Carissa G. Fonseca

The Cardiac Atlas Project—an imaging database for computational modeling and statistical atlases of the heart

Motivation: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape and wall motion and characterize cardiac function among and within population groups. Results: Three main open-source software components were developed: (i) a database with web-interface; (ii) a modeling client for 3D + time visualization and parametric description of shape and motion; and (iii) open data formats for semantic characterization of models and annotations. The database was implemented using a three-tier architecture utilizing MySQL, JBoss and Dcm4chee, in compliance with the DICOM standard to provide compatibility with existing clinical networks and devices. Parts of Dcm4chee were extended to access image specific attributes as search parameters. To date, approximately 3000 de-identified cardiac imaging examinations are available in the database. All software components developed by the CAP are open source and are freely available under the Mozilla Public License Version 1.1 (http://www.mozilla.org/MPL/MPL-1.1.txt). Availability: http://www.cardiacatlas.org Contact: a.young@auckland.ac.nz Supplementary information: Supplementary data are available at Bioinformatics online.

Rationale and design for the Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) trial.

Background: Cardiac magnetic resonance imaging (CMR) can accurately determine infarct size. Prior studies using indirect methods and CMR to assess infarct size have shown that patients with larger myocardial infarctions have worse prognoses. Implantable cardioverter defibrillators (ICD) have been shown to improve survival among patients with severe left ventricular (LV) dysfunction. However, the majority of cardiac arrests occur in patients with higher ejection fractions.

Cardiomyopathy is associated with structural remodelling of heart valve extracellular matrix

AIMS To increase the supply, many countries harvest allograft valves from explanted hearts of transplant recipients with ischaemic (ICM) or dilated cardiomyopathy (DCM). This study determines the structural integrity of valves from cardiomyopathic hearts. METHODS AND RESULTS Extracellular matrix (ECM) was examined in human valves obtained from normal, ICM, and DCM hearts. To confirm if ECM changes were directly related to the cardiomyopathy, we developed a porcine model of chronic ICM. Histology and immunohistostaining, as well as non-invasive multiphoton and second harmonic generation (SHG) imaging revealed marked disruption of ECM structures in human valves from ICM and DCM hearts. The ECM was unaffected in valves from normal and acute ICM pigs, whereas chronic ICM specimens showed ECM alterations similar to those seen in ICM and DCM patients. Proteins and proteinases implicated in ECM remodelling, including Tenascin C, TGFbeta1, Cathepsin B, MMP2, were upregulated in human ICM and DCM, and porcine chronic ICM specimens. CONCLUSION Valves from cardiomyopathic hearts showed significant ECM deterioration with a disrupted collagen and elastic fibre network. It will be important to determine the impact of this ECM damage on valve durability and calcification in vivo if allografts are to be used from these donors.

Atlas-Based Quantification of Cardiac Remodeling Due to Myocardial Infarction

Myocardial infarction leads to changes in the geometry (remodeling) of the left ventricle (LV) of the heart. The degree and type of remodeling provides important diagnostic information for the therapeutic management of ischemic heart disease. In this paper, we present a novel analysis framework for characterizing remodeling after myocardial infarction, using LV shape descriptors derived from atlas-based shape models. Cardiac magnetic resonance images from 300 patients with myocardial infarction and 1991 asymptomatic volunteers were obtained from the Cardiac Atlas Project. Finite element models were customized to the spatio-temporal shape and function of each case using guide-point modeling. Principal component analysis was applied to the shape models to derive modes of shape variation across all cases. A logistic regression analysis was performed to determine the modes of shape variation most associated with myocardial infarction. Goodness of fit results obtained from end-diastolic and end-systolic shapes were compared against the traditional clinical indices of remodeling: end-diastolic volume, end-systolic volume and LV mass. The combination of end-diastolic and end-systolic shape parameter analysis achieved the lowest deviance, Akaike information criterion and Bayesian information criterion, and the highest area under the receiver operating characteristic curve. Therefore, our framework quantitatively characterized remodeling features associated with myocardial infarction, better than current measures. These features enable quantification of the amount of remodeling, the progression of disease over time, and the effect of treatments designed to reverse remodeling effects.

Left ventricular shape variation in asymptomatic populations: the multi-ethnic study of atherosclerosis

BackgroundAlthough left ventricular cardiac geometric indices such as size and sphericity characterize adverse remodeling and have prognostic value in symptomatic patients, little is known of shape distributions in subclinical populations. We sought to quantify shape variation across a large number of asymptomatic volunteers, and examine differences among sub-cohorts.MethodsAn atlas was constructed comprising 1,991 cardiovascular magnetic resonance (CMR) cases contributed from the Multi-Ethnic Study of Atherosclerosis baseline examination. A mathematical model describing regional wall motion and shape was used to establish a coordinate map registered to the cardiac anatomy. The model was automatically customized to left ventricular contours and anatomical landmarks, corrected for breath-hold mis-registration between image slices. Mathematical techniques were used to characterize global shape distributions, after removal of translations, rotations, and scale due to height. Differences were quantified among ethnicity, sex, smoking, hypertension and diabetes sub-cohorts.ResultsThe atlas construction process yielded accurate representations of global shape (errors between manual and automatic surface points in 244 validation cases were less than the image pixel size). After correction for height, the dominant shape component was associated with heart size, explaining 32% of the total shape variance at end-diastole and 29% at end-systole. After size, the second dominant shape component was sphericity at end-diastole (13%), and concentricity at end-systole (10%). The resulting shape components distinguished differences due to ethnicity and risk factors with greater statistical power than traditional mass and volume indices.ConclusionsWe have quantified the dominant components of global shape variation in the adult asymptomatic population. The data and results are available at cardiacatlas.org. Shape distributions were principally explained by size, sphericity and concentricity, which are known correlates of adverse outcomes. Atlas-based global shape analysis provides a powerful method for quantifying left ventricular shape differences in asymptomatic populations.Trial registrationClinicalTrials.gov NCT00005487

Characterization of myocardial scars: Electrophysiological imaging correlates in a porcine infarct model

BACKGROUND Definition of myocardial scars as identified by electroanatomic mapping is integral to catheter ablation of ventricular tachycardia (VT). Myocardial imaging can also identify scars prior to ablation. However, the relationship between imaging and voltage mapping is not well characterized. OBJECTIVE The purpose of this study was to verify the anatomic location and heterogeneity of scars as obtained by electroanatomic mapping with contrast-enhanced MRI (CeMRI) and histopathology, and to characterize the distribution of late potentials in a chronic porcine infarct model. METHODS In vivo 3-dimensional cardiac CeMRI was performed in 5 infarcted porcine hearts. High-density electroanatomic mapping was used to generate epicardial and endocardial voltage maps. Scar surface area and position on CeMRI were then correlated with voltage maps. Locations of late potentials were subsequently identified. These were classified according to their duration and fractionation. All hearts underwent histopathological examination after mapping. RESULTS The total dense scar surface area and location on CeMRI correlated to the total epicardial and endocardial surface scar on electroanatomic maps. Electroanatomic mapping (average of 1,532 ± 480 points per infarcted heart) showed that fractionated late potentials were more common in dense scars (<0.50 mV) as compared with border zone regions (0.51 to 1.5 mV), and were more commonly observed on the epicardium. CONCLUSION In vivo, CeMRI can identify areas of transmural and nontransmural dense scars. Fractionated late diastolic potentials are more common on the epicardium than the endocardium in dense scar. These findings have implications for catheter ablation of VT and for targeting the delivery of future therapies to scarred regions.

Pulmonary MR perfusion at 3.0 Tesla using a blood pool contrast agent: Initial results in a swine model

To prospectively evaluate the technical feasibility of a highly accelerated pulmonary MR perfusion protocol at 3.0T using a blood pool contrast agent in a swine model.

The cardiac atlas project: preliminary description of heart shape in patients with myocardial infarction

The Cardiac Atlas Project seeks to establish a standardized database of cardiovascular imaging examinations, together with derived analyses, for the purposes of statistical characterization of global and regional heart function abnormalities. We present preliminary results from a subset of cases contributed from the Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) study of patients with myocardial infarction. Finite element models were fitted to the epicardial and endocardial surfaces throughout the cardiac cycle in 200 patients using a standardized procedure. The control points of the shape model were used in a principal component analysis of shape and motion. The modes were associated with well-known clinical indices of adverse remodeling in heart disease, including heart size, sphericity and mitral valve geometry. These results therefore show promise for the clinical application of a statistical analysis of shape and motion in patients with myocardial infarction.

The cardiac atlas project: rationale, design and preliminary results

Author(s): Medrano-Gracia, Pau; Backhaus, Michael; Bluemke, David A; Chung, Jae; Cowan, Brett R; Finn, Paul J; Fonseca, Carissa G; Hunter, Peter J; Kadish, Alan H; Lee, Daniel C; Lima, Joao AC; Shivkumar, Kalyanam; Tao, Wenchao; Young, Alistair A

The cardiac atlas project: development of a framework integrating cardiac images and models

We describe the software design, architecture and infrastructure employed in the Cardiac Atlas Project (CAP), an international collaboration to establish a web-accessible structural and functional atlas of the normal and pathological heart. Cardiac imaging data is de-identified in a HIPAA compliant manner using the LONI Debabeler with customized DICOM mappings. A production database and web-interface were employed based on existing tools developed by LONI. A new open-source database and web interface have been developed for research purposes. After consideration and evaluation of several software frameworks, the research database has been implemented based on a 3-tier architecture utilizing MySQL, JBoss and Dcm4chee. Parts of Dcm4chee have been extended to enable access to MRI specific attributes and arbitrary search parameters. An XML schema has been designed representing the elements associated with the creation and curation of volumetric shape models. The research database is implemented compliant to the DICOM standard, thus providing compatibility with existing clinical networks and devices. A modeling tool, the CAP client, has been developed to enable browsing of 3D image data and creation and modification of volumetric shape models. All software components developed by the CAP are open source and are freely available under the Mozilla license.