Search Results (55)

Living myocardial slices (LMSs) have shown great promise in cardiac research, allowing multicellular and complex interplay analyses with disease and patient specificity, yet their wider clinical use is limited by the large tissue sizes usually required. We therefore produced mini-LMSs (<10 mm²) from routine human cardiac surgery specimens and compared them with medium (10–30 mm²) and large (>30 mm²) slices. Size effects on biomechanical properties were examined with mathematical modeling, and viability, contraction profiles, and histological integrity were followed for 14 days. In total, 34 mini-, 25 medium, and 30 large LMS were maintained viable, the smallest measuring only 2 mm². Peak twitch force proved to be size-independent, whereas time-to-peak shortened as slice area decreased. Downsized LMSs displayed excellent contractile behavior for five to six days, after which a gradual functional decline and micro-architectural changes emerged. These findings confirm, for the first time, that mini-LMSs are feasible and viable, enabling short-term, patient-specific functional studies and pharmacological testing when tissue is scarce. Full article

Background: The use of photon-counting detector computed tomography (PCD-CT) has improved image quality in cardiac, pulmonary, and musculoskeletal imaging. Abdominal imaging research, especially about the use of PCD-CT in hepatocellular carcinoma (HCC), is sparse. Objectives: We aimed to compare the image quality of tumors, the liver parenchyma, and the vasculature in patients with HCC using PCD-CT reconstructions at different slice thicknesses and kernels to identify the most appropriate settings for the clinical routine. Methods: CT exams from twenty adult patients with HCC performed with a clinically approved, first-generation PCD-CT scanner (Naeotom Alpha^®, Siemens Healthineers), were retrospectively reviewed. For each patient, images were reconstructed at four different sharp kernels, designed for abdominal imaging (Br40; Br44; Br48; Br56) and at three slice thicknesses (0.4 mm; 1 mm; 3 mm). The reconstruction with the Br40 kernel at 3 mm (Br40_{3 mm}) was used as a clinical reference. Three readers independently assessed the image quality of different anatomical abdominal structures and hypervascular HCC lesions using a five-point Likert scale. In addition, image sharpness was assessed using line-density profiles. Results: Compared with the clinical reference, the Br44_{1 mm} and Br48_{1 mm} reconstructions were rated superior for the assessment of the hepatic vasculature (median difference +0.67 [+0.33 to +1.33], p < 0.001 and +1.00 [+0.67 to +1.67], p < 0.001). Reconstructions for Br40_{1 mm} (+0.33 [−0.67 to +1.00], p < 0.001), and Br44_{3 mm} (+0.0 [0.0 to +1.00], p = 0.030) were scored superior for overall image quality. The noise demonstrated a continuous increase when using sharper kernels and thinner slices than Br40_{3 mm} (p < 0.001), leading to a decrease in contrast-to-noise ratio. Although there was a trend toward increased image sharpness using the slope analysis with higher kernels, this was not significantly different compared with the reference standard. Conclusion: PCD-CT reconstruction Br40_{1 mm} was the most suitable setting for overall image quality, while reconstructions with sharper kernels (Br44_{1 mm} and Br48_{1 mm}) can be considered for the assessment of the hepatic vasculature in patients with HCC. Full article

Background/Objectives: While T₂^* mapping effectively assesses cerebral blood oxygenation, its utility for capturing cardiac phase-dependent myocardial changes in hypertrophic cardiomyopathy (HCM) is underexplored. This study investigates T₂^* dynamics in an HCM mouse model, to validate T₂^* as a clinically relevant biomarker for improved HCM diagnosis and treatment monitoring. Methods: A cardiac-specific Mybpc3 genetic mouse model, closely mirroring human HCM, was used with 12 young mice (6–11 weeks old), including both male and female wild-type (WT) and Mybpc3-KI (HCM) groups. The cardiac function was assessed using self-gated multi-slice 2D CINE imaging. To investigate myocardial T₂^* variations across the cardiac cycle, multi-gradient echo (MGE) imaging was employed. This approach used retrospective gating and continuous acquisition synchronization with pulse oximetry at 9.4 T small animal MRI. Results: Mybpc3-KI mice demonstrated left-ventricular (LV) hypertrophy compared to WT (HCM = 50.08 ± 4.68 µm/g vs. WT = 45.80 ± 20.07 µm/g, p < 0.01) and reduced ejection fraction (HCM = 38.55 ± 5.39% vs. WT= 72.53 ± 3.95%, p < 0.01). Myocardial T₂^* was significantly elevated in HCM across all cardiac phases (HCM = 12.14 ± 1.54 ms vs. WT = 7.93 ± 1.57 ms, p = 0.002). Strong correlations were observed between myocardial T₂^* and LV mass (rho = 0.88, p = 0.03). Conclusions: T₂^* was elevated in HCM with increased LV mass, highlighting the potential of T₂^* MRI as a sensitive biomarker for distinguishing healthy mice from those with HCM and revealing possible myocardial abnormalities. Full article

Objective: Cerebral vascularization is made of the symmetrical arterial system, with muscular walls, and the venous system, more variable and dominated by sinuses and jugular veins. Factors like age and posture influence this network, complicating its study. Phase-contrast MRI is the gold standard for quantifying cerebral circulation. This study aimed to quantify the dynamics of the cerebral blood system using PC-MRI. Materials and Methods: Thirty-six healthy adults participated. Imaging was performed on a 3T MRI (Philips Achieva) in a supine position. Two slices were acquired: intracranial and extracranial. In-house software analyzed flow curves over a cardiac cycle. Each vessel’s contribution was evaluated. Results: Extracranial venous drainage was categorized as jugular-dominant, equivalent, or peripheral-dominant. A similar classification applied intracranially. Intracranial flows showed low variability (5–9%), while extracranial venous flows, especially in the internal jugular veins, had higher variability (17–21%). Some extracranial veins were absent. Conclusions: There is significant venous heterogeneity in the extracranial region. PC-MRI enables the quantification of cerebral dynamics. Full article

Atrial fibrillation (AF) is associated with energetic deficiency and oxidative stress due to mitochondrial dysfunction, resulting in electric remodeling. Long-term treatment was found to ameliorate mitochondrial function and decrease inducibility in animal models. No studies examine the short-term effect of SGLT-2 inhibitors administration in AF. In the present study, the samples of the right atrial appendage collected from 10 patients subjected to elective cardiac surgery were sliced and incubated in a control buffer (EMPA 0), 0.2 µmol/L empagliflozin (EMPA 0.2), or 1.0 µmol/L (EMPA 1). The expression of mitochondrial biogenesis, fission, and fusion proteins was measured by Western blot after 30 min of electrical stimulation (control—1 Hz or tachypacing—5 Hz). The PGC-1α protein expression was increased after 30 min of stimulation with 1 Hz when incubated under a higher concentration of empagliflozin. After tachypacing, EMPA 0.2 increased PGC-1α, while EMPA 1.0 upregulated NRF-1. Both concentrations increased NRF-2 during control stimulation. The oxygen consumption was higher in AF, and was decreased by SGLT-2i. Empagliflozin exerts dynamic effects on the expression of PGC-1α and other proteins involved in mitochondrial function and oxidative stress in cardiomyocytes and may modulate cellular response to tachycardia. Full article

Proof-of-concept to determine the direct biomechanical effects of cardiac contractility modulation (CCM) on living myocardial slices (LMS) from patients with end-stage heart failure (HF). Left ventricular LMS from patients with end-stage HF were produced and cultured in a biomimetic system with mechanical loading and electrical stimulation. CCM stimulation (80 mA, 40 ms delay, 21 ms duration) enhanced maximum contractile force (CCM: 1229 µN (587–2658) vs. baseline: 1066 µN (529–2128), p = 0.05) and area under the contractile curve (CCM: 297 (151–562) vs. baseline: 243 (129–464), p = 0.05) but did not significantly impact contractile duration, time to peak, or time to relaxation. Increasing CCM stimulation delay, duration, and amplitude resulted in a higher fraction of LMS with a positive inotropic response. Furthermore, CCM attenuated the negative force-frequency relationship in HF-LMS. CCM stimulation enhanced contractile force in HF-LMS. The fraction of LMS exerting a positive inotropic response to CCM increased with increasing delay, duration, and amplitude settings, suggesting that personalizing stimulation parameters could optimize the beneficial effects of CCM. CCM is a novel device-based therapy that may improve contractile function, ejection fraction, functional outcomes, and quality of life in patients with heart failure. However, continuous efforts are needed to identify true responders to CCM therapy, understand the exact mechanisms, and optimize the contractile response to CCM stimulation. The present study revealed that CCM enhanced the contractile force of HF-LMS in a stimulation setting-dependent manner, reaching a larger fraction of the myocardium while increasing delay, duration, and amplitude. This understanding may contribute to the individualization of CCM stimulation settings. Full article

Background/Objective: Left atrial (LA) fibrosis imaging improves the guidance of LA catheter ablation. Cardiac computed tomography (CT) may be a reasonable alternative to CMR. The aim was to evaluate late enhancement (LE) fibrosis mapping by CT, and to correlate the results with low-voltage areas on electroanatomical mapping (EAM). Methods: In patients with atrial fibrillation who underwent 128-slice dual-source CT angiography (CTA) prior to LA catheter ablation, an additional LE-CT scan was performed 7 min after CTA. (1) Left atrial wall thickness (LAWT) was measured at three sites along the LA ridge. (2) Late enhancement (LE) was quantified co-axially aligned to LAWT and compared with low-voltage areas (LVA) on EAM. Results: Of 137 patients (age: 59.8 years; 27.7% females), 108 were included. The prevalence of LE was higher in patients with LAWT > 2 mm compared with 1.5 mm, with 78 (91.7%) vs. 77 (80.2%) (p = 0.022). Of 78 patients with LE, 60 (77.1%) had focal, 13 (16.5%) had diffuse, and 5 (6.3%) had mixed LE patterns. The CT density of focal LE was not different from that of diffuse patterns (104.2 +/− 21 HU vs. 98.9 +/− 18 HU; p = 0.360). Increasing LAWT and LE-HU were weakly correlated (r = 0.229; p = 0.041). LA wall artifacts had higher CT density compared with LE (154.1 HU vs. 114.2 HU; p = 0.002). The effective radiation dose was 0.95 mSv (range, 0.52–1.2 mSv) for LE-CT. The agreement of LE-CT was 80% for LVA < 0.5 mV and 86.6% for LVA < 0.7 mV in a subset of 30 patients. Conclusions: Left atrial fibrosis mapping by LE-CT is feasible. Late enhancement was found more frequently in LAWTs of more than 2 mm, and LE was correlated with increasing LA remodeling and low-voltage areas. Full article

Background: The utilization of hemodynamic parameters, whose estimation is often cumbersome, can fasten diagnostics and decision-making related to congenital heart diseases. The main goal of this study is to investigate the relationship between hemodynamic and morphometric features of the thoracic aorta and to construct corresponding predictive models. Methods: Multi-slice spiral computed tomography images of the aortas of patients with coarctation diagnoses and patients without cardiac or vascular diseases were evaluated to obtain numerical models of the aorta and branches of the aortic arch. Hemodynamic characteristics were estimated in key subdomains of the aorta and three branches using computational fluid dynamics methods. The key morphometric features (diameters) were calculated at locations in proximity to the domains, where hemodynamic characteristics are evaluated. Results: The functional dependencies for velocities and pressure on the corresponding diameters have been fitted, and a metamodel has been constructed employing the predicted values from these models. Conclusions: The metamodel demonstrated high accuracy in classifying aortas into their respective types, thereby confirming the adequacy of the predicted hemodynamic characteristics by morphometric characteristics. The proposed methodology is applicable to other heart diseases without fundamental changes. Full article

Brain swelling after cardiac arrest may affect brain ventricular volume. This study aimed to investigate the prognostic implications of ventricular volume on early thin-slice brain computed tomography (CT) after cardiac arrest. We measured the gray-to-white matter ratio (GWR) and the characteristics and volumes of the lateral, third, and fourth ventricles. The primary outcome was a poor 6-month neurological outcome. Of the 166 patients, 115 had a poor outcome. The fourth ventricle was significantly smaller in the poor outcome group (0.58 cm³ [95% CI, 0.43–0.80]) than in the good outcome group (0.74 cm³ [95% CI, 0.68–0.99], p < 0.001). Ventricular characteristics and other ventricular volumes did not differ between outcome groups. The area under the curve for the fourth ventricular volume was 0.68, comparable to 0.69 for GWR. Lower GWR (<1.09) and lower fourth ventricular volume (<0.41 cm³) predicted poor outcomes with 100% specificity and sensitivities of 8.7% (95% CI, 4.2–15.4) and 20.9% (95% CI, 13.9–29.4), respectively. Combining these measures improved the sensitivity to 25.2% (95% CI, 17.6–34.2). After adjusting for covariates, the fourth ventricular volume was independently associated with neurologic outcome. A marked decrease in fourth ventricular volume, with concomitant hypoattenuation on CT scans, more accurately predicted outcomes. Full article

Endothelial progenitor cells (EPCs) play a critical role in cardiovascular regeneration. Enhancement of their native properties would be highly beneficial to ensuring the proper functioning of the cardiovascular system. As androgens have a positive effect on the cardiovascular system, we hypothesized that dihydrotestosterone (DHT) could also influence EPC-mediated repair processes. To evaluate this hypothesis, we investigated the effects of DHT on cultured human EPCs’ proliferation, viability, morphology, migration, angiogenesis, gene and protein expression, and ability to integrate into cardiac tissue. The results showed that DHT at different concentrations had no cytotoxic effect on EPCs, significantly enhanced the cell proliferation and viability and induces fast, androgen-receptor-dependent formation of capillary-like structures. DHT treatment of EPCs regulated gene expression of androgen receptors and the genes and proteins involved in cell migration and angiogenesis. Importantly, DHT stimulation promoted EPC migration and the cells’ ability to adhere and integrate into murine cardiac slices, suggesting it has a role in promoting tissue regeneration. Mass spectrometry analysis further highlighted the impact of DHT on EPCs’ functioning. In conclusion, DHT increases the proliferation, migration, and androgen-receptor-dependent angiogenesis of EPCs; enhances the cells’ secretion of key factors involved in angiogenesis; and significantly potentiates cellular integration into heart tissue. The data offer support for potential therapeutic applications of DHT in cardiovascular regeneration and repair processes. Full article

In cardiac cine imaging, acquiring high-quality data is challenging and time-consuming due to the artifacts generated by the heart’s continuous movement. Volumetric, fully isotropic data acquisition with high temporal resolution is, to date, intractable due to MR physics constraints. To assess whole-heart movement under minimal acquisition time, we propose a deep learning model that reconstructs the volumetric shape of multiple cardiac chambers from a limited number of input slices while simultaneously optimizing the slice acquisition orientation for this task. We mimic the current clinical protocols for cardiac imaging and compare the shape reconstruction quality of standard clinical views and optimized views. In our experiments, we show that the jointly trained model achieves accurate high-resolution multi-chamber shape reconstruction with errors of <13 mm HD95 and Dice scores of >80%, indicating its effectiveness in both simulated cardiac cine MRI and clinical cardiac MRI with a wide range of pathological shape variations. Full article

Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutation in the dystrophin gene. Currently there is no cure for DMD. We introduced a novel human Dystrophin Expressing Chimeric (DEC) cell therapy of myoblast origin and confirmed the safety and efficacy of DEC in the mdx mouse models of DMD. In this study, we assessed histological and morphological changes in the cardiac, diaphragm, and gastrocnemius muscles of the mdx/scid mice after the transplantation of human DEC therapy via the systemic-intraosseous route. The efficacy of different DEC doses was evaluated at 90 days (0.5 × 10⁶ and 1 × 10⁶ DEC cells) and 180 days (1 × 10⁶ and 5 × 10⁶ DEC cells) after administration. The evaluation of Hematoxylin & Eosin (H&E)-stained sectional slices of cardiac, diaphragm, and gastrocnemius muscles included assessment of muscle fiber size by minimal Feret’s diameter method using ImageJ software. The overall improvement in muscle morphology was observed in DMD-affected target muscles in both studies, as evidenced by a shift in fiber size distribution toward the wild type (WT) phenotype and by an increase in the mean Feret’s diameter compared to the vehicle-injected controls. These findings confirm the long-term efficacy of human DEC therapy in the improvement of overall morphological pathology in the muscles affected by DMD and introduce DEC as a novel therapeutic approach for DMD patients. Full article

This article is the third in our series dedicated to the analysis of cardiac myoarchitecture as a nematic chiral liquid crystal (NCLC). Previously, we introduced the concept of topological defects (disclinations) and focused on their visual identification inside the compact myocardium. Herein, we investigate these using a mathematical and automated algorithm for the reproducible identification of a larger panel of topological defects throughout the myocardium of 13 perinatal and 11 early infant hearts. This algorithm identified an average of 29 ± 11 topological defects per slice with a 2D topological charge of m = +1/2 and an average of 27 ± 10 topological defects per slice with a 2D topological charge of m = −1/2. The excess of defects per slice with a 2D topological charge of m = +1/2 was statistically significant (p < 0.001). There was no significant difference in the distribution of defects with a 2D topological charge of m = +1/2 and m = −1/2 between perinatal and early infant hearts. These defects were mostly arranged in pairs, as expected in nematics, and located inside the trabecular myocardium. When isolated, defects with a 2D topological charge of m = +1/2 were located near the luminal extremity of the trabeculae and those with a 2D topological charge of m = −1/2 were located at the anterior and posterior part of the interventricular septum. These findings constitute an advance in the characterization of the deep cardiac myoarchitecture for application in developmental and pathological studies. Full article

Background: Anomalous aortic origin of a coronary artery (AAOCA) is the most prevalent form of coronary anomaly. One variant of AAOCA is the anomalous origin of the left circumflex artery from the right sinus of Valsalva, which can be detected using cardiac computed tomography (CT). However, limited data are available regarding the natural history of this anomaly, its impact on myocardial function, and associated symptoms. Methods: We conducted a retrospective analysis of 16,680 CT exams (cardiac and chest) performed between 2015 and 2022 at our Heart Imaging Department, utilising a dual-source 128-slice CT scanner (SOMATOM Definition Flash, Siemens Healthineers, Forchheim, Germany). A registry of patients with anomalous origin of the circumflex artery from the right sinus of Valsalva (RCx) was established. The study included 56 cases of RCx (0.33%). Clinical information was obtained from medical records. RCx was defined as a circumflex artery originating from the right sinus of Valsalva (type I or II) or the right coronary artery (type III). Two researchers independently reevaluated each CT exam in our study group to ensure accurate radiologic descriptions and provide additional precise radiologic information regarding the anomaly, including high-risk features. Results: Our study comprised 56 patients, with approximately equal distribution between males (n = 30, 54%) and females (n = 26, 46%), and with a median age of 59 years. Coronary heart disease (CAD) was known in 23% of patients (n = 13), while 11% (n = 6) were obese (defined as a BMI > 30 kg/m²), and 13% (n = 7) were diagnosed with type 2 diabetes. Only 9% of patients (n = 5) were smokers. Dyslipidemia was the most prevalent atherosclerotic risk factor, affecting approximately one third of patients (n = 17, 30%). In 14% (n = 8) of patients, heart failure was observed, while 13% (n = 7) were diagnosed with atrial fibrillation. Type I RCx was the most common subtype, identified in 48% of patients (n = 27) with this anomaly. Type II and Type III were found in 25% (n = 14) and 27% (n = 15) of patients, respectively. Conclusions: Our findings suggest that RCx is frequently encountered as an incidental finding, and we did not identify a consistent clinical characteristic in all patients with this type of anomaly. Furthermore, no gender predominance was associated with RCx. The natural history of this anomaly and its clinical implications seem benign. Further research is warranted to better understand this anomaly’s natural course and clinical implications. Full article

Objective: This study aims to evaluate image quality in patients with heart rates above or equal to 70 beats per minute (bpm), performed on a 16 cm scanner (256-slice General Electric Revolution) in comparison to a CT scanner with only 4 cm of coverage (64 slice Volume CT). Background: Recent advancements in image acquisition, such as whole-heart coverage in a single rotation and post-processing methods in coronary computed tomographic angiography (CCTA), include motion-correction algorithms, such as SnapShot Freeze (SSF), which improve temporal resolution and allow for the assessment of coronary artery disease (CAD) with lower motion scores and better image qualities. Studies from the comprehensive evaluation of high temporal- and spatial-resolution cardiac CT using a wide coverage system (CONVERGE) registry (a multicenter registry at four centers) have shown the 16 cm CT scanner having a better image quality in comparison to the 4 cm scanner. However, these studies failed to include patients with undesirable or high heart rates due to well-documented poor image acquisition on prior generations of CCTA scanners. Methods: A prospective, observational, multicenter cohort study comparing image quality, quantitively and qualitatively, on scans performed on a 16 cm CCTA in comparison to a cohort of images captured on a 4 cm CCTA at four centers. Participants were recruited based on broad inclusion criteria, and each patient in the 16 cm CCTA arm of the study received a CCTA scan using a 256-slice, whole-heart, single-beat scanner. These patients were then matched by age, gender, and heart rate to patients who underwent CCTA scans on a 4 cm CT scanner. Image quality was graded based on the signal-to-noise ratio, contrast-to-noise ratio, and on a Likert scale of 0–4: 0, very poor—4, excellent. Results: 104 patients were evaluated for this study. The mean heart rate was 75 ± 7 in the 4 cm scanner and 75 ± 7 in the 16 cm one (p = 0.426). The signal-to-noise and contrast-to-noise ratios were higher in the 16 cm scanner (p = 0.0001). In addition, more scans were evaluated as having an excellent quality on the 16 cm scanner than on the 4 cm scanner (p < 0.0001) based on a 4-point Likert scale. Conclusions: The 16 cm scanner has a superior image quality for fast heart rates compared to the 4 cm scanner. This study shows that there is a significantly higher frequency of excellent and good studies showing better contrast-to-noise and signal-to-noise ratios with the 16 cm scanner compared to the 4 cm scanner. Full article