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4. Accuracy and Reproducibility of Myocardial Blood Flow Quantification by Single Photon Emission Computed Tomography Imaging in Patients With Known or Suspected Coronary Artery Disease

Author

de Souza, Ana Carolina do AH, Harms, Hendrik J, Martell, Laurel, Bibbo, Courtney, Harrington, Meagan, Sullivan, Kyle, Hainer, Jon, Dorbala, Sharmila, Blankstein, Ron, Taqueti, Viviany R, Kijewski, Marie Foley, Park, Mi-Ae, Meretta, Alejandro, Breault, Christopher, Roth, Nathaniel, Poitrasson-Rivière, Alexis, Soman, Prem, Gullberg, Grant T, and Di Carli, Marcelo F

Subjects
Heart Disease - Coronary Heart Disease, Cardiovascular, Biomedical Imaging, Clinical Research, Heart Disease, Prevention, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Ammonia, Cadmium, Coronary Artery Disease, Coronary Circulation, Humans, Myocardial Perfusion Imaging, Positron-Emission Tomography, Reproducibility of Results, Technetium Tc 99m Sestamibi, Tomography, Emission-Computed, Single-Photon, Zinc, myocardial blood flow, myocardial flow reserve, positron emission tomography, tomography, emission-computed, single-photon, tomography, emission-computed, single-photon, Clinical Sciences, Cardiovascular System & Hematology
Abstract

BackgroundSingle photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique.MethodsAccuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio.ResultsSPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P0.05 for all).ConclusionsMBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation.

Published
2022

15. Outcome prediction by myocardial external efficiency from 11C-acetate positron emission tomography in cardiac amyloidosis

Author

Rosengren, Sara, Skibsted Clemmensen, Tor, Hvitfeldt Poulsen, Steen, Tolbod, Lars, Harms, Hendrik J., Wikström, Gerhard, Kero, Tanja, Thyrsted Ladefoged, Bertil, Sörensen, Jens, Rosengren, Sara, Skibsted Clemmensen, Tor, Hvitfeldt Poulsen, Steen, Tolbod, Lars, Harms, Hendrik J., Wikström, Gerhard, Kero, Tanja, Thyrsted Ladefoged, Bertil, and Sörensen, Jens

Abstract

Aims This study aimed to study the prognostic value of myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) from 11C-acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients. Methods and results Forty-eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11C-acetate PET and echocardiography. MVO2, forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11C-acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11C-acetate PET parameters was analysed. MVO2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11C-acetate PET-derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N-terminal pro-brain natriuretic peptide, and the 11C-acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11C-acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1 mL/g (95% confidence interval 0.39–0.81, P = 0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut-off of 15.7% (P = 0.032). Survival was significantly shorter with FSV/LVM below 0.27 mL/g (P < 0.001), also when separating AL- and ATTR-CA. Conclusions Reduced MEE was associated with shorter survival in CA patients, but FSV/LVM was the strongest survival predictor and the only independently prognostic 11C-acetate PET parameter in multivariate analysis.

Published
2024
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16. Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Author

Team Medisch, Circulatory Health, Dahdal, Jorge, Bakker, Frank, Svanerud, Johan, Danad, Ibrahim, Driessen, Roel S., Raijmakers, Pieter G., Harms, Hendrik J., Lammertsma, Adriaan A., van de Hoef, Tim P., Appelman, Yolande, van Royen, Niels, Knaapen, Paul, de Waard, Guus A., Team Medisch, Circulatory Health, Dahdal, Jorge, Bakker, Frank, Svanerud, Johan, Danad, Ibrahim, Driessen, Roel S., Raijmakers, Pieter G., Harms, Hendrik J., Lammertsma, Adriaan A., van de Hoef, Tim P., Appelman, Yolande, van Royen, Niels, Knaapen, Paul, and de Waard, Guus A.

Published
2024

21. Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion.

Author

Dahdal, Jorge, Bakker, Frank, Svanerud, Johan, Danad, Ibrahim, Driessen, Roel S., Raijmakers, Pieter G., Harms, Hendrik J., Lammertsma, Adriaan A., van de Hoef, Tim P., Appelman, Yolande, van Royen, Niels, Knaapen, Paul, and de Waard, Guus A.

Subjects
POSITRON emission tomography, MYOCARDIAL perfusion imaging, DIASTOLIC blood pressure, CORONARY artery stenosis, PERFUSION, RECEIVER operating characteristic curves, CORONARY artery disease
Abstract

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Coronary Microvascular Dysfunction, Left Ventricular Remodeling, and Clinical Outcomes in Patients With Chronic Kidney Impairment

Author

Bajaj, Navkaranbir S., Singh, Amitoj, Zhou, Wunan, Gupta, Ankur, Fujikura, Kana, Byrne, Christina, Harms, Hendrik J., Osborne, Michael T., Bravo, Paco, Andrikopolou, Efstathia, Divakaran, Sanjay, Bibbo, Courtney F., Hainer, Jon, Skali, Hicham, Taqueti, Viviany, Steigner, Michael, Dorbala, Sharmila, Charytan, David M., Prabhu, Sumanth D., Blankstein, Ron, Deo, Rahul C., Solomon, Scott D., and Di Carli, Marcelo F.

Published
2020
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25. Myocardial External Efficiency in Asymptomatic Severe Primary Mitral Regurgitation Using 11C-Acetate PET

Author

Sörensen, Jens, Bergsten, Johannes, Baron, Tomasz, Örndahl, Lovisa Holm, Kero, Tanja, Bjerner, Tomas, Hedin, Eva-Maria, Harms, Hendrik J., Astudillo, Rafael, Flachskampf, Frank, Sörensen, Jens, Bergsten, Johannes, Baron, Tomasz, Örndahl, Lovisa Holm, Kero, Tanja, Bjerner, Tomas, Hedin, Eva-Maria, Harms, Hendrik J., Astudillo, Rafael, and Flachskampf, Frank

Abstract

Subjects with asymptomatic moderate-severe or severe primary mitral regurgitation (MR) are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial metabolic function in progression of MR is poorly understood. We used 11C-acetate positron emission tomography (PET) to non-invasively measure myocardial external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular oxygen consumption. Methods and Results: 47 patients in surveillance with MR and no or minimal symptoms prospectively underwent PET, echocardiography and cardiac magnetic resonance imaging (CMR) on the same day. PET was used to simultaneously measure cardiac output, LV mass and oxygen consumption to establish MEE. PET in patients were compared to healthy volunteers (n = 9). MEE and standard imaging indicators of regurgitation severity, LV volumes and function were studied as predictors of time to surgical intervention. Patients were followed median 3.0 years (interquartile range 2.0-3.8) and the endpoint was reached in 22 subjects (47%). MEE in patients reaching the endpoint (23.8±5.0%) was lower than in censored patients (28.5±4.5%, P = 0.002) and in healthy volunteers (30.1±4.9%, 0.001). MEE with a cut-off lower than 25.7% was significantly associated with the outcome (hazard ratio of 7.5 (95%CI: 2.7-20.6, p<0.0001) and retained independent significance when compared to standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve surgery in patients with asymptomatic moderate-severe or severe primary MR. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in MR.

Published
2023
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26. Outcome prediction by myocardial external efficiency from 11C‐acetate positron emission tomography in cardiac amyloidosis.

Author

Rosengren, Sara, Skibsted Clemmensen, Tor, Hvitfeldt Poulsen, Steen, Tolbod, Lars, Harms, Hendrik J., Wikström, Gerhard, Kero, Tanja, Thyrsted Ladefoged, Bertil, and Sörensen, Jens

Subjects
POSITRON emission tomography, BRAIN natriuretic factor, CARDIAC amyloidosis, IMMUNOGLOBULIN light chains
Abstract

Aims: This study aimed to study the prognostic value of myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) from 11C‐acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients. Methods and results: Forty‐eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11C‐acetate PET and echocardiography. MVO2, forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11C‐acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11C‐acetate PET parameters was analysed. MVO2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11C‐acetate PET‐derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N‐terminal pro‐brain natriuretic peptide, and the 11C‐acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11C‐acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1 mL/g (95% confidence interval 0.39–0.81, P = 0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut‐off of 15.7% (P = 0.032). Survival was significantly shorter with FSV/LVM below 0.27 mL/g (P < 0.001), also when separating AL‐ and ATTR‐CA. Conclusions: Reduced MEE was associated with shorter survival in CA patients, but FSV/LVM was the strongest survival predictor and the only independently prognostic 11C‐acetate PET parameter in multivariate analysis. [ABSTRACT FROM AUTHOR]

Published
2024
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30. 3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography Depicts Heterogeneous Proliferation Pathology in Idiopathic Pulmonary Arterial Hypertension Patient Lung: A Potential Biomarker for Pulmonary Arterial Hypertension

Author

Ashek, Ali, Spruijt, Onno A., Harms, Hendrik J., Lammertsma, Adriaan A., Cupitt, John, Dubois, Olivier, Wharton, John, Dabral, Swati, Pullamsetti, Soni Savai, Huisman, Marc C., Frings, Virginie, Boellaard, Ronald, de Man, Frances S., Botros, Lisa, Jansen, Samara, Vonk Noordegraaf, Anton, Wilkins, Martin R., Bogaard, Harm J., and Zhao, Lan

Published
2018
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32. Accuracy and Reproducibility of Myocardial Blood Flow Quantification by SPECT Imaging in Patients With Known or Suspected Coronary Artery Disease

Author

de Souza, Ana Carolina do A. H., Harms, Hendrik J., Martell, Laurel, Bibbo, Courtney, Harrington, Meagan, Sullivan, Kyle, Hainer, Jon, Dorbala, Sharmila, Blankstein, Ron, Taqueti, Viviany R., Kijewski, Marie Foley, Park, Mi-Ae, Meretta, Alejandro, Breault, Christopher, Roth, Nathaniel, Poitrasson-Rivière, Alexis, Soman, Prem, Gullberg, Grant T., and Di Carli, Marcelo F.

Subjects
Technetium Tc 99m Sestamibi, Tomography, Emission-Computed, Single-Photon, Zinc, Ammonia, Coronary Circulation, Positron-Emission Tomography, Myocardial Perfusion Imaging, Humans, Reproducibility of Results, Coronary Artery Disease, Article, Cadmium
Abstract

BACKGROUND: Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease (CAD). Gamma cameras with cadmium zinc telluride (CZT) detectors allow the quantification of absolute myocardial blood flow (MBF) and flow reserve (MFR). However, evidence of its accuracy is limited and of its reproducibility is lacking. We aimed to validate (99m)Tc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared to (13)N-ammonia PET in a cohort of patients with known or suspected CAD and to evaluate the reproducibility of this technique. METHODS: Accuracy was assessed in thirty four participants who underwent dynamic (99m)Tc-sestamibi SPECT and (13)N-ammonia PET and reproducibility in fourteen participants who underwent two (99m)Tc-sestamibi SPECT studies, all within two weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model and MFR was derived as the stress/rest MBF ratio. RESULTS: SPECT global MBF with splines showed good correlation with (13)N-ammonia PET (r=0.81, p0.05 for all). CONCLUSIONS: MBF and MFR quantification using (99m)Tc-sestamibi CZT SPECT with spatiotemporal spline fitting improved the correlation with (13)N-ammonia PET flow estimates and test/re-test reproducibility. The use of splines may represent an important step towards standardization of SPECT flow estimation.

Published
2022

34. Left-ventricular volumes and ejection fraction from cardiac ECG-gated 15O-water positron emission tomography compared to cardiac magnetic resonance imaging using simultaneous hybrid PET/MR.

Author

Nordström, Jonny, Kvernby, Sofia, Kero, Tanja, Sörensen, Jens, Harms, Hendrik J., and Lubberink, Mark

Abstract

Background: 15O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner. Methods: Twenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland–Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities. Results: The correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR. Conclusion: LV volumes and EF can be calculated by first-pass analysis of a 15O-water PET scan with high accuracy and comparable precision as with CMR. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Quantitative relationship between coronary artery calcium score and hyperemic myocardial blood flow as assessed by hybrid 15O-water PET/CT imaging in patients evaluated for coronary artery disease

Author

Danad, Ibrahim, Raijmakers, Pieter G., Appelman, Yolande E., Harms, Hendrik J., de Haan, Stefan, Marques, Koen M., van Kuijk, Cornelis, Allaart, Cornelis P., Hoekstra, Otto S., Lammertsma, Adriaan A., Lubberink, Mark, van Rossum, Albert C., and Knaapen, Paul

Published
2012
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48. Gene-specific increase in the energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations

Author

Witjas-Paalberends, E. Rosalie, Güçlü, Ahmet, Germans, Tjeerd, Knaapen, Paul, Harms, Hendrik J, Vermeer, Alexa M.C., Christiaans, Imke, Wilde, Arthur A.M., Dos Remedios, Cris, Lammertsma, Adriaan A., van Rossum, Albert C., Stienen, Ger J.M., van Slegtenhorst, Marjon, Schinkel, Arend F., Michels, Michelle, Ho, Carolyn Y., Poggesi, Corrado, and van der Velden, Jolanda

Published
2014
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50. Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET

Author

Sörensen, Jens, primary, Nordström, Jonny, additional, Baron, Tomasz, additional, Mörner, Stellan, additional, Granstam, Sven-Olof, additional, Lubberink, Mark, additional, Tolbod, Lars, additional, van den Berg, Jeffrey, additional, Flachskampf, Frank A., additional, Kero, Tanja, additional, Magnusson, Peter, additional, and Harms, Hendrik J., additional

Published
2021
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