High-resolution wide-field imaging of perfused capillaries without the use of contrast agent

Abstract

Darin A Nelson1, Zvia Burgansky-Eliash1,2, Hila Barash1, Anat Loewenstein3, Adiel Barak4, Elisha Bartov2, Tali Rock2, Amiram Grinvald51Optical Imaging Ltd, Rehovot, Israel; 2Department of Ophthalmology, Edith Wolfson Medical Center, Holon, Israel; 3Department of Ophthalmology, Tel Aviv Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Israel; 4Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 5Department of Neurobiology, The Weizmann Institute of Science, Rehovot, IsraelPurpose: Assessment of capillary abnormalities facilitates early diagnosis, treatment, and follow-up of common retinal pathologies. Injected contrast agents like fluorescein are widely used to image retinal capillaries, but this highly effective procedure has a few disadvantages, such as untoward side effects, inconvenience of injection, and brevity of the time window for clear visualization. The retinal function imager (RFI) is a tool for monitoring retinal functions, such as blood velocity and oximetry, based on intrinsic signals. Here we describe the clinical use of hemoglobin in red blood cells (RBCs) as an intrinsic motion-contrast agent in the generation of detailed noninvasive capillary-perfusion maps (nCPMs).Patients and methods: Multiple series of nCPM images were acquired from 130 patients with diabetic retinopathy, vein occlusion, central serous retinopathy, age-related macular degeneration, or metabolic syndrome, as well as from 37 healthy subjects. After registration, pixel value distribution parameters were analyzed to locate RBC motion.Results: The RFI yielded nCPMs demonstrating microvascular morphology including capillaries in exquisite detail. Maps from the same subject were highly reproducible in repeated measurements, in as much detail and often better than that revealed by the very best fluorescein angiography. In patients, neovascularization and capillary nonperfusion areas were clearly observed. Foveal avascular zones (FAZ) were sharply delineated and were larger in patients with diabetic retinopathy than in controls (FAZ diameter: 641.5 ± 82.3 versus 463.7 ± 105 µm; P < 0.001). Also visible were abnormal vascular patterns, such as shunts and vascular loops.Conclusion: Optical imaging of retinal capillaries in human patients based on motion contrast is noninvasive, comfortable, safe, and can be repeated as often as required for early diagnosis, treatment guidance, and follow up of retinal disease progression.Keywords: noninvasive, capillary maps, motion contrast, foveal avascular zone, retinal imaging, injection, fluorescein