This mentored career development award will enable the training and career transition of a productive, innovative, successful junior scientist. A key element is training and mentorship by thought-leaders in the field of cardiovascular diagnostic imaging and medicine. The applicant, Dr. Mitsouras, has been trained in computer science, physics, and applied mathematics at Brown and MIT. He is a successful MR physicist with important contributions to the field. He is Assistant Professor of Radiology at Harvard, and the Director of MR Physics and Engineering of the BWH Applied Imaging Science Lab (AISL), directed by Dr. Rybicki. A successful PI and skilled mentor, Dr. Rybicki will enthusiastically support and mentor Dr. Mitsouras to career independence. Noninvasive imaging for patients with coronary artery disease (CAD) is gravitating to CT;the proposed research addresses some of its current limitations in clinical care. The AISL evaluates new CT technologies, and has studied and published the potential of coronary enhancement to extend clinical information. It is recognized that the next leap in clinical cardiac CT is flow quantification;Dr. Mitsouras proposes a transformative new approach to this body of work. For the candidate, the transition from MR basic physics to clinical CT applications creates a large, unmet training need. Classroom based (Harvard/MIT Division of Health Sciences and Technology) and practical imaging based (BWH noninvasive cardiovascular imaging program) training will ideally bridge this gap. This K01 proposal also integrates mentorship from renowned experts who know and are eager to work with Dr. Mitsouras. The team includes Dr. Mel Clouse, an exceptional clinician and mentor, Dr. Xiaochuan Pan, an expert in CT physics, Dr. Tae Bae, an expert in contrast delivery, Dr. Al Lardo, an expert in modeling myocardial perfusion, and Dr. Joao Lima, an expert in advanced clinical applications. This exceptional team will navigate Dr. Mitsouras in a structured research project, capitalizing on their collective expertise and Dr. Mitsouras'existing skills. Together, tey will extend the role of noninvasive CAD imaging by applying innovative methods to extract blood flow from clinical CT angiography. At present, noninvasive access to flow is limited to simulated fluid dynamics using an arterial lumen segmented from clinical images. We advance this field with a novel transition from such CT-based flow, to CT-derived flow: quantitative flow that is derived either directly or indirectly from the spatio-temporal patterns of arterial contrast enhancement observed in vivo. A growing body of literature supports qualitative flow information is embedded in CTA enhancement patterns across an artery. We show these patterns in fact possess smooth space and time variations that are intrinsically linked to flow. By unifying signal processing and pattern recognition with high-performance fluid dynamics modeling, this information will be accessed for the first time to quantify true patient-specific flow and yield lesion-specific hemodynamic metrics such as fractional flow reserve.

Public Health Relevance

A growing body of literature accesses coronary contrast enhancement patterns from CT angiograms with the promise of identifying those patients with compromised blood flow who will benefit from intervention. This career development will provide expert mentorship and an exceptional learning and work environment for a highly productive, innovative basic scientist to achieve career independence as a funded investigator. Potential long-term clinical benefits are novel mathematical formulations and computational technologies that will be translated to noninvasive angiography for enhanced clinical management decisions in patients with coronary artery disease.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Scientist Development Award - Research & Training (K01)
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Special Emphasis Panel (ZEB1-OSR-B (J2))
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Erim, Zeynep
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Brigham and Women's Hospital
United States
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Mitsouras, Dimitris; Lee, Thomas C; Liacouras, Peter et al. (2017) Three-dimensional printing of MRI-visible phantoms and MR image-guided therapy simulation. Magn Reson Med 77:613-622
George, Elizabeth; Barile, Maria; Tang, Anji et al. (2017) Utility and reproducibility of 3-dimensional printed models in pre-operative planning of complex thoracic tumors. J Surg Oncol 116:407-415
Gitsioudis, Gitsios; Chatzizisis, Yiannis S; Wolf, Peter et al. (2017) Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas. Eur Heart J Cardiovasc Imaging 18:19-30
George, E; Liacouras, P; Lee, T C et al. (2017) 3D-Printed Patient-Specific Models for CT- and MRI-Guided Procedure Planning. AJNR Am J Neuroradiol 38:E46-E47
Guenette, Jeffrey P; Himes, Nathan; Giannopoulos, Andreas A et al. (2016) Computer-Based Vertebral Tumor Cryoablation Planning and Procedure Simulation Involving Two Cases Using MRI-Visible 3D Printing and Advanced Visualization. AJR Am J Roentgenol 207:1128-1131
Mitsouras, Dimitris; Mulkern, Robert V; Maier, Stephan E (2016) Multicomponent T2 relaxation studies of the avian egg. Magn Reson Med 75:2156-64
Cai, Tianrun; Giannopoulos, Andreas A; Yu, Sheng et al. (2016) Natural Language Processing Technologies in Radiology Research and Clinical Applications. Radiographics 36:176-91
Ripley, Beth; Kelil, Tatiana; Cheezum, Michael K et al. (2016) 3D printing based on cardiac CT assists anatomic visualization prior to transcatheter aortic valve replacement. J Cardiovasc Comput Tomogr 10:28-36
George, Elizabeth; Giannopoulos, Andreas A; Aghayev, Ayaz et al. (2016) Contrast inhomogeneity in CT angiography of the abdominal aortic aneurysm. J Cardiovasc Comput Tomogr 10:179-83
Chatzizisis, Yiannis S; Toutouzas, Konstantinos; Giannopoulos, Andreas A et al. (2016) Association of global and local low endothelial shear stress with high-risk plaque using intracoronary 3D optical coherence tomography: Introduction of 'shear stress score'. Eur Heart J Cardiovasc Imaging :

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