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Ischemic Heart Disease Research Program

Ischemic heart disease (IHD) refers to a class of heart disease that stems from reduced oxygen supply to the heart muscle and is the most common cause of death in the western countries. The focus of the program is to better understand IHD from the standpoint of structural, compositional and functional changes to the heart in the early, progressive and terminal stages of the disease using an integrated multidisciplinary approach.

Diagram of Integrated Therapeutics for the Ischemic Heart Disease Research Program includes: Pathology, Cell Biology & Mechanisms; AI-Driven Investigations, Biophysics & Physiology; Cardiac Imaging; Clinical Trials; and Physics & Engineering.

This is accomplished with sophisticated imaging technologies, particularly MRI and PET, biomedical engineering methods, molecular Immunopathological studies, multi-omics and informatics.

Funded both by the National Institutes of Health and the American Heart Association, the IHD program has a long-term goal of early diagnosis of disease through development of biomarkers for non-invasive, early and reliable detection of myocardial injury in the progressive phase of disease advancement. The major thematic areas of foci that are driven to advance integrated therapeutics for IHD are represented in the corresponding illustration.

Integrated Therapeutics

The program builds on the knowledge gained from the multifaceted interdisciplinary investigations into ischemic heart disease, to develop:

  • Targeted therapeutics that will maximize cardio-protection in myocardial infarction. Therapeutics are being evaluated through in vitro as well as in vivo experiments.
  • Non-invasive diagnostic tools that will compliment imaging diagnostics and allow for development of timely implementation of mitigation strategies.
  • Point-of-care devices that improve the efficacy of disease management.

Developing personalized targeted treatment and integrating the tools listed above have the potential to radically change the standard of care in IHD. Learn more about:


Featured Publication

Intramyocardial Hemorrhage Drives Fatty Degeneration of Infarcted Myocardium

Cokic I, Chang SF, Nair AR, Guan X, YangHJ, Liu T, Chen Y, HernandoD, Sykes J, Tang R, Butler J, Dohnalkova A, Kovarik L, Finney R, Kali A, Sharif B, Bouchard L, Gupta R, Krishnam MS, Vora K, Tamarappoo B, Howarth A, Kumar A, Francis J, Reeder SB, Wood JC, Prato FS, Dharmakumar R. Nat Commun13, 6394 (2022).

graphic from this publication shows an overarching model of how hemorrhagic infarction promotes chronic heart failure via fat deposition

Cardiac Imaging

A key aspect of our cardiac imaging focus is the technical development of methodologies to overcome unmet needs in caring for ischemic heart disease patients. Current emphasis include:

  • Contrast-free (native) imaging
  • Detection and optimization of image contrast
  • Fast/robust time-resolved 3D imaging in the presence of motion (cardiac, respiratory and flow)
  • Optimized MRI/PET acquisitions

We have made several seminal contributions to the field, including:

  • Imaging oxygenation changes in the heart
  • Arterial CO2 as an alternate stressor to pharmacological agents
  • Enabled imaging of myocardial infarctions without contrast agents
  • Development of methods exposing mechanisms accelerating chronic heart failure.
  • Jointly characterized ischemic myocardium through simultaneous magnetic resonance imaging (MRI)- and positron emission tomography (PET)
  • Developed novel imaging markers of heart failure and ventricular arrhythmia in IHD

Featured Publication

Influence of Myocardial Hemorrhage on Staging of Reperfused Myocardial Infarctions With T2 Cardiac Magnetic Resonance Imaging: Insights Into the Dependence on Infarction Type With Ex Vivo Validation

Wang G, Yang HJ, Cokic I, Qi Y, Xie G, Francis J, Li S, Dharmakumar R. J Am Coll Cardiol Img.2019 Apr, 12 (4) 693–703.

graphic from this publication shows LGE + noncontrast-enhanced relaxation maps of canine hearts in acute and chronic phases of reperfused MI at 1.5-T

Physics and Engineering

Physics and engineering play an integral part in the conceptualization, design and development of algorithms, tools and instrumentation that support multiple areas of IHD investigations. Key areas of focus in physics for our team include:

  • Magnetic resonance relaxometry
  • Electrical conduction in tissue
  • Fluid mechanics in small and large blood vessels
Engineering efforts are focused on:
  • Advanced imaging and reconstruction strategies
  • Development and optimization of image contrast
  • Development of devices and instrumentation to monitor and deliver therapies.

Featured Publication

Iron Deposition Following Chronic Myocardial Infarction as a Substrate for Cardiac Electrical Anomalies: Initial Findings in a Canine Model

Cokic I, Kali A, Wang X, Yang H, Tang RLQ, Thajudeen A, Shehata M, Amorn AM, Enzhao L, Stewart B, Bennett N, Harlev D, Tsaftaris SA, Jackman WM, Chugh S, and Dharmakumar R. PLoS One 2013 Sep 16;8(9):e73193.

graphic from this publication shows imaging scans of the association between ILPs and iron deposition following myocardial infarction

Artificial Intelligence-Driven Investigations

The artificial intelligence (A.I.)-driven investigations into IHD is tightly interwoven with cardiac imaging as well as use of A.I. to develop predictive models that can be embedded in detection systems. Key advances (and ongoing work) include:

  • Amplification of native T1 image contrast via data-driven native contrast mapping for rapid visual detection of chronic myocardial infarction without contrast media
  • Automated detection of and characterization of coronary artery collaterals with deep learning
  • Predictive modeling outcomes in MI patients using explainable-A.I.

Featured Publication

Amplifying Native-T1-based Image Contrast via Data-Driven Native Modelling for Rapid Visual Detection of Chronic Myocardial Infarction without Contrast Media: A Proof-of-Concept Preclinical Study with Ex-vivo Validation (Under Review, July 2023)

Yousef K, Zhang X, Yoosefian G, Chen Y, Fai-Chan S, Yang HJ, Vora K, Howarth AG, Kumar A, Sharif B, Dharmakumar R.

graphic from this publication shows data driven native mapping with a deep-learning modeling pipeline

Pathology, Cell Biology and Mechanisms

The IHD research program has a robust team of faculty investigators who specialize in pathology, cell/molecular biology, with an emphasis on omic studies. We are deliberate in our investigations into understanding the pathological changes the heart undergoes during the progression of ischemic heart disease. We conduct research into fundamental processes driving pathological changes observable across multitudes of spatial scales [visual (cm), noninvasive imaging (mm), histology (um), electron microscopy (nm)]. We use observations and fundamental cell biology paradigms to develop and refine mechanisms that drive pathophysiological processes. Our team is focused on various aspects of myocardial infarction which broadly span:

  • Biomarker development
  • Drug discovery and testing
  • Cardiac immunopathology
  • Neuro-Myocardial interaction

Salient areas of research include: 

  • Identifying a set of time-dependent signaling cascade events initiated by the red-blood-cell derived iron to drive fat depositions in the myocardial infarction territory during intracardial hemorrhage using lipidomic and proteomic analysis
  • Neuromuscular interactions following reperfused myocardial infarction Studying the immune responses in myocardial infarction
  • Development of bioinformatic tools from immunopathological sections to evaluate disease progression as well as efficacy of therapeutics

Our contributions to date include the:

  • Inception of the “Crystal hypothesis,” driving post infarction heart failure
  • Processes driving lipomatous metaplasia of infarcted myocardium, an adverse physiological response to myocardial infarction
  • Delineation of Infarct expansion in the setting of hemorrhagic myocardial infarction
  • Novel testing of iron-chelation therapy to mitigate chronic heart failure

Featured Publication

Persistent Microvascular Obstruction Culminates in the Confluence of Iron Oxide Nanocrystal Formation, Proinflammatory Burden and Adverse Left Ventricular Remodeling in Chronic Myocardial Infarction

Kali A, Cokic I, Tang R, Dohnalkova A, Kovarik L, Yang HJ, Kumar A, Prato FS, Wood JC, Underhill D, Marban E, Dharmakumar R. Circulation: Cardiovascular Imaging 2016 Nov;9(11). pii: e004996

graphic from this publication shows chronic iron deposition in reperfusion myocardial infarctions

Biophysics and Physiology

Discovery work is an important aspect of our investigations into ischemic heart disease. In addition to developing pathophysiological insights, the program aspires to develop novel biophysical and physiological insights into cardiac function. Active investigations include:

  • Time dependence of myocardial oxygenation throughout cardiac cycle in health and IHD
  • Effect of arterial blood gases on red blood cells, vascular endothelium and cardiomyocytes
  • Modulation of mitochondrial function in response to temperature changes
  • Mechanisms modulating rest perfusion in the heart
Our contributions to date include:
  • Delineation of cyclic blood volume and oxygenation changes at rest and during pharmacological stress
  • Hypercapnia as a potent coronary vasodilator
  • Rest perfusion in myocardial infarction

Featured publication

Accurate Needle-Free Assessment of Myocardial Oxygenation for Ischemic Heart Disease

Yang HJ, Ilkary O, Dey D, Sykes J, Klein M, Butler J, Kovacs MS, Sobczyk O, Cokic I, Slomka P, Bi X, Li D, Tighiouart M, Prato FS, Tsaftaris SA, Fisher JA, Dharmakumar R. Science Translational Medicine. 2019 May 29;11(494).

publication highlight for accurate needle-free assessment. Diagram shows application of cardiac fMRI approach for reliable identification of healthy myocardium

Clinical Trials

We are leading multiple clinical trials across the globe with multi-center investigations into myocardial infarction, novel IHD diagnosis methods and AI applications in IHD. Our primary clinical trial focus areas include:

  • Interventional trials fueled by novel therapeutic target
  • Diagnostics trials for detection of disease
  • Predictive models to identify most vulnerable IHD patients
Our contributions to date include:
  • Identification of biomarkers that enable detection of hemorrhagic myocardial infarctions
  • Modulation in myocardial oxygenation in response to hypercapnia, a buildup of carbon dioxide in the blood stream
  • Detection of chronic myocardial infarction without exogenous contrast media

Featured Publication

A Multi-Center Study on the Diagnostic Performance of Native-T1 CMR of Chronic Myocardial Infarctions at 3T

Wang G, Lee S, Yang Q, Sadras V, Patel S, Yang HJ, Sharif B, Kali A, Cokic I, Tighiouart M, Collins J, Li D, Berman DS, Chang HJ, Dharmakumar R. Circulation: Cardiovascular Imaging, 2020;13(6).

graphic from this publication shows representative native T1 maps and late gadolinium enhancement images from patients with left anterior, left circumflex nad right coronary artery infarctions at 3.0T

Publications, Funding and Inventions

Select Publications (past five years)

Select Funding (past five years)

  • NIH 1R01-HL147133-01 (MPI: Dharmakumar R (contact); Francis J)
    Mechanistic Insights to a Translatable Therapy for Acute Reperfused Hemorrhagic Myocardial Infarctions
  • NIH R01-HL148788 (PI: Dharmakumar R)
    Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents
  • NIH R01-HL133407 (MPI: Dharmakumar R (contact); Underhill)
    Developing a MRI-guided Disease-Modifying Therapy for Post Infarction Chronic Heart Failure
  • NIH R01-HL136578 (PI: Dharmakumar R)
    An Accurate Non-Contrast-Enhanced Cardiac MRI Method for Imaging Chronic Myocardial Infarctions: Technical Developments to Rapid Clinical Validation

Select Patents (past five years)

  • Dharmakumar R and Hsin-Jung Yang. Robust Myocardial Blood Oxygen Level Dependent Magnetic Resonance Imaging with Improved Patient Comfort. (Filed: Sep 30, 2016; Granted: Sept 9, 2022) US11,445,912 B2
  • Dharmakumar R. Methods for reducing ischemia-reperfusion injury. (Filed: Aug 05, 2014; Granted: Nov 11, 2019). US2016/0166606 A1
  • Dharmakumar R and Cokic I. Assessment of Iron Deposition Post Myocardial Infarction as a Marker of Myocardial Hemorrhage. USPTO Application Number: 14/125,307 filed on June 13, 2011. Assignee: Cedars-Sinai Medical Center. Awarded February 27, 2020.
  • Dharmakumar R and Cokic I. Assessment of Iron Deposition Post Myocardial Infarction as a Marker of Myocardial. Continuation in Part, Application Number: 15/064,817 filed on March 9, 2016. Assignee: Cedars-Sinai Medical Center. Awarded February 27, 2020.
  • Dharmakumar R, Li D, Tsaftaris SA. Assessment of Coronary Heart Disease with Carbon Dioxide. USPTO Application Number: (Filed: May 07, 2012; Granted: Sept 13, 2022) US 11,439,309 B2

Ischemic Heart Disease Scientists

Principal Investigator
60337-Dharmakumar, Rohan

Rohan Dharmakumar, PhD

Executive Director of the Krannert Cardiovascular Research Center

Read Bio Rohan Dharmakumar, PhD

Associate Professors

Ramesh Subramanian, PhD

Associate Research Professor of Medicine

Assistant Professors

Gregory Anthony, PhD

Assistant Professor of Radiology & Imaging Sciences

Shing Fai Chan, PhD

Assistant Research Professor of Medicine

Gabriel Gruionu, PhD

Assistant Research Professor of Medicine

Nithya Jambunathan, PhD

Assistant Research Professor of Medicine

Dhirendra P. Singh, PhD

Assistant Research Professor of Medicine

Keyur Vora, MD

Assistant Research Professor of Medicine

Khalid Youssef, PhD

Senior Scientist in Medicine

Senior Scientists

Richard L. Tang, MD

Associate Scientist in Medicine

Research Staff

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Garrett Hunter, MS

Research Manager

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Faris Khan, BMSc

Biomedical Data Assistant

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Chandana Saha, PhD, MPH

Clinical Research Coordinator



Pedro Giro, MD

Pedro Giro, MD

Cardiovascular Disease Fellow

61319-Guan, Xingmin

Xingmin Guan, PhD

Postdoctoral Fellow in Medicine

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Chirag D. Shah, MD, MPH

Anderson Cardiovascular Innovation Fellow


Graduate Students

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Ghazal Yoosefian, BS

MS Candidate

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Yuheng Chris Huang, MS

PhD Candidate

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Xinheng James Zhang, MS

PhD Candidate


Undergraduate Students

Faculty Profile Picture Placeholder IUSM Logo

Elizabeth Murphy

Purdue University


High School Students

portrait of sanjana dharmakumar

Sanjana Dharmakumar


Research Alumni

2005 - Present

Jain Mangalathu Arumana, BS, Scientist, Siemens Healthineers

Xiangzhi Zhou, PhD, Scientist, Canon Medical

Veronica Rundell, PhD, Post-doctoral Fellow

Swati Gupta, MS, Graduate Student

Ying Liu, MD/PhD, Post-doctoral Fellow

Sotirios A Tsaftaris, PhD, Chaired Professor, University of Edinburgh, UK

Anindya Sen, PhD, Post-doctoral fellow

Ivan Cokic, MD, Assistant Professor, Cedars-Sinai Medical Center

Teodora Lakic, Summer/Undergrad Student

Ryan Middleton, Summer/Undergrad Student

Vignesh Sadras, Summer/Undergrad Student

Suraj Patel, BS, Summer Medical Student

Avinash Kali, PhD, Associate Director, Bristol Myers

Hsin-Jung Yang, PhD, Assistant Professor, Cedars-Sinai Medical Center

Andreas Kumar, MD, MSc, Associate Professor, Northern Ontario School of Medicine

Past and Present Collaborators

Central Indiana Collaborations

Ankur Kalra, MD, Franciscan Health

National Collaborations


Rajesh Gupta, MD, University of Toledo

Scott Reeder, MD/PhD, University of Wisconsin

Diego Hernando, PhD, University of Wisconsin


Nikolas Frangogiannis, MD, Albert Einstein University


Joseph Francis, PhD, Louisiana State University


Daniel Berman, MD, Cedars-Sinai MC

Louis Bouchard, University of  California, Los Angeles (UCLA)

Sumeet Chugh, MD, Cedars-Sinai MC

Damini Dey, PhD, Cedars-Sinai MC

Alice Dohnalkova, Pacific Northwest National Laboratory (PNNL)

Jennifer Van Eyk, PhD, Cedars-Sinai MC

Hui Han, PhD, Cedars-Sinai MC

Libor Kovarik, PhD, Pacific Northwest National Laboratory (PNNL)

Debiao Li, PhD, Cedars-Sinai MC

Daniel Luthringer, MD, Cedars-Sinai MC

Eduardo Marban, MD/PhD, Cedars-Sinai MC

Prediman K Shah, MD, Cedars-Sinai MC

Piotr Slomka, PhD, Cedars-Sinai MC

Balaji Tamarappoo, MD/PhD, University of Arizona

David Underhill, PhD, Cedars-Sinai MC

John Wood, MD/PhD, University of Southern California

Hsin-Jung Yang, Cedars-Sinai MC

International Collaborations


Joseph A Fisher, University of Toronto

Andrew Howarth, MD/PhD, University of Calgary

Andreas Kumar, MD, Northern Ontario School of Medicine

Michael Kovacs, PhD, Lawson Health Research Institute

Frank Prato, PhD, Lawson Health Research Institute

James White, MD, University of Calgary

United Kingdom

Vanessa Ferreria, MD/PhD, Oxford University

Pier Masci, MD, Kings College

Mayooran Shanmuganathan, MD/PhD, Oxford University

Sotirios Tsaftaris, University of Edinburgh, UK


Yang Qi, MD/PhD, Beijing, China

Industry Collaborations

Cook Medical

Janssen Pharmaceutical Companies of Johnson & Johnson

Larmor Bio, LLC

Lipomed AG


Siemens Healthineers

Thornhill Medical