Advances in Diagnostic Imaging for Cardiac Sarcoidosis

Sarcoidosis is a systemic granulomatous disease of unknown etiology, and its clinical presentation depends on the affected organ. Cardiac sarcoidosis (CS) is one of the leading causes of death among patients with sarcoidosis. The clinical manifestations of CS are heterogeneous, and range from asymptomatic to life-threatening arrhythmias and progressive heart failure due to the extent and location of granulomatous inflammation in the myocardium. Advances in imaging techniques have played a pivotal role in the evaluation of CS because histological diagnoses obtained by myocardial biopsy tend to have lower sensitivity. The diagnosis of CS is challenging, and several approaches, notably those using positron emission tomography and cardiac magnetic resonance imaging (MRI), have been reported. Delayed-enhanced computed tomography (CT) may also be used for diagnosing CS in patients with MRI-incompatible devices and allows acceptable evaluation of myocardial hyperenhancement in such patients. This article reviews the advances in imaging techniques for the evaluation of CS.


Introduction
Sarcoidosis is an inflammatory granulomatous disease of unknown etiology that can affect any organ, including the lungs, lymphatic system, skin, eyes, and heart [1]. Cardiac sarcoidosis (CS) is clinically recognized in approximately 5% of patients with systemic sarcoidosis, whereas CS has been recorded in at least 25% of autopsy or imaging studies [2,3]. The incidence and prevalence of CS vary substantially over different geographical regions and ethnic groups. An autopsy series of patients with systemic sarcoidosis showed that approximately 27% from the United States and 80% from Japan were revealed to have CS [4]. CS is a potentially life-threatening condition that can lead to conduction disturbances, such as atrial and ventricular arrhythmias and heart failure. Therefore, screening for CS, including medical interviews, physical examinations, and electrocardiography (ECG), is recommended for patients newly diagnosed with sarcoidosis [1].
The presentation of CS varies from asymptomatic to chest pain, dyspnea, syncope, palpitations, and sudden cardiac death. Endomyocardial biopsies are highly specific for the diagnosis of CS, but their sensitivity is not very high; therefore, findings on cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) are used for clinical diagnosis [4]. Recent studies have demonstrated that advanced cardiac imaging with CMR or PET can be useful not only for diagnosis but also for monitoring and predicting adverse cardiovascular events. In addition to visual evaluations, various quantitative evaluations have been proposed, and new imaging and analysis methods are also attracting attention. This article reviews the advances in imaging techniques for the evaluation of CS.  [11,12].

Histological diagnosis group
Cardiac sarcoidosis is confirmed when endomyocardial biopsy specimens demonstrate noncaseating epithelioid cell granulomas with a histological or clinical diagnosis of extracardiac sarcoidosis.

Clinical diagnosis group
Cardiac sarcoidosis is confirmed when, despite the absence of noncaseating epithelioid cell granulomas on endomyocardial biopsy specimens, extracardiac sarcoidosis is diagnosed histologically or clinically and the following conditions and the following diagnostic criteria are satisfied: (a) Two or more of the five major criteria are met; OR (b) One of the five major criteria and two or more of the three minor criteria are met. Major criteria (1) Advanced atrioventricular block or sustained ventricular tachycardia.
(3) Endomyocardial biopsy: interstitial fibrosis or monocyte infiltration of moderate grade.   LGE and FDG uptake in the LV and RV myocardium were detected. The physiological myocardial FDG uptake was suppressed. The MIP image also shows several regions of FDG uptake in the right supraclavicular, mediastinum, hilar, and abdominal lymph nodes. MIP images of post-anti-inflammatory therapy show that the uptake of some lymph nodes persisted, but abnormal cardiac accumulation was almost decreased (B). MIP, maximum intensity projection; FDG, 18 F-fluorodeoxyglucose; PET, positron emission tomography; MRI, magnetic resonance imaging; LGE, late gadolinium enhancement; LV, left ventricular; RV, right ventricular. LGE and FDG uptake in the LV and RV myocardium were detected. The physiological myocardial FDG uptake was suppressed. The MIP image also shows several regions of FDG uptake in the right supraclavicular, mediastinum, hilar, and abdominal lymph nodes. MIP images of post-anti-inflammatory therapy show that the uptake of some lymph nodes persisted, but abnormal cardiac accumulation was almost decreased (B). MIP, maximum intensity projection; FDG, 18 F-fluorodeoxyglucose; PET, positron emission tomography; MRI, magnetic resonance imaging; LGE, late gadolinium enhancement; LV, left ventricular; RV, right ventricular.

FDG-PET
FDG-PET is now routinely used to assess the infiltration of sarcoidosis in the myocardium. FDG is a glucose analog, and its uptake is associated with the expression of glucose transporters (GLUTs). Increased uptake of FDG in inflammatory diseases, including sarcoidosis, can be attributed to the activation of inflammatory cells, such as macrophages, lymphocytes, and granulocytes, with increased levels of GLUT.
The pitfall of using FDG-PET for evaluation of CS is that living myocardial cells also use glucose as their energy source. Therefore, physiological myocardial FDG uptake often makes it difficult to detect active CS lesions. Patients with suspected CS require adequate preparation, such as prolonged fasting, a low-carbohydrate diet, and/or a high-fat, highprotein diet to suppress the false-positive association with physiological myocardial FDG uptake ( Figure 2) ( Table 4) [13][14][15]. Sample foods for dietary preparation prior to FDG-PET scan are well summarized in the Japanese Society of Nuclear Cardiology recommendation [13]. Multivariate analysis of patients without cardiac disease, including the factors such as body mass index, fasting blood sugar, gender, age, and long fasting, demonstrated that only long fasting was independently associated with the suppression of physiological FDG uptake [16]. Measurement of serum free fatty acid levels at the injection of FDG can be used to determine whether the uptake was physiological [17]. Typical patterns of FDG accumulation in CS are focal and focal-on-diffuse in the myocardium, which often corresponds to a decrease in myocardial perfusion [13]. FDG-PET with an adequate preparation protocol is ideal for detecting active lesions and assessing the response to anti-inflammatory therapy in patients with CS [18]. The inter-observer interpretation of cardiac FDG uptake patterns was improved by proper dietary preparation [19]. A metaanalysis of data collected from 891 patients showed that PET or PET/CT had a pooled sensitivity of 84% and a pooled specificity of 83% for diagnosing CS [20]. In particular, the specificity of FDG in the detection of CS varies and is relatively low compared with its sensitivity. Possible explanations for this include nonspecific physiological uptake, uptake of other myocardial diseases such as ischemic disease and hypertrophic cardiomyopathy, and early-stage sarcoid lesions in patients who do not meet the diagnostic criteria for CS. Cardiac PET enhances the prognostic assessment of patients with suspected CS. Blankstein et al. showed that patients with abnormal FDG uptake and focal perfusion defects had a higher risk of death or ventricular tachycardia in their retrospective study of 118 patients with known or suspected CS [21].  Focal FDG uptake in the right ventricle (RV) is more reliable for the diagnosis of CS because physiological FDG uptake in the RV is less frequently observed than in the LV [22]. FDG uptake by the RV is associated with positive endomyocardial biopsy findings in patients with CS [23]. Assessment of RV FDG uptake provides useful information for diagnosing CS and predicting cardiac events. CS with FDG uptake in the RV is associated with subsequent death or ventricular tachycardia (VT) [21].  Focal FDG uptake in the right ventricle (RV) is more reliable for the diagnosis of CS because physiological FDG uptake in the RV is less frequently observed than in the LV [22]. FDG uptake by the RV is associated with positive endomyocardial biopsy findings in patients with CS [23]. Assessment of RV FDG uptake provides useful information for diagnosing CS and predicting cardiac events. CS with FDG uptake in the RV is associated with subsequent death or ventricular tachycardia (VT) [21].

Quantitative Analysis of FDG-PET Findings
PET enables quantitative estimation of disease activity in vivo. Semi-quantitative methods, SUV measurement, and especially SUVmax evaluations, are most frequently used to assess the degree of FDG uptake. SUV is the ratio of the tissue radioactivity concentration divided by the injected dose and body weight. When fasting for over 18 h followed a low-carbohydrate diet, quantification of myocardial SUVmax provided higher diagnostic accuracy for diagnosing CS in comparison with visual analysis [24]. The pretreatment FDG uptake index, defined as the product of the SUVmax and the number of LV segments with abnormal uptake, was a predictor of the response to immunosuppressive therapy in patients with CS [25].
SUVmax is a simple measurement, and the SUVmax value reflects only the value of a single voxel that is hampered by physical, biological, and technical processes and does not reflect the metabolism of the entire target lesion. Cardiac metabolic volume (CMV) and cardiac metabolic activity (CMA) have emerged as volume-based parameters, which are mainly useful for assessing active CS lesions [17,26]. CMV is a measurement of the volume with a high metabolism in the myocardium within a given boundary determined by a threshold, such as the liver uptake and the blood pool SUV (Figure 3). On the other hand, CMA is defined as the product of the mean SUV and the CMV. Osborne et al. reported that a reduction in SUVmax and CMV after immunotherapy was associated with improvement in the left ventricular ejection fraction (LVEF) [27]. Ahmadian et al. reported that CMA was greater in patients with lower LVEF and that an elevated CMA preceded adverse clinical events in their study of CS [26].
An alternative method to assess CS that employs quantitative evaluation of the heterogeneity of myocardial FDG uptake has been proposed by several groups [28][29][30]. Quantitative measures of the coefficient of variation (COV) of myocardial FDG uptake provide an incremental diagnostic and prognostic advantage in CS patients. Tahara et al. reported that the standard deviation and COV were significantly higher in patients with CS than in control participants, sarcoidosis patients without cardiac lesions, and dilated cardiomyopathy patients [28]. Recently, the textural features of FDG-PET images of CS have been studied for their diagnostic and prognostic value [31,32]. The quantitative assessment of FDG uptake heterogeneity may be reflected in the inhomogeneous formation of noncaseating granulomas in the myocardium of patients with CS. Novel semiconductor PET/CT with high temporal and spatial resolution enables a more detailed distribution evaluation of CS [33,34]. An alternative method to assess CS that employs quantitative evaluation of the heterogeneity of myocardial FDG uptake has been proposed by several groups [28][29][30]. Quantitative measures of the coefficient of variation (COV) of myocardial FDG uptake provide an incremental diagnostic and prognostic advantage in CS patients. Tahara et al. reported that the standard deviation and COV were significantly higher in patients with CS than in control participants, sarcoidosis patients without cardiac lesions, and dilated cardiomyopathy patients [28]. Recently, the textural features of FDG-PET images of CS have been studied for their diagnostic and prognostic value [31,32]. The quantitative assessment of FDG uptake heterogeneity may be reflected in the inhomogeneous formation of noncaseating granulomas in the myocardium of patients with CS. Novel semiconductor PET/CT with high temporal and spatial resolution enables a more detailed distribution evaluation of CS [33,34].

The Other Tracers
Although FDG-PET provides high diagnostic value for the detection of active CS, physiological accumulation may occasionally make it difficult to determine whether the finding is pathological or not. Several other PET tracers without physiological myocardial uptake have been used to evaluate CS. Somatostatin receptors (SSTRs) are known to be present in inflammatory cells, including granuloma macrophages, epithelioid cells, and giant cells [35]. Therefore, 68 Ga-DOTA-Tyr-octreotide (DOTATOC), which is a PET tracer that targets SSTRs, is used to assess sarcoidosis [36,37] (Table 5). 18 F-fluoromisonidazole (FMISO) is a PET tracer that accumulates in hypoxic tissues. Increased FMISO uptake has been reported in patients with suspected CS [38]. A small prospective study demonstrated that FMISO-PET has the potential to detect hypoxic lesions of CS without physiological

The Other Tracers
Although FDG-PET provides high diagnostic value for the detection of active CS, physiological accumulation may occasionally make it difficult to determine whether the finding is pathological or not. Several other PET tracers without physiological myocardial uptake have been used to evaluate CS. Somatostatin receptors (SSTRs) are known to be present in inflammatory cells, including granuloma macrophages, epithelioid cells, and giant cells [35]. Therefore, 68 Ga-DOTA-Tyr-octreotide (DOTATOC), which is a PET tracer that targets SSTRs, is used to assess sarcoidosis [36,37] (Table 5). 18 F-fluoromisonidazole (FMISO) is a PET tracer that accumulates in hypoxic tissues. Increased FMISO uptake has been reported in patients with suspected CS [38]. A small prospective study demonstrated that FMISO-PET has the potential to detect hypoxic lesions of CS without physiological myocardial uptake [39]. 3 -Deoxy-3-[ 18 F]-fluorothymidine (FLT) is another PET tracer used to evaluate cellular proliferative activity. Although FLT uptake is significantly lower than that of FDG, FLT PET/CT can detect cardiac and extracardiac sarcoidosis [40]. Martineau et al. examined the relationship between FLT, FDG, and perfusion PET imaging in patients with CS [41]. They hypothesized that FLT might identify areas likely to develop myocardial scarring due to the strong correlation between FLT uptake and perfusion defects.

Late Gadolinium Enhancement
Gadolinium-based contrast agents are distributed within the extracellular space of the myocardium, and their distribution is influenced by different regional conditions such as edema, scar tissue, fibrosis, and necrosis. Evaluation of LGE on CMR is a basic technique used for tissue characterization, particularly fibrosis and scar formation in the myocardium, and is an essential tool for assessing CS (Figure 4). Although the presence of LGE is a non-specific finding, the appearance of mid-wall and/or epicardial LGE sparing the subendocardium in the basal heart, particularly the septum and lateral wall, may increase the specificity for the diagnosis of CS [42][43][44][45]. A meta-analysis of data collected from 649 participants with histologically proven extra-cardiac sarcoidosis and/or with a suspicion of CS showed that CMR had a pooled sensitivity of 93% and a pooled specificity of 85% for diagnosing CS [46]. The findings showing contiguous extension to the right ventricle was also a typical pattern for CS [47]. The presence of LGE on CMR is known to be an independent predictor of all-cause mortality and adverse cardiovascular events in sarcoidosis patients [48,49]. Conversely, the prognosis is favorable for patients without abnormal LGE on CMR. A quantitative method to estimate the LGE percentage of LV mass has been proposed, and a large extent of LGE correlates with a high incidence of adverse outcomes in patients with CS [50]. According to a retrospective cohort study by Kazmirczak et al., patients with LGE extent > 5.7% had high annualized event rates [51]. used to evaluate cellular proliferative activity. Although FLT uptake is significantly lower than that of FDG, FLT PET/CT can detect cardiac and extracardiac sarcoidosis [40]. Martineau et al. examined the relationship between FLT, FDG, and perfusion PET imaging in patients with CS [41]. They hypothesized that FLT might identify areas likely to develop myocardial scarring due to the strong correlation between FLT uptake and perfusion defects.

Late Gadolinium Enhancement
Gadolinium-based contrast agents are distributed within the extracellular space of the myocardium, and their distribution is influenced by different regional conditions such as edema, scar tissue, fibrosis, and necrosis. Evaluation of LGE on CMR is a basic technique used for tissue characterization, particularly fibrosis and scar formation in the myocardium, and is an essential tool for assessing CS (Figure 4). Although the presence of LGE is a non-specific finding, the appearance of mid-wall and/or epicardial LGE sparing the subendocardium in the basal heart, particularly the septum and lateral wall, may increase the specificity for the diagnosis of CS [42][43][44][45]. A meta-analysis of data collected from 649 participants with histologically proven extra-cardiac sarcoidosis and/or with a suspicion of CS showed that CMR had a pooled sensitivity of 93% and a pooled specificity of 85% for diagnosing CS [46]. The findings showing contiguous extension to the right ventricle was also a typical pattern for CS [47]. The presence of LGE on CMR is known to be an independent predictor of all-cause mortality and adverse cardiovascular events in sarcoidosis patients [48,49]. Conversely, the prognosis is favorable for patients without abnormal LGE on CMR. A quantitative method to estimate the LGE percentage of LV mass has been proposed, and a large extent of LGE correlates with a high incidence of adverse outcomes in patients with CS [50]. According to a retrospective cohort study by Kazmirczak et al., patients with LGE extent > 5.7% had high annualized event rates [51].  Nevertheless, the presence of LGE cannot distinguish between active inflammation and chronic fibrotic changes. In this regard, a high signal intensity on T2-weighted images reflects active inflammation due to the indication of edema [52]. Tonegawa-Kuji et al. analyzed T2-weighted short-tau-inversion-recovery black-blood imaging data by measuring the myocardium-to-spleen ratio and concluded that semi-quantitative analysis was useful for the detection of active CS [53]. Currently, the development of novel techniques for CMR imaging, such as T1 and T2 mapping, has the potential to allow assessment of CS. The ECV fraction was calculated using pre-and post-enhanced T1 mapping. T1 and T2 native values are directly estimated by mapping sequences that allow reliable tissue characterization of the myocardium. Previous reports have shown that T1 and T2 values are longer in patients with systemic sarcoidosis than in healthy individuals [54,55]. T1 and T2 mapping may also be useful for recognizing cardiac involvement in patients with systemic sarcoidosis. T1 and T2 values can also be used for monitoring disease activity because these values are reduced by anti-inflammatory treatment [54].

Integrated PET/MRI
The hybrid PET/MRI system is a novel instrument that allows simultaneous data acquisition by combining functional, structural, and molecular imaging in a single scan [56]. Several studies have evaluated the utility of PET/MRI for the evaluation of CS [57][58][59][60]. Wisenberg et al. showed that PET/CT and PET/MRI provided similar diagnostic data for FDG uptake in a same-day protocol in 10 CS patients [58]. Comprehensive imaging with cardiac PET/MRI holds great promise for providing further insights regarding the disease process underlying CS. The combination of information on active inflammation from FDG-PET and fibrotic scars from LGE on MRI can provide incremental value in the development of therapeutic strategies for CS [57]. Wicks et al. assessed the diagnostic and prognostic utility of simultaneous cardiac PET/MRI in 51 consecutive patients with suspected CS. In their results, hybrid PET/MRI was superior to PET and MRI alone for detecting CS, and the presence of LGE and FDG uptake on PET/MRI was a predictor of major adverse cardiac events [59]. More recently, Guelich et al. demonstrated the utility of T1 and T2 mapping in addition to LGE in hybrid PET/MRI for the identification of active CS [60]. Thus, hybrid PET/MRI may have implications for the assessment of disease presence, activity, and prognosis in CS in a single examination.

Regional Myocardial Function
Cardiac involvement of sarcoidosis can show different manifestations ranging from early active granuloma to inactive scars in the myocardium [61]. This heterogeneity can also reflect the dyssynchrony of left ventricular wall motion. A recent meta-analysis of speckletracking echocardiography data demonstrated that left ventricular global longitudinal and circumferential strain, which represent the change in length in proportion to the baseline length from longitudinal and circumferential directions, was significantly lower in patients with extracardiac sarcoidosis but without any cardiac symptoms [62]. Assessment of global and regional ventricular function is one of the important functions of CMR. Accurate and reproducible measurements of left ventricular (LV) ejection fraction (EF) and LV volume are possible using CMR. Myocardial tissue-tracking imaging techniques, such as tagging, strain-encoded MRI, and myocardial feature-tracking deformation imaging, are useful for measuring regional myocardial contractile function ( Figure 5). These CMR-derived strain parameters have the potential to facilitate early detection and prediction of disease outcome in patients with CS [63,64]. Velangi et al. reported that RV systolic dysfunction was present in 12.1% of 290 patients with sarcoidosis with known or suspected CS, and RV systolic dysfunction was independently associated with all-cause death [65] (Table 6).  Figure 1. Each regional strain is presented in the same colored curve, and the white curve represents the average of all regions. Inhomogeneous longitudinal strain due to cardiac sarcoidosis not only in the LV wall but also in the RV wall. LV, left ventricular; RV, right ventricular. PET-derived phase-analysis data can improve the sensitivity of scar detection in CS [66]. Phase analysis on gated PET [66] and single-photon emission computed tomography (SPECT) [67] images also has the potential to add incremental diagnostic or predictive value for patients with CS.  PET-derived phase-analysis data can improve the sensitivity of scar detection in CS [66]. Phase analysis on gated PET [66] and single-photon emission computed tomogra-phy (SPECT) [67] images also has the potential to add incremental diagnostic or predictive value for patients with CS.

Computed Tomography
Coronary CT angiography is useful for excluding coronary artery disease in patients with suspected CS. Furthermore, delayed-phase contrast-enhanced CT, which is often performed 6-15 min after contrast injection, can be used to detect cardiac involvement in patients with systemic sarcoidosis in a manner similar to CMR ( Figure 6) [5]. The iodine-based CT contrast material accumulates in the myocardial scar in a manner similar to gadolinium-based CMR contrast material [68]. Therefore, contrast-enhanced CT has the potential to serve as a "one-stop shop" for evaluation of coronary artery disease, systemic disease, and cardiac involvement in patients with sarcoidosis [69]. Delayed-enhanced CT can also be performed for patients with MRI-incompatible devices. We previously demonstrated that the image quality of delayed-enhanced CT is acceptable for evaluation of myocardial hyperenhancement in patients with or without implantable devices [5]. The disadvantages of contrast-enhanced CT are the relative contraindication to chronic kidney disease and the lower contrast-to-noise ratio in comparison with LGE-CMR [70]. Low tube voltage CT scanning with iterative model reconstruction [5] or virtual monochromatic imaging in dual-energy CT [71] may offer a more accurate assessment of myocardial hyperenhancement in this setting. Statistical texture analysis-based approaches have emerged as more objective and reproducible methods than visual assessment for detecting myocardial hyperenhancement in delayed-enhanced CT [72].

Computed Tomography
Coronary CT angiography is useful for excluding coronary artery disease in patients with suspected CS. Furthermore, delayed-phase contrast-enhanced CT, which is often performed 6-15 min after contrast injection, can be used to detect cardiac involvement in patients with systemic sarcoidosis in a manner similar to CMR ( Figure 6) [5]. The iodinebased CT contrast material accumulates in the myocardial scar in a manner similar to gadolinium-based CMR contrast material [68]. Therefore, contrast-enhanced CT has the potential to serve as a "one-stop shop" for evaluation of coronary artery disease, systemic disease, and cardiac involvement in patients with sarcoidosis [69]. Delayed-enhanced CT can also be performed for patients with MRI-incompatible devices. We previously demonstrated that the image quality of delayed-enhanced CT is acceptable for evaluation of myocardial hyperenhancement in patients with or without implantable devices [5]. The disadvantages of contrast-enhanced CT are the relative contraindication to chronic kidney disease and the lower contrast-to-noise ratio in comparison with LGE-CMR [70]. Low tube voltage CT scanning with iterative model reconstruction [5] or virtual monochromatic imaging in dual-energy CT [71] may offer a more accurate assessment of myocardial hyperenhancement in this setting. Statistical texture analysis-based approaches have emerged as more objective and reproducible methods than visual assessment for detecting myocardial hyperenhancement in delayed-enhanced CT [72]. LGE can also reveal obvious hyperintensity areas consistent with CT. Higher ECV values corresponded to LGE.

Conclusions
In this review, we have summarized the diagnostic approach for CS, including recent advances in PET, CMR, and CT. Current international recommendations for diagnosing CS are based on a multimodal approach (Figure 7). Among the existing modalities, FDG-PET and LGE evaluations on CMR are essential tools, and further advancements using novel techniques may be useful for the non-invasive diagnosis and prognosis assessment of CS. LGE can also reveal obvious hyperintensity areas consistent with CT. Higher ECV values corresponded to LGE.

Conclusions
In this review, we have summarized the diagnostic approach for CS, including recent advances in PET, CMR, and CT. Current international recommendations for diagnosing CS are based on a multimodal approach (Figure 7). Among the existing modalities, FDG-PET and LGE evaluations on CMR are essential tools, and further advancements using novel techniques may be useful for the non-invasive diagnosis and prognosis assessment of CS. Figure 7. Diagnostic algorithm for a patient with suspected cardiac sarcoidosis. Both cardiac MRI and FDG-PET scans are effective in patients with suspected cardiac sarcoidosis. These scans are sometimes difficult to perform and interpret accurately unless the experts understand the potential pitfalls and artifacts. It is important to differentiate CS from other cardiac diseases such as coronary artery diseases, which might be false-positive for FDG-PET and CMR. Therefore, it is necessary to select the appropriate diagnostic protocol for each facility. FDG-PET should be considered to assess inflammatory activity before initiating anti-inflammatory therapy. In patients with implantable devices, PET would be the first choice. For detection of late enhancement, delayed iodine enhanced CT would be one option for the evaluation of coronary artery disease, systemic disease, and cardiac involvement in patients with sarcoidosis.  . Diagnostic algorithm for a patient with suspected cardiac sarcoidosis. Both cardiac MRI and FDG-PET scans are effective in patients with suspected cardiac sarcoidosis. These scans are sometimes difficult to perform and interpret accurately unless the experts understand the potential pitfalls and artifacts. It is important to differentiate CS from other cardiac diseases such as coronary artery diseases, which might be false-positive for FDG-PET and CMR. Therefore, it is necessary to select the appropriate diagnostic protocol for each facility. FDG-PET should be considered to assess inflammatory activity before initiating anti-inflammatory therapy. In patients with implantable devices, PET would be the first choice. For detection of late enhancement, delayed iodine enhanced CT would be one option for the evaluation of coronary artery disease, systemic disease, and cardiac involvement in patients with sarcoidosis.