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  • 1.
    Frostfeldt, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Valind, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Development of myocardial microcirculation and metabolism in acute ST-elevation myocardial infarction evaluated with positron emission tomography2005In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 12, no 1, p. 43-54Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Early reperfusion is an established therapeutic objective in acute myocardial infarction (MI). The relationship of regional myocardial microcirculation and metabolism toward outcome in acute human MI is not well known.

    METHODS AND RESULTS: In 8 patients, positron emission tomography (PET) was performed with oxygen 15-labeled water at 3 hours, 24 hours, and 3 weeks after the start of fibrinolytic treatment, with carbon 11 acetate at 3 hours and with fluorine 18 fluorodeoxyglucose at 24 hours and 3 weeks. Absolute quantification of perfusion and water-perfusable tissue fraction (PTF), metabolic activity, and substrate extraction in 4 regions of interest was performed. Coronary angiography was performed at 24 hours. Short-term outcome at 3 weeks was evaluated by contractile reserve with dobutamine stress echocardiography and lung water measurements with PET. Early regional perfusion, PTF, and extraction and utilization of oxygen and glucose decreased closer to the infarct region ( P < .001 for all). Infarct-related oxygen utilization and extraction of oxygen and glucose were closely related to outcome ( P < .01 for all). PTF improved significantly in the infarct-related regions over time in proportion to early oxygen extraction and utilization.

    CONCLUSIONS: This pilot study indicates that PET might be useful in the evaluation of treatment efficacy and that restoration of oxidative metabolism is more closely related to myocardial damage recovery than perfusion in the early phase after MI.

  • 2. Grönman, Maria
    et al.
    Tarkia, Miikka
    Stark, Christoffer
    Vähäsilta, Tommi
    Kiviniemi, Tuomas
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Halonen, Paavo
    Kuivanen, Antti
    Saunavaara, Virva
    Tolvanen, Tuula
    Teuho, Jarmo
    Teräs, Mika
    Savunen, Timo
    Pietilä, Mikko
    Ylä-Herttuala, Seppo
    Roivainen, Anne
    Knuuti, Juhani
    Saraste, Antti
    Assessment of myocardial viability with [15O]water PET: A validation study in experimental myocardial infarction.2019In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI).

    METHODS AND RESULTS: Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively.

    CONCLUSIONS: Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability.

  • 3. Hansson, Nils Henrik
    et al.
    Tolbod, Lars
    Harms, Johannes
    Wiggers, Henrik
    Kim, Won Yong
    Hansen, Esben
    Zaremba, Tomas
    Frøkiær, Jørgen
    Jakobsen, Steen
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evaluation of ECG-gated [(11)C]acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency2016In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 23, no 4, p. 670-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [(11)C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [(11)C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [(11)C]acetate PET.

    METHODS: Thirty-five subjects with aortic valve stenosis underwent ECG-gated [(11)C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE.

    RESULTS: LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias -3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness.

    CONCLUSIONS: Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [(11)C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

  • 4. Harms, Hendrik J
    et al.
    Hansson, Nils Henrik S
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Tolbod, Lars P
    Kim, Won Y
    Frøkiær, Jørgen
    Flachskampf, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wiggers, Henrik
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Automatic calculation of myocardial external efficiency using a single 11C-acetate PET scan.2018In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, no 6, p. 1937-1944Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO2) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single 11C-acetate PET scan without ECG-gating.

    METHODS AND RESULTS: Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO2 was calculated using washout of 11C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEEPET-CMR and MEEPET was high (r = 0.85, P < 0.001) without significant bias. MEEPET was 23.6 ± 4.2% for controls and was lowered in AVS (17.2 ± 4.3%, P < 0.001) and in MVR (18.0 ± 5.2%, P = 0.004). MEEPET was strongly associated with both NYHA class (P < 0.001) and the magnitude of valvular dysfunction (mean aortic gradient: P < 0.001, regurgitant fraction: P = 0.009).

    CONCLUSION: A single 11C-acetate PET yields accurate and automated MEE results on different scanners. MEE might provide an unbiased measurement of the phenotypic response to valvular disease.

  • 5.
    Kero, Tanja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Edvin
    Engström, Mathias
    Eggers, Kai M
    Johansson, Lars
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Evaluation of quantitative CMR perfusion imaging by comparison with simultaneous 15O-water-PET.2019In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference with a fully integrated PET-MR scanner.

    METHODS: 15 patients underwent simultaneous DCE MRI and 15O-water PET scans at rest and adenosine-stress on an integrated PET-MR scanner. Correlation and agreement between MRI- and PET-based global and regional MBF values were assessed using correlation and Bland-Altman analysis.

    RESULTS: Three subjects were excluded due to technical problems. Global mean (± SD) MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for PET (P = 0.66 and P = 0.81). The correlations between global and regional MRI- and PET-based MBF values were strong (r = 0.86 and r = 0.75). The biases were negligible for both global and regional MBF comparisons (0.01 and 0.00 mL/min/g for both), but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values.

    CONCLUSION: The correlation between simultaneous MBF measurements with DCE MRI and 15O-water PET measured in an integrated PET-MRI was strong but the agreement was only moderate indicating that MRI-based quantitative MBF measurements is not ready for clinical introduction.

  • 6.
    Kero, Tanja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindsjö, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Accurate analysis and visualization of cardiac (11)C-PIB uptake in amyloidosis with semiautomatic software2016In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 23, no 4, p. 741-750Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: (11)C-PIB PET is a promising non-invasive diagnostic tool for cardiac amyloidosis. Semiautomatic analysis of PET data is now available but it is not known how accurate these methods are for amyloid imaging. The aim of this study was to evaluate the feasibility of one semiautomatic software tool for analysis and visualization of (11)C-PIB left ventricular retention index (RI) in cardiac amyloidosis.

    METHODS AND RESULTS: Patients with systemic amyloidosis and cardiac involvement (n = 10) and healthy controls (n = 5) were investigated with dynamic (11)C-PIB PET. Two observers analyzed the PET studies with semiautomatic software to calculate the left ventricular RI of (11)C-PIB and to create parametric images. The mean RI at 15-25 min from the semiautomatic analysis was compared with RI based on manual analysis and showed comparable values (0.056 vs 0.054 min(-1) for amyloidosis patients and 0.024 vs 0.025 min(-1) in healthy controls; P = .78) and the correlation was excellent (r = 0.98). Inter-reader reproducibility also was excellent (intraclass correlation coefficient, ICC > 0.98). Parametric polarmaps and histograms made visual separation of amyloidosis patients and healthy controls fast and simple.

    CONCLUSION: Accurate semiautomatic analysis of cardiac (11)C-PIB RI in amyloidosis patients is feasible. Parametric polarmaps and histograms make visual interpretation fast and simple.

  • 7.
    Marchesseau, Stephanie
    et al.
    A STAR NUS, Clin Imaging Res Ctr, Singapore, Singapore.
    Seneviratna, Aruni
    Natl Univ Heart Ctr, Dept Cardiol, Singapore, Singapore.
    Sjöholm, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. A STAR NUS, Clin Imaging Res Ctr, Singapore, Singapore.
    Qin, Daphne Liang
    Natl Univ Heart Ctr, Dept Cardiol, Singapore, Singapore.
    Ho, Jamie X. M.
    A STAR NUS, Clin Imaging Res Ctr, Singapore, Singapore.
    Hausenloy, Derek J.
    UCL, Hatter Cardiovasc Inst, London, England;UCL, Hosp Biomed Res Ctr, Natl Inst Hlth Res, London, England;Natl Heart Ctr Singapore, Natl Heart Res Inst Singapore, Singapore, Singapore;Duke Natl Univ Singapore, Med Sch, Cardiovasc & Metab Disorders Program, Singapore, Singapore.
    Townsend, David W.
    A STAR NUS, Clin Imaging Res Ctr, Singapore, Singapore.
    Richards, A. Mark
    Natl Univ Heart Ctr, Dept Cardiol, Singapore, Singapore;NUHS, Cardiovasc Res Inst, Singapore, Singapore.
    Totman, John J.
    A STAR NUS, Clin Imaging Res Ctr, Singapore, Singapore.
    Chan, Mark Y. Y.
    Hybrid PET/CT and PET/MRI imaging of vulnerable coronary plaque and myocardial scar tissue in acute myocardial infarction2018In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, no 6, p. 2001-2011Article in journal (Refereed)
    Abstract [en]

    BackgroundFollowing an acute coronary syndrome, combined CT and PET with F-18-NaF can identify coronary atherosclerotic plaques that have ruptured or eroded. However, the processes behind F-18-NaF uptake in vulnerable plaques remain unclear. Methods and ResultsTen patients with STEMI were scanned after F-18-NaF injection, for 75minutes in a Siemens PET/MR scanner using delayed enhancement (LGE). They were then scanned in a Siemens PET/CT scanner for 10minutes. Tissue-to-background ratio (TBR) was compared between the culprit lesion in the IRA and remote non-culprit lesions in an effort to independently validate prior studies. Additionally, we performed a proof-of-principle study comparing TBR in scar tissue and remote myocardium using LGE images and PET/MR or PET/CT data. From the 33 coronary lesions detected on PET/CT, TBRs for culprit lesions were higher than for non-culprit lesions (TBR=2.110.45 vs 1.46 +/- 0.48; P<0.001). Interestingly, the TBR measured on the PET/CT was higher for infarcted myocardium than for remote myocardium (TBR=0.81 +/- 0.10 vs 0.71 +/- 0.05; P=0.003). These results were confirmed using the PET/MR data (TBR=0.81 +/- 0.10 for scar, TBR=0.71 +/- 0.06 for healthy myocardium, P=0.03). Conclusions We confirmed the potential of F-18-NaF PET/CT imaging to detect vulnerable coronary lesions. Moreover, we demonstrated proof-of-principle that F-18-NaF concurrently detects myocardial scar tissue.

  • 8. Pilebro, Björn
    et al.
    Arvidsson, Sandra
    Lindqvist, Per
    Sundström, Torbjörn
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Suhr, Ole
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR)2018In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, no 1, p. 240-248Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing (11)C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer's disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis.

    METHODS: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers.

    RESULTS: PIB-RI was increased in all patients (P < 0.001), but was significantly higher in type B than in type A (0.129 ± 0.041 vs 0.040 ± 0.006 min(-1), P = 0.009). Cardiac DPD uptake was elevated in group A and absent in group B.

    CONCLUSION: PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis.

  • 9. Vermeltfoort, Ilse A.
    et al.
    Raijmakers, Pieter G.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Germans, Tjeerd
    van Rossum, Albert C.
    Lammertsma, Adriaan A.
    Knaapen, Paul
    Feasibility of subendocardial and subepicardial myocardial perfusion measurements in healthy normals with (15)O-labeled water and positron emission tomography2011In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 18, no 4, p. 650-656Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) enables robust and reproducible measurements of myocardial blood flow (MBF). However, the relatively limited resolution of PET till recently prohibited distinction between the subendocardial and the subepicardial layers in non-hypertrophied myocardium. Recent developments in hard- and software, however, have enabled to identify a transmural gradient difference in animal experiments. The aim of this study is to determine the feasibility of subendocardial and subepicardial MBF in normal human hearts assessed with (15)O-labeled water PET. Twenty-seven healthy subjects (mean age 41 +/- A 13 years; 11 men) were studied with (15)O-labeled water PET to quantify resting and hyperaemic (adenosine) MBF at a subendocardial and subepicardial level. In addition, cardiac magnetic resonance imaging was performed to determine left ventricular (LV) volumes and function. Mean rest MBF was 1.46 +/- A 0.49 in the subendocardium, and 1.14 +/- A 0.342 mL center dot A min(-1) center dot A g(-1) in the subepicardium (P < .001). MBF during vasodilation was augmented to a greater extent at the subepicardial level (subendocardium vs subepicardium: 3.88 +/- A 0.86 vs 4.14 +/- A 0.88 mL center dot A min(-1) center dot A g(-1), P = .013). The endocardial-to-epicardial MBF ratio decreased significantly during hyperaemia (1.35 +/- A 0.23 to 1.12 +/- A 0.20, P < .001). Hyperaemic transmural MBF was inversely correlated with left ventricular end-diastolic volume index (LVEDVI) (r (2) = 0.41, P = .0003), with greater impact however at the subendocardial level. (15)O-labeled water PET enables MBF measurements with distinction of the subendocardial and subepicardial layers in the normal human heart and correlates with LVEDVI. This PET technique may prove useful in evaluating patients with signs of ischaemia due to coronary artery disease or microvascular dysfunction.

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