Cette thèse porte sur le développement et l’évaluation de techniques d’imagerie en échocardiographie. L’objectif est de proposer des méthodes d’imagerie ultrasonore ultrarapide pour estimer le mouvement cardiaque 2-D et 3-D.Première modalité d’imagerie du cœur, l’échocardiographie conventionnelle permet la mesure des déformations myocardiques à 80 images/s. Cette cadence d’imagerie est insuffisante pour quantifier les mouvements de la totalité du myocarde lors de tests d’efforts, utiles en évaluation clinique, au cours desquels le rythme cardiaque est augmenté. De plus, la résolution temporelle actuelle en échocardiographie 3-D limite ses applications, pourtant essentielles pour une caractérisation complète du cœur.Les contributions présentées ici sont 1) le développement et l’évaluation, pour l’application cardiaque, d’une méthode originale d’estimation de mouvement 2-D par imagerie ultrarapide et marquage des images, 2) l’étude de faisabilité de la mesure globale des déformations cardiaques avec une méthode innovante d’imagerie ultrasonore ultrarapide 2-D et 3) la généralisation de cette approche en 3-D pour l’imagerie des volumes cardiaques à haute résolution temporelle. Cette technique est basée sur l’émission d’ondes divergentes, et l’intégration d’une compensation de mouvement dans le processus de formation des volumes cardiaques.La méthode proposée permet l’estimation des mouvements cardiaques 2-D et l’échocardiographie ultrarapide 3-D. L’évaluation de notre approche pour la quantification des déformations myocardiques locales 2-D et 3-D pourrait permettre de proposer des pistes innovantes pour poursuivre nos études et améliorer le diagnostic en routine clinique / This PhD work focuses on the development and the evaluation of imaging techniques in echocardiography. Our objective is to propose ultrafast ultrasound imaging methods for 2-D and 3-D cardiac motion estimations.Echocardiography is one of the most widespread modality for cardiovascular imaging. Conventional clinical scanners allow measurement of myocardial velocities and deformations at 80 images / s. In some situations, it can be recommended to increase the heart rate during a stress echocardiographic examination. Motion estimation of the whole myocardium at such heart rates is challenging with the conventional imaging systems. In addition, the low temporal resolution of the current conventional 3-D echocardiography limits quantitative applications, which would be needed for a complete characterization of the heart.The three contributions presented here are 1) the development and evaluation of an original method for 2-D cardiac motion estimation, with ultrafast imaging and image tagging, 2) the feasibility study of the global myocardial deformation measurement using an innovative 2-D ultrafast ultrasound imaging method and 3) the generalization of this approach in three dimensions for high frame-rate 3-D echocardiography. This method is based on the transmission of divergent waves and the integration of motion compensation, during the imaging process, to produce high-quality volumetric images of the heart.The proposed method allows 2-D cardiac motion estimation and 3-D echocardiography at high frame-rate. The evaluation of our approach for local 2-D and 3-D myocardial deformation measurements should permit to conduct further study in order to improve medical diagnosis

The Objectives of this thesis are: 1) To study possible atrial interaction in patients with right and left ventricular outflow tract obstruction due to significant pulmonary (PS) and aortic valve stenosis (AS), respectively. 2) To assess left atrial (LA) intrinsic myocardial function and its relationship to indirect measures of left ventricular (LV) filling pressures in patients with paroxysmal atrial fibrillation (PAF). 3) To test the hypothesis that the LA function is affected in patients with pulmonary arterial hypertension (PAH). 4) To test the hypothesis that raised LA pressure as shown by pulmonary capillary wedge pressure (PCWP) correlates with severity of LA intrinsic systolic function. We conducted 4 studies to achieve the objective sabove. Study I Methods: We studied 41 PS patients (age 36±10 year) and 41 AS patients (age 35 ± 12 year) and compared them with 27 controls (age 30 ± 7 year). RV and LV filling were recorded by conventional PW Doppler. Biventricular segmental function was studied using the PW tissue Doppler imaging (TDI) and M mode techniques. Results: The 2 patient groups had similar degree of ventricular outflow tract obstruction. In the pressureoverloaded ventricle, global systolic function was preserved but long axis function was impaired.Patients had higher peak late filling (Awave)and TDI late diastolic (a’) velocities recorded in the disease free ventricles despite having similar peak early filling velocities (E wave), E wave deceleration time and E/e’ ratios were not different from controls (p>0.05 for all). The accentuation of atrial activity (A wave) was moderately correlated with the degree of contra lateral ventricular outflow tract obstruction (p<0.001 for both). Conclusion: In the pressure overloaded ventricle long axis function is more sensitive than global function in revealing myocardial dysfunction. The increased contra lateral atrial systolic activity suggests an evidence for atrial interaction in the form of ‘Cross Talk’. Study II Methods: Twentyfive PAF patients (age 68±7 year, 10 males) with Doppler signs of raised filling pressures were studied using speckle tracking echocardiography and compared with 21 controls. LA segmental longitudinal strain (S), strain rate (SR) and myocardial velocities during atrial systole were measured as were LA longitudinal and transverse diameters. Markers of LV filling pressures were E/A andE/e’. Results: LA longitudinal diameter was larger in patients (5.5±0.6 vs. 4.8±0.6cm,p<0.01) and global LAS and SR were reduced (p<0.05 for both) and correlated with E/A (r=0.52 and r=0.43, p<0.05 for both). LA segmental S and SR were uniformly reduced compared with controls (p<0.05 for all) and also correlated with E/A (p<0.05 for all). LA myocardial velocities (TDI) were highest at the annular level and lowest at the rear in both patients and controls (p<0.01 for all), with the absolute values at each level not different between groups. Myocardial velocities negatively correlated with E/A at the annular level only in patients (septal: r=0.52; lateral: r=0.62, p<0.01 for both). Conclusion: In PAF patients, LA systolic function is suppressed and is directly related to the raised filling pressures. While intrinsic global and segmental function can reproducibly be studied by S and SR, myocardial velocities reflect only regional motion. These findings provide a sound explanation to the known beneficial effect of vasodilators in PAF patients. Study III Methods: We studied LA size and reservoir function in 35 patients (age 63 ± 15 years, 16 male) with idiopathic PAH using speckle tracking echocardiography who also underwent right heart catheterization simultaneously to assess pulmonary artery systolic pressure, and compared them with 27 age and gender normal controls. Results: In PAH patients, LA longitudinal diameter was not different from controls but transverse diameter was reduced (3.0 ± 0.6 vs. 3.7 ± 0.5cm, p<0.001). LA lateral wall strain rate (SR) during LV systole (atrial reservoir function was reduced at annular (p<0.001) and mid cavity (p<0.01) levels as were septal segments (p<0.03, for both) compared to controls. Opposite to controls, the two LA walls responded differently to right heart pressures. Lateral SR inversely correlated with pulmonary artery systolic pressure (PASP) (annular: r=0.45, p<0.005 and midcavity: r=0.43, p<0.01), but not with right atrial pressure (RAP). In contrast, septal SR inversely correlated with RAP (annular: r=0.39, p=0.02 and midcavity: r=0.38, p=0.03) but not with PASP. Conclusion: In patients with PAH, LA reservoir function is significantly impaired showing reduced myocardial strain rate properties. In addition,segmental function differs in their response to raised right heart pressures with the septal wall related to right atrial pressure and lateral wall related to the PASP. These findings suggest an evidence for atrial interaction in PAH, which is likely to have significant impact on LV performance. Study IV Methods: We studied 46 patients, mean age 61 ± 13 years, 17 males, of various etiologies with exertional breathlessness who underwent right heart catheterization and simultaneous transthoracic Doppler echocardiography using spectral, tissue Doppler and speckle tracking echocardiography techniques for assessing LA structure and function. Results: PCWP correlated with direct measurements of LA structure and function: LA volume (r= 0.43, p<0.01), LA global systolic strain rate (r=0.79, p<0.001) and to a lesser extent with LA systolic filling fraction (r=0.52, p<0.001). PCWP also correlated with indirect measures of LA pressure: LV E/A (r=0.66, p<0.001), E wave deceleration time (r=0.54, p<0.001), lateral E/e’ (r=0.49, p<0.001) and LV isovolumic relaxation time (r=0.36, p<0.01). LA strain rate was 78% sensitive and 84% specific in identifying patients with PCWP>15 mmHg, having accurately predicted PCWP in 63% of the cases. Conclusion: PCWP correlates with LA intrinsic systolic function and to a much lesser degree with indirect Doppler measures of raised LV filling pressures. These findings should have significant clinical implications in identifying breathless patients with raised LA pressure.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous, often familial disease, characterized by cardiac hypertrophy, predominantly affecting the interventricular septum. To date, no study has systematically analysed the genetic and phenotypic aspects of the disease in a Swedish population. The aim of this thesis was to identify the genotypes causing HCM in northern Sweden, to characterize the disease phenotypes and correlate these findings. Forty-six patients were recruited for the genetic studies (21 women), 11 familial and 35 sporadic cases. Eight sarcomeric protein genes were screened for mutations. A total of 11 different disease causing mutations were found in four genes. Six of the mutations were previously not described. A novel mutation (a 33 base pair deletion) in the troponin I gene was found in one HCM family. Despite the severe genetic defect, the associated phenotype displayed only mild cardiac hypertrophy and few symptoms. Most mutations (64%) were identified in the myosin binding protein C gene, a gene considered to have a low penetrance. Mutations were identified in 10 of 11 familial HCM cases, but only in three of the 35 sporadic cases. It was found that cardiac amyloidosis can sometimes present itself as HCM. Three HCM patients (7%) carried the ATTR Val30Met mutation, also found in Swedish patients with familial amyloid polyneuropathy (FAP). The patients had no symptoms of polyneuropathy, but cardiac amyloidosis as the cause of hypertrophy was verified by myocardial biopsy in an index case. Amyloid heart disease should therefore be considered as a differential diagnosis in patients with HCM. By studying heart rate variability (HRV), it was found that young patients with HCM had signs of autonomic dysfunction, expressed as a reduced HRV. Treatment with beta-blockade attenuated these effects. Abnormal autonomic function might be a substrate for lethal arrhythmias, most often encountered in younger patients with HCM. The results suggest a possible protective effect of beta-blockade, remaining to be studied further. Ventricular function is frequently abnormal in HCM. In particular, diastolic dysfunction has been demonstrated. The recently described myocardial performance index allows the assessment of cardiac function by combining systolic and diastolic performance. We found that patients with hypertrophic cardiomyopathy had evidence of global and regional right ventricular dysfunction, besides left ventricular dysfunction. Hypertrophic cardiomyopathy is traditionally considered to be a disease of the left ventricle. The results show that hypertrophic cardiomyopathy should more be regarded as a biventricular disease. In conclusion, the myosin binding protein C gene is the most common gene causing familial HCM in northern Sweden. This disease gene is considered to be associated with a mild, late-onset disease with ≈50% penetrance at 30 years of age. The low disease penetrance emphasizes the importance of adequate family screening when evaluating patients with HCM, since the familial nature of the disease might easily be overlooked. These particular disease features in northern Sweden contrast to most previous reports, which indicate another disease gene as the most frequent in HCM, associated with a much higher penetrance. Amyloid heart disease, requiring different treatment than HCM, should be kept in mind as a differential diagnosis in the management of patients with HCM. Key words: Hypertrophic cardiomyopathy, genetics, autonomic nervous system, familial amyloid polyneuropathy, echocardiography.

<p>Clutter is a problematic noise artifact in a variety of ultrasound applications. Clinical tasks complicated by the presence of clutter include detecting cancerous lesions in abdominal organs (e.g. livers, bladders) and visualizing endocardial borders to assess cardiovascular health. In this dissertation, an analytical expression for contrast loss due to clutter is derived, clutter is quantified in abdominal images, and sources of abdominal clutter are identified. Novel clutter reduction methods are also presented and tested in abdominal and cardiac images. </p><p>One of the novel clutter reduction methods is Short-Lag Spatial Coherence (SLSC) imaging. Instead of applying a conventional delay-and-sum beamformer to measure the amplitude of received echoes and form B-mode images, the spatial coherence of received echoes are measured to form SLSC images. The world's first SLSC images of simulated, phantom, and <italic>in vivo</italic> data are presented herein. They demonstrate reduced clutter and improved contrast, contrast-to-noise, and signal-to-noise ratios compared to conventional B-mode images. In addition, the resolution characteristics of SLSC images are quantified and compared to resolution in B-mode images. </p><p>A clinical study with 14 volunteers was conducted to demonstrate that SLSC imaging offers 19-33% improvement in the visualization of endocardial borders when the quality of B-mode images formed from the same echo data was poor. There were no statistically significant improvements in endocardial border visualization with SLSC imaging when the quality of matched B-mode images was medium to good.</p> / Dissertation

名古屋大学博士学位論文 学位の種類 : 医学博士(論文) 学位授与年月日:平成4年7月20日 宮口和彦氏の博士論文として提出された

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 5 uppsatser.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy

Background/Objective: Reperfusion injury is a serious consequence of blood flow reestablishment after myocardial infarction (MI) mediated by reactive oxygen species and neutrophilic cellular damage. Following MI, the left ventricle (LV) undergoes remodeling characterized by progressive wall thinning and cavity dilatation. Heme-Oxygenase-1 (HO-1) dependent decrease in oxidative stress may attenuate injury in part by inhibiting transcription factor NFκB-mediated inflammation. Hypothesis: I hypothesized that upregulation of HO-1 by hemin administration confers acute and chronic cardioprotection against I/R injury in rats and attenuates LV remodeling post-MI. I proposed the HO-1-dependent decrease in oxidative stress attenuates post-ischemic myocardial injury in part by inhibiting NFκB-mediated inflammation. Methods: Six week old male Wistar rats were randomly assigned to sham, vehicle, or hemin-treated groups. Vehicle and hemin were administered intraperitoneally once daily for 3 consecutive days prior to left anterior descending (LAD) coronary artery occlusion. Administration resumed 48 hours post-operatively and continued once every 3 days. Infarct size was determined by H&E histological analysis and fibrosis was quantified by Masson’s Trichrome staining. Transthoracic echocardiography was used to assess LV parameters and wall motion. Results: Hemin increased HO-1 expression, decreased infarct size and fibrosis, and attenuated LV remodeling in the short-term (4 days post-infarction). The decrease in infarct size and area of fibrosis in the hemin group was accompanied by a decrease in NFκB activity. No significant difference in infarct size and area of fibrosis between hemin and vehicle-treated groups was observed at 3 months. LV diameter and cardiac function did not differ significantly between the two groups at 3 months despite an attenuation of anterior wall thinning in the hemin group. Conclusion: HO-1 upregulation by hemin administration conferred acute cardioprotection and attenuated LV remodeling, possibly by inhibiting NFκB-mediated inflammation. However, chronic treatment with hemin did not prevent long-term post-infarction LV remodeling. It is possible that cardioprotection afforded by HO-1 upregulation is strong enough to curtail inflammation post-reperfusion and prevent LV remodeling acutely, but is not robust enough to protect the myocardium to the same degree in the long-term. Future research should focus on optimal HO-1 upregulation to attenuate long-term LV remodeling due to reperfusion injury. / Thesis (Master, Physiology) -- Queen's University, 2007-09-25 19:01:33.87

Biomedical image processing is a very important research area. Image analysis is one of the most important techniques in studies related to heart functions. The clinical assessment of LV function is very important to evaluate the heart function for patients or suspected heart disease sufferers. 2D echocardiography allows us to study the dynamic analysis of the heart which results in obtaining the quantitative and qualitative analysis of the LV. Cardiac function quantitative analysis depends on the heart’s shape characteristics like the enclosed area and heart wall thickness. The segmentation of medical images and obtaining the traces of the LV boundaries is an essential procedure to get the quantitative and qualitative analysis. Yet, in clinical procedure, this task depends on manual tracing which is slow, tedious and time consuming job. Hence, automating this clinical procedure during the cardiac cycle is of great importance. The aim of this thesis is to automate the manual process of detecting and tracking the LV boundaries of 2D echocardiographic image sequence. Instead of depending only on the imaging based techniques, the designed and implemented framework utilizes the LV mechanics beside the imaging based techniques. When it comes to information extraction from patterns which have been classified, it has been proved that the different contour detection methods complement each other. As a result, efficient combination of different contour detectors is expected to achieve better contour detection than if only one detector is used. This combination of contour detectors produces incremental gains in overall performance. In the first framework, the detection and tracking are accomplished by employing the extended Kalman filter framework to combine the contours estimated by the biomechanical model and the contours extracted using the deformable models. An alternative framework is used by employing averaging fusion followed by level set method. A gold standard is created from three manual outlines and utilized in the experimental results to evaluate the automated results. The tracking and segmentation of LV during the cardiac cycle was accomplished successfully in all cases. The results showed limits of agreement for an average perpendicular distance of 1.277 ±0.252 mm versus the created gold standard. This proved that this framework achieved better performance in tracking and segmenting the LV through the cardiac cycle.