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. 2023 Sep 28;5(5):e220292. doi: 10.1148/ryct.220292

Combined FDG PET/MRI versus Standard-of-Care Imaging in the Evaluation of Cardiac Sarcoidosis

Constantin A Marschner 1, Faisal Aloufi 1, Matthew Aitken 1, Edward Cheung 1, Paaladinesh Thavendiranathan 1, Robert M Iwanochko 1, Meyer Balter 1, Yasbanoo Moayedi 1, Juan Duero Posada 1, Kate Hanneman 1,✉
PMCID: PMC10698587  PMID: 38076597

Abstract

Purpose

To compare combined cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI with standard-of-care evaluation using cardiac MRI, 18F-FDG PET/CT, and SPECT perfusion imaging in suspected cardiac sarcoidosis (CS) with respect to radiation dose, imaging duration, and diagnostic test performance.

Materials and Methods

Consecutive patients with suspected CS undergoing clinical evaluation with cardiac 18F-FDG PET/CT and gated rest technetium 99m sestamibi SPECT perfusion imaging were prospectively recruited between November 2017 and May 2021 for parallel assessment with combined cardiac 18F-FDG PET/MRI on the same day (ClinicalTrials.gov identifier, NCT03356756). Total effective radiation dose and imaging duration were compared between approaches (combined cardiac PET/MRI vs separate cardiac MRI, PET/CT, and SPECT). MRI findings were initially interpreted without PET data, and then PET and late gadolinium enhancement images were fused and interpreted together. Final diagnosis of CS was established using Japanese Ministry of Health and Welfare guidelines.

Results

Forty participants (mean age, 54 years ± 14 [SD]; 26 [65%] male participants) were included, 14 (35%) with a final diagnosis of CS. Compared with separate cardiac MRI, PET/CT, and SPECT perfusion imaging, combined cardiac PET/MRI had 52% lower total radiation dose (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001) and 43% lower total imaging duration (122 minutes ± 15 vs 214 minutes ± 26, P < .001). Combined PET/MRI had the highest area under the curve for diagnosis of CS (0.84) with 96% specificity and 71% sensitivity for colocalized FDG uptake and late gadolinium enhancement in a pattern typical for CS.

Conclusion

In the evaluation of suspected CS, combined cardiac 18F-FDG PET/MRI had a lower radiation dose, shorter imaging duration, and higher diagnostic performance compared with standard-of-care imaging.

Clinical trial registration no. NCT03356756

Keywords: Cardiac Sarcoidosis, 18F-FDG PET/MRI, 18F-FDG PET/CT, SPECT Perfusion Imaging, Cardiac MRI, Standard-of-Care Imaging

Supplemental material is available for this article.

© RSNA, 2023

Keywords: Cardiac Sarcoidosis, 18F-FDG PET/MRI, 18F-FDG PET/CT, SPECT Perfusion Imaging, Cardiac MRI, Standard-of-Care Imaging

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Summary

Combined cardiac fluorine 18 fluorodeoxyglucose (18F-FDG) PET/MRI had a lower radiation dose and shorter imaging duration in the evaluation of cardiac sarcoidosis compared with separate cardiac MRI, 18F-FDG PET/CT, and technetium 99m sestamibi SPECT perfusion imaging.

Key Points

  • ■ In a prospective study of 40 participants with suspected cardiac sarcoidosis, combined cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI had a 52% lower radiation dose (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001) and 43% lower imaging duration (122 minutes ± 15 vs 214 minutes ± 26, P < .001) compared with standard-of-care imaging with cardiac MRI, 18F-FDG PET/CT, and technetium 99m sestamibi SPECT perfusion imaging.

  • ■ Combined PET/MRI had the highest area under the receiver operating characteristic curve for diagnosis of cardiac sarcoidosis (0.84), with 96% specificity and 71% sensitivity for colocalized FDG uptake and late gadolinium enhancement in a pattern typical for cardiac sarcoidosis.

Introduction

Sarcoidosis is a systemic disease characterized by noncaseating granulomas that can involve multiple organs including the heart. In the absence of treatment, cardiac sarcoidosis (CS) can lead to irreversible fibrosis, arrhythmias, ventricular dysfunction, and sudden cardiac death (1).

Timely diagnosis is important given the availability of treatment and preventative options (2). However, the diagnosis of CS remains a challenge even in patients with known extracardiac disease, as there is no reliable reference standard. Endomyocardial biopsy findings can confirm CS, although the sensitivity of biopsy is low, and there are associated risks (3). Therefore, imaging plays an important role in the noninvasive evaluation of suspected CS.

Fluorine 18–labeled (18F) fluorodeoxyglucose (FDG) PET/CT is often used for evaluation of active CS (4). Focal myocardial FDG uptake typically reflects metabolically active immune cells (5). Given that there is often no FDG uptake in the setting of chronic or “burnt-out” CS, cardiac PET/CT images are usually interpreted in conjunction with SPECT or PET perfusion images (6).

Cardiac MRI is also useful for detection of CS, with typical features including subepicardial or nodular midwall late gadolinium enhancement (LGE) and T2 hyperintensity in areas of edema (6,7). Although there is no consensus on the optimal imaging approach for patients with suspected cardiac sarcoidosis, cardiac MRI is often performed first with subsequent FDG PET imaging performed if LGE or high T2 signal intensity is identified at MRI. Combined PET/MRI has become available more recently, allowing for simultaneous imaging with both modalities (8–10). However, there are limited data on its comparative effectiveness versus standard-of-care imaging.

The purpose of this study was to compare combined cardiac 18F-FDG PET/MRI with standard-of-care evaluation using cardiac MRI, 18F-FDG PET/CT, and SPECT perfusion imaging in suspected CS with respect to radiation dose, imaging duration, and diagnostic performance. We hypothesized that combined cardiac PET/MRI would have lower total radiation dose, shorter imaging duration, and similar diagnostic test performance compared with standard-of-care imaging.

Materials and Methods

This prospective cohort study was approved by the institutional research ethics board of the University Health Network. The study was registered at ClinicalTrials.gov (NCT03356756). Written informed consent was obtained from all participants. Between November 2017 and May 2021, consecutive patients aged 18 years or older with suspected CS who were referred for clinically indicated technetium 99m (99mTc)–labeled methoxyisobutylisonitrile (sestamibi) SPECT and same-day 18F-FDG PET/CT were recruited for same-day cardiac PET/MRI. Exclusion criteria included implanted cardiac pacemaker and defibrillator devices, impaired renal function (glomerular filtration rate < 30 mL/min/m2), inability or unwillingness to follow the required diet instructions, and lack of same-day SPECT and PET/CT acquisitions. Clinical data were obtained from patient history at the time of recruitment and the electronic patient record. We previously reported results related to the diagnostic and prognostic value of PET/MRI findings alone in 42 participants with suspected CS which partially overlaps with the current cohort (39 participants) (1). The current study expands on the prior analysis by including comparison to standard-of-care imaging with PET/CT and SPECT perfusion imaging and assessment of radiation dose and imaging duration.

SPECT and PET/CT Acquisition and Analysis

For standard-of-care imaging, all participants underwent SPECT with intravenous injection of 99mTc-sestamibi for rest perfusion imaging 30–90 minutes following radiotracer injection with high-resolution collimators according to current guidelines (Symbia T Series; Siemens Healthineers) (11). All participants were provided with detailed preparation instructions to suppress physiologic myocardial glucose uptake, including a high-fat, high-protein, low-carbohydrate diet for the entire day before 18F-FDG PET/CT imaging, followed by a complete fast with the exception of water for the immediate 12-hour period prior to imaging. Adherence was confirmed through direct questioning and evaluation of blood glucose level prior to intravenous injection of 18F-FDG. Cardiac PET/CT was performed 60–90 minutes after intravenous administration of 18F-FDG (Biograph Vision; Siemens Healthineers) with low-dose CT for attenuation correction and one bed position centered over the heart (10 minutes).

SPECT and PET/CT images were reconstructed in short- and long-axis reconstructions and were analyzed while blinded to all clinical information by an experienced fellowship-trained cardiologist (R.M.I.). Findings were evaluated globally and according to the American Heart Association 17-segment model (12). Regional uptake on SPECT images was scored as normal or impaired or absent perfusion in each segment (13). Left ventricular volumes and function were quantified using dedicated software (QGS+QPS; Cedars-Sinai). Myocardial 18F-FDG uptake was categorized as none, diffuse, focal, or focal-on-diffuse. Focal or focal-on-diffuse patterns of myocardial FDG uptake were considered positive for inflammation, no FDG uptake was considered negative, and diffuse FDG uptake was considered nondiagnostic due to inadequate physiologic myocardial glucose suppression (14).

SPECT and PET/CT findings were also evaluated together. Segments with focal (or focal-on-diffuse) FDG uptake alone were considered active inflammation and those with colocalizing FDG uptake and a resting perfusion abnormality were considered active on chronic inflammation.

18F-FDG PET/MRI Acquisition and Analysis

Combined cardiac PET/MRI was performed on the same day within 3 hours of PET/CT acquisition with a 3-T scanner (Biograph mMR; Siemens Healthineers). With the exception of water, participants fasted in between imaging. The MRI protocol included the following: long-axis (two-, three-, and four-chamber) and a stack of short-axis balanced cine steady-state free precession sections; T1 mapping using a modified Look-Locker inversion-recovery technique at basal, mid, and apical short-axis locations both before and 15 minutes after contrast agent administration (0.15 mmol/kg of gadolinium-based contrast agent, gadobutrol; Bayer); T2 mapping using a fast low-angle shot technique for matching short-axis locations prior to contrast agent administration; and a phase-sensitive inversion-recovery LGE technique starting 12 minutes after contrast agent administration. Pixel-based T1 and T2 maps were automatically generated on the scanner with application of inline motion correction algorithms. List-mode PET acquisition occurred simultaneously with the MRI examination in one bed position centered over the heart, with electrocardiographic gating and three-dimensional image reconstruction using ordered subset expectation maximization (three iterations and 21 subsets). A two-point Dixon scan was acquired for attenuation correction, and a four-compartment model attenuation map including air, fat, water, and tissue was calculated.

PET/MRI studies were analyzed by two experienced fellowship-trained cardiac radiologists (C.A.M. and F.A.) who were blinded to all clinical information. MRI acquisitions were initially interpreted in isolation without PET data. A separate cardiac MRI was not performed on the same day as part of the research protocol as many participants had undergone a prior clinical cardiac MRI. Given that cardiac MRI is often the first cardiac imaging study performed for evaluation of CS, we considered the cardiac MRI finding from PET/MRI alone as part of standard of care for the purpose of comparison in this study. Ventricular volumes, function, and mass were assessed as per established standards for cardiac MRI (Circle cmr42; Circle Cardiovascular Imaging) (15). Global and segmental LGE was evaluated visually. Global and segmental T1 and T2 relaxation times were assessed by contouring endocardial and epicardial borders on all short-axis images, applying a 15% offset adjustment to eliminate in-plane partial volume artifacts. Extracellular volume was calculated with input of pre- and postcontrast T1 values and hematocrit measurements (16). Maximum native T1, T2, and extracellular volume were defined as the highest segmental value for each parameter, and values were categorized as normal or abnormal based on established scanner specific local reference ranges (elevated T2 values > 45 msec; elevated T1 values > 1289 msec; and elevated extracellular volume > 30%) (17). LGE images were evaluated visually for presence of any myocardial LGE and LGE in a pattern typical for CS, defined as subepicardial and midwall LGE at the basal to mid interventricular septum and inferior lateral wall, including extension from the anterior or inferior septum to the right ventricular wall in a “hook sign” (18,19).

Subsequently, combined PET/MRI findings were evaluated together, and PET and LGE images were fused by translating and rotating PET images onto the MRI coordinate system. Findings were evaluated globally and according to the American Heart Association 17-segment model. Myocardial FDG uptake was qualitatively categorized as none, diffuse, focal, or focal-on-diffuse. Similar to PET/CT, focal or focal-on-diffuse patterns of myocardial FDG uptake were considered positive for inflammation, no FDG uptake was considered negative, and diffuse FDG uptake was considered nondiagnostic (14).

PET/MRI findings were considered to colocalize when abnormalities were present in the same myocardial segment based on the American Heart Association 17-segment model. Segments with focal 18F-FDG uptake alone were considered active inflammation, those with colocalizing 18F-FDG uptake and LGE in a pattern typical for CS were considered active on chronic inflammation, and those with LGE alone were considered chronic, burnt-out disease.

Outcomes

Total imaging duration was calculated separately for each imaging test. For SPECT, this was defined as the time between injection of 99mTc-sestamibi and the end of SPECT image acquisition. For PET/CT, this was defined as the time interval between injection of 18F-FDG and the end of PET/CT image acquisition. For cardiac MRI, this was defined as the time for the MRI acquisition alone. For combined PET/MRI, this was defined as the time from injection of 18F-FDG to start of PET/CT imaging (ie, the standard delay following FDG injection to the start of imaging) plus the total time for the PET/MRI acquisition. We did not include patient preparation time in the study duration for any of the studies. For standard of care, the total image acquisition time was summed for SPECT, PET/CT, and cardiac MRI components (including patient preparation and the time between sequences for MRI) but did not include the time between studies as this varied depending on clinical scheduling.

Total effective radiation dose was estimated in millisieverts separately for each imaging test component, including radiotracers and CT. The effective dose for CT was estimated from dose-length product using a published conversion coefficient of 0.015 mSv/(mGy · cm) (20–22). For 99mTc-sestamibi, the effective radiation dose was estimated from the injected dose using a published conversion coefficient of 0.009 mSv/mBq (23). For 18F-FDG, the effective radiation dose was estimated from the injected dose using a published conversion coefficient of 0.019 mSv/mBq (24).

Diagnostic test performance for diagnosis of CS was evaluated for combined PET/MRI and standard-of-care evaluation with PET/CT, SPECT, and cardiac MRI. Participants were classified as having a final diagnosis of CS or not using the 2006 revised Japanese Ministry of Health and Welfare guidelines as the reference standard, with exclusion of LGE as a minor criterion (Appendix S1) (25). In participants without CS, the final alternate diagnosis was recorded based on all available information. Myocarditis was diagnosed using the modified Lake Louise criteria at MRI (26).

Statistical Analysis

Statistical analysis was performed using a commercially available software package (Stata version 14.1; StataCorp). A two-tailed P value of less than .05 was considered statistically significant. All continuous data were tested for normal distribution using the Shapiro-Wilk test. Comparisons between standard of care and combined PET/MRI were evaluated using the paired t test, Wilcoxon signed rank test, or McNemar test as appropriate. Diagnostic performance was evaluated, including sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).

Results

Participant Characteristics

Sixty-five patients were evaluated for eligibility (Fig 1). Eighteen were excluded due to an implanted cardiac device, three due to impaired renal function, two due to inability to follow the diet instructions, and two due to a lack of same-day SPECT and PET/CT acquisitions. A total of 40 participants (mean age, 54 years ± 14 [SD]; 26 [65%] male participants; 14 [35%] female participants) were included in this study, 14 (35%) of which had a final diagnosis of CS (Table 1).

Figure 1:

Flowchart demonstrates participant selection. ICD = implantable cardioverter defibrillator, PM = pacemaker.

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Flowchart demonstrates participant selection. ICD = implantable cardioverter defibrillator, PM = pacemaker.

Table 1:

Baseline Demographic and Clinical Parameters of Study Participants

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Imaging Findings

FDG uptake on 18F-FDG PET/CT images was positive in 10 of 14 (71%) participants with CS compared with six of 26 (23%) without (P = .006) (Table 2) (Figs 2, 3). No participants had diffuse FDG uptake. Among participants with CS, LGE in a pattern typical for CS was present in 13 (93%), elevated T2 values in six (43%), elevated T1 values in 13 (93%), and elevated extracellular volume (ECV) in 13 (93%). On combined PET/MR images, at least one segment with colocalizing FDG uptake and LGE was present in 10 of 14 (71%) participants with CS compared with six of 26 (23%) without (P = .006). Left ventricular ejection fraction was higher when quantified at SPECT compared with MRI (60% ± 15 vs 52% ± 11, P < .001).

Table 2:

Imaging Findings, Duration, Radiation Dose, and Cost

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Figure 2:

Images in a 52-year-old female participant with cardiac sarcoidosis. Standard-of-care imaging (top row) demonstrates a perfusion defect on SPECT images (top left) and corresponding fluorodeoxyglucose (FDG)–uptake on fluorine 18 (18F)–FDG PET/CT image (top right) at the interventricular septum (green arrows). On combined 18F-FDG PET/MR images (bottom row), there is nodular late gadolinium enhancement (LGE) at the interventricular septum (orange arrows) with corresponding FDG uptake (blue arrows).

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Images in a 52-year-old female participant with cardiac sarcoidosis. Standard-of-care imaging (top row) demonstrates a perfusion defect on SPECT images (top left) and corresponding fluorodeoxyglucose (FDG)–uptake on fluorine 18 (18F)–FDG PET/CT image (top right) at the interventricular septum (green arrows). On combined 18F-FDG PET/MR images (bottom row), there is nodular late gadolinium enhancement (LGE) at the interventricular septum (orange arrows) with corresponding FDG uptake (blue arrows).

Figure 3:

Images in a 62-year-old female participant with extracardiac sarcoidosis but no cardiac involvement. Standard-of-care imaging (top row) demonstrates normal perfusion on SPECT images (top left) and no myocardial fluorodeoxyglucose (FDG) uptake on fluorine 18 (18F) FDG PET/CT image (top right). On combined 18F-FDG PET/MR images (bottom row), there is no late gadolinium enhancement (LGE) and no myocardial FDG uptake.

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Images in a 62-year-old female participant with extracardiac sarcoidosis but no cardiac involvement. Standard-of-care imaging (top row) demonstrates normal perfusion on SPECT images (top left) and no myocardial fluorodeoxyglucose (FDG) uptake on fluorine 18 (18F) FDG PET/CT image (top right). On combined 18F-FDG PET/MR images (bottom row), there is no late gadolinium enhancement (LGE) and no myocardial FDG uptake.

Imaging Duration

For standard of care, the total imaging duration was 73 minutes ± 20 for SPECT, 90 minutes ± 20 for PET/CT, and 51 minutes ± 9 for cardiac MRI. For combined PET/MRI, total imaging duration was 122 minutes ± 15. Overall, the total imaging duration was 43% lower for combined PET/MRI compared with standard of care (122 minutes ± 15 vs 214 minutes ± 26, P < .001) when only the patient preparation and imaging duration were considered.

Radiation Dose

The mean injected dose of sestamibi was 844 MBq ± 70, corresponding to an effective radiation dose of 7.6 mSv ± 0.6. The mean injected dose for FDG was 424 MBq ± 65, corresponding to an effective radiation dose of 8.0 mSv ± 1.2. The mean dose-length product for CT was 79 mGy · cm ± 23, corresponding to an effective radiation dose of 1.1 mSv ± 0.2. The total effective radiation dose was 52% lower for combined PET/MRI compared with standard of care (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001).

Diagnostic Performance

For diagnosis of CS, combined PET/MRI had the highest AUC (0.84; 95% CI: 0.71, 0.97), with 96% (25 of 26) specificity and 71% (10 of 14) sensitivity for colocalized FDG uptake and LGE in a pattern typical for CS (Table 3). For standard of care, FDG uptake on PET/CT images had an AUC of 0.74 (95% CI: 0.59, 0.89; 71% sensitivity [10 of 14] and 77% specificity [20 of 26]), LGE in a pattern typical for CS on cardiac MR images (when interpreted alone) had an AUC of 0.83 (95% CI: 0.72, 0.94; 93% sensitivity [13 of 14] and 73% [eight of 26] specificity), and high T2 values had an AUC of 0.61 (95% CI: 0.46, 0.77; 43% sensitivity [six of 14] and 80% [20 of 26] specificity) (Table 3).

Table 3:

Diagnostic Test Performance for Cardiac Sarcoidosis

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Discussion

This prospective cohort study compared combined cardiac 18F-FDG PET/MRI versus standard-of-care imaging in the evaluation of 40 consecutive adult participants with suspected CS with respect to effective radiation dose, imaging duration, and diagnostic performance. We found that combined cardiac 18F-FDG PET/MRI had a 52% lower radiation dose (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001) and 43% shorter imaging duration (122 minutes ± 15 vs 214 minutes ± 26, P < .001) compared with a standard-of-care approach with separate cardiac MRI, 18F-FDG PET/CT, and 99mTc-sestamibi SPECT perfusion imaging tests. Combined PET/MRI had the highest AUC for diagnosis of CS (0.84), with 96% specificity and 71% sensitivity for colocalized FDG uptake and LGE in a pattern typical for CS.

To our knowledge, there are no prior reports comparing radiation exposure and imaging duration for combined PET/MRI versus standard-of-care evaluation with separate imaging tests in CS to date. Cumulative radiation dose from medical imaging is an important consideration, particularly in younger patients with CS who may require follow-up imaging. As expected, total radiation dose was substantially lower for combined PET/MRI compared with combined PET/CT and SPECT perfusion imaging due to both the lack of CT for attenuation correction and the lack of a nuclear medicine perfusion study. In keeping with the principle of “as low as reasonably achievable,” radiation exposure to patients due to imaging should be minimized when feasible with strategies including dose optimization or by choosing other imaging modalities that use less radiation (27). Of note, some centers interpret FDG PET imaging with PET perfusion (including rubidium 82) rather than SPECT perfusion, as PET perfusion has lower associated radiation (28). Although not frequently performed in the context of suspected CS in clinical practice, perfusion could also be evaluated using cardiac MRI. Combined evaluation with FDG PET for assessment of inflammation and PET perfusion imaging would result in a shorter overall imaging time compared with having a separate SPECT perfusion study. However, access to PET perfusion tracers remains somewhat limited given the need for an on-site cyclotron or expensive generators (29).

We also demonstrated that total imaging duration is substantially shorter for combined PET/MRI compared with standard-of-care evaluation which is an important consideration for patients with heart failure and shortness of breath who may have difficulty with prolonged imaging. We did not include the interval between SPECT, PET/CT, and MRI in the calculation of total imaging duration for the standard-of-care approach given that this was dependent on scheduling. Our analysis of time for each imaging approach included the time for patient preparation and between sequences. In reality, the standard-of-care approach with multiple separate imaging tests would have necessary delays between studies even if scheduled consecutively, further increasing the difference in time between this approach and combined PET/MRI assessment. Of note, not all patients with suspected CS might necessarily need to undergo assessment with all modalities in clinical practice if imaging was ordered sequentially. For example, a patient might first undergo cardiac MRI. If the MRI findings are normal, no further testing may be indicated if the posttest probability of CS was low (30).

A major challenge with respect to diagnostic evaluation of CS is that there is no definitive reference standard to confirm the diagnosis. Imaging is frequently relied on for assessment of cardiac disease, although there is no consensus on the optimal imaging approach for patients with suspected CS (31). Combined evaluation with both FDG PET and cardiac MRI potentially provides complementary information (10). Although our comparison is limited by the sample size, we found that combined PET/MRI had the highest diagnostic performance for CS (0.84) compared with standard-of-care evaluation with FDG PET/CT (0.74) and cardiac MRI alone (0.83). Recent meta-analyses have demonstrated that cardiac MRI has higher sensitivity than 18F-FDG PET/CT for diagnosis of CS (95% vs 84%, P = .002) but similar specificity (85% vs 82%, P = .85) and prognostic value (30,31). The results of the current study suggest that the high specificity of colocalized findings on combined PET/MR (96%) images might add incremental value to either imaging modality alone in diagnosing CS.

In addition to radiation dose and time savings compared with separate imaging tests, access to combined cardiac PET/MRI could also result in improved resource utilization. Sarcoidosis is associated with very high health care–related costs, estimated to be a mean of $19 714 per patient per year in the United States (32). Therefore, strategies to reduce costs are warranted. An analysis based on an individual-level, continuous, time-state transition model in CS found that combined cardiac PET/MRI was associated with lower overall medical costs on average ($8761 vs $10 777) and improved expected quality of life-years compared with standard-of-care evaluation (33). With respect to patient experience, combined PET/MRI could lead to shorter overall wait times and less hassle compared with three separate imaging tests. A single combined imaging test might also lead to shorter time between symptom onset and final diagnosis. Although the results of this study support the rationale for use of combined PET/MRI in the evaluation of CS, access remains limited (34).

Our study had several limitations. There is a potential for selection bias given that participants volunteered for the study and therefore may not reflect the entire population of patients with suspected CS. Furthermore, individuals with a contraindication to PET/MRI were excluded. Although CS is relatively rare, the number of participants included is modest. The fixed order of investigations with standard of care first followed by combined PET/MRI was required due to institutional constraints on scheduling research studies after standard-of-care imaging. The timing of PET imaging could potentially impact FDG uptake. However, we did not focus on comparison of quantitative FDG uptake between modalities for this reason. Standard-of-care imaging in suspected CS varies by center which would impact radiation dose and time savings compared with combined evaluation with PET/MRI. Finally, a substantial number of individuals with implanted cardiac devices were excluded due to lack of institutional approval as the PET/MRI scanner at our center is not located in a clinical area. There is a growing body of literature to support the safety of MRI in select patients with implanted cardiac devices. Therefore, future larger studies should evaluate the utility of combined PET/MRI in patients with implanted devices (35).

In summary, we found that combined cardiac 18F-FDG PET/MRI had significantly lower total radiation dose and a shorter imaging duration compared with standard-of-care evaluation with separate sequential cardiac MRI, 18F-FDG PET/CT, and 99mTc-sestamibi SPECT perfusion imaging and demonstrated high diagnostic test performance. However, further research is needed to evaluate the cost-effectiveness of this approach while taking into consideration the cost of PET/MRI systems and competing demands with oncologic indications.

Study supported by the Peter Munk Cardiac Centre Innovation Fund and the University of Toronto Joint Department of Medical Imaging academic incentive fund.

Data sharing: Data generated or analyzed during the study are available from the corresponding author by request.

Disclosures of conflicts of interest: C.A.M. No relevant relationships. F.A. No relevant relationships. M.A. No relevant relationships. E.C. No relevant relationships. P.T. No relevant relationships. R.M.I. No relevant relationships. M.B. Advisory board member for AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, and Valeo Pharma; honoraria paid to company from AstraZeneca, Boehringer Ingelheim, GSK, and Valeo Pharma. Y.M. No relevant relationships. J.D.P. Quality improvement grant from Pfizer; honoraria from Abbott Laboratories; clinical expert for the Canadian Agency for Drugs and Technologies in Health in the review of medical therapies seeking indication approval for heart failure; leadership roles with the Transplant Performance Measurement and Evaluation Committee and the Pan-Canadian Organ Donation and Transplantation Data and Performance Reporting System with the Canadian Institute for Health Information. K.H. Funding from Peter Munk Cardiac Centre Innovation Fund and the University of Toronto Joint Department of Medical Imaging academic incentive fund; payment from Sanofi; editorial board member for Radiology and Radiology: Cardiothoracic Imaging.

Abbreviations:

AUC
area under the receiver operating characteristic curve
CS
cardiac sarcoidosis
FDG
fluorodeoxyglucose
LGE
late gadolinium enhancement

References

  • 1. Cheung E , Ahmad S , Aitken M , et al . Combined simultaneous FDG-PET/MRI with T1 and T2 mapping as an imaging biomarker for the diagnosis and prognosis of suspected cardiac sarcoidosis . Eur J Hybrid Imaging 2021. ; 5 ( 1 ): 24 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Kazmirczak F , Chen KA , Adabag S , et al . Assessment of the 2017 AHA/ACC/HRS Guideline Recommendations for Implantable Cardioverter-Defibrillator Implantation in Cardiac Sarcoidosis . Circ Arrhythm Electrophysiol 2019. ; 12 ( 9 ): e007488 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Gilotra N , Okada D , Sharma A , Chrispin J . Management of Cardiac Sarcoidosis in 2020 . Arrhythm Electrophysiol Rev 2020. ; 9 ( 4 ): 182 – 188 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Blankstein R , Osborne M , Naya M , et al . Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis . J Am Coll Cardiol 2014. ; 63 ( 4 ): 329 – 336 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Jones HA , Cadwallader KA , White JF , Uddin M , Peters AM , Chilvers ER . Dissociation between respiratory burst activity and deoxyglucose uptake in human neutrophil granulocytes: implications for interpretation of (18)F-FDG PET images . J Nucl Med 2002. ; 43 ( 5 ): 652 – 657 . [PubMed] [Google Scholar]
  • 6. Ahmadian A , Brogan A , Berman J , et al . Quantitative interpretation of FDG PET/CT with myocardial perfusion imaging increases diagnostic information in the evaluation of cardiac sarcoidosis . J Nucl Cardiol 2014. ; 21 ( 5 ): 925 – 939 . [DOI] [PubMed] [Google Scholar]
  • 7. Slart RHJA , Glaudemans AWJM , Lancellotti P , et al . A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology . J Nucl Cardiol 2018. ; 25 ( 1 ): 298 – 319 . [DOI] [PubMed] [Google Scholar]
  • 8. Coulden RA , Sonnex EP , Abele JT , Crean AM . Utility of FDG PET and Cardiac MRI in Diagnosis and Monitoring of Immunosuppressive Treatment in Cardiac Sarcoidosis . Radiol Cardiothorac Imaging 2020. ; 2 ( 4 ): e190140 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Hanneman K , Kadoch M , Guo HH , et al . Initial Experience With Simultaneous 18F-FDG PET/MRI in the Evaluation of Cardiac Sarcoidosis and Myocarditis . Clin Nucl Med 2017. ; 42 ( 7 ): e328 – e334 . [DOI] [PubMed] [Google Scholar]
  • 10. Vita T , Okada DR , Veillet-Chowdhury M , et al . Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis . Circ Cardiovasc Imaging 2018. ; 11 ( 1 ): e007030 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Hyafil F , Gimelli A , Slart RHJA , et al . EANM procedural guidelines for myocardial perfusion scintigraphy using cardiac-centered gamma cameras . Eur J Hybrid Imaging 2019. ; 3 ( 1 ): 11 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Cerqueira MD , Weissman NJ , Dilsizian V , et al . Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association . Circulation 2002. ; 105 ( 4 ): 539 – 542 . [DOI] [PubMed] [Google Scholar]
  • 13. Vachatimanont S , Sirisalipoch S , Chantadisai M . Comparison of the Diagnostic Performance of Myocardial Perfusion Scintigraphy with and Without Attenuation Correction . Mol Imaging Radionucl Ther 2022. ; 31 ( 2 ): 130 – 138 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Ohira H , Tsujino I , Yoshinaga K . 18F-Fluoro-2-deoxyglucose positron emission tomography in cardiac sarcoidosis . Eur J Nucl Med Mol Imaging 2011. ; 38 ( 9 ): 1773 – 1783 . [DOI] [PubMed] [Google Scholar]
  • 15. Schulz-Menger J , Bluemke DA , Bremerich J , et al . Standardized image interpretation and post-processing in cardiovascular magnetic resonance - 2020 update : Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing . J Cardiovasc Magn Reson 2020. ; 22 ( 1 ): 19 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Robison S , Karur GR , Wald RM , Thavendiranathan P , Crean AM , Hanneman K . Noninvasive hematocrit assessment for cardiovascular magnetic resonance extracellular volume quantification using a point-of-care device and synthetic derivation . J Cardiovasc Magn Reson 2018. ; 20 ( 1 ): 19 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Warnica W , Al-Arnawoot A , Stanimirovic A , et al . Clinical Impact of Cardiac MRI T1 and T2 Parametric Mapping in Patients with Suspected Cardiomyopathy . Radiology 2022. ; 305 ( 2 ): 319 – 326 . [DOI] [PubMed] [Google Scholar]
  • 18. Feldman DR , Rowin EJ , Carrick RT , et al . Cardiac Sarcoidosis Mimicking Hypertrophic Cardiomyopathy: The Importance of Cardiac Magnetic Resonance Imaging . JACC Case Rep 2020. ; 2 ( 13 ): 2060 – 2062 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Hulten E , Aslam S , Osborne M , Abbasi S , Bittencourt MS , Blankstein R . Cardiac sarcoidosis-state of the art review . Cardiovasc Diagn Ther 2016. ; 6 ( 1 ): 50 – 63 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Hanneman K , Faughnan ME , Prabhudesai V . Cumulative radiation dose in patients with hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations . Can Assoc Radiol J 2014. ; 65 ( 2 ): 135 – 140 . [DOI] [PubMed] [Google Scholar]
  • 21. Li Y , Jiang L , Wang H , Cai H , Xiang Y , Li L . Effective Radiation Dose of 18f-Fdg Pet/Ct: How Much Does Diagnostic Ct Contribute? Radiat Prot Dosimetry 2019. ; 187 ( 2 ): 183 – 190 . [DOI] [PubMed] [Google Scholar]
  • 22. Valentin J ; International Commission on Radiation Protection. Managing patient dose in multi-detector computed tomography(MDCT). ICRP Publication 102 . Ann ICRP 2007. ; 37 ( 1 ): 1 – 79 , iii . [DOI] [PubMed] [Google Scholar]
  • 23. Mattsson S , Johansson L , Leide Svegborn S , et al . Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances . Ann ICRP 2015. ; 44 ( 2 Suppl ): 7 – 321 . [Published corrections appear in Ann ICRP 2019;48(1):96 and Ann ICRP 2019;48(1):97.] [DOI] [PubMed] [Google Scholar]
  • 24. ICRP . Radiation dose to patients from radiopharmaceuticals. Addendum 3 to ICRP Publication 53. ICRP Publication 106. Approved by the Commission in October 2007 . Ann ICRP 2008. ; 38 ( 1-2 ): 1 – 197 . [DOI] [PubMed] [Google Scholar]
  • 25. Hiraga HYK , Hiroe M . Diagnostic standard and guidelines for sarcoidosis [in Japanese] . Jpn J Sarcoidosis and Granulomatous Disorders 2007. ; 27 : 89 – 102 . [Google Scholar]
  • 26. Sanchez Tijmes F , Thavendiranathan P , Udell JA , Seidman MA , Hanneman K . Cardiac MRI Assessment of Nonischemic Myocardial Inflammation: State of the Art Review and Update on Myocarditis Associated with COVID-19 Vaccination . Radiol Cardiothorac Imaging 2021. ; 3 ( 6 ): e210252 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Tonkopi E , Ross AA , MacDonald A . JOURNAL CLUB: CT dose optimization for whole-body PET/CT examinations . AJR Am J Roentgenol 2013. ; 201 ( 2 ): 257 – 263 . [DOI] [PubMed] [Google Scholar]
  • 28. Thompson RC , Cullom SJ . Issues regarding radiation dosage of cardiac nuclear and radiography procedures . J Nucl Cardiol 2006. ; 13 ( 1 ): 19 – 23 . [DOI] [PubMed] [Google Scholar]
  • 29. Higgins AR , Jaber W . SPECT and PET MPI: The future has arrived but it is unevenly distributed . J Nucl Cardiol 2020. ; 27 ( 2 ): 417 – 418 . [DOI] [PubMed] [Google Scholar]
  • 30. Aitken M , Davidson M , Chan MV , et al . Prognostic Value of Cardiac MRI and FDG PET in Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis . Radiology 2023. ; 307 ( 2 ): e222483 . [DOI] [PubMed] [Google Scholar]
  • 31. Aitken M , Chan MV , Urzua Fresno C , et al . Diagnostic Accuracy of Cardiac MRI versus FDG PET for Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis . Radiology 2022. ; 304 ( 3 ): 566 – 579 . [DOI] [PubMed] [Google Scholar]
  • 32. Rice JB , White A , Lopez A , et al . Economic burden of sarcoidosis in a commercially-insured population in the United States . J Med Econ 2017. ; 20 ( 10 ): 1048 – 1055 . [DOI] [PubMed] [Google Scholar]
  • 33. Subramanian K , Martinez J , Osborne JR , et al . Access to cardiac PET/CT by sarcoidosis patients and cost-effectiveness analysis of cardiac PET/MR compared to the standard of care . Clin Imaging 2023. ; 94 : 50 – 55 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Bailey DL , Pichler BJ , Gückel B , et al . Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany . Mol Imaging Biol 2018. ; 20 ( 1 ): 4 – 20 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Bhuva AN , Moralee R , Brunker T , et al . Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices . Eur Heart J 2022. ; 43 ( 26 ): 2469 – 2478 . [DOI] [PMC free article] [PubMed] [Google Scholar]

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