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.

BACKGROUND: Although 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. METHODS: An 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. RESULTS: The 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. CONCLUSIONS: We 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 REGISTRATION: ClinicalTrials.gov NCT00005487.

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.

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.

Changes in mitral annular geometry and dynamics with ß-blockade in patients with degenerative mitral valve disease.

BACKGROUND: remodeling of the mitral annulus contributes to progression of mitral regurgitation (MR). In patients with moderate-to-severe MR, short-term treatment with ß-blockers has been shown to increase left ventricular (LV) end-diastolic and end-systolic volume, and this could deleteriously increase mitral valve annular dimensions. The objective of this study was to quantify the effects of a short duration of ß-blocker treatment on mitral annular dimensions and dynamics in patients with MR due to primary degenerative valve disease. METHODS AND RESULTS: twenty-five patients with moderate-to-severe degenerative MR and normal LV systolic function were studied in a double-blind crossover experiment using a ß1-selective adrenergic blocker and placebo administered for 14±3 days. Cardiac MRI images were acquired after each treatment period to quantify mitral annular dimensions. At end diastole, there was no change in annular area (1659±331 versus 1632±299 mm(2); P<0.19), annular perimeter (154.3±16.4 versus 152±13.9 mm; P<0.13), septal-lateral (SL) dimension (38.0±5 versus 39.0±4.5 mm; P<0.15), or annular height (9.8±3.8 versus 9.5±2.5 mm; P<0.53). ß-blockade resulted in significant end-diastole decreases in commissure-commissure dimension (48.9±4.6 versus 47.2±4.0 mm; P<0.01) and eccentricity (1.3±0.2 versus 1.2±0.1; P<0.01). At end systole (ES), ß-blockade conferred a small, but significant decrease in annular perimeter (161.0±19.3 versus 156.8±16.9 mm; P<0.04) and eccentricity (1.2±0.1 versus 1.1±0.1; P<0.02), and the SL dimension significantly increased (41.5±5.7 versus 43.0±5.3 mm; P<0.03). Commissure-commissure dimension, annular area, and annular height at ES were not significantly different. CONCLUSIONS: despite significant increases in LV end-diastolic and end-systolic volume, short-term ß-blocker treatment of patients with moderate-to-severe MR reduced or preserved all mitral annular dimensions except SL at ES.

Contrast agents used in cardiovascular magnetic resonance imaging: current issues and future directions.

Cardiovascular MRI is being increasingly used in the evaluation of ischemic heart disease, cardiac masses, complex congenital heart disease, and morphologic evaluation of the vascular anatomy throughout the body. Many and varied contrast media may be used to increase the sensitivity and specificity of detecting and evaluating various pathologies, and a knowledge of the different mechanisms of action, distributions and safety profiles of these agents is required for safe and effective imaging. This article reviews the currently available magnetic resonance (MR) contrast media, discusses the risks and benefits, and gives illustrated examples of current clinical applications in cardiovascular disease. A literature search covered the period 1990 to the present with the use of multiple databases including MEDLINE, PUBMED, SciSearch and Google Medical. All identified studies containing information relevant to the topic of cardiovascular MRI and cardiovascular MR contrast agents and their uses and properties were evaluated. Evaluation was limited to studies in English. The conclusions were that the use of contrast agents vastly increases the diagnostic yield, sensitivity and specificity of cardiovascular MRI in the non-invasive diagnosis of the full breadth of cardiovascular pathology. The use of contrast MRI for investigating ischemic heart disease, cardiac masses, and congenital heart disease and in angiography is now well established, and the referring physician, cardiologist, or radiologist requires an in-depth knowledge of the safety profiles and correct dosing of commonly prescribed contrast agents. As the number of MR contrast agents on the market continues to increase, knowledge of the basic mechanism of action is vital for keeping abreast of how new and emerging agents will affect clinical practice in the future.

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. METHODS: The Defibrillators To Reduce Risk By Magnetic Resonance Imaging Evaluation study (DETERMINE) is a prospective, multicenter, randomized, clinical trial in patients with coronary artery disease (CAD) and mild-to-moderate LV dysfunction. The purpose of this trial is to test the hypothesis that patients with an infarct size > or = 10% of LV mass, randomized to ICD plus appropriate medical therapy will have improved survival compared with patients randomized to medical therapy alone. Cine and myocardial delayed contrast CMR will be performed in patients with CAD. The primary endpoint will be death from any cause. At least 10,000 patients with CAD will undergo CMR. The target enrollment is 1,550 patients with an estimated 36-month enrollment period. The patients will be followed up for 24 months after the last patient randomization. During the follow-up period, 330 deaths are estimated to occur. This study is powered to detect a 28% reduction in mortality by ICD therapy. CONCLUSION: The DETERMINE trial will assess the efficacy of ICD therapy to improve survival among patients with CAD, mild-to-moderate LV dysfunction, and infarct size > or = 10% of LV mass as measured by CMR.

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.

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

PURPOSE: 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. MATERIALS AND METHODS: Twelve pigs underwent time-resolved pulmonary MR angiography (MRA) on a 3.0T MR system under anesthesia and controlled mechanical ventilation. After intravenous injection of 0.05 mmol/kg of Gadomer-17 at 4 mL/second, a fast time-resolved MRA sequence with temporal echo-sharing (three segmented k-space) and highly accelerated parallel acquisition was used to acquire 3D data sets with an in-plane resolution of 1 x 1 mm(2) (slice thickness = 6 mm) and temporal resolution of one second. Image quality was evaluated independently by two radiologists, and quantitative analysis of perfusion parameters was performed using pre-released perfusion software. RESULTS: All studies were identified by both readers as having diagnostic image quality (range = 2-3, median = 3) and there was excellent interobserver agreement (kappa = 0.89; 95% CI = 0.83, 0.95). A quantitative analysis of perfusion indices was performed, with excellent overall goodness-of-fit (chi(2) value = 1.4, degree of freedom (DF) = 1). Successfully derived perfusion parameters included the time to peak (TTP, 5.1 +/- 0.7 second), mean transit time (MTT, 6.6 +/- 0.9 second), maximal signal intensity (MSI, 1051.2 +/- 718.9 arbitrary units [A.U.]), and maximal upslope of the curve (MUS, 375.9 +/- 263.4 A.U./second). CONCLUSION: 3.0T pulmonary MR perfusion using a blood pool contrast agent in a swine model is feasible. The higher available signal-to-noise ratio (SNR) at 3.0T and the high T1 relaxivity of Gadomer-17 effectively support highly accelerated parallel acquisition, and improve the performance of time-resolved pulmonary MRA.

Three-dimensional assessment of left ventricular systolic strain in patients with type 2 diabetes mellitus, diastolic dysfunction, and normal ejection fraction.

Left ventricular (LV) diastolic dysfunction often occurs in patients with type 2 diabetes mellitus (DM) independent of atherosclerotic coronary artery disease, myocardial ischemia, and regional wall motion anomalies. Limited information exists on LV myocardial tissue strain in this patient group. We measured 3-dimensional (3-D) parameters of LV systolic and diastolic functions in 28 patients who had type 2 DM (age 33 to 70 years), standard echocardiographic evidence of LV diastolic dysfunction, and normal LV ejection fraction, and 31 normal control subjects (age 19 to 74 years) who had no evidence of cardiac disease, with multislice cine anatomic and tagged magnetic resonance imaging. Three-dimensional analysis of the resulting images showed that peak systolic mitral valve plane displacement was 12% smaller (p = 0.040) and peak diastolic mitral valve plane velocity was 21% lower (p = 0.008) in patients who had DM than in normal controls. Peak systolic circumferential and longitudinal strains and principal 3-D shortening strain were 14%, 22%, and 10% smaller, respectively, in the DM group (p <0.001 for each). Peak diastolic rate of relaxation of circumferential and longitudinal strains and principal 3-D shortening strain were 35%, 32%, and 33% lower, respectively, in the DM group (p <0.001 for each). Thus, LV systolic circumferential, longitudinal and 3-D principal strains, and diastolic strain rates are impaired in patients who have type 2 DM, LV diastolic dysfunction, and normal LV ejection fraction.

Age-related changes in myocardial relaxation using three-dimensional tagged magnetic resonance imaging.

PURPOSE: Marked changes in left ventricular diastolic filling occur with advancing age, but alterations in myocardial movement accompanying these findings have not been previously documented. We aimed to identify differences in myocardial motion during relaxation and diastole using magnetic resonance imaging (MRI), with tagging, which uniquely allows accurate, noninvasive assessment of myocardial movement in three dimensions. METHODS: Tagged MRI images from two groups of normal individuals were analyzed using dedicated computer software to provide values for group comparison of apical rotation, torsion, and circumferential and longitudinal strain throughout the cardiac cycle. RESULTS: The mean age of the younger group was 22 years, (n = 15) and that of the older group was 69 years, (n = 16). In the older group, peak apical rotation and torsion were increased during systole and significantly more apical rotation, torsion, circumferential, and longitudinal strain persisted during myocardial relaxation and diastole. In addition, peak normalized reversal of apical rotation was reduced (-5.1 +/- 1.2 degrees s-1 vs. -6.7 +/- 1.2 degrees s-1, p = 0.001), and there were slower peak rates of circumferential lengthening (76.2 +/- 28% s-1 vs. 142.5 +/- 17% s-1, p < 0.001) and longitudinal lengthening (62.7 +/- 21% s-1 vs. 122.5 +/- 20% s-1, p < 0.001). CONCLUSIONS: Tagged MRI is a unique, noninvasive imaging method that can identify significant prolongation and reduction of myocardial relaxation in older compared with young normal individuals.

Aging alters patterns of regional nonuniformity in LV strain relaxation: a 3-D MR tissue tagging study.

Although age-related impairment of diastolic function is well documented, patterns of regional tissue relaxation impairment with age have not been characterized. MRI tissue tagging with a regional three-dimensional (3-D) analysis was performed in 15 younger (age 19-26 yr) and 16 older (age 60-74 yr) normal, healthy volunteers. The peak rate of relaxation of circumferential strain (RC) was decreased in the older group (on average, 105 +/- 28 vs. 163 +/- 18 %/s for older vs. younger, mean +/- SD, P < 0.001) to a greater extent in the lateral wall than in the septum (P = 0.016) and to a greater extent in the apex than in the base (P < 0.001). Peak rate of relaxation of longitudinal strain (RL) was also reduced with age (94 +/- 27 vs. 155 +/- 18 %/s, P < 0.001) to a greater extent in the apex than in the base (P < 0.001). Both RC and RL were greater in the apex than in the base only in the younger subjects (P < 0.001 for each). Peak rate of torsion reversal (RT) was reduced with age (74 +/- 16 vs. 91 +/- 15 degrees/s, P = 0.006) to a greater extent in the base than in the apex (P = 0.035). An increase in regional asynchrony in time to RC and time to RL (P < 0.001 for each), but not time to RT, occurred with age. Thus patterns of regional nonuniformity of myocardial relaxation are altered in a consistent fashion with aging.

Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy.

Following brain injury, and during the process of neurodegeneration, a reactive astrocytic proliferation occurs. This is accompanied by an increase in the synthesis of neuropeptides, cytokines, growth factors and glial fibrillary acidic protein (GFAP), a cell-specific marker for reactive astrocytes. Astrocytes are extensively coupled by gap junctions of the Cx43 connexin subtype. Several studies have shown that in severe trauma, coupling between astrocytes may add to the spread of the damaged area. In this study we ask whether the astrocytosis which is a feature of other neurodegenerative diseases also occurs in mesial temporal lobe epilepsy (MTLE) and whether it is accompanied by an increase in astrocytic communication through an upregulation of Cx43 gap junction channel proteins. In order to examine the astrocytic response and the expression pattern of Cx43 protein, double immunohistochemical labeling studies were undertaken using antibodies against GFAP and Cx43 applied to human hippocampal tissue resected from patients with MTLE, and to normal human control hippocampal tissue. Immunofluorescent labeling of astrocytes and Cx43 was examined using confocal laser scanning microscopy. The images obtained were quantitatively analysed and reconstructed using three-dimensional volume rendering. The results of this study have established that not only is astrocytosis greater in MTLE-affected tissues than previously suggested, but it is accompanied by a highly significant increase in astrocytic Cx43 protein levels. We hypothesize that this surprisingly large upregulation in Cx43 may exacerbate generalized seizures in the progression of MTLE.