Eli Konen

Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine.

OBJECTIVES This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). BACKGROUND Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. METHODS We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. RESULTS Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 +/- 0.1 mm vs. 1.9 +/- 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. CONCLUSIONS Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.

Deformation Dynamics and Mechanical Properties of the Aortic Annulus by 4-Dimensional Computed Tomography Insights Into the Functional Anatomy of the Aortic Valve Complex and Implications for Transcatheter Aortic Valve Therapy

OBJECTIVES The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. BACKGROUND Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation. METHODS Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Youngs elastic module was calculated from the stress-strain relationship of the annulus. RESULTS In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Youngs modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects. CONCLUSIONS The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.

X-ray Categorization and Retrieval on the Organ and Pathology Level, Using Patch-Based Visual Words

In this study we present an efficient image categorization and retrieval system applied to medical image databases, in particular large radiograph archives. The methodology is based on local patch representation of the image content, using a “bag of visual words” approach. We explore the effects of various parameters on system performance, and show best results using dense sampling of simple features with spatial content, and a nonlinear kernel-based support vector machine (SVM) classifier. In a recent international competition the system was ranked first in discriminating orientation and body regions in X-ray images. In addition to organ-level discrimination, we show an application to pathology-level categorization of chest X-ray data, the most popular examination in radiology. The system discriminates between healthy and pathological cases, and is also shown to successfully identify specific pathologies in a set of chest radiographs taken from a routine hospital examination. This is a first step towards similarity-based categorization, which has a major clinical implications for computer-assisted diagnostics.

Spiral CT and 3D image reconstruction of vascular rings and associated tracheobronchial anomalies

Objective Spiral CT (SCT) angiography and three-dimensional (3D) reconstruction methods represent noninvasive tools in diagnosis of vascular rings and associated tracheobronchial anomalies in the pediatric age group. Materials and Methods Three patients suspected on clinical and conventional radiological grounds of having vascular and tracheobronchial anomalies were examined using SCT. Three-dimensional images were reconstructed using a surface rendering technique. Results In one case the diagnosis of complete double aortic arch was confirmed by angiography. In the other two patients the SCT and 3D reconstruction established the diagnosis of pulmonary sling and right aortic arch associated with left aberrant subclavian artery and angiography could be avoided. Conclusion Spiral CT and color-coded 3D reconstruction represent important additional tools and perhaps alternatives to angiography or other noninvasive techniques used in evaluation of vascular anomalies of the thoracic aorta and pulmonary arteries in infants and children.

Tenosynovitis of the flexor tendons of the hand detected by MRI: an early indicator of rheumatoid arthritis

OBJECTIVE To evaluate the potential of MRI of finger and wrist joints for diagnosing early RA. MRI was evaluated as a stand-alone tool and in combination with ACR criteria and serum markers such as RF. METHODS Ninety-nine patients (31 men, 68 women; median age 46 years) with unspecified arthritis or suspected RA and negative X-ray findings were included. MR images of the hand and wrist of these patients were retrospectively evaluated for the presence of synovitis, erosions and tenosynovitis. The clinical diagnosis (early RA or non-RA) was made by a rheumatologist after clinical follow-up for 6-41 months. Clinical and laboratory data were collected from all patients. RESULTS Fifty-eight patients had a clinical diagnosis of RA and 41 were diagnosed as non-RA. Step-wise logistic regression of all MR parameters evaluated identified tenosynovitis of the flexor tendons to be the most powerful predictor of early RA (sensitivity = 60%, specificity = 73%). Including ACR criteria in the analysis, positive serum RF and tenosynovitis were the strongest predictors of early RA (sensitivity = 83%, specificity = 63%). When serum anti-cyclic citrullinated peptides (CCP), ANA and CRP were included as additional parameters, anti-CCP and flexor tenosynovitis were the strongest predictors of early RA (sensitivity = 79%, specificity = 73%). CONCLUSIONS Flexor tenosynovitis diagnosed by MRI of the hand is a strong predictor of early RA. Combining flexor tenosynovitis on MRI with positive serum anti-CCP or positive RF is an even stronger predictor of early RA.

The role of ECG-gated MDCT in the evaluation of aortic and mitral mechanical valves: initial experience.

OBJECTIVE The objective of our study was to evaluate the role of ECG-gated MDCT in the functional evaluation of mechanical prosthetic aortic and mitral valves. MATERIALS AND METHODS Twenty sequential patients with 23 mechanical prosthetic valves were evaluated with an ECG-gated 40- or 64-MDCT scanner. Multiplanar reformation, maximal-intensity-projection, volume-rendering, and volume-averaging techniques were used for visualization of valve leaflets in systole and diastole. The visibility of each mechanical valve was evaluated by consensus of a radiologist and a cardiologist using a subjective 5-point scale (0-4). MDCT findings were correlated with fluoroscopic opening and closing angle measurements and echocardiographic pressure gradient measurements in 11 and 19 valves, respectively. RESULTS The series included 18 bileaflet and five single-leaflet mechanical valves. The visibility score for the bileaflet mechanical valves was excellent (score of 4) in all 18 cases, but it was lower for single-leaflet valves (mean score, 2.8; range, 1-4) (p = 0.04). Bland-Altman plots showed high agreement between MDCT and fluoroscopy for measurements of opening and closing angles of bileaflet mechanical valves. In four patients, a stuck valve was seen on MDCT and was confirmed by fluoroscopy. Doppler echocardiography showed increased transvalvular pressure in two of the four patients with a stuck mitral valve and increased transaortic pressure in four patients with normal prosthetic aortic valve motion. CONCLUSION Our preliminary results suggest that MDCT is a promising technique for functional evaluation of bileaflet mechanical valves, allowing reliable measurements of opening and closing leaflet angles. However, the role of MDCT in the evaluation of single-leaflet valves might be limited.

Chest pathology detection using deep learning with non-medical training

In this work, we examine the strength of deep learning approaches for pathology detection in chest radiographs. Convolutional neural networks (CNN) deep architecture classification approaches have gained popularity due to their ability to learn mid and high level image representations. We explore the ability of CNN learned from a non-medical dataset to identify different types of pathologies in chest x-rays. We tested our algorithm on a 433 image dataset. The best performance was achieved using CNN and GIST features. We obtained an area under curve (AUC) of 0.87-0.94 for the different pathologies. The results demonstrate the feasibility of detecting pathology in chest x-rays using deep learning approaches based on non-medical learning. This is a first-of-its-kind experiment that shows that Deep learning with ImageNet, a large scale non-medical image database may be a good substitute to domain specific representations, which are yet to be available, for general medical image recognition tasks.

Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron

Erythropoiesis in long‐term hemodialyzed (LTH) patients is supported by erythropoietin (rHuEpo) and intravenous (IV) iron. This treatment may end up in iron overload (IO) in major organs. We studied such patients for the parameters of IO in the serum and in major organs.

Titin Mutation in Familial Restrictive Cardiomyopathy

BACKGROUND Familial restrictive cardiomyopathy (RCM) caused by a single gene mutation is the least common of the inherited cardiomyopathies. Only a few RCM-causing mutations have been described. Most mutations causing RCM are located in sarcomere protein genes which also cause hypertrophic cardiomyopathy (HCM). Other genes associated with RCM include the desmin and familial amyloidosis genes. In the present study we describe familial RCM with severe heart failure triggered by a de novo mutation in TTN, encoding the huge muscle filament protein titin. METHODS AND RESULTS Family members underwent physical examination, ECG and Doppler echocardiogram studies. The family comprised 6 affected individuals aged 12-35 years. Linkage to candidate loci was performed, followed by gene sequencing. Candidate loci/gene analysis excluded 18 candidate genes but showed segregation with a common haplotype surrounding the TTN locus. Sequence analysis identified a de novo mutation within exon 266 of the TTN gene, resulting in the replacement of tyrosine by cysteine. p.Y7621C affects a highly conserved region in the protein within a fibronectin-3 domain, belonging to the A/I junction region of titin. No other disease-causing mutation was identified in cardiomyopathy genes by whole exome sequencing. CONCLUSIONS Our study shows, for the first time, that mutations in TTN can cause restrictive cardiomyopathy. The giant filament titin is considered to be a determinant of a resting tension of the sarcomere and this report provides genetic evidence of its crucial role in diastolic function.

Acute Myocarditis: Noninvasive Evaluation with Cardiac MRI and Transthoracic Echocardiography

OBJECTIVE The diagnosis of acute myocarditis is challenging. Nonspecific clinical presentation and an overlap with the diagnosis of acute myocardial infarction present a diagnostic dilemma. The purpose of this article is to describe the role of cardiac MRI and transthoracic echocardiography (TTE) in the diagnosis of acute myocarditis. MATERIALS AND METHODS Thirty-two sequential patients (all male; average age, 33 years) with clinically suspected myocarditis were included. All patients underwent cardiac MRI with sequences dedicated for the evaluation of myocardial delayed enhancement and TTE for the evaluation of wall motion abnormalities (WMAs). Nine patients were excluded because of diagnosis of acute myocardial infarction (n=2) or inadequate cardiac MRI technique (n=7). Retrospective analysis of the images of the remaining 23 patients was performed. RESULTS An epicardial pattern of abnormal patchy myocardial delayed enhancement was seen on cardiac MRI in 21 of 23 (91%) patients. WMAs were seen on TTE in eight of 23 (35%) patients. Regional rather than global involvement was seen mainly in the inferolateral segments, with a predominance in the midventricular portion. CONCLUSION Cardiac MRI might have a greater impact than TTE in confirming the presence of acute myocarditis and evaluating the extent of myocardial involvement. Cardiac MRI provides noninvasive imaging that may obviate invasive procedures such as coronary catheter angiography or endomyocardial biopsy.