Works in Progress: University of Michigan

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1 Works in Progress: University of Michigan Adam L. Dorfman, MD Professor, Departments of Pediatrics and Radiology University of Michigan Medical School

2 Disclosures No financial disclosures Gadolinium contrast is not FDA approved for MR angiography 2

3 Project #1 Image-based Multi-scale Modeling Framework of the Cardiopulmonary System: Longitudinal Calibration and Assessment of Therapies in Pediatric Pulmonary Hypertension Alberto Figueroa, Ph.D. Collaborators at Michigan State, Drs. Baek and Lee (mechanical engineering), Ohio State, Dr. Gajarski (cardiology) Funded by NIH UO1 HL

4 Disclosures I am not an Engineer 4

5 Disclosures I like pictures 5

6 Disclosures I like pictures 6

7 Disclosures I don t particularly like this Stress Baek, Valentin & Humphrey, Ann Biomed Eng

8 Pulmonary Hypertension Rare disease in pediatrics Severe, chronic disease with high mortality rate Pathophysiology is complex Changes occur to hemodynamics that describe the circulation Changes occur to the structures of the cardiovascular system Changes to pulmonary vasculature and right ventricle over time 8

9 Pulmonary Hypertension Aims of our study: Produce Multi-scale computational model of the cardio-pulmonary circulation that accounts for hemodynamics of pulmonary hypertension Include in this computational model the effects of growth and remodeling of the cardio-pulmonary system over time Calibrate this model using hemodynamic data acquired via cath, CMR and echo in a longitudinal fashion to account for both instantaneous hemodynamics and change in substrate over time Apply this multiscale framework to investigate the effects of pharmacologic therapies for pulmonary hypertension 9

10 Pulmonary Hypertension Based on principle of vascular homeostasis Vascular tissue, cells, and fibers adapt such that a constant homeostatic value of stress is maintained Understanding models for behavior of tissue components such as collagen, elastin and smooth muscle allow prediction of growth and remodeling of tissue Multiscale problem in both space and time Hemodynamic loads determine the long-term fate of the tissues Poses a unique modeling challenge Requires multiple data points for a given subject 10

11 Fluid-Solid-Growth Modeling Figueroa, Baek, Taylor & Humphrey, CMAME

12 Courtesy of Dr. Figueroa 12

13 Gathering Data 13

14 Data Gathering CMR Vasculature: 3-D Anatomic imaging with contrast or non-contrast MRA methods Cine imaging of the pulmonary vessels for pulsatility and distensibility Phase contrast imaging for flow analysis 14

15 Data Gathering CMR Cath Vasculature: Heart 3-D Anatomic imaging with contrast or non-contrast MRA methods Cine imaging of the pulmonary vessels for pulsatility and distensibility Phase contrast imaging for flow analysis Cine imaging for function SENC to assess RV strain T1 Mapping/ECV for tissue characteristics Invasive pressure measurements in heart and vessels Repeat measurements under different condition (100% O2, ino, etc.) 15

16 Modeling Cath and MRI physiologic data provide the boundary conditions for the 3-D model derived from anatomic data Courtesy of Dr. Figueroa 16

17 Plans We plan to enroll 20 pulmonary hypertension patients 5 controls (patients s/p heart transplant with normal PVR) Exclude former single ventricle patients Subjects will be studied twice over 5 years for longitudinal data Five have been enrolled and studied at time 0 thus far 17

18 Returning to Objectives The model must be able to describe the different time and space processes associated with evolving hemodynamics, tissue remodeling, and pharmacological interventions Ultimately, the goals are: Risk stratify patients based on parameters from the model Virtual testing of pharmacologic interventions to better understand their long term effects on the pulmonary hypertension patient Hopefully will bring some interesting data back to this meeting in the future! 18

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