In accordance with the latest recommendations on clinical indications for cardiac PET/MR,6,7 we prospectively included patients older than 15 years referred to the nuclear medicine department for PET to evaluate myocardial viability, cardiac masses, or endocarditis, and to the cardiac imaging unit for MR to assess myocardial viability in known coronary disease or inconsistent findings in other ischemia screening tests, to evaluate cardiac masses and inflammatory or infiltrative heart disease, or to assess endocarditis with an inconclusive diagnosis on echocardiography. We excluded patients with electrical devices or claustrophobia, pregnant women, and those with a persistent glucose concentration >200mg/dL following the PET scan preparation requirements. Before programming the PET/MR study, patients were classified into 2 groups: a) a coronary group when the examination was destined to assess myocardial viability, and b) a noncoronary group when the study was performed to assess inflammatory/infiltrative heart disease, a cardiac mass, or endocarditis. This was done to provide suitable pretest preparation, as a patient's preparation requirements differ according to the imaging protocol assigned. The study was approved by the local hospital ethics committee.

The radiotracer used was 18F-fluorodeoxyglucose (18F-FDG) because of its widespread availability and long half-life, following a described method.7 Patients in the coronary group fasted for 12hours, and based on the pre-test blood glucose level, were administered an oral overload of glucose or insulin, according to the protocol (figure 1 of the supplementary data). Patients in the noncoronary group received a carbohydrate-free, fat-rich diet during the previous 24hours and were given an intravenous dose of unfractionated heparin at 50 IU/kg before the study. In each case, the calculated 18F-FDG dose was adjusted to the patient's weight and the extent of the PET scan, and patients waited at rest for 45minutes after the injection to avoid extracardiac uptake. The radiation administered was in accordance with the recommendations derived from current radioprotection laws and the ALARA (As Low As Reasonably Achievable) precept.8

Image acquisition was done on an integrated 3T MR and PET system (Biograph mMR, Siemens Healthcare, Germany),9 with HD technology, 16-channel surface coils, and cardiac synchronization. The PET/MR study began with attenuation correction sequences. Cardiac PET was then planned to include the area from the aortic arch to the upper border of the diaphragm (12cm, with an approximate duration of 30minutes). Last, multiparametric MR sequences7 were performed simultaneously with PET. These included cine sequences (SSFP) and short-axis delayed-enhancement sequences at 10minutes following Gadovist (0.2 mmol/kg) injection, with coverage from the base to apex of the heart. In addition, based on the clinical indication, T1- or T2-weighted turbo spin echo, perfusion, and valvular phase contrast sequences were added to the protocol. In some cases directed toward assessing endocarditis, full-body PET/MR was included.10

The MR, PET, and fused PET/MR images were analyzed by diagnostic imaging specialists using the Syngo.via program (Siemens Healthineers, Germany). Initially, each MR study was assessed by cardiologists and each PET study by nuclear medicine specialists separately, and then, the PET/MR analysis was performed together. In the MR cine images, the epicardial and endocardial contours of each short-axis view of the left ventricle were traced manually to calculate the volumes and heart function (Simpson method). Dilatation, hypertrophy, and segmental abnormalities were assessed using the 17-segment model of the American Heart Association,11 and the anatomic location/extent of lesions, valve function, T1/T2 hyperintensities, and perfusion patterns were determined according to the indication. Gadolinium uptake was defined as areas of hyperenhancement on delayed images relative to enhancement of the normal myocardium in each of the 17 myocardial segments by subjective evaluation, a highly reproducible method used in daily practice in most imaging units.12 Segments were considered to have a subendocardial pattern when the extent of enhancement was <50% (viable myocardium), an intermediate pattern when the extent of transmural enhancement was 50% to 75% (viability inconclusive),14 and a transmural pattern when enhancement was 75% to 100% (nonviable).13,14 In PET images, preserved metabolism was established on 18F-FDG uptake >50% (viable myocardium) and severe hypometabolism on uptake <50% (viability inconclusive); no uptake indicated nonviable myocardium.15,16 A segment-by-segment analysis was carried out to determine agreement between the viability findings of PET and MR for the 17 myocardial segments, and a patient-by-patient analysis to facilitate translation of the results to real-life practice, in which decisions are made for each individual patient. To establish viability and nonviability in each case, we used the extent of enhancement and regional and overall contractility on MR, and the degree of metabolism on PET.17,18 A study was considered inconclusive for myocardial viability when at least 2 segments showed intermediate enhancement on MR or severe hypometabolism on PET,17,18 and for noncoronary disease when PET or MR separately did not provide sufficient information to reach an imaging diagnosis. Lastly, PET/MR was considered useful when the simultaneous combination of imaging findings (contractility, segmental abnormalities, myocardial thinning, late enhancement, and metabolism) and the interaction between imaging specialists (cardiology and nuclear medicine) improved the diagnosis achieved with MR or PET separately, or helped with the patient's treatment. To further evaluate the diagnostic accuracy of the PET/MR study, the diagnosis was confirmed by clinical follow-up.

Categorical values were compared using the Wilcoxon test and expressed as number and percentage, whereas continuous variables were compared with the Mann-Whitney U test and expressed as the mean±standard deviation. Statistical analyses were performed using SPSS version 21. The kappa concordance index was used to assess interobserver variability between 2 experienced diagnostic imaging specialists to qualitatively determine the usefulness of integrated PET/MR findings vs PET or MR results separately in each patient.

The analysis included 323 myocardial segments, in which contractility, enhancement, and 18F-FDG uptake (table 2) were evaluated. In total 26.9% (87/323) of segments showed abnormalities, mainly hypokinesia in 57.5% (50/87). Enhancement was detected in 21.7% (70/323), including intermediate enhancement in 7.4% (24/323) and transmural enhancement in 9.9% (32/323). In the PET images, 7.7% (25/323) of segments showed severe hypometabolism and 12.4% (40/323) no uptake. Comparison of the MR and PET findings, yielded agreement in 79.3% (256/323) of segments, with a similar prevalence of segments with inconclusive results for viability. An analysis of the inconclusive segments on MR (intermediate enhancement) was performed to assess the usefulness of fusion with PET, and 75% of them (18/24) showed preserved metabolism. In a subanalysis, 16/24 inconclusive segments showed transmurality closer to 50% and all were viable on PET, whereas 8/24 showed transmurality closer to 75% and all segments except 2 were nonviable on PET.

In the patient-by-patient analysis, MR studies yielded a diagnosis of myocardial viability in 7 patients and nonviability in 4, with 8 inconclusive studies, whereas PET findings indicated viability in 4 patients and nonviability in 7, with 8 inconclusive studies (table 3). In the comparison of MR and PET separately, there were 9 discordant cases: in 3 patients (cases 1, 20, and 44), MR indicated viability based on preserved contractility and absent or minimal enhancement, whereas PET was inconclusive; in 5 other patients (cases 12, 16, 41, 45, and 46), the hybrid technique was helpful by integrating segmental abnormalities, intermediate enhancement, and 18F-FDG uptake <50%; and in 1 patient (case 19) the data obtained were inconsistent. In 4 patients the diagnosis was inconclusive by both MR and PET (cases 2, 8, 14, and 43) and fusion was helpful in 3 of them. In 6 patients (cases 5, 9, 15, 37, 38, and 40) PET/MR did not provide additional information. Therefore, integrated PET/MR was useful in 42.1% (8/19) of patients in the coronary group. Among cases in which the diagnosis was inconclusive by MR (n=8) or by PET (n=8), PET/MR reclassified 87.5% (7/8) to a conclusive diagnosis with respect to MR and 87.5% (7/8) with respect to PET; that is, 87.5% (14/16) of inconclusive cases by both techniques. The contribution of PET/MR in the diagnosis of myocardial viability in our series is shown in figure 3.

Figure 3.

Added value of PET/MR in the diagnosis of myocardial viability. MR, magnetic resonance; PET, positron emission tomography.

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PET/MR was useful in 88.9% (16/18) of studies: in 13 it provided additional data for the diagnosis and in 3 it aided a biopsy procedure. There was no added value in only 2 patients, 1 with myocarditis (case 34, because of redundant information) and 1 with native valve endocarditis (case 39). The case-by-case usefulness of PET/MR is shown in table 3. MR suggested malignant disease in 2 cases of tumors, but without conclusive metabolic information, whereas PET provided information in 6 patients, although spatial resolution was limited to assess anatomic extent and cardiac infiltration; hence, fusion with MR images was required. None of the 6 patients with suspected endocarditis had an inconclusive diagnosis on MR imaging. PET provided information in 5 of these patients, but fusion with MR was needed because of poor resolution; in addition MR provided information on valvular and ventricular function, and possible perivalvular complications. In patients with myocarditis, MR was useful in 1 of the 3 cases included and PET was helpful in 2 by showing active foci; anatomic fusion with MR was also beneficial. The performance of each technique separately was poor in infiltrative disease and pericardial disease, whereas integration of anatomic and metabolic images was helpful for guiding biopsy and ruling out active disease. In summary, MR yielded 83.3% (15/18) of inconclusive cases and PET 27.8% (5/18), with high diagnostic value. Among the inconclusive cases by MR or PET, PET/MR reclassified 80% (12/15) to a conclusive diagnosis with respect to MR and 40% (2/5) with respect to PET. That is 70% (14/20) of inconclusive cases by both techniques (figure 4).

Figure 4.

Added value of PET/MR in the diagnosis of noncoronary disease. MR, magnetic resonance; PET, positron emission tomography.

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Agreement was found to be excellent in the analysis comparing PET/MR findings vs the results of PET or MR alone in individual patients in both the groups studied (κ=0.913). Furthermore, in 10 patients in the coronary group and 16 in the noncoronary group with diagnostic confirmation over follow-up, PET/MR provided an accurate diagnosis in 8 (80%) and 14 (87.5%) patients, respectively (table 2 of the supplementary data). Hence, agreement was high between the viability diagnosis provided by PET/MR and the findings on clinical follow up in the coronary group and the same was true for the findings in noncoronary patients.

Among the limitations of the study, we mention the difficulty of defining a patient's condition as being viable or nonviable because the cardiac segments analyzed could have different degrees of transmurality or metabolism. However, we sought a simple classification system to facilitate interpretation of the findings and comparison between the techniques when offering a diagnosis to guide a patient's treatment, as is done in clinical practice. Discrepancies in which segments showed hypometabolism and no enhancement may be related to the poor spatial resolution of PET, which tends to magnify hypocaptant areas when evaluated only by this technique.7 In these cases, MR provides better definition of the extent of damage; thus, spatial resolution is improved by combined PET/MR.

The design of our analysis (comparison of MR and PET studies evaluated separately with the PET/MR study by consensus) could be considered a limitation, as joint image reading might make it difficult to separate the value of the technique itself from the added value of the interaction between imaging specialists. However, this type of analysis reflects standard practice in the interpretation of hybrid studies that implicate different imaging modalities.

Another limitation is the small number of studies included and the technical problems of the raw PET data a posteriori in relation to the learning curve, inherent to a new technology. Nonetheless, we believe it is of interest to describe our experience considering the limited available evidence on the clinical and scientific development of PET/MR in cardiology, this being the first published experience in Spain.

Although the inclusion of diverse diseases (coronary and noncoronary) in the same study may seem to be a weakness, with the added difficulty of there being no single reference pattern common to all of them, our objective was to evaluate the usefulness of PET/MR in clinical practice and contribute to consolidating its indications in cardiology, which are still to be defined. The diagnostic confirmation over follow-up enabled evaluation of the diagnostic performance of PET/MR. In the future it will be necessary to carry out cost-effectiveness studies with a larger number of patients and a longer follow-up to monitor clinical and experimental situations where this new diagnostic tool can provide the greatest benefits and cost value.