Retinal image synthesis from multiple-landmarks input with generative adversarial networks.

BACKGROUND: Medical datasets, especially medical images, are often imbalanced due to the different incidences of various diseases. To address this problem, many methods have been proposed to synthesize medical images using generative adversarial networks (GANs) to enlarge training datasets for facilitating medical image analysis. For instance, conventional methods such as image-to-image translation techniques are used to synthesize fundus images with their respective vessel trees in the field of fundus image. METHODS: In order to improve the image quality and details of the synthetic images, three key aspects of the pipeline are mainly elaborated: the input mask, architecture of GANs, and the resolution of paired images. We propose a new preprocessing pipeline named multiple-channels-multiple-landmarks (MCML), aiming to synthesize color fundus images from a combination of vessel tree, optic disc, and optic cup images. We compared both single vessel mask input and MCML mask input on two public fundus image datasets (DRIVE and DRISHTI-GS) with different kinds of Pix2pix and Cycle-GAN architectures. A new Pix2pix structure with ResU-net generator is also designed, which has been compared with the other models. RESULTS AND CONCLUSION: As shown in the results, the proposed MCML method outperforms the single vessel-based methods for each architecture of GANs. Furthermore, we find that our Pix2pix model with ResU-net generator achieves superior PSNR and SSIM performance than the other GANs. High-resolution paired images are also beneficial for improving the performance of each GAN in this work. Finally, a Pix2pix network with ResU-net generator using MCML and high-resolution paired images are able to generate good and realistic fundus images in this work, indicating that our MCML method has great potential in the field of glaucoma computer-aided diagnosis based on fundus image.

A super-resolution method-based pipeline for fundus fluorescein angiography imaging.

BACKGROUND: Fundus fluorescein angiography (FFA) imaging is a standard diagnostic tool for many retinal diseases such as age-related macular degeneration and diabetic retinopathy. High-resolution FFA images facilitate the detection of small lesions such as microaneurysms, and other landmark changes, in the early stages; this can help an ophthalmologist improve a patient's cure rate. However, only low-resolution images are available in most clinical cases. Super-resolution (SR), which is a method to improve the resolution of an image, has been successfully employed for natural and remote sensing images. To the best of our knowledge, no one has applied SR techniques to FFA imaging so far. METHODS: In this work, we propose a SR method-based pipeline for FFA imaging. The aim of this pipeline is to enhance the image quality of FFA by using SR techniques. Several SR frameworks including neighborhood embedding, sparsity-based, locally-linear regression and deep learning-based approaches are investigated. Based on a clinical FFA dataset collected from Second Affiliated Hospital to Xuzhou Medical University, each SR method is implemented and evaluated for the pipeline to improve the resolution of FFA images. RESULTS AND CONCLUSION: As shown in our results, most SR algorithms have a positive impact on the enhancement of FFA images. Super-resolution forests (SRF), a random forest-based SR method has displayed remarkable high effectiveness and outperformed other methods. Hence, SRF should be one potential way to benefit ophthalmologists by obtaining high-resolution FFA images in a clinical setting.

In vivo long-term investigation of tumor bearing mKate2 by an in-house fluorescence molecular imaging system.

BACKGROUND: Optical imaging is one of the most common, low-cost imaging tools used for investigating the tumor biological behavior in vivo. This study explores the feasibility and sensitivity of a near infrared fluorescent protein mKate2 for a long-term non-invasive tumor imaging in BALB/c nude mice, by using a low-power optical imaging system. METHODS: In this study, breast cancer cell line MDA-MB-435s expressing mKate2 and MDA-MB-231 expressing a dual reporter gene firefly luciferase (fLuc)-GFP were used as cell models. Tumor cells were implanted in different animal body compartments including subcutaneous, abdominal and deep tissue area and closely monitored in real-time. A simple and low-power optical imaging system was set up to image both fluorescence and bioluminescence in live animals. RESULTS: The presence of malignant tissue was further confirmed by histopathological assay. Considering its lower exposure time and no need of substrate injection, mKate2 is considered a superior choice for subcutaneous imaging compared with fLuc. On the contrary, fLuc has shown to be a better option when monitoring the tumor in a diffusive area such as abdominal cavity. Furthermore, both reporter genes have shown good stability and sensitivity for deep tissue imaging, i.e. tumor within the liver. In addition, fLuc has shown to be an excellent method for detecting tumor cells in the lung. CONCLUSIONS: The combination of mKate2 and fLuc offers a superior choice for long-term non-invasive real-time investigation of tumor biological behavior in vivo.

A modularly designed fluorescence molecular tomography system for multi-modality imaging.

Nowadays multi-modality imaging has gained great interest in biology research by offering complementary information. In this paper, a modularly designed fluorescence molecular tomography (FMT) system has been developed, which can be not only used as a standalone imaging device, but also feasibly integrated with other imaging modalities, such as X-ray computed tomography (X-CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET), to perform multi-modality imaging in a sequential manner. The system rotates the CCD camera and the excitation light source in the vertical plane, while the animal is stationed on a horizontally moveable transparent animal holder at its natural prone position. FMT and other imaging modalities are co-registered automatically. Phantom and animal experiments have been carried out to demonstrate the performance of the system. The accurate results show that this innovative flexible FMT system has a great potential to be a powerful tool for the study of small animal disease models.

Boosting Weakly Supervised Object Localization and Segmentation With Domain Adaption.

Weakly supervised object localization (WSOL), adopting only image-level annotations to learn the pixel-level localization model, can release human resources in the annotation process. Most one-stage WSOL methods learn the localization model with multi-instance learning, making them only activate discriminative object parts rather than the whole object. In our work, we attribute this problem to the domain shift between the training and test process of WSOL and provide a novel perspective that views WSOL as a domain adaption (DA) task. Under this perspective, a DA-WSOL pipeline is elaborated to better assist WSOL with DA approaches by considering the specificities for the adaption of WSOL. Our DA-WSOL pipeline can discern the source-related and the Universum samples from other target samples based on a proposed target sampling strategy and then utilize them to solve the sample unbalancing and label unmatching between the source and target domain of WSOL. Experiments show that our pipeline outperforms SOTA methods on three WSOL benchmarks and can improve the performance of downstream weakly supervised semantic segmentation tasks. Codes are available at https://github.com/zh460045050/dawsol.

Megahertz multi-parametric ophthalmic OCT system for whole eye imaging.

An ultrahigh-speed, wide-field OCT system for the imaging of anterior, posterior, and ocular biometers is crucial for obtaining comprehensive ocular parameters and quantifying ocular pathology size. Here, we demonstrate a multi-parametric ophthalmic OCT system with a speed of up to 1 MHz for wide-field imaging of the retina and 50 kHz for anterior chamber and ocular biometric measurement. A spectrum correction algorithm is proposed to ensure the accurate pairing of adjacent A-lines and elevate the A-scan speed from 500 kHz to 1 MHz for retinal imaging. A registration method employing position feedback signals was introduced, reducing pixel offsets between forward and reverse galvanometer scanning by 2.3 times. Experimental validation on glass sheets and the human eye confirms feasibility and efficacy. Meanwhile, we propose a revised formula to determine the "true" fundus size using all-axial length parameters from different fields of view. The efficient algorithms and compact design enhance system compatibility with clinical requirements, showing promise for widespread commercialization.

PSCAT: a lightweight transformer for simultaneous denoising and super-resolution of OCT images.

Optical coherence tomography (OCT), owing to its non-invasive nature, has demonstrated tremendous potential in clinical practice and has become a prevalent diagnostic method. Nevertheless, the inherent speckle noise and low sampling rate in OCT imaging often limit the quality of OCT images. In this paper, we propose a lightweight Transformer to efficiently reconstruct high-quality images from noisy and low-resolution OCT images acquired by short scans. Our method, PSCAT, parallelly employs spatial window self-attention and channel attention in the Transformer block to aggregate features from both spatial and channel dimensions. It explores the potential of the Transformer in denoising and super-resolution for OCT, reducing computational costs and enhancing the speed of image processing. To effectively assist in restoring high-frequency details, we introduce a hybrid loss function in both spatial and frequency domains. Extensive experiments demonstrate that our PSCAT has fewer network parameters and lower computational costs compared to state-of-the-art methods while delivering a competitive performance both qualitatively and quantitatively.

PCNet: Prior Category Network for CT Universal Segmentation Model.

Accurate segmentation of anatomical structures in Computed Tomography (CT) images is crucial for clinical diagnosis, treatment planning, and disease monitoring. The present deep learning segmentation methods are hindered by factors such as data scale and model size. Inspired by how doctors identify tissues, we propose a novel approach, the Prior Category Network (PCNet), that boosts segmentation performance by leveraging prior knowledge between different categories of anatomical structures. Our PCNet comprises three key components: prior category prompt (PCP), hierarchy category system (HCS), and hierarchy category loss (HCL). PCP utilizes Contrastive Language-Image Pretraining (CLIP), along with attention modules, to systematically define the relationships between anatomical categories as identified by clinicians. HCS guides the segmentation model in distinguishing between specific organs, anatomical structures, and functional systems through hierarchical relationships. HCL serves as a consistency constraint, fortifying the directional guidance provided by HCS to enhance the segmentation model's accuracy and robustness. We conducted extensive experiments to validate the effectiveness of our approach, and the results indicate that PCNet can generate a high-performance, universal model for CT segmentation. The PCNet framework also demonstrates a significant transferability on multiple downstream tasks. The ablation experiments show that the methodology employed in constructing the HCS is of critical importance. The prompt and HCS can be accessed at https://github.com/YixinChen-AI/PCNet.

Choroidal Vascularity Index and Choroidal Structural Changes in Children With Nephrotic Syndrome.

Purpose: To investigate the choroidal vascularity index (CVI) and choroidal structural changes in children with nephrotic syndrome. Methods: This was a cross-sectional study involving 45 children with primary nephrotic syndrome and 40 normal controls. All participants underwent enhanced depth imaging-optical coherence tomography examinations. An automatic segmentation method based on deep learning was used to segment the choroidal vessels and stroma, and the choroidal volume (CV), vascular volume (VV), and CVI within a 4.5 mm diameter circular area centered around the macular fovea were obtained. Clinical data, including blood lipids, serum proteins, renal function, and renal injury indicators, were collected from the patients. Results: Compared with normal controls, children with nephrotic syndrome had a significant increase in CV (nephrotic syndrome: 4.132 ± 0.464 vs. normal controls: 3.873 ± 0.574; P = 0.024); no significant change in VV (nephrotic syndrome: 1.276 ± 0.173 vs. normal controls: 1.277 ± 0.165; P = 0.971); and a significant decrease in the CVI (nephrotic syndrome: 0.308 [range, 0.270-0.386] vs. normal controls: 0.330 [range, 0.288-0.387]; P < 0.001). In the correlation analysis, the CVI was positively correlated with serum total protein, serum albumin, serum prealbumin, ratio of serum albumin to globulin, and 24-hour urine volume and was negatively correlated with total cholesterol, low-density lipoprotein cholesterol, urinary protein concentration, and ratio of urinary transferrin to creatinine (all P < 0.05). Conclusions: The CVI is significantly reduced in children with nephrotic syndrome, and the decrease in the CVI parallels the severity of kidney disease, indicating choroidal involvement in the process of nephrotic syndrome. Translational Relevance: Our findings contribute to a deeper understanding of how nephrotic syndrome affects the choroid.

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.

Progress in the development of CdZnTe unipolar detectors for different anode geometries and data corrections.

CdZnTe detectors have been under development for the past two decades, providing good stopping power for gamma rays, lightweight camera heads and improved energy resolution. However, the performance of this type of detector is limited primarily by incomplete charge collection problems resulting from charge carriers trapping. This paper is a review of the progress in the development of CdZnTe unipolar detectors with some data correction techniques for improving performance of the detectors. We will first briefly review the relevant theories. Thereafter, two aspects of the techniques for overcoming the hole trapping issue are summarized, including irradiation direction configuration and pulse shape correction methods. CdZnTe detectors of different geometries are discussed in detail, covering the principal of the electrode geometry design, the design and performance characteristics, some detector prototypes development and special correction techniques to improve the energy resolution. Finally, the state of art development of 3-D position sensing and Compton imaging technique are also discussed. Spectroscopic performance of CdZnTe semiconductor detector will be greatly improved even to approach the statistical limit on energy resolution with the combination of some of these techniques. 

Discriminative ensemble meta-learning with co-regularization for rare fundus diseases diagnosis.

Deep neural networks (DNNs) have been widely applied in the medical image community, contributing to automatic ophthalmic screening systems for some common diseases. However, the incidence of fundus diseases patterns exhibits a typical long-tailed distribution. In clinic, a small number of common fundus diseases have sufficient observed cases for large-scale analysis while most of the fundus diseases are infrequent. For these rare diseases with extremely low-data regimes, it is challenging to train DNNs to realize automatic diagnosis. In this work, we develop an automatic diagnosis system for rare fundus diseases, based on the meta-learning framework. The system incorporates a co-regularization loss and the ensemble-learning strategy into the meta-learning framework, fully leveraging the advantage of multi-scale hierarchical feature embedding. We initially conduct comparative experiments on our newly-constructed lightweight multi-disease fundus images dataset for the few-shot recognition task (namely, FundusData-FS). Moreover, we verify the cross-domain transferability from miniImageNet to FundusData-FS, and further confirm our method's good repeatability. Rigorous experiments demonstrate that our method can detect rare fundus diseases, and is superior to the state-of-the-art methods. These investigations demonstrate that the potential of our method for the real clinical practice is promising.

Background-Aware Classification Activation Map for Weakly Supervised Object Localization.

Weakly supervised object localization (WSOL) relaxes the requirement of dense annotations for object localization by using image-level annotation to supervise the learning process. However, most WSOL methods only focus on forcing the object classifier to produce high activation score on object parts without considering the influence of background locations, causing excessive background activations and ill-pose background score searching. Based on this point, our work proposes a novel mechanism called the background-aware classification activation map (B-CAM) to add background awareness for WSOL training. Besides aggregating an object image-level feature for supervision, our B-CAM produces an additional background image-level feature to represent the pure-background sample. This additional feature can provide background cues for the object classifier to suppress the background activations on object localization maps. Moreover, our B-CAM also trained a background classifier with image-level annotation to produce adaptive background scores when determining the binary localization mask. Experiments indicate the effectiveness of the proposed B-CAM on four different types of WSOL benchmarks, including CUB-200, ILSVRC, OpenImages, and VOC2012 datasets.

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.

Comprehensive prognostic modeling of locoregional recurrence after radiotherapy for patients with locoregionally advanced hypopharyngeal squamous cell carcinoma.

Purpose: To propose and evaluate a comprehensive modeling approach combing radiomics, dosiomics and clinical components, for more accurate prediction of locoregional recurrence risk after radiotherapy for patients with locoregionally advanced HPSCC. Materials and methods: Clinical data of 77 HPSCC patients were retrospectively investigated, whose median follow-up duration was 23.27 (4.83-81.40) months. From the planning CT and dose distribution, 1321 radiomics and dosiomics features were extracted respectively from planning gross tumor volume (PGTV) region each patient. After stability test, feature dimension was further reduced by Principal Component Analysis (PCA), yielding Radiomic and Dosiomic Principal Components (RPCs and DPCs) respectively. Multiple Cox regression models were constructed using various combinations of RPC, DPC and clinical variables as the predictors. Akaike information criterion (AIC) and C-index were used to evaluate the performance of Cox regression models. Results: PCA was performed on 338 radiomic and 873 dosiomic features that were tested as stable (ICC1 > 0.7 and ICC2 > 0.95), yielding 5 RPCs and DPCs respectively. Three comprehensive features (RPC0, P<0.01, DPC0, P<0.01 and DPC3, P<0.05) were found to be significant in the individual Radiomic or Dosiomic Cox regression models. The model combining the above features and clinical variable (total stage IVB) provided best risk stratification of locoregional recurrence (C-index, 0.815; 95%CI, 0.770-0.859) and prevailing balance between predictive accuracy and complexity (AIC, 143.65) than any other investigated models using either single factors or two combined components. Conclusion: This study provided quantitative tools and additional evidence for the personalized treatment selection and protocol optimization for HPSCC, a relatively rare cancer. By combining complementary information from radiomics, dosiomics, and clinical variables, the proposed comprehensive model provided more accurate prediction of locoregional recurrence risk after radiotherapy.

A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics.

Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-ß signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.

3-D Convolutional Neural Networks for RGB-D Salient Object Detection and Beyond.

RGB-depth (RGB-D) salient object detection (SOD) recently has attracted increasing research interest, and many deep learning methods based on encoder-decoder architectures have emerged. However, most existing RGB-D SOD models conduct explicit and controllable cross-modal feature fusion either in the single encoder or decoder stage, which hardly guarantees sufficient cross-modal fusion ability. To this end, we make the first attempt in addressing RGB-D SOD through 3-D convolutional neural networks. The proposed model, named, aims at prefusion in the encoder stage and in-depth fusion in the decoder stage to effectively promote the full integration of RGB and depth streams. Specifically, first conducts prefusion across RGB and depth modalities through a 3-D encoder obtained by inflating 2-D ResNet and later provides in-depth feature fusion by designing a 3-D decoder equipped with rich back-projection paths (RBPPs) for leveraging the extensive aggregation ability of 3-D convolutions. Toward an improved model, we propose to disentangle the conventional 3-D convolution into successive spatial and temporal convolutions and, meanwhile, discard unnecessary zero padding. This eventually results in a 2-D convolutional equivalence that facilitates optimization and reduces parameters and computation costs. Thanks to such a progressive-fusion strategy involving both the encoder and the decoder, effective and thorough interactions between the two modalities can be exploited and boost detection accuracy. As an additional boost, we also introduce channel-modality attention and its variant after each path of RBPP to attend to important features. Extensive experiments on seven widely used benchmark datasets demonstrate that and perform favorably against 14 state-of-the-art RGB-D SOD approaches in terms of five key evaluation metrics. Our code will be made publicly available at https://github.com/PPOLYpubki/RD3D.

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.

Triplet Cross-Fusion Learning for Unpaired Image Denoising in Optical Coherence Tomography.

Optical coherence tomography (OCT) is a widely-used modality in clinical imaging, which suffers from the speckle noise inevitably. Deep learning has proven its superior capability in OCT image denoising, while the difficulty of acquiring a large number of well-registered OCT image pairs limits the developments of paired learning methods. To solve this problem, some unpaired learning methods have been proposed, where the denoising networks can be trained with unpaired OCT data. However, majority of them are modified from the cycleGAN framework. These cycleGAN-based methods train at least two generators and two discriminators, while only one generator is needed for the inference. The dual-generator and dual-discriminator structures of cycleGAN-based methods demand a large amount of computing resource, which may be redundant for OCT denoising tasks. In this work, we propose a novel triplet cross-fusion learning (TCFL) strategy for unpaired OCT image denoising. The model complexity of our strategy is much lower than those of the cycleGAN-based methods. During training, the clean components and the noise components from the triplet of three unpaired images are cross-fused, helping the network extract more speckle noise information to improve the denoising accuracy. Furthermore, the TCFL-based network which is trained with triplets can deal with limited training data scenarios. The results demonstrate that the TCFL strategy outperforms state-of-the-art unpaired methods both qualitatively and quantitatively, and even achieves denoising performance comparable with paired methods. Code is available at: https://github.com/gengmufeng/TCFL-OCT.

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.