1357575 - Imaging reactive oxygen species in ischemia-reperfusion injury in swine with multimodal [18F]-ROStrace PET/CT and CMR

Wednesday, January 25, 2023

9:20 AM – 9:30 AM

Location: Silver Pearl 1

Presenting Author(s)

SS

Sophia Swago

PhD Candidate
University of Pennsylvania
Philadelphia, Pennsylvania, United States

Primary Author(s)

SS

Sophia Swago

PhD Candidate
University of Pennsylvania
Philadelphia, Pennsylvania, United States

Co-Author(s)

ET

Elizabeth W. Thompson, BSc

MD-PhD Student
University of Pennsylvania, United States
AL

Annefleur Loth

Medical Student
Amsterdam Medical Center, Netherlands
AB

Abhijit Bhattaru, BA

Medical Student
Rutgers New Jersey Medical School
Ewing, New Jersey, United States
Brianna F. Moon, PhD

Research Fellow
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School
Charlestown, Massachusetts, United States
GF

Giovanni Ferrari, PhD

Associate Professor
Columbia University
New York, New York, United States
EC

Estibaliz Castillero, PhD

Associate Research Scientist
Columbia University
New York, New York, United States
Victor A. Ferrari, MD

Chair, Penn Cardiovascular Imaging Council
Hospital of the University of Pennsylvania and Penn Cardiovascular Institute
Phila., Pennsylvania, United States
RG

Robert C. Gorman, MD

Professor of Surgery
University of Pennsylvania
Philadelphia, Pennsylvania, United States
CT

Cory Tschabrunn, PhD

Assistant Professor
University of Pennsylvania, Massachusetts, United States
RM

Robert Mach, PhD

Professor of Radiology
University of Pennsylvania, United States
JK

Joel Karp, PhD

Professor of Radiologic Physics
University of Pennsylvania, United States
WW

Walter R. Witschey, PhD

Associate Professor of Radiology
University of Pennsylvania
Philadelphia, Pennsylvania, United States
PB

Paco Bravo, MD

Assistant Professor
University of Pennsylvania, United States

Disclosure(s):

Victor A. Ferrari, MD: No financial relationships to disclose

Background: Additional injury may occur after blood flow is restored to ischemic myocardium, and the presence of this ischemia-reperfusion injury (IRI) is predictive of long-term adverse clinical outcomes¹. However, understanding of the molecular underpinnings of IRI remains limited. While reactive oxygen species (ROS) have been shown to increase in cardiomyocytes 60 minutes post-ischemia-reperfusion², the spatial and temporal distribution of ROS after acute injury is unknown. In this study, we directly imaged cardiac ROS activity in vivo in a swine model of subacute IRI using sequential cardiac magnetic resonance (CMR) and PET/CT imaging.

Methods: IRI was induced in three healthy Yorkshire Swine by occlusion of the mid- left anterior descending coronary artery for 180 minutes (N=1) or 90 minutes (N=2) using a balloon catheter, followed by restoration of flow. Three days following IRI, swine were imaged the same day with ECG-gated CMR for late gadolinium enhancement (LGE) using a phase-sensitive inversion recovery (PSIR) segmented gradient echo sequence at 1.5 T (Avanto, Siemens Healthcare) and on the PennPET Explorer using a multitracer protocol that included 82-Rubidium [⁸²Rb] and [¹⁸F]ROStrace³ administered sequentially via IV bolus. Then, 3-dimensional list-mode scans were acquired for 8 and 60 minutes to measure myocardial blood flow (MBF) and in vivo ROS activity respectively.

LGE and PET images were co-registered using MIM 7.1.5. Regions of interest (ROIs) were drawn on LGE images in remote myocardium, infarcted myocardium, and blood pool. Time-activity curves were generated from each ROI and ROStrace fractional uptake rate (FUR [s^-1]) was calculated: FUR= C_T(t)/∫C_a(t)dt where C_T(t) is the tracer concentration in the tissue at time=t, measured at equilibrium, and ∫C_a(t)dt is the arterial input function. ROStrace FUR was corrected for MBF (ml/min/g) using a simple flow model⁴ for ⁸²Rb. Infarct size and microvascular obstruction (MVO) size were quantified using QMass 8.1 (Medis Suite 4.0).

Results: Registered LGE and PET images are shown in Figure 1. Time activity curves (Fig. 2) show the uptake in regions of infarct, remote myocardium, and the blood pool (N=3). MBF-corrected ROStrace FUR in the infarct ranged from 0.24 to 0.32 ml/g and in remote myocardium ranged from 0.09 to 0.17 ml/g (Table 1). Infarct size (% myocardium) measured on LGE ranged from 16.7 to 21.7 and MVO area (% myocardium) in one animal was 3.91. Across all three animals, ROS activity showed a trend of increase in the infarcted compared to remote myocardium.

Conclusion: For the first time, we utilized a comprehensive and complementary protocol using sequential CMR and PET to measure ROS activity in the LGE-defined infarcted and remote myocardium in a swine model of subacute ischemia-reperfusion injury.