Maria Drangova

The University of Western Ontario, London, Ontario, Canada

Are you Maria Drangova?

Claim your profile

Publications (146)410.08 Total impact

  • [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 01/2015; · 2.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: -Left ventricular (LV) and right ventricular (RV) 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 3D navigational model displaying both LV and RV pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated.
    Circulation Arrhythmia and Electrophysiology 09/2014; · 5.95 Impact Factor
  • [Show abstract] [Hide abstract]
    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 04/2014; · 2.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; · 3.27 Impact Factor
  • [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.
    02/2014;
  • [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. 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 01/2014; · 3.12 Impact Factor
  • Source
    [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. · 4.44 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. · 2.91 Impact Factor
  • Source
    [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.
    Circulation Cardiovascular Imaging 06/2013; · 5.80 Impact Factor
  • Source
    [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; · 5.70 Impact Factor
  • International Society for Magnetic Resonance in Medicine 2013 Annual Meeting, Salt Lake City, Utah; 04/2013
  • [Show abstract] [Hide abstract]
    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. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 04/2013; · 2.57 Impact Factor
  • [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.
    Acta Radiologica 02/2013; · 1.33 Impact Factor
  • Source
    [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.
    Circulation Cardiovascular Imaging 02/2013; · 5.80 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%.
    IEEE Transactions on Biomedical Engineering 01/2013; 60(4):899-905. · 2.35 Impact Factor
  • Source
    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
  • Source
    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cholinergic neurons are known to regulate striatal circuits; however striatal-dependent physiological outcomes influenced by acetylcholine (ACh) are still poorly understood. Here we used VAChT(D2-Cre-flox/flox) mice, in which we selectively ablated the vesicular acetylcholine transporter in the striatum to dissect the specific roles of striatal ACh in metabolic homeostasis. We report that VAChT(D2-Cre-flox/flox) mice are lean at a young age and maintain this lean phenotype with time. The reduced body weight observed in these mutant mice is not attributable to reduced food intake or to a decrease in growth rate. In addition, changed activity could not completely explain the lean phenotype, as only young VAChT(D2-Cre-flox/flox) mice showed increased physical activity. Interestingly, VAChT(D2-Cre-flox/flox) mice show several metabolic changes, including increased plasma levels of insulin and leptin. They also show increased periods of wakefulness when compared to littermate controls. Taken together our data suggest that striatal ACh has an important role in the modulation of metabolism and highlight the importance of striatum cholinergic tone in the regulation of energy expenditure. These new insights on how cholinergic neurons influence homeostasis open new avenues for the search of drug targets to treat obesity. © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12128.
    Journal of Neurochemistry 12/2012; · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    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 11/2012; · 6.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Myocardial fibrosis (MF) is a common pathophysiologic endpoint in non-ischemic cardiomyopathy and may be identified by Late Gadolinium Enhancement (LGE) MRI. While associated with future cardiovascular events in Hypertrophic Cardiomyopathy (HCM) and Dilated Cardiomyopathy (DCM) the influence of MF on interim quality of life (QOL) has not been explored. In this study we investigate for associations between MF and validated indices of QOL in patients with HCM and DCM. Ninety-eight patients with known cardiomyopathy (n = 56-HCM/n = 42-DCM) underwent LGE-MRI in addition to standardized testing for QOL using the disease-specific Minnesota Living With Heart Failure (MLWHF) and the generic SF-12 questionnaires. LGE-MRI images were blindly analyzed for the presence and volume of MF using validated techniques. All analyses were stratified according to cardiomyopathy sub-type. The mean age of the population was 56.8 ± 12.9 years. MF was identified in 82 % of patients with HCM and 74 % of patients with DCM with respective mean MF burdens of 20.0 and 13.7 % of the left ventricular mass (p = 0.008). QOL scores for those with HCM or DCM, as assessed by both MLWHF and SF-12, were not significantly different between those with versus those without MF, and showed no association with MF burden by quantitative signal analysis. In this study we identified no association between QOL and MF burden by LGE-MRI in patients with HCM or DCM. Therefore, the severity of underlying myocardial tissue disease, a recognized substrate for ventricular arrhythmia, cannot and should not be inferred from the patient's symptom status or QOL.
    The international journal of cardiovascular imaging 08/2012; · 2.15 Impact Factor

Publication Stats

2k Citations
410.08 Total Impact Points

Institutions

  • 1991–2014
    • The University of Western Ontario
      • • Department of Medical Biophysics
      • • Department of Anatomy and Cell Biology
      • • Department of Medicine
      • • Robarts Research Institute
      London, Ontario, Canada
    • University of Toronto
      • Department of Medical Biophysics
      Toronto, Ontario, Canada
  • 1992–2013
    • Robarts Research Institute
      • Imaging Research Laboratories
      London, Ontario, Canada
  • 2012
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 1996–2011
    • Stanford University
      • • Department of Radiology
      • • Department of Electrical Engineering
      Stanford, CA, United States
  • 2007–2009
    • Ryerson University
      • Department of Physics
      Toronto, Ontario, Canada
  • 2008
    • Grand River Hospital
      Kitchener, Ontario, Canada
  • 2005
    • King's College London
      • Department of Clinical Neuroscience
      London, ENG, United Kingdom
    • Lawson Health Research Institute
      London, Ontario, Canada