Accurate estimates of absolute left ventricular volumes from equilibrium radionuclide angiographic count data using a simple geometric attenuation correction

To simplify and clarify the methods of obtaining attenuation-corrected equilibrium radionuclide angiographic estimates of absolute left ventricular volumes, 27 patients who also had biplane contrast cineangiography were evaluated. Background-corrected left ventricular end-diastolic and end-systolic counts were obtained by semiautomated variable and hand-drawn regions of interest and were normalized to cardiac cycles processed, frame rate and blood sample counts. Blood sample counts were acquired on (d°) and at a distance (d′) from the collimator. A simple geometric attenuation correction was performed to obtain absolute left ventricular volume estimates.Using blood sample counts obtained at d° or d′, the attentuation.corrected radionuclide left ventricular end-diastolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-diastolic volumes (r = 0.95 to 0.96). However, both mean radionuclide semiautomated variable left ventricular end-diastolic volumes (179 ± 100 [± 1 standard deviation] and 185 ± 102 ml, p < 0.001) were smaller than the average cineangiographic end-diastolic volume (217 ± 102 ml), and both mean hand-drawn left ventricular end-diastolic volumes (212 ± 104 and 220 ± 106 ml) did not differ from the average cineangiographic end-diastolic volume. Using the blood sample counts obtained at d° or d′, the attenuation-corrected radionuclide left ventricular end-systolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-systolic volumes (r = 0.96 to 0.98). Also, using blood sample counts at d°, the mean radionuclide semiautomated variable left ventricular end-systolic volume (116 ± 98 ml, p < 0.05) was less than the average cineangiographic end-systolic volume (128 ± 98 ml), and the other radionuclide end-systolic volumes did not differ from the average cineangiographic end-systolic volume.Therefore, it is concluded that: 1) a simple geometric attenuation-correction of radionuclide left ventricular end-diastolic and end-systolic count data provides accurate estimates of biplane cineangiographic end-diastolic and end-systolic volumes; and 2) the hand-drawn region of interest selection method, unlike the semiautomated variable method that underestimates end-diastolic and end-systolic volumes, provides more accurate estimates of biplane cineangiographic left ventricular volumes irrespective of the distance blood sample counts are acquired from the collimator

Accurate estimates of absolute left ventricular volumes from equilibrium radionuclide angiographic count data using a simple geometric attenuation correction

To simplify and clarify the methods of obtaining attenuation-corrected equilibrium radionuclide angiographic estimates of absolute left ventricular volumes, 27 patients who also had biplane contrast cineangiography were evaluated. Background-corrected left ventricular end-diastolic and end-systolic counts were obtained by semiautomated variable and hand-drawn regions of interest and were normalized to cardiac cycles processed, frame rate and blood sample counts. Blood sample counts were acquired on (d°) and at a distance (d′) from the collimator. A simple geometric attenuation correction was performed to obtain absolute left ventricular volume estimates.Using blood sample counts obtained at d° or d′, the attentuation.corrected radionuclide left ventricular end-diastolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-diastolic volumes (r = 0.95 to 0.96). However, both mean radionuclide semiautomated variable left ventricular end-diastolic volumes (179 ± 100 [± 1 standard deviation] and 185 ± 102 ml, p < 0.001) were smaller than the average cineangiographic end-diastolic volume (217 ± 102 ml), and both mean hand-drawn left ventricular end-diastolic volumes (212 ± 104 and 220 ± 106 ml) did not differ from the average cineangiographic end-diastolic volume. Using the blood sample counts obtained at d° or d′, the attenuation-corrected radionuclide left ventricular end-systolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-systolic volumes (r = 0.96 to 0.98). Also, using blood sample counts at d°, the mean radionuclide semiautomated variable left ventricular end-systolic volume (116 ± 98 ml, p < 0.05) was less than the average cineangiographic end-systolic volume (128 ± 98 ml), and the other radionuclide end-systolic volumes did not differ from the average cineangiographic end-systolic volume.Therefore, it is concluded that: 1) a simple geometric attenuation-correction of radionuclide left ventricular end-diastolic and end-systolic count data provides accurate estimates of biplane cineangiographic end-diastolic and end-systolic volumes; and 2) the hand-drawn region of interest selection method, unlike the semiautomated variable method that underestimates end-diastolic and end-systolic volumes, provides more accurate estimates of biplane cineangiographic left ventricular volumes irrespective of the distance blood sample counts are acquired from the collimator

A dual propagation contours technique for semi-automated assessment of systolic and diastolic cardiac function by CMR

<p>Abstract</p> <p>Background</p> <p>Although cardiovascular magnetic resonance (CMR) is frequently performed to measure accurate LV volumes and ejection fractions, LV volume-time curves (VTC) derived ejection and filling rates are not routinely calculated due to lack of robust LV segmentation techniques. VTC derived peak filling rates can be used to accurately assess LV diastolic function, an important clinical parameter. We developed a novel geometry-independent dual-contour propagation technique, making use of LV endocardial contours manually drawn at end systole and end diastole, to compute VTC and measured LV ejection and filling rates in hypertensive patients and normal volunteers.</p> <p>Methods</p> <p>39 normal volunteers and 49 hypertensive patients underwent CMR. LV contours were manually drawn on all time frames in 18 normal volunteers. The dual-contour propagation algorithm was used to propagate contours throughout the cardiac cycle. The results were compared to those obtained with single-contour propagation (using either end-diastolic or end-systolic contours) and commercially available software. We then used the dual-contour propagation technique to measure peak ejection rate (PER) and peak early diastolic and late diastolic filling rates (ePFR and aPFR) in all normal volunteers and hypertensive patients.</p> <p>Results</p> <p>Compared to single-contour propagation methods and the commercial method, VTC by dual-contour propagation showed significantly better agreement with manually-derived VTC. Ejection and filling rates by dual-contour propagation agreed with manual (dual-contour – manual PER: -0.12 ± 0.08; ePFR: -0.07 ± 0.07; aPFR: 0.06 ± 0.03 EDV/s, all P = NS). However, the time for the manual method was ~4 hours per study versus ~7 minutes for dual-contour propagation. LV systolic function measured by LVEF and PER did not differ between normal volunteers and hypertensive patients. However, ePFR was lower in hypertensive patients vs. normal volunteers, while aPFR was higher, indicative of altered diastolic filling rates in hypertensive patients.</p> <p>Conclusion</p> <p>Dual-propagated contours can accurately measure both systolic and diastolic volumetric indices that can be applied in a routine clinical CMR environment. With dual-contour propagation, the user interaction that is routinely performed to measure LVEF is leveraged to obtain additional clinically relevant parameters.</p

Activation of the hexosamine biosynthesis pathway and protein O-GlcNAcylation modulate hypertrophic and cell signaling pathways in cardiomyocytes from diabetic mice

Patients with diabetes have a much greater risk of developing heart failure than non-diabetic patients, particularly in response to an additional hemodynamic stress such as hypertension or infarction. Previous studies have shown that increased glucose metabolism via the hexosamine biosynthesis pathway (HBP) and associated increase in O-linked-β-N-acetylglucosamine (O-GlcNAc) levels on proteins contributed to the adverse effects of diabetes on the heart. Therefore, in this study we tested the hypothesis that diabetes leads to impaired cardiomyocyte hypertrophic and cell signaling pathways due to increased HBP flux and O-GlcNAc modification on proteins. Cardiomyocytes isolated from type 2 diabetic db/db mice and non-diabetic controls were treated with 1 μM ANG angiotensin II (ANG) and 10 μM phenylephrine (PE) for 24 h. Activation of hypertrophic and cell signaling pathways was determined by assessing protein expression levels of atrial natriuretic peptide (ANP), α-sarcomeric actin, p53, Bax and Bcl-2 and phosphorylation of p38, ERK and Akt. ANG II and PE significantly increased levels of ANP and α-actin and phosphorylation of p38 and ERK in the non-diabetic but not in the diabetic group; phosphorylation of Akt was unchanged irrespective of group or treatment. Constitutive Bcl-2 levels were lower in diabetic hearts, while there was no difference in p53 and Bax. Activation of the HBP and increased protein O-GlcNAcylation in non-diabetic cardiomyocytes exhibited a significantly decreased hypertrophic signaling response to ANG or PE compared to control cells. Inhibition of the HBP partially restored the hypertrophic signaling response of diabetic cardiomyocytes. These results suggest that activation of the HBP and protein O-GlcNAcylation modulates hypertrophic and cell signaling pathways in type 2 diabetes

Cardiac O-GlcNAcylation blunts autophagic signaling in the diabetic heart

Increased O-linked attachment of β-N-acetylglucosamine (O-GlcNAc) to proteins has been implicated in the adverse effects of diabetes on the heart, although this has typically been based on models of severe hyperglycemia. Diabetes has also been associated with dysregulation of autophagy, a critical cell survival process; however, little is known regarding autophagy in the diabetic heart or whether this is influenced by O-GlcNAcylation or hemodynamic stress. Young male rats were assigned to control (12% kcal fat/19% protein/69% carbohydrate), high fat diet (60/19/21%) and type 2 diabetic (high fat diet+low dose streptozotocin) groups for 8weeks, followed by sham or pressure overload surgeries; animals were sacrificed 8weeks after surgery. A modest increase in arterial pressure resulted in no significant effects on cardiac function in control or high fat groups, while diabetic hearts exhibited contractile dysfunction and increased apoptosis and scar formation. Immunoprecipitation studies revealed, for the first time, that Beclin-1, which plays a critical early role in autophagy, and the anti-apoptotic Bcl-2, are targets for O-GlcNAcylation. Interestingly, we also found that cardiomyocytes isolated from type 2 diabetic db/db mice exhibited a blunted autophagic response and this was at least partially reversed by inhibiting glucose entry into the hexosamine biosynthesis pathway, which regulates O-GlcNAc synthesis. We also found that acutely augmenting O-GlcNAc levels in non-diabetic cardiomyocytes mimicked the effects of diabetes by blunting autophagic signaling. These data suggest that O-GlcNAc-mediated inhibition of autophagy may contribute to the abnormal response of diabetic hearts to hemodynamic stress