PhD, University of Southern California
Senior Administrative Assistant (Research): Tasneem Dalal
Phone: (416) 480-4975
Fax: (416) 480-5003
Email Tasneem Dalal
At A Glance
- Development and validation of quantitative cardiac Magnetic Resonance Imaging (MRI) techniques
- Establishing Image-guidance technologies for cardiac regenerative medicine
- Development of cardiac blood oxygen level dependent (BOLD) imaging
- Detection of microvascular dysfunction in heart disease
- Development of novel preclinical models of heart disease
Dr. Nilesh Ghugre is a Scientist in the Schulich Heart Program at Sunnybrook Research Institute with a focus on imaging in cardiovascular disease. His interest is to develop novel experimental models, coupled with new imaging biomarkers to understand the underlying pathophysiology of disease.
Acute myocardial infarction (or a heart attack) occurs when blood supply to the heart muscle is interrupted. This can destroy heart cells and severely compromise pumping action, resulting in progression toward heart failure. Dr. Ghugre’s research focus is to utilize advanced cardiac MRI biomarkers to characterize the post-infarct “remodeling” process and determine efficacy of novel therapeutic interventions to prevent heart failure. To this end, he is involved in exploring novel experimental models that represent clinical manifestation of heart disease.
His lab is developing MRI tools to probe cardiac pathophysiology parameters including viability, edema and inflammation, hemorrhage, perfusion, strain and microvascular integrity and function. Quantitative T1, T2 and T2-star MRI relaxation mechanisms form the basis for this in vivo tissue characterization, allowing for intra- and inter-subject comparisons. Another focus has been the in vivo assessment of microvascular dysfunction, including abnormal blood flow and perfusion reserve in patients with diabetes or severe infarction. This assessment is done using cardiac blood oxygenation level dependent (BOLD) imaging and arterial spin-label imaging.
His lab is also advancing image-guidance technologies for cardiac regenerative medicine. Given that the human heart lacks regenerative capacity, stem cell-based therapies are a revolutionary means to repopulate lost cells in scar tissue and regain lost contractile function. The lab aims to develop MRI-based technologies that will facilitate minimally invasive and accurate cell delivery to the infarct scar, and image cell fate, tissue response and outcomes, all within the same framework.
MRI Relaxometry and Calibration in Iron-Overloaded Tissues
In 2005, we probed the mechanisms of tissue-iron interaction using MRI relaxation - R1 (1/T1), R2 (1/T2) and multi-echo R2 in fresh human liver biopsy specimens taken from patients with transfusion-dependent anemia. Our study demonstrated that to standardize in vivo calibration (inter-site and -sequence variability), it is important to understand the complex interaction of stored iron particles and water protons within the tissue of interest. In 2011, we were the first to develop a ‘human-derived’ Monte-Carlo framework for probing the underlying biophysics in hepatic iron overload; this demonstrated that knowledge of iron susceptibility/distribution and proton mobility are sufficient to characterize MRI relaxation. In 2015, we demonstrated the use of this model to predict R2- and R2*-iron relationship at higher field strengths in patients. The important application of such tissue-specific models is in the iron calibration of inaccessible organs like heart, where tissue biopsy is not an option. Establishing these models will avoid recalibration in patients for MRI sequence, field strength, iron-chelation therapy and organ.
Quantitative MRI in Myocardial Infarction (MI)
In 2011, we demonstrated that multi-parametric MRI exploiting T2 and T2* relaxation and the BOLD response can assess the state of myocardial tissue (edema, hemorrhage, microvascular reactivity) in vivo in a preclinical model of MI. In 2013, we demonstrated that such characterization can further distinguish the intrinsic remodeling mechanisms based on severity of injury. A figure from this publication was featured on the cover of the journal Magnetic Resonance in Medicine. Thus, quantitative MRI techniques allow regional, longitudinal, and cross-subject comparisons, and hence are powerful tools for evaluating treatment strategies, potentially improving clinical outcomes.
Impact of Hemorrhage in MI
In 2017, we were the first to mechanistically demonstrate that reperfusion hemorrhage is an active contributor to inflammation and myocardial and microvascular damage post-MI, beyond the initial ischemic insult. We have recently further demonstrated that hemorrhagic iron deposition can result in chronic adverse remodeling post-MI as well along with vasodilator dysfunction and matrix alterations in the remote myocardial regions.
Complementing the preclinical framework, our validated MRI protocol has also been successfully translated into our clinical research program. The human studies clearly demonstrate the role of MRI relaxation parameters in monitoring heart disease progression in a quantitative manner. Since 2012, we have had several publications demonstrating the utility of MRI mapping techniques to evaluate risk factors associated with diabetes including inflammation and microvascular disease. The striking correspondence between clinical and experimental findings has been very encouraging justifying the use of these quantitative MRI protocols for clinical translation.
Imaging for Cardiac Regenerative Medicine
My group has been collaborating with stem cell biologists to determine efficacy of stem cell derived cardiomyocytes in remuscularizing scar tissue to improve outcomes. Using MRI biomarkers for cardiac function and viability, we have shown that these cells can demonstrate successful engraftment in the scar region in an experimental model of MI (published in Stem Cell Reports). To aid accurate cell delivery and improve engraftment, my group is the first to explore an integrative image guidance system utilizing 3D MRI roadmaps and augmented reality (AR) for improving the intraoperative workflow for cell delivery.
- Romagnuolo R, Masoudpoor H, Porta-Sanchez A, Qiang B, Barry J, Qi X, Masse S, Magtibay K, Laskary A, Kawajiri H, Wu J, Sadikov TV, Rothberg J, Panchalingam K, Titus E, Li R-K, Zandstra P, Wright GA, Nanthakumar K, Ghugre NR, Keller G, Laflamme MA. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias, Stem Cell Reports, 2019 May 14;12(5):967-981.
- Do HP, Ramanan V, Qi X; Barry J; Wright GA, Ghugre NR, Nayak KS. Non-contrast Assessment of Microvascular Integrity using Arterial Spin Labeled CMR in a Porcine Model of Acute Myocardial Infarction. J Cardiovasc Magn Reson. 2018 Jul 2;20(1):45.
- Ghugre NR, Pop M, Thomas R, Newbigging S, Qi X, Barry J, Strauss BH, Wright GA. Hemorrhage promotes inflammation and myocardial damage following acute myocardial infarction: Insights from a novel preclinical model and cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson. 2017 July 4;19:50
- Roifman I, Ghugre NR, Zia MI, Farkouh ME, Zavodni A, Wright GA, Connelly KA. Diabetes is an independent predictor of right ventricular dysfunction post ST-elevation myocardial infarction. Cardiovasc Diabetol. 2016 Feb 18;15(1):34.
- Ghugre NR, Doyle EK, Storey P, Wood JC. Relaxivity-iron calibration in hepatic iron overload: Predictions of a Monte Carlo model, Magn Reson Med. 2015 Sep;74(3):879-83
- Ghugre NR, Pop M, Barry J, Connelly KA, Wright GA. Quantitative magnetic resonance imaging can distinguish remodeling mechanisms after acute myocardial infarction based on the severity of ischemic insult. Magn Reson Med. 2013 Oct;70(4):1095–1105.
- Zia MI, Ghugre NR, Connelly KA, Strauss BH, Dick AJ, Wright GA. Characterizing myocardial edema and hemorrhage using quantitative T2 and T2* mapping at multiple time intervals post ST elevation myocardial infarction. Circ Cardiovasc Imaging. 2012 Sep 1;5(5):566–72.
- Ghugre NR, Ramanan V, Pop M, Yang Y, Barry J, Qiang B, Connelly K, Dick AJ, Wright GA. Myocardial BOLD imaging at 3T using quantitative T2: Application in a myocardial infarct model. Magn Reson Med. 2011 Dec;66(6):1739–47.
- Ghugre NR, Ramanan V, Pop M, Yang Y, Barry J, Qiang B, Connelly K, Dick AJ, Wright GA. Quantitative tracking of edema, hemorrhage and microvascular obstruction in sub-acute myocardial infarction in a porcine model by MRI. Magn Reson Med. 2011 Oct;66(4):1129–41.