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<p class="MsoNormal"><span style="font-size:13.5pt;font-family:"Arial",sans-serif;color:black"><img width="599" height="171" style="width:6.2395in;height:1.7812in" id="Picture_x0020_2" src="cid:image001.png@01DBA31A.9AE61A10" alt="Dissertation Defense Announcement at the Cullen College of Engineering"></span><span style="font-size:13.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none"><o:p></o:p></span></p>
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<b><span style="font-size:18.0pt;font-family:"Times New Roman",serif;color:#C8102E;mso-ligatures:none">Engineered Approaches Coupled with Imaging of the Heart and Vascular System to Improve Predictive Outcomes, Diagnoses, and Delivery<o:p></o:p></span></b></p>
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<b><span style="font-size:13.5pt;font-family:"Times New Roman",serif;color:black;mso-ligatures:none">Antonio Martino</span></b><span style="font-size:13.5pt;font-family:"Times New Roman",serif;mso-ligatures:none"><o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">April 14, 2025, 10:30 a.m. to 12:20 p.m. (CST)<br>
Location: Engineering Building 1- Room S234, or </span><span style="color:black;mso-ligatures:none"><a href="https://urldefense.com/v3/__https://houstonmethodist.zoom.us/j/98672687980?pwd=puzUIsgoiOYaZlaIWbNFFepPca8Tni.1__;!!LkSTlj0I!FxfpK_pQbdoERrIgS_qiDQX9swDCV1xYw3yfkanxOtcIrwKFpNLoxBtQq344_AKe85fU4JXOCv4WGNZi9QwgQxIVxsI$"><span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:#0563C1">Zoom</span></a></span><span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">
<br>
Passcode: 810649</span><span style="font-size:10.5pt;font-family:"Arial",sans-serif;mso-ligatures:none"><o:p></o:p></span></p>
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<b><span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Committee Chair:</span></b><span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none"><br>
Dr. Richard C. Willson, Ph.D.</span><span style="font-size:10.5pt;font-family:"Arial",sans-serif;mso-ligatures:none"><o:p></o:p></span></p>
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<b><span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Committee Members:</span></b><span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none"><br>
Dr. Carly S. Filgueira, Ph.D. | Dr. Chin-Yo Lin, Ph.D. | Dr. Pieremanuele Canepa, Ph.D. |
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Dr. Rohith K. Reddy, Ph.D.</span><span style="font-size:10.5pt;font-family:"Arial",sans-serif;mso-ligatures:none"><o:p></o:p></span></p>
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<b><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:#C8102E;mso-ligatures:none">Abstract<o:p></o:p></span></b></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">The cardiovascular system’s complexity and remodeling response to disease pathology highlight the dynamic behavior necessary for the body to adapt or compensate to
external stressors. This response by the cardiac and vascular system to its changing environment further complicates our ability to rapidly diagnose disease abnormalities and deliver timely therapeutics to prevent disease progression. Addressing these challenges
requires innovative solutions to improve predictive modeling, enhance diagnostic precision, and optimize therapeutic interventions.
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Computational modeling provides test conditions for simulating changing vascular flow dynamics, tissue mechanics, and mass transport, yielding predictive insights to
guide treatment. Concurrently, imaging technologies, such as computed tomography (CT) and magnetic resonance imaging (MRI), which serve as the gold standards for structural and functional clinical assessments, are not always feasible for intraprocedural evaluation.
The lack of real-time, intraoperative imaging modalities limits precision and a direct means to confirm treatment efficacy.
<o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Beyond diagnostics, improving drug delivery to the heart and vascular system is crucial, as common administration routes suffer from limited retention, reducing long-term
therapeutic efficacy. Optimizing drug localization and sustaining therapeutic release within the myocardium is fundamental to advance precision-targeted therapies. This dissertation integrates computational modeling, imaging technologies, and engineered drug
delivery strategies to improve predictive outcomes, diagnoses, and therapeutic delivery. A computational modeling approach based on experimentally acquired parameters is described as a preclinical means to characterize coronary anatomy and hemodynamics. Using
morphometric analysis and computational fluid dynamics (CFD) derived from micro-computed tomography (micro-CT) vascular reconstructions, a novel portfolio of geometric and hemodynamic descriptors is presented to provide insights into species-specific arterial
characteristics. In parallel, to study the remodeling of peripheral and pathological vasculature, a finite element-based transport model, the Kojic Transport Model (KTM), is utilized to predict intratumoral pressure and velocity distributions in solid murine
Lewis lung carcinoma (LLC) tumors. Experimentally derived heat maps capturing vascular density, capillary diameter, and permeability are integrated into the computational network, offering a quantitative framework to assess the influence of tumor vascular
dynamics on mass transport. <o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">With respect to innovative imaging solutions, the present work also investigates the feasibility of photoacoustic-ultrasound (PA-US) imaging for real-time procedural
guidance during cardiac interventions. Feasibility of direct epicardial PA-US imaging is demonstrated in healthy and ablated porcine (i.e., intraprocedural lesions were made using radiofrequency ablation (RFA)). Data supports that when compared to conventional
US transducer handheld imaging, stand-off imaging, and integration of a custom 3D-printed suction coupler without and with vacuum the mean axial displacements were significantly reduced from 0.89, 0.49, 0.49, versus 0.15 mm, respectively (p-value ˜8.65e-7).
Comparing the coupler without suction to that with suction, applied lateral interframe displacement reduced from 4.58 to 2.01 mm, respectively (p-value = 5.07e-23) with overall reduced cardiac tissue motion. PA-US based measurements of RFA lesion dimensions
matched (<0.7 mm error) gross pathologic assessment, yielding in vivo feasibility data to provide intraoperative lesion dimensions.
<o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Moving towards treatment approaches, an intramyocardial in situ delivery strategy is evaluated in live porcine models to locally distribute gold nanoshells through
incorporation in a calcium alginate hydrogel (GNS gel). Both transepicardial and transendocardial injections demonstrated successful myocardial retention of the GNS gel for up to 3 hours in acute studies, with 3D reconstruction and volumetric quantification
performed based on CT images. By integrating in silico, in vitro, and in vivo methodologies, this dissertation advances computational modeling, diagnostic imaging, and precision-targeted therapies, accelerating use of these preclinical approaches towards clinical
cardiac and vascular care.<o:p></o:p></span></p>
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<span style="font-size:13.5pt;font-family:"Arial",sans-serif;color:black"><img border="0" width="599" height="82" style="width:6.2395in;height:.8541in" id="Picture_x0020_1" src="cid:image002.png@01DBA31A.9AE61A10" alt="Engineered For What's Next"></span><b><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:#C8102E;mso-ligatures:none"><o:p></o:p></span></b></p>
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