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Biomedical subjects

Brett R Cowan

Publications and source records attributed to Brett R Cowan.

9 recordsLinked to original sources

Impaired subendocardial contractile myofiber function in asymptomatic aged humans, as detected using MRI.

With aging, structural and functional changes occur in the myocardium without obvious impairment of systolic left ventricular (LV) function. Transmural differences in myocardial vulnerability for these changes may result in increase of transmural inhomogeneity in contractile myofiber function. Subendocardial fibrosis and impairment of subendocardial perfusion due to hypertension might change the transmural distribution of contractile myofiber function. The ratio of LV torsion to endocardial circumferential shortening (torsion-to-shortening ratio; TSR) during systole reflects the transmural distribution of contractile myofiber function. We investigated whether the transmural distribution of systolic contractile myofiber function changes with age. Magnetic resonance tissue tagging was performed to derive LV torsion and endocardial circumferential shortening. TSR was quantified in asymptomatic young [age 23.2 (SD 2.6) yr, n = 15] and aged volunteers [age 68.8 (SD 4.4) yr, n = 16]. TSR and its standard deviation were significantly elevated in the aged group [0.47 (SD 0.12) aged vs. 0.34 (SD 0.05) young; P = 0.0004]. In the aged group, blood pressure and the ratio of LV wall mass to end-diastolic volume were mildly elevated but could not be correlated to the increase in TSR. There were no significant differences in other indexes of systolic LV function such as end-systolic volume and ejection fraction. The elevated systolic TSR in the asymptomatic aged subjects suggests that aging is associated with local loss of contractile myofiber function in the subendocardium relative to the subepicardium potentially caused by subclinical pathological incidents.

Adult↗

Reperfused myocardial infarction in mice: 3D mapping of late gadolinium enhancement and strain.

We developed mathematical modeling tools for mapping 3D infarct geometry from multislice late gadolinium enhancement data, allowing fusion with multislice MR tagging data, in mice with myocardial infarction. Five C57BL/6 mice were imaged at baseline, 1, 7 and 28 days after 60 min occlusion of the left anterior descending coronary artery. The 3D infarct geometry was mapped in material coordinates, and registered with 3D strain, showing permanent dysfunction in infarcted segments, intermediate function in the adjacent zone, and maintained function in the remote zone. 3D mapping of late enhancement and strain allows registration of multiple studies in a consistent framework.

Analysis of Variance↗

Midwall shortening after coarctation repair: the effect of through-plane motion on single-plane indices of left ventricular function.

Left ventricular midwall function is increased after repair of coarctation of the aorta (CoA). The cause is unclear. This study aimed to examine the variance between fiber shortening derived from 3-dimensional models of myocardial deformation, and 1- and 2-dimensional indices of left ventricular systolic function. In all, 15 young adults after CoA and 15 matched control subjects were recruited. Endocardial and midwall fractional shortening were calculated using M-mode echocardiography. Ejection fraction, midwall fractional shortening, and myocardial deformation were calculated or measured from magnetic resonance (MR) imaging. Echocardiographic and cine-MR imaging midwall fractional shortening were increased after CoA (P = .02 and < .001). In contrast, 3-dimensional MR tagging demonstrated normal midwall circumferential shortening and decreased longitudinal shortening in the CoA group (P < .01). Cine MR midwall shortening, recalculated to allow for through-plane motion, was similar to tagged midwall shortening, with no difference between the CoA and control groups. After CoA, measures of left ventricular function systematically overestimate midwall fiber shortening unless the methodology accounts for through-plane motion.

Adult↗

Method and apparatus for soft tissue material parameter estimation using tissue tagged Magnetic Resonance Imaging.

We describe an experimental method and apparatus for the estimation of constitutive parameters of soft tissue using Magnetic Resonance Imaging (MRI), in particular for the estimation of passive myocardial material properties. MRI tissue tagged images were acquired with simultaneous pressure recordings, while the tissue was cyclically deformed using a custom built reciprocating pump actuator A continuous three-dimensional (3D) displacement field was reconstructed from the imaged tag motion. Cavity volume changes and local tissue microstructure were determined from phase contrast velocity and diffusion tensor MR images, respectively. The Finite Element Method (FEM) was used to solve the finite elasticity problem and obtain the displacement field that satisfied the applied boundary conditions and a given set of material parameters. The material parameters which best fit the FEM predicted displacements to the displacements reconstructed from the tagged images were found by nonlinear optimization. The equipment and method were validated using inflation of a deformable silicon gel phantom in the shape of a cylindrical annulus. The silicon gel was well described by a neo-Hookian material law with a single material parameter C1=8.71+/-0.06kPa, estimated independently using a rotational shear apparatus. The MRI derived parameter was allowed to vary regionally and was estimated as C1 =8.80+/-0.86kPa across the model. Preliminary results from the passive inflation of an isolated arrested pig heart are also presented, demonstrating the feasibility of the apparatus and method for isolated heart preparations. FEM based models can therefore estimate constitutive parameters accurately and reliably from MRI tagging data.

Algorithms↗

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.

Adult↗

Regeneration of the heart in diabetes by selective copper chelation.

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Although altered systemic regulation of transition metals in diabetes has been the subject of previous investigation, it is not known whether changed transition metal metabolism results in heart disease in common forms of diabetes and whether metal chelation can reverse the condition. We found that administration of the Cu-selective transition metal chelator trientine to rats with streptozotocin-induced diabetes caused increased urinary Cu excretion compared with matched controls. A Cu(II)-trientine complex was demonstrated in the urine of treated rats. In diabetic animals with established heart failure, we show here for the first time that 7 weeks of oral trientine therapy significantly alleviated heart failure without lowering blood glucose, substantially improved cardiomyocyte structure, and reversed elevations in left ventricular collagen and beta(1) integrin. Oral trientine treatment also caused elevated Cu excretion in humans with type 2 diabetes, in whom 6 months of treatment caused elevated left ventricular mass to decline significantly toward normal. These data implicate accumulation of elevated loosely bound Cu in the mechanism of cardiac damage in diabetes and support the use of selective Cu chelation in the treatment of this condition.

Animals↗

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.

Adult↗

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.

Adult↗

Temporal evolution of left ventricular strain late after repair of coarctation of the aorta using 3D MR tissue tagging.

PURPOSE: Following repair of coarctation of the aorta (CoA), LV mass is increased along with morbidity and mortality. Previous studies have reported increased shortening indices and impaired diastolic function. However, direct measurements of local material motion and temporal evolution of strain have been lacking. METHODS: Magnetic resonance (MR) tissue tagging was used to quantify regional three-dimensional myocardial deformation throughout systole and much of diastole in 14 patients (aged 19-23) who had CoA repair 17-23 years previously, and 15 age-, sex- and BSA-matched normal volunteers (NV). RESULTS: Mass to end-diastolic volume ratio was increased in the CoA group (1.23 +/- 0.12 g/mL CoA vs. 1.14 +/- 0.10 g/mL NV, p = 0.039), together with ejection fraction (65.3 +/- 4.4 vs. 60.8 +/-1.9%, p = 0.001) and systolic blood pressure (132.5 +/- 14.5 vs. 117.3 +/- 11.6 mmHg, p = 0.004). At end-systole, circumferential shortening was normal, but longitudinal shortening was decreased (14.9 +/- 1.3 vs. 16.8 +/- 1.4%, p < 0.001). Although systolic strain rates were not significantly different, early diastolic strain rate (EDSR) in the CoA group was increased in the circumferential direction (-71 +/- 23 vs. -52 +/- 20%/sec, p = 0.029), but decreased in the longitudinal direction (-27 +/- 12 vs. -39 +/- 11%/sec, p = 0.015). Longitudinal shortening and circumferential EDSR were related to right arm-leg pressure gradient (R2 = 0.20, p = 0.016 and R2 = 0.38, p < 0.001, respectively) and to mass index (R2 = 0.18, p = 0.024 and R2 = 014, p = 0.049, respectively). CONCLUSIONS: MR tagging allows quantitative information on the temporal evolution of myocardial deformation. Directionally dependent changes in strain evolution are seen late after CoA repair. These changes are related to both persistent arm-leg pressure gradient and degree of hypertrophy and may be indicators of developing dysfunction.

Adult↗