Retinal segmentation is a prerequisite for quantifying retinal structural features and diagnosing related ophthalmic diseases. Canny operator is recognized as the best boundary detection operator so far, and is often used to obtain the initial boundary of the retina in retinal segmentation. However, the traditional Canny operator is susceptible to vascular shadows, vitreous artifacts, or noise interference in retinal segmentation, causing serious misdetection or missed detection. This paper proposed an improved Canny operator for automatic segmentation of retinal boundaries. The improved algorithm solves the problems of the traditional Canny operator by adding a multi-point boundary search step on the basis of the original method, and adjusts the convolution kernel. The algorithm was used to segment the retinal images of healthy subjects and age-related macular degeneration (AMD) patients; eleven retinal boundaries were identified and compared with the results of manual segmentation by the ophthalmologists. The average difference between the automatic and manual methods is: 2–6 microns (1–2 pixels) for healthy subjects and 3–10 microns (1–3 pixels) for AMD patients. Qualitative method is also used to verify the accuracy and stability of the algorithm. The percentage of “perfect segmentation” and “good segmentation” is 98% in healthy subjects and 94% in AMD patients. This algorithm can be used alone or in combination with other methods as an initial boundary detection algorithm. It is easy to understand and improve, and may become a useful tool for analyzing and diagnosing eye diseases.

Amyloid $\beta$ ($\mathrm{A}\beta$) peptides are naturally occurring cleavage products of the amyloid precursor protein via sequential proteolytic processes called $\beta$- and $\gamma$-secretase.¹ A primary neuropathological hallmark of Alzheimer’s disease (AD) involves extracellular $\mathrm{A}\beta$ deposition to form senile plaques, leading to neuronal death and cognitive degeneration.² Therefore, $\mathrm{A}\beta$ deposit elimination has been a major focus of $\mathrm{A}\beta$-based AD therapeutics over the past decades. Currently, there are more than one hundred agents in clinical trials for AD therapeutics.³ Although, Aducanumab, an anti-$\mathrm{A}\beta$ human monoclonal antibody, was approved by the U.S. Food and Drug Administration in 2021 for early AD.⁴ The efficacy of this drug remains highly controversial.^5,6 In addition, amyloid-related imaging abnormalities (ARIA) often co-occur during anti-$\mathrm{A}\beta$ immunotherapy (also seen with Aducanumab).^7,8 The high incidence of ARIA makes it a major adverse effect of $\mathrm{A}\beta$-targeted immunotherapies, which hinders the drug to reach the primary clinical endpoints.^{9 – 11} ARIA can be detected by magnetic resonance imaging (MRI) as hyperintensities on fluid-attenuated inversion recovery but is mostly asymptomatic.^7,12 It is suggested that the phenomena might be due to the breakdown of the $\mathrm{A}\beta$ plaque, liberating abundant amount of soluble $\mathrm{A}\beta$ peptides that overwhelm the capacity of $\mathrm{A}\beta$ clearance through perivascular cerebrospinal fluid (CSF) bulk flow system.^{13 – 17} This leads to greater $\mathrm{A}\beta$ deposition in the vessel wall and causes a self-reinforcing cycle, thereby exacerbating the development of cerebral amyloid angiopathy (CAA), a common feature of AD that has been reported to affect 80% to 90% of AD cases.^{9,13,14,18,19} Besides, under pathological conditions of mild cognitive impairment and AD, the balance between $\mathrm{A}\beta$ production and clearance is disrupted so the decline of the clearance system, rather than the $\mathrm{A}\beta$ overproduction, contributes to $\mathrm{A}\beta$ deposition.^20,21 Perivascular drainage is a major route of amyloid clearance from brain²² and a key contributor is the glymphatic system, which involves CSF entering the brain along paravascular spaces surrounding penetrating arteries and exchanging with interstitial fluid, which then exit the brain alongside veins.^{23 – 25} It has been reported that ventricular CSF clearance of $\mathrm{A}\beta$ is negatively related with the magnitude of brain $\mathrm{A}\beta$ deposition.²⁶ Consequently, efficient $\mathrm{A}\beta$ clearance via the glymphatic transport system is crucial for maintaining brain health and efficacious AD therapeutics; therefore, it is necessary to monitor the clearance dysfunction. Although ARIA occurs during anti-$\mathrm{A}\beta$ treatment, it does not correlate with the speed of $\mathrm{A}\beta$ elimination and might not have adequate sensitivity.²⁷ Pathological modification to the cerebral vascular architecture represents one of the earliest events in the AD pathological cascade and are evident earlier than the classical hallmark of the disease, $\mathrm{A}\beta$ deposition, and the onset of cognitive impairment.^{28 – 30} While the significance of vascular dysfunction is widely appreciated, its pathological changes caused by the $\mathrm{A}\beta$ clearance deficit through glymphatic transport are not clear. This raises the urgent need to characterize and quantitively evaluate vascular modifications after $\mathrm{A}\beta$ overload in CSF in preclinical settings. This may help us unravel the direct vascular consequences of $\mathrm{A}\beta$ clearance dysfunction and may also guide better treatment adjustments in patients receiving $\mathrm{A}\beta$-targeted immunotherapy.

Cerebral edema is a serious complication of ischemic cerebrovascular disease and mannitol is a commonly used dehydrating agent for relieving cerebral edema. However, the edema state and surrounding vascular perfusion level during mannitol treatment remains unclear, which affects the clinical application of the medicine. In this paper, we demonstrated the role of swept-source optical coherence tomography (OCT) in the evaluation of mannitol efficacy using mouse models. The OCT-based angiography and attenuation imaging technology were used to obtain the cerebral vascular perfusion level and cerebral edema state at different times. Vascular parameters and edema parameters were quantified and compared. Experimental results show that mannitol can significantly reduce the water content in the central region of edema, effectively inhibiting the rapid growth of the edema area, and restoring cerebral blood flow. On average, the edema area decreased by 33% after 2 h, and the vascular perfusion density increased by 12% after 5 h. This work helps to provide a valuable theoretical basis and research ideas for the clinical treatment of cerebral edema.

Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative condition that constitutes the predominant form of dementia, encompassing 60% to 80% of cases. AD manifests with an insidious onset; its evolution is nonreversible once initiated. The preclinical phase can span multiple decades;¹ consequently, many patients are already in the intermediate to advanced stages at the point of clinical diagnosis. Presently, there remains an absence of established therapeutic strategies.¹ The etiopathogenesis of AD is intricate, with multiple prevailing theories regarding its causative factors and fundamental mechanisms, yet a consensus remains elusive. In recent two decades, the amyloid-$\beta$ ($\mathrm{A}\beta$) toxicity paradigm has garnered widespread endorsement within the scientific realm. Intriguingly, a mere few years before identifying $\mathrm{A}\beta$ protein variants, certain researchers posited that cerebral microangiopathy and inflammatory processes might be intrinsic initiators of AD.^{2 – 5} Within the pathophysiological framework of AD, deep cerebral microvasculature assumes an incrementally critical function. The microvasculature not only orchestrates the provision of essential nutrients and oxygen to cerebral tissues but also oversees the evacuation of metabolic waste products. Anomalies in vascular structures, particularly in cerebral regions, are postulated to have a direct nexus with AD pathogenesis.⁶ In our previous study, we reported the direct effects of cerebrospinal fluid-$\mathrm{A}\beta$ on cerebrovascular morphology and brain tissue.⁷ Due to the technique limitation, microvasculature change of the deep cortex was not evaluated specifically.

Magnetomotive optical coherence tomography (MMOCT) is a promising imaging method for noninvasive three-dimensional tracking of magnetic nanoparticle (MNP) motions in target tissues or organs. The external B -field is the driving force that provides MMOCT contrast. However, B -field modulation also introduces modulation noise, thereby decreasing the quality of the MMOCT image. In this paper, a common-path–based device is designed for modulation noise reduction. The device is capable of adjusting interference distance, reference light intensity, and imaging position ( X − Y translation). The sensitivity of the MMOCT is increased by ∼ 20 times with the new device. Using the proposed device, the distribution of MNPs injected in zebrafish was imaged.