Abstract
Purpose
This retrospective study investigates the relationship between cardiac and extra-thoracic sarcoid findings on FDG PET-CT using a 72-hour pretest high-fat, high-protein, and very low-carbohydrate (HFHPVLC) diet.
Patients and methods
A total of 196 consecutive FDG PET-CT scans with 72-hour HFHPVLC diet preparation were performed between December 2014 and December 2015 in known sarcoid patients. Of these scans, 5 were excluded for non-adherence to diet preparation or underlying cancer. Cardiac and extra-thoracic sarcoid lesions were categorized and measured for radiotracer uptake.
Results
A total of 188 patients had 191 eligible FDG PET/CT scans (3 follow-up scans), of which there were 20 (10%) positive, 6 indeterminate (3%), and 165 (86%) negative for CS. Among the 20 scans positive for CS, 8 (40%) had findings of both cardiac and extra-thoracic sarcoid.
Conclusion
Our study shows that 40% of CS patients also have FDG PET-CT findings of extra-thoracic sarcoid. This makes an intriguing case for FDG PET-CT use with pretest diet prep over cardiac MRI (CMR) for cardiac sarcoid evaluation, given that CMR is likely to overlook these extra-thoracic sites of disease.
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Introduction
Sarcoidosis is a systemic granulomatous disease that can affect multiple organs, which is definitively diagnosed with biopsy, usually from skin lesions, pulmonary nodules, or lymph nodes, looking for non-caseating epithelioid-cell granulomas in the absence of organisms or particles.1 Cardiac sarcoidosis (CS) is reported to be symptomatic in only 5% of patients with sarcoidosis,2 but it has been found in 27% of patients at autopsy.3 CS is potentially fatal, and has a wide spectrum of clinical manifestations, including conduction abnormality and sudden death. Diagnosing CS through endomyocardial biopsy is an invasive procedure and has a sensitivity of only 20-30% because it often misses areas of CS involvement, and usually the left ventricle is not accessible for biopsy.4 The diagnosis of CS is therefore challenging and lacking an imaging gold standard. The imaging modality of choice for CS diagnosis is still debated.5,6,-7
The background physiological FDG activity in normal myocardium can interfere with the detection of active CS and is the major hurdle in utilizing FDG PET/CT to diagnose CS.8 Different strategies, including 12-18 hr pretest fasting, pretest administration of unfractionated heparin, and overnight high-fat, low-carbohydrate diet modification, have been proposed to minimize physiological cardiac FDG activity but only with suboptimal results.9,10,11,12,13,14,-15 With the use of a 72-hour pretest high-fat, high-protein, and very low-carbohydrate (HFHPVLC) diet preparation FDG PET-CT protocol,16 we have been able to successfully suppress background FDG uptake in the myocardium and minimize the rate of indeterminate findings to diagnose CS.
As sarcoidosis is a systemic disease, we set to investigate the relationship between cardiac and extra-thoracic sarcoid findings on FDG PET-CT using this protocol. Our aim is to determine if sarcoid patients being evaluated for cardiac involvement would benefit from a more thorough imaging evaluation of the body with FDG PET-CT vs limited thoracic imaging evaluation with cardiac MRI (CMR).
Methods
Patients
The institutional review board (IRB) approved a retrospective study, which initially investigated a total of 196 consecutive FDG PET-CT scans with 72-hour HFHPVLC diet preparation performed between December 2014 and December 2015 with 10-22 months follow-up. Of note, patients in this study include a subset of known sarcoid patients from our prior published series.16 Demographic information for these patients is summarized in Table 1. Of these scans, 5 were excluded for non-adherence to diet preparation (n = 3) and underlying cancer (n = 2) for a total of 191 final included scans. Suspected dietary non-compliance was initially detected by a staff nuclear medicine physician after image acquisition. Patients suspected to be non-compliant were contacted regarding their diet preparation. All 3 suspected non-compliant patients reported non-adherent dietary intake.
Imaging protocol
All patients underwent a 72-hour HFHPVLC diet preparation including breakfast approximately 4 hours before scanning.16 Patients were then asked to fast post breakfast on scan day. The HFHPVLC diet was written as a menu of permitted and prohibited foods. A menu of the diet preparation protocol is shown in Table 2. Patients on steroids for treatment of sarcoidosis and on antidiabetic medication were instructed to hold off these medications for 24 hours before FDG PET/CT and were monitored with serum glucose levels.
All FDG PET/CT examinations were performed on a GE Discovery 690 FDG PET/CT scanner (GE Medical Systems, Milwaukee, WI) using ASNC/SNMMI guidelines.17 All patients had a blood glucose level of less than 200 mg/dL at the time of FDG injection. Dedicated PET/CT scans from the skull base to the upper thighs were obtained 60 to 90 minutes after intravenous injection of 0.370-0.481 GBq of FDG. CT parameters were as follows: 120 kV, 120 mAs, pitch 0.813, 16 × 1.5-mm collimation, slice thickness of 3 mm with an increment of 1.5 mm. CT scan was used for attenuation correction. PET parameters were as follows: 2 min/bed for the non-cardiac fields and 10 min/bed for fields covering the heart. Image acquisition was performed using non-cardiac-gated technique.
Imaging analysis
Quantitative cardiac FDG uptake was measured as SUVmax in the myocardium and compared with SUVmean in the ascending aorta as mediastinal blood pool background. Extra-thoracic sarcoid lesions were categorized and measured for SUVmax and compared to the liver background SUVmean. All the FDG PET-CT studies were retrospectively read, or reread, by 3 imaging physicians. Imaging diagnosis was made based on data from literature9,10,-11,13,14,-15,18,19 and our previous study.16 We visually classified the pattern of cardiac FDG uptake into the following: “none” and “ring-like diffuse at base” (negative for CS),18 “focal”(positive for CS),20 and “diffuse” (indeterminate for CS). A sample case demonstrating the myocardial suppression achieved using the 72-hour HFHPVLC diet protocol is shown in Figure 1. Final diagnoses were made with consensus among imaging physicians and a referring clinician in view of all available comprehensive clinical information and diagnostic test results, including 12-lead ECG, cardiac MRI, echocardiogram, and nuclear stress test, with reference to the modified Japanese Ministry of Health and Welfare criteria.21
Results
A total of 188 patients had 191 eligible FDG PET/CT scans (3 follow-up scans), of which there were 20 (10%) positive, 6 indeterminate (3%), and 165 (86%) negative for CS. Myocardial uptake patterns are summarized in Table 3. The SUVmax of PET positive myocardial lesions ranges from 3.4 to 12.5, while mediastinal blood pool SUVmean ranges from 1.1 to 3.6. All positive myocardial activity was higher than liver background which had an average SUV mean of 2.7 ± 0.6 (SD). Among the 20 scans positive for CS, 8 (40%) had findings of both cardiac and extra-thoracic sarcoid and 12 (60%) had findings of cardiac but no extra-thoracic sarcoidosis. Of the 165 scans negative for CS, 56 (34%) had findings of extra-thoracic sarcoid but no CS, and 109 (66%) were negative for extra-thoracic sarcoidosis. Of the 6 indeterminate scans, 2 (33%) were positive for extra-thoracic sarcoid and 4 (66%) were negative for extra-thoracic sarcoid. These results are summarized in Fig. 2.
Average liver background SUVmean was 2.7 ± 0.6. SUVmax ranges for extra-thoracic organ involvement were as follows: 3.8-4.4 for bone, 3.3-18.7 for liver, 3.1-14.8 for spleen, 3.7-22.8 for extra-thoracic lymph node, and 5.1-14.1 for cutaneous nodules. Extra-thoracic FDG PET-CT findings are summarized in Table 4.
Discussion
Previous studies have established that extra-thoracic sarcoid and CS occur with significant frequency.2,3,22,23,24,25,26,27,28,29,30,-31 Our results show an association between FDG PET-CT findings of extra-thoracic and CS, with 40% of CS patients (8 out of 20 patients) also having extra-thoracic sarcoid, while 60% of CS patients (12 out of 20) had CS without findings of extra-thoracic sarcoid. This makes an intriguing case for using FDG PET-CT over cardiac MRI (CMR) for CS evaluation given that the narrower field of view with CMR is likely to overlook these extra-thoracic sites of disease. An example of extra-thoracic sarcoid lesions in a CS patient which would customarily be outside the field of view and thus non-detectable by CMR is illustrated in Fig. 3.
A prior study by Blankstein et al. shows that the presence of extra-cardiac sarcoid did not alter patients’ prognosis, whereas CS was a prognostic indicator.32 While the presence of extra-cardiac sarcoid may not alter immediate management, it does serve as a way to stage disease and provides a sense of granuloma burden. Identifying extra-cardiac involvement alerts the treating physicians to which symptoms need attention and possible follow-up. Although not the focus of our study, FDG PET-CT also has an added benefit of easily being able to monitor therapeutic response, thus allowing for adjustments in treatment if necessary. A sample case of disease progression after 17-month steroid therapy prompting therapy change is shown in Fig. 4.
Prior meta-analysis has reported sensitivity and specificity of FDG PET-CT for detection of CS at 89% and 78%, respectively.33 This is similar, if not better than prior studies showing CMR sensitivity and specificity of 75%-100% and 76.9%-78%, respectively.34,35 Reservations regarding the use of FDG PET-CT have focused on incomplete myocardial suppression36 which can be interpreted as indeterminate or intermediate evidence for CS. FDG PET-CT using a 72-hour HFHPVLC diet preparation has been shown to be very effective in evaluation of CS.16 The indeterminate rate in our study was only 3%.
Although ours was a retrospective single-center study, it is the largest to date case series comparing the occurrence of CS and extra-thoracic sarcoid and it is the only one using a 72-hour HFHPVLC diet protocol. It reaffirms the association between cardiac and extra-thoracic sarcoid on FDG PET-CT that highlights the benefits of its wide field of view over CMR for CS evaluation.
New Knowledge Gained
When performing FDG PET-CT using a 72-hour HFHPVLC diet preparation for detection of cardiac sarcoid, 40% of patients with cardiac sarcoid patients also have extra-thoracic sarcoid disease. These sites of extra-thoracic disease would be non-detectable on CMR.
Conclusion
Our study shows an association between FDG PET-CT findings of CS and extra-thoracic sarcoidosis. This makes an intriguing case for FDG PET-CT use with 72-hour pretest HFHPVLC diet preparation over MRI for cardiac sarcoid evaluation given that CMR is likely to overlook these extra-thoracic sites of disease. If cardiac involvement is the only clinical concern, then cardiac PET or CMR might be considered as the imaging modality of choice. However, for more complete disease extent evaluation, the expanded field of view from skull base to thigh achieved with full body FDG PET-CT would provide complete evaluation of disease extent. For this reason, in these cases where extra-thoracic disease is suspected or complete extent of disease is unknown, preference may be given to FDG PET-CT with 72-hour HFHPVLC diet preparation over MRI for cardiac sarcoid evaluation.
Abbreviations
- HFHPVLC:
-
High-fat, high-protein, and very low-carbohydrate
- CS:
-
Cardiac sarcoid
- CMR:
-
Cardiac MRI
- IRB:
-
Institutional review board
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All the authors, Darshan C. Patel, Senthil S. Gunasekaran, Christopher Goettl, Nadera J. Sweiss, and Yang Lu, state that they have nothing to disclose.
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Patel, D.C., Gunasekaran, S.S., Goettl, C. et al. FDG PET-CT findings of extra-thoracic sarcoid are associated with cardiac sarcoid: A rationale for using FGD PET-CT for cardiac sarcoid evaluation. J. Nucl. Cardiol. 26, 486–492 (2019). https://doi.org/10.1007/s12350-017-0962-4
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DOI: https://doi.org/10.1007/s12350-017-0962-4