Gerald Wisenberg

University of Ottawa, Ottawa, Ontario, Canada

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Publications (79)290.44 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rubidium-ARMI (alternative radiopharmaceutical for myocardial imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences > 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. Qualifying scores of SSS = 2, SDS = 2 were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores had site-core differences ≤ 3, respectively. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences ≤ 3. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.
    Journal of Nuclear Medicine 11/2013; · 5.77 Impact Factor
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    ABSTRACT: Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging. This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry. AIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative 'advanced' imaging technologies.Trial registration: NCT01288560.
    Trials 07/2013; 14(1):218. · 2.21 Impact Factor
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    ABSTRACT: The hybridization of positron emission tomography (PET) and magnetic resonance imaging (MRI) within a single imaging bore is a major advance in noninvasive imaging. Intrinsic co-registration of metabolic/molecular probe imaging with morphological, functional, and tissue imaging presents new opportunities for disease characterization. Sarcoidosis is a multisystem inflammatory disease hall- marked by inflammation, noncaseating granuloma formation, and organ dysfunction. Cardiac involvement accounts for up to 25% of disease-related mortality and is conventionally diagnosed with the Japanese Ministry criteria. However, studies using cardiac PET and MRI suggest a robust capacity to identify cardiac involvement—PET through identification of active inflammation and MRI through identification of mature fibrosis or scar. In this report, we describe the first clinical use of simultaneous PET-MRI to assist in the diagnosis of cardiac disease: active cardiac sarcoidosis.
    Circulation 06/2013; 127(22):e639-41. · 15.20 Impact Factor
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    ABSTRACT: Severe aortic insufficiency with minimal aortic annular calcification has been considered a relative contraindication to transcatheter aortic valve implantation (TAVI) because of a lack of calcium for fluoroscopic visualization and radial stent fixation. We report a patient with severe aortic insufficiency after previous coronary artery bypass and aortic valve repair who underwent successful TAVI. Intraoperative transesophageal echocardiography was critical to guide valve implantation and previous surgical pledgets were used to seat an oversized TAVI prosthesis within the aortic annulus. In follow-up, the patient remained New York Heart Association class I and echocardiography demonstrated a well-functioning TAVI prosthesis with no aortic insufficiency.
    The Canadian journal of cardiology 03/2013; · 3.12 Impact Factor
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    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
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    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
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    ABSTRACT: Stem cell transplantation following AMI has shown promise for the repair or reduction of the amount of myocardial injury. There is some evidence that these treatment effects appear to be directly correlated to cell residence time. This study aims to assess the effects of (a) the timing of stem cell injection following myocardial infarction, and (b) flow milieu, on cell residence times at the site of transplantation by comparing three time points (day of infarction, week 1 and week 4-5), and two models of acute myocardial infarction (sustained occlusion or reperfusion). Twenty-one dogs received 2 injections of 30 million endothelial progenitor cells. The first injections were administered by epicardial (n = 8) or endocardial injection (n = 13) either on the day of infarction (n = 15) or at 1 week (n = 6). The second injections were administered by only endocardial injection (n = 18) 4 weeks following the first injection. Cell clearance half-lives were comparable between early and late injections. However, transplants into sustained occlusion infarcts resulted in slower cell clearance 77.1 ± 6.1 (n = 18) versus reperfused 59.4 ± 2.9 h (n = 21) p = 0.009. Sustained occlusion infarcts had longer cell retention in comparison to reperfusion whereas the timing of injection did not affect clearance rates. If the potential for myocardial regeneration associated with cell transplantation is, at least in part, linked to cell residence times, then greater benefit may be observed with transplants into infarcts associated with persistent coronary artery occlusion.
    The international journal of cardiovascular imaging 06/2012; · 2.15 Impact Factor
  • Society of Nuclear Medicine Annual Meeting 2012; 06/2012
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    ABSTRACT: Scar signal quantification using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) identifies patients at higher risk of future events, both in ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). However, the ability of scar signal burden to predict events in such patient groups at the time of referral for implantable cardioverter-defibrillator (ICD) has not been well explored. This study evaluates the predictive use of multiple scar quantification measures in ICM and DCM patients being referred for ICD. One hundred twenty-four consecutive patients referred for ICD therapy (59 with ICM and 65 with DCM) underwent a standardized LGE-CMR protocol with blinded, multithreshold scar signal quantification and, for those with ICM, peri-infarct signal quantification. Patients were followed prospectively for the primary combined outcome of appropriate ICD therapy, survived cardiac arrest, or sudden cardiac death. At a mean follow-up of 632 ± 262 days, 18 patients (15%) had suffered the primary outcome. Total scar was significantly higher among those suffering a primary outcome, a relationship maintained within each cardiomyopathy cohort (P<0.01 for all comparisons). Total scar was the strongest independent predictor of the primary outcome and demonstrated a negative predictive value of 86%. In the ICM subcohort, peri-infarct signal showed only a nonsignificant trend toward elevation among those having a primary end point. Myocardial scar quantification by LGE-CMR predicts arrhythmic events in patients being evaluated for ICD eligibility irrespective of cardiomyopathy etiology.
    Circulation Cardiovascular Imaging 05/2012; 5(4):448-56. · 5.80 Impact Factor
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    ABSTRACT: Cardiac sarcoidosis is a potentially fatal complication of sarcoidosis. The 1993 guidelines of the Ministry of Health, Labour, and Welfare (MHLW) of Japan have been used as the diagnostic gold standard and for comparison with imaging modalities. (18)F-FDG PET is not currently included in the guidelines. However, studies have shown promising data using (18)F-FDG PET. We conducted a systematic review of studies that evaluated the accuracy of (18)F-FDG PET for the diagnosis of cardiac sarcoidosis compared with MHLW guidelines. Data from a prospective Ontario provincial registry are also reported and included in the metaanalysis. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies that satisfied predetermined criteria. Quality evaluation using the Quality Assessment for Diagnostic Accuracy Studies was performed by 2 independent masked observers. Data were extracted and analyzed to measure study-specific and pooled accuracy for (18)F-FDG PET compared with the MHLW as the reference. A total of 519 titles was identified; 7 studies, including the Ontario registry, were selected for inclusion. Metaanalysis of these 7 studies was conducted, with a total of 164 patients, most of whom had been diagnosed with systemic sarcoidosis. The prevalence of cardiac sarcoidosis was 50% in the whole population. Pooled estimates for (18)F-FDG PET yielded 89% sensitivity (95% confidence interval [CI], 79%-96%), 78% specificity (95% CI, 68%-86%), a 4.1 positive likelihood ratio (95% CI, 1.7-10), and a 0.19 negative likelihood ratio (95% CI, 0.1-0.4). The overall diagnostic odds ratio was 25.6 (95% CI, 7.3-89.5), and the area under the summary receiver operator characteristic curve was 93% ± 3.5. The Ontario study yielded sensitivity and specificity of 79% and 70%, respectively. The high diagnostic accuracy determined for (18)F-FDG PET in this metaanalysis suggests potential value for diagnosis of cardiac sarcoidosis compared with the MHLW guidelines. These results may affect patient care by providing supportive evidence for more effective use of (18)F-FDG PET in the diagnosis of cardiac sarcoidosis. Large-scale multicenter studies are required to further evaluate this role.
    Journal of Nuclear Medicine 02/2012; 53(2):241-8. · 5.77 Impact Factor
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    ABSTRACT: A challenge with cardiac cell therapy is determining the location of cells relative to infarct tissue. As cells are viable following ¹¹¹In-labeling, and first-pass CT imaging can identify regions of myocardial infarction, we evaluated the feasibility of a SPECT/CT system to localize cells relative to infarcted myocardium in a canine model. Ten canines underwent surgical ligation of the left-anterior-descending artery and endothelial progenitor cells labeled with ¹¹¹In-tropolone were transplanted endocardially or epicardially. SPECT/CT was performed on day of transplantation, 4 and 10 days post-transplantation. For each imaging session first-pass perfusion CT was performed to delineate the area of reduced perfusion. SPECT and first-pass CT images were fused and evaluated. Contrast-to-noise ratios (CNR) were calculated for ¹¹¹In-SPECT images to evaluate cell detection. The zone of reduced perfusion was well delineated on first-pass perfusion CT in all canines. The ¹¹¹In signal was visualized within this zone in all cases. Analysis of the CNRs suggests that cells may be followed for 11 effective half-lives using the images from first-pass perfusion CT to provide the anatomic landmarks. In the setting of an acute myocardial infarction SPECT/[first-pass perfusion CT] is an effective hybrid platform for the localization of cells in relation to the area of reduced blood flow.
    Contrast Media & Molecular Imaging 01/2012; 7(1):76-84. · 2.87 Impact Factor
  • Contrast Media & Molecular Imaging 01/2012; · 2.87 Impact Factor
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    ABSTRACT: The purpose of this study was to validate T2*-weighted cardiac magnetic resonance (T2*-CMR) for the detection and quantification of reperfusion hemorrhage in vivo against an ex vivo gold standard, and to investigate the relationship of hemorrhage to microvascular obstruction, infarct size, and left ventricular (LV) functional parameters. Hemorrhage can contribute to reperfusion injury in myocardial infarction and may have significant implications for patient management. There is currently no validated imaging method to assess reperfusion hemorrhage in vivo. T2*-CMR appears suitable because it can create image contrast on the basis of magnetic field effects of hemoglobin degradation products. In 14 mongrel dogs, myocardial infarction was experimentally induced. On day 3 post-reperfusion, an in vivo CMR study was performed including a T2*-weighted gradient-echo imaging sequence for hemorrhage, standard sequences for LV function, and post-contrast sequences for microvascular obstruction and myocardial necrosis. Ex vivo, thioflavin S imaging and triphenyl-tetrazoliumchloride (TTC) staining were performed to assess microvascular obstruction, hemorrhage, and myocardial necrosis. Images were analyzed by blinded observers, and comparative statistics were performed. Hemorrhage occurred only in the dogs with the largest infarctions and the greatest extent of microvascular obstruction, and it was associated with more compromised LV functional parameters. Of 40 hemorrhagic segments on TTC staining, 37 (92.5%) were positive for hemorrhage on T2*-CMR (kappa = 0.96, p < 0.01 for in vivo/ex vivo segmental agreement). The amount of hemorrhage in 13 affected tissue slices as determined by T2*-CMR in vivo correlated strongly with ex vivo results (20.3 ± 2.3% vs. 17.9 ± 1.6% per slice; Pearson r = 0.91; r(2) = 0.83, p < 0.01 for both). Hemorrhage size was not different between in vivo T2*-CMR and ex vivo TTC (mean difference 2.39 ± 1.43%; p = 0.19). T2*-CMR accurately quantified myocardial reperfusion hemorrhage in vivo. Hemorrhage was associated with more severe infarct-related injury.
    JACC. Cardiovascular imaging 12/2011; 4(12):1274-83. · 14.29 Impact Factor
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    ABSTRACT: We developed a quantitative Dynamic Contrast-Enhanced CT (DCE-CT) technique for measuring Myocardial Perfusion Reserve (MPR) and Volume Reserve (MVR) and studied their relationship with coronary stenosis. Twenty-six patients with Coronary Artery Disease (CAD) were recruited. Degree of stenosis in each coronary artery was classified from catheter-based angiograms as Non-Stenosed (NS, angiographically normal or mildly irregular), Moderately Stenosed (MS, 50-80% reduction in luminal diameter), Severely Stenosed (SS, >80%) and SS with Collaterals (SSC). DCE-CT at rest and after dipyridamole infusion was performed using 64-slice CT. Mid-diastolic heart images were corrected for beam hardening and analyzed using proprietary software to calculate Myocardial Blood Flow (MBF, in mL∙min(-1)∙100 g(-1)) and Blood Volume (MBV, in mL∙100 g(-1)) parametric maps. MPR and MVR in each coronary territory were calculated by dividing MBF and MBV after pharmacological stress by their respective baseline values. MPR and MVR in MS and SS territories were significantly lower than those of NS territories (p < 0.05 for all). Logistic regression analysis identified MPR∙MVR as the best predictor of ≥50% coronary lesion than MPR or MVR alone. DCE-CT imaging with quantitative CT perfusion analysis could be useful for detecting coronary stenoses that are functionally significant.
    European Radiology 09/2011; 22(1):39-50. · 4.34 Impact Factor
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    ICNC 10 (Nuclear Cardiology & Cardiac CT); 05/2011
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    Journal of Cardiovascular Magnetic Resonance 01/2011; · 4.44 Impact Factor
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    ABSTRACT: Introduction. Previously we proposed a cellular imaging technique to determine the surviving fraction of transplanted cells in vivo. Epicardial kinetics using Indium-111 determined the Debris Impulse Response Function (DIRF) and leakage coefficient parameters. Convolution-based modeling which corrected for these signal contributions indicated that (111)In activity was quantitative of cell viability with half-lives within 20 hrs to 37 days. We determine if the 37-day upper limit remains valid for endocardial injections by comparing previous epicardial cell leakage parameter estimates to those for endocardial cells. Methods. Normal canine myocardium was injected ((111)In-tropolone) epicardially (9 injections) or endocardially (10 injections). Continuous whole body and SPECT scans for 5 hours were acquired with three weekly follow-up imaging sessions up to 20-26 days. Time-activity curves evaluated each injection type. Results. The epicardial and endocardial kinetics were not significantly different (Epi: 1286 ± 253; Endo: 1567 ± 470 hours P = .62). Conclusion. The original epicardial estimate of leakage kinetics has been validated for use in endocardial injections.
    International journal of molecular imaging. 01/2011; 2011:472375.
  • Medical Physics 01/2011; 38(6):3431-. · 2.91 Impact Factor

Publication Stats

1k Citations
290.44 Total Impact Points

Institutions

  • 2013
    • University of Ottawa
      • Department of Medicine
      Ottawa, Ontario, Canada
    • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2004–2013
    • London Health Sciences Centre
      • Division of Cardiology
      London, Ontario, Canada
  • 1984–2013
    • The University of Western Ontario
      • • Department of Medicine
      • • Department of Medical Biophysics
      • • Division of Nuclear Medicine
      London, Ontario, Canada
  • 1999–2012
    • Lawson Health Research Institute
      London, Ontario, Canada
  • 2009
    • St. Joseph's Health Care London
      London, Ontario, Canada
  • 1987–1989
    • Saint Joseph Hospital
      Chicago, Illinois, United States
  • 1988
    • St. Joseph's Health Centre, Toronto
      • Department of Medicine
      Toronto, Ontario, Canada
    • Victoria General Hospital
      Winnipeg, Manitoba, Canada