The retinal oxygen metabolism and hemodynamics as a substitute for biochemical tests to predict nonproliferative diabetic retinopathy.

Predicting the occurrence of nonproliferative diabetic retinopathy (NPDR) using biochemical parameters is invasive, which limits large-scale clinical application. Noninvasive retinal oxygen metabolism and hemodynamics of 215 eyes from 73 age-matched healthy subjects, 90 diabetic patients without DR, 40 NPDR, and 12 DR with postpanretinal photocoagulation were measured with a custom-built multimodal retinal imaging device. Diabetic patients underwent biochemical examinations. Two logistic regression models were developed to predict NPDR using retinal and biochemical metrics, respectively. The predictive model 1 using retinal metrics incorporated male gender, insulin treatment condition, diastolic duration, resistance index, and oxygen extraction fraction presented a similar predictive power with model 2 using biochemical metrics incorporated diabetic duration, diastolic blood pressure, and glycated hemoglobin A1c (area under curve: 0.73 vs. 0.70; sensitivity: 76% vs. 68%; specificity: 64% vs. 62%). These results suggest that retinal oxygen metabolic and hemodynamic biomarkers may replace biochemical parameters to predict the occurrence of NPDR .

Predicting the cognitive impairment with multimodal ophthalmic imaging and artificial neural network for community screening.

BACKGROUND/AIMS: To investigate the comprehensive prediction ability for cognitive impairment in a general elder population using the combination of the multimodal ophthalmic imaging and artificial neural networks. METHODS: Patients with cognitive impairment and cognitively healthy individuals were recruited. All subjects underwent medical history, blood pressure measurement, the Montreal Cognitive Assessment, medical optometry, intraocular pressure and custom-built multimodal ophthalmic imaging, which integrated pupillary light reaction, multispectral imaging, laser speckle contrast imaging and retinal oximetry. Multidimensional parameters were analysed by Student's t-test. Logistic regression analysis and back-propagation neural network (BPNN) were used to identify the predictive capability for cognitive impairment. RESULTS: This study included 104 cognitive impairment patients (61.5% female; mean (SD) age, 68.3 (9.4) years), and 94 cognitively healthy age-matched and sex-matched subjects (56.4% female; mean (SD) age, 65.9 (7.6) years). The variation of most parameters including decreased pupil constriction amplitude (CA), relative CA, average constriction velocity, venous diameter, venous blood flow and increased centred retinal reflectance in 548 nm (RC548) in cognitive impairment was consistent with previous studies while the reduced flow acceleration index and oxygen metabolism were reported for the first time. Compared with the logistic regression model, BPNN had better predictive performance (accuracy: 0.91 vs 0.69; sensitivity: 93.3% vs 61.70%; specificity: 90.0% vs 68.66%). CONCLUSIONS: This study demonstrates retinal spectral signature alteration, neurodegeneration and angiopathy occur concurrently in cognitive impairment. The combination of multimodal ophthalmic imaging and BPNN can be a useful tool for predicting cognitive impairment with high performance for community screening.

SGLSA: Sphygmus gated laser speckle angiography for microcirculation hemodynamics imaging.

Hemodynamics imaging of the retinal microcirculation has been demonstrated to be potential access to evaluating ophthalmic diseases, cardio-cerebrovascular diseases, and metabolic diseases. However, existing structural and functional imaging techniques are insufficient in spatial or temporal resolution. The sphygmus gated laser speckle angiography (SGLSA) is proposed for structural and functional imaging with high spatiotemporal resolution. Compared with classic LSCI algorithms, SGLSA presents a much clearer perfusion image and higher signal-to-noise ratio pulsatility. The SGLSA algorithm also shows better performance on patients than traditional LSCI methods. The high spatiotemporal resolution provided by the SGLSA algorithm greatly enhances the ability of retinal microcirculation analysis, which makes up for the deficiency of the LSCI technology, and attaches great significance to retinal hemodynamic imaging, biomarker research, and clinical diagnosis.

Bayesian statistics-guided label refurbishment mechanism: Mitigating label noise in medical image classification.

PURPOSE: Deep neural networks (DNNs) have been widely applied in medical image classification, benefiting from its powerful mapping capability among medical images. However, these existing deep learning-based methods depend on an enormous amount of carefully labeled images. Meanwhile, noise is inevitably introduced in the labeling process, degrading the performance of models. Hence, it is significant to devise robust training strategies to mitigate label noise in the medical image classification tasks. METHODS: In this work, we propose a novel Bayesian statistics-guided label refurbishment mechanism (BLRM) for DNNs to prevent overfitting noisy images. BLRM utilizes maximum a posteriori probability in the Bayesian statistics and the exponentially time-weighted technique to selectively correct the labels of noisy images. The training images are purified gradually with the training epochs when BLRM is activated, further improving classification performance. RESULTS: Comprehensive experiments on both synthetic noisy images (public OCT & Messidor datasets) and real-world noisy images (ANIMAL-10N) demonstrate that BLRM refurbishes the noisy labels selectively, curbing the adverse effects of noisy data. Also, the anti-noise BLRMs integrated with DNNs are effective at different noise ratio and are independent of backbone DNN architectures. In addition, BLRM is superior to state-of-the-art comparative methods of anti-noise. CONCLUSIONS: These investigations indicate that the proposed BLRM is well capable of mitigating label noise in medical image classification tasks.

Functional imaging of human retina using integrated multispectral and laser speckle contrast imaging.

A novel integration of retinal multispectral imaging (MSI), retinal oximetry and laser speckle contrast imaging (LSCI) is presented for functional imaging of retinal blood vessels that could potentially allow early detection or monitoring of functional changes. We designed and built a cost-effective, scalable, retinal imaging instrument that integrates structural and functional retinal imaging techniques, including MSI, retinal oximetry and LSCI. Color fundus imaging was performed with 470 nm, 550 nm and 600 nm wavelength light emitting diode (LED) illumination. Retinal oximetry was performed using 550 nm and 600 nm LED illumination. LSCI of blood flow was performed using 850 nm laser diode illumination at 82 frames per second. LSCI can visualize retinal and choroidal vasculature without requiring exogenous contrast agents and can provide time-resolved information on blood flow, generating a cardiac pulse waveform from retinal vasculature. The technology can rapidly acquire structural MSI images, retinal oximetry and LSCI blood flow information in a simplified clinical workflow without requiring patients to move between instruments. Results from multiple modalities can be combined and registered to provide structural as well as functional information on the retina. These advances can reduce barriers for clinical adoption, accelerating research using MSI, retinal oximetry and LSCI of blood flow for diagnosis, monitoring and elucidating disease pathogenesis.

Retinal oxygen kinetics imaging and analysis (ROKIA) based on the integration and fusion of structural-functional imaging.

The retina is one of the most metabolically active tissues in the body. The dysfunction of oxygen kinetics in the retina is closely related to the disease and has important clinical value. Dynamic imaging and comprehensive analyses of oxygen kinetics in the retina depend on the fusion of structural and functional imaging and high spatiotemporal resolution. But it's currently not clinically available, particularly via a single imaging device. Therefore, this work aims to develop a retinal oxygen kinetics imaging and analysis (ROKIA) technology by integrating dual-wavelength imaging with laser speckle contrast imaging modalities, which achieves structural and functional analysis with high spatial resolution and dynamic measurement, taking both external and lumen vessel diameters into account. The ROKIA systematically evaluated eight vascular metrics, four blood flow metrics, and fifteen oxygenation metrics. The single device scheme overcomes the incompatibility of optical design, harmonizes the field of view and resolution of different modalities, and reduces the difficulty of registration and image processing algorithms. More importantly, many of the metrics (such as oxygen delivery, oxygen metabolism, vessel wall thickness, etc.) derived from the fusion of structural and functional information, are unique to ROKIA. The oxygen kinetic analysis technology proposed in this paper, to our knowledge, is the first demonstration of the vascular metrics, blood flow metrics, and oxygenation metrics via a single system, which will potentially become a powerful tool for disease diagnosis and clinical research.

PMS-GAN: Parallel Multi-Stream Generative Adversarial Network for Multi-Material Decomposition in Spectral Computed Tomography.

Spectral computed tomography is able to provide quantitative information on the scanned object and enables material decomposition. Traditional projection-based material decomposition methods suffer from the nonlinearity of the imaging system, which limits the decomposition accuracy. Inspired by the generative adversarial network, we proposed a novel parallel multi-stream generative adversarial network (PMS-GAN) to perform projection-based multi-material decomposition in spectral computed tomography. By designing the differential map and incorporating the adversarial network into loss function, the decomposition accuracy was significantly improved with robust performance. The proposed network was quantitatively evaluated by both simulation and experimental study. The results show that PMS-GAN outperformed the reference methods with certain robustness. Compared with Pix2pix-GAN, PMS-GAN increased the structural similarity index by 172% on the contrast agent Ultravist370, 11% on bones, and 71% on bone marrow, respectively, in a simulated test scenario. In an experimental test scenario, 9% and 38% improvements of the structural similarity index on the biopsy needle and on a torso phantom were observed, respectively. The proposed network demonstrates its capability of multi-material decomposition and has certain potential toward clinical applications.

Wavelength selection for portable noninvasive blood component measurement system based on spectral difference coefficient and dynamic spectrum.

Noninvasive blood component analysis by spectroscopy has been a hotspot in biomedical engineering in recent years. Dynamic spectrum provides an excellent idea for noninvasive blood component measurement, but studies have been limited to the application of broadband light sources and high-resolution spectroscopy instruments. In order to remove redundant information, a more effective wavelength selection method has been presented in this paper. In contrast to many common wavelength selection methods, this method is based on sensing mechanism which has a clear mechanism and can effectively avoid the noise from acquisition system. The spectral difference coefficient was theoretically proved to have a guiding significance for wavelength selection. After theoretical analysis, the multi-band spectral difference coefficient-wavelength selection method combining with the dynamic spectrum was proposed. An experimental analysis based on clinical trial data from 200 volunteers has been conducted to illustrate the effectiveness of this method. The extreme learning machine was used to develop the calibration models between the dynamic spectrum data and hemoglobin concentration. The experiment result shows that the prediction precision of hemoglobin concentration using multi-band spectral difference coefficient-wavelength selection method is higher compared with other methods.