[Show abstract][Hide abstract] ABSTRACT: Myocardial strain analysis has been proposed as a surrogate for regional replacement fibrosis (scar) in patients with ischemic cardiomyopathy (ICM). However, contractile function is often degraded in non-scarred tissue, conceivably due to a composite of interstitial fibrosis, metabolic aberrations and abnormal electro-mechanical coupling. We tested a novel 4D strain analysis tool to examine strain characteristics of scarred and non-scarred myocardium in patients with advanced ICM.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to measure changes in cardiac function as cardiomyopathy progresses in a mouse model of Duchenne muscular dystrophy using 3-D ECG-gated echocardiography. This study is the first to correlate cardiac volumes acquired using 3-D echocardiography with those acquired using retrospectively gated micro-computed tomography (CT). Both were further compared with standard M-mode echocardiography and histologic analyses. We found that although each modality measures a decrease in cardiac function as disease progresses in mdx/utrn–/– mice (n = 5) compared with healthy C57BL/6 mice (n = 8), 3-D echocardiography has higher agreement with gold-standard measurements acquired by gated micro-CT, with little standard deviation between measurements. M-Mode echocardiography measurements, in comparison, exhibit considerably greater variability and user bias. Given the radiation dose associated with micro-CT and the geometric assumptions made in M-mode echocardiography to calculate ventricular volume, we suggest that use of 3-D echocardiography has important advantages that may allow for the measurement of early disease changes that occur before overt cardiomyopathy.
Ultrasound in Medicine & Biology 12/2014; 40(12):2857-2867. DOI:10.1016/j.ultrasmedbio.2014.07.015 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background-Left ventricular (LV) and right ventricular pacing site characteristics have been shown to influence response to cardiac resynchronization therapy (CRT). This study aimed to determine the clinical feasibility of image-guided lead delivery using a 3-dimensional navigational model displaying both LV and right ventricular (RV) pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated. Methods and Results-Thirty-one consecutive patients underwent preimplant cardiac MRI with the generation of a 3-dimensional navigational model depicting optimal segmental targets for LV and RV leads. Lead delivery was guided by the model in matched views to intraprocedural fluoroscopy. Blinded assessment of final lead tip location was performed from postprocedural cardiac computed tomography. Clinical and LV remodeling response criteria were assessed at baseline, 3 months, and 6 months using a 6-minute hall walk, quality of life questionnaire, and echocardiography. Mean age and LV ejection fraction was 66 +/- 8 years and 26 +/- 8%, respectively. LV leads were successfully delivered to a target or adjacent segment in 30 of 31 patients (97%), 68% being nonposterolateral. RV leads were delivered to a target or adjacent segment in 30 of 31 patients (97%), 26% being nonapical. Twenty-three patients (74%) met standard criteria for response (LV end-systolic volume reduction >= 15%), 18 patients (58%) for super-response (LV end-systolic volume reduction >= 30%). LV ejection fraction improved at 6 months (31 +/- 8 versus 26 +/- 8%, P=0.04). Conclusions-This study demonstrates clinical feasibility of dual cardiac resynchronization therapy lead delivery to optimal targets using a 3-dimensional navigational model. High procedural success, acceptable procedural times, and a low rate of early procedural complications were observed.
[Show abstract][Hide abstract] ABSTRACT: Background
Aortic valve sclerosis (AVS) is a chronic, progressive disease involving lipid infiltration, inflammation, and tissue calcification. Despite its high prevalence, there are currently no clinically-approved pharmaceuticals for the management of AVS. The objective of the current study was to elucidate the effects of an angiotensin II type 1 receptor blocker, alone or in combination with statin therapy, on the progression of AVS.
Male New Zealand White rabbits were fed an atherogenic diet for a period of 12 months to induce AVS. Once disease was established, rabbits were block randomly assigned to receive either no treatment, olmesartan medoxomil, atorvastatin calcium, or a combination of both drugs for a period of 6 months. Disease progression was monitored in vivo using clinically-relevant magnetic resonance imaging and aortic valve cusps were examined ex vivo using histological and immunohistochemical methods.
Cusp thickness significantly increased (0.58 ± 0.03 versus 0.39 ± 0.03 mm for Cholesterol and Control, respectively; P <0.0001) and all classic hallmarks of disease progression — including lipid infiltration, inflammation, and tissue calcification — were observed after 12 months. Unfortunately, neither olmesartan medoxomil nor atorvastatin calcium were able to reverse or delay disease progression during the 6 month treatment period. However, several histological changes were observed in the valvular microenvironment.
The current study suggests that angiotensin receptor blockers, alone or in combination with statin therapy, may not be suitable for management of clinical AVS.
The Canadian journal of cardiology 09/2014; 30(9). DOI:10.1016/j.cjca.2013.12.027 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: For radiofrequency (RF) catheter ablation of the left atrium, safe and effective dosing of RF energy requires transmural left atrium ablation without injury to extra-cardiac structures. The thickness of the left atrial wall may be a key parameter in determining the appropriate amount of energy to deliver. While left atrial wall-thickness is known to exhibit inter- and intra-patient variation, this is not taken into account in the current clinical workflow. Our goal is to develop a tool for presenting patient-specific left atrial thickness information to the clinician in order to assist in the determination of the proper RF energy dose. METHODS: We use an interactive segmentation method with manual correction to segment the left atrial blood pool and heart wall from contrast-enhanced cardiac CT images. We then create a mesh from the segmented blood pool and determine the wall thickness, on a per–vertex basis, orthogonal to the mesh surface. The thickness measurement is visualized by assigning colors to the vertices of the blood pool mesh. We applied our method to 5 contrast-enhanced cardiac CT images. RESULTS: Left atrial wall-thickness measurements were generally consistent with published thickness ranges. Variations were found to exist between patients, and between regions within each patient. CONCLUSION: It is possible to visually determine areas of thick vs. thin heart wall with high resolution in a patient-specific manner.
[Show abstract][Hide abstract] ABSTRACT: Cardiac ischemic injuries can be classified into two main categories: reversible and irreversible. Treatment of reversible damages is possible through revascularization therapies. Clinically, it is quite vital to determine the reversibility of ischemic injuries and local efficiency using accurate diagnostics techniques. For this purpose, a number of imaging techniques have been developed. To our knowledge, while some of these techniques are capable of assessing tissue viability which is believed to be correlated with ischemic injuries reversibility, none of them are capable of providing information about local myocardial tissue efficiency. Note that this efficiency indicates the local tissue contribution to the overall (global) heart mechanical function which is characterized by parameters such as ejection fraction. While contraction force generation of the myocardium is a reliable and straightforward mechanical measure for the local myocardium functionality, it is also hypothesized that the level of damage reversibility expected from therapy is proportional to the intensity and distribution of these forces. As such this research involves developing a new imaging technique for cardiac contraction force quantification. This work is also geared towards another application, namely Cardiac Resynchronization Therapy (CRT), specifically for electrode leads configuration optimization. The latter has not been tackled through a systematic technique thus far. In the proposed method, contraction force reconstruction is accomplished by an inverse problem algorithm solved through an optimization framework which uses forward mechanical modelling of the myocardium iteratively to obtain the contraction forces field. As a result, the method requires a forward mechanical model of the myocardium which is computationally efficient and robust against divergence. Therefore, we developed such a model which considers all aspects of the myocardial mechanics including hyperelasticity, anisotropy, and active contraction forces of the fibers. This model assumes two major parts for the myocardium consisting background tissue and reinforcement bars simulating myocardial fibers. The finite element simulations of this model demonstrated reasonably good performance in mimicking left ventricle (LV) contractile function.
Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2043722 · 0.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS.
Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index.
The mean age of the population was 59.8 +/- 12.5 years. MetS + patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 +/- 10.6, 28.6 +/- 12.6, 30.6 +/- 12.3, and 35.2 +/- 11.4 ml/kg/m2, (p = 0.002)). Among MetS + patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02).
ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation.
Journal of Cardiovascular Magnetic Resonance 09/2013; 15(1):77. DOI:10.1186/1532-429X-15-77 · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To design, construct, and commission a set of computer-controlled motorized jaws for a micro-CT∕RT system to perform conformal image-guided small animal radiotherapy.Methods: The authors designed and evaluated a system of custom-built motorized orthogonal jaws, which allows the delivery of off-axis rectangular fields on a GE eXplore CT 120 preclinical imaging system. The jaws in the x direction are independently driven, while the y-direction jaws are symmetric. All motors have backup encoders, verifying jaw positions. Mechanical performance of the jaws was characterized. Square beam profiles ranging from 2 × 2 to 60 × 60 mm(2) were measured using EBT2 film in the center of a 70 × 70 × 22 mm(3) solid water block. Similarly, absolute depth dose was measured in a solid water and EBT2 film stack 50 × 50 × 50 mm(3). A calibrated Farmer ion chamber in a 70 × 70 × 20 mm(3) solid water block was used to measure the output of three field sizes: 50 × 50, 40 × 40, and 30 × 30 mm(2). Elliptical target plans were delivered to films to assess overall system performance. Respiratory-gated treatment was implemented on the system and initially proved using a simple sinusoidal motion phantom. All films were scanned on a flatbed scanner (Epson 1000XL) and converted to dose using a fitted calibration curve. A Monte Carlo beam model of the micro-CT with the jaws has been created using BEAMnrc for comparison with the measurements. An example image-guided partial lung irradiation in a rat is demonstrated.Results: The averaged random error of positioning each jaw is less than 0.1 mm. Relative output factors measured with the ion chamber agree with Monte Carlo simulations within 2%. Beam profiles and absolute depth dose curves measured from the films agree with simulations within measurement uncertainty. Respiratory-gated treatments applied to a phantom moving with a peak-to-peak amplitude of 5 mm showed improved beam penumbra (80%-20%) from 3.9 to 0.8 mm.Conclusions: A set of computer-controlled motorized jaws for a micro-CT∕RT system were constructed with position reliably better than a tenth of a millimeter. The hardware system is ready for image-guided conformal radiotherapy for small animals with capability of respiratory-gated delivery.
Medical Physics 08/2013; 40(8):081706. DOI:10.1118/1.4812422 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: -Transmural scar occupying left ventricular pacing regions has been associated with reduced response to cardiac resynchronization therapy (CRT). However, spatial influences of lead tip delivery relative to scar at both pacing sites remains poorly explored. This study evaluated scar distribution relative to left ventricular (LV) and right ventricular (RV) lead tip placement through co-registration of Late Gadolinium Enhancement (LGE) MRI and cardiac computed tomography (CT) findings. Influences on CRT response were assessed by serial echocardiography. METHODS AND RESULTS: -Sixty patients receiving CRT underwent pre-implant LGE-MRI, post-implant cardiac CT and serial echocardiography. Blinded segmental evaluations of mechanical delay, percent scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LVESV ≥15% at 6 months. The mean age and LVEF were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT non-responders for both the LV [23±23 vs. 8±14% (p=0.01) and RV pacing regions [40±32 vs. 24±30% (p=0.04)]. Significant pacing region scar was identified in 13% of LV pacing regions and 37% of RV pacing regions. Absence of scar in both regions was associated with an 81% response rate, compared to 55%, 25% and 0%, respectively when the RV, LV or both pacing regions contained scar. LV pacing region dysynchrony was not predictive of response. CONCLUSIONS: -Myocardial scar occupying the LV pacing region is associated with non-response to CRT. Scar occupying the RV pacing region is encountered at higher frequency and appears to provide a more intermediate influence on CRT response.
[Show abstract][Hide abstract] ABSTRACT: Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the STI1 gene, supported a unique role for STI1 during embryonic development. The response of STI1 haploinsufficient mice to cellular stress seemed compromised, and mutant mice showed increased vulnerability to ischemic insult. At the cellular level, ischemia increased the secretion of STI1 from wild-type astrocytes by 3-fold, whereas STI1 haploinsufficient mice secreted half as much STI1. Interesting, extracellular STI1 prevented ischemia-mediated neuronal death in a prion protein-dependent way. Our study reveals essential roles for intracellular and extracellular STI1 in cellular resilience.-Beraldo, F. H., Soares, I. N., Goncalves, D. F., Fan, J., Thomas, A. A., Santos, T. G., Mohammad, A. H., Roffe, M., Calder, M. D., Nikolova, S., Hajj, G. N., Guimaraes, A. N., Massensini, A. R., Welch, I., Betts, D. H., Gros, R., Drangova, M., Watson, A. J., Bartha, R., Prado, V. F., Martins, V. R., and Prado, M. A. M. Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein.
The FASEB Journal 05/2013; 27(9). DOI:10.1096/fj.13-232280 · 5.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A remote catheter navigation system compatible with magnetic resonance imaging (MRI) has been developed to facilitate MRI-guided catheterization procedures. The interventionalist's conventional motions (axial motion and rotation) on an input catheter - acting as the master - are measured by a pair of optical encoders, and a custom embedded system relays the motions to a pair of ultrasonic motors. The ultrasonic motors drive the patient catheter (slave) within the MRI scanner, replicating the motion of the input catheter. The performance of the remote catheter navigation system was evaluated in terms of accuracy and delay of motion replication outside and within the bore of the magnet. While inside the scanner bore, motion accuracy was characterized during the acquisition of frequently used imaging sequences, including real-time gradient echo. The effect of the catheter navigation system on image signal-to-noise ratio (SNR) was also evaluated. The results show that the master-slave system has a maximum time delay of 41 ± 21 ms in replicating motion; an absolute value error of 2 ± 2° was measured for radial catheter motion replication over 360° and 1.0 ± 0.8 mm in axial catheter motion replication over 100 mm of travel. The worst-case SNR drop was observed to be 2.5%.
[Show abstract][Hide abstract] ABSTRACT: Background
Micro-computed tomography (micro-CT) offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of X-ray dose accumulated over the course of the experiment.PurposeTo scan C57BL/6 mice multiple times per week for 6 weeks, in order to determine the effect of the cumulative dose on pulmonary and cardiac tissue at the end of the study.Material and MethodsC57BL/6 male mice were split into two groups (irradiated group = 10, control group = 10). The irradiated group was scanned (80 kVp/50mA) three times weekly for 6 weeks, resulting in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from week 6 were reconstructed and the lungs and heart were analyzed.ResultsOverall, there was no significant difference in lung volume or lung density or in left ventricular volume or ejection fraction between the control group and the irradiated group. Histological samples taken from excised lung and myocardial tissue also showed no evidence of inflammation or fibrosis in the irradiated group.Conclusion
This study demonstrated that a 5 Gy X-ray dose accumulated over 6 weeks during a longitudinal micro-CT study had no significant effects on the pulmonary and myocardial tissue of C57BL/6 mice. As a result, the many advantages of micro-CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: -Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance (CMR) imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with HCM. METHODS AND RESULTS: -One hundred consecutive patients with HCM underwent CMR imaging. Cine, stress perfusion (SP), late gadolinium enhancement (LGE) and T2-weighted imaging techniques were employed. Each was spatially co-registered according to pre-defined segmental and sub-segmental models and blindly analyzed for abnormalities using validated techniques. Spatial associations between SP, LGE and T2 imaging were made at segmental and sub-segmental levels. Of the 100 patients studied the phenotype was septal in 86 and apical in 14. LGE imaging was abnormal in 79 (79%). Eighty-six patients met pre-specified safety criteria to undergo SP and ischemia was identified in 46 (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segments with hypertrophy. Sub-segmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from LGE and T2 abnormalities, typically seen in mid-wall and sub-epicardial zones. CONCLUSIONS: -Inducible hypoperfusion is a common finding in HCM and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena appears distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.