A moving liver phantom in an anthropomorphic thorax for SPECT MP imaging

Cranio-caudal respiratory motion and liver activity cause a variety of complex myocardial perfusion (MP) artifacts, especially in the inferior myocardial wall, that may also mask cardiac defects. To assess and characterise such artifacts, an anthropomorphic thorax with moving thoracic phantoms can be utilised in SPECT MP imaging. In this study, a liver phantom was developed and anatomically added into an anthropomorphic phantom that also encloses an ECG beating cardiac phantom and breathing lungs’ phantom. A cranio-caudal respiratory motion was also developed for the liver phantom and it was synchronised with the corresponding ones of the other thoracic phantoms. This continuous motion was further divided into isochronous dynamic respiratory phases, from end-exhalation to end-inspiration, to perform SPECT acquisitions in different respiratory phases. The new motions’ parameters and settings were measured by mechanical means and also validated in a clinical environment by acquiring CT images and by using two imaging software packages. To demonstrate the new imaging capabilities of the phantom assembly, SPECT/CT MP acquisitions were performed and compared to previous phantom and patients studies. All thoracic phantoms can precisely perform physiological motions within the anthropomorphic thorax. The new capabilities of the phantom assembly allow to perform SPECT/CT MP acquisitions for different cardiac-liver activity ratios and cardiac-liver proximities in supine and, for first time, in prone position. Thus, MP artifacts can be characterised and motion correction can be performed due to these new capabilities. The impact of artifacts and motion correction on defect detection can be also investigated.

Desmoglein 2 regulates cardiogenesis by restricting hematopoiesis in the developing murine heart

Cardiac morphogenesis relies on intricate intercellular signaling. Altered signaling impacts cardiac function and is detrimental to embryonic survival. Here we report an unexpected regulatory role of the desmosomal cell adhesion molecule desmoglein 2 (Dsg2) on murine heart development. A large percentage of Dsg2-mutant embryos develop pericardial hemorrhage. Lethal myocardial rupture is occasionally observed, which is not associated with loss of cardiomyocyte contact but with expansion of abnormal, non-myocyte cell clusters within the myocardial wall. Two types of abnormal cell clusters can be distinguished: Type A clusters involve endocard-associated, round-shaped CD31+ cells, which proliferate and invade the myocardium. They acquire Runx1- and CD44-positivity indicating a shift towards a hematopoietic phenotype. Type B clusters expand subepicardially and next to type A clusters. They consist primarily of Ter119+ erythroid cells with interspersed Runx1+/CD44+ cells suggesting that they originate from type A cell clusters. The observed pericardial hemorrhage is caused by migration of erythrocytes from type B clusters through the epicardium and rupture of the altered cardiac wall. Finally, evidence is presented that structural defects of Dsg2-depleted cardiomyocytes are primary to the observed pathogenesis. We propose that cardiomyocyte-driven paracrine signaling, which likely involves Notch1, directs subsequent trans-differentiation of endo- and epicardial cells. Together, our observations uncover a hitherto unknown regulatory role of Dsg2 in cardiogenesis.

The influence of region of interest width in fetal 2D-speckle tracking echocardiography late in pregnancy

Speckle tracking echocardiography is a promising method for assessment of myocardial function in fetal and neonatal hearts, but further studies are necessary to validate and optimize the settings for use in fetal cardiology. Previous studies have shown that the definition of the region of interest (ROI) affects strain values in adults. The aim of this study was to investigate how different widths of ROI influences measurements of four-chamber longitudinal systolic strain in fetuses late in pregnancy. Thirty-one singleton, healthy fetuses born to healthy mothers underwent an echocardiographic examination during gestational week 37. Speckle tracking was performed with two different settings for ROI width; the narrowest and second most narrow, provided both widths were assessed as suitable for the myocardial wall thickness of the fetus. We found an inverse correlation between the ROI width and the strain values. Four-chamber longitudinal strain changed from − 20.7 ± 3.6% to − 18.0 ± 4.4% (p < 0.001) with increasing ROI width. Further, strain decreased from the endocardium to the epicardium with multilayer measurements. Different widths of ROI influenced the strain measurements significantly in the fetal heart, comparable to what has been reported in adults. A standardization of the ROI setting could improve the interpretation, and reduce variability in fetal strain measurements.

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

RationalEstablishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells (EPDCs) instruct myocardial growth by secreting essential factors including fibroblast growth factor 9 (FGF9) and insulin-like growth factor 2 (IGF2). However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation.ObjectiveTo understand whether and how histone deacetylase 3 (HDAC3) in the developing epicardium regulates myocardial growth.Methods and ResultsWe deleted Hdac3 in the developing murine epicardium and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of EPDCs. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells (MECs) also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly down-regulated in Hdac3 KO MECs. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO MECs and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO MECs.ConclusionsOur findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322/miR-503, providing novel insights in elucidating etiology of congenital heart defects, and conceptual strategies to promote myocardial regeneration.

COMPARISON OF TWO THICK SHELL MODELS PERFORMANCE IN NONINVASIVE EVALUATION OF MYOCARDIAL WALL STRESS

Coronary artery stenosis is the most common heart disease, leading to altered myocardial mechanics. This study aimed to compare Ghista–Sandler and Mirsky wall stress models and evaluate the discriminant analysis of noninvasive wall stress based on these models. 59 Coronary artery disease (CAD) patients were divided into two groups; moderate stenosis and severe stenosis in the left anterior descending artery proximal part were enrolled in this study. The wall stress in the end-systolic and end-diastolic phases at LV anterior and interventricular septum wall segments calculated by using the equation proposed by Ghista–Sandler and Mirsky. The specificity and sensitivity of wall stress at groups were calculated by Ghista–Sandler and Mirsky models. The wall thickness and principal radius of segments in healthy subjects and patients with severe and moderate stenosis were shown statistically differences in some segments of anterior and septum walls ([Formula: see text]). Statistical analysis showed that calculated stresses in myocardial wall segments of patients with severe and moderate coronary stenosis and healthy people had a significant difference in systole and diastolic phase. Results of the discriminant analysis showed the specificity value obtained by the Ghista–Sandler model were higher in most wall stress combinations than the Mirsky model. Sensitivity in identifying patients with severe stenosis was higher in the Ghista–Sandler model. It is concluded that specificity and sensitivity based on wall stresses calculated by the Ghista–Sandler model were higher in comparison with the Mirsky model. The Ghista–Sandler model has better performance than the Mirsky model in diagnosing patients with stenosis.

Effect of respiratory motion correction and CT-based attenuation correction on dual-gated cardiac PET image quality and quantification

Background Dual-gating reduces respiratory and cardiac motion effects but increases noise. With motion correction, motion is minimized and image quality preserved. We applied motion correction to create end-diastolic respiratory motion corrected images from dual-gated images. Methods [18F]-fluorodeoxyglucose ([18F]-FDG) PET images of 13 subjects were reconstructed with 4 methods: non-gated, dual-gated, motion corrected, and motion corrected with 4D-CT (MoCo-4D). Image quality was evaluated using standardized uptake values, contrast ratio, signal-to-noise ratio, coefficient of variation, and contrast-to-noise ratio. Motion minimization was evaluated using myocardial wall thickness. Results MoCo-4D showed improvement for contrast ratio (2.83 vs 2.76), signal-to-noise ratio (27.5 vs 20.3) and contrast-to-noise ratio (14.5 vs 11.1) compared to dual-gating. The uptake difference between MoCo-4D and non-gated images was non-significant (P > .05) for the myocardium (2.06 vs 2.15 g/mL), but significant (P < .05) for the blood pool (.80 vs .86 g/mL). Non-gated images had the lowest coefficient of variation (27.3%), with significant increase for all other methods (31.6-32.5%). MoCo-4D showed smallest myocardial wall thickness (16.6 mm) with significant decrease compared to non-gated images (20.9 mm). Conclusions End-diastolic respiratory motion correction and 4D-CT resulted in improved motion minimization and image quality over standard dual-gating.

The Influence of Region of Interest Width In Fetal 2D-Speckle Tracking Echocardiography Late In Pregnancy

Purpose: Speckle tracking echocardiography is a promising method for assessment of myocardial function in fetal and neonatal hearts, but further studies are necessary to validate and optimize the settings for use in fetal cardiology. Previous studies have shown that the definition of the region of interest (ROI) affects strain values in adults. The aim of this study was to investigate how different widths of ROI influences measurements of four-chamber longitudinal systolic strain in fetuses late in pregnancy.Methods: Thirty-one singleton, healthy fetuses born to healthy mothers underwent an echocardiographic examination during gestational week 37. Speckle tracking was performed with two different settings for ROI width; the narrowest and second most narrow, provided both widths were assessed as suitable for the myocardial wall thickness of the fetus. Results: We found an inverse correlation between the ROI width and the strain values. Four-chamber longitudinal strain changed from -20.7 ± 3.6% to -18.0 ± 4.4% (p<0.001) with increasing ROI width. Further, strain decreased from the endocardium to the epicardium with multilayer measurements.Conclusions: Different widths of ROI influenced the strain measurements significantly in the fetal heart, comparable to what has been reported in adults. A standardization of the ROI setting could improve the interpretation, and reduce variability in fetal strain measurements.

A Moving Liver Phantom in An Anthropomorphic Thorax for SPECT MP Imaging

Cranio-caudal respiratory motion and liver activity cause a variety of complex myocardial perfusion (MP) artifacts, especially in the inferior myocardial wall, that may also mask cardiac defects. To assess and characterize such artifacts, an anthropomorphic thorax with moving thoracic phantoms can be utilized in SPECT MP imaging. In this study, a liver phantom was developed, and anatomically added into an anthropomorphic phantom, that encloses an ECG beating cardiac phantom and breathing lungs phantom. A cranio-caudal respiratory motion was also developed for the liver phantom and it was synchronized with the corresponding ones of the cardiac and lungs phantoms. This continuous motion could also be further divided into dynamic respiratory phases, from end-exhalation to end-inspiration, to perform SPECT acquisitions in different respiratory phases. The motion parameters, displacements and volumes, were validated by the acquired CT slices, the OsiriX and Vitrea software. Sample SPECT/16-slice-CT myocardial MP acquisitions were also performed and compared to the literature. The cardiac, lungs and liver phantoms can precisely perform, in time interval of 0.1 sec, physiological thoracic motions within an anthropomorphic thorax. This dynamic phantom assembly can be utilized for SPECT MP supine and, for first time, prone imaging to access and characterize artifacts due to different cranio-caudal respiratory amplitudes and cardiac-liver activity ratios.

The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression

The transcription factor Snai1, a well-known regulator of epithelial-to-mesenchymal transition, has been implicated in early cardiac morphogenesis as well as in cardiac valve formation. However, a role for Snai1 in regulating other aspects of cardiac morphogenesis has not been reported. Using genetic, transcriptomic, and chimeric analyses in zebrafish, we find that Snai1b is required in cardiomyocytes for myocardial wall integrity. Loss of snai1b increases the frequency of cardiomyocyte extrusion away from the cardiac lumen. Extruding cardiomyocytes exhibit increased actomyosin contractility basally as revealed by enrichment of p-myosin and α-catenin epitope α-18, as well as disrupted intercellular junctions. Transcriptomic analysis of wild-type and snai1b mutant hearts revealed the dysregulation of intermediate filament genes, including desmin b (desmb) upregulation. Cardiomyocyte-specific desmb overexpression caused increased cardiomyocyte extrusion, recapitulating the snai1b mutant phenotype. Altogether, these results indicate that Snai1 maintains the integrity of the myocardial epithelium, at least in part by repressing desmb expression.