Supervised machine learning based multi-task artificial intelligence classification of retinopathies

Artificial intelligence (AI) classification holds promise as a novel and affordable screening tool for clinical management of ocular diseases. Rural and underserved areas, which suffer from lack of access to experienced ophthalmologists may particularly benefit from this technology. Quantitative optical coherence tomography angiography (OCTA) imaging provides excellent capability to identify subtle vascular distortions, which are useful for classifying retinovascular diseases. However, application of AI for differentiation and classification of multiple eye diseases is not yet established. In this study, we demonstrate supervised machine learning based multi-task OCTA classification. We sought 1) to differentiate normal from diseased ocular conditions, 2) to differentiate different ocular disease conditions from each other, and 3) to stage the severity of each ocular condition. Quantitative OCTA features, including blood vessel tortuosity (BVT), blood vascular caliber (BVC), vessel perimeter index (VPI), blood vessel density (BVD), foveal avascular zone (FAZ) area (FAZ-A), and FAZ contour irregularity (FAZ-CI) were fully automatically extracted from the OCTA images. A stepwise backward elimination approach was employed to identify sensitive OCTA features and optimal-feature-combinations for the multi-task classification. For proof-of-concept demonstration, diabetic retinopathy (DR) and sickle cell retinopathy (SCR) were used to validate the supervised machine leaning classifier. The presented AI classification methodology is applicable and can be readily extended to other ocular diseases, holding promise to enable a mass-screening platform for clinical deployment and telemedicine.Comment: Supplemental material attached at the en

A portable widefield fundus camera with high dynamic range imaging capability

Fundus photography is indispensable for clinical detection and management of eye diseases. Limited image contrast and field of view (FOV) are common limitations of conventional fundus cameras, making it difficult to detect subtle abnormalities at the early stages of eye diseases. Further improvements of image contrast and FOV coverage are important to improve early disease detection and reliable treatment assessment. We report here a portable fundus camera, with a wide FOV and high dynamic range (HDR) imaging capabilities. Miniaturized indirect ophthalmoscopy illumination was employed to achieve the portable design for nonmydriatic, widefield fundus photography. Orthogonal polarization control was used to eliminate illumination reflectance artifact. With independent power controls, three fundus images were sequentially acquired and fused to achieve HDR function for local image contrast enhancement. A 101{\deg} eye-angle (67{\deg} visual-angle) snapshot FOV was achieved for nonmydriatic fundus photography. The effective FOV can be readily expanded up to 190{\deg} eye-angle (134{\deg} visual-angle) with the aid of a fixation target, without the need of pharmacologic pupillary dilation. The effectiveness of HDR imaging was validated with both normal healthy and pathologic eyes, compared to a conventional fundus camera.Comment: 12 pages, 8 figure

Simultaneous detection of cerebral blood perfusion and cerebral edema using swept‐source optical coherence tomography

The progression of ischemic cerebral edema (CE) is closely related to the level of cerebral blood perfusion (CBP) and affects each other. Simultaneous detection of CBP and CE is helpful in understanding the mechanisms of ischemic CE development. In this article, a wide field of view swept‐source optical coherence tomography system was used to detect CE status and CBP levels simultaneously in middle cerebral artery occlusion rats. Images reflecting these two physiological states can be reconstructed with only one C‐scan. We quantify these two physiological states into four parameters, which contain two vascular parameters (vascular displacement distance and vascular perfusion density) and two edema parameters (optical attenuation coefficient and edema area). The association between the two vascular parameters and the two edema parameters was analyzed. The results show that there is a strong linear relationship between blood flow parameters and edema parameters. This work provides a new option for CE in vivo detection, and is very likely to play an important role in the development of relevant drugs or in selection of treatment options.In this article, a wide field of view swept‐source optical coherence tomography system was used to detect cerebral edema status and cerebral blood perfusion levels simultaneously in middle cerebral artery occlusion rats. Images reflecting these two physiological states can be reconstructed with only one C‐scan. We quantify these two physiological states into four parameters, which contain two vascular parameters and two edema parameters. The association between the two vascular parameters and the two edema parameters was analyzed. The results show that there is a strong linear relationship between blood flow parameters and edema parameters.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153673/1/jbio201960087_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153673/2/jbio201960087.pd

Whole‐brain microcirculation detection after ischemic stroke based on swept‐source optical coherence tomography

The occurrence and development of ischemic stroke are closely related to cerebral blood flow. Real‐time monitoring of cerebral perfusion level is very useful for understanding the mechanisms of the disease. A wide field of view (FOV) is conducive to capturing lesions and observing the progression of the disease. In this paper, we attempt to monitor the whole‐brain microcirculation in middle cerebral artery occlusion (MCAO) rats over time using a wide FOV swept‐source OCT (SS‐OCT) system. A constrained image registration algorithm is used to remove motion artifacts that are prone to occur in a wide FOV angiography. During ischemia, cerebral perfusion levels in the left and right hemispheres, as well as in the whole brain were quantified and compared. Changes in the shape and location of blood vessels were also recorded. The results showed that the trend in cerebral perfusion levels of both hemispheres was highly consistent during MCAO, and the position of the blood vessels varied over time. This work will provide new insights of ischemic stroke and is helpful to assess the effectiveness of potential treatment strategies.En face maximum intensity projections (MIP) of the whole‐brain vascular networks obtained by wide field of view (FOV) swept‐source optical coherence tomography (SS‐OCT) system.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151895/1/jbio201900122_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151895/2/jbio201900122.pd

Optical imaging of fast, dynamic neurophysiological function.

Fast evoked responses were imaged from rat dorsal medulla and whisker barrel cortex. To investigate the biophysical mechanisms involved, fast optical responses associated with isolated crustacean nerve stimulation were recorded using birefringence and scattered light. Such studies allow optimization of non-invasive imaging techniques being developed for use in humans

Serum 25-hydroxyvitamin D3 is associated with advanced glycation end products (AGEs) measured as skin autofluorescence: The Rotterdam Study

Advanced glycation end products (AGEs) accumulate in tissues with aging and may influence age-related diseases. They can be estimated non-invasively by skin autofluorescence (SAF) using the AGE Reader™. Serum 25-hydroxyvitamin D3 (25(OH)D3) may inhibit AGEs accumulation through anti-oxidative and anti-inflammatory properties but evidence in humans is scarce. The objective was to investigate the association between serum 25(OH)D3 and SAF in the population-based cohort study. Serum 25(OH)D3 and other covariates were measured at baseline. SAF was measured on average 11.5 years later. Known risk factors for AGE accumulation such as higher age, BMI, and coffee intake, male sex, smoking, diabetes, and decreased renal function were measured at baseline. Linear regression models were adopted to explore the association between 25(OH)D3 and SAF with adjustment for confounders. Interaction terms were tested to identify effect modification. The study was conducted in the general community. 2746 community-dwelling participants (age ≥ 45 years) from the Rotterdam Study were included. Serum 25(OH)D3 inversely associated with SAF and explained 1.5% of the variance (unstandardized B = − 0.002 (95% CI[− 0.003, − 0.002]), standardized β = − 0.125), independently of known risk factors and medication intake. The association was present in both diabetics (B = − 0.004 (95% CI[− 0.008, − 0.001]), β = − 0.192) and non-diabetics (B = − 0.002 (95% CI[− 0.003, − 0.002]), β = − 0.122), both sexes, both smokers and non-smokers and in each RS subcohort. Serum 25(OH)D3 concentration was significantly and inversely associated with SAF measured prospectively, also after adjustment for known risk factors for high SAF and the number of medication used, but the causal chain is yet to be explored in future studies. Clinical Trial Registry (1) Netherlands National Trial Register: Trial ID: NTR6831 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831). (2) WHO International Clinical Trials Registry Platform: under shared catalogue number NTR6831 (www.who.int/ictrp/network/primary/en/)

Evidence for an Excitonic Insulator State in Ta2_2Pd3_3Te5_5

The excitonic insulator (EI) is an exotic ground state of narrow-gap semiconductors and semimetals arising from spontaneous condensation of electron-hole pairs bound by attractive Coulomb interaction. Despite research on EIs dating back to half a century ago, their existence in real materials remains a subject of ongoing debate. In this study, through systematic experimental and theoretical investigations, we provide evidence for the existence of an EI ground state in a van der Waals compound Ta$_2$Pd$_3$Te$_5$. Density-functional-theory calculations suggest that it is a semimetal with a small band overlap, whereas various experiments exhibit an insulating ground state with a clear band gap. Upon incorporating electron-hole Coulomb interaction into our calculations, we obtain an EI phase where the electronic symmetry breaking opens a many-body gap. Angle-resolved photoemission spectroscopy measurements exhibit that the band gap is closed with a significant change in the dispersions as the number of thermally excited charge carriers becomes sufficiently large in both equilibrium and nonequilibrium states. Structural measurements reveal a slight breaking of crystal symmetry with exceptionally small lattice distortion in the insulating state, which cannot account for the significant gap opening. Therefore, we attribute the insulating ground state with a gap opening in Ta$_2$Pd$_3$Te$_5$ to exciton condensation, where the coupling to the symmetry-breaking electronic state induces a subtle change in the crystal structure.Comment: 10 pages, 5 figure