Maria Drangova

Robarts Research Institute, London, Ontario, Canada

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Publications (162)501.09 Total impact

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    ABSTRACT: Background: Remote catheter navigation systems protect interventionalists from scattered ionizing radiation. However, these systems typically require specialized catheters and extensive operator training. Methods: A new compact and sterilizable telerobotic system is described, which allows remote navigation of conventional tip-steerable catheters, with three degrees of freedom, using an interface that takes advantage of the interventionalist's existing dexterity skills. The performance of the system is evaluated ex vivo and in vivo for remote catheter navigation and ablation delivery. Results: The system has absolute errors of 0.1 ± 0.1 mm and 7 ± 6° over 100 mm of axial motion and 360° of catheter rotation, respectively. In vivo experiments proved the safety of the proposed telerobotic system and demonstrated the feasibility of remote navigation and delivery of ablation. Conclusion: The proposed telerobotic system allows the interventionalist to use conventional steerable catheters; while maintaining a safe distance from the radiation source, he/she can remotely navigate the catheter and deliver ablation lesions. Copyright © 2015 John Wiley & Sons, Ltd.
    International Journal of Medical Robotics and Computer Assisted Surgery 11/2015; DOI:10.1002/rcs.1711 · 1.53 Impact Factor
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    ABSTRACT: Myocardial fibrosis imaging using late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) has been validated as a quantitative predictive marker for response to medical, surgical, and device therapy. To date, all such studies have examined conventional, non-phase corrected magnitude images. However, contemporary practice has rapdily adopted phase-corrected image reconstruction. We sought to investigate the existence of any systematic bias between threshold-based scar quantification performed on conventional magnitude inversion recovery (MIR) and matched phase sensitive inversion recovery (PSIR) images. In 80 patients with confirmed ischemic (N = 40), or non-ischemic (n = 40) myocardial fibrosis, and also in a healthy control cohort (N = 40) without fibrosis, myocardial late enhancement was quantified using a Signal Threshold Versus Reference Myocardium technique (STRM) at ≥2, ≥3, and ≥5 SD threshold, and also using the Full Width at Half Maximal (FWHM) technique. This was performed on both MIR and PSIR images and values compared using linear regression and Bland-Altman analyses. Linear regression analysis demonstrated excellent correlation for scar volumes between MIR and PSIR images at all three STRM signal thresholds for the ischemic (N = 40, r = 0.96, 0.95, 0.88 at 2, 3, and 5 SD, p < 0.0001 for all regressions), and non ischemic (N = 40, r = 0.86, 0.89, 0.90 at 2, 3, and 5 SD, p < 0.0001 for all regressions) cohorts. FWHM analysis demonstrated good correlation in the ischemic population (N = 40, r = 0.83, p < 0.0001). Bland-Altman analysis demonstrated a systematic bias with MIR images showing higher values than PSIR for ischemic (3.3 %, 3.9 % and 4.9 % at 2, 3, and 5 SD, respectively), and non-ischemic (9.7 %, 7.4 % and 4.1 % at ≥2, ≥3, and ≥5 SD thresholds, respectively) cohorts. Background myocardial signal measured in the control population demonstrated a similar bias of 4.4 %, 2.6 % and 0.7 % of the LV volume at 2, 3 and 5 SD thresholds, respectively. The bias observed using FWHM analysis was -6.9 %. Scar quantification using phase corrected (PSIR) images achieves values highly correlated to those obtained on non-corrected (MIR) images. However, a systematic bias exists that appears exaggerated in non-ischemic cohorts. Such bias should be considered when comparing or translating knowledge between MIR- and PSIR-based imaging.
    Journal of Cardiovascular Magnetic Resonance 08/2015; 17(1):66. DOI:10.1186/s12968-015-0163-8 · 4.56 Impact Factor
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    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.
    18th Annual SCMR Scientific Sessions; 02/2015
  • Mohammad Tavallaei · Seyed Farokh Atashzar · Maria Drangova ·

    IEEE Transactions on Industrial Electronics 01/2015; DOI:10.1109/TIE.2015.2499723 · 6.50 Impact Factor
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    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 · 2.21 Impact Factor
  • Junmin Liu · Maria Drangova ·
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    ABSTRACT: PurposeTo develop and evaluate a multiecho phase-unwrapping-based B0 mapping method.Methods The proposed method estimates a B0 map by Non-Iterative Correction of phase-Errors (B0-NICE). The B0-NICE method generates an initial B0 map from a “pseudo in-phase” data set by introducing a bias frequency shift to the multipeak fat model, followed by correcting the phase errors using both phase and magnitude information. The performance of the B0-NICE method was evaluated with all data cases from the 2012 ISMRM Challenge.ResultsThe B0 field estimates from B0-NICE were compared with those generated by GlObally Optimal Surface Estimation (GOOSE). In the presence of large B0 inhomogeneity, the B0-NICE method was able to generate more realistic B0 maps from multiecho data, compared with GOOSE. Accurate estimation of fat-fraction (FF) map was also achieved using the proposed algorithm.Conclusion The primary finding of the present study is that accurate FF and B0 maps are achievable if magnitude data is processed independently and used to correct phase errors existing in B0 maps generated by phase unwrapping. The B0-NICE software is freely available to the scientific community. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 10/2014; 74(4). DOI:10.1002/mrm.25497 · 3.57 Impact Factor
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    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. Clinical trial registration url: Unique identifier: NCT01640769.
    Circulation Arrhythmia and Electrophysiology 09/2014; 7(6). DOI:10.1161/CIRCEP.114.001729 · 4.51 Impact Factor
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    ABSTRACT: Recent studies have investigated histological staining compounds as micro-computed tomography (micro-CT) contrast agents, delivered by soaking tissue specimens in stain and relying on passive diffusion for agent uptake. This study describes a perfusion approach using iodine or phosphotungstic acid (PTA) stains, delivered to an intact mouse, to capitalize on the microvasculature as a delivery conduit for parenchymal staining and direct contact for staining artery walls. Twelve C57BL/6 mice, arterially perfused with either 25% Lugol's solution or 5% PTA solution were scanned intact and reconstructed with 26 µm isotropic voxels. The animals were fixed and the heart and surrounding vessels were excised, embedded and scanned; isolated heart images were reconstructed with 13 µm isotropic voxels. Myocardial enhancement and artery diameters were measured. Both stains successfully enhanced the myocardium and vessel walls. Interestingly, Lugol's solution provided a significantly higher enhancement of the myocardium than PTA [2502 ± 437 vs 656 ± 178 Hounsfield units (HU); p < 0.0001], delineating myofiber architecture and orientation. There was no significant difference in vessel wall enhancement (Lugol's, 1036 ± 635 HU; PTA, 738 ± 124 HU; p = 0.29), but coronary arteries were more effectively segmented from the PTA-stained hearts, enabling segmented imaging of fifth- order coronary artery branches. The combination of whole mouse perfusion delivery and use of heavy metal-containing stains affords high-resolution imaging of the mouse heart and vasculature by micro-CT. The differential imaging patterns of Lugol's- and PTA-stained tissues reveals new opportunities for micro-analyses of cardiac and vascular tissues. Copyright © 2014 John Wiley & Sons, Ltd.
    Contrast Media & Molecular Imaging 09/2014; 9(5). DOI:10.1002/cmmi.1588 · 2.92 Impact Factor
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    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. Methods 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. Results 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. Conclusions 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
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    Junmin Liu · David A. Rudko · Joseph S. Gati · Ravi S. Menon · Maria Drangova ·
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    ABSTRACT: PurposeTo develop and evaluate a local frequency shift (LFS) mapping method specifically designed for multi-echo acquisitions and multi-channel receive coils.Methods The proposed method uses the pixel-by-pixel inter-echo variance (IEV) as a weighting factor during channel-combination. Five healthy volunteers were scanned at 7 T. The IEV-weighted method was quantitatively compared to established (adaptive and Hermitian product) channel-combination methods with respect to IEV of LFS over the entire brain.ResultsIn all experiments, the IEV-weighted method generated LFS maps free of artifacts caused by unwrapping errors. Based on measurements of the inter-echo frequency variance throughout the whole brain, the IEV-weighted method produced the lowest variation and the best contrast at the edge of the brain.Conclusion The primary finding of the present study is that accurate LFS maps are achievable if the data from each channel is processed independently prior to combination followed by a weighted combination using IEV as the weighting term. The software is freely available to the scientific community. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 04/2014; 73(4). DOI:10.1002/mrm.25247 · 3.57 Impact Factor
  • Jiro Inoue · Allan C. Skanes · James A. White · Martin Rajchl · Maria Drangova ·
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    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.
    SPIE Medical Imaging; 03/2014
  • Seyyed M. H. Haddad · Maria Drangova · James A. White · Abbas Samani ·
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    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; 9038. DOI:10.1117/12.2043722 · 0.20 Impact Factor

  • Journal of Biomedical Science and Engineering 01/2014; 07(04):157-172. DOI:10.4236/jbise.2014.74020
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    ABSTRACT: Purpose: To determine the accuracy and reproducibility of late gadolinium enhancement (LGE) MRI scar quantification using visual sub-segmental analysis (VSSA) versus signal threshold-based analysis in ischemic and nonischemic cardiomyopathy. Materials and methods: One-hundred sixty-one patients with abnormal LGE imaging underwent VSSA and signal threshold-based analysis. VSSA was performed using a 68 sub-segmental model. Signal threshold-based analysis was performed using cutoffs of ≥2, ≥3, and ≥5 standard deviations (SD) above the mean signal of normal myocardium. Comparison of VSSA and signal threshold-based analysis was performed by linear regression and Bland Altman plots. Results: Seventy (44%) patients had ischemic scar, 76 (47%) had nonischemic scar, and 15 (9%) had a combined pattern. Correlation coefficients for VSSA versus signal threshold-based analysis at ≥2, ≥3, and ≥5SD thresholds were r = 0.63, r = 0.79, r = 0.81 (P < 0.001) for all patients, r = 0.74, r = 0.81, r = 0.81 (P < 0.001) in those with ischemic scar, and r = 0.46, r = 0.69, r = 0.72 (P < 0.001) in those with nonischemic scar. Bland Altman analysis revealed no significant bias in total scar volume among all patients (-4.3 ± 7.9%), those with ischemic scar (-4.8 ± 7.8%), or those with nonischemic scar (-2.6 ± 7.6%). Intra-observer and inter-observer variability of the VSSA technique was excellent with a mean difference in total percent scar of 0.3% (-8.3-8.9%) and -0.4% (-9.5-8.5%), respectively. Conclusion: A VSSA-based model of myocardial scar quantification is accurate and reproducible in ischemic and nonischemic cardiomyopathy.
    Journal of Magnetic Resonance Imaging 12/2013; 38(6). DOI:10.1002/jmri.24116 · 3.21 Impact Factor
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    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 · 4.56 Impact Factor
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    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 mm2 were measured using EBT2 film in the center of a 70×70×22 mm3 solid water block. Similarly, absolute depth dose was measured in a solid water and EBT2 film stack 50×50×50 mm3. A calibrated Farmer ion chamber in a 70×70×20 mm3 solid water block was used to measure the output of three field sizes: 50×50, 40×40, and 30×30 mm2. 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 · 2.64 Impact Factor
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    ABSTRACT: Background: Transmural scar occupying left ventricular (LV) 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 remain poorly explored. This study evaluated scar distribution relative to LV and right ventricular (RV) lead tip placement through coregistration of late gadolinium enhancement MRI and cardiac computed tomographic (CT) findings. Influences on CRT response were assessed by serial echocardiography. Methods and results: Sixty patients receiving CRT underwent preimplant late gadolinium enhancement MRI, postimplant cardiac CT, and serial echocardiography. Blinded segmental evaluations of mechanical delay, percentage scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LV end-systolic volume ≥15% at 6 months. The mean age and LV ejection fraction were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT nonresponders for both the LV (23±23% versus 8±14% [P=0.01]) and RV pacing regions (40±32% versus 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 with 55%, 25%, and 0%, respectively, when the RV, LV, or both pacing regions contained scar. LV pacing region dyssynchrony was not predictive of response. Conclusions: Myocardial scar occupying the LV pacing region is associated with nonresponse to CRT. Scar occupying the RV pacing region is encountered at higher frequency and seems to provide a more intermediate influence on CRT response.
    Circulation Cardiovascular Imaging 06/2013; 6(4). DOI:10.1161/CIRCIMAGING.111.000146 · 5.32 Impact Factor
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    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 · 5.04 Impact Factor
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    ABSTRACT: Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory spondyloarthropathy, characterized by ectopic calcification of spinal tissues. Symptoms include spine pain and stiffness, and in severe cases dysphagia and spinal cord compression. The etiology of DISH is unknown and there are no specific treatments. Recent studies have suggested a role for purine metabolism in the regulation of biomineralization. Equilibrative nucleoside transporter 1 (ENT1) transfers hydrophilic nucleosides, such as adenosine, across the plasma membrane. In mice lacking ENT1, we observed the development of calcified lesions resembling DISH. By 12 months of age, ENT1(-/-) mice exhibited signs of spine stiffness, hind limb dysfunction, and paralysis. Micro-CT revealed ectopic mineralization of paraspinal tissues in the cervical-thoracic region at 2 months of age, which extended to the lumbar and caudal regions with advancing age. Energy-dispersive X-ray microanalysis of lesions revealed a high content of calcium and phosphorus with a ratio similar to that of cortical bone. At 12 months of age, histological examination of ENT1(-/-) mice revealed large, irregular accumulations of eosinophilic material in paraspinal ligaments and entheses, intervertebral discs and sternocostal articulations. There was no evidence of mineralization in appendicular joints or blood vessels, indicating specificity for the axial skeleton. Plasma adenosine levels were significantly greater in ENT1(-/-) mice than in wild-type, consistent with loss of ENT1-a primary adenosine uptake pathway. There was a significant reduction in the expression of Enpp1, Ank and Alpl in intervertebral discs from ENT1(-/-) mice compared to wild-type mice. Elevated plasma levels of inorganic pyrophosphate in ENT1(-/-) mice indicated generalized disruption of pyrophosphate homeostasis. This is the first report of a role for ENT1 in regulating the calcification of soft tissues. Moreover, ENT1(-/-) mice may be a useful model for investigating pathogenesis and evaluating therapeutics for the prevention of mineralization in DISH and related disorders. © 2012 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2013; 28(5). DOI:10.1002/jbmr.1826 · 6.83 Impact Factor
  • David A Rudko · Junmin Liu · Ravi S. Menon · Maria Drangova ·

    International Society for Magnetic Resonance in Medicine 2013 Annual Meeting, Salt Lake City, Utah; 04/2013

Publication Stats

2k Citations
501.09 Total Impact Points


  • 1992-2015
    • Robarts Research Institute
      • Imaging Research Laboratories
      London, Ontario, Canada
  • 1990-2015
    • The University of Western Ontario
      • • Department of Medical Biophysics
      • • Department of Physiology and Pharmacology
      • • Robarts Research Institute
      London, Ontario, Canada
  • 2012
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
    • Western University
      London, Ontario, Canada
  • 1995-1997
    • Stanford University
      • Department of Radiology
      Palo Alto, California, United States