Lima Lab
Overview
Dr. Lima has dedicated a large portion of his efforts to training young investigators in clinical and populational science?. Several of his formers trainees have pursued academic careers in institutions across the US and abroad.
Dr. Lima has concentrated his professional effort on clinical investigation and clinical scholarship as well as in academic teaching. His primary contribution to the advancement of cardiovascular medicine has been the development of MRI methods to measure infarct size and the extent and severity of microvascular obstruction in patients with acute myocardial infarction, ischemic and non-ischemic cardiomyopathies.
Dr. Lima’s initial work was focused on the pathophysiology of left ventricular remodeling after myocardial infarction using non-invasive techniques, such as MRI tagging and echocardiography to evaluate regional left ventricular function after myocardial infarction. He was one of the first investigators to measure infarct size using MRI. He later developed accurate CT imaging methods for identification of the atherosclerotic coronary artery diseases compared to the invasive angiography.
Dr. Lima has also been directly involved in applying imaging phenotyping methods in population research. His involvement in the Multi-Ethnic Study on Atherosclerosis (MESA) has been concentrated on the investigation of myocardial damage and dysfunction among asymptomatic individuals of different ethnicities living in the United States. His efforts have also included the biomechanical analysis of aortic function. His studies as a MESA investigator have concentrated on the determinants of incident heart failure and progressive ventricular dysfunction as a consequence of subclinical atherosclerosis and hypertensive heart disease. Dr. Lima has also developed contrast enhanced MRI methods to predict sudden death in patients who suffered myocardial infarction. The majority of Dr. Lima’s clinical efforts have been dedicated to clinical scholarship and program development at the Johns Hopkins Hospital. He directed the Echocardiography Laboratory at Hopkins for several years and spearheaded revolutionary programs in cardiovascular MRI and cardiac CT. His leadership in mentoring cardiology and radiology trainees in cardiovascular imaging has also been significant both clinically and in clinical investigation.
Bharath Ambale Venkatesh PhD, leads multiple projects in Big Data and Machine Learning: New approaches on machine learning techniques and informatics methods for dimension reduction on MESA study – cooperation with University of Auckland to apply dimension reduction techniques to extract meaningful information on ventricular remodeling in MESA. He also works with random survival forests, a machine learning statistical technique to a data-rich dataset in MESA encompassing measurements from imaging, electrocardiography, questionnaires, lab tests, etc. to maximize event prediction and demonstrate a method of biomarker discovery. We plan to extend some of these developed methods to the current projects.
Facilities
We have excellent research lab facilities located at both the main and Bayview campuses of the Johns Hopkins Hospital complexes. Our research labs are innovative and include state of the art equipment for image analysis and results reporting. We have high end computers with dual monitors for easy analyst viewing and are fully supported by the University Administration and Information Technology Departments. IT support is available as needed and full wired/wireless internet capability is available throughout the all campuses of Johns Hopkins University.
Johns Hopkins and Canon Medical Research Institute -- Center for Advanced Imaging and Research Science (CAIRS):
Dr. Lima’s lab has a unique partnership with Canon Medical Research Institute, USA, to collaborate on cutting-edge medical imaging research. The Center for Advanced Imaging and Research Science is located in the brand new Science + Technology Park located at 1812 Ashland Ave, a few short blocks from Johns Hopkins Hospital. Through this partnership, Dr. Lima’s lab has access to Canon’s Galan 3T magnetic resonance scanner and has begun work on several interdisciplinary studies, with hopes to expand access to advanced medical imaging to other researchers in the future.
Imaging Core Labs
Our Cardiovascular Core Laboratory at Johns Hopkins is a research-dedicated, very productive, and highly experienced Cardiac Imaging Core Laboratory. The Core Lab is concentrated on the development and application of imaging and technology to address scientific and clinical problems involving the heart and vascular system. Our experience in assessing cardiac structure, function, and deformation is well known in the scientific community and goes beyond our participation in the CARDIA and MESA studies, with a large number of presentations in national major cardiology meetings (AHA and ASE), as well as manuscripts in high impact publications. Over the last decade, we have been involved in training Field Center technologists, implementing cardiac imaging protocols, developing new tools to assess cardiac structure and function, and analyzing cardiac images in large cohort studies. In addition, during all these processes, we developed instruments to guarantee high standards in quality.
Members
Faculty
- Principal Investigator: João A.C. Lima, M.D.
- Bharath Ambale Venkatesh, Ph.D.
Staff
- Ela Chamera
- Dawn Wolfe
- Jennifer Weighman
- Kathleen Lensch
- Kimberly Keck
- Laura Perrotta
- Jaclyn Sesso
- Jason Ortman
- Joanna Kozlowski
- Vladimir Olenichev
Fellows
- Mohammad R. Ostovaneh
- Mohammadali Habibi
- Henrique Doria De Vasconcellos
- Yoko Kato
- Mateus Marques
- Luisa Ciuffo
- Vinithra Varadarjan
- Kaveh Rezaei Bookani
- Hooman Bakhshi
- Aakanksha Sharma
- Tarek Zghaib
- Victor Nauffal
- Pedro Vinícius Amorim De Medeiros Patriota
- Chike C. Nwabuo
- Ashkan Abdollahi
- Omar Chehab
- Ralph Zeitoun
Students
- Raquel Weinberg
- Caroline Ward
- Srivathsa Pasumarthi Venkata
- Shrey Kapoor
- Joanna Guo
- Ujjawal Sharma
Projects
- Cardiovascular CT Core Lab
- Echocardiography Core Lab
- Cardiac MRI Core Lab
- Artificial Intelligence for Health Extension
- SuperPACS
- Resilience in Older Adults – Functional Assessment via Whole Body Magnetic Resonance Imaging ?
Cardiovascular CT Core Lab
The Coronary Artery Evaluation using 64-row Multidetector Computed Tomography Angiography (CORE64) study was a prospective, multicenter diagnostic study that utilized centralized blinded analysis to determine the diagnostic accuracy of 64-detector 0.5 mm slice thickness Multi-detector Computed Tomography (MDCT) angiography in comparison with conventional coronary angiography (CCA), in patients with suspected CAD. The study was designed to determine whether 64-detector MDCT angiography can reliably define the presence or absence of obstructive disease and also identify those patients who may require coronary revascularization. Nine centers enrolled 291 patients who completed MDCT angiography prior to CCA, and had calcium scores >600. Diameter stenosis >50% were considered obstructive. The CORE-64 trial showed that 64-detector MDCT angiography has reliable accuracy for the diagnosis of obstructive coronary disease. The area under the receiver operating characteristic curve of 0.93 is consistent with robust diagnostic performance and indicates that 64-detector MDCT angiography has powerful discriminative ability to identify patients with and without coronary obstruction. Additionally, MDCT angiography compared well against CCA in predicting clinically-driven revascularization and severity of obstructive CAD, which supports its clinical utility for identifying symptomatic patients who may need coronary interventions. The main results of this study were published in New England Journal of Medicine. Our lab was the Cardiovascular CT Core Lab for assessment of the endpoints of the study.
The CORE320 study was a multi-center intercontinental study (United States, Canada, Asia, and Europe) that evaluated the diagnostic accuracy of multi-detector computed tomography using 320 detectors for identifying the combination of coronary artery stenosis ? 50% and a corresponding myocardium perfusion defect in a patient with suspected coronary artery disease compared with conventional coronary angiography and single photon emission computed tomography myocardium perfusion imaging. The study showed that the combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ?50 stenosis by ICA, causing a perfusion defect by SPECT/MPI. The main results of the study were published in European Heart Journal. Our lab was the Cardiovascular CT Core Lab for assessment of the endpoints of the study.
The DYNAMIC trial evaluated cardiosphere-derived stem cells for patients who have advanced heart failure. Patients received stem cells in up to three coronary arteries, enabling delivery of the drug product to more of the diseased heart tissue. The cardiac function in this study was assessed using cardiac CT. Our lab was the Cardiovascular CT Core Lab for assessment of the endpoints of the study.
The purpose of this study was to test the hypothesis that screening asymptotic high-risk diabetic patients for the presence of obstructive coronary artery disease with 64-slice CT scanning will result in a significant reduction in death or myocardial infarction over two-years of follow-up. JHU served as the cardiovascular CT Core Lab for quality control purposes for a portion (n=276) of patients randomized to the CT arm of the trial.
Dynamic Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease
The purpose of this study is to test the diagnostic accuracy of “dynamic CT perfusion imaging” for detection of hemodynamically significant coronary artery disease. Dynamic CT perfusion (CTP) is a novel technique that permits direct quantification of Myocardial Blood Flow (MBF) at both the “global” and “regional” left ventricular level and is at least as good as SPECT for detection of perfusion defects. Dynamic CTP imaging can be completed simultaneously with CT angiography (CTA) imaging (sequentially) and is able to assess the degree of coronary stenosis and the hemodynamic significance of any given coronary plaque identified in coronary CTA. Participants are recruited to this study in our lab.
Echocardiography Core Lab
Coronary Artery Risk Development in Young Adults (CARDIA)
The CARDIA study investigates the distribution and change in risk factors during young adulthood in Caucasian and African American men and women. This population-based cohort study of African American and Caucasian participants began in 1985 with 5,116 black and white women and men, age 18-30 years, recruited and examined in four urban areas: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota, and Oakland, California. Johns Hopkins served as the Echocardiography Core Lab in 2010-2011 (Year-25 follow-up exam) and 2015-2016 (Year-30 follow-up exam). The JHU ERC received 3,474 echocardiograms in the Year-25 follow-up and 3,175 echocardiograms during the Year-30 follow-up for interpretation.
Multi-center AIDS Cohort Study (MACS)
The MACS is an ongoing study of men who have sex with other men (MSM) that enrolled a total of 7,343 participants in 1984-5, 1987–1991, 2001-3, and in 2010 – present. The men are seen every six months at the study sites located in Baltimore/Washington, D.C., Chicago, Los Angeles, Pittsburgh, and Ohio. As of 2016, MACS has been following 2,392 men who are still alive with both active and passive data collection. Overall, 54% of the current cohort is HIV-infected, 12.4% are Hispanic, and 38% are non-White among the non-Hispanics. The median age of the cohort was 58 years in October 2016. Johns Hopkins serves as both the echo analysis core lab as well as the Baltimore echo imaging site for the visit 68 and 69 cohort (2017-2018).
Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)
The TODAY study was a 15-site multicenter, randomized clinical trial funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The TODAY study compared Metformin monotherapy with two alternative approaches—one combining Metformin with a second pharmacologic agent (rosiglitazone) and one combining Metformin with an intensive lifestyle-intervention program—to test the hypothesis that combination therapy initiated early in the course of youth-onset type 2 diabetes would maintain acceptable glycemic control better than Metformin alone. The JHU ERC received echocardiograms in 2010-2011 (baseline exam) for 545 participants and 452 participants in 2015-2015 (5-year follow-up exam). The JHU ERC also completed an ancillary control study for this cohort which included 130 participants in 2011-2012.
Cardiac MRI Core Lab
The Multi-Ethnic Study of Atherosclerosis (MESA)
MESA is an important prospective cohort study that involves more than 6,000 men and women from six communities in the United States. Participants in MESA come from diverse racial and ethnic groups, including African Americans, Latinos, Asians, and Caucasians. Participants have received a cardiac MRI at baseline (MESA exam 1), and then 5 and 10 years later (MESA exams 4 and 5, respectively). Our MRI Core Lab has been awarded the contract for development and implementation of the MRI protocol, quality assurance, quality control, interpretation of the MRI images and management of the MRI data. The MESA study has had an important impact in implementing cardiac MRI in large population based studies, and developing novel MRI methods for characterization of cardiovascular disease. Our lab has published hundreds of scientific papers using the MESA MRI database.
Multi-Ethnic Study of Atherosclerosis - Chronic Obstructive Pulmonary Disease (MESA-COPD)
The MESA-COPD Study recruited smokers with COPD and controls ages 50-79 years with ?10 pack-years. This is a follow-up ancillary study to the original MESA-COPD study that occurred in 2010-2012. The purpose of this study is to examine how changes in the blood vessels in the lungs may relate to the progression of emphysema over time and to understand the effects of COPD on the heart. Recruitment occurred at four field centers (Columbia University, Johns Hopkins University, Northwestern University, and University of California, Los Angeles).
The ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) trial
ALLSTAR is a Phase I/II trial evaluating the safety and efficacy of the CAP-1002 therapeutic candidate–Capricor’s allogeneic, off-the-shelf, cardiosphere-derived cell product candidate. The trial is being sponsored by Capricor Therapeutics. The trial was conducted at approximately 40 sites across the U.S and in Canada. The Phase I portion of the trial was funded in part by the National Institutes of Health and completed enrollment in December 2013, and the Phase II portion of the trial was largely supported in by the California Institute for Regenerative Medicine (CIRM). Our lab was appointed as the MRI Core Lab for assessment of the primary and secondary endpoints of the study. Participants underwent cardiac MRI at baseline and at 6- and 12-month follow-up visits to assess the efficacy of stem cells versus placebo. Our role was in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management.
The Halt cardiomyOPathy progrEssion in Duchenne (HOPE) trial
HOPE-Duchenne is a Phase I/II trial evaluating cardio-sphere derived stem cells for the first time in boys and young men with Duchenne muscular dystrophy (DMD) who have significant cardiac involvement. Cardiomyopathy is currently the leading cause of death in patients with DMD, having recently surpassed respiratory causes due to treatment improvements for that aspect of the disease. The trial is being funded, in part, through the support of the California Institute for Regenerative Medicine (CIRM). The Phase I/II HOPE-Duchenne trial is designed as a randomized open-label usual care controlled multi-center study evaluating the safety and preliminary efficacy of stem cells in 25 subjects. Our lab was appointed as the MRI Core Lab for assessment of the primary and secondary endpoints of the study. Participants underwent cardiac MRI at baseline and at 6- and 12-month follow-up visits to assess the efficacy of stem cells versus placebo. Our role was in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management.
CONCERT-HF is a randomized, placebo-controlled clinical trial sponsored by Cardiovascular Cell Therapy Research Network (CCTRN) of the National Heart, Lung and Blood Institute (NHLBI). This study is designed to evaluate the feasibility, safety, and effect of Combo, MSCs alone, and CSCs alone compared with placebo as well as each other in subjects with heart failure of ischemic etiology. A total of 160 subjects are randomized (1:1:1:1) to receive Combo, MSCs, CSCs, or placebo. After randomization, baseline imaging, relevant harvest procedures, and study product injection, subjects will be followed up at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months post study product injection. All subjects receive study product injection (cells or placebo) using the NOGA® XP Mapping and Navigation System. Our lab was appointed as the MRI Core Lab for assessment of the primary and secondary endpoints of the study. Subjects undergo cardiac MRI scans to assess scar size and LV function and structure at baseline and at 6 and 12 months post study product administration. All endpoints are assessed at the 6 and 12 month visits which occur 180 ±30 days and 365 ±30 days respectively from the day of study product injection (Day 0). Our role is in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management. The design of this trial is published in Circulation Research.
Stem Cell Injection in Cancer Survivors (SENECA)
SENECA is a Phase I, randomized, placebo-controlled clinical trial sponsored by Cardiovascular Cell Therapy Research Network (CCTRN) of the National Heart, Lung and Blood Institute (NHLBI) designed to evaluate the safety and feasibility of allo-MSCs administered by transendocardial injection in thirty-six subjects with anthracycline-induced cardiomyopathy (AIC). The subjects are randomized 1:1 to receive allo-MSCs or placebo. All subjects undergo cardiac catheterization and study product administration using the NOGA Myostar catheter injection system. Our lab was appointed as the MRI Core Lab for assessment of the primary and secondary endpoints of the study. Subjects undergo cardiac MRI scans to assess scar size and LV function and structure at baseline and at 6 and 12 months post study product administration. All endpoints are assessed at the 6 and 12 month visits which occur 180 ±30 days and 365 ±30 days respectively from the day of study product injection (Day 0). Our role is in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management.
Patients With Intermittent Claudication Injected With ALDH Bright Cells (PACE)
PACE was a randomized, placebo-controlled clinical trial sponsored by Cardiovascular Cell Therapy Research Network (CCTRN) of the National Heart, Lung and Blood Institute (NHLBI) that was designed to find out if aldehyde dehydrogenase bright (ALDHbr) cells taken from a patient's bone marrow can be placed safely, via intramuscular injections, into their affected calf and lower thigh muscles and improve blood flow and/or peak walking time in patients experiencing pain associated with blocked blood vessels in the leg. Our lab was appointed as the MRI Core Lab for assessment of the primary and secondary endpoints of the study. Subjects underwent MRI scans at baseline and at 6 and 12 months post study product administration. Our role was in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management. The MRI methods of this study was published in American Heart Journal and the main results of the study was published in Circulation.
This is a Phase 2b randomized, blinded (subject/MedImmune blinded, investigator unblinded), placebo-controlled study to evaluate the efficacy, safety, PK/pharmacodynamic, and immunogenicity of repeat doses of a new drug, MEDI6012, in adult subjects presenting with acute STEMI. This study is sponsored by MedImmune, LLC and is being conducted in 11 countries in Europe and Israel. Our lab was appointed as the MRI Core Lab for assessment of the primary endpoint of the study using Cardiac MRI. Our role is in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management.
Evaluation of HIV-Associated Cardiac Dysfunction in Women
This is a sub-study of The Women’s Interagency HIV Study (WIHS) to prospectively assess the cardiac dysfunction in HIV-infected and well-matched uninfected women. This is the first long-term longitudinal assessment of LV dysfunction in HIV-infected and uninfected women, and a well-sized evaluation of myocardial deformation in such individuals. Cardiac MRI is used for assessment of interstitial fibrosis and myocardial triglyceride content, as well as infarct. Our lab has been appointed as the MRI Core Lab for this study. Our role is in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management.
Laser Atherectomy for STemi, Pci Analysis with Scintigraphy Study (LAST-PASS)
LAST-PASS is a prospective multi-center, single-blinded, randomized clinical trial to investigate the impact of (Excimer Laser Coronary Atherectomy (ELCA) on myocardial salvage in anterior STEMI patients. The study is conducted in 17 Japanese field centers and is sponsored by Boston Scientific. Cardiac MRI is performed as a sub-study to assess myocardial infarction size, myocardial salvage, cardiac function, and microvascular obstruction as the endpoints of the study. Our lab was appointed as the MRI Core Lab for this multi-center study. Our role is in MRI protocol development and implementation, technologist training and certification, quality assurance, quality control, collecting and analyzing MRI data, image transfer and storage and data management.
Magnetic Resonance Imaging Based Assessment of Peripheral Arterial Disease
The goal of this study is to create a comprehensive imaging exam for peripheral arterial disease (PAD) using the Galan 3T MR scanner to evaluate different aspects of skeletal muscle function, arterial anatomy, and muscle morphology combined into one imaging session. We aim to identify and improve our understanding of physiologic adaptations associated with PAD to serve as reliable surrogate outcome measures in these patients.
Feasibility of Magnetic Resonance Imaging Based Phenotyping for ‘Heart Like Mine’
The goal of the ‘Heart Like Mine’ project is to develop and exploit cutting-edge computational tools to advance the understanding of the fundamental mechanisms that underlie rhythm and contractile disorders. This study aims to encapsulate different aspects of cardiac function, anatomy, and morphology all into one imaging session.
Artificial Intelligence for Health Extension
Our innovation is in developing artificial intelligence (AI) software that is embedded within a standard picture archiving communications system (PACS) hardware installed within clinical/imaging facilities. In conjunction with the SuperPACS automatically reported data, AIHEX will curate disparate aspects of patient histories and imaging data for predictive measures of patients at risk for cardiovascular disease. We aim to further understand the pathogenesis of heart failure and cardiovascular events and identify the most important predictors of outcomes using machine learning. This may lead to greater insights regarding the role or subclinical disease markers without prior assumptions of causality.
SuperPACS
SuperPACS is a core intelligence platform in development for DICOM cardiovascular image receiving, viewing, repository, and retrieval from multiple modalities (MRI, CT, and ultrasound) integrated with our artificial intelligence software (AIHEX) to convert image data into qualitative and quantitative metrics. These metrics have the potential to be overlaid with electronic medical reports for patient specific predictive analytics and decision support. Our machine learning algorithms have the capability to automatically quantify images normalizing for human error, reader variability and predicting patients at high risk for cardiovascular events.
Resilience in Older Adults – Functional Assessment via Whole Body Magnetic Resonance Imaging
This project is currently in development. The goal of this research is to use whole-body magnetic resonance imaging techniques, in addition to physical assessments and biomarkers of aging, to elucidate the biological pathways contributing to the development of frailty in the aging population. This study will be completed through a partnership with the Older Americans Independence Center (OAIC).