Use of XyCAM RI for Noninvasive Visualization and Analysis of Retinal Blood Flow Dynamics During Clinical Investigations

Ocular blood flow plays a critical role in eye health by nourishing the retinal and ocular tissues with oxygen and nutrients and removal of ocular metabolic waste. Imaging of retinal and optic blood flow may provide insights for early and more specific diagnoses of ocular vascular disorder and facilitate eye-based biomarkers applicable to neurological health assessment and research. The ability of the XyCAM RI (Vasoptic Medical Inc., MD, USA) to visualize and to analyze ocular blood flow dynamics XyCAM RI using laser speckle contrast imaging is reviewed and compared with concurrent clinical ophthalmic imaging technologies like optical coherence tomography - angiography (OCT-A), fundus imaging, fluorescein angiography (FA), indocyanine green angiography (ICGA), laser Doppler flowmetry (LDF), and laser speckle flowgraphy (LSFG). XyCAM RI, with its unprecedented imaging capabilities to assess blood flow dynamics provides a powerful tool to ophthalmic researchers and doctors to obtain greater clinical insights into the physiological status of the posterior segment and treatment approaches for various diseases in a very patient-friendly, noninvasive manner, unlike dye-based angiographic techniques such as FA or ICG. XyCAM RI is well suited as a modality that could close the gap between current screening and comprehensive eye exams

Investigating retinal blood flow characteristics and amyloid formation in patients with type 2 diabetes and mild cognitive impairment

Background Patients with type 2 diabetes (T2D) have almost a two‐fold greater risk of developing Alzheimer’s disease. Recent studies suggest that one link between the two conditions may be the processes underlying amyloidosis. Our previous studies have demonstrated that cognitive impairment (CI) is not limited to the brain but also affects the retina. In this pilot study, we quantified blood flow within the optic nerve head (ONH) using the XyCAM RI (Vasoptic Medical Inc.), an investigational non‐invasive, laser speckle‐based retinal imager, in cognitively healthy subjects (HC) and patients with mild cognitive impairment (MCI) and T2D. Method Thirty‐six individuals (8 HC, 16 T2D, and 12 MCI) were imaged using the XyCAM RI. One imaging session of 6 seconds duration was conducted on each eye of each subject. Only one eye (OS) was used in the analysis. Retinal blood flow (RBF) was agregated in a circular region of interest (ROI), spanning all vessels around the optic nerve head (ONH) (Figure 1). RBF was determined for one complete cardiac cycle without motion artifacts at its trough, mean, and peak per eye. The details of the RBF metrics extracted are included in the Table 1 legend. Result Patients with MCI had a longer TtS and SSVI than HC (p=0.007 and p=0.046 as per the independent sample t‐test, respectively, Table 1). Also, a significantly higher SSVI in MCI subjects demonstrated increased contractility compared to HC and T2D subjects. The Kruskal‐Wallis test confirmed that there is a statistically significant difference in the TtS between HC, MCI, and T2D (p=0.043). The average BFVI results are reported in Table 2. Conclusion Individuals with MCI and T2D have different RBF characteristics compared to cognitively healthy subjects. These results may be related to systemic changes in parameters such as arterial stiffness and increased blood pressure, which have been correlated with declined cognition. While our results obtained from a limited study population are suggestive, larger studies are needed to confirm the clinical applicability of our approach and the use of RBF‐based metrics as potential biomarkers of amyloidosis status

Multiexposure laser speckle contrast imaging of the angiogenic microenvironment

We report the novel use of laser speckle contrast imaging (LSCI) at multiple exposure times (meLSCI) for enhanced in vivo imaging of the microvascular changes that accompany angiogenesis. LSCI is an optical imaging technique that can monitor blood vessels and the flow therein at a high spatial resolution without requiring the administration of an exogenous contrast agent. LSCI images are obtained under red (632 nm) laser illumination at seven exposure times (1–7 ms) and combined using a curve-fitting approach to obtain high-resolution meLSCI images of the rat brain vasculature. To evaluate enhancement in in vivo imaging performance, meLSCI images are statistically compared to individual LSCI images obtained at a single exposure time. We find that meLSCI reduced the observed variability in the LSCI-based blood-flow estimates by 30% and improved the contrast-to-noise ratio in regions with high microvessel density by 41%. The ability to better distinguish microvessels, makes meLSCI uniquely suited to longitudinal imaging of changes in the vascular microenvironment induced by pathological angiogenesis. We demonstrate this utility of meLSCI by sequentially monitoring, over days, the microvascular changes that accompany wound healing in a mouse ear model

Portable, non-invasive video imaging of retinal blood flow dynamics

Retinal blood flow (RBF) information has the potential to offer insight into ophthalmic health and disease that is complementary to traditional anatomical biomarkers as well as to retinal perfusion information provided by fluorescence or optical coherence tomography angiography (OCT-A). The present study was performed to test the functional attributes and performance of the XyCAM RI, a non-invasive imager that obtains and assesses RBF information. The XyCAM RI was installed and used in two different settings to obtain video recordings of the blood flow in the optic nerve head region in eyes of healthy subjects. The mean blood flow velocity index (BFVi) in the optic disc and in each of multiple arterial and venous segments was obtained and shown to reveal a temporal waveform with a peak and trough that correlates with a cardiac cycle as revealed by a reference pulse oximeter (correlation between respective peak-to-peak distances was 0.977). The intra-session repeatability of the XyCAM RI was high with a coefficient of variation (CV) of 1.84 ± 1.13% across both sites. Artery-vein comparisons were made by estimating, in a pair of adjacent arterial and venous segments, various temporal waveform metrics such as pulsatility index, percent time in systole and diastole, and change in vascular blood volume over a cardiac cycle. All arterial metrics were shown to have significant differences with venous metrics (p < 0.001). The XyCAM RI, therefore, by obtaining repeatable blood flow measurements with high temporal resolution, permits the differential assessment of arterial and venous blood flow patterns in the retina that may facilitate research into disease pathophysiology and biomarker development for diagnostics