Quantitative analysis of retinal vasculature in normal eyes using ultra-widefield fluorescein angiography

AIM: To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography (UWFA). METHODS: In a retrospective study, UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients. Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader. The length from the center of the optic disc to the edge of retinal vascularity (RVL) in each quadrant and the total retinal vascular perfusion area (RVPA) were determined by the grader using OptosAdvance software. The density of retinal vascularity (RVD) was quantified in different zones of central-steered images using Image J software. RESULTS: Among 42 healthy eyes, the values for mean RVL in each quadrant were 19.007±0.781 mm (superior), 18.467±0.869 mm (inferior), 17.738±0.622 mm (nasal) and 24.241±1.336 mm (temporal). The mean RVPA was 1140.117±73.825 mm2. The mean RVD of the total retina was 4.850%±0.638%. RVD varied significantly between different retina zones (P<0.001), and significant differences existed in the RVD values for total retinal area in patients over 50 years old compared to those under 50 years old (P=0.033). No gender difference was found. CONCLUSION: The UWFA device can be a promising tool for analyzing the overall retinal vasculature and may provide a better understanding of retinal vascular morphology in normal eyes. Aging may be related to lower RVD.

Npr2 mutant mice show vasodilation and undeveloped adipocytes in mesentery

Objective The biological importance for the signaling of C-type natriuretic peptide (CNP) and natriuretic peptide receptor B (NPR-B) has been recognized. However, the details remain unclear and are debatable. The Npr2 is a gene of NPR-B, and we previously reported a unique phenotype of a spontaneous mutant mouse lacking Npr2 (Npr2slw/slw), such as severe ileus-like disorder with bloodless blood vessels. In this study, we analyzed the bloodless mesenteric vascular morphology of Npr2slw/slw by histological observation to clarify the effects of the CNP/NPR-B signal deficiency. Results Blood vessels in the mesentery were clearly dilated in the preweaning Npr2slw/slw mice. Additionally, in the Npr2slw/slw mice, the lacteals were partially dilation or randomly direction mucosal epithelial cells in villi, and mesenteric adipocytes were undeveloped. These findings provide important information for understanding the role of CNP/NPR-B signals on intestine with mesentery.

ITVT-10. Using functional Ultrasound (fUS) for real-time, depth-resolved functional and vascular delineation of brain tumors with micrometer-millisecond precision

BACKGROUND Neurosurgical practice still relies heavily on pre-operatively acquired images to guide tumor resections, a practice which comes with inherent pitfalls such as registration inaccuracy due to brain shift, and lack of real-time functional or morphological feedback. Here we describe functional Ultrasound (fUS) as a new high-resolution, depth-resolved, MRI/CT-registered imaging technique able to detect functional regions and vascular morphology during awake and anesthesized tumor resections. MATERIALS AND METHODS fUS relies on high-frame-rate (HFR) ultrasound, making the technique sensitive to very small motions caused by vascular dynamics (µDoppler) and allowing measurements of changes in cerebral blood volume (CBV) with micrometer-millisecond precision. This opens up the possibility to 1) detect functional response, as CBV-changes reflect changes in metabolism of activated neurons through neurovascular coupling, and 2) visualize in-vivo vascular morphology of pathological and healthy tissue with high resolution at unprecedented depths. During a range of anesthetized and awake neurosurgical procedures we acquired vascular and functional images of brain and spinal cord using conventional ultrasound probes connected to a research acquisition system. Building on Brainlab’s Intra-Operative Navigation modules, we co-registered our intra-operative Power Doppler Images (PDIs) to patient-registered MRI/CT-data in real-time. RESULTS During meningioma and glioma resections, our co-registered PDIs revealed fUS’ ability to visualize the tumor’s feeding vessels and vascular borders in real-time, with a level of detail unprecedented by conventional MRI-sequences. During awake resections, fUS was able to detect distinct, ESM-confirmed functional areas as activated during conventional motor and language tasks. In all cases, images were acquired with micrometer-millisecond (300 µm, 1.5–2.0 ms) precision at imaging depths exceeding 5 cm. CONCLUSION fUS is a new real-time, high-resolution and depth-resolved imaging technique, combining favorable imaging specifications with characteristics such as mobility and ease of use which are uniquely beneficial for a potential image-guided neurosurgical tool.

LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis

Background: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression. Methods: LRP-1 involvement in a TNBC model was assessed using an RNA interference strategy in MDA-MB-231 cells. In vivo, tumorigenic and angiogenic effects of LRP-1-repressed cells were evaluated using an orthotopic xenograft model and two angiogenic assays (Matrigel® plugs, CAM). DCE-MRI, FMT, and IHC were used to complete a tumor longitudinal follow-up and obtain morphological and functional vascular information. In vitro, HUVECs’ angiogenic potential was evaluated using a tumor secretome, subjected to a proteomic analysis to highlight LRP-1-dependant signaling pathways. Results: LRP-1 repression in MDA-MB-231 tumors led to a 60% growth delay because of, inter alia, morphological and functional vascular differences, confirmed by angiogenic models. In vitro, the LRP-1-repressed cells secretome restrained HUVECs’ angiogenic capabilities. A proteomics analysis revealed that LRP-1 supports tumor growth and angiogenesis by regulating TGF-β signaling and plasminogen/plasmin system. Conclusions: LRP-1, by its wide spectrum of interactions, emerges as an important matricellular player in the control of cancer-signaling events such as angiogenesis, by supporting tumor vascular morphology and functionality.

Impact of vascular morphology and plaque characteristics on computed tomography derived fractional flow reserve in early stage coronary artery disease

Background FFRCT gradually decreases from the proximal to the distal part of a vessel and reach the pathological threshold for significant ischemia even in the absence of obstructive coronary artery disease (CAD). The exact mechanisms of such gradual FFRCT decline remain unknown. Purpose The aims of this study are (1) to clarify the mechanisms of the gradual decline of computed tomography (CT) derived fractional flow reserve (FFRCT); and (2) to identify the predictive factors of an FFRCT decline below the pathological value of 0.80 in no apparent CAD vessels. Methods A total of 1058 outpatients with suspected CAD and who underwent CT angiography (CTA) with FFRCT analysis between January 2017 and December 2019 were evaluated. Among them, 150 consecutive patients who had both a CTA coupled to an FFRCT analysis and an invasive angiogram showing &lt;25% coronary stenosis were included for analysis. Vessels were divided into two groups according to FFRCT at the distal vessel: FFRCT &gt;0.80 (n=317) and FFRCT ≤0.80 (n=114). ΔFFRCT was defined as the magnitude of the change in FFRCT from the proximal to the distal vessel. Plaque characterization and vessel morphology measurements were performed semi-automatically. Vessel constituents were characterized based on Hounsfield units (HU) into lumen volume (&lt;−50 HU), non-calcified plaque (NCP) (−50–150 HU), and calcified plaque (&gt;150 HU). Results FFRCT decreased continuously from the proximal to distal across the three major vessels in both FFRCT&gt;0.80 and FFRCT ≤0.80 groups (Figure 1). Compared to FFRCT&gt;0.80 group, NCP volume was significantly higher in all three major vessels in FFRCT ≤0.80 group (210.2±83.6 mm3 vs. 140.9±139.3 mm3 for the RCA, p=0.01; 177.5±150.2 mm3 vs. 133.2±112.2 mm3 for the LAD, p=0.04; 127.6±91.5 mm3 vs. 58.7±57.7 mm3 for the LCX, p&lt;0.01). Next, we investigated the vessel parameters that correlated with ΔFFRCT. ΔFFRCT was correlated with lumen volume in FFRCT&gt;0.80 group (r=−0.24, p&lt;0.0001), whereas ΔFFRCT was correlated with NCP volume in FFRCT ≤0.80 group (r=0.42, p&lt;0.001) (Figure 2). An NCP volume above 44.8 mm3 was the strongest predictor of distal FFRCT of ≤0.80 (area under the curve 0.69, p&lt;0.0001, sensitivity 95%, specificity 39%). Conclusions FFRCT is affected by vascular morphology and plaque characteristics even in the early stage of coronary artery disease. Our study highlights that subclinical coronary artery disease strongly influences FFRCT by effects unrelated to coronary stenosis. The presence of NCP is a major predictor of the gradual decrease of FFRCT toward pathological values. Anatomical findings as vessel morphology and plaque characteristics should be taken into consideration when interpreting numerical values of FFRCT to avoid unnecessary referrals for invasive coronary angiography or percutaneous coronary intervention. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Angiographic and Hemodynamic Features in Asymptomatic Hemispheres of Patients With Moyamoya Disease

Background and Purpose: There is also a risk of stroke in the asymptomatic hemispheres of moyamoya disease (MMD), but it does not draw enough attention. The study investigated the differences between the three types of asymptomatic hemispheres in MMD and their associations with the two types of symptomatic hemispheres, respectively. Methods: Retrospectively reviewed clinical and imaging characteristics of asymptomatic and symptomatic hemispheres in consecutive cases of single-center MMD patients, with an emphasis on imaging characterization regarding vascular morphology and cerebral perfusion. MMD hemispheres were categorized into 5 types: hemorrhagic hemispheres, ischemic hemispheres, asymptomatic hemispheres in unilateral hemorrhagic MMD, asymptomatic hemispheres in unilateral ischemic MMD, and bilateral asymptomatic hemispheres in MMD. Angiographic feature was assessed by Suzuki’s angiographic stage, while hemodynamic feature was assessed by preinfarction period stage. Results: One hundred ninety-four MMD patients with 388 hemispheres were enrolled. Asymptomatic hemispheres in unilateral hemorrhagic MMD were largely similar to hemorrhagic hemispheres, both had more advanced Suzuki’s angiographic stage and lower degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral ischemic MMD. Asymptomatic hemispheres in unilateral ischemic MMD were similar to ischemic hemispheres, both had less advanced Suzuki’s angiographic stage and higher degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral hemorrhagic MMD. Bilateral asymptomatic hemispheres in MMD were different from the other hemispheres and had less advanced Suzuki’s angiographic stage and lower degree of hemodynamic failure. ConclusionS: The three types of asymptomatic hemispheres in MMD are defined and have unique angiographic and hemodynamic features. Different combinations of the two features can reflect the tendency of pathological evolution in these different asymptomatic hemispheres.