Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer’s disease

Abstract

Studies of rodent models of Alzheimer’s disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aβ), may serve as surrogate markers of brain Aβ levels. As Aβ has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aβ. Significant differences in the retinal reflectance spectra are found between individuals with high Aβ burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aβ loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aβ in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aβ load.

Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina

“…The discovery of pathogenic Aβ deposits and early pericyte loss in retinal blood vessels of MCI and AD could shed light onto the pathophysiological mechanisms of vascular disruption, increased BRB permeability, insufficient blood supply, disrupted immune responses, and neuronal degeneration. In light of the recent advances in live imaging of retinal blood microvessels (OCT angiography) [26,42,62,82], pericyte imaging using adaptive optics [68], and retinal amyloid imaging [35,47], these results should lead to future development of noninvasive retinal vascular amyloid and pericyte imaging technologies to facilitate early screening and monitoring of AD.…”

“…Notably, the pathological hallmarks of AD-Aβ plaques and tauopathy-were further identified in the retina of AD patients, including early-stage cases [25,46,47,50]. Noninvasive high-resolution retinal imaging technologies such as fundus imaging, optical coherence tomography (OCT), as well as recently developed OCT angiography [42,62,72], retinal amyloid imaging [46][47][48], and retinal hyperspectral imaging [35,59] incentivize the use of feasible and inexpensive retinal imaging in the clinical setting to improve AD screening and monitoring.…”

Hyperspectral terahertz microscopy via nonlinear ghost imaging

“…Hyperspectral imaging assumes a broader probing significance in time-resolved systems; in particular, the delay of each frequency component can be profitably used to access the 3D morphology of the spectral phase response of a target, i.e., its spatially resolved complex dielectric function. Modern photonic approaches have produced essential breakthroughs in medicine, biology, and material science imaging [11][12][13][14][15]. In this context, the ability to reconstruct the time-domain waveforms provides direct access to the field [16] , although these approaches are well established in microwave and ultrasound imaging [2,5,6], they are sensibly less diffused in photonics.…”

The AppNL-G-F mouse retina is a site for preclinical Alzheimer’s disease diagnosis and research

“…2b). A hyperspectral score was calculated for each mouse from the ex vivo retinal reflectance data, using a modification of methods developed for in vivo hyperspectral retinal imaging 27 . Hyperspectral scores were significantly higher in App NL-G-F mice compared to agematched WT mice at both ages (p=0.0014 at 3 months, p=0.0002 at 18 months) ( Fig.…”

“…This imaging spectroscopy technique is based on the fact that soluble Aβ aggregates -most likely Aβ42 -interfere with traversing light, leading to Rayleigh light scattering and a characteristic hyperspectral signature, the magnitude of which appear to be proportional to the amount of Aβ present 9,10 . In the past year, following promising post mortem and in vivo studies in both animal and human retinas 9,10,43 , results of the first clinical trial showing that in vivo retinal hyperspectral imaging can discriminate between Aβ PET-positive cases and controls emerged 27 . This, together with our data, suggests that hyperspectral imaging can be used to monitor retinal Aβ accumulation, with the potential to provide quantitative measures of Aβ oligomers.…”