IU Indianapolis ScholarWorks :: Browsing by Author "Arciero, Julia"

Browsing by Author "Arciero, Julia"

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Assessing the hemodynamic contribution of capillaries, arterioles, and collateral arteries to vascular adaptations in arterial insufficiency
(Wiley, 2019) Arciero, Julia; Lembcke, Lauren; Franko, Elizabeth; Unthank, Joseph; Mathematical Sciences, School of Science
Objective There is currently a lack of clarity regarding which vascular segments contribute most significantly to flow compensation following a major arterial occlusion. This study uses hemodynamic principles and computational modeling to demonstrate the relative contributions of capillaries, arterioles, and collateral arteries at rest or exercise following an abrupt, total, and sustained femoral arterial occlusion. Methods The vascular network of the simulated rat hindlimb is based on robust measurements of blood flow and pressure in healthy rats from exercise and training studies. The sensitivity of calf blood flow to acute or chronic vascular adaptations in distinct vessel segments is assessed. Results The model demonstrates that decreasing the distal microcirculation resistance has almost no effect on flow compensation, while decreasing collateral arterial resistance is necessary to restore resting calf flow following occlusion. Full restoration of non‐occluded flow is predicted under resting conditions given all chronic adaptations, but only 75% of non‐occluded flow is restored under exercise conditions. Conclusion This computational method establishes the hemodynamic significance of acute and chronic adaptations in the microvasculature and collateral arteries under rest and exercise conditions. Regardless of the metabolic level being simulated, this study consistently shows the dominating significance of collateral vessels following an occlusion.
Blood flow regulation and oxygen transport in a heterogeneous model of the mouse retina
(Elsevier, 2020-11) Fry, Brendan C.; Harris, Alon; Siesky, Brent; Arciero, Julia; Mathematical Sciences, School of Science
Elevated intraocular pressure is the primary risk factor for glaucoma, yet vascular health and ocular hemodynamics have also been established as important risk factors for the disease. The precise physiological mechanisms and processes by which flow impairment and reduced tissue oxygenation relate to retinal ganglion cell death are not fully known. Mathematical modeling has emerged as a useful tool to help decipher the role of hemodynamic alterations in glaucoma. Several previous models of the retinal microvasculature and tissue have investigated the individual impact of spatial heterogeneity, flow regulation, and oxygen transport on the system. This study combines all three of these components into a heterogeneous mathematical model of retinal arterioles that includes oxygen transport and acute flow regulation in response to changes in pressure, shear stress, and oxygen demand. The metabolic signal (Si) is implemented as a wall-derived signal that reflects the oxygen deficit along the network, and three cases of conduction are considered: no conduction, a constant signal, and a flow-weighted signal. The model shows that the heterogeneity of the downstream signal serves to regulate flow better than a constant conducted response. In fact, the increases in average tissue PO2 due to a flow-weighted signal are often more significant than if the entire level of signal is increased. Such theoretical work supports the importance of the non-uniform structure of the retinal vasculature when assessing the capability and/or dysfunction of blood flow regulation in the retinal microcirculation.
Diagnostic Capability of OCTA-Derived Macular Biomarkers for Early to Moderate Primary Open Angle Glaucom
(MDPI, 2024-07-18) Verticchio Vercellin, Alice; Harris, Alon; Oddone, Francesco; Carnevale, Carmela; Siesky, Brent A.; Arciero, Julia; Fry, Brendan; Eckert, George; Sidoti, Paul A.; Antman, Gal; Alabi, Denise; Coleman-Belin, Janet C.; Pasquale, Louis R.; Mathematical Sciences, School of Science
Background/Objectives: To investigate macular vascular biomarkers for the detection of primary open-angle glaucoma (POAG). Methods: A total of 56 POAG patients and 94 non-glaucomatous controls underwent optical coherence tomography angiography (OCTA) assessment of macular vessel density (VD) in the superficial (SCP), and deep (DCP) capillary plexus, foveal avascular zone (FAZ) area, perimeter, VD, choriocapillaris and outer retina flow area. POAG patients were classified for severity based on the Glaucoma Staging System 2 of Brusini. ANCOVA comparisons adjusted for age, sex, race, hypertension, diabetes, and areas under the receiver operating characteristic curves (AUCs) for POAG/control differentiation were compared using the DeLong method. Results: Global, hemispheric, and quadrant SCP VD was significantly lower in POAG patients in the whole image, parafovea, and perifovea (p < 0.001). No significant differences were found between POAG and controls for DCP VD, FAZ parameters, and the retinal and choriocapillaris flow area (p > 0.05). SCP VD in the whole image and perifovea were significantly lower in POAG patients in stage 2 than stage 0 (p < 0.001). The AUCs of SCP VD in the whole image (0.86) and perifovea (0.84) were significantly higher than the AUCs of all DCP VD (p < 0.05), FAZ parameters (p < 0.001), and retinal (p < 0.001) and choriocapillaris flow areas (p < 0.05). Whole image SCP VD was similar to the AUC of the global retinal nerve fiber layer (RNFL) (AUC = 0.89, p = 0.53) and ganglion cell complex (GCC) thickness (AUC = 0.83, p = 0.42). Conclusions: SCP VD is lower with increasing functional damage in POAG patients. The AUC for SCP VD was similar to RNFL and GCC using clinical diagnosis as the reference standard.
Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects
(The Company of Biologists, 2013-08-14) Sarmah, Swapnalee; Muralidharan, Pooja; Curtis, Courtney L.; McClintick, Jeanette N.; Buente, Bryce B.; Holdgrafer, David J.; Ogbeifun, Osato; Olorungbounmi, Opeyemi C.; Patino, Liliana; Lucas, Ryan; Gilbert, Sonya; Groninger, Evan S.; Arciero, Julia; Edenberg, Howard J.; Marrs, James A.; Biology, School of Science
Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell), prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented that characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression was not affected by ethanol exposure, but E-cadherin distribution, which controls epiboly and gastrulation, was changed. E-cadherin was redistributed into cytoplasmic aggregates in blastomeres and dramatically redistributed in the extraembryonic yolk cell. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a), which controls epiboly, was significantly reduced in ethanol exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue) microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.
Heterogeneity of Ocular Hemodynamic Biomarkers among Open Angle Glaucoma Patients of African and European Descent
(MDPI, 2023-02-06) Siesky, Brent; Harris, Alon; Verticchio Vercellin, Alice; Arciero, Julia; Fry, Brendan; Eckert, George; Guidoboni, Giovanna; Oddone, Francesco; Antman, Gal; Mathematical Sciences, School of Science
This study investigated the heterogeneity of ocular hemodynamic biomarkers in early open angle glaucoma (OAG) patients and healthy controls of African (AD) and European descent (ED). Sixty OAG patients (38 ED, 22 AD) and 65 healthy controls (47 ED, 18 AD) participated in a prospective, cross-sectional study assessing: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), visual field (VF) and vascular densities (VD) via optical coherence tomography angiography (OCTA). Comparisons between outcomes were adjusted for age, diabetes status and BP. VF, IOP, BP and OPP were not significantly different between OAG subgroups or controls. Multiple VD biomarkers were significantly lower in OAG patients of ED (p < 0.05) while central macular VD was lower in OAG patients of AD vs. OAG patients of ED (p = 0.024). Macular and parafoveal thickness were significantly lower in AD OAG patients compared to those of ED (p = 0.006–0.049). OAG patients of AD had a negative correlation between IOP and VF index (r = −0.86) while ED patients had a slightly positive relationship (r = 0.26); difference between groups (p < 0.001). Age-adjusted OCTA biomarkers exhibit significant variation in early OAG patients of AD and ED.
Intraocular pressure, blood pressure, and retinal blood flow autoregulation: a mathematical model to clarify their relationship and clinical relevance
(Association for Research in Vision and Opthalmology, 2014-07) Guidoboni, Giovanna; Harris, Alon; Cassani, Simone; Arciero, Julia; Siesky, Brent; Amireskandari, Annahita; Tobe, Leslie; Egan, Patrick; Januleviciene, Ingrida; Park, Joshua; Department of Mathematical Sciences, School of Science
PURPOSE: This study investigates the relationship between intraocular pressure (IOP) and retinal hemodynamics and predicts how arterial blood pressure (BP) and blood flow autoregulation (AR) influence this relationship. METHODS: A mathematical model is developed to simulate blood flow in the central retinal vessels and retinal microvasculature as current flowing through a network of resistances and capacitances. Variable resistances describe active and passive diameter changes due to AR and IOP. The model is validated by using clinically measured values of retinal blood flow and velocity. The model simulations for six theoretical patients with high, normal, and low BP (HBP-, NBP-, LBP-) and functional or absent AR (-wAR, -woAR) are compared with clinical data. RESULTS: The model predicts that NBPwAR and HBPwAR patients can regulate retinal blood flow (RBF) as IOP varies between 15 and 23 mm Hg and between 23 and 29 mm Hg, respectively, whereas LBPwAR patients do not adequately regulate blood flow if IOP is 15 mm Hg or higher. Hemodynamic alterations would be noticeable only if IOP changes occur outside of the regulating range, which, most importantly, depend on BP. The model predictions are consistent with clinical data for IOP reduction via surgery and medications and for cases of induced IOP elevation. CONCLUSIONS: The theoretical model results suggest that the ability of IOP to induce noticeable changes in retinal hemodynamics depends on the levels of BP and AR of the individual. These predictions might help to explain the inconsistencies found in the clinical literature concerning the relationship between IOP and retinal hemodynamics.
Mathematical Models of Major Arterial Occlusion
(2025-05) Zhao, Erin; Arciero, Julia; Barber, Jared; Kuznetsov, Alexey; Zhu, Luoding
The occlusion of a major artery constitutes a serious health concern as it can restrict blood flow and oxygen transport to dependent tissue regions. Fortunately, the vasculature surrounding the occlusion has mechanisms by which it can adapt to try to restore and maintain adequate perfusion to these regions, though the details of these compensatory mechanisms are not well understood. The aim of the present study is to use mathematical modeling to investigate the effects of major arterial occlusion in multiple tissues and vascular geometries. A network representing the vasculature of the rat hindlimb is used to study peripheral arterial disease characterized by femoral artery occlusion. This work couples responses that occur on different time scales, namely vessel dilation and constriction on a short time scale and structural changes including arteriogenesis and angiogenesis on a long time scale. In the acute time frame, the responses that contribute most to changes in vascular tone are increases in flow and shear stress in collateral vessels and increases in metabolic signaling in distal arterioles. On the chronic scale, arteriogenesis is found to have a significantly larger effect on flow restoration than angiogenesis. A model of the major arteries and regions of the human brain is used to assess the impact of stroke caused by middle cerebral artery occlusion and the role of leptomeningeal collaterals in restoring flow downstream of the occlusion. The effects of incorporating pulsatile blood flow and arterial distensibility are also examined. The model demonstrates that the leptomeningeal collaterals are critical to restoring blood flow to the middle region, but the degree to which this is successful is highly dependent on conditions such as oxygen demand and arterial pressure. Overall, the results obtained from this study provide valuable insight into the vascular response mechanisms that contribute the most to flow compensation after occlusion and factors that may improve or worsen perfusion deficits. Insight from these models will inform the mechanisms and/or vessels to target in potential new treatments for peripheral arterial disease and stroke.
Metabolic blood flow regulation in a hybrid model of the human retinal microcirculation
(Elsevier, 2023) Albright, Amanda; Fry, Brendan C.; Verticchio, Alice; Siesky, Brent; Harris, Alon; Arciero, Julia; Mathematical Sciences, School of Science
The retinal vascular network supplies perfusion to vital visual structures, including retinal ganglion cells responsible for vision. Impairments in retinal blood flow and oxygenation are involved in the progression of many ocular diseases, including glaucoma. In this study, an established theoretical hybrid model of a retinal microvascular network is extended to include the effects of local blood flow regulation on oxygenation. A heterogeneous representation of the arterioles based on confocal microscopy images is combined with a compartmental description of the downstream capillaries and venules. A Green’s function method is used to simulate oxygen transport in the arterioles, and a Krogh cylinder model is applied to the capillary and venular compartments. Acute blood flow regulation is simulated in response to changes in pressure, shear stress, and metabolism. Model results predict that both increased intraocular pressure and impairment of blood flow regulation can cause decreased tissue oxygenation, indicating that both mechanisms represent factors that could lead to impaired oxygenation characteristic of ocular disease. Results also indicate that the metabolic response mechanism reduces the fraction of poorly oxygenated tissue but that the pressure- and shear stress-dependent response mechanisms may hinder the vascular response to changes in oxygenation. Importantly, the heterogeneity of the vascular network demonstrates that traditionally reported average values of tissue oxygen levels hide significant localized defects in tissue oxygenation that may be involved in disease processes, including glaucoma. Ultimately, the model framework presented in this study will facilitate future comparisons to sectorial-specific clinical data to better assess the role of impaired blood flow regulation in ocular disease.
Metabolic Signaling in a Theoretical Model of the Human Retinal Microcirculation
(MDPI, 2021) Arciero, Julia; Fry, Brendan; Albright, Amanda; Mattingly, Grace; Scanlon, Hannah; Abernathy, Mandy; Siesky, Brent; Verticchio Vercellin, Alice; Harris, Alon; Mathematical Sciences, School of Science
Impaired blood flow and oxygenation contribute to many ocular pathologies, including glaucoma. Here, a mathematical model is presented that combines an image-based heterogeneous representation of retinal arterioles with a compartmental description of capillaries and venules. The arteriolar model of the human retina is extrapolated from a previous mouse model based on confocal microscopy images. Every terminal arteriole is connected in series to compartments for capillaries and venules, yielding a hybrid model for predicting blood flow and oxygenation throughout the retinal microcirculation. A metabolic wall signal is calculated in each vessel according to blood and tissue oxygen levels. As expected, a higher average metabolic signal is generated in pathways with a lower average oxygen level. The model also predicts a wide range of metabolic signals dependent on oxygen levels and specific network location. For example, for high oxygen demand, a threefold range in metabolic signal is predicted despite nearly identical PO2 levels. This whole-network approach, including a spatially nonuniform structure, is needed to describe the metabolic status of the retina. This model provides the geometric and hemodynamic framework necessary to predict ocular blood flow regulation and will ultimately facilitate early detection and treatment of ischemic and metabolic disorders of the eye.
Modeling acute and chronic vascular responses to a major arterial occlusion
(Wiley, 2022-01) Zhao, Erin; Barber, Jared; Sen, Chandan K.; Arciero, Julia; Mathematical Sciences, School of Science
Objective To incorporate chronic vascular adaptations into a mathematical model of the rat hindlimb to simulate flow restoration following total occlusion of the femoral artery. Methods A vascular wall mechanics model is used to simulate acute and chronic vascular adaptations in the collateral arteries and collateral-dependent arterioles of the rat hindlimb. On an acute timeframe, the vascular tone of collateral arteries and distal arterioles is determined by responses to pressure, shear stress, and metabolic demand. On a chronic timeframe, sustained dilation of arteries and arterioles induces outward vessel remodeling represented by increased passive vessel diameter (arteriogenesis), and low venous oxygen saturation levels induce the growth of new capillaries represented by increased capillary number (angiogenesis). Results The model predicts that flow compensation to an occlusion is enhanced primarily by arteriogenesis of the collateral arteries on a chronic time frame. Blood flow autoregulation is predicted to be disrupted and to occur for higher pressure values following femoral arterial occlusion. Conclusions Structural adaptation of the vasculature allows for increased blood flow to the collateral-dependent region after occlusion. Although flow is still below pre-occlusion levels, model predictions indicate that interventions which enhance collateral arteriogenesis would have the greatest potential for restoring flow.

Browsing by Author "Arciero, Julia"

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