IU Indianapolis ScholarWorks :: Browsing by Author "Guidoboni, Giovanna"

Browsing by Author "Guidoboni, Giovanna"

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Analysis of nonlinear poro-elastic and poro-visco-elastic models
(Springer, 2016-12) Bociu, Lorena; Guidoboni, Giovanna; Sacco, Riccardo; Webster, Justin T.; Department of Mathematical Sciences, School of Science
We consider the initial and boundary value problem for a system of partial differential equations describing the motion of a fluid–solid mixture under the assumption of full saturation. The ability of the fluid phase to flow within the solid skeleton is described by the permeability tensor, which is assumed here to be a multiple of the identity and to depend nonlinearly on the volumetric solid strain. In particular, we study the problem of the existence of weak solutions in bounded domains, accounting for non-zero volumetric and boundary forcing terms. We investigate the influence of viscoelasticity on the solution functional setting and on the regularity requirements for the forcing terms. The theoretical analysis shows that different time regularity requirements are needed for the volumetric source of linear momentum and the boundary source of traction depending on whether or not viscoelasticity is present. The theoretical results are further investigated via numerical simulations based on a novel dual mixed hybridized finite element discretization. When the data are sufficiently regular, the simulations show that the solutions satisfy the energy estimates predicted by the theoretical analysis. Interestingly, the simulations also show that, in the purely elastic case, the Darcy velocity and the related fluid energy might become unbounded if indeed the data do not enjoy the time regularity required by the theory.
Artificial Intelligence to Aid Glaucoma Diagnosis and Monitoring: State of the Art and New Directions
(MDPI, 2022) Nunez, Roberto; Harris, Alon; Ibrahim, Omar; Keller, James; Wikle, Christopher K.; Robinson, Erin; Zukerman, Ryan; Siesky, Brent; Verticchio, Alice; Rowe, Lucas; Guidoboni, Giovanna; Ophthalmology, School of Medicine
Recent developments in the use of artificial intelligence in the diagnosis and monitoring of glaucoma are discussed. To set the context and fix terminology, a brief historic overview of artificial intelligence is provided, along with some fundamentals of statistical modeling. Next, recent applications of artificial intelligence techniques in glaucoma diagnosis and the monitoring of glaucoma progression are reviewed, including the classification of visual field images and the detection of glaucomatous change in retinal nerve fiber layer thickness. Current challenges in the direct application of artificial intelligence to further our understating of this disease are also outlined. The article also discusses how the combined use of mathematical modeling and artificial intelligence may help to address these challenges, along with stronger communication between data scientists and clinicians.
Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions
(PLOS, 2019-08-14) Salerni, Fabrizia; Repetto, Rodolfo; Harris, Alon; Pinsky, Peter; Prud'homme, Christophe; Szopos, Marcela; Guidoboni, Giovanna; Ophthalmology, School of Medicine
This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight.
Blood circulation and aqueous humor flow in the eye : multi-scale modeling and clinical applications
(2016-06-14) Cassani, Simone; Guidoboni, Giovanna; Arciero, Julia Concetta; Harris, Alon
Glaucoma is a multi-factorial ocular disease associated with death of retinal ganglion cells and irreversible vision loss. Many risk factors contribute to glaucomatous damage, including elevated intraocular pressure (IOP), age, genetics, and other diseases such as diabetes and systemic hypertension. Interestingly, alterations in retinal hemodynamics have also been associated with glaucoma. A better understanding of the factors that contribute to these hemodynamic alterations could lead to improved and more appropriate clinical approaches to manage and hopefully treat glaucoma patients. In this thesis, we develop several mathematical models aimed at describing ocular hemodynamics and oxygenation in health and disease. Precisely we describe: (i) a time-dependent mathematical model for the retinal circulation that includes macrocirculation, microcirculation, phenomenological vascular regulation, and the mechanical effect of IOP on the retinal vasculature; (ii) a steady-state mathematical model for the retinal circulation that includes macrocirculation, microcirculation, mechanistic vascular regulation, the effect of IOP on the central retinal artery and central retinal vein, and the transport of oxygen in the retinal tissue using a Krogh cylinder type model; (iii) a steady-state mathematical model for the transport of oxygen in the retinal microcirculation and tissue based on a realistic retinal anatomy; and (iv) a steady-state mathematical model for the production and drainage of aqueous humor (AH). The main objective of this work is to study the relationship between IOP, systemic blood pressure, and the functionality of vascular autoregulation; the transport and exchange of oxygen in the retinal vasculature and tissue; and the production and drainage of AH, that contributes to the level of IOP. The models developed in this thesis predict that (i) the autoregulation plateau occurs for different values of IOP in hypertensive and normotensive patients. Thus, the level of blood pressure and functionality of autoregulation affect the changes in retinal hemodynamics caused by IOP and might explain the inconsistent outcomes of clinical studies; (ii) the metabolic and carbon dioxide mechanisms play a major role in the vascular regulation of the retina. Thus, the impairment of either of these mechanisms could cause ischemic damage to the retinal tissue; (iii) the multi-layer description of transport of oxygen in the retinal tissue accounts for the effect of the inner and outer retina, thereby improving the predictive ability of the model; (iv) a greater reduction in IOP is obtained if topical medications target AH production rather that AH drainage and if IOP-lowering medications are administrated to patients that exhibit a high initial level of IOP. Thus, the effectiveness of IOP-lowering medications depend on a patient’s value of IOP. In conclusion, the results of this thesis demonstrate that the insight provided by mathematical modeling alongside clinical studies can improve the understanding of diseases and potentially contribute to the clinical development of new treatments.
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.
A hybridizable discontinuous Galerkin method for nonlinear porous media viscoelasticity with applications in ophthalmology
(2016-12) Prada, Daniele; Guidoboni, Giovanna
The interplay between biomechanics and blood perfusion in the optic nerve head (ONH) has a critical role in ocular pathologies, especially glaucomatous optic neuropathy. Elucidating the complex interactions of ONH perfusion and tissue structure in health and disease using current imaging methodologies is difficult, and mathematical modeling provides an approach to address these limitations. The biophysical phenomena governing the ONH physiology occur at different scales in time and space and porous media theory provides an ideal framework to model them. We critically review fundamentals of porous media theory, paying particular attention to the assumptions leading to a continuum biphasic model for the phenomenological description of fluid flow through biological tissues exhibiting viscoelastic behavior. The resulting system of equations is solved via a numerical method based on a novel hybridizable discontinuous Galerkin finite element discretization that allows accurate approximations of stresses and discharge velocities, in addition to solid displacement and fluid pressure. The model is used to theoretically investigate the influence of tissue viscoelasticity on the blood perfusion of the lamina cribrosa in the ONH. Our results suggest that changes in viscoelastic properties of the lamina may compromise tissue perfusion in response to sudden variations of intraocular pressure, possibly leading to optic disc hemorrhages.
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.
IUPUI Center for Mathematical Biosciences
(Office of the Vice Chancellor for Research, 2010-04-09) Boukai, Benzion; Chin, Ray; Dziubek, Andrea; Fokin, Vladimir; Ghosh, Samiran; Kuznetsov, Alexey; Li, Fang; Li, Jiliang; Rader, Andrew; Rubchinsky, Leonid; Sarkar, Jyotirmoy; Guidoboni, Giovanna; Worth, Robert; Zhu, Luoding
At-Large Mission: “to serve as an umbrella center for spearheading research and programmatic activities in the general bio-mathematics area” • promote and facilitate faculty excellence in mathematical and Computational research in the biosciences; • provide a mechanism and an environment that fosters collaborative research activities across the mathematical sciences and the life and health sciences schools at IUPUI— specifically with the IUSOM; • provide foundations and resources for further strategic development in targeted areas of mathematical and computational biosciences research; and • create greater opportunities and increase competitiveness in seeking and procuring extramural funding.
Multiscale mathematical modeling of ocular blood flow and oxygenation and their relevance to glaucoma
(2016-06-14) Carichino, Lucia; Guidoboni, Giovanna; Harris, Alon; Arciero, Julia Concetta
Glaucoma is a multifactorial ocular disease progressively leading to irreversible blindness. There is clear evidence of correlations between alterations in ocular hemodynamics and glaucoma; however, the mechanisms giving rise to these correlations are still elusive. The objective of this thesis is to develop mathematical models and methods to help elucidate these mechanisms. First, we develop a mathematical model that describes the deformation of ocular structures and ocular blood flow using a reduced-order fluid-structure interaction model. This model is used to investigate the relevance of mechanical and vascular factors in glaucoma. As a first step in expanding this model to higher dimensions, we propose a novel energy-based technique for coupling partial and ordinary differential equations in blood flow, using operator splitting. Next, we combine clinical data and model predictions to propose possible explanations for the increase in venous oxygen saturation in advanced glaucoma patients. We develop a computer-aided manipulation process of color Doppler images to extract novel waveform parameters to distinguish between healthy and glaucomatous individuals. The results obtained in this work suggest that: 1) the increase in resistance of the retinal microcirculation contributes to the influence of intraocular pressure on retinal hemodynamics; 2) the influence of cerebrospinal fluid pressure on retinal hemodynamics is mediated by associated changes in blood pressure; 3) the increase in venous oxygen saturation levels observed among advanced glaucoma patients depends on the value of the patients’ intraocular pressure; 4) the normalized distance between the ascending and descending limb of the ophthalmic artery velocity profile is significantly higher in glaucoma patients than in healthy individuals.
Ocular blood flow as a clinical observation: Value, limitations and data analysis
(Elsevier, 2020) Harris, Alon; Guidoboni, Giovanna; Siesky, Brent; Mathew, Sunu; Verticchio Vercellin, Alice C.; Rowe, Lucas; Arciero, Julia; Radiology and Imaging Sciences, School of Medicine
Alterations in ocular blood flow have been identified as important risk factors for the onset and progression of numerous diseases of the eye. In particular, several population-based and longitudinal-based studies have provided compelling evidence of hemodynamic biomarkers as independent risk factors for ocular disease throughout several different geographic regions. Despite this evidence, the relative contribution of blood flow to ocular physiology and pathology in synergy with other risk factors and comorbidities (e.g., age, gender, race, diabetes and hypertension) remains uncertain. There is currently no gold standard for assessing all relevant vascular beds in the eye, and the heterogeneous vascular biomarkers derived from multiple ocular imaging technologies are non-interchangeable and difficult to interpret as a whole. As a result of these disease complexities and imaging limitations, standard statistical methods often yield inconsistent results across studies and are unable to quantify or explain a patient's overall risk for ocular disease. Combining mathematical modeling with artificial intelligence holds great promise for advancing data analysis in ophthalmology and enabling individualized risk assessment from diverse, multi-input clinical and demographic biomarkers. Mechanism-driven mathematical modeling makes virtual laboratories available to investigate pathogenic mechanisms, advance diagnostic ability and improve disease management. Artificial intelligence provides a novel method for utilizing a vast amount of data from a wide range of patient types to diagnose and monitor ocular disease. This article reviews the state of the art and major unanswered questions related to ocular vascular anatomy and physiology, ocular imaging techniques, clinical findings in glaucoma and other eye diseases, and mechanistic modeling predictions, while laying a path for integrating clinical observations with mathematical models and artificial intelligence. Viable alternatives for integrated data analysis are proposed that aim to overcome the limitations of standard statistical approaches and enable individually tailored precision medicine in ophthalmology.

Browsing by Author "Guidoboni, Giovanna"

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