Changes In Vasculature Research Articles

Abstract P3002: Role Of Vascular Fibroblast Growth Factor Signaling In Group 3 Hypoxia-induced Pulmonary Hypertension

Pulmonary hypertension (PH) is a debilitating disease characterized by pathologic changes in the pulmonary vasculature that increases pulmonary vascular resistance and leads to right heart failure. Group 3 PH is caused by lung disease and/or hypoxia, including bronchopulmonary dysplasia (BPD) and chronic obstructive lung disease (COPD), and is the second largest cause of mortality in PH patients. PH further increases the morbidity and mortality in both COPD and BPD patients. Fibroblast Growth Factor 2 (FGF2) and FGF Receptor 1 (FGFR1) expression is elevated in lung tissue of PH patients. To study the role of FGF signaling in the pathogenesis of group 3 PH, we developed a physiologically relevant mouse model in which mice are challenged with 10% hypoxia for 2 weeks. Following hypoxia exposure, cardiac catheterization is used to measure right ventricular (RV) pressure that mimics Group 3 PH. Lung tissue is then analyzed for histological and molecular changes. Our initial work showed that inactivation of FGFRs in endothelial cells (EC) worsened hypoxia-induced PH while expression of a constitutively active FGFR1 (caFGFR1) in ECs protected against hypoxia-induced PH. Here we hypothesize that FGF signaling may also affect the pathogenic response to hypoxia of vascular smooth muscle (VSMC), potentially by limiting vascular muscularization in response to hypoxia. We show that in vitro inhibition of FGF2 signaling in human pulmonary artery VSMCs reduced hypoxia-induced proliferation while promoting a contractile phenotype, and in vivo inactivation of FGFRs 1 and 2 worsened hypoxia-induced vascular remodeling. These data suggest the potential for a dual beneficial effect of activation of FGF signaling, both in regulating EC-VSMC interactions and directly preventing VSMC remodeling.

Fatal cerebrovascular accident in a captive red panda (Ailurus fulgens fulgens) with concurrent amdoparvovirus infection

We report the pathological and molecular findings in an adult male Himalayan red panda (Ailurus fulgens fulgens) whose death was attributed to parenchymal brain haemorrhage (PBH) of the thalamus. Post-mortem examination revealed severe, acute PBH and intraventricular haemorrhage with major involvement of the thalamus, as well as scattered chronic microinfarctions. Vascular disease in the brain and other organs was suggestive of systemic hypertension. Histological lesions included arteriolar hyalinosis and varying degrees of arteriosclerosis, arterial tunica media hypertrophy and hyperplasia and infiltration of arterial walls by lipid-laden macrophages. Other relevant findings included marked myocardial fibrosis, lymphoplasmacytic tubulointerstitial nephritis, lymphoplasmacytic meningoencephalitis and chronic mitral valve degeneration. The changes in the cerebral vasculature were consistent with hypertensive encephalopathy and a cerebrovascular accident, specifically PBH, which has not been previously reported in this species. Additionally, polymerase chain reaction analysis for red panda amdoparvovirus (RPAV) was positive in the brain and kidneys. Preceded by hypertensive vascular changes and brain microinfarctions, sudden death in this animal likely resulted from fatal PBH with intraventricular haemorrhage. The clinicopathological role of RPAV infection is unknown in this case, although its contribution to the chronic renal disease is considered possible in the context of our current understanding of RPAV-associated pathology.

Comparison of effects of peripheral vasculature on tonometric radial pulse and cuff-based brachial pulse waveform as used in estimation of central aortic pressures.

Aortic pressure estimation requires reliable peripheral pulse waveform acquisition. The peripheral waveform can change with local vascular effects that can be independent of aortic pressure. This study quantifies the effects of peripheral vasculature changes on radial and brachial waveforms. In 20 subjects (37± 15 years, 7 female), brachial volumetric displacement (cuff-based) and radial tonometry waveforms were simultaneously measured whilst a cuff around the hand on the same arm was inflated to induce transmural pressures of -60, -30, -15, 0, 15 and 30 mmHg, altering local peripheral resistance and compliance by graded arterial wall unloading. Aortic blood pressure (BP), augmentation index (AIx) and ejection duration were calculated from the measurements using a generalized transfer function. The parameters under unloaded conditions were compared to baseline measurements. Brachial systolic and diastolic BP did not change throughout the experiment. Altering peripheral resistance and compliance did not significantly change calculated aortic BP values, although changes were nominally greater for radial (maximum +8±1 mmHg) compared to brachial (maximum +2±1 mmHg) waveforms. AIx at 0 mmHg transmural pressure (maximum arterial wall unloading) was higher when derived from radial waveforms (+24±3%, p<0.001) but not when derived from brachial waveforms. Localized changes in peripheral resistance and compliance affect tonometer acquired radial waveforms but not volumetric displacement acquired brachial pressure waveforms, as judged by computed central aortic augmentation pressure parameters. This suggests aortic pressure estimation from the brachial cuff waveform is less sensitive to peripheral vasculature disturbances that alter the peripheral arterial pulse morphology.

Assessing the effects of prenatal poly-drug exposure on fetal brain vasculature using optical coherence angiography.

Maternal exposure to drugs during pregnancy is known to have detrimental effects on the fetus. Alcohol (ethanol) and nicotine are two of the most commonly co-abused substances during pregnancy, and prenatal poly-drug exposure is common due, in part, to the prevalence of unplanned pregnancies. The second trimester is a critical period for fetal neurogenesis and angiogenesis. When drug exposure occurs during this time, fetal brain development is affected. Several behavioral, morphological, and functional studies have evaluated the changes in fetal brain development due to exposure to these drugs individually. However, research on the combined effects of ethanol and nicotine is far more limited, specifically on fetal vasculature changes and development. We use correlation mapping optical coherence angiography (cm-OCA) to evaluate acute changes in fetal brain vasculature caused by maternal exposure to a combination of ethanol and nicotine. Ethanol (16.6% v/v, at a dose of ) and nicotine (at a dose of ) were administered to pregnant mice after initial cm-OCA measurements in utero. Subsequent measurements were taken at 5-min intervals for a total period of 45min. Results from these experiments were compared to results from our previous studies in which the mother was exposed to only ethanol (dose: ) or nicotine (dose: ). While results from exposure to ethanol or nicotine independently showed vasoconstriction, no significant change in vasculature was observed with combined exposure. Results suggested antagonistic effects of ethanol and nicotine on fetal brain vasculature.

Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice

Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)−/− mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3−/− mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3−/− mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3−/− mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3−/− mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3−/− mice without notable changes in pulmonary vasculature under CIH conditions.

Dilated superior ophthalmic vein: systemic associations

PurposeTo review systemic associations of patients with dilated superior ophthalmic veins (SOV) in the absence of orbital, cavernous sinus, or neurological disease.MethodsRetrospective review of patients who had dilated SOVs with a diameter of ≥ 5.0 mm. Patients with a dilated SOV secondary to orbital, cavernous sinus or neurological disease were excluded. Patient demographics, past medical history, and SOV diameters on initial and follow up scans were collected. The maximum diameter of the SOV was taken perpendicular to the long axis of the SOV.ResultsNine cases were identified. Patients ranged in age from 58 to 89 years and six out of nine were female. The dilated SOV involved both eyes in two cases, left eye in five cases and right eye in two cases. Three patients had dilated SOV likely secondary to raised venous pressures from decompensated right heart failure (n = 1), pericardial effusion (n = 1) and left ventricle dysfunction secondary to a myocardial infarction (n = 1). Five patients had a significant history of previous ischaemic heart or peripheral vascular disease. Two patients had risk factors for venous clotting disease whilst one patient had a history of giant cell arteritis and vertebral artery dissection.ConclusionA dilated SOV may raise concern for life threatening conditions such as a carotid cavernous fistula and may prompt additional investigations. A dilated SOV may be reversible and secondary to raised venous pressures due to cardiac failure. Other cases may be seen in patients with significant cardiovascular risk factors, possibly due to changes in vasculature.

Choroidal vasculature act as predictive biomarkers of long-term ocular elongation in myopic children treated with orthokeratology: a prospective cohort study

BackgroundDespite receiving orthokeratology (ortho-k), the efficacy of retarding ocular elongation during myopia varies among myopic children. The current study aimed to investigate the early changes of choroidal vasculature at one month after ortho-k treatment and its association with one-year ocular elongation, as well as the role of such choroidal responses in predicting the one-year control efficacy of ortho-k treatment.MethodsA prospective cohort study was conducted in myopic children treated with ortho-k. Myopic children aged between 8 and 12 years who were willing to wear ortho-k lenses were recruited consecutively from the Eye Hospital of Wenzhou Medical University. Subfoveal choroidal thickness (SFCT), submacular total choroidal luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow deficit (CcFD) were evaluated by optical coherence tomography (OCT) and OCT angiography over a one-year period.ResultsFifty eyes from 50 participants (24 males) who finished one-year follow-ups as scheduled were included, with a mean age of 10.31 ± 1.45 years. The one-year ocular elongation was 0.19 ± 0.17 mm. The LA (0.03 ± 0.07 mm2), SA (0.02 ± 0.05 mm2) increased proportionally after one-month of ortho-k wear (both P < 0.01), as did the SFCT (10.62 ± 19.98 μm, P < 0.001). Multivariable linear regression analyses showed that baseline CVI (β = − 0.023 mm/1%, 95% CI: − 0.036 to − 0.010), one-month LA change (β = − 0.009 mm/0.01 mm2, 95% CI: − 0.014 to − 0.003), one-month SFCT change (β = − 0.035 mm/10 µm, 95% CI: − 0.053 to − 0.017) were independently associated with one-year ocular elongation during ortho-k treatment after adjusting with age and sex (all P < 0.01). The area under the receiver operating characteristic curve of prediction model including baseline CVI, one-month SFCT change, age, and sex achieved 0.872 (95% CI: 0.771 to 0.973) for discriminating children with slow or fast ocular elongation.ConclusionsChoroidal vasculature is associated with ocular elongation during ortho-k treatment. Ortho-k treatment induces increases in choroidal vascularity and choroidal thickness as early as one month. Such early changes can act as predictive biomarkers of myopia control efficacy over a long term. The utilization of these biomarkers may help clinicians identify children who can benefit from ortho-k treatment, and thus has critical implications for the management strategies towards myopia control.

Towards continuous non-invasive blood pressure measurements-interpretation of the vasculature response to cuff inflation.

Blood pressure (BP) surrogates, such as pulse transit time (PTT) or pulse arrival time (PAT), have been intensively explored with the goal of achieving cuffless, continuous, and accurate BP inference. In order to estimate BP, a one-point calibration strategy between PAT and BP is typically used. Recent research focuses on advanced calibration procedures exploiting the cuff inflation process to improve calibration robustness by active and controlled modulation of peripheral PAT, as measured via plethysmograph (PPG) and electrocardiogram (ECG) combination. Such methods require a detailed understanding of the mechanisms behind the vasculature's response to cuff inflation; for this, a model has recently been developed to infer the PAT-BP calibration from measured cuff-induced vasculature changes. The model, while promising, is still preliminary and only partially validated; in-depth analysis and further developments are still needed. Therefore, this work aims to improve our understanding of the cuff-vasculature interaction in this model; we seek to define potential opportunities and to highlight which aspects may require further study. We compare model behaviors with clinical data samples based on a set of observable characteristics relevant for BP inference and calibration. It is found that the observed behaviors are qualitatively well represented with the current simulation model and complexity, with limitations regarding the prediction of the onset of the distal arm dynamics and behavior changes at high cuff pressures. Additionally, a sensitivity analysis of the model's parameter space is conducted to show the factors that influence the characteristics of its observable outputs. It was revealed that easily controllable experimental variables, such as lateral cuff length and inflation rate, have a significant impact on cuff-induced vasculature changes. An interesting dependency between systemic BP and cuff-induced distal PTT change is also found, revealing opportunities for improved methods for BP surrogate calibration. However, validation via patient data shows that this relation does not hold for all patients, indicating required model improvements to be validated in follow up studies. These results provide promising directions to improve the calibration process featuring cuff inflation towards accurate and robust non-invasive blood pressure estimation.

The Research Progress of Vascular Aging Related Diseases

The aging-related factors of population, environment, physical inactivity and unhealthy diet have emerged as significant contributors to the onset of vascular aging, which poses a crucial risk for various diseases including hypertension, coronary heart disease, heart failure and stroke. The structural, phenotypic, and functional changes in vasculature resulting from aging are critical in the pathogenesis of vascular aging-related diseases. Numerous molecular and cellular phenomena, including oxidative stress, mitochondrial dysfunction, vascular inflammation, cellular senescence, and epigenetic alterations, are closely linked to the pathophysiology of vascular aging. Given the escalating hospitalization rates attributed to vascular aging-related illness, the need for efficacious interventions to counteract the decline in vascular function is becoming increasingly pressing. This review provides an overview of recent developments in vascular aging-related disorders, encompassing cardiovascular diseases, neurodegenerative diseases, chronic kidney diseases, and sarcopenia. Furthermore, a comprehensive examination of the pathogenesis of aging is conducted, and the implementation of intervention strategies (including drug and lifestyle interventions) can effectively mitigate the onset and progression of aging-related ailments, thereby facilitating the achievement of healthy aging and longevity.

Effects of beetroot juice supplementation on vascular functional and structural changes in aged mice.

This study investigated whether beetroot juice (BRJ) ingestion ameliorates aging-induced functional and structural changes in vasculature. Aged mice (98-100 weeks old) were supplemented with BRJ (nitrate: 3.5 mmol/L) or drinking water for 4 weeks and compared with young mice (12-15 weeks old). The vasorelaxant response of isolated aortas to acetylcholine was markedly weaker in aged mice than in young mice, but the attenuated relaxation was significantly improved in BRJ-supplemented aged mice. The acetylcholine-induced relaxation was completely abolished by Nω -nitro-l-arginine methyl ester in all groups. Additionally, the response to sodium nitroprusside was comparable among the three groups. The aortic medial thickness was significantly greater in aged mice than in young mice, and BRJ supplementation did not suppress this thickening. Plasma nitrate levels were significantly higher in BRJ-supplemented aged mice than in non-supplemented aged mice. Conversely, non-supplemented aged mice had high plasma levels of thiobarbituric acid-reactive substances, but the levels were suppressed in BRJ-supplemented aged mice. These findings suggest that BRJ ingestion improves vascular endothelial dysfunction associated with aging, at least in part, by enhancing nitric oxide bioavailability and reducing oxidative stress. Therefore, beetroot ingestion may be a highly useful self-medication option to prevent vascular aging.

Multiple instance learning based classification of diabetic retinopathy in weakly-labeled widefield OCTA en face images

Diabetic retinopathy (DR), a pathologic change of the human retinal vasculature, is the leading cause of blindness in working-age adults with diabetes mellitus. Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography, has shown potential as a tool for early diagnosis of DR through its ability to visualize the retinal vasculature in all spatial dimensions. Previously introduced deep learning-based classifiers were able to support the detection of DR in OCTA images, but require expert labeling at the pixel level, a labor-intensive and expensive process. We present a multiple instance learning-based network, MIL-ResNet,14 that is capable of detecting biomarkers in an OCTA dataset with high accuracy, without the need for annotations other than the information whether a scan is from a diabetic patient or not. The dataset we used for this study was acquired with a diagnostic ultra-widefield swept-source OCT device with a MHz A-scan rate. We were able to show that our proposed method outperforms previous state-of-the-art networks for this classification task, ResNet14 and VGG16. In addition, our network pays special attention to clinically relevant biomarkers and is robust against adversarial attacks. Therefore, we believe that it could serve as a powerful diagnostic decision support tool for clinical ophthalmic screening.

Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy

BackgroundResponse assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy.MethodsLow malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry.ResultsTherapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage.ConclusionDCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.

Visual inertial odometry enabled 3D ultrasound and photoacoustic imaging.

There is an increasing need for 3D ultrasound and photoacoustic (USPA) imaging technology for real-time monitoring of dynamic changes in vasculature or molecular markers in various malignancies. Current 3D USPA systems utilize expensive 3D transducer arrays, mechanical arms or limited-range linear stages to reconstruct the 3D volume of the object being imaged. In this study, we developed, characterized, and demonstrated an economical, portable, and clinically translatable handheld device for 3D USPA imaging. An off-the-shelf, low-cost visual odometry system (the Intel RealSense T265 camera equipped with simultaneous localization and mapping technology) to track free hand movements during imaging was attached to the USPA transducer. Specifically, we integrated the T265 camera into a commercially available USPA imaging probe to acquire 3D images and compared it to the reconstructed 3D volume acquired using a linear stage (ground truth). We were able to reliably detect 500 µm step sizes with 90.46% accuracy. Various users evaluated the potential of handheld scanning, and the volume calculated from the motion-compensated image was not significantly different from the ground truth. Overall, our results, for the first time, established the use of an off-the-shelf and low-cost visual odometry system for freehand 3D USPA imaging that can be seamlessly integrated into several photoacoustic imaging systems for various clinical applications.

In vivo ocular microvasculature imaging in rabbits with 3D ultrasound localization microscopy

Morphological and hemodynamic changes in the ocular vasculature are important signs of various ocular diseases. The evaluation of the ocular microvasculature with high resolution is valuable in comprehensive diagnoses. However, it is difficult for current optical imaging techniques to visualize the posterior segment and retrobulbar microvasculature due to the limited penetration depth of light, particularly when the refractive medium is opaque. Thus, we have developed a 3D ultrasound localization microscopy (ULM) imaging method to visualize the ocular microvasculature in rabbits with micron-scale resolution. We used a 32 × 32 matrix array transducer (center frequency: 8 MHz) with a compounding plane wave sequence and microbubbles. Block-wise singular value decomposition spatiotemporal clutter filtering and block-matching 3D denoising were implemented to extract the flowing microbubble signals at different imaging depths with high signal-to-noise ratios. The center points of microbubbles were localized and tracked in 3D space to achieve the micro-angiography. The in vivo results demonstrate the ability of 3D ULM to visualize the microvasculature of the eye in rabbits, where vessels down to 54 μm were successfully revealed. Moreover, the microvascular maps indicated the morphological abnormalities in the eye with retinal detachment. This efficient modality shows potential for use in the diagnosis of ocular diseases.

The alleviative effect of Calendula officinalis L. extract against Parkinson's disease-like pathology in zebrafish via the involvement of autophagy activation.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, effective preventative or therapeutic agents for PD remain largely limited. Marigold Calendula officinalis L. (CoL) has been reported to possess a wide range of biological activities, but its neuroprotective activity including anti-neurodegenerative diseases is unclear. Here, we aim to investigate whether the extract of CoL (ECoL) has therapeutic activity on PD. We identified the chemical composition of flavonoid, an important active ingredient in ECoL, by a targeted HPLC-Q-TOF-MS analysis. Subsequently, we evaluated the anti-PD effect of ECoL by using zebrafish PD model induced by 1-methyl-4-phenyl-1-1,2,3,6-tetrahydropyridine (MPTP). After ECoL+MPTP co-treatments, the changes of dopaminergic neurons, neural vasculature, nervous system, and locomotor activity were examined, respectively. The expressions of genes related to neurodevelopment and autophagy were detected by RT-qPCR. Further, the interaction between autophagy regulators and ECoL flavonoids was predicted using molecular docking method. As a result, 5 kinds of flavonoid were identified in ECoL, consisting of 121 flavones and flavonols, 32 flavanones, 22 isoflavonoids, 11 chalcones and dihydrochalcones, and 17 anthocyanins. ECoL significantly ameliorated the loss of dopaminergic neurons and neural vasculature, restored the injury of nervous system, and remarkably reversed the abnormal expressions of neurodevelopment-related genes. Besides, ECoL notably inhibited the locomotor impairment in MPTP-induced PD-like zebrafish. The underlying anti-PD effect of ECoL may be implicated in activating autophagy, as ECoL significantly upregulated the expressions of genes related to autophagy, which contributes to the degradation of α-synuclein aggregation and dysfunctional mitochondria. Molecular docking simulation showed the stable interaction between autophagy regulators (Pink, Ulk2, Atg7, and Lc3b) and 10 main compounds of flavonoid in ECoL, further affirming the involvement of autophagy activation by ECoL in anti-PD action. Our results suggested that ECoL has the anti-PD effect, and ECoL might be a promising therapeutic candidate for PD treatment.

Impaired fin regeneration and angiogenesis in aged zebrafish and turquoise killifish.

Impaired wound healing is associated with aging and has significant effects on human health on an individual level, but also on the whole health-care sector. Deficient angiogenesis appears to be involved in the process, but the underlying biology is still poorly understood. This is at least partially being explained by complexity and costs in using mammalian aging models. To understand aging-related vascular biology of impaired wound healing, we used zebrafish and turquoise killifish fin regeneration models. The regeneration of caudal fin after resection was significantly reduced in old individuals in both species. Age-related changes in angiogenesis, vascular density and expression levels of angiogenesis biomarker VEGF-A were observed. Furthermore, the anti-angiogenic drug vascular endothelial growth factor receptor blocking inhibitor SU5416 reduced regeneration, indicating a key role for angiogenesis in the regeneration of aging caudal fin despite aging-related changes in vasculature. Taken together, our data indicate that these fish fin regeneration models are suitable for studying aging-related decline in wound healing and associated alterations in aging vasculature.

The Role of Widefield Optical Coherence Tomography Angiography in the Diagnosis and Management of Acute Vogt–Koyanagi–Harada Disease

ABSTRACT Purpose We explore the choroid vasculature changes of acute Vogt–Koyanagi–Harada (VKH) disease using widefield optical coherence tomography angiography (OCTA). Methods In this retrospective, observational, longitudinal study, 16 patients with acute VKH disease (32 eyes, mean age: 42.19 ±13.66 years) were measured using widefield OCTA. Results In this study, we first described the multiple dark foci in choriocapillaris and Sattler’s layer in the panoramic montage of the five 12x12mm images in 30 eyes (93.8%) of acute VKH disease. OCTA follow-up in these 30 eyes demonstrated the diminished size and number of these dark foci in choriocapillaris and Sattler’s layer after the initiation of treatment. Conclusions Widefield OCTA enables noninvasive identification of characteristics of flow void at the level of superficial choroidal vessels in the acute phase and may be a novel valuable tool for diagnosis and monitoring of disease progression in VKH disease in the future.

Abstract 5569: Quantification of tumor-associated vasculature as an imaging biomarker for monitoring the response of triple-negative breast cancer to neoadjuvant chemotherapy

Abstract Introduction: Patients with locally advanced, triple-negative breast cancer (TNBC) typically receive neoadjuvant systemic therapy (NAST). However, the response of TNBC to NAST is varied and a prognostic marker is still lacking. Since angiogenesis plays an important role in cancer progression, the quantification of changes in the tumor vasculature during treatment has the potential to provide useful information for characterizing the treatment response. We have recently developed a method to quantify changes in tumor-associated vasculature through a novel analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In this study, we investigated its ability to monitor the response of TNBC to NAST. Methods: Dynamic contrast-enhanced (DCE) MRI was acquired in TNBC patients (N = 50; 25 pathological complete response (pCR), 25 non-pCR) before, after 2 and 4 cycles of Adriamycin/Cyclophosphamide (A/C), as part of the ARTEMIS trial (NCT02276433). Using DCE-MRI, we identified the tumor-associated vessels via a breast vasculature analysis. Specifically, the difference between pre- and post-contrast DCE-MRI images was enhanced by a histogram-based intensity transfer function. The 3D vasculature in the breast was then segmented by applying a Hessian filter. Given the vasculature segmented by the algorithms and the tumor masks segmented by radiologists, a lowest-cost tracking algorithm was used to automatically detect the vessels that are most likely to contact the tumor. These vessels are defined as tumor-associated vessels (TAV). The number of TAVs per patient was tabulated and the Wilcoxon rank sum test compared the TAV values before (V1), after 2 cycles (V2), and after 4 cycles of NAST (V3). Additionally, we compared the percent change of TAV from V1 to V3 between the pCR patients and non-pCR patients. Statistical significance was defined as P &amp;lt; 0.05. Results: A significant decrease in the number of TAVs was observed during the NAST. In particular, the number of TAVs has a median (interquartile range) of 15 (7 - 24), 7 (3 - 14), and 2 (0 - 8) at V1, V2, V3, respectively, which are (pair-wise) significantly different (P &amp;lt; 0.01). Moreover, pCR patients showed a significantly greater decrease in the number of TAVs as compared to non-pCR patients. The percent changes in the number of TAVs from V1 to V3 have a median (range) of -88.89% (-100.00% - -60.00%) and -66.67% (-87.85% - -40.88%) in the pCR and non-pCR patients, respectively (P &amp;lt; 0.05). Conclusion: These preliminary results demonstrate that tumor-associated vasculature may be a valuable imaging biomarker for monitoring the response of TNBC to NAST. Ongoing efforts include additional investigation of the TAVs beyond their number, as well as applying the analysis to more patients. Citation Format: Chengyue Wu, Casey E. Stowers, Zhan Xu, Ernesto A. B. F. Lima, Clinton Yam, Jong Bum Son, Jingfei Ma, Gaiane M. Rauch, Thomas E. Yankeelov. Quantification of tumor-associated vasculature as an imaging biomarker for monitoring the response of triple-negative breast cancer to neoadjuvant chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5569.

OCT Angiography in Noninfectious Uveitis: A Description of Five Cases and Clinical Applications.

Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality used to analyze the retinochoroidal vasculature and detect vascular flow. The resulting images can be segmented to view each vascular plexus individually. While fluorescein angiography is still the gold standard for the diagnosis of posterior uveitis, it has limitations, and can be replaced by OCTA in some cases. This case series describes five patients with posterior noninfectious uveitis and their description by OCTA. Cases included lupus retinopathy (n = 1) for which OCTA showed ischemic maculopathy as areas of flow deficit at the superficial and deep capillary plexus; choroidal granulomas (n = 1) with a non-detectable flow signal in the choroid; active punctate inner choroiditis and multifocal choroiditis (n = 1) with OCTA that showed active inflammatory chorioretinal lesions as non-detectable flow signals in choriocapillaris and choroid; dense type 2 inflammatory secondary neovascularization (n = 1) associated with active choroiditis; and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1) without flow abnormalities at the superficial and deep retinal plexuses but non-detectable flow at the levels of the choriocapillaris and choroid. Ophthalmologists can use OCTA to identify inflammatory changes in retinal and choroidal vasculature, aiding in the diagnosis, management, and monitoring of posterior uveitis.

EVALUATION OF OPTIC DISK AND MACULAR VASCULARITY CHANGES IN CRVO USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To quantify changes in optic disk and macular vasculature in patients with central retinal vein occlusion using optical coherence tomography angiography and detect its correlation with visual acuity. The study included 20 eyes of 20 patients with treatment-naive central retinal vein occlusion and 20 age-matched controls. Optical coherence tomography and optical coherence tomography angiographywere performed on the macula and optic disk. Central 1-mm subfield foveal thickness was measured. Vessel densities (VD) of superficial and deep macular capillary plexuses with whole disk VD, inside disk VD, and radial peripapillary capillary plexus were analyzed. Macular ischemia was evaluated by fundus fluorescein angiography. Visual acuity was correlated with measured parameters. All measured macular and disk VDs differed significantly between cases and controls except inside disk VD. Visual acuity showed a highly significant negative correlation with whole disk VD ( P = 0.005) and radial peripapillary capillary ( P = 0.002), borderline correlation with central subfield foveal thickness ( P = 0.06), and insignificant correlation with macular VDs. Radial peripapillary capillary VD showed a significant correlation with deep parafoveal ( P = 0.04), and superficial and deep perifoveal VDs ( P = 0.01). Optic disk VD could provide more accurate indication of retinal blood supply than macular VD in cases of central retinal vein occlusion with severe macular edema.