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.

Changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus: Assessed by optical coherence tomography angiography.

OBJECTIVE: The aim was to investigate the changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus (SLE) using optical coherence tomography angiography (OCTA). METHODS: Twenty-nine patients with SLE (29 eyes) and 25 control subjects (25 eyes) were enrolled. SLE activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Retinal thickness (RT), inner retinal thickness (IRT), outer retinal thickness (ORT), choroidal thickness (ChT), retinal superficial vascular density (SVD), retinal deep vascular density (DVD), choriocapillary vascular density (CCVD), foveal avascular zone (FAZ), superficial FAZ (sFAZ), and deep FAZ (dFAZ) were measured using OCTA. The retinal and choroidal thickness and vascular density between the control group and SLE group were compared. The relationships between SLEDAI scores and the retinal and choroidal thickness and vascular density in SLE group were analyzed. RESULTS: The SVD was significantly increased, and the DVD and CCVD were significantly decreased in the SLE group compared to the control group (p < .05). The results of receiver operating characteristic (ROC) showed that the area under the curve (AUC) values of SVD, DVD, and CCVD were 0.873, 0.729, and 0.727, indicating a high accuracy in discriminating patients with SLE from controls. Correlation analysis showed that the SLEDAI scores were positively correlated with dFAZ (r = 0.589, p = .001) and FAZ (r = 0.451, p = .018), and negatively correlated with DVD (r = -0.491, p = .009) and CCVD (r = -0.521, p = .005). CONCLUSIONS: DVD and CCVD were decreased in the SLE and might be related to the disease activity. SVD, DVD, and CCVD may hold promise in the discovery of biomarkers for diagnosing SLE.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

AIM: The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. METHODS: In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. RESULTS: MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. CONCLUSIONS: Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

Decreased retinal vascular density is associated with cognitive impairment in CADASIL: an optical coherence tomography angiography study.

PURPOSE: This study aimed to assess alterations in retinal vascular density in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients using optical coherence tomography angiography (OCTA) and investigate their association with MRI and cognitive features. METHODS: Twenty-five patients with CADASIL and forty healthy controls were evaluated by Cirrus HD-OCT 5000 with AngioPlex OCTA to determine changes in macular retinal vasculature. Retinal vasculature parameters between two groups were compared. The MRI lesion burden and neuropsychological scales were also examined in patients. The association between OCTA parameters and MRI/cognitive features was evaluated using partial Spearman rank correlation. RESULTS: The vessel density and perfusion density of whole image in macular region (vessel density: t = - 2.834, p = 0.005; perfusion density: t = - 2.691, p = 0.007) were significantly decreased in patients with CADASIL. Moreover, vessel density of whole image in macular region was negatively associated with Fazekas scores (ρ = - 0.457; p = 0.025) and the number of lacunar infractions (ρ = - 0.425, p = 0.038) after adjustment for age. Decreased macular vessel density and perfusion density of whole image were also associated with MoCA scores (vessel density: ρ = 0.542, p = 0.006; perfusion density: ρ = 0.478, p = 0.018) and other domain-specific neuropsychological tests (p < 0.05) after adjustment for age. CONCLUSION: Decreased retinal vascular density was associated with increased MRI lesion burden and cognitive impairment in patients with CADASIL. Our findings suggest that the degree of retinal vascular involvement, as demonstrated by OCTA, may be consistent with the severity of MRI lesions and the degree of cognitive impairment in patients.

Chorioretinal biomarkers in hypothalamic amenorrhea.

PURPOSE: The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea. METHODS: Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients' group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol. RESULTS: SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes (p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH. CONCLUSION: When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular "compaction" could be a first phase of hypoestrogenism adaptation.

Anatomical changes in idiopathic epiretinal membrane at 2-year follow-up assessed using spectral domain optical coherence tomography and optical coherence tomographic angiography.

PURPOSE: To evaluate anatomical changes in the low-stage partial attachment-type idiopathic epiretinal membrane (iERM) over 2 years. METHODS: Data from patients with low-stage partial attachment-type iERM (stage 2) were analyzed. The main outcome measures were anatomical changes, including changes in the foveal avascular zone (FAZ) area, vessel density (VD) in the vascular plexus, and thickness of retinal sublayers during the follow-up period. RESULTS: Thirty patients (mean age: 68±12 years) were included in the study. The FAZ area on the superficial vascular plexus (SVP) significantly decreased from baseline (0.12±0.08 mm2) to month 24 (0.10±0.08 mm2, p=0.024). However, the FAZ area on the deep vascular plexus (DVP) did not significantly decrease from baseline (0.15±0.13 mm2) to month 24 (0.14±0.14 mm2, p=0.099). VDs on both the SVP and DVP did not show significant change from baseline (29.51±8.14% vs. 28.35±5.63%) to month 24 (29.79±9.77%, p=0.564 vs. 28.17±5.75%, p=0.417). Parafoveal ganglion cell and inner plexiform layer (GCIPL) thickness decreased from baseline (108.77±13.61 µm) to month 24 (103.03±15.54 µm, p=0.004). The central total retinal layer thickness did not significantly change from baseline (396.07±64.86 µm) to month 24 (392.04±72.72 µm, p=0.570). CONCLUSION: Even in low-stage ERM, inner retinal changes, including GCIPL thickness, occurred during follow-up periods, which might be owing to degenerative changes or centrifugal movement.

Optical coherence tomography angiography evaluation of retinal and choroidal microvascular changes in pregnant women with a history of unexplained recurrent spontaneous abortions.

PURPOSE: To study retinal and choroidal microcirculation by optical coherence tomography angiography (OCTA) in pregnant women with unexplained recurrent spontaneous abortion (RSA) and to compare them with healthy pregnant and nonpregnant subjects. METHODS: Pregnant women with an unexplained history of RSA (group 1), healthy pregnant (group 2), and healthy non-pregnant women (group 3) were included in the study. After a thorough ophthalmologic examination:best-corrected visual acuity, intraocular pressure,slit-lamp biomicroscopy, fundus examination,autorefractometer, biometry, and axial length measurement; OCT and OCTA measurements were performed with Swept Source OCT-Angiography (Topcon Co, Japan). RESULTS: The nonpregnant group had higher values for central foveal superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD) and lower values for superior, inferior, and mean VD compared with pregnant groups (p < 0.001). Choriocapillaris values (CC) VD were higher in groups 1 and 2 than in group 3 (p < 0.001). The group with unexplained RSA had a relatively smaller FAZ (foveal avascular zone) area than the group of healthy pregnant women (p:0.047). There were no statistically significant differences between groups in the retina, retinal nerve fiber layer, ganglion cell layer, and choroidal thickness (p > 0.05). CONCLUSION: Although our study did not identify any etiology in pregnant women with RSA, we observed detectable differences in FAZ area and vessel density values using OCTA, when comparing them with healthy pregnant women and healthy nonpregnant controls. We believe that OCTA, as used in many pathologies such as diabetic and hypertensive retinopathy and retinal vascular occlusion, can also be extended to unexplained RSA both to detect etiology and to monitor treatment in studies with a larger number of patients.

Investigation of Gastrointestinal Toxicities Associated with Concurrent Abdominal Radiation Therapy and the Tyrosine Kinase Inhibitor Sunitinib in a Mouse Model.

Tyrosine kinase inhibitors (TKIs) may be combined with radiation therapy (RT) to enhance tumor control; however, increased incidences of gastrointestinal (GI) toxicity have been reported with this combination. We hypothesize that toxicity is due to compromised intestinal healing caused by inhibition of vascular repair and proliferation pathways. This study explores underlying tissue toxicity associated with abdominal RT and concurrent sunitinib in a mouse model. Four groups of CD-1 mice were treated with 12 Gy abdominal RT, oral sunitinib, abdominal RT + sunitinib, or sham treatment. Mice received oral sunitinib or the vehicle via gavage for 14 days. On day 7, mice were irradiated with 12 Gy abdominal RT or sham treated. Mice were euthanized on day 14 and intestinal tract was harvested for semiquantitative histopathologic evaluation and immunohistochemical quantification of proliferation (Ki67) and vascular density (CD31). Non-irradiated groups had stable weights while abdominal irradiation resulted in weight loss, with mice receiving RT + SUN having greater weight loss than mice receiving RT alone. Semiquantitative analysis showed significant increases in inflammation in irradiated groups. The difference in the density of CD31+ cells was significantly increased in RT alone compared to SUN alone. Ki67+ density was not significant. In summary, we identify a lack of angiogenic response in irradiated GI tissues when abdominal RT is combined with a TKI, which may correlate with clinical toxicities seen in canine and human patients receiving combined treatment.

Analysis of Macular Vascularization Using Optical Coherence Tomography Angiography in Patients with Obstructive Sleep Apnea Syndrome: A Prospective Clinical Study.

Background and Objectives: Given the conflicting data available in the literature, this study aimed to investigate the impact of obstructive sleep apnea syndrome (OSAS) on the macular vascular density (VD) and perfusion density (PD). Materials and Methods: Based on the obstructive apnea-hypopnea index (OAHI), 61 prospectively recruited patients were assigned to either a control group (n = 12; OAHI < 5/h) or an OSAS group (n = 49; OAHI ≥ 5/h). The macular VD and PD of the superficial and deep capillary plexuses (SCP and DCP, respectively) were measured in the parafoveolar and perifoveolar areas using Zeiss PLEX Elite 9000 (6 × 6 mm). The values were compared between the control and OSAS groups. Results: Compared with the control group, the OSAS group demonstrated an increased VD of the DCP in the parafoveolar and perifoveolar areas and PD of the DCP in the perifoveolar area. No significant differences in either the macular VD or PD of the SCP were observed. There was no correlation between the OAHI and macular VD or PD. Conclusions: This study indicates that collateral vessel formation and possible retinal vasodilation occur in the DCP of patients with OSAS.

Changes in retinal vascular density measured by optical coherence tomography angiography in patients with carotid artery stenosis after carotid artery stenting and angioplasty.

PURPOSE: The aim of this study was to compare the effect of carotid artery stenting and angioplasty (CASA) on retinal vascular density (VD) in patients with severe carotid stenosis with a healthy control group and to evaluate using optical coherence tomography angiography (OCTA). METHODS: For this prospective study, eyes on the operated side constituted the ipsilateral eye group, and the other eye constituted the contralateral eye group. 40 eyes of 40 patients with ipsilateral eye of carotisid artery stenosis (CAS), 34 eyes on contralateral side, and 30 healthy eyes (control group) were included in this study. We performed quantitative OCTA analyses of retinal VD changes, before and after CASA. The main outcome measures were the quantitative changes of VD of superficial capillary plexus (SCP) and deep capillary plexus (DCP). RESULTS: We evaluated the VD of ipsilateral eyes and contralateral eyes separately before and after the procedure. All patients did not have visual symptoms. There was no significant difference in the VD of SCP in all groups before the procedure. No significant change was observed in all groups when the VD of the SCP was compared before and after the procedure. The VD of the DCP in the ipsilateral and contralateral group improved significantly after CASA. CONCLUSION: OCTA could noninvasively detect retinal VD improvements after CASA in CAS patients. Quantitative changes in VD evaluated using OCTA are thought to be early indicators in the diagnosis of CAS and in the follow-up of treatment success.

Comparison of macular and optic disc vessel density in thyroid orbitopathy: a comparative octa study.

PURPOSE: To determine the microvascular and structural changes in the peripapillary and macular areas observed in patients with active thyroid orbitopathy(TO) before and after steroid treatment and compare with inactive TO and the control group by optical coherence tomography angiography (OCTA). MATERIAL AND METHOD: This cross-sectional study included 34 eyes of 17 active TO patients, 108 eyes of 54 inactive TO patients, and 60 eyes of 30 healthy controls. Central macular thickness (CMT), ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, central choroidal thickness (CCT), retinal nerve fiber layer (RNFL) thickness, choroidal thickness in the peripapillary region, superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris vessel densities were determined by OCTA in before and after 12-week steroid treatment of active TO cases, inactive TO and control groups. RESULTS: Between the three groups in macula OCTA, a statistically significant difference was observed in the inferior and nasal quadrants in SCP (all p = 0.01) and only in the temporal quadrant choriocapillaris (p = 0.005). In peripapillary OCTA, a statistically significant difference was found only in the central choriocapillaris (p = 0.03). In the comparison of the active group before and after treatment, there was a statistically significant decrease in CMT and CCT; a statistically significant increase was observed in GCL-IPL (all p < 0.01). There was a statistically significant decrease in SCP and DCP only in the central (all p < 0.01). There was a statistically significant increase was found in the lower quadrant macular SCP vessel density and mean macular DCP in post-treatment measurements (p = 0.01 and p = 0.03, respectively). Peripapillary SCP and DCP vessel density was increased after treatment (p < 0.01). CONCLUSION: Active TO group had lower vessel density than inactive group and after treatment, vessel density was increased. Non-invasive quantitative analysis of retinal and optic disc perfusion using OCTA could be useful in early treatment before complications occur and monitoring patients with TO.

Vascular changes of the peripapillary choroidal area in the thyroid orbitopathy.

PURPOSE: The aim of this study was to investigate the peripapillary choroidal vascular changes in thyroid orbitopathy (TO). METHODS: The study included 20 eyes of 10 patients with active TO (aTO), 30 eyes of 15 patients with inactive TO (inaTO) and 30 eyes of 30 healthy subjects. The peripapillary choroidal vascular change was assessed with peripapillary choroidal vascular index (pCVI), peripapillary choroidal luminal area (pLA), peripapillary choroidal stromal area (pSA), peripapillary total choroidal area (pTCA). RESULTS: Compared to the control group, there was a reduction in the nasal and temporal areas of pCVI in both the aTO and inaTO groups (aTO vs control: nasal p = 0.001 and temporal p = 0.004; inaTO vs control: nasal p = 0.007 and temporal p < 0.001), while the inferior area was lower only in the inaTO group (p = 0.001). Compared to the other groups, the inaTO group exhibited a decrease pSA (vs aTO: total p = 0.004, inferior p = 0.02 and vs control: total p = 0.01, inferior p = 0.03), pLA (vs aTO: total p = 0.02, inferior p = 0.02, temporal p < 0.001 and vs control: total p = 0.002, inferior p < 0.001, temporal p < 0.001) and pTCA (vs aTO: total p = 0.009, inferior p = 0.01, temporal p < 0.001 and vs control: total p = 0.003, inferior p = 0.001, temporal p < 0.001). CONCLUSION: The horizontal area (nasal and temporal area) of the peripapillary choroidal vascular structure may be more sensitive than the vertical area in TO patients. The first affected quadrant of RPC-VD in the active TO may be the inferior quadrant. Structural or vascular choroidal changes may occur during the chronic or post-active phase of the disease.

Longitudinal evaluation of macular vascular density alterations in unilateral amblyopic children undergoing therapy: An optical coherence tomographic angiography study.

Importance: Understanding the pathophysiology of the macula in amblyopic eyes is an active research area. Objective: To correlate macular retinal vascular density changes with best-corrected visual acuity changes following occlusion therapy for amblyopia in children. Design: A prospective cohort study of children visiting the Pediatric Ophthalmology Division of our institution between January 2020 and January 2022 was conducted. Setting: A specialist eye hospital in Saudi Arabia. Participants: Thirty children with unilateral amblyopia. Exposure: Occlusion therapy for amblyopia.Main Outcome and Measures: Best corrected visual acuity (logMAR) before and at each of the four optical coherence tomographic angiographies was compared in amblyopic and fellow eyes. The effect of pretreatment determinants on the correlation between best-corrected visual acuity and retinal vascular density changes was reviewed. Results: In this cohort of 30 amblyopic and 30 fellow eyes from 30 children (mean age 8.7 ± 1.4 years; male: female 18:12. The best-corrected visual acuity improved from a median of 0.6 (interquartile range 0.5; 1.1) pretreatment to a median of 0.4 (interquartile range 0.2; 0.6) posttreatment in amblyopic eyes, and from a median of 0.1 to 0.05 in the fellow eyes. The total percentage change in retinal vascular density in the amblyopic eye was significantly higher than that in the fellow eye (Z = -1.92, P = 0.05). The change in best-corrected visual acuity in the amblyopic eye after a median of 98 months (interquartile range, 69-126 months) of intervention was significantly correlated with the refraction-adjusted change in retinal vascular density (B = -0.03, 95 % confidence interval -0.04, -0.02, P < 0.001) and was influenced by strabismus (B = -0.46, 95 % confidence interval -0.59, -0.34, P < 0.001), type of amblyopia (B = 0.24, 95 % confidence interval 0.12, 0.36, P < 0.001), duration of occlusion (B = -0.43, 95 % confidence interval -0.65, -0.22, P < 0.001), and occlusion compliance (B = 0.24, 95 % confidence interval 0.11, 0.36, P < 0.001). Conclusions: and Relevance: The RVD in amblyopic eyes in the first six months of therapy was significantly lower than that in fellow eyes, but not in subsequent assessments.

Liraglutide improves adipose tissue remodeling and mitochondrial dynamics in a visceral obesity model induced by a high-fat diet.

Central obesity is characterized by visceral adipose tissue (VAT) expansion, considered one of the main risk factors for metabolic complications. In recent years, new drugs have been studied for obesity treatment. Liraglutide (LGT), a GLP-1 agonist, decreases body weight, however, several mechanisms of action on VAT are still unknown. Aim: to study the effect of LGT on factors associated with VAT remodeling and mitochondrial dynamics in mice fed a high-fat diet (HFD). Methods: C57BL/6 mice were divided into Control (C) and HFD. After 15 weeks of feeding, each group was subdivided according to LGT administration for 5 weeks: C, C + LGT, HFD, and HFD + LGT. In epididymal AT (EAT) we evaluated histological and mitochondrial characteristics, vascularity, gelatinase activity (MMPs), and galectin-3 expression. Results: HFD presented larger adipocytes (p < 0.05), and lower vascular density and MMP-9 activity (p < 0.01) than C, while a major number of smaller adipocytes (p < 0.05) and an increase in vascularity (p < 0.001) and MMP-9 activity (p < 0.01) was observed in HFD + LGT. Collagen content was higher (p < 0.05) in EAT from HFD and decreased in HFD + LGT. In C, C + LGT, and HFD + LGT, mitochondria were predominantly tubular-shaped while in HFD mitochondria were mostly spherical (p < 0.001). Conclusion: LGT positively influences VAT behavior by modulating gelatinase activity, enhancing vascularization, and improving adipocyte histological characteristics. Additionally, LGT improves mitochondrial dynamics, a process that would favor VAT functionality.

Novel intravital approaches to quantify deep vascular structure and perfusion in the aging mouse brain using ultrasound localization microscopy (ULM).

Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Traditional imaging methods face difficulties with the thicker skull of older brains, making high-resolution imaging and cerebral blood flow (CBF) assessment challenging. However, functional ultrasound (fUS) imaging, an emerging non-invasive technique, provides real-time CBF insights with notable spatial-temporal resolution. This study introduces an enhanced longitudinal fUS method for aging brains. Using elderly (24-month C57BL/6) mice, we detail replacing the skull with a polymethylpentene window for consistent fUS imaging over extended periods. Ultrasound localization mapping (ULM), involving the injection of a microbubble (<<10 µm) suspension allows for recording of high-resolution microvascular vessels and flows. ULM relies on the localization and tracking of single circulating microbubbles in the blood flow. A FIJI-based analysis interprets these high-quality ULM visuals. Testing on older mouse brains, our method successfully unveils intricate vascular specifics even in-depth, showcasing its utility for longitudinal studies that require ongoing evaluations of CBF and vascular aspects in aging-focused research.

Retinal Microvasculature Causally Affects the Brain Cortical Structure: A Mendelian Randomization Study.

Purpose: To reveal the causality between retinal vascular density (VD), fractal dimension (FD), and brain cortex structure using Mendelian randomization (MR). Design: Cross-sectional study. Participants: Genome-wide association studies of VD and FD involving 54 813 participants from the United Kingdom Biobank were used. The brain cortical features, including the cortical thickness (TH) and surface area (SA), were extracted from 51 665 patients across 60 cohorts. Surface area and TH were measured globally and in 34 functional regions using magnetic resonance imaging. Methods: Bidirectional univariable MR (UVMR) was used to detect the causality between FD, VD, and brain cortex structure. Multivariable MR (MVMR) was used to adjust for confounding factors, including body mass index and blood pressure. Main Outcome Measures: The global and regional measurements of brain cortical SA and TH. Results: At the global level, higher VD is related to decreased TH (ß = -0.0140 mm, 95% confidence interval: -0.0269 mm to -0.0011 mm, P = 0.0339). At the functional level, retinal FD is related to the TH of banks of the superior temporal sulcus and transverse temporal region without global weighted, as well as the SA of the posterior cingulate after adjustment. Vascular density is correlated with the SA of subregions of the frontal lobe and temporal lobe, in addition to the TH of the inferior temporal, entorhinal, and pars opercularis regions in both UVMR and MVMR. Bidirectional MR studies showed a causation between the SA of the parahippocampal and cauda middle frontal gyrus and retinal VD. No pleiotropy was detected. Conclusions: Fractal dimension and VD causally influence the cortical structure and vice versa, indicating that the retinal microvasculature may serve as a biomarker for cortex structural changes. Our study provides insights into utilizing noninvasive fundus images to predict cortical structural deteriorations and neuropsychiatric disorders. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Does Placental Efficiency and Vascularization Affect Puppy Health? A Study in Boxer and Dobermann Dogs.

BACKGROUND: The anatomical and functional characteristics of the placenta influence the adaptive ability of the fetus to the extrauterine environment. Placental efficiency, measured as the gram of neonate produced by each gram of placenta, summarizes these characteristics. In the present study, placental efficiency and its impact on the 7-day postpartum life of the puppies were studied in canine large breeds. METHODS: Placental efficiency (PE) was computed using chorioallantois weight (WPE) and surface (SPE) efficiency for puppies born from natural delivery or elective cesarean section. Capillary density was also histologically determined. Neonate viability was estimated by the APGAR score and the daily weight gain (DWG) was recorded on day 7 after delivery. RESULTS: from 15 large-breed bitches, 69 live puppies were born by natural delivery (24 puppies) and elective cesarean section (45 puppies). Cluster analysis detected a group of neonates for which reduced placental efficiency (8 for the WPE, 9 for the SPE) was identified, despite a placental weight and surface within the mean and no difference in capillary density. In this group, the DWG was lower and the mortality within 7 days was higher. CONCLUSIONS: the results suggest that placental efficiency could be an additional tool for the evaluation of a puppy in the first 7 days after delivery.

Comparison of choroidal thickness, superficial and deep retinal vascular indices, and foveal avascular zones: Martial arts athletes vs healthy non-athletes.

AIM: The study aims to compare choroidal thickness, deep and superficial retinal capillary plexuses, and foveal avascular zone (FAZ) parameters in elite martial arts athletes and a healthy sedentary control group. METHODS: The study included martial arts athletes (32 individuals, 64 eyes) and healthy sedentary persons (43 individuals with healthy sedentary lifestyles, 86 eyes) aged 18-35 years. In this single non-repeated observational and cross-sectional study, choroidal thickness, superficial and deep retinal capillary plexuses, and FAZ measurements were measured using Swept-source optical coherence tomography angiography (SS-OCTA) and compared between groups. RESULTS: No statistically significant differences were found (p > 0.05) in age, IOP, AL (axial length), and best-corrected visual acuity (BCVA) parameters between groups. There were no statistically significant differences between the groups in choroidal thickness, superficial and deep retinal capillary plexuses, and FAZ parameters determined by the OCTA method (p > 0.05). CONCLUSION: In our study, we observed that the retinal and choroidal structures of martial art athletes and healthy sedentary individuals were similar. This observation implies that the putative microvascular effects on the choroid and retina in martial arts, especially those based on the anaerobic energy system, may reflect similar outcomes to those observed in individuals with sedentary lifestyles characterized by healthiness.

Retinal capillary plexus in Parkinson's disease using optical coherence tomography angiography.

AIM: To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson's disease (PD) using optical coherence tomography angiography (OCT-A). METHODS: A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens, "Georgios Gennimatas" from March 2021 to March 2022 was conducted. Totally 44 patients with PD were included and 18 healthy controls were examined, hence a total of 124 eyes were enrolled in the study. The foveal and parafoveal superficial and deep capillary plexus vascular density (fSCP-VD, fDCP-VD, pSCP-VD, pDCP-CD) and foveal avascular zone (FAZ) were quantified with OCTA. Optical coherence tomography (OCT) was used to measure macular thickness. Our statistical analysis was conducted by using a mixed effect linear regression model. RESULTS: After adjustment for age and gender, the mean parafoveal superficial capillary plexus vascular density (pSCP-VD) and mean parafoveal deep capillary plexus vascular density (pDCP-VD) were significantly decreased in individuals with PD (P<0.001 in both) by -2.35 (95%CI -3.3, -1.45) and -7.5 (95%CI -10.4, -4.6) respectively. fSCP-VD and fDCP-VD didn't approach statistical significance. The FAZ area and perimeter were significantly decreased (P<0.001 in both) by -0.1 mm2 (95%CI -0.13, -0.07) and -0.49 mm2 (95%CI -0.66, -0.32) respectively. Circularity didn't approach statistical significance. Central retinal thickness (CRT) was significantly decreased in individuals with PD (P<0.001) by -23.1 µm (95%CI -30.2, -16) and temporal retinal thickness (TRT) was decreased (P=0.025) by -11 µm (95%CI -22, -1.5) while nasal retinal thickness (NRT) only approached statistical significance (P=0.066). CONCLUSION: The mean pSCP-VD, pDCP-VD, CRT and TRT are significantly decreased and FAZ is altered in individuals with PD. These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Eye signs as a novel risk predictor in pulmonary arterial hypertension associated with systemic lupus erythematosus.

OBJECTIVE: To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). METHODS: This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1-3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded. RESULTS: A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC (r = -0.413, p = 0.026) and NT-proBNP (r = -0.472, p = 0.010), as well as a positive correlation with the 6MWD (r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r = -0.408, p = 0.028) and NT-proBNP (r = -0.472, p = 0.010) and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95-52.36), MFI (OR 7.85, 95% CI 1.73-35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP. CONCLUSION: SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.