Comparison of Global and Regional Myocardial Blood Flow Quantification using Dynamic Solid-State Detector SPECT and Tc-99m-sestamibi or Tc-99m-tetrofosmin in a routine clinical setting

Comparison of Global and Regional Myocardial Blood Flow Quantification using Dynamic Solid-State Detector SPECT and Tc-99m-sestamibi or Tc-99m-tetrofosmin in a routine clinical setting | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of Global and Regional Myocardial Blood Flow Quantification using Dynamic Solid-State Detector SPECT and Tc-99m-sestamibi or Tc-99m-tetrofosmin in a routine clinical setting Wiebke Wieting, Frank M. Bengel, Johanna Diekmann This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5431655/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jan, 2025 Read the published version in The International Journal of Cardiovascular Imaging → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose: Solid-state detector single photon emission computed tomography (SPECT) enables the acquisition of dynamic data for calculation of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Here, we report about our experiences on clinical usefulness and robustness using Tc-99m-sestamibi and Tc-99m-tetrofosmin. Methods: 307 patients underwent dynamic list-mode myocardial perfusion imaging (MPI) and standard static MPI for clinical workup of coronary artery disease on a dedicated cardiac SPECT camera. MBF and MFR were calculated using a 1-tissue‐compartment model. Attenuation correction was performed for all patients using an external computed tomogram. Patients underwent stress-only scans, both stress and rest scans or rest-only scans using Tc-99m-tetrofosmin or Tc-99m-sestamibi. 30 patients without known cardiovascular comorbidities and without perfusion defect on static scans were compared in a sub analysis. Results: Global stress myocardial blood flow (MBF) was significantly higher than rest MBF (2.3 vs. 1.1 ml/min/g; p < 0.001), and showed a high variability among individuals. Global myocardial flow reserve (MFR) was 2.1 (range 0.5–7.8). An analysis of 30 patients without known cardiovascular comorbidities yielded similar stress MBF measures for Tc-99m-sestamibi and Tc-99m-tetrofosmin (3.1 ± 1.2 vs. 2.8 ± 0.9 ml/min/g; p = 0.429). The use of attenuation correction lead to systematically lower MBF measures. Patients who underwent a one-day protocol had notably higher rest MBF (1.2 ± 0.5 vs. 1.0 ± 0.46 ml/min/g; p = 0.009) and consequently a lower MFR. Summed defect scores from standard static scans and presence of cardiovascular comorbidities negatively impacted MBF and MFR. Conclusion: Quantitative SPECT MBF and MFR in a clinical routine setting yields flow measures in range of expectation at an albeit wide range and is comprehensibly linked with results from standard static scan and patients history of cardiovascular diseases. Use of one-day protocols and attenuation corrections systematically alters quantitative results. Absolute quantitative SPECT myocardial perfusion imaging myocardial blood flow myocardial flow reserve Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 INTRODUCTION Quantitative measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR) derived from positron emission tomography (PET) are readily obtained and have been shown to provide diagnostic and prognostic benefit 1 – 8 . Therefore, quantitative perfusion assessment from PET has entered clinical routine. Static myocardial perfusion imaging (MPI) using single photon emission computed tomography (SPECT) is the clinical gold standard and the most widely used tool for evaluation of myocardial perfusion in nuclear medicine. Quantitative perfusion analysis using SPECT is possible but has not been widely established yet due to technically demanding methodology. Semiconductor cameras with a high temporal resolution and improved count density enable dynamic list-mode acquisition. Initially, feasibility of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) calculation was demonstrated using conventional SPECT cameras 9 – 13 . In a porcine model, MBF and MFR results for three standard SPECT tracers (Tl-201, Tc-99m-tetrofosmin and Tc-99m-sestamibi) acquired on a dedicated SPECT camera correlated well with results from microsphere-derived flow 8 . Multiple studies have validated MBF measures by direct comparison to angiographic findings 14 – 19 and demonstrated a prognostic value 20 . Added value of MBF calculation has been reported for microcirculation and multivessel disease 21 , 22 . However, the real-world feasibility and usefulness of CZT-SPECT-derived MBF and MFR needs to be supported by more reports from standard clinical settings with diverse patient populations. Here, we summarize our initial experience measuring MBF and MFR derived from solid-state detector SPECT in clinical practice using Tc-99m-sestamibi and Tc-99m-tetrofosmin. MATERIALS AND METHODS Study population 307 patients who were referred for the clinical workup of coronary artery disease (CAD) underwent dynamic and static myocardial perfusion imaging from June 2017 to December 2020. Dynamic and standard static scans were conducted in clinical routine, based on camera availability without any other preselection. All patients gave written informed consent prior to imaging. Based on clinical indication patients underwent either stress-only (n=57), stress-first two-day (n=99), stress-first one-day (n=90, total stress scans n=189) or rest-only protocols (n=61, figure 1 ). Few scans were excluded from analysis due to high spillover from infradiaphragmatic activity (n=21), inconclusive static imaging results (negative summed difference score, n=8) or other technical difficulties in image acquisition (n=4). For a subanalysis, only patients without static scan defects and a negative cardiovascular history were included and 15 Tc-99m-tetrofosmin and 15 Tc-99m-sestamibi were compared. The study design and its implementation were approved by the local ethical committee. Dynamic, static and gated SPECT and low-dose CT data acquisition Patients were positioned in a supine position with arms above their head without prior tracer injection. For stress SPECT imaging patients abstained from caffeine for 24 hours. The used SPECT workflow is depicted in figure 2 . After injection of a test dose of 40 MBq Tc-99m-sestamibi or Tc-99m-tetrofosmin, the heart was centered in the field of view of the CZT camera (Discovery NM 530c; GE Healthcare, Haifa, Israel). Dynamic list-mode acquisition over 6 minutes was started. After a 60 seconds prerun to monitor baseline activity, 342 ± 78 MBq Tc-99m-sestamibi or 320 ± 80 MBq Tc-99m-tetrofosmin for stress imaging and 489 ± 150 MBq Tc-99m-sestamibi or 471 ± 118 MBq Tc-99m-tetrofosmin for rest studies, were continuously injected via bolus pump over 30 seconds (Braun Bolus Pump FM, Germany). Mean administered stress dose for one-day protocols was 280 ± 69 MBq, rest dose was 607 ± 112 MBq. For two-day protocols mean stress dose was 390 ± 46 MBq and rest dose was 394 ± 45 MBq. For stress protocols, patients were injected with 400 µg Regadenoson at 30 seconds into the pre-run. 45 to 60 minutes after finished list-mode acquisition, seven minutes of standard static and gated scans were additionally acquired according to our clinical standards. For gating the raw data acquisition, a detected R-R interval was divided into eight equally spaced bins in time. The respective bins of all detected R-R intervals were summed and individually reconstructed. In the reconstructed data, contour detection of the cardiac surface of the left ventricle was performed using isocontours. The endocardial surface allowed the calculation of an inner volume of the LV for each bin. The left ventricular ejection fraction was determined from the ratio of the respective maximum and minimum volumes of the bins. An external low dose CT for attenuation correction was conducted in all patients (120 mA, 120 keV, slice thickness 2.5 mm, 16 x 1.25 mm detector rows, standard kernel, cine mode). Data processing Dynamic studies were processed using Corridor 4DM v2017 SPECT MBF software (Invia, Ann Arbor, MI) on a Xeleris 4.1 workstation (GE Healthcare, Haifa, Israel). List-mode data were resampled and reconstructed into 18 frames of 10 seconds duration and 6 frames of 30 seconds each. All datasets were reconstructed with CT-based attenuation correction (AC) and without attenuation correction (NC) using a standard iterative reconstruction algorithm provided by the manufacturer. Myocardial contours were automatically determined and manually adjusted as necessary. Manual motion correction was conducted for all dynamic frames. Residual activity was detected within the acquisition’s first 60 seconds and subtracted from the dynamic image. A region-of-interest (ROI) for blood-pool sampling was placed on the base of the septal wall. Global and regional time activity curves were created. Quality control included a manual control for the presence of a single bolus peak between 65-150 seconds without any double peaks or plateaus. The uptake rate constant (K1) was calculated based on the dynamic image series using a 1-tissue-compartment model. K1 was converted to MBF using a Renkin-Crone extraction-fraction correction function 17 . Finally, global and regional stress and rest MBF and MFR were calculated. Separately acquired static and gated SPECT images were reconstructed with and without measured AC. Polar maps were calculated (Invia, Ann Arbor, MI) and summed stress (SSS), summed rest (SRS) and summed difference scores (SDS) were calculated using the AHA 17-segments model. Calcium score was determined using 4DM software only in patients without iatrogenic foreign material close to the heart. Statistical Analysis Categorical parameters are given as number and percentage. Continuous variables are given as mean ± standard deviation (SD) or as median and interquartile range (IQR) as suitable. A two-sided p-value of <0.05 was considered as statistically significant. Correlation between quantitative variables was calculated using the students t-test and Person chi-square. Wilcoxon test was used for the comparison of two dependent variables. All statistical analyses were performed with SPSS statistical software, version 27 (IBM Corp., Armonk, New York, United States). The graphs were created with GraphPad Prism, version 9.0.2 (GraphPad Software, San Diego, United States). RESULTS Global and regional MBF and MFR shows high variance Baseline patient characteristics, medical history and cardiovascular risk factors are summarized in table 1. Global stress MBF was significantly higher than rest MBF (stress MBF 2.3 ± 1.1 ml/min/g vs. rest MBF 1.1 ± 0.5 ml/min/g; p<0.001, all patients). A high interindividual variance was detected. Global stress MBF ranged from 0.4 to 7.4 ml/min/g and rest MBF ranged from 0.3 to 3.7 ml/min/g. Mean calculated global MFR was 2.1 ± 1.1 (range 0.5 – 7.8). Regional MBF was determined for coronary territories and results are summarized in table 2 . Highest mean MBF and highest variance was detected in the right coronary territory. Men presented with lower stress MBF and a tendency towards lower MFR in comparison to females (2.0 ± 0.8 ml/min/g vs. 2.9 ± 1.2 ml/min/g, p<0.001 and 1.9 ± 1.0 vs. 2.4 ± 1.4, p=0.054) while rest MBF was similar (1.1 ± 0.5 ml/min/g vs. 1.2 ± 0.5 ml/min/g, p=0.200). MBF and MFR are comparable for Tc-99m- sestamibi and Tc-99m- tetrofosmin A total of 85 patients underwent a one-day protocol and 79 patients performed a two-day protocol. 41/85 one-day protocols and 32/79 two-day protocols were performed using Tc-99m-tetrofosmin. 58 patients underwent rest-only studies of which 23 were performed with Tc-99m-tetrofosmin. 19/58 stress-only studies were performed with Tc-99m-tetrofosmin. Global stress MBF was significantly higher when Tc-99m-sestamibi was used (2.4 ± 1.1 ml/min/g vs. 2.1 ± 0.9 ml/min/g; p=0.049). This was also true in a regional MBF analysis for the LAD (2.6 ± 1.2 ml/min/g vs. 2.2 ± 1.0 ml/min/g; p=0.031) and RCA (3.0 ± 1.3 ml/min/g vs. 2.7 ± 1.1 ml/min/g; p=0.049) territory ( table 3 ). No significant differences were detected for calculated global rest MBF (1.1 ± 0.4 ml/min/g vs. 1.1 ± 0.6 ml/min/g, p=0.259) or MFR (2.2 ± 1.3 ml/min/g vs. 1.9 ± 1.0 ml/min/g; p=0.109). Additionally, 30 stress-only patients (15 Tc-99m-sestamibi and 15 Tc-99m-tetrofosmin) without known cardiovascular comorbidities and without perfusion defects on static scans were compared in a subanalysis. Here, no relevant differences in global (3.1 ± 1.2 ml/min/g vs. 2.8 ± 0.9 ml/min/g; p=0.429) or regional stress MBF were detected. O ne-day stress first protocol yields higher global rest MBF Patients who underwent either a one-day or a two-day stress-first protocol showed no differences in stress MBF. Significantly higher rest MBF values were calculated when a one day protocol was used (1.2 ± 0.5 ml/min/g vs. 1.0 ± 0.46 ml/min/g; p=0.009, figure 3). Consequently MFR was lower in patients that underwent one day protocols (MFR NC 1.9 ± 1.0 ml/min/g vs. 2.2 ± 1.3 ml/min/g; p=0.035; figure 3 ). This effect was not observed, when AC was used. A separate analysis for Tc-99m-sestamibi and Tc-99m-tetrofosmin showed that the global observation was driven by Tc-99m-tetrofosmin scans (one day protocoll 1.4 ± 0.7 ml/min/g vs. two day protocol 1.0 ± 0.5 ml/min/g; p=0.014) while in Tc-99m-sestamibi scans no differences based on protocol use were detected (1.1 ± 0.4 ml/min/g vs. 1.0 ± 0.47 ml/min/g; p=0.338). Use of attenuation correction lowers calculated MBF Mean global stress and rest MBF were significantly lower when AC was used (NC 2.3 ± 1.1 ml/min/g vs. AC 1.8 ± 0.8 ml/min/g; p<0.001; NC 1.1 ± 0.5 ml/min/g vs. AC 0.9 ± 0.4 ml/min/g; p<0.001, figure 4 ). Similar results were found for the regional analysis. However, there were no significant differences in the calculated MFR (NC 2.1 ± 1.1 ml/min/g vs. AC 2.1 ± 1.1 ml/min/g; p=0.626). A patient example for calculation of global and regional stress MBF and effect of AC s given in figure 5 . Presence of perfusion defects in standard static scans is associated with lower global and regional MBF Relevant perfusion defects were defined as three or more segments with reduced perfusion in one coronary territory based on the 17-segments-AHA model, results of standard static scans are presented in table 1 . Presence of perfusion defects in static scans were associated with lower global stress and rest MBF (no defect: 2.6 ± 1.1 ml/min/g vs. defect 1.7 ± 0.7 ml/min/g; p<0.001 and no defect 1.2 ± 0.5 ml/min/g vs. defect: 1.0 ± 0.4 ml/min/g; p<0.001; figure 5 ). However, there were no significant differences for MFR between patients with and without defects in static scans (no defect p=0.143; defect p=0.234). Analogue results were found for AC MBF and MFR measures and for regional analysis. Summed defect scores derived from standard static scans correlate with global MBF Significant correlations between summed stress scores (SSS) and global stress MBF as well as summed rest scores (SRS) and global rest MBF were found ( figure 6 ). However, no significant correlation was detected between summed difference scores (SDS=SSS-SRS) and MFR NC (r=0.05, p=0.556). Analogue correlations were calculated when AC was used. Lower LVEF is associated with lower MBF Mean stress left ventricular ejection fraction (LVEF) was 58.8% and rest LVEF was 54.2%. Higher stress (r=0.52, p<0.001) and rest LVEF (r=0.28, p<0.001) correlated significantly with higher MBF measures ( figure 7 ). No significant correlation was detected between stress or rest LVEF and MFR. Influence of cardiovascular comorbidities on MBF Patients with known coronary artery disease (CAD) had a significantly lower global stress (1.9 ± 0.9 ml/min/g vs. 2.6 ± 1.1 ml/min/g, p<0.001) and rest MBF (1.0 ± 0.4 ml/min/g vs. 1.3 ± 0.6 ml/min/g, p=0.002) than patients without known CAD ( figure 8 ). No significant reduction of MFR was seen in patients with history of CAD (p=0.283). Presence of cardiovascular risk factors (i.e. CAD, MI, hypertension, diabetes, obesity or smoking) lead to a significant reduction of calculated MBF. Patients with two or more known cardiovascular risk factors had significantly lower MBF than patients with less or without cardiovascular risk factors (global stress MBF: 2.1 ± 1.0 ml/min/g vs. 2.7 ± 1.0 ml/min/g, p<0.001; global rest MBF: 1.0 ± 0.4 ml/min/g vs. 1.4 ± 0.6 ml/min/g, p=0.004). For MFR, no significant difference was found (2.1 ± 1.2 ml/min/g vs. 1.8 ± 0.7 ml/min/g, p=0.124). DISCUSSION Dynamic list mode imaging with CZT cameras now facilitates SPECT derived measurement of MBF and MFR 15 . In PET, being the gold standard, quantitative MBF assessment provides enhanced diagnostic precision, facilitating a comprehensive evaluation of myocardial perfusion abnormalities and aiding in risk stratification 23, 24 . The ability to measure flow reserve enables identification of subtle perfusion deficits and microcirculation abnormalities thus providing valuable prognostic information 21 . However, PET imaging is currently only feasible in larger hospitals or cardiovascular centers due to high costs and the need for an on-site cyclotron 25 . SPECT is a widely accessible technique, therefore calculating MBF and MFR from SPECT would be desirable. In this analysis, SPECT MBF quantification was performed as part of our clinical routine without any specific preselection. The detected mean stress and rest MBF and MFR were in range of expectation. Of note, few patients presented with extraordinary high flow measures which we re-analyzed but high measures without detectable reason persisted. We chose not to exclude these scans from our global analysis in order to show the high MBF variance. Expectedly, regionally highest variance was found in the RCA territory, which is the most complex region for SPECT most likely due to attenuation-related effects and infradiaphragmatic spillover. We showed that patients with high defect scores derived from standard static scans and patients with lower LVEF had impaired MBF. When employing Tc-99m-sestamibi, there was slight yet significant increase in global stress in comparison to Tc-99m-tetrofosmin analyzing all patients, however no differences were detected in the provided sub analysis. Slight differences between the tracers might be caused by the respective tracer extraction fraction. No other relevant differences between the two used tracers were found. Available data on patient history, laboratory values and cardiac interventions reflect a real-world situation where parts of information may be incomplete. Also, we did not systematically compare global or regional MBF with the current coronary status. In this regard, we still detected significant correlations between presence of cardiovascular comorbidities including CAD and calculated MBF and MFR. Concordant to other studies specifically evaluating angiographic findings and SPECT MBF 18, 19, 26-29 , our results further support credibility of this technique. However, clinical utility of absolute quantitative MBF and MFR measures is not yet clear and several open questions have to be addressed to facilitate routine clinical use. It is well known that challenges accompany the acquisition of absolute quantitative MBF 30, 31 . The complexity of data processing, including the need for corrections in attenuation, scatter, and partial volume effects, pose hurdles in standardizing protocols across different centers. Dynamic image acquisition is more sophisticated than standard static acquisition. Patients have to be positioned without an injected full tracer dose and patient movement needs to be as small as possible. Limitations in hardware, specifically the spatial and temporal resolution of traditional SPECT systems, affect the accuracy of absolute MBF quantification, particularly in dynamic assessments 31 . For CZT-SPECT systems, CT AC is usually acquired on a separate camera since these systems are not equipped with CT. MBF calculation in PET however is always done with AC. The effect of CT AC on calculated SPECT MBF and MFR has been evaluated in few studies. We here observed a generally lower stress and rest MBF when AC was used but no effect on MFR was detected. This finding is consistent with results from Bailly et al 32 . Other studies evaluated AC MBF results in comparison to PET and found partially inconclusive effects on global and regional MBF 17, 33 . Zavadovsky et al. found an improved correlation between stenosis severity and regional stress MBF and higher diagnostic accuracy for multivessel CAD when AC was used 22 . In summary, effects of AC have not yet been fully understood and therefore careful interpretation is obligatory. In our clinical routine, both one-day and two-day protocols were used as appropriate. As recommended 34 for one-day protocols we took care that a stress / rest dosing ratio of at least 1:2.5 or better 1:3 was maintained. We also corrected the second scan for residual activity. Still, we observed significantly higher rest MBF values and a consequently lower MFR. Interestingly, this effect was less pronounced, when AC or Tc-99m-Sestamibi was used. This finding warrants further investigation. Ultimately, two-day protocols may be more suitable for accurate SPECT MBF and MFR calculation. In summary, obtaining SPECT MBF and MFR is feasible in a clinical routine setting yielding values in range of expectation. Yet, currently available analysis methods are time-consuming and technically demanding. There is a need for improved automated motion correction in order to bring the application to clinical routine use. Moreover, use of AC and selection of protocol distinctly influence MBF and MFR results. Harmonization of imaging protocols between cardiovascular centers will improve inter-site comparability in the future 35 . Until then, absolute quantitative SPECT acquisition of MBF remains a possibility to enhance diagnostic value for specific clinical scenarios. Limitations This is an observational study. Presented data is based on routinely acquired SPECT imaging without any study-related pre-selection of patients. Available data on patient history, laboratory values and cardiac interventions reflect a real-world situation where parts of information may be incomplete. To date there is no reliable reference standard for flow measurements derived from SPECT. Tc-99m-labeled perfusion tracers have a high-count statistic and low extraction fraction at high flow rates which determines reduced contrast between stress and rest flow in comparison to values known from PET. No systematical comparison to PET data or findings from coronary angiography was included. Declarations Disclosure: This work was partially supported by a research project in collaboration with GE Healthcare. Author Contribution W.W. and J.D. wrote the main manuscript text and prepared all data, figures and tables. F.M.B. reviewed the manuscript. Available data on patient history, laboratory values and cardiac interventions reflect a real-world situation where parts of information may be incomplete. 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Cardiol Clin . 2023;41:117-127. Bailly M, Thibault F, Courtehoux M, et al. Impact of attenuation correction for CZT-SPECT measurement of myocardial blood flow. J Nucl Cardiol . 2021;28:2560-2568. Giubbini R, Bertoli M, Durmo R, et al. Comparison between N(13)NH(3)-PET and (99m)Tc-Tetrofosmin-CZT SPECT in the evaluation of absolute myocardial blood flow and flow reserve. J Nucl Cardiol . 2021;28:1906-1918. Dorbala S, Ananthasubramaniam K, Armstrong IS, et al. Single Photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging Guidelines: Instrumentation, Acquisition, Processing, and Interpretation. J Nucl Cardiol . 2018;25:1784-1846. Wells RG, Bengel FM, Camoni L, et al. Multicenter Evaluation of the Feasibility of Clinical Implementation of SPECT Myocardial Blood Flow Measurement: Intersite Variability and Imaging Time. Circ Cardiovasc Imaging . 2023;16:e015009. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files TABLES.docx Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2025 Read the published version in The International Journal of Cardiovascular Imaging → Version 1 posted Editorial decision: Revision requested 05 Dec, 2024 Reviews received at journal 04 Dec, 2024 Reviews received at journal 26 Nov, 2024 Reviewers agreed at journal 14 Nov, 2024 Reviewers agreed at journal 12 Nov, 2024 Reviewers invited by journal 11 Nov, 2024 Editor assigned by journal 11 Nov, 2024 Submission checks completed at journal 11 Nov, 2024 First submitted to journal 11 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5431655","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":382838736,"identity":"3ee5edd3-08a5-4d75-9fec-34f7174cd6b7","order_by":0,"name":"Wiebke Wieting","email":"","orcid":"","institution":"Hannover Medical School","correspondingAuthor":false,"prefix":"","firstName":"Wiebke","middleName":"","lastName":"Wieting","suffix":""},{"id":382838739,"identity":"07d891d8-11ef-4826-a2df-2c2daefc6c51","order_by":1,"name":"Frank M. Bengel","email":"","orcid":"","institution":"Hannover Medical School","correspondingAuthor":false,"prefix":"","firstName":"Frank","middleName":"M.","lastName":"Bengel","suffix":""},{"id":382838742,"identity":"82a61478-8bb5-400d-9a1e-4eb1d8abed12","order_by":2,"name":"Johanna Diekmann","email":"data:image/png;base64,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","orcid":"","institution":"Hannover Medical School","correspondingAuthor":true,"prefix":"","firstName":"Johanna","middleName":"","lastName":"Diekmann","suffix":""}],"badges":[],"createdAt":"2024-11-11 11:38:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5431655/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5431655/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10554-025-03339-4","type":"published","date":"2025-01-30T15:57:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71555353,"identity":"5618aa3b-067b-4169-824c-6e0641beecaf","added_by":"auto","created_at":"2024-12-16 16:22:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":260350,"visible":true,"origin":"","legend":"\u003cp\u003eThe study flow chart gives an overview of the included dynamic perfusion scans for calculation of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Scans are divided in three groups: stress-only (blue), stress / rest (yellow) and rest-only scans (red). Total numbers and specific numbers for Tc-99m-Sestamibi and Tc-99m-Tetrofosmin scans are given. Reasonsfor exclusion of scans are described in the methods.\u003c/p\u003e","description":"","filename":"Figure1neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/50c58829feaa086939a8bade.jpg"},{"id":71554059,"identity":"0b3ce863-e3a0-42d1-bb1f-3c07322322d7","added_by":"auto","created_at":"2024-12-16 16:14:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":70343,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline for dynamic and static image acquisition. Dynamic scan: First, patient will be visually positioned under the CZT camera, then a 40 MBq tracer test dose is intravenously injected. After optimizing patient position, dynamic list mode acquisition is started (duration 6 minutes). Static scan: After a break of 45 minutes according to our clinical standards, a seven minutes static scan is additionally acquired.\u003c/p\u003e","description":"","filename":"Figure2neu.png","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/fab253c0d68ccdc2368054ca.png"},{"id":71554068,"identity":"4fa3d93e-13af-49b9-aca6-f4b7050d687c","added_by":"auto","created_at":"2024-12-16 16:14:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":151619,"visible":true,"origin":"","legend":"\u003cp\u003eIn Tc-99m-tetrofosmin scans rest global myocardial blood flow (MBF) was significantly lower when a two day protocol was used. Consecutively, myocardial flow reserve (MFR) was higher when a two day protocol was used. Significant differences were not detectable when Tc-99m-sestamibi was used or after attenuation correction (AC).\u003c/p\u003e","description":"","filename":"Figure3neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/0b7b7b5f78b986e9b907fdc7.jpg"},{"id":71555357,"identity":"c4b125de-5c10-4ee6-9a0e-cb1b008f82be","added_by":"auto","created_at":"2024-12-16 16:22:51","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":75905,"visible":true,"origin":"","legend":"\u003cp\u003eUse of attenuation correction (AC) systematically and significantly lowered the measured global myocardial blood flow (MBF) at stress and rest. No effect on myocardial flow reserve (MFR) was detected.\u003c/p\u003e","description":"","filename":"Figure4neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/7cf85d1a35cbe89153108ea7.jpg"},{"id":71558648,"identity":"6e8e5f27-446d-46f0-afa7-70e14fb228aa","added_by":"auto","created_at":"2024-12-16 16:38:51","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":279755,"visible":true,"origin":"","legend":"\u003cp\u003ePatient example of a dynamic stress study analyzed in Corridor 4DM reserve software. Given are from left to right: time-activity curves without and with attenuation correction (AC), perfusion polar maps, flow polar maps and calculated regional absolute quantitative flow measures (ml/min/g).\u003c/p\u003e","description":"","filename":"Figure5neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/3316e4adade80614afa5381c.jpg"},{"id":71557161,"identity":"2f4f6674-16ee-4295-ab25-a42c5f2a5617","added_by":"auto","created_at":"2024-12-16 16:30:51","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":79986,"visible":true,"origin":"","legend":"\u003cp\u003ePresence of perfusion defects in standard static scans systematically lead to significantly lower global myocardial blood flow (MBF) at stress and rest in both non-attenuation (NC) and attenuation corrected (AC) flow measures.\u003c/p\u003e","description":"","filename":"Figure6neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/d5b778b3569fa4d56e82efc2.jpg"},{"id":71557160,"identity":"5af1ff3f-49e0-42bb-bdf2-4192f6358435","added_by":"auto","created_at":"2024-12-16 16:30:51","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":90417,"visible":true,"origin":"","legend":"\u003cp\u003eSignificant inverse correlations were detected between (A) global stress myocardial blood flow (MBF) and summed stress scores (SSS) and (B) global rest MBF and summed stress scores (SRS). (C) No significant correlation was detected between global myocardial flow reserve (MFR) and summed difference scores (SDS).\u003c/p\u003e","description":"","filename":"Figure7neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/dc2cdbdd942ad152437ec8d3.jpg"},{"id":71554063,"identity":"ce2267bc-d2ad-480b-8e65-14f4f8c4a51b","added_by":"auto","created_at":"2024-12-16 16:14:51","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":144478,"visible":true,"origin":"","legend":"\u003cp\u003eSignificant correlations between (A) stress myocardial blood flow (MBF) and stress left ventricular ejection fraction (LVEF) and (B) rest MBF and rest LVEF were detected. Myocardial flow reserve (MFR) tended to correlate stress LVEF (C) and significantly correlated with rest LVEF (D).\u003c/p\u003e","description":"","filename":"Figure8neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/03841af1b7b625f5e196e797.jpg"},{"id":71557163,"identity":"c222821b-781c-49ed-828d-595d4c4a9a35","added_by":"auto","created_at":"2024-12-16 16:30:51","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":123421,"visible":true,"origin":"","legend":"\u003cp\u003ePatients with known coronary artery disease (CAD) had significantly lower global myocardial blood flow (MBF) at stress and rest in both non-attenuation (NC) and attenuation corrected (AC) flow measures. No significant reduction of myocardial flow reserve (MFR) was found.\u003c/p\u003e","description":"","filename":"Figure9neu.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/ee1308c4d05d57207c82831d.jpg"},{"id":75351273,"identity":"176e5fa6-c6a0-48c2-882f-6bc162a5088e","added_by":"auto","created_at":"2025-02-03 16:08:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2048459,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/9ad9bc9c-9282-4319-aaad-9c2d974233e9.pdf"},{"id":71554061,"identity":"5cd78a52-1b54-46c2-be48-518e64effa3f","added_by":"auto","created_at":"2024-12-16 16:14:51","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":108157,"visible":true,"origin":"","legend":"","description":"","filename":"TABLES.docx","url":"https://assets-eu.researchsquare.com/files/rs-5431655/v1/145f09519650ca4092a2ae30.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Global and Regional Myocardial Blood Flow Quantification using Dynamic Solid-State Detector SPECT and Tc-99m-sestamibi or Tc-99m-tetrofosmin in a routine clinical setting","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eQuantitative measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR) derived from positron emission tomography (PET) are readily obtained and have been shown to provide diagnostic and prognostic benefit\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Therefore, quantitative perfusion assessment from PET has entered clinical routine.\u003c/p\u003e \u003cp\u003eStatic myocardial perfusion imaging (MPI) using single photon emission computed tomography (SPECT) is the clinical gold standard and the most widely used tool for evaluation of myocardial perfusion in nuclear medicine. Quantitative perfusion analysis using SPECT is possible but has not been widely established yet due to technically demanding methodology. Semiconductor cameras with a high temporal resolution and improved count density enable dynamic list-mode acquisition. Initially, feasibility of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) calculation was demonstrated using conventional SPECT cameras\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. In a porcine model, MBF and MFR results for three standard SPECT tracers (Tl-201, Tc-99m-tetrofosmin and Tc-99m-sestamibi) acquired on a dedicated SPECT camera correlated well with results from microsphere-derived flow\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Multiple studies have validated MBF measures by direct comparison to angiographic findings\u003csup\u003e\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e and demonstrated a prognostic value\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Added value of MBF calculation has been reported for microcirculation and multivessel disease\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, the real-world feasibility and usefulness of CZT-SPECT-derived MBF and MFR needs to be supported by more reports from standard clinical settings with diverse patient populations. Here, we summarize our initial experience measuring MBF and MFR derived from solid-state detector SPECT in clinical practice using Tc-99m-sestamibi and Tc-99m-tetrofosmin.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e307 patients who were referred for the clinical workup of coronary artery disease (CAD) underwent dynamic and static myocardial perfusion imaging from June 2017 to December 2020. Dynamic and standard static scans were conducted in clinical routine, based on camera availability without any other preselection. All patients gave written informed consent prior to imaging. Based on clinical indication patients underwent either stress-only (n=57), stress-first two-day (n=99), stress-first one-day (n=90, total stress scans n=189) or rest-only protocols (n=61, \u003cstrong\u003efigure 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFew scans were excluded from analysis due to high spillover from infradiaphragmatic activity (n=21), inconclusive static imaging results (negative summed difference score, n=8) or other technical difficulties in image acquisition (n=4). For a subanalysis, only patients without static scan defects and a negative cardiovascular history were included and 15 Tc-99m-tetrofosmin and 15 Tc-99m-sestamibi were compared.\u003c/p\u003e\n\u003cp\u003eThe study design and its implementation were approved by the local ethical committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDynamic, static and gated SPECT and low-dose CT data acquisition\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were positioned in a supine position with arms above their head without prior tracer injection. For stress SPECT imaging patients abstained from caffeine for 24 hours. The used SPECT workflow is depicted in \u003cstrong\u003efigure 2\u003c/strong\u003e. After injection of a test dose of 40 MBq Tc-99m-sestamibi or Tc-99m-tetrofosmin, the heart was centered in the field of view of the CZT camera (Discovery NM 530c; GE Healthcare, Haifa, Israel). Dynamic list-mode acquisition over 6 minutes was started. After a 60 seconds prerun to monitor baseline activity, 342 \u0026plusmn; 78 MBq Tc-99m-sestamibi or 320 \u0026plusmn; 80 MBq Tc-99m-tetrofosmin for stress imaging and 489 \u0026plusmn; 150 MBq Tc-99m-sestamibi or 471 \u0026plusmn; 118 MBq Tc-99m-tetrofosmin for rest studies, were continuously injected via bolus pump over 30 seconds (Braun Bolus Pump FM, Germany). Mean administered stress dose for one-day protocols was 280 \u0026plusmn; 69 MBq, rest dose was 607 \u0026plusmn; 112 MBq. For two-day protocols mean stress dose was 390 \u0026plusmn; 46 MBq and rest dose was 394 \u0026plusmn; 45 MBq. For stress protocols, patients were injected with 400 \u0026micro;g Regadenoson at 30 seconds into the pre-run.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e45 to 60 minutes after finished list-mode acquisition, seven minutes of standard static and gated scans were additionally acquired according to our clinical standards. For gating the raw data acquisition, a detected R-R interval was divided into eight equally spaced bins in time. The respective bins of all detected R-R intervals were summed and individually reconstructed. In the reconstructed data, contour detection of the cardiac surface of the left ventricle was performed using isocontours. The endocardial surface allowed the calculation of an inner volume of the LV for each bin. The left ventricular ejection fraction was determined from the ratio of the respective maximum and minimum volumes of the bins.\u003c/p\u003e\n\u003cp\u003eAn external low dose CT for attenuation correction was conducted in all patients (120 mA, 120 keV, slice thickness 2.5 mm, 16 x 1.25 mm detector rows, standard kernel, cine mode).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData processing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDynamic studies were processed using Corridor 4DM v2017 SPECT MBF software (Invia, Ann Arbor, MI) on a Xeleris 4.1 workstation (GE Healthcare, Haifa, Israel). List-mode data were resampled and reconstructed into 18 frames of 10 seconds duration and 6 frames of 30 seconds each. All datasets were reconstructed with CT-based attenuation correction (AC) and without attenuation correction (NC) using a standard iterative reconstruction algorithm provided by the manufacturer. Myocardial contours were automatically determined and manually adjusted as necessary. Manual motion correction was conducted for all dynamic frames. Residual activity was detected within the acquisition\u0026rsquo;s first 60 seconds and subtracted from the dynamic image. A region-of-interest (ROI) for blood-pool sampling was placed on the base of the septal wall. \u0026nbsp;Global and regional time activity curves were created. Quality control included a manual control for the presence of a single bolus peak between 65-150 seconds without any double peaks or plateaus. The uptake rate constant (K1) was calculated based on the dynamic image series using a 1-tissue-compartment model. K1 was converted to MBF using a Renkin-Crone extraction-fraction correction function\u003csup\u003e17\u003c/sup\u003e. Finally, global and regional stress and rest MBF and MFR were calculated.\u003c/p\u003e\n\u003cp\u003eSeparately acquired static and gated SPECT images were reconstructed with and without measured AC. Polar maps were calculated (Invia, Ann Arbor, MI) and summed stress (SSS), summed rest (SRS) and summed difference scores (SDS) were calculated using the AHA 17-segments model.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCalcium score was determined using 4DM software only in patients without iatrogenic foreign material close to the heart.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCategorical parameters are given as number and percentage. Continuous variables are given as mean \u0026plusmn; standard deviation (SD) or as median and interquartile range (IQR) as suitable. A two-sided p-value of \u0026lt;0.05 was considered as statistically significant. Correlation between quantitative variables was calculated using the students t-test and Person chi-square. Wilcoxon test was used for the comparison of two dependent variables. All statistical analyses were performed with SPSS statistical software, version 27 (IBM Corp., Armonk, New York, United States). The graphs were created with GraphPad Prism, version 9.0.2 (GraphPad Software, San Diego, United States).\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eGlobal and regional MBF and MFR shows high variance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaseline patient characteristics, medical history and cardiovascular risk factors are summarized in \u003cstrong\u003etable 1.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGlobal stress MBF was significantly higher than rest MBF (stress MBF 2.3 \u0026plusmn; 1.1 ml/min/g vs. rest MBF 1.1 \u0026plusmn; 0.5 ml/min/g; p\u0026lt;0.001, all patients). A high interindividual variance was detected. Global stress MBF ranged from 0.4 to 7.4 ml/min/g and rest MBF ranged from 0.3 to 3.7 ml/min/g. Mean calculated global MFR was 2.1 \u0026plusmn; 1.1 (range 0.5 \u0026ndash; 7.8). Regional MBF was determined for coronary territories and results are summarized in \u003cstrong\u003etable 2\u003c/strong\u003e. Highest mean MBF and highest variance was detected in the right coronary territory. Men presented with lower stress MBF and a tendency towards lower MFR in comparison to females (2.0 \u0026plusmn; 0.8 ml/min/g vs. 2.9 \u0026plusmn; 1.2 ml/min/g, p\u0026lt;0.001 and 1.9 \u0026plusmn; 1.0 vs. 2.4 \u0026plusmn; 1.4, p=0.054) while rest MBF was similar (1.1 \u0026plusmn; 0.5 ml/min/g vs. 1.2 \u0026plusmn; 0.5 ml/min/g, p=0.200).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMBF and MFR are comparable for Tc-99m-\u003c/strong\u003e\u003cstrong\u003esestamibi and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTc-99m-\u003c/strong\u003e\u003cstrong\u003etetrofosmin\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 85 patients underwent a one-day protocol and 79 patients performed a two-day protocol. 41/85 one-day protocols and 32/79 two-day protocols were performed using Tc-99m-tetrofosmin. 58 patients underwent rest-only studies of which 23 were performed with Tc-99m-tetrofosmin. 19/58 stress-only studies were performed with Tc-99m-tetrofosmin.\u003c/p\u003e\n\u003cp\u003eGlobal stress MBF was significantly higher when Tc-99m-sestamibi was used (2.4 \u0026plusmn; 1.1 ml/min/g vs. 2.1 \u0026plusmn; 0.9 ml/min/g; p=0.049). This was also true in a regional MBF analysis for the LAD (2.6 \u0026plusmn; 1.2 ml/min/g vs. 2.2 \u0026plusmn; 1.0 ml/min/g; p=0.031) and RCA (3.0 \u0026plusmn; 1.3 ml/min/g vs. 2.7 \u0026plusmn; 1.1 ml/min/g; p=0.049) territory (\u003cstrong\u003etable 3\u003c/strong\u003e). No significant differences were detected for calculated global rest MBF (1.1 \u0026plusmn; 0.4 ml/min/g vs. 1.1 \u0026plusmn; 0.6 ml/min/g, p=0.259) or MFR (2.2 \u0026plusmn; 1.3 ml/min/g vs. 1.9 \u0026plusmn; 1.0 ml/min/g; p=0.109).\u003c/p\u003e\n\u003cp\u003eAdditionally, 30 stress-only patients (15 Tc-99m-sestamibi and 15 Tc-99m-tetrofosmin) without known cardiovascular comorbidities and without perfusion defects on static scans were compared in a subanalysis. Here, no relevant differences in global (3.1 \u0026plusmn; 1.2 ml/min/g vs. 2.8 \u0026plusmn; 0.9 ml/min/g; p=0.429) or regional stress MBF were detected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003cstrong\u003ene-day stress first protocol yields higher global rest MBF\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients who underwent either a one-day or a two-day stress-first protocol showed no differences in stress MBF. Significantly higher rest MBF values were calculated when a one day protocol was used (1.2 \u0026plusmn; 0.5 ml/min/g vs. 1.0 \u0026plusmn; 0.46 ml/min/g; p=0.009, figure 3). Consequently MFR was lower in patients that underwent one day protocols (MFR NC 1.9 \u0026plusmn; 1.0 ml/min/g vs. 2.2 \u0026plusmn; 1.3 ml/min/g; p=0.035; \u003cstrong\u003efigure 3\u003c/strong\u003e). \u0026nbsp;This effect was not observed, when AC was used. \u0026nbsp;A separate analysis for Tc-99m-sestamibi and Tc-99m-tetrofosmin showed that the global observation was driven by Tc-99m-tetrofosmin scans (one day protocoll 1.4 \u0026plusmn; 0.7 ml/min/g vs. two day protocol 1.0 \u0026plusmn; 0.5 ml/min/g; p=0.014) while in Tc-99m-sestamibi scans no differences based on protocol use were detected (1.1 \u0026plusmn; 0.4 ml/min/g vs. 1.0 \u0026plusmn; 0.47 ml/min/g; p=0.338).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUse of attenuation correction lowers calculated MBF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMean global stress and rest MBF were significantly lower when AC was used (NC 2.3 \u0026plusmn; 1.1 ml/min/g vs. AC 1.8 \u0026plusmn; 0.8 ml/min/g; p\u0026lt;0.001; NC 1.1 \u0026plusmn; 0.5 ml/min/g vs. AC 0.9 \u0026plusmn; 0.4 ml/min/g; p\u0026lt;0.001, \u003cstrong\u003efigure 4\u003c/strong\u003e). \u0026nbsp;Similar results were found for the regional analysis. However, there were no significant differences in the calculated MFR (NC 2.1 \u0026plusmn; 1.1 ml/min/g vs. AC 2.1 \u0026plusmn; 1.1 ml/min/g; p=0.626). A patient example for calculation of global and regional stress MBF and effect of AC s given in \u003cstrong\u003efigure 5\u003c/strong\u003e. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePresence of perfusion defects in standard static scans is associated with lower global and regional MBF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRelevant perfusion defects were defined as three or more segments with reduced perfusion in one coronary territory based on the 17-segments-AHA model, results of standard static scans are presented in \u003cstrong\u003etable 1\u003c/strong\u003e. Presence of perfusion defects in static scans were associated with lower global stress and rest MBF (no defect: 2.6 \u0026plusmn; 1.1 ml/min/g vs. defect 1.7 \u0026plusmn; 0.7 ml/min/g; p\u0026lt;0.001 and no defect 1.2 \u0026plusmn; 0.5 ml/min/g vs. defect: 1.0 \u0026plusmn; 0.4 ml/min/g; p\u0026lt;0.001; \u003cstrong\u003efigure 5\u003c/strong\u003e). However, there were no significant differences for MFR between patients with and without defects in static scans (no defect p=0.143; defect p=0.234). Analogue results were found for AC MBF and MFR measures and for regional analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSummed defect scores derived from standard static scans correlate with global MBF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSignificant correlations between summed stress scores (SSS) and global stress MBF as well as summed rest scores (SRS) and global rest MBF were found (\u003cstrong\u003efigure 6\u003c/strong\u003e). \u0026nbsp;However, no significant correlation was detected between summed difference scores (SDS=SSS-SRS) and MFR NC (r=0.05, p=0.556). Analogue correlations were calculated when AC was used.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLower LVEF is associated with lower MBF\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMean stress left ventricular ejection fraction (LVEF) was 58.8% and rest LVEF was 54.2%. \u0026nbsp;Higher stress (r=0.52, p\u0026lt;0.001) and rest LVEF (r=0.28, p\u0026lt;0.001) correlated significantly with higher MBF measures (\u003cstrong\u003efigure 7\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo significant correlation was detected between stress or rest LVEF and MFR.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInfluence of cardiovascular comorbidities on MBF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with known coronary artery disease (CAD) had a significantly lower global stress (1.9 \u0026plusmn; 0.9 ml/min/g vs.\u0026nbsp;2.6 \u0026plusmn; 1.1 ml/min/g, p\u0026lt;0.001) and rest MBF (1.0 \u0026plusmn; 0.4 ml/min/g vs. 1.3 \u0026plusmn; 0.6 ml/min/g, p=0.002)\u0026nbsp;than patients without known CAD (\u003cstrong\u003efigure 8\u003c/strong\u003e). No significant reduction of MFR was seen in patients with history of CAD (p=0.283).\u003c/p\u003e\n\u003cp\u003ePresence of cardiovascular risk factors (i.e. CAD, MI, hypertension, diabetes, obesity or smoking) lead to a significant reduction of calculated MBF. Patients with two or more known cardiovascular risk factors had significantly lower MBF than patients with less or without cardiovascular risk factors (global stress MBF: 2.1 \u0026plusmn; 1.0 ml/min/g vs. 2.7 \u0026plusmn; 1.0 ml/min/g, p\u0026lt;0.001; global rest MBF: 1.0 \u0026plusmn; 0.4 ml/min/g vs. 1.4 \u0026plusmn; 0.6 ml/min/g, p=0.004). For MFR, no significant difference was found (2.1 \u0026plusmn; 1.2 ml/min/g vs. 1.8 \u0026plusmn; 0.7 ml/min/g, p=0.124).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eDynamic list mode imaging with CZT cameras now facilitates SPECT derived measurement of MBF and MFR\u003csup\u003e15\u003c/sup\u003e. In PET, being the gold standard, quantitative MBF assessment provides enhanced diagnostic precision, facilitating a comprehensive evaluation of myocardial perfusion abnormalities and aiding in risk stratification\u003csup\u003e23, 24\u003c/sup\u003e. The ability to measure flow reserve enables identification of subtle perfusion deficits and microcirculation abnormalities thus providing valuable prognostic information\u003csup\u003e21\u003c/sup\u003e. However, PET imaging is currently only feasible in larger hospitals or cardiovascular centers due to high costs and the need for an on-site cyclotron\u003csup\u003e25\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eSPECT is a widely accessible technique, therefore calculating MBF and MFR from SPECT would be desirable. In this analysis, SPECT MBF quantification was performed as part of our clinical routine without any specific preselection. The detected mean stress and rest MBF and MFR were in range of expectation. Of note, few patients presented with extraordinary high flow measures which we re-analyzed but high measures without detectable reason persisted. We chose not to exclude these scans from our global analysis in order to show the high MBF variance. Expectedly, regionally highest variance was found in the RCA territory, which is the most complex region for SPECT most likely due to attenuation-related effects and infradiaphragmatic spillover. We showed that patients with high defect scores derived from standard static scans and patients with lower LVEF had impaired MBF. When employing Tc-99m-sestamibi, there was slight yet significant increase in global stress in comparison to Tc-99m-tetrofosmin analyzing all patients, however no differences were detected in the provided sub analysis. Slight differences between the tracers might be caused by the respective tracer extraction fraction.\u0026nbsp;No other relevant differences between the two used tracers were found.\u003c/p\u003e\n\u003cp\u003eAvailable data on patient history, laboratory values and cardiac interventions reflect a real-world situation where parts of information may be incomplete. Also, we did not systematically compare global or regional MBF with the current coronary status. In this regard, we still detected significant correlations between presence of cardiovascular comorbidities including CAD and calculated MBF and MFR. Concordant to other studies specifically evaluating angiographic findings and SPECT MBF\u003csup\u003e18, 19, 26-29\u003c/sup\u003e, our results further support credibility of this technique.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, clinical utility of absolute quantitative MBF and MFR measures is not yet clear and several open questions have to be addressed to facilitate routine clinical use. It is well known that challenges accompany the acquisition of absolute quantitative MBF\u003csup\u003e30, 31\u003c/sup\u003e. The complexity of data processing, including the need for corrections in attenuation, scatter, and partial volume effects, pose hurdles in standardizing protocols across different centers. Dynamic image acquisition is more sophisticated than standard static acquisition. Patients have to be positioned without an injected full tracer dose and patient movement needs to be as small as possible. Limitations in hardware, specifically the spatial and temporal resolution of traditional SPECT systems, affect the accuracy of absolute MBF quantification, particularly in dynamic assessments\u003csup\u003e31\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFor CZT-SPECT systems, CT AC is usually acquired on a separate camera since these systems are not equipped with CT. MBF calculation in PET however is always done with AC. The effect of CT AC on calculated SPECT MBF and MFR has been evaluated in few studies. We here observed a generally lower stress and rest MBF when AC was used but no effect on MFR was detected. This finding is consistent with results from Bailly et al\u003csup\u003e32\u003c/sup\u003e. Other studies evaluated AC MBF results in comparison to PET and found partially inconclusive effects on global and regional MBF\u003csup\u003e17, 33\u003c/sup\u003e. Zavadovsky et al. found an improved correlation between stenosis severity and regional stress MBF and higher diagnostic accuracy for multivessel CAD when AC was used\u003csup\u003e22\u003c/sup\u003e. In summary, effects of AC have not yet been fully understood and therefore careful interpretation is obligatory.\u003c/p\u003e\n\u003cp\u003eIn our clinical routine, both one-day and two-day protocols were used as appropriate. As recommended\u003csup\u003e34\u003c/sup\u003e for one-day protocols we took care that a stress / rest dosing ratio of at least 1:2.5 or better 1:3 was maintained. \u0026nbsp;We also corrected the second scan for residual activity. Still, we observed significantly higher rest MBF values and a consequently lower MFR. Interestingly, this effect was less pronounced, when AC or Tc-99m-Sestamibi was used. This finding warrants further investigation. Ultimately, two-day protocols may be more suitable for accurate SPECT MBF and MFR calculation.\u003c/p\u003e\n\u003cp\u003eIn summary, obtaining SPECT MBF and MFR is feasible in a clinical routine setting yielding values in range of expectation. Yet, currently available analysis methods are time-consuming and technically demanding. There is a need for improved automated motion correction in order to bring the application to clinical routine use. Moreover, use of AC and selection of protocol distinctly influence MBF and MFR results. Harmonization of imaging protocols between cardiovascular centers will improve inter-site comparability in the future\u003csup\u003e35\u003c/sup\u003e. Until then, absolute quantitative SPECT acquisition of MBF remains a possibility to enhance diagnostic value for specific clinical scenarios.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is an observational study. Presented data is based on routinely acquired SPECT imaging without any study-related pre-selection of patients. Available data on patient history, laboratory values and cardiac interventions reflect a real-world situation where parts of information may be incomplete. To date there is no reliable reference standard for flow measurements derived from SPECT. \u0026nbsp; Tc-99m-labeled perfusion tracers have a high-count statistic and low extraction fraction at high flow rates which determines reduced contrast between stress and rest flow in comparison to values known from PET. \u0026nbsp;No systematical comparison to PET data or findings from coronary angiography was included.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDisclosure:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThis work was partially supported by a research project in collaboration with GE Healthcare.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eW.W. and J.D. wrote the main manuscript text and prepared all data, figures and tables. F.M.B. reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAvailable data\u003c/h2\u003e \u003cp\u003eon patient history, laboratory values and cardiac interventions reflect a real-world situation where parts of information may be incomplete. Also, we did not systematically compare global or regional MBF with the current coronary status. In this regard, we still detected significant correlations between presence of cardiovascular comorbidities including CAD and calculated MBF and MFR. Concordant to other studies specifically evaluating angiographic findings and SPECT MBF\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, our results further support credibility of this technique.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZiadi MC, Dekemp RA, Williams KA, et al. Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia. \u003cem\u003eJ Am Coll Cardiol\u003c/em\u003e.\u003cem\u003e \u003c/em\u003e2011;58:740-748.\u003c/li\u003e\n\u003cli\u003edeKemp RA, Yoshinaga K, Beanlands RS. 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Advances in Single-Photon Emission Computed Tomography: Hardware, Software, and Myocardial Flow Reserve. \u003cem\u003eCardiol Clin\u003c/em\u003e.\u003cem\u003e \u003c/em\u003e2023;41:117-127.\u003c/li\u003e\n\u003cli\u003eBailly M, Thibault F, Courtehoux M, et al. Impact of attenuation correction for CZT-SPECT measurement of myocardial blood flow. \u003cem\u003eJ Nucl Cardiol\u003c/em\u003e.\u003cem\u003e \u003c/em\u003e2021;28:2560-2568.\u003c/li\u003e\n\u003cli\u003eGiubbini R, Bertoli M, Durmo R, et al. Comparison between N(13)NH(3)-PET and (99m)Tc-Tetrofosmin-CZT SPECT in the evaluation of absolute myocardial blood flow and flow reserve. \u003cem\u003eJ Nucl Cardiol\u003c/em\u003e.\u003cem\u003e \u003c/em\u003e2021;28:1906-1918.\u003c/li\u003e\n\u003cli\u003eDorbala S, Ananthasubramaniam K, Armstrong IS, et al. Single Photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging Guidelines: Instrumentation, Acquisition, Processing, and Interpretation. \u003cem\u003eJ Nucl Cardiol\u003c/em\u003e.\u003cem\u003e \u003c/em\u003e2018;25:1784-1846.\u003c/li\u003e\n\u003cli\u003eWells RG, Bengel FM, Camoni L, et al. Multicenter Evaluation of the Feasibility of Clinical Implementation of SPECT Myocardial Blood Flow Measurement: Intersite Variability and Imaging Time. \u003cem\u003eCirc Cardiovasc Imaging\u003c/em\u003e.\u003cem\u003e \u003c/em\u003e2023;16:e015009.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-international-journal-of-cardiovascular-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caim","sideBox":"Learn more about [The International Journal of Cardiovascular Imaging](https://www.springer.com/journal/10554)","snPcode":"10554","submissionUrl":"https://submission.nature.com/new-submission/10554/3","title":"The International Journal of Cardiovascular Imaging","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Absolute quantitative SPECT, myocardial perfusion imaging, myocardial blood flow, myocardial flow reserve","lastPublishedDoi":"10.21203/rs.3.rs-5431655/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5431655/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e \u003cp\u003eSolid-state detector single photon emission computed tomography (SPECT) enables the acquisition of dynamic data for calculation of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Here, we report about our experiences on clinical usefulness and robustness using Tc-99m-sestamibi and Tc-99m-tetrofosmin.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003e307 patients underwent dynamic list-mode myocardial perfusion imaging (MPI) and standard static MPI for clinical workup of coronary artery disease on a dedicated cardiac SPECT camera. MBF and MFR were calculated using a 1-tissue‐compartment model. Attenuation correction was performed for all patients using an external computed tomogram. Patients underwent stress-only scans, both stress and rest scans or rest-only scans using Tc-99m-tetrofosmin or Tc-99m-sestamibi. 30 patients without known cardiovascular comorbidities and without perfusion defect on static scans were compared in a sub analysis.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eGlobal stress myocardial blood flow (MBF) was significantly higher than rest MBF (2.3 vs. 1.1 ml/min/g; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and showed a high variability among individuals. Global myocardial flow reserve (MFR) was 2.1 (range 0.5\u0026ndash;7.8). An analysis of 30 patients without known cardiovascular comorbidities yielded similar stress MBF measures for Tc-99m-sestamibi and Tc-99m-tetrofosmin (3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 vs. 2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 ml/min/g; p\u0026thinsp;=\u0026thinsp;0.429). The use of attenuation correction lead to systematically lower MBF measures. Patients who underwent a one-day protocol had notably higher rest MBF (1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 vs. 1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46 ml/min/g; p\u0026thinsp;=\u0026thinsp;0.009) and consequently a lower MFR. Summed defect scores from standard static scans and presence of cardiovascular comorbidities negatively impacted MBF and MFR.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eQuantitative SPECT MBF and MFR in a clinical routine setting yields flow measures in range of expectation at an albeit wide range and is comprehensibly linked with results from standard static scan and patients history of cardiovascular diseases. Use of one-day protocols and attenuation corrections systematically alters quantitative results.\u003c/p\u003e","manuscriptTitle":"Comparison of Global and Regional Myocardial Blood Flow Quantification using Dynamic Solid-State Detector SPECT and Tc-99m-sestamibi or Tc-99m-tetrofosmin in a routine clinical setting","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 16:14:46","doi":"10.21203/rs.3.rs-5431655/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-05T17:21:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-04T18:33:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-26T11:09:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116722397335604136088912845276720654813","date":"2024-11-14T06:36:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"73578613276400226539435684390506080413","date":"2024-11-12T06:17:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-11T23:51:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-11T13:52:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-11T13:52:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"The International Journal of Cardiovascular Imaging","date":"2024-11-11T11:24:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-international-journal-of-cardiovascular-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caim","sideBox":"Learn more about [The International Journal of Cardiovascular Imaging](https://www.springer.com/journal/10554)","snPcode":"10554","submissionUrl":"https://submission.nature.com/new-submission/10554/3","title":"The International Journal of Cardiovascular Imaging","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5abf0e75-2c11-47fd-b726-607496fd29e0","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:02:56+00:00","versionOfRecord":{"articleIdentity":"rs-5431655","link":"https://doi.org/10.1007/s10554-025-03339-4","journal":{"identity":"the-international-journal-of-cardiovascular-imaging","isVorOnly":false,"title":"The International Journal of Cardiovascular Imaging"},"publishedOn":"2025-01-30 15:57:42","publishedOnDateReadable":"January 30th, 2025"},"versionCreatedAt":"2024-12-16 16:14:46","video":"","vorDoi":"10.1007/s10554-025-03339-4","vorDoiUrl":"https://doi.org/10.1007/s10554-025-03339-4","workflowStages":[]},"version":"v1","identity":"rs-5431655","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5431655","identity":"rs-5431655","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}