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Biomedical subjects

Albert C Lardo

Publications and source records attributed to Albert C Lardo.

14 recordsLinked to original sources

Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy.

OBJECTIVES: The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI). BACKGROUND: Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood. METHODS: We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone. RESULTS: Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 +/- 0.2 mm to 2.0 +/- 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infarct scar (5.1 +/- 0.5 mm to 3.6 +/- 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 +/- 0.2 mum vs. 12.6 +/- 0.2 mum, p < 0.05). CONCLUSIONS: With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.

Animals↗

Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable-cardioverter defibrillators at 1.5 tesla.

BACKGROUND: Magnetic resonance imaging (MRI) is an important diagnostic modality currently unavailable for millions of patients because of the presence of implantable cardiac devices. We sought to evaluate the diagnostic utility and safety of noncardiac and cardiac MRI at 1.5T using a protocol that incorporates device selection and programming and limits the estimated specific absorption rate of MRI sequences. METHODS AND RESULTS: Patients with no imaging alternative and with devices shown to be MRI safe by in vitro phantom and in vivo animal testing were enrolled. Of 55 patients who underwent 68 MRI studies, 31 had a pacemaker, and 24 had an implantable defibrillator. Pacing mode was changed to "asynchronous" for pacemaker-dependent patients and to "demand" for others. Magnet response and tachyarrhythmia functions were disabled. Blood pressure, ECG, oximetry, and symptoms were monitored. Efforts were made to limit the system-estimated whole-body average specific absorption rate to 2.0 W/kg (successful in >99% of sequences) while maintaining the diagnostic capability of MRI. No episodes of inappropriate inhibition or activation of pacing were observed. There were no significant differences between baseline and immediate or long-term (median 99 days after MRI) sensing amplitudes, lead impedances, or pacing thresholds. Diagnostic questions were answered in 100% of nonthoracic and 93% of thoracic studies. Clinical findings included diagnosis of vascular abnormalities (9 patients), diagnosis or staging of malignancy (9 patients), and assessment of cardiac viability (13 patients). CONCLUSIONS: Given appropriate precautions, noncardiac and cardiac MRI can potentially be safely performed in patients with selected implantable pacemaker and defibrillator systems.

Artifacts↗

Multidetector computed tomography myocardial perfusion imaging during adenosine stress.

OBJECTIVES: The purpose of this study is to validate the accuracy of multidetector computed tomography (MDCT) to measure differences in regional myocardial perfusion during adenosine stress in a canine model of left anterior descending (LAD) artery stenosis, during first-pass, contrast-enhanced helical MDCT. BACKGROUND: Myocardial perfusion imaging by MDCT may have significant implications in the diagnosis and treatment of coronary artery disease. METHODS: Eight dogs were prepared with a LAD stenosis, and contrast-enhanced MDCT imaging was performed 5 min into adenosine infusion (0.14 to 0.21 mg/kg/min). Images were analyzed using a semiautomated approach to define the regional signal density (SD) ratio (myocardial SD/left ventricular blood pool SD) in stenosed and remote territories, and then compared with microsphere myocardial blood flow (MBF) measurements. RESULTS: Mean MBF in stenosed versus remote territories was 1.37 +/- 0.46 ml/g/min and 1.29 +/- 0.48 ml/g/min at baseline (p = NS) and 2.54 +/- 0.93 ml/g/min and 8.94 +/- 5.74 ml/g/min during adenosine infusion, respectively (p < 0.05). Myocardial SD was 92.3 +/- 39.5 HU in stenosed versus 180.4 +/- 41.9 HU in remote territories (p < 0.001). There was a significant linear association of the SD ratio with MBF in the stenosed territory (R = 0.98, p = 0.001) and between regional myocardial SD ratio and MBF <8 ml/g/min, slope = 0.035, SE = 0.007, p < 0.0001. Overall, there was a significant non-linear relationship over the range of flows studied (LR chi-square [2 degrees of freedom] = 31.8, p < 0.0001). CONCLUSIONS: Adenosine-augmented MDCT myocardial perfusion imaging provides semiquantitative measurements of myocardial perfusion during first-pass MDCT imaging in a canine model of LAD stenosis.

Adenosine↗

CT angiography in highly calcified arteries: 2D manual vs. modified automated 3D approach to identify coronary stenoses.

BACKGROUND: Two-dimensional axial and manually-oriented reformatted images are traditionally used to analyze coronary data provided by multidetector-row computed tomography angiography (MDCTA). While apparently more accurate in evaluating calcified vessels, 2D methods are time-consuming compared with automated 3D approaches. The purpose of this study was to evaluate the performance of a modified automated 3D approach (using manual vessel isolation and different window and level settings) in a population with high calcium scores who underwent coronary half-millimeter 16-detector-row CT angiography (16 x 0.5-MDCTA). METHODS: ECG-gated 16 x 0.5-MDCTA (16 x 0.5 mm cross-sections, 0.35 x 0.35 x 0.35 mm3 isotropic voxels, 400 ms rotation) was performed after injection of iopamidol (120-ml, 300 mg/ml) in 19 consecutive patients (11 male, 62+/-10 years-old). Native arteries were independently evaluated for >or=50%-stenoses using both manual 2D and modified automated 3D approaches. Stents and bypass grafts were excluded. Conventional coronary angiography was visually analyzed by 2 observers. RESULTS: Median Agatston calcium score was 434. Sensitivities, specificities, positive and negative predictive values for detection of >or=50% coronary stenoses using the 2D and modified 3D approaches were, respectively: 74%/63%, 76%/80%, 45%/34%, and 91%/93% (p=NS for all comparisons). Overall diagnostic accuracies were 75 and 78%, respectively (p=NS). Uninterpretable vessels were, respectively: 37% (77/209) and 35% (73/209) - p=NS. Time to analyze a single study was 160+/-23 and 53+/-11 min, respectively (p<0.01). CONCLUSIONS: This modified automated 3D approach is equivalent to and significantly less time consuming than the traditional manual 2D method for evaluation of >or=50%-stenoses by 16 x 0.5-MDCTA in native coronary arteries of patients with high calcium scores.

Adult↗

Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar.

BACKGROUND: The ability to distinguish dysfunctional but viable myocardium from nonviable tissue has important prognostic implications after myocardial infarction. The purpose of this study was to validate the accuracy of contrast-enhanced multidetector computed tomography (MDCT) for quantifying myocardial necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion myocardial infarction. METHODS AND RESULTS: Ten dogs and 7 pigs underwent balloon occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm x 32 slice) was performed before occlusion and 90 minutes (canine) or 8 weeks (porcine) after reperfusion. MDCT images were analyzed to define infarct size/extent and microvascular obstruction and compared with postmortem myocardial staining (triphenyltetrazolium chloride) and microsphere blood flow measurements. Acute and chronic infarcts by MDCT were characterized by hyperenhancement, whereas regions of microvascular obstruction were characterized by hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium chloride staining (acute infarcts 21.1+/-7.2% versus 20.4+/-7.4%, mean difference 0.7%; chronic infarcts 4.15+/-1.93% versus 4.92+/-2.06%, mean difference -0.76%) and accurately reflected morphology and the transmural extent of injury in all animals. Peak hyperenhancement of infarcted regions occurred approximately 5 minutes after contrast injection. MDCT-derived regions of microvascular obstruction were also identified accurately in acute studies and correlated with reduced flow regions as measured by microsphere blood flow. CONCLUSIONS: The spatial extent of acute and healed myocardial infarction can be determined and quantified accurately with contrast-enhanced MDCT. This feature, combined with existing high-resolution MDCT coronary angiography, may have important implications for the comprehensive assessment of cardiovascular disease.

Acute Disease↗

Characterization of radiofrequency ablation lesions with gadolinium-enhanced cardiovascular magnetic resonance imaging.

OBJECTIVES: This study was designed to evaluate the characteristics of gadolinium-enhanced imaging of radiofrequency ablations. BACKGROUND: Gadolinium-enhanced magnetic resonance imaging (MRI) has been used successfully to evaluate tissue necrosis after myocardial infarction. In electrophysiology, radiofrequency energy is used to create a targeted myocardial necrosis for the treatment of various arrhythmias. METHODS: Using a power-controlled, cooled-tip 7-F catheter system, radiofrequency lesions (10 to 40 W for 30 s) were created on the epicardium of the right ventricle in eight mongrel dogs. After injection of 0.225 mmol/kg gadolinium, T1-weighted fast gradient echo images were obtained during a follow-up of 10 h using an intrathoracic high-resolution coil. Radiofrequency ablations were analyzed on the MR images and compared with gross anatomy and histopathology. RESULTS: Four distinct phases of signal enhancement were observed. After gadolinium injection, radiofrequency lesions were delineated clearly as contrast-free areas of low signal intensity (contrast-to-noise ratio [CNR] = -21.1 +/- 19.8). Signal enhancement in the lesion periphery started 4.0 +/- 1.8 min after injection and progressively extended toward the lesion center at a rate of 0.02 mm/min. Full delayed enhancement was observed after 98 +/- 21 min (CNR = +17.8 +/- 9.0). During the follow-up period, CNR started to decrease, but the lesions were detectable for as long as 10 h of follow-up. During the first three phases of enhancement, MRI correlated well with the pathological findings (r = 0.88, r = 0.88, and r = 0.86 [p < 0.001], respectively). CONCLUSIONS: Radiofrequency ablation can be evaluated accurately by using gadolinium-enhanced MRI, which may allow the noninvasive assessment of procedural success. The dissimilar wash-in and wash-out kinetics compared with myocardial infarction suggest a different pathophysiological process with complete loss of microvasculature.

Animals↗

Integrated electroanatomic mapping with three-dimensional computed tomographic images for real-time guided ablations.

BACKGROUND: New ablation strategies for atrial fibrillation or nonidiopathic ventricular tachycardia are increasingly based on anatomic consideration and require the placement of ablation lesions at the correct anatomic locations. This study sought to evaluate the accuracy of the first clinically available image integration system for catheter ablation on 3-dimensional (3D) computed tomography (CT) images in real time. METHODS AND RESULTS: After midline sternotomy, 2.3-mm CT fiducial markers were attached to the epicardial surface of each cardiac chamber in 9 mongrel dogs. Detailed 3D cardiac anatomy was reconstructed from contrast-enhanced, high-resolution CT images and registered to the electroanatomic maps of each cardiac chamber. To assess accuracy, targeted ablations were performed at each of the fiducial markers guided only by the reconstructed 3D images. At autopsy, the position error was 1.9+/-0.9 mm for the right atrium, 2.7+/-1.2 mm for the right ventricle, 1.8+/-1.0 mm for the left atrium, and 2.3+/-1.1 mm for the left ventricle. To evaluate the system's guidance of more complex clinical ablation strategies, ablations of the cavotricuspid isthmus (n=4), fossa ovalis (n=4), and pulmonary veins (n=6) were performed, which resulted in position errors of 1.8+/-1.5, 2.2+/-1.3, and 2.1+/-1.2 mm, respectively. Retrospective analysis revealed that a combination of landmark registration and the target chamber surface registration resulted in <3 mm accuracy in all 4 cardiac chambers. CONCLUSIONS: Image integration with high-resolution 3D CT allows accurate placement of anatomically guided ablation lesions and can facilitate complex ablation strategies. This may provide significant advantages for anatomically based procedures such as ablation of atrial fibrillation and nonidiopathic ventricular tachycardia.

Animals↗

Imaging of myocardial dyssynchrony in congestive heart failure.

Heart failure constitutes a major health problem in USA and Europe. Angiotensin converting enzyme inhibitors and _ blockers were shown to reduce morbidity and mortality in patients with CHF. Yet, their effectiveness is limited. A significant number of patients with heart failure manifest myocardial conduction abnormalities. Conduction abnormalities, especially in the form of left bundle branch block (LBBB) may be associated with abnormal mechanical function. Several studies demonstrated that these patients may gain benefit from biventricular (BiV) pacing in terms of improvement in exercise tolerance, heart failure morbidity and even decreased mortality. BiV pacing was also associated with improvement in ejection fraction, reduction in the extent of mitral regurgitation and a decrease in cardiac size (reverse remodeling). However, a significant number of patients do not gain benefit from biventricular pacing despite having conduction abnormalities. The underlying reason is that the electrical activity may not closely reflect mechanical activity. Several imaging modalities and techniques have been proposed to improve the selection of patients who may benefit from biventricular pacemakers. Of those, echo-Doppler, and especially, Tissue Doppler Imaging has been demonstrated as important tools for evaluating patients for cardiac resynchronization therapy (CRT) and following their response. The advantages of echo include accessibility, portability, its cost and a high temporal resolution. Yet, it is limited by its acoustic windows and scanning angles. MRI is a useful tool for evaluating patients for CRT by providing 3-D image of myocardial function. However, it is limited for follow-up after implantation due to its cost and a potential damage to the patients or pacemakers. Dyssnchrony imaging is a rapidly evolving field. New imaging techniques such as speckle tracking are promising and close update is needed to keep track of the developments and the changes in this exciting field.

Bundle-Branch Block↗

Magnetic resonance imaging assessment of ventricular dyssynchrony: current and emerging concepts.

Despite the numerous documented benefits of cardiac resynchronization therapy (CRT), a significant proportion of patients undergoing CRT do not demonstrate symptomatic or morphologic improvement, triggering the search to improve targeting of this therapy. Many studies now support direct assessment of mechanical dyssynchrony as a method to better identify CRT responders. Among the methods used, echo-Doppler imaging has taken center stage and is covered in other articles in this special issue; however, these methods have several inherent limitations, and other alternatives are also being explored such as magnetic resonance imaging (MRI). This review discusses the concepts and clinical use of MRI methods for quantitative assessment of mechanical dyssynchrony, highlighting newer acquisition and analysis methods and focusing on how the data can be synthesized into robust indexes of dyssynchronous heart failure.

Cardiac Output, Low↗

Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy.

BACKGROUND: Patients with left ventricular dysfunction have an elevated risk of sudden cardiac death. However, the substrate for ventricular arrhythmia in patients with nonischemic cardiomyopathy remains poorly understood. We hypothesized that the distribution of scar identified by MRI is predictive of inducible ventricular tachycardia. METHODS AND RESULTS: Short-axis cine steady-state free-precession and postcontrast inversion-recovery gradient-echo MRI sequences were obtained before electrophysiological study in 26 patients with nonischemic cardiomyopathy. Left ventricular ejection fraction was measured from end-diastolic and end-systolic cine images. The transmural extent of scar as a percentage of wall thickness (percent scar transmurality) in each of 12 radial sectors per slice was calculated in all myocardial slices. The percentages of sectors with 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100% scar transmurality were determined for each patient. Predominance of scar distribution involving 26% to 75% of wall thickness was significantly predictive of inducible ventricular tachycardia and remained independently predictive in the multivariable model after adjustment for left ventricular ejection fraction (odds ratio, 9.125; P=0.020). CONCLUSIONS: MR assessment of scar distribution can identify the substrate for inducible ventricular tachycardia and may identify high-risk patients with nonischemic cardiomyopathy currently missed by ejection fraction criteria.

Cardiomyopathies↗

Cardiac dyssynchrony analysis using circumferential versus longitudinal strain: implications for assessing cardiac resynchronization.

BACKGROUND: QRS duration is commonly used to select heart failure patients for cardiac resynchronization therapy (CRT). However, not all patients respond to CRT, and recent data suggest that direct assessments of mechanical dyssynchrony may better predict chronic response. Echo-Doppler methods are being used increasingly, but these principally rely on longitudinal motion (epsilonll). It is unknown whether this analysis yields qualitative and/or quantitative results similar to those based on motion in the predominant muscle-fiber orientation (circumferential; epsiloncc). METHODS AND RESULTS: Both epsilonll and epsiloncc strains were calculated throughout the left ventricle from 3D MR-tagged images for the full cardiac cycle in dogs with cardiac failure and a left bundle conduction delay. Dyssynchrony was assessed from both temporal and regional strain variance analysis. CRT implemented by either biventricular (BiV) or left ventricular-only (LV) pacing enhanced systolic function similarly and correlated with improved dyssynchrony based on epsiloncc-based metrics. In contrast, longitudinal-based analyses revealed significant resynchronization with BiV but not LV for the overall cycle and correlated poorly with global functional benefit. Furthermore, unlike circumferential analysis, epsilonll-based indexes indicated resynchronization in diastole but much less in systole and had a lower dynamic range and higher intrasubject variance. CONCLUSIONS: Dyssynchrony assessed by longitudinal motion is less sensitive to dyssynchrony, follows different time courses than those from circumferential motion, and may manifest CRT benefit during specific cardiac phases depending on pacing mode. These results highlight potential limitations to epsilonll-based analyses and support further efforts to develop noninvasive synchrony measures based on circumferential deformation.

Animals↗

Evaluation of the female urethra with intraurethral magnetic resonance imaging.

The purpose of this study was to demonstrate feasibility of intraurethral magnetic resonance imaging (MRI) for in vivo assessment of the female urethra and to determine the anatomy of the urethra and periurethral attachments as depicted using an endourethral MR coil. Twenty-three continent volunteers were studied with a 14F endourethral MR coil. Intraurethral MRI allowed detailed visualization and measurements of the muscular layers of the urethral sphincter and permitted the evaluation of supporting ligaments. This technique may become useful in the evaluation of anatomical defects associated with female urethral sphincter deficiency.

Adult↗

Stereotactic magnetic resonance guidance for anatomically targeted ablations of the fossa ovalis and the left atrium.

INTRODUCTION: Targets for radiofrequency ablation (RFA) of atrial fibrillation are increasingly being selected based on anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures, we evaluated whether stereotactic catheter guidance might facilitate anatomical catheter navigation and RFA to the great vessels, the fossa ovalis and the left atrium (LA). METHODS AND RESULTS: An electromagnetic catheter's position system was superimposed on three-dimensional (3D) MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MRI in real-time. To assess the reproducibility of RFA, repeat ablations were created at the identical anatomic site in the inferior vena cava (IVC) in 5 swine. Average distance of the repeated ablations was 4.4 +/- 2.4 mm.In five swine the catheter was anatomically guided with the MRI to the fossa ovalis and a single RFA was performed. On the pathological specimen all ablation sites were located within the fossa ovalis with an average distance of 3.9 +/- 2.1 mm from its center. In two of the experiments the ablation catheter was passed into the left atrium and anatomically targeted ablation performed in the lateral wall of the left atrial appendage. Catheter location and ablation site were confirmed by autopsy and histology. CONCLUSION: Real-time display of the catheter position on 3D-MRI allows anatomically targeted catheter navigation and RFA in the IVC, the fossa ovalis, and the left atrium. This may facilitate anatomically based interventions like septal puncture or pulmonary vein ablation and decrease fluoroscopy times.

Animals↗

Multifunctional interventional devices for MRI: a combined electrophysiology/MRI catheter.

The design and application of a two-wire electrophysiology (EP) catheter that simultaneously records the intracardiac electrogram and receives the MR signal for active catheter tracking is described. The catheter acts as a long loop receiver, allowing for visualization of the entire catheter length while simultaneously behaving as a traditional two-wire EP catheter, allowing for intracardiac electrogram recording and ablation. The application of the device is demonstrated by simultaneously tracking the catheter and recording the intracardiac electrogram in canine models using 7 and 10 frame/sec real-time imaging sequences. Using solely MR imaging, the entire catheter was visualized and guided from the jugular vein into the cardiac chambers, where the intracardiac electrogram was recorded. By combining several functions in a single, simple structure, the excellent tissue contrast and functional imaging capabilities of MR can be used to improve the efficacy of EP interventions. This catheter will facilitate MR-guided interventions and demonstrates the design of multifunctional interventional devices for use in MRI.

Animals↗