3D Myocardial Scar Prediction Model Derived from Multimodality Analysis of Electromechanical Mapping and Magnetic Resonance Imaging.

Many cardiac catheter interventions require accurate discrimination between healthy and infarcted myocardia. The gold standard for infarct imaging is late gadolinium-enhanced MRI (LGE-MRI), but during cardiac procedures electroanatomical or electromechanical mapping (EAM or EMM, respectively) is usually employed. We aimed to improve the ability of EMM to identify myocardial infarction by combining multiple EMM parameters in a statistical model. From a porcine infarction model, 3D electromechanical maps were 3D registered to LGE-MRI. A multivariable mixed-effects logistic regression model was fitted to predict the presence of infarct based on EMM parameters. Furthermore, we correlated feature-tracking strain parameters to EMM measures of local mechanical deformation. We registered 787 EMM points from 13 animals to the corresponding MRI locations. The mean registration error was 2.5 ± 1.16 mm. Our model showed a strong ability to predict the presence of infarction (C-statistic = 0.85). Strain parameters were only weakly correlated to EMM measures. The model is accurate in discriminating infarcted from healthy myocardium. Unipolar and bipolar voltages were the strongest predictors.

Multimodality imaging for real-time image-guided left ventricular lead placement during cardiac resynchronization therapy implantations.

This study was performed to evaluate the feasibility of intra-procedural visualization of optimal pacing sites and image-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT). In fifteen patients (10 males, 68 ± 11 years, 7 with ischemic cardiomyopathy and ejection fraction of 26 ± 5%), optimal pacing sites were identified pre-procedurally using cardiac imaging. Cardiac magnetic resonance (CMR) derived scar and dyssynchrony maps were created for all patients. In six patients the anatomy of the left phrenic nerve (LPN) and coronary sinus ostium was assessed via a computed tomography (CT) scan. By overlaying the CMR and CT dataset onto live fluoroscopy, aforementioned structures were visualized during LV lead implantation. In the first nine patients, the platform was tested, yet, no real-time image-guidance was implemented. In the last six patients real-time image-guided LV lead placement was successfully executed. CRT implant and fluoroscopy times were similar to previous procedures and all leads were placed close to the target area but away from scarred myocardium and the LPN. Patients that received real-time image-guided LV lead implantation were paced closer to the target area compared to patients that did not receive real-time image-guidance (8 mm [IQR 0-22] vs 26 mm [IQR 17-46], p = 0.04), and displayed marked LV reverse remodeling at 6 months follow up with a mean LVESV change of -30 ± 10% and a mean LVEF improvement of 15 ± 5%. Real-time image-guided LV lead implantation is feasible and may prove useful for achieving the optimal LV lead position.

Validation of a novel stand-alone software tool for image guided cardiac catheter therapy.

Comparison of the targeting accuracy of a new software method for MRI-fluoroscopy guided endomyocardial interventions with a clinically available 3D endocardial electromechanical mapping system. The new CARTBox2 software enables therapy target selection based on infarction transmurality and local myocardial wall thickness deduced from preoperative MRI scans. The selected targets are stored in standard DICOM datasets. Fusion of these datasets with live fluoroscopy enables real-time visualization of MRI defined targets during fluoroscopy guided interventions without the need for external hardware. In ten pigs (60-75 kg), late gadolinium enhanced (LGE) MRI scans were performed 4 weeks after a 90-min LAD occlusion. Subsequently, 10-16 targeted fluorescent biomaterial injections were delivered in the infarct border zone (IBZ) using either the NOGA 3D-mapping system or CARTBox2. The primary endpoint was the distance of the injections to the IBZ on histology. Secondary endpoints were total procedure time, fluoroscopy time and dose, and the number of ventricular arrhythmias. The average distance of the injections to the IBZ was similar for CARTBox2 (0.5 ± 3.2 mm) and NOGA (- 0.7 ± 2.2 mm; p = 0.52). Injection procedures with CARTBox2 and NOGA required 69 ± 12 and 60 ± 17 min, respectively (p = 0.36). The required endocardial mapping procedure with NOGA prior to injections, leads to a significantly longer total procedure time (p < 0.001) with NOGA. Fluoroscopy time with NOGA (18.7 ± 11.0 min) was significantly lower than with CARTBox2 (43.4 ± 6.5 min; p = 0.0003). Procedures with CARTBox2 show a trend towards less ventricular arrhythmias compared to NOGA. CARTBox2 is an accurate and fast software-only system to facilitate cardiac catheter therapy based on gold standard MRI imaging and live fluoroscopy.

3D Whole-heart Myocardial Tissue Analysis.

Cardiac regenerative therapies aim to protect and repair the injured heart in patients with ischemic heart disease. By injecting stem cells or other biologicals that enhance angio- or vasculogenesis into the infarct border zone (IBZ), tissue perfusion is improved, and the myocardium can be protected from further damage. For maximum therapeutic effect, it is hypothesized that the regenerative substance is best delivered to the IBZ. This requires accurate injections and has led to the development of new injection techniques. To validate these new techniques, we have designed a validation protocol based on myocardial tissue analysis. This protocol includes whole-heart myocardial tissue processing that enables detailed two-dimensional (2D) and three-dimensional (3D) analysis of the cardiac anatomy and intramyocardial injections. In a pig, myocardial infarction was created by a 90-min occlusion of the left anterior descending coronary artery. Four weeks later, a mixture of a hydrogel with superparamagnetic iron oxide particles (SPIOs) and fluorescent beads was injected in the IBZ using a minimally-invasive endocardial approach. 1 h after the injection procedure, the pig was euthanized, and the heart was excised and embedded in agarose (agar). After the solidification of the agar, magnetic resonance imaging (MRI), slicing of the heart, and fluorescence imaging were performed. After image post-processing, 3D analysis was performed to assess the IBZ targeting accuracy. This protocol provides a structured and reproducible method for the assessment of the targeting accuracy of intramyocardial injections into the IBZ. The protocol can be easily used when the processing of scar tissue and/or validation of the injection accuracy of the whole heart is desired.

NADP+ -dependent IDH1 R132 mutation and its relevance for glioma patient survival.

The isocitrate dehydrogenase 1 (IDH1) mutation occurs in high frequency in glioma and secondary glioblastoma (GBM). Mutated IDH1 produces the oncometabolite 2-hydroxyglutarate rather than α-ketoglutarate or isocitrate. The oncometabolite is considered to be the major cause of the association between the IDH1 mutation and gliomagenesis. On the other hand, the IDH1 mutation in GBM is associated with prolonged patient survival. This association is not well understood yet but IDH1 involvement in epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme is considered to be an important mechanism. However, it was shown recently that the IDH1 mutation and MGMT silencing are independent prognostic factors. Here, we hypothesize that the IDH1 mutation reduces the capacity to produce NADPH and thus reduces the capacity to scavenge reactive oxygen species that are generated during irradiation and chemotherapy. IDH1 activity is responsible for two-thirds of the NADPH production capacity in normal brain, whereas the IDH1 mutation reduces this capacity by almost 40%. Therefore, we hypothesize that the reduced NADPH production capacity due to the IDH1 mutation renders GBM cells more vulnerable to irradiation and chemotherapy thus prolonging survival of the patients.

[Recovery from blindness following smallpox or measles: Dutch miracle stories, 14th-18th century]. / Genezing van blindheid na pokken of mazelen: Nederlandse mirakelverhalen, 14e-18e eeuw.

Over recent decades, stories of miracles dating from 1380-1726 have been transcribed and are now generally available. These texts only contain a limited amount of medical information. This article closely examines the stories of being cured of blindness after being infected by smallpox or measles. Most of these stories concern children. Eleven of a total of 1700 stories that took place during the above-mentioned period of time concern this type of miracle. The article examines the possible relationship between these miracles and a lack of vitamin A.

The influence of sex hormones on cytokines in multiple sclerosis and experimental autoimmune encephalomyelitis: a review.

The female predominance of multiple sclerosis (MS) has suggested that hormonal differences between the sexes must confer some protective effect on males or enhance the susceptibility of females to this disease. There has been evidence that gonadal hormones can modulate the immune response regulated by antigen presenting cells and T cells. These cells control the immune response by the production of interacting pro- and anti-inflammatory cytokines. The first include the acute phase pro-inflammatory cytokines of the innate immune response as well as the T-helper 1 (Th1) cytokines, while the later contain the Th2 cytokines as well as the suppressor cytokines. There is some evidence that MS and experimental autoimmune encephalitis (EAE) are Th1 cell-mediated diseases. For this reason many studies have been done to influence the pro-inflammatory cytokine production of these Th1 cells in favour of an anti-inflammatory immune response as mediated by Th2 cells. However the role of the regulatory T cells in this context is not clearly understood. Here we review the studies concerning the role of sex hormones on the cytokine production in relation to the disease course of MS and EAE and in particular in the light of the recent revival of the regulatory T cells and their suppressive cytokines.