrated SHARP, a computational aberration correction method compatible with phase unstable systems, into a PS-OCT system with inter--A-line polarization modulation. Together with the spectral binning technique to mitigate chromatic polarization effects in system components, we show image quality enhancement in tissue polarimetry of swine eye anterior segment ex vivo, demonstrating the potential of computational refocusing in PS-OCT.

Polarimetric Signatures of Coronary Thrombus in Patients With Acute Coronary Syndrome.

Abstract: Background: Intravascular polarization-sensitive optical frequency domain imaging (PS-OFDI) offers a novel approach to measure tissue birefringence, which is elevated in collagen and smooth muscle cells, that in turn plays a critical role in healing coronary thrombus (HCT). This study aimed to quantitatively assess polarization properties of coronary fresh and organizing thrombus with PS-OFDI in patients with acute coronary syndrome (ACS). Methods and Results: The POLARIS-I prospective registry enrolled 32 patients with ACS. Pre-procedural PS-OFDI pullbacks using conventional imaging catheters revealed 26 thrombus-regions in 21 patients. Thrombus was manually delineated in conventional OFDI cross-sections separated by 0.5 mm and categorized into fresh thrombus caused by plaque rupture, stent thrombosis, or erosion in 18 thrombus-regions (182 frames) or into HCT for 8 thrombus-regions (141 frames). Birefringence of coronary thrombus was compared between the 2 categories. Birefringence in HCTs was significantly higher than in fresh thrombus (∆n=0.47 (0.37–0.72) vs. ∆n=0.25 (0.17–0.29), P=0.007). In a subgroup analysis, when only using thrombus-regions from culprit lesions, ischemic time was a significant predictor for birefringence (s (∆n)=0.001 per hour, 95% CI [0.0002–0.002], P=0.023). Conclusions: Intravascular PS-OFDI offers the opportunity to quantitatively assess the polarimetric properties of fresh and organizing coronary thrombus, providing new insights into vascular healing and plaque stability.

Segmentation of Anatomical Layers and Artifacts in Intravascular Polarization Sensitive Optical Coherence Tomography Using Attending Physician and Boundary Cardinality Lost Terms.

Abstract: Cardiovascular diseases are the leading cause of death and require a spectrum of diagnostic procedures as well as invasive interventions. Medical imaging is a vital part of the healthcare system, facilitating both diagnosis and guidance for intervention. Intravascular ultrasound and optical coherence tomography are widely available for characterizing coronary stenoses and provide critical vessel parameters to optimize percutaneous intervention. Intravascular polarization-sensitive optical coherence tomography (PS-OCT) can simultaneously provide high-resolution cross-sectional images of vascular structures while also revealing preponderant tissue components such as collagen and smooth muscle and thereby enhance plaque characterization. Automated interpretation of these features would facilitate the objective clinical investigation of the natural history and significance of coronary atheromas. Here, we propose a convolutional neural network model and optimize its performance using a new multi-term loss function to classify the lumen, intima, and media layers in addition to the guidewire and plaque artifacts. Our multi-class classification model outperforms the state-of-the-art methods in detecting the anatomical layers based on accuracy, Dice coefficient, and average boundary error. Furthermore, the proposed model segments two classes of major artifacts and detects the anatomical layers within the thickened vessel wall regions, which were excluded from analysis by other studies. The source code and the trained model are publicly available at this https URL .

Confocal 3D reflectance imaging through multimode fibers without wavefront shaping

Abstract: Imaging through optical multimode fibers (MMFs) has the potential to enable hair-thin endoscopes that reduce the invasiveness of imaging deep inside tissues and organs. Current approaches predominantly require active wavefront shaping and fluorescent labeling, which limits their use to preclinical applications and frustrates imaging speed. Here we present a computational approach to reconstruct depth-gated confocal images using a raster-scanned, focused input illumination. We demonstrate the compatibility of this approach with quantitative phase, dark-field, and polarimetric imaging. Computational imaging through MMF opens a new pathway for minimally invasive imaging in medical diagnosis and biological investigations.

Apparatus for providing micro-optical coherence tomography inside a respiratory system

Abstract: Optical coherence tomography apparatus using a pulmonary micro optical coherence tomography probe for investigation in an organ inside a respiratory system of humans or animals. By measuring dynamic tracking data of micrometric particles in a sample, determination of biomechanical properties of the sample such as the viscosity is obtained.

Method and apparatus for measuring intravascular blood flow using a backscattering contrast

Abstract: An apparatus including: an imaging system; a probe for insertion into a vessel, the probe being coupled to the imaging system; a flow delivery system associated with the probe to release a differential-contrast fluid into the vessel at a location proximal to an end of the probe; and a processor to: collect data from the imaging system based on release of the differential-contrast fluid into the vessel, analyze the collected data to identify a presence or absence of the differential-contrast fluid as a function of time, and determine a flow rate in the vessel based on analyzing the collected data.

Whole Murine Brain Imaging Based on Optical Elastic Scattering.

Abstract: Imaging whole brains is one of the central efforts of biophotonics. While the established imaging modalities used in radiology, such as MRI and CT, have enabled in vivo investigations of various cognitive and affective processes, the prevailing resolution of one-cubic-millimeter has limited their use in studying the “ground-truth” of neuronal activities. On the other hand, electron microscopy (EM) visualizes the finest anatomic structures at a resolution of around 30 nm. However, the extensive tissue preparation process and the required large-scale morphological reconstruction restrict this method to small sample volumes. Light microscopy (LM) has the potential to bridge the above two spatial scales, with a resolution ranging from a few hundred nanometers to a few micrometers. Recent advances in tissue clearing have paved the way for optical investigation of large intact tissue volumes. However, most of these LM studies rely on fluorescence—a nonlinear optical process to provide contrast. This chapter introduces an alternative type of LM that is solely based on a linear optical process—elastic scattering, which has some unique advantages over conventional LM methods for the investigation of large-scale biological systems, such as intact murine brains. Here, we will first lay out the background and the motivation of developing this scattering-based method. Then, the basic principle of this approach will be introduced, including controlling tissue scattering and coherent imaging. Next, we explore current implementation and practical considerations. Up-to-date results and the utility of this method will also be demonstrated. Finally, we discuss current limitations and future directions in this promising field.