Microglia in the hypothalamic paraventricular nucleus sense hemodynamic disturbance and promote sympathetic excitation in hypertension.

Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.

Portable, handheld, and affordable blood perfusion imager for screening of subsurface cancer in resource-limited settings.

Precise information on localized variations in blood circulation holds the key for noninvasive diagnostics and therapeutic assessment of various forms of cancer. While thermal imaging by itself may provide significant insights on the combined implications of the relevant physiological parameters, viz. local blood perfusion and metabolic balance due to active tumors as well as the ambient conditions, knowledge of the tissue surface temperature alone may be somewhat inadequate in distinguishing between some ambiguous manifestations of precancer and cancerous lesions, resulting in compromise of the selectivity in detection. This, along with the lack of availability of a user-friendly and inexpensive portable device for thermal-image acquisition, blood perfusion mapping, and data integration acts as a deterrent against the emergence of an inexpensive, contact-free, and accurate in situ screening and diagnostic approach for cancer detection and management. Circumventing these constraints, here we report a portable noninvasive blood perfusion imager augmented with machine learning-based quantitative analytics for screening precancerous and cancerous traits in oral lesions, by probing the localized alterations in microcirculation. With a proven overall sensitivity >96.66% and specificity of 100% as compared to gold-standard biopsy-based tests, the method successfully classified oral cancer and precancer in a resource-limited clinical setting in a double-blinded patient trial and exhibited favorable predictive capabilities considering other complementary modes of medical image analysis as well. The method holds further potential to achieve contrast-free, accurate, and low-cost diagnosis of abnormal microvascular physiology and other clinically vulnerable conditions, when interpreted along with complementary clinically evidenced decision-making perspectives.

Intravoxel incoherent motion as a surrogate marker of perfused vascular density in rat brain.

Intravoxel incoherent motion (IVIM) MRI has emerged as a valuable technique for the assessment of tissue characteristics and perfusion. However, there is limited knowledge about the relationship between IVIM-derived measures and changes at the level of the vascular network. In this study, we investigated the potential use of IVIM MRI as a noninvasive tool for measuring changes in cerebral vascular density. Variations in quantitative immunohistochemical measurements of the vascular density across different regions in the rat brain (cortex, corpus callosum, hippocampus, thalamus, and hypothalamus) were related to the pseudo-diffusion coefficient D* and the flowing blood fraction f in healthy Wistar rats. We assessed whether region-wise differences in the vascular density are reflected by variations in the IVIM measurements and found a significant positive relationship with the pseudo-diffusion coefficient (p < 0.05, ß = 0.24). The effect of cerebrovascular alterations, such as blood-brain barrier (BBB) disruption on the perfusion-related IVIM parameters, is not well understood. Therefore, we investigated the effect of BBB disruption on the IVIM measures in a rat model of metabolic and vascular comorbidities (ZSF1 obese rat) and assessed whether this affects the relationship between the cerebral vascular density and the noninvasive IVIM measurements. We observed increased vascular permeability without detecting any differences in diffusivity, suggesting that BBB leakage is present before changes in the tissue integrity. We observed no significant difference in the relationship between cerebral vascular density and the IVIM measurements in our model of comorbidities compared with healthy normotensive rats.

Effects of 2 Hz flickering light on refractive state, fundus imaging and visual function of C57BL/6 mice.

In this study, we investigated the effects of flickering light on refractive development of mice and the changes of fundus structure and function during this process. C57BL/6 mice were randomly divided into control group and flickering light-induced myopia (FLM) group. Mice in the control group were fed under normal lighting. FLM group mice were fed under lighting with a duty cycle of 50% and flash frequency of 2 Hz. Refractive status, axial length (AL), corneal radius of curvature (CRC), and electroretinogram signals were measured in all animals before treatment and at 2 and 4 weeks after treatment. Retinal thickness (RT), choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). After 4 weeks of flickering light stimulation, the mice became myopia, the AL increased, but the CRC remained constant. The induction of myopia reduced the implicit time and amplitude of a-wave and b-wave in electroretinogram, which affects the function of retina. Full-layer retinal thickness, ChT and ChBP decreased at both 2 and 4 weeks after flickering light induction. The superficial and middle layers of the retina were significantly thinner, while the deep layer was only slightly thinner without statistical significance. Calculated by the concentric circle algorithm, the decrease of choroidal blood perfusion in FLM was mainly concentrated in the concentric circle area with the optic disc as the center radius of 150-450 µm. In conclusion, the present study shows that flickering light can successfully induce myopia in C57BL/6 mice, affect the electrophysiological activity of retina, and cause changes in fundus tissue structure and blood flow.

Retinal and choroidal structure and vascularity in Chinese emmetropic and myopic children.

PURPOSE: This study evaluated the structural features of the retinal and choroidal regions and their correlations with ocular biometric and vascular parameters in Chinese children using optical coherence tomography angiography (OCTA). METHODS: A total of 159 children, 6-13 years of age, were included in this prospective study. The sample consisted of 55 emmetropes (spherical equivalent ≤ +0.75 and > -0.50 D), 53 low-moderate myopes (≤ -0.50 to > -6.00 D) and 51 high myopes without pathological changes (≤ -6.00 D). Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Swept-source optical coherence tomography/OCTA was used to assess the macular structures and vascular characteristics in a 6 × 6 mm region centred on the macula. RESULTS: In a comprehensive analysis adjusting for age, sex, AL, macular blood perfusion, intraocular pressure and anterior segment parameters, retinal thickness (RT) showed a significant positive association with deep retinal vascular density and superficial retinal vascular density in the foveal area, but not with AL. Moreover, RT exhibited a significant negative association with AL in the parafoveal and perifoveal regions. Further, a significant positive correlation was observed between choroidal thickness and both choroidal vascular volume and choriocapillaris perfusion area, along with a negative correlation with AL across the entire macular region. CONCLUSIONS: This study showed that the thickness of retina and choroid in Chinese children was not only associated with AL but also showed dynamic properties such as the blood perfusion of the retina and choroid, particularly in the foveal area.

Dietary ω-3 polyunsaturated fatty acids are protective for myopia.

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

Polyurethane foam dressing with non-adherent membrane improves negative pressure wound therapy in pigs.

OBJECTIVE: Negative pressure wound therapy (NPWT) is considered to be an effective technique to promote the healing of various wounds. The aim of this study was to evaluate different wound dressings combined with NPWT in treating wounds in Wuzhishan pigs. METHOD: Excisions were made in the backs of the pigs and were covered with polyvinyl alcohol (PVA) dressing, polyurethane (PU) dressing or PU dressing with non-adherent membrane (PU-non-ad). NPWT was applied to the wound site. In the control group, basic occlusive dressing (gauze) without NPWT was applied. On days 0, 3, 7, 14, 21 and 28 post-surgery, the wound size was measured during dressing change, and wound healing rate (WHR) was calculated. In addition, blood perfusion within 2cm of the surrounding wound was measured by laser doppler flowmetry. Dressing specimen was collected and microbiology was analysed. Granulation tissues from the central part of the wounds were analysed for histology, vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) mRNA expression. RESULTS: The PU-non-ad-NPWT significantly (p<0.01) accelerated wound healing in the pigs. Further pathological analysis revealed that the non-adherent membrane effectively protected granulation tissue formation in PU-NPWT treated wounds. The blood perfusion analysis suggested that the non-adherent membrane improved the blood supply to the wound area. Microbiological analysis showed that non-adherent membrane decreased the bacterial load in the PU-NPWT dressing. VEGF and CD31 mRNA expression was upregulated in the wound tissue from the PU-non-ad-NPWT treated groups. CONCLUSION: In this study, the PU dressing with non-adherent membrane was an ideal dressing in NPWT-assisted wound healing.

Establishment of Early Blood Perfusion Promotes CXCL12 Expression and Recruits Monocytes/Macrophages in Damaged Adipose Tissue in Mice Model.

BACKGROUND: Blood perfusion in the recipient site is important for adipose tissue repair after fat grafting. It delivers host-derived macrophages derived from monocytes in bone marrow to initiate inflammatory reactions and regenerative responses. According to the ability of CXCL12, a stromal cell-derived factor, to recruit monocytes/macrophages, we studied its effect on adipose tissue repair and regeneration under ischemic and normal conditions. METHODS: Each inguinal fat pad was crushed for 30 seconds with a clamp in mice (n = 35). The left inguinal vessels were divided and cut off (ischemic group), while the right inguinal vessels were kept patent (control group). Seven animals were sacrificed at 1, 3, 7, 14, and 30 days after surgery, and macrophages (Mac2 and CD206) and adipocytes (perilipin) were assessed. Levels of inflammatory factors (interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α) and CXCL12 were measured by quantitative PCR. RESULTS: The number of macrophages was higher in the control group than in the ischemic group at day 3 (10.33 ± 2.40 vs. 1.33 ± 0.33, p = 0.021). The percentage of M2 macrophages was higher in the control group than in the ischemic group at day 7 (p<0.05). The levels of inflammatory factors and CXCL12 were higher in the control group than in the ischemic group at the early stage (p = 0.038). CONCLUSIONS: Established blood perfusion leads to up-regulation of CXCL12 during adipose tissue repair and regeneration, which may increase recruitment of monocytes to damaged adipose tissue. These findings increase understanding of the cellular events involved in fat graft survival after grafting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The effect of traction force on eyelid blood perfusion during closure of defects.

PURPOSE: In oculoplastic surgery the eyelid tissue is frequently stretched in order to repair defects after tumor surgery. However, there is a paucity of research regarding how stretching affects eyelids. The purpose of this study was to gain insight into how traction force affects eyelid stretch as well as tissue perfusion, using a laser-based in vivo monitoring technique. METHOD: Lower-lid pentagonal resections were performed in eight patients and a total of nine eyelids. The medial section of the eyelid was then stretched using a dynamometer up to a force of 2.3 Newtons (N), and eyelid stretching and blood perfusion were continuously measured using laser speckle contrast imaging. RESULTS: Tissue perfusion decreased exponentially when eyelid tissue was stretched, with an initial sharp decline followed by a more gradual reduction. Perfusion approached zero at a force of approximately 2.0 N. The length of the eyelid increased with increasing force up to 1.5 N, after which there was only a very slight increase in length. CONCLUSIONS: Eyelid tissue seems to respond to traction in a non-linear fashion, where the initial force results in the greatest eyelid stretching and reduction in blood perfusion. The results provide information on the effects of a large force for direct closure of large eyelid defects. Considering how quickly perfusion approaches zero, the high success rate of eyelid reconstruction surgery is likely a testament to the extensive vascularization of the periocular region.

Acute Effects of the Dry Needling Session on Gastrocnemius Muscle Biomechanical Properties, and Perfusion with Latent Trigger Points - A Single-Blind Randomized Controlled Trial in Mixed Martial Arts Athletes.

The study aimed to evaluate the immediate effects of a dry needling (DN) therapy session on biomechanical properties, muscle power, perfusion, and pressure pain threshold of the gastrocnemius muscle with latent trigger points. Twenty mixed martial arts athletes (MMA) were randomly divided into two groups: experimental (eDN, n = 10) and sham (qDN, n = 10) to undergo one session of DN either with a real or a qazi needle. The measurements were taken at rest, 1-5 minutes after the DN (Post1-5min) and 24h after the DN (Post24h). DN significantly increased the muscle perfusion (Post1-5min and Post24h, p < 0.001), reduced its tone (Post1-5min and Post24h, p < 0.001) and stiffness (Post1-5min, p < 0.05; Post24 h, p < 0.001), and improved its elasticity (Post1-5min and Post24h, p < 0.001). DN also caused a significant increase in pressure pain threshold (Post1-5min, p < 0.001; Post24h, p < 0.05) and in muscle power (Post24h, p < 0.01). The DN session increased the blood perfusion and improved the biomechanical properties of the gastrocnemius muscle, which led to improved muscle power. The DN also had an analgesic effect. These effects were maintained at 24 h, which suggests that DN could facilitate muscle recovery in a post-exercise period of MMA athletes.

Serum lipidomics-based study of electroacupuncture for skin wound repair in rats.

Lipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with six rats in each group. After the intervention, orbital venous blood was collected for lipid metabolomics analysis, wound perfusion was detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 11 differential metabolites in the model versus sham-operated group. There were 115 differential metabolites in the model versus electro-acupuncture group. 117 differential metabolites in the electro-acupuncture versus sham-operated group. There were two differential metabolites common to all three groups. Mainly cholesteryl esters and sphingolipids were elevated after electroacupuncture and triglycerides were largely decreased after electroacupuncture. The electroacupuncture group recovered faster than the model group in terms of blood perfusion and wound healing (p < 0.05). Electroacupuncture may promote rat skin wound repair by improving lipid metabolism and improving local perfusion.

Novel noninvasive identification of patient-specific epileptic networks in focal epilepsies: Linking single-photon emission computed tomography perfusion during seizures with resting-state magnetoencephalography dynamics.

Single-photon emission computed tomography (SPECT) during seizures and magnetoencephalography (MEG) during the interictal state are noninvasive modalities employed in the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy (DRFE). The present study aims to investigate whether there exists a preferentially high MEG functional connectivity (FC) among those regions of the brain that exhibit hyperperfusion or hypoperfusion during seizures. We studied MEG and SPECT data in 30 consecutive DRFE patients who had resective epilepsy surgery. We parcellated each ictal perfusion map into 200 regions of interest (ROIs) and generated ROI time series using source modeling of MEG data. FC between ROIs was quantified using coherence and phase-locking value. We defined a generalized linear model to relate the connectivity of each ROI, ictal perfusion z score, and distance between ROIs. We compared the coefficients relating perfusion z score to FC of each ROI and estimated the connectivity within and between resected and unresected ROIs. We found that perfusion z scores were strongly correlated with the FC of hyper-, and separately, hypoperfused ROIs across patients. High interictal connectivity was observed between hyperperfused brain regions inside and outside the resected area. High connectivity was also observed between regions of ictal hypoperfusion. Importantly, the ictally hypoperfused regions had a low interictal connectivity to regions that became hyperperfused during seizures. We conclude that brain regions exhibiting hyperperfusion during seizures highlight a preferentially connected interictal network, whereas regions of ictal hypoperfusion highlight a separate, discrete and interconnected, interictal network.

Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation†.

Maternal use of antidepressants has increased throughout the last decades; selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressants. Despite the widespread use of SSRI by women during reproductive age and pregnant women, an increasing amount of research warns of possible detrimental effects of maternal use of SSRI during pregnancy including low birthweight/small for gestational age and preterm birth. In this review, we revisited the impact of maternal use of SSRI during pregnancy, its impact on serotonin homeostasis in the maternal and fetal circulation and the placenta, and its impact on pregnancy outcomes-particularly intrauterine growth restriction and preterm birth. Maternal use of SSRI increases maternal and fetal serotonin. The increase in maternal circulating serotonin and serotonin signaling likely promotes vasoconstriction of the uterine and placental vascular beds decreasing blood perfusion to the uterus and consequently to the placenta and fetus with potential impact on placental function and fetal development. Several adverse pregnancy outcomes are similar between women, sheep, and rodents (decreased placental size, decreased birthweight, shorter gestation length/preterm birth, neonatal morbidity, and mortality) highlighting the importance of animal studies to assess the impacts of SSRI. Herein, we address the complex interactions between maternal SSRI use during gestation, circulating serotonin, and the regulation of blood perfusion to the uterus and fetoplacental unit, fetal growth, and pregnancy complications.

Choroidal blood perfusion could predict the sensitivity of myopia formation in Guinea pigs.

In this study, we explored the predictive role of choroidal blood perfusion (ChBP) and choroidal thickness (ChT) on the development of myopia in guinea pigs. Optical Coherence Tomography Angiography (OCTA) was used to assess the baseline choroidal blood perfusion (ChBP) and choroidal thickness (ChT) in 4-week-old guinea pigs. Refraction and axial length (AL) were measured at baseline. Myopia was induced for one week using form-deprivation (FD) or negative lenses followed by measurements of refraction, axial length and choroidal parameters (ChT and ChBP). The correlations were evaluated between the baseline choroidal values and the magnitude of myopia induced, along with the magnitude of changes in ChT and ChBP after myopia induction. There was a significant correlation between the baseline choroidal parameters and ocular refraction. Myopia induction led to choroidal thinning and less ChBP as well as longer eyes. On the other hand, following exposure to the same non-obstructed visual induction period, the myopic shift was less, and it was associated with thicker choroids and more ChBP at baseline. One week of myopia induction also resulted in thinner choroids and less ChBP, and these declines also correlated with their baseline values. In conclusion, the present study shows that the changes in the baseline choroidal ChT and ChBP parameters are proportional to the magnitude of myopia development and axial elongation in guinea pigs. These significant correlations between baseline ChBP and ChT and myopia development suggest that they may be a viable predictor of this process in guinea pigs.

Feasibility of the novel vascular disrupting agent C118P for facilitating high-intensity focused ultrasound ablation of uterine fibroids.

OBJECTIVE: In this study, C118P, a novel vascular disrupting agent (VDA), was evaluated for its ability in improving the ablative effect of high-intensity focused ultrasound (HIFU) on uterine fibroids by reducing blood perfusion. METHODS: Eighteen female rabbits were infused with isotonic sodium chloride solution (ISCS), C118P or oxytocin for 30 min, and an HIFU ablation of the leg muscles was performed within the last 2 min. Blood pressure, heart rate and laser speckle flow imaging (LSFI) of the auricular blood vessels were recorded during perfusion. Ears with vessels, uterus and muscle ablation sites were collected and sliced for hematoxylin-eosin (HE) staining to compare vascular size, as well as nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) staining to observe necrosis after ablation. RESULTS: Analyses revealed that the perfusion of C118P or oxytocin steadily reduced blood perfusion in the ears to approximately half by the end of the perfusion, constricted the blood vessels of the ears and uterus, and improved HIFU ablation in the muscle tissues. C118P increased blood pressure and decreased heart rate. The degree of contraction of the auricular and uterine blood vessels was positively correlated. CONCLUSION: This study confirmed that C118P could reduce blood perfusion in various tissues and had a better synergistic effect with HIFU ablation of muscle (the same tissue type as fibroids) than did oxytocin. C118P could therefore possibly replace oxytocin in facilitating HIFU ablation of uterine fibroids; however, electrocardiographic monitoring is required.

Microalgae share key features with human erythrocytes and can safely circulate through the vascular system in mice.

As animal cells cannot produce oxygen, erythrocytes are responsible for gas interchange, being able to capture and deliver oxygen upon tissue request. Interestingly, several other cells in nature produce oxygen by photosynthesis, raising the question of whether they could circulate within the vascular networks, acting as an alternative source for oxygen delivery. To address this long-term goal, here some physical and mechanical features of the photosynthetic microalga Chlamydomona reinhardtii were studied and compared with erythrocytes, revealing that both exhibit similar size and rheological properties. Moreover, key biocompatibility aspects of the microalgae were evaluated in vitro and in vivo, showing that C. reinhardtii can be co-cultured with endothelial cells, without affecting each other's morphology and viability. Moreover, short-term systemic perfusion of the microalgae showed a thoroughly intravascular distribution in mice. Finally, the systemic injection of high numbers of microalgae did not trigger deleterious responses in living mice. Altogether, this work provides key scientific insights to support the notion that photosynthetic oxygenation could be achieved by circulating microalgae, representing another important step towards human photosynthesis. KEY POINTS: • C. reinhardtii and endothelial cells are biocompatible in vitro. • C. reinhardtii distribute throughout the entire vasculature after mice perfusion. • C. reinhardtii do not trigger deleterious responses after injection in mice.

Real-time semi-quantitative assessment of anastomotic blood perfusion in mini­invasive rectal resections by Sidestream Dark Field (SDF) imaging technology: a prospective in vivo pilot study.

PURPOSE: Anastomotic leakage (AL) is one of the severe complications after rectal surgery, and anastomotic ischemia is one of the main factors. This prospective in vivo pilot study aimed to evaluate the effectiveness of Sidestream Dark Field (SDF) imaging in quantitative assessment of anastomotic microcirculation and to analyze its correlation with AL. METHODS: Thirty-three patients with rectal cancer who underwent laparoscopic low anterior resection from 2019 to 2020 were enrolled. Microcirculation was measured by SDF imaging at the descending colon, the mesocolon transection line (MTL), and 1 cm and 2 cm distal to the MTL. Anastomotic microcirculation was measured at the stapler anvil edge before anastomosis. Quantitative perfusion-related parameters were as follows: microcirculation flow index (MFI), perfused vessel density (PVD), proportion of perfused vessels (PPV), and total vessel density (TVD). RESULTS: All patients obtained stable microcirculation images. Functional microcirculation parameters (MFI, PPV, PVD) decreased successively from the descending colon, the colon at MTL, and 1 cm and 2 cm distal to the MTL (all P < 0.01). Extremely poor microcirculation was found at the intestinal segment 2 cm distal to the MTL. Micro-perfusion was significantly lower at the colonic limb of the anastomosis compared with the descending colon (all P < 0.001). Anastomotic leakage occurred in 3 patients (9.1%) whose anastomotic microcirculation was significantly lower than those without AL (all P < 0.01). Blood perfusion at the colonic limb of the anastomosis was significantly higher in patients with left colic artery preservation than in controls. CONCLUSION: SDF imaging is a promising technique for evaluating anastomotic microcirculation and has potential clinical significance for risk stratification of AL.

Effect of red-light therapy on retinal and choroidal blood perfusion in myopic children.

OBJECTIVE: To investigate the effect of repeated low-level red-light therapy (RLRLT) on retinal and choroidal blood perfusion in myopic children. METHODS: Forty-seven myopic children (mean spherical equivalent refractive error [SE]: -2.31 ± 1.26 D; age range: 8.0-11.0 years) were enrolled and received RLRLT (power 2 mW, wavelength 650 nm) for 3 min twice a day, while 20 myopic children (SE: -2.75 ± 0.84 D; age range: 7.0-10.0 years) were included as a control group. All participants wore single-vision distance glasses. Refractive error, axial length (AL) and other biometric parameters were measured at baseline and during follow-up visits in the first, second and fourth weeks after initiation of treatment. Retinal thickness, subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI) were obtained using optical coherence tomography (OCT). The percentage retinal vascular density (VD%) and choriocapillaris flow voids (FV%) were measured using en-face OCT angiography. RESULTS: After 4 weeks of treatment, a significant increase in SFCT was observed in the RLRLT group, with an average increase of 14.5 µm (95% confidence interval [CI]: 9.6-19.5 µm), compared with a decrease of -1.7 µm (95% CI: -9.1 to 5.7 µm) in the control group (p < 0.0001). However, no significant changes in retinal thickness or VD% were observed in either group (all p > 0.05). In the OCT images from the RLRLT group, no abnormal retinal morphology related to photodamage was observed. The horizontal scans revealed an increase in TCA, LA and CVI over time (all p < 0.05), while SA and FV% remained unchanged (both p > 0.05). CONCLUSIONS: These findings indicate that RLRLT can enhance choroidal blood perfusion in myopic children, demonstrating a cumulative effect over time.

Brain perfusion, cognition, and plasma Alzheimer's biomarkers in moyamoya disease.

INTRODUCTION: Because growing interest has been focusing on cerebral blood flow (CBF) to predict, prevent, and treat Alzheimer's disease (AD), it is important to clarify the role of CBF in AD pathology and cognitive decline. METHODS: In a moyamoya disease (MMD) cohort, we examined CBF, specific cognitive domains, and plasma AD biomarkers, as well as correlations among these variables. RESULTS: CBF was significantly reduced in newly diagnosed MMD patients, while plasma phosphorylated tau181 was elevated and positively correlated with hypoperfusion accumulation. MMD patients scored significantly lower than controls in multiple cognitive tests. Revascularization increased CBF to the recipient brain territories as well as cognitive performance but produced no significant change in AD biomarker levels. DISCUSSION: These data suggest a link between accumulated reductions in CBF and cognitive decline, as well as a possible role of AD-like pathological burden. Further studies in MMD will provide opportunities to explore new treatment strategies.

Assessment of chronic limb threatening ischemia using thermal imaging.

OBJECTIVES: Current chronic limb threatening ischemia (CLTI) diagnostics require expensive equipment, using ionizing radiation or contrast agents, or summative surrogate methods lacking in spatial information. Our aim is to develop and improve contactless, non-ionizing and cost-effective diagnostic methods for CLTI assessment with high spatial accuracy by utilizing dynamic thermal imaging and the angiosome concept. APPROACH: Dynamic thermal imaging test protocol was suggested and implemented with a number of computational parameters. Pilot data was measured from 3 healthy young subjects, 4 peripheral artery disease (PAD) patients and 4 CLTI patients. The protocol consists of clinical reference measurements, including ankle- and toe-brachial indices (ABI, TBI), and a modified patient bed for hydrostatic and thermal modulation tests. The data was analyzed using bivariate correlation. RESULTS: The thermal recovery time constant was on average higher for the PAD (88%) and CLTI (83%) groups with respect to the healthy young subjects. The contralateral symmetry was high for the healthy young group and low for the CLTI group. The recovery time constants showed high negative correlation to TBI (ρ = -0.73) and ABI (ρ = -0.60). The relation of these clinical parameters to the hydrostatic response and absolute temperatures (|ρ|<0.3) remained unclear. CONCLUSION: The lack of correlation for absolute temperatures or their contralateral differences with the clinical status, ABI and TBI disputes their use in CLTI diagnostics. Thermal modulation tests tend to augment the signs of thermoregulation deficiencies and accordingly high correlations were found with all reference metrics. The method is promising for establishing the connection between impaired perfusion and thermography. The hydrostatic modulation test requires more research with stricter test conditions.