Perfusion, Viability, Edema and Hemorrhage: How it Can (and Should) Change Clinical Practice. Rohan Dharmakumar, Ph.D.

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Perfusion, Viability, Edema and Hemorrhage: How it Can (and Should) Change Clinical Practice Rohan Dharmakumar, Ph.D. Director, Translational Cardiac Imaging Research Associate Director, Biomedical Imaging g Research Institute Associate Professor, Biomedical Sciences Cedars-Sinai Medical Center Cardiovascular MR anatomy & morphology coronary MRA function & wall motion perfusion viability 1

Cardiac MRI Functional Categories n Localization n Morphology n Function n Perfusion -- scouts, slice planning -- dark-blood static anatomy -- cine imaging -- first-pass n Viability -- delayed enhancement n New tissue characterization -- edema, hemorrhage n Angiography -- coronaries MRI Single Heartbeat Scout Images Freely selectable scan planes Cardiac axis image orientation 2

High Resolution Anatomy Cardiac Function Cine at each slice position acquired in a breath-hold of <10 seconds. 3

Contrast Agents n Standard Gd-based contrast agents: Magnevist, Vasovist, Schering Omniscan, Nycomed/Amersham Prohance, Multihance, Bracco OptiMARK, Mallinkrodt Medical n Most are T1-shortening, paramagnetic agents n Typically extra-vascular, extra-cellular. n Rapid diffusion through capillary walls into interstitial space. Contrast-enhanced MRI of the Heart T1-we eighted MR Signal In ntensity contrast Injection (bolus) Normal Myocardium Ischemic Myocardium < 1 min First-Pass time 4

Contrast-Enhanced MRI of Myocardium First-Pass Perfusion Study performed with pharmacological stress Images acquired dynamically during bolus injection of contrast agent Detection of regional reduction in hyperemic flow identifies territories of myocardial ischemia Limitations Typically 2-3 slices can be imaged Limited resolution dark-rim artifacts at times Contrast-Enhanced MRI of Myocardium Recent Advances (Sharif B et al) Stress 3-slice Cartesian FLASH Scan; (apical to basal image series) Stress 6-slice Radial Scan; (apical to basal image series) Spatial Resolution: 2.7mm x 1.9mm Cartesian scan (mid and basal) shows transient dark-rim artifacts. Spatial Resolution: 1.6mm x 1.6mm Radial is free of artifact and as 2x the spatial resolution. 5

Contrast-enhanced MRI of the Heart T1-we eighted MR Signal In ntensity contrast injection Normal Myocardium < 1 min First-Pass Infarcted Myocardium ~10 min Delayed Enhancement time Delayed (Late) Gadolinium Enhancement MRI performed at rest images acquired 10-15 min after contrast injection necrotic Slower clearance of contrast from necrotic regions Nulling of viable myocardium delayed enhancement indicates shows regions of acute and chronic infarctions viable 6

Delayed (Late) Gadolinium Enhancement MRI Contrast-Enhanced MRI of Myocardium LAD Stenosis Hypoperfusion CTO of RCA Transmural inf No Stenosis Subendocardial inf (normal on SPECT) Greenwod et al Lancet 2012 7

Contrast-Enhanced MRI of Myocardium prospective trial 752 patients ~40% CHD Largest CMR trial Sensitivity: 87%* Specificity: 83% PPV: 77% NPV: 91%* Greenwod et al Lancet 2012 Myocardial Edema : Acute Vs. Chronic MI Acute myocardial infarction leads to myocardial edema Non-contrast approach; increased water content increases MR signals of edematous regions permits differentiation between acute & chronic injury LGE Edema (raw) Edema (processed) Hasan et al Circ. 2004 8

Cardiac Phase-Resolved Edema Imaging in Acute MI Patients at 1.5T Healthy Volunteer Patient with inferior wall MI Standard edema image Kumar et al, JACC CV Imaging 2011. Viability image (Necrosis) Myocardial Edema : Myocarditis Edema image Viability image (Necrosis) Friedrich MG et al JACC 2009 (White Paper) 9

Myocardial Edema - Early Marker of Ischemia Edema Viability Raman SV et al JACC 2010 (White Paper) Imaging Marker of Severe I-R Injury: Hemorrhage Reperfusion therapy can lead to no reflow Microvascular obstruction is one of the strongest predictors of adverse outcome in reperfused AMI severe MVO, is associated with intramyocardial hemorrhage Kloner et al Circ 1982 TTC Thioflavin S Current question: what is the role of hemorrhage in infarct remodeling? 10

LV Remodeling : Impact of Intramyocardial Hemorrhage Ganame J et al. Eur Heart 2009 Towards Mechanistic Insight into the Role of Intramyocardial Hemorrhage Kali A et al Circulation: CV Imaging (In Press, 2013) 11

Chronic Iron Deposition from Hemorrhagic Infarctions Kali A et al Circulation: CV Imaging (In Press, 2013) Prolonged Inflammatory Burden from Chronic Iron Deposition Kali A et al Circulation: CV Imaging (In Press, 2013) 12

Summary Powerful imaging modality with unique ability to generate a wide-variety of image contrast Routinely used to assess cardiac function and viability Extensive efforts are being made to make it a one stop shop for comprehensive cardiac exam New non-invasive imaging biomarkers are emerging for the assessment of myocardial injury that does not require exogenous contrast media Faster, more simplified imaging protocols are necessary for greater integration in cardiac imaging 13