Skip to main content

Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper

JACC White Paper

J Am Coll Cardiol, 53 (17) 1475–1487
Sections

Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., “Lake Louise Criteria”).

Background: Myocarditis

Incidence and Etiology

In this paper, myocarditis is defined as inflammation of myocardial tissue. Myocarditis has been reported in up to 12% of young adults presenting with sudden death (1–4) and is an important underlying etiology of other myocardial diseases such as dilated (5) and arrhythmogenic right ventricular (6) cardiomyopathy. The incidence of nonfatal myocarditis is likely greater than actually diagnosed, mostly as a result of the challenges of establishing the diagnosis in standard clinical settings.

Infectious disease accounts for most cases in previously healthy patients typically either because of a direct viral infection or post-viral immune-mediated reaction. Myocardial inflammation, however, also may be triggered by reversible and/or irreversible toxic, ischemic, or mechanical injury, drug-related inflammation, transplant rejection, or other immune reactions.

Pathogenesis and Pathology

The pathogenetic features of myocarditis are reviewed in detail elsewhere (7). After the initial injury, local and systemic immune responses activate cytokines and B cells with subsequent edema, additional myocyte injury, and autoantibody production. Although the molecular and cellular pathophysiology may differ between different etiologies, cellular infiltration, edema, necrosis, and (in later stages) fibrotic scars are common features.

Diagnostic Approaches to Myocarditis and Their Limitations

Currently, no single clinical or imaging finding confirms the diagnosis of myocarditis with absolute certainty. Rather, an integrated synopsis, including history, clinical assessment, and noninvasive test results, should be used to diagnose the disease and guide treatment.

History and physical exam

Although of limited specificity, a careful history and thorough clinical assessment have to precede further diagnostic tests. Patients may appear almost normal, may have nonspecific symptoms, but also may present with features of acute myocardial infarction or heart failure with hemodynamic compromise. Physical exams of patients with myocarditis are often unremarkable.

Ventricular functional analysis

Although many patients with myocarditis have regional or global wall motion abnormalities (8–10), dysfunction is not specific to inflammation, and its sensitivity is limited (9,11–13). Biventricular dysfunction in myocarditis, however, was found to be the main predictor of death and transplantation (14).

Electrocardiogram (ECG)

The ECG findings associated with myocarditis may include ST-segment and T-wave changes, Q waves, atrioventricular block, and bundle-branch block. Arrhythmias such as ventricular tachycardia and ventricular fibrillation occur. The diagnostic value of the ECG in myocarditis, however, is limited. Aside from a low specificity, either ST-segment elevation or T-wave inversion is present as the most sensitive ECG criterion in <50% of patients, even during the first weeks of the disease (15).

Biomarkers

Depending on the severity and time of testing during the course of disease, serum biomarkers of myocardial injury such as creatine kinase, creatine kinase-myocardial band, and troponin may be increased. When present, the magnitude of increase as well as the time to clearance is similar to that of a small- to medium-sized myocardial infarction and indicates more severe disease. The prevalence of an increased troponin T in biopsy-proven myocarditis, however, is only 35% to 45% (16).

Biopsy

Endomyocardial biopsy (EMB) is a widely accepted method for diagnosing myocarditis, based upon histopathology, immunohistology, and molecular techniques to identify viral genomes. A Joint Scientific Statement of several professional societies on its use in various clinical scenarios has been published (17).

Some limitations of EMB have to be considered. First, the sensitivity of EMB is limited as the result of so-called sampling error (18–21). Second, severe complications (perforation, tamponade) occur in 0.1% to 0.5%, and the overall complication rate is 6% (17). Third, substantial debate exists regarding diagnostic criteria for analyzing myocardial tissue specimens (22). The utility of the Dallas criteria (23), with inflammatory infiltration and associated myocyte necrosis uncharacteristic for an ischemic event as disease markers, is limited by poor interobserver agreement (24,25).

Immunohistochemistry has a greater sensitivity than standard histopathology for the diagnosis of myocarditis (26,27), and immunohistology protocols and evaluation criteria have been proposed (10,28). Cost, availability, and limited standardization, however, have limited the widespread use of immunohistology and viral genome analysis. Finally, in adults, the recommended indications for endomyocardial biopsy are confined to patients with heart failure (17) and, therefore, EMB is not recommended in many patients with myocarditis.

In summary, history, clinical exam, ECG, and serology have an unsatisfactory diagnostic accuracy in myocarditis. Biopsy, including immunohistochemistry, remains the widely accepted standard, but may not be appropriate for many patients, especially those with less severe disease.

Imaging Modalities Other Than CMR

A detailed review of noninvasive imaging in myocarditis can be found elsewhere (29). Ultrasound studies of the heart in myocarditis typically are performed to visualize associated functional abnormalities, wall thickness, and pericardial effusion (8,30). The diagnostic value of echocardiography is limited by the fact that many patients with less severe myocarditis have a normal echocardiogram and the highly variable echocardiographic findings lack specificity (8).

111Indium antimyosin antibody and 67gallium nuclear imaging have been used to diagnose myocarditis (31). The specificity of these approaches, however, is very limited (32). Nuclear medicine techniques also are hampered by the limited availability of tracers mentioned previously, poor spatial resolution, and radiation issues. In current clinical practice, nuclear medicine is used only rarely to diagnose myocarditis.

CMR in Myocarditis

Published Data

The use of CMR imaging offers a unique combination of safety, clarity of anatomical visualization, interobserver consistency, and quantitative accuracy. Furthermore, it allows for the comprehensive use of a wide spectrum of diagnostic targets, especially the modifiable inherent tissue contrast. This modality has become a standard tool in many medical centers and currently is considered by many to be the most versatile and powerful cardiovascular imaging modality.

Since the first description of T2-weighted CMR findings in children with myocarditis by Gagliardi et al. in 1991 (33) and the first controlled clinical study using contrast-enhanced CMR in 1998 (9), numerous investigators have studied the diagnostic utility of noncontrast (11,13,34) and contrast-enhanced (11–13,34–43) CMR in patients with myocarditis. Results have consistently shown the clinical feasibility and high diagnostic accuracy with different single-technique or combined CMR protocols. Tables 1 to 4show a list of published controlled trials on CMR in myocarditis (Table 1), and data on the diagnostic accuracy of left ventricular (LV) dysfunction (Table 2) and of CMR criteria for myocarditis (Table 3: individual criteria; Table 4: combined criteria).

Table 1. Published Controlled Studies on Cardiovascular Magnetic Resonance in Myocarditis

ValidationNo. of PatientsNo. of Control Patients
Friedrich et al., Circulation1998 (9)Clinical1918
Laissy et al., Chest2002 (11)Clinical207
Rieker et al., Rofo2002 (36)Clinical1110
Laissy et al., Radiology2005 (37)*Clinical2431
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical2522
Mahrholdt et al., Circulation2006 (40)Histology8726
Gutberlet et al., Radiology2008 (34)Histology4835
Yilmaz et al., Heart2008 (43)Histology5530
Total289179

* Compared with patients with acute myocardial infarction.

† Compared with patients with clinical evidence but lack of immunohistologic evidence for chronic myocarditis.

Table 2. Diagnostic Accuracy of LV Dysfunction as Assessed in Controlled Trials

LV Dysfunction (EF <55%)ValidationSensitivity (%)Specificity (%)Accuracy (%)PPV (%)NPV (%)
Friedrich et al., Circulation1998 (9)Clinical100100100100100
Laissy et al., Chest2002 (11)Clinical621007510058
Laissy et al., Radiology2005 (37)*Clinical4662573770
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical381006110049
Gutberlet et al., Radiology2008 (34)Histology5063556548
Pooled data (n = 276)54%76%64%71%60%

EF = ejection fraction; LV = left ventricular; NPV = negative predictive value; PPV = positive predictive value.

* Compared with patients with acute myocardial infarction.

Table 3. Overview of the Diagnostic Accuracy of Individual Tissue Criteria as Assessed in Controlled Trials

ValidationSensitivity (%)Specificity (%)Accuracy (%)PPV (%)NPV (%)
Early myocardial gadolinium enhancement
Friedrich et al., Circulation1998 (9)Clinical8489868984
Laissy et al., Chest2002 (11)Clinical851008910070
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical8068747475
Gutberlet et al., Radiology2008 (34)Histology6386728663
Pooled data (n = 194)7483788670
T2
Rieker et al., Rofo2002 (36)Clinical100507669100
Laissy et al., Chest2002 (11)Clinical451005910039
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical8474797881
Gutberlet et al., Radiology2008 (34)Histology6769677460
Pooled data (n = 178)7071707763
Late enhancement
Rieker et al., Rofo2002 (36)Clinical4560525650
Abdel-Aty et al., J Am Coll Cardiol2005 (18)Clinical44100717862
Mahrholdt et al., Circulation2006 (40)Histology9596969981
Gutberlet et al., Radiology2008 (34)Histology2780496544
Yilmaz et al., Heart2008 (43)Histology3583518138
Pooled data (n = 336)5986688953

Abbreviations as in Table 2.

Table 4. Overview of the Diagnostic Accuracy of Several Combinations of Tissue Criteria

ValidationSensitivity (%)Specificity (%)Accuracy (%)PPV (%)NPV (%)
T2 + LGE
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical401006910061
Gutberlet et al., Radiology2008 (34)Histology1791487344
Pooled data (n = 130)2595568650
T2 and/or LGE
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical88748110085
Gutberlet et al., Radiology2008 (34)Histology5057528025
Pooled data (n = 130)6066627943
Any 1 of 3
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical100487568100
Gutberlet et al., Radiology2008 (42)Histology8149676865
Pooled data (n = 130)8848706876
Any 2 of 3
Abdel-Aty et al., J Am Coll Cardiol2005 (13)Clinical7696859579
Gutberlet et al., Radiology2008 (34)Histology6389738863
Pooled data (n = 130)6791789169

LGE = late gadolinium enhancement; other abbreviations as in Table 2.

Although published data on diagnostic accuracy provide solid evidence for the use of CMR in clinical settings, it is important to emphasize that most of these studies were single-center reports and had a small sample size, variable inclusion criteria, and nonuniform patient populations. Furthermore, CMR studies were performed at variable time points after disease onset, used different imaging diagnostic criteria, and mostly did not include biopsy for confirmation.

Furthermore, the specificity was mostly compared with normal control patients or those with myocardial infarction and not to other heart diseases with similar clinical presentation, such as acute coronary syndrome or other secondary cardiomyopathies. Current data do not allow for a clear definition of the diagnostic accuracy of CMR in various clinical, histological, and immunohistochemical subgroups, and data from larger (multicenter) trials with standardized protocols comparing comprehensive CMR studies to biopsy-derived criteria are lacking.

The prognostic value of CMR criteria for myocarditis remains to be defined. In a small study, increased myocardial early gadolinium enhancement ratio at 4 weeks after clinical onset of the disease was associated with an impaired prognosis regarding functional recovery and symptoms after a 3-year follow-up (44). Confirmative studies on the prognostic value of the various parameters are required.

Diagnostic Targets of CMR in Myocarditis

Different from other diagnostic modalities, targets for CMR not only include functional and morphological abnormalities but also tissue pathology as diagnostic features of myocardial inflammation.

Functional abnormalities

The CMR assessment of right ventricular and LV function is very reproducible and thus allows for identifying, quantifying, and following even mild functional abnormalities, if present. In patients with more severe myocarditis, global LV dysfunction is frequent. It is, however, re-emphasized that regional or less severe LV wall motion abnormalities have a low specificity for the underlying pathophysiology.

Pericardial effusion

Pericardial effusion has been reported in 32% to 57% of patients with myocarditis (45–47). Although not specific for myocarditis, its presence is supportive evidence for active inflammation.

Regional distribution and extent and hemodynamic significance of pericardial effusion can be assessed by the use of standard short- and long-axis steady-state free precession (SSFP) images acquired for morphology and function. This sequence type has an inherent T2 sensitivity, rendering pericardial fluid bright signal intensity (Fig. 1A).The differentiation from epicardial fat (which also appears bright) is straightforward: the latter is found around coronary vessels (which are embedded in the epicardial fat layer) or in the AV groove and, in SSFP images, typically separated from effusion by a (single-pixel) thin chemical shift artifact layer, that is, a fine line without signal. Furthermore, fat mostly appears with a slightly lower signal intensity, and effusion may have a more “deformable” appearance through the cardiac cycle. In T1-weighted images (e.g., spin-echo images) fluid has low signal intensity. In phase-sensitive inversion-recovery sequences, however, it may be black or white, depending on the inversion time settings.

Figure 1.
Figure 1.

Short-Axis CMR Views in a Patient With Clinically Acute Myocarditis

(A)Still frames from a cine series at end-diastole (left)and end-systole (right)showing only very mild septal hypokinesis (arrow)with preserved ejection fraction. Small pericardial effusion is present along the lateral segments (arrowheads). These findings represent 2 supportive criteria for myocarditis. (B)T1-weighted spin-echo images before (left)and shortly after (right)gadolinium administration with early gadolinium accumulation in the septum (arrows). Quantitative evaluation of the signal enhancement (skeletal-muscle normalized myocardial enhancement ratio of ≥4.0 or an absolute enhancement of ≥45%) is required to use information from this pulse sequence as a positive criterion. (C) (Left)T2-weighted spin-echo image with high signal intensity of the septum and lateral wall (arrows). Evidence for regional edema, or a signal intensity ratio of ≥2.0 (signal intensity normalized to skeletal muscle in the same slice), renders T2 findings positive. (Right)Late enhancement image without evidence for significant delay of gadolinium washout. The thin subepicardial layer of high signal intensity in the inferolateral region represents fat.

Small, physiological accumulations of pericardial fluid are not circumferential and may not be considered pathologic. A fluid layer that contains nonfluid components (fibrinous deposits, thrombus) is pathologic.

Morphological abnormalities

A transient increase of wall thickness during myocarditis was first described in echocardiography studies (48) and may serve as a supportive finding during follow-up. A decrease of LV mass during the course of uncomplicated myocarditis was found to be associated with edema as assessed by T2-weighted CMR (49). A transient increase of LV volumes has been observed in the course of myocarditis (9) and may also may serve as retrospective, supportive evidence for recent myocarditis.

Tissue Characterization With CMR

Given the unique potential of CMR to visualize tissue changes, this area is of special interest. As outlined previously, expected tissue pathology in active myocarditis includes intracellular and interstitial edema, capillary leakage, hyperemia, and, in more severe cases, cellular necrosis and subsequent fibrosis (50).

Edema

An important hallmark of inflammatory cell injury is the increased permeability of cellular membranes. Whereas initial membrane defects are of a functional nature, leading to Na+influx and subsequent intracellular edema, a more severe injury allows for a net efflux of water and transmembranous leakage of larger molecules such as troponin, eventually leading to loss of cellular functions.

T2-weighted imaging sensitively detects tissue edema with the long T2 of water-bound protons as the contrast-generating mechanism, resulting in a high signal intensity of edematous tissue (Fig. 1C). Triple inversion recovery turbo spin echo sequences with inversion pulses for fat and blood suppression (51) provide excellent contrast between regional edema and normal myocardium because of the dual suppression of the fat and flowing blood signal. Double inversion recovery sequences may provide a greater signal-to-noise ratio and be used alternatively. Importantly, edema in patients with myocarditis may have a global myocardial distribution and, thus, a quantitative signal intensity analysis of the entire myocardium may be necessary. A high diagnostic accuracy has been shown for this approach in acute inflammatory or ischemic injury (13,34,52).

Regional edema visible on T2-weighted CMR images was not observed in “borderline myocarditis” but could be found in 36% of patients with histologically “active myocarditis” as defined by the Dallas criteria (39). Thus, regional edema may have a limited sensitivity in less severe inflammation. Short-axis views typically provide a more robust image quality than long axis images, although apical slices may have to be discarded because of artifacts related to intraventricular blood signal.

The signal-to-noise ratio of T2-weighted images strongly depends on sequence parameters. Particularly in patients with arrhythmia and other motion artifacts, image quality may not allow for reliable visualization or quantification of edema. Newly developed sequences may yield a more consistent image quality and better diagnostic accuracy than currently used fast spin-echo triple inversion recovery prepared protocols (53,54).

Hyperemia and capillary leak (myocardial early gadolinium enhancement)

Regional vasodilatation is an integral feature of tissue inflammation. The increased blood volume in the inflamed area leads to an increased uptake of contrast agents during the early vascular phase. Because gadolinium-based contrast agents distribute quickly into the interstitial space after administration, this phase lasts for the first minutes after the contrast bolus. Contrast-enhanced fast spin-echo T1-weighted MR during this time can be used to assess experimentally induced myocardial hyperemia (55) and to detect muscular inflammation (56). Accordingly, the purpose of myocardial early gadolinium enhancement ratio (EGEr) is to detect an overall increased volume of gadolinium distribution into the intravascular and interstitial space during the early washout period.

The diagnostic utility of contrast-enhanced T1-weighted imaging in patients with clinically acute and chronic myocarditis has been shown in several studies (9,13,34,35).

Currently, fast spin-echo sequences are used, which are vulnerable to inconsistent image quality in patients with varying heart rate and irregular breathing patterns. New sequences to assess the early phase of gadolinium kinetics may overcome existing limitations of image quality.

Necrosis and fibrosis (late gadolinium enhancement [LGE])

Myocardial LGE specifically reflects irreversible myocardial injury (i.e., necrosis and fibrosis). This type of imaging uses an inversion pulse to decrease the signal response from normal myocardium, thereby highlighting areas with increased accumulation of gadolinium as bright regions.

In earlier stages of necrosis, gadolinium enters the cells through acutely injured cell membranes (7). Hence, the volume of distribution of gadolinium is increased (12) and visualizes myocarditis-related necrosis (Fig. 2).After inflammatory clearance of necrotic regions, a mesh of fibrocytes with a large interstitial component replaces formerly viable tissue, again increasing the volume of distribution for gadolinium into this extracellular space during the late washout period. Thus, the late sequelae of inflammatory tissue damage also can be observed by LGE.

Figure 2.
Figure 2.

Late Enhancement Patterns in Myocarditis

(A)Normal myocardium with no evidence of irreversible myocyte injury. (B)Regional subepicardial enhancement of the lateral wall (arrow). (C)Subepicardial enhancement of lateral and midwall enhancement of the septal wall (arrows). (D)Diffuse subepicardial enhancement.

Microscopic (57), animal (58), and clinical (59) studies have confirmed the role of LGE imaging as s gold standard for in vivo detection of irreversible myocardial injury associated with myocardial infarction. In patients with myocarditis, several studies have demonstrated a high specificity of LGE for the detection of such injury in myocarditis (12,13,37,38,40). The regional distribution of injury as defined by LGE not only allows differentiating ischemic (with mandatory subendocardial involvement) from nonischemic injury (60), but also may indicate the underlying etiology of the nonischemic insult (61).

As a potential limitation, LGE showed a variable sensitivity to detect active or chronic inflammation, depending on the selection of patients (12,13,34,39,40,43). Using the Dallas criteria, De Cobelli et al. (39) found LGE to be less sensitive in “borderline” myocarditis (44%) than in “active” myocarditis (84%).

One reason may be that active myocarditis may not always lead to large-enough regions of necrotic myocytes to be visually detectable, given the pixel size in CMR images. This contrasts with the situation in ischemic necrosis for which LGE has been shown to be highly sensitive. Therefore, LGE may be insensitive for the detection of symptomatic myocarditis with limited or nonfocal irreversible injury. More studies are needed to address this issue.

Combined use of tissue pathology markers

Two studies have compared all 3 tissue-based markers as well as various combinations of these. Abdel-Aty et al. (13) used combined clinical criteria for active myocarditis, whereas Gutberlet et al. (34) assessed patients with chronic myocarditis, validated against histopathological criteria of myocardial inflammation. In both studies, the approach with the best overall diagnostic accuracy was found by the combined use of all 3 tissue-based CMR parameters, with the presence of at least 2 positive criteria defining the CMR study as positive for myocarditis (Tables 3 and 4).

Indications, Procedure, and Protocol of CMR

Indications for CMR

A CMR study should only be performed if patients are symptomatic, if there is sufficient clinical evidence for myocarditis, and if the CMR result will likely affect clinical management. Thus, it is generally indicated in patients with current or persisting symptoms, evidence for significant myocardial injury, and suspected viral etiology. CMR is of potential use in patients with chest pain, elevated troponin, and normal coronary arteries, where it was shown to identify myocarditis in more than 30% of patients (62).

Additional indications may exist for subjects with possible myocarditis being exposed to strenuous physical exercise (e.g., professional athletes) or for patients with otherwise unexplained new ECG findings consistent with myocarditis, even in the absence of symptoms suggestive of myocarditis. Table 5lists recommended criteria for requesting a CMR study in patients with suspected myocarditis.

Table 5. Indications for Cardiovascular Magnetic Resonance in Patients With Suspected Myocarditis

New Onset or Persisting Symptoms Suggestive of MyocarditisPlusEvidence for Recent/Ongoing Myocardial InjuryPlusSuspected Viral Etiology
Dyspnea ororthopnea orpalpitations oreffort intolerance/malaise orchest painVentricular dysfunction ornew or persisting ECG abnormalities orelevated troponinHistory of recent systemic viral disease or previous myocarditis orabsence of risk factors for coronary artery disease or age <35 yrs orsymptoms not explained by coronary stenosis on coronary angiogram orrecent negative ischemic stress test

ECG = electrocardiogram.

The CMR Procedure

The patient should be monitored throughout the session, including ECG, blood pressure, breathing, and O2saturation. Furthermore, communication to the patient should be ensured by the use of intercom devices. A physician trained in cardiac resuscitation should be available. As for all cardiac diagnostic modalities, drugs and equipment for immediate interventions should be within reach.

Typically, patients are examined in a supine position. A dedicated cardiac phased-array surface coil should be used to acquire functional images. It is very important to emphasize that for all sequences used to analyze signal intensity (qualitatively or quantitatively), either a signal intensity correction algorithm or the body coil should be used. The inhomogeneous sensitivity field of surface coils may otherwise lead to false negative (inferolateral wall) or false positive (septum) results.

The coverage of the heart should allow for assessing all 17 LV segments according to published recommendations (63). Images of the apex may be of insufficient image quality and may have to be excluded.

Published data on contrast-enhanced CMR in myocarditis mostly have been obtained with the use of gadolinium gadopentetate dimeglumine and, thus, recommendations are only valid for this substance or compounds with an equivalent pharmacokinetic profile.

The CMR Protocol

Recommended imaging parameters and detailed protocol recommendations are provided in the Online Appendixof this article. CMR sequences generally will be ECG-gated and performed by the use of breath-hold protocols. These recommendations are based on the current evidence as published in peer-reviewed literature as of January 2009. Some of the currently recommended sequences have distinct limitations. Images obtained by T1-weighted spin-echo sequences during free breathing may have limited diagnostic quality, and T2-weighted spin-echo images suffer from an inherently low signal-to-noise ratio. Although new sequences are being tested for these purposes, their value and clinical role remains to be defined.

Evaluation of CMR Images in Suspected Myocarditis

The versatility, accuracy, and reproducibility of CMR and the generally high expectations of referring physicians call for a careful, responsible evaluation of all available parameters. Table 6summarizes CMR findings and proposed terminology in patients with suspected myocarditis.

Table 6. Proposed Terminologies for Describing CMR Findings

NormalCMR Findings Consistent With Myocardial Inflammation
EdemaLack of evidence for myocardial edemaPatchy areas or regions of high T2 signal intensity indicating focal or regional edema*Subepicardial or septal layer of high T2 signal intensity indicating regional edemaTransmural high T2 signal intensity indicating regional edema, consistent with but not specific for myocardial inflammationGlobal high T2 signal intensity indicating global edema
Hyperemia Capillary leakLack of evidence for increased myocardial early gadolinium enhancement ratioIncreased myocardial early gadolinium enhancement ratio
Irreversible cell injuryLack of evidence for regional late gadolinium enhancementPatchy areas of late gadolinium enhancement indicating focal injurySubepicardial or septal layer of late gadolinium enhancement indicating regional injuryTransmural late gadolinium enhancement, consistent with but not specific for myocardial inflammation
NormalSupportive CMR Findings
LV dysfunctionNormal LV functionRegional systolic dysfunctionGlobal systolic dysfunction
Pericardial effusionLack of evidence for pericardial effusionSmall pericardial effusionModerately large pericardial effusionLarge pericardial effusion without hemodynamic relevanceLarge pericardial effusion with hemodynamic relevance

CMR = cardiovascular magnetic resonance; LV = left ventricular.

* To avoid misinterpretation of artifacts, areas with abnormal signal intensity should consist of at least 10 adjacent pixels to be regarded as relevant.

† Global high T2 signal is defined by a signal intensity ratio between myocardium and skeletal muscle of ≥2.0.

‡ An increased myocardial early gadolinium enhancement ratio is defined by either a signal intensity enhancement ratio between myocardium and skeletal muscle of ≥4.0 or an absolute myocardial enhancement of ≥45%.

Edema

Myocardial edema appears as an area of high signal intensity in T2-weighted images (Fig. 1C, left panel). In myocarditis, it may be regional or global. It is important to keep in mind that, in the absence of LGE, edema reflects reversible myocardial injury (52,64).

Regional edema can be identified visually (Fig. 1C), although a quantitative assessment of the signal abnormality seems appropriate. Evaluation software allows for verifying edema as regions with signal intensity more than 2 standard deviations above the mean value of normal tissue. The lower signal-to-noise of T2-weighted images should be considered, limiting the ability to correctly identify small regions of signal inhomogeneity. Thus, it is recommended to consider only areas of at least 10 adjacent pixels with high signal intensity as relevant. Areas with abnormally low signal in T2-weighted images (e.g., fibrotic scars) should not be used for normalization.

In myocarditis, edema may be global and thus not recognizable to the eye. A quantitative analysis by normalizing the signal intensity of the myocardium to that of skeletal muscle has been shown to allow for the detection of a global T2 signal abnormality. Values for the T2 ratio (for calculation, see the Online Appendix) of more than 1.9 indicate myocarditis (13).

Involvement of skeletal muscle in systemic inflammation may limit the sensitivity of a signal intensity analysis normalized to skeletal muscle (11) and should be taken into consideration in patients with evidence for ongoing myositis. Future studies will have to address the diagnostic accuracy in different scenarios.

When analyzing signal intensity, great care should be taken to exclude high signal of inadequately suppressed slowly flowing cavitary blood. This should not be a problem in visual analysis because slow flow signal would have an apparent “subendocardial” location, whereas the T2 signal hyperintensity of myocarditis is almost always subepicardial or transmural. The identification of skeletal muscle to calculate myocardium to skeletal muscle ratio in the same slice may be difficult with a fat-suppressed sequence. The viewing of T2 images side by side with colocalized SSFP or T1-weighted images is recommended to correctly identify skeletal muscle and differentiate it from subcutaneous fat.

Hyperemia and capillary leakage (myocardial early gadolinium enhancement)

The EGEr is defined as an increased normalized gadolinium gadopentetate dimeglumine accumulation in the myocardium during the early washout period. Although sometimes visually appreciated (Fig. 1B), quantitative evaluation of myocardial EGEr is required. Normalization of the signal intensity in T1-weighted images to that of skeletal muscle may be hampered by coexisting myositis. In patients with evidence for skeletal muscle involvement as indicated by a skeletal muscle signal intensity increase of 20% or higher or by a recent history of muscular pain, an absolute myocardial signal intensity increase between pre- and post-gadolinium images of more than 45% should be used as a threshold consistent with myocarditis instead of the normalized myocardial early gadolinium enhancement ratio (11). In patients with irregular breathing patterns or significant arrhythmia, image quality may be reduced or even be nondiagnostic.

Necrosis and fibrosis (LGE)

Several patterns of LGE may be seen in patients with active myocarditis (Fig. 2). Focal signal increases typically are localized to the subepicardial regions of the LV and extend to a variable extent through the ventricular wall. The LGE may be localized in inferolateral and, less frequently, anteroseptal segments (Fig. 1B). However, LGE may be multifocal or diffuse in distribution (Figs. 1C and 1D). As a rule, the subendocardium typically is not involved in an isolated fashion, clearly distinguishing this injury pattern from ischemia-mediated injury. In the basal septum, the LV outflow tract and the membraneous septum may mimic septal LGE in short axis images and lead to false-positive results. Also, a line of increased signal intensity may appear in the basal septum on transverse, long-axis, or short-axis images that may not represent pathologic LGE but may be related to the fusion of the right ventricular moderator band to the right ventricular portion of the interventricular septum.

Comprehensive use of CMR criteria (“Lake Louise Criteria”)

Because of the lack of large-scale multicenter data, current recommendations can only reflect the experts' best-achievable consensus based on currently available literature. It is important to re-emphasize that rigorous test data of the pulse sequences evaluated against the gold standard of myocardial biopsy in clearly defined clinical subsets of patients are still scarce. The sensitivity and specificity as compared with endomyocardial biopsy for the pulse sequences recommended in this article are based on the limited number of patients in controlled trials. At the current time, this needs to be kept in mind when employing CMR for making the diagnosis of myocarditis.

The authors recommend the combined use of all 3 tissue markers. If all sequences can be performed and 2 or more of the 3 tissue-based criteria are positive, myocardial inflammation can be predicted or ruled out with a diagnostic accuracy of 78% (pooled data, Table 4); if only LGE imaging is performed, the diagnostic accuracy is 68% (pooled data, Table 3).

The authors acknowledge that there may be clinical settings that require a greater sensitivity, even if this comes with a reduced specificity, or vice versa. One example may be the use of CMR to assess patients with a high pre-test probability or children with suspected inflammation after cardiac transplantation. It is re-emphasized that both referring physicians and CMR readers should use the reported criteria as part of a comprehensive diagnostic approach, which also includes clinical, functional, and other information. Table 7summarizes the recommended diagnostic CMR criteria for myocardial inflammation.

Table 7. Proposed Diagnostic CMR Criteria (i.e., Lake Louise Consensus Criteria) for Myocarditis

In the setting of clinically suspected myocarditis,*CMR findings are consistent with myocardial inflammation, if at least 2 of the following criteria are present:
Regional or global myocardial SI increase in T2-weighted images.
Increased global myocardial early gadolinium enhancement ratio between myocardium and skeletal muscle in gadolinium-enhanced T1-weighted images.
There is at least 1 focal lesion with nonischemic regional distribution in inversion recovery-prepared gadolinium-enhanced T1-weighted images (“late gadolinium enhancement”).§
A CMR study is consistent with myocyte injury and/or scar caused by myocardial inflammation if Criterion 3 is present.
A repeat CMR study between 1 and 2 weeks after the initial CMR study is recommended if
None of the criteria are present, but the onset of symptoms has been very recent and there is strong clinical evidence for myocardial inflammation.
One of the criteria is present.
The presence of LV dysfunction or pericardial effusion provides additional, supportive evidence for myocarditis.

Abbreviations as in Table 6.

* The clinical suspicion for active myocarditis should be based on the criteria listed in Table 5.

† Images should be obtained using a body coil or a surface coil with an effective surface coil intensity correction algorithm; global signal intensity (SI) increase has to be quantified by an SI ratio of myocardium over skeletal muscle of ≥2.0). If the edema is more subendocardial or transmural in combination with a colocalized ischemic (including the subendocardial layer) pattern of late gadolinium enhancement, acute myocardial infarction is more likely and should be reported.

‡ Images should be obtained using a body coil or a surface coil with an effective surface coil intensity correction algorithm; a global SI enhancement ratio of myocardium over skeletal muscle of ≥4.0 or an absolute myocardial enhancement of ≥45% is consistent with myocarditis.

§ Images should be obtained at least 5 min after gadolinium injection; foci typically exclude the subendocardial layer, are often multifocal, and involve the subepicardium. If the late gadolinium enhancement pattern clearly indicates myocardial infarction and is colocalized with a transmural regional edema, acute myocardial infarction is more likely and should be reported.

Follow-Up of Myocarditis by CMR

The decision regarding follow-up of patients with active myocarditis depends on the individual scenario. Anecdotal evidence suggests that CMR studies during the first days of myocarditis may be less sensitive than those obtained 7 days after clinical onset of the disease (65). This may be due to the focal nature of early stages of the disease. Thus, in a patient with strong clinical evidence for myocarditis yet negative criteria in the initial CMR study, a repeat scan may be needed to establish the diagnosis. A follow-up at least 4 weeks after the onset of disease may be useful to differentiate uncomplicated involvement of the myocardium in a systemic viral illness from a complicated course with viral persistence or autoimmunologic disease, as viral clearance usually is completed within the first days after infection and tissue inflammation should not take more than 2 to 3 weeks. Indeed, pilot data indicate a prognostic relevance of persisting CMR markers for inflammation at 4 weeks after onset (44).

Reporting of CMR Results

The report for a CMR study should address the specific questions raised by the referring physician. In suspected myocarditis, this will usually include the inflammatory activity, LV function, and other information such as pericardial effusion, cardiac index, and extent of scarring.

There was consensus that for the time being the presence or absence of the 3 criteria, if acquired, should be reported. The report summary should include components as listed in Table 8.The report should relate quantitative values to published reference values. References may be cited as deemed appropriate.

Table 8. Summary of Recommended Components for the CMR Study Report

LV volume and function
  • LV end-diastolic volume and volume index

  • LV end-systolic volume and volume index

  • Ejection fraction

  • Cardiac index

  • LV mass and mass index

Presence or absence of markers for inflammatory activity and injury
  • T2 signal/edema (regional edema or global T2 ratio)

  • Calculated global myocardial early gadolinium enhancement ratio

  • Myocardial late gadolinium enhancement with nonischemic regional distribution

ConclusionOn the basis of the presence or absence of 2 or more criteria, considering additional evidence by the presence of LV dysfunction and/or pericardial effusion
Recommendation for follow-up
  • Based on clinical setting

  • A follow-up >4 weeks after the onset of symptoms may have prognostic implications and thus is recommended.

Abbreviations as in Table 6.

It is important to be aware that CMR, like myocardial biopsy, depicts the patient's status at one point in time and cannot characterize acute, chronic, or relapsing forms. These attributes are based on the clinical course rather than imaging (or biopsy) findings. The consensus group therefore recommends against using the terms acute, chronic, and so on with respect to CMR findings, but rather to comment on the presence or absence of “active” or “ongoing” inflammation.

Future Developments of CMR for Myocarditis

The CMR methodology is evolving at a rapid pace. Among numerous interesting developments, many can be expected to be useful for application in myocarditis. As hardware and coil technology are improving, image quality and thus diagnostic yield will be more consistent. But, more importantly, novel approaches for characterizing tissue such as time-resolved assessment of gadolinium wash-out, T1 mapping, T2 mapping, parametric imaging, and the combination of imaging criteria with seromarkers will likely further increase the utility of CMR.

Conclusions

This work provides recommendations on the use of CMR as part of a comprehensive diagnostic approach in patients with suspected myocardial inflammation. The use of CMR appears suitable to identify patients with significant ongoing inflammation, which may be especially important for patients with recurrent or persisting symptoms and in patients with new onset heart failure.

On the basis of published data, we propose a comprehensive CMR protocol to determine the extent and regional distribution of reversible and irreversible myocardial injury, as well as to detect functional and other abnormalities. Furthermore, we suggest consensus criteria providing evidence for or against myocardial inflammation based on CMR findings. We are aware that these recommendations are based on limited data and that not all centers will be able to apply all components of the suggested protocol. New hardware, software, and contrast agent techniques may become available to further improve diagnostic and procedural efficiency of CMR in myocarditis.

Appendix

  • 1. Fabre A. and Sheppard M.N. : "Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death". Heart 2006; 92: 316.

    CrossrefMedlineGoogle Scholar
  • 2. Doolan A., Langlois N. and Semsarian C. : "Causes of sudden cardiac death in young Australians". Med J Aust 2004; 180: 110.

    CrossrefMedlineGoogle Scholar
  • 3. Puranik R., Chow C.K., Duflou J.A., Kilborn M.J. and McGuire M.A. : "Sudden death in the young". Heart Rhythm 2005; 2: 1277.

    CrossrefMedlineGoogle Scholar
  • 4. Virmani R., Burke A.P. and Farb A. : "Sudden cardiac death". Cardiovasc Pathol 2001; 10: 211.

    CrossrefMedlineGoogle Scholar
  • 5. Kawai C. : "From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future". Circulation 1999; 99: 1091.

    CrossrefMedlineGoogle Scholar
  • 6. Calabrese F., Basso C., Carturan E., Valente M. and Thiene G. : "Arrhythmogenic right ventricular cardiomyopathy/dysplasia: is there a role for viruses?". Cardiovasc Pathol 2006; 15: 11.

    CrossrefMedlineGoogle Scholar
  • 7. Liu P.P. and Mason J.W. : "Advances in the understanding of myocarditis". Circulation 2001; 104: 1076.

    CrossrefMedlineGoogle Scholar
  • 8. Pinamonti B., Alberti E., Cigalotto A.et al. : "Echocardiographic findings in myocarditis". Am J Cardiol 1988; 62: 285.

    CrossrefMedlineGoogle Scholar
  • 9. Friedrich M.G., Strohm O., SchulzMenger J., Marciniak H., Luft F.C. and Dietz R. : "Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis". Circulation 1998; 97: 1802.

    CrossrefMedlineGoogle Scholar
  • 10. Maisch B., Portig I., Ristic A., Hufnagel G. and Pankuweit S. : "Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus: A status report". Herz 2000; 25: 200.

    CrossrefMedlineGoogle Scholar
  • 11. Laissy J.P., Messin B., Varenne O.et al. : "MRI of acute myocarditis: a comprehensive approach based on various imaging sequences". Chest 2002; 122: 1638.

    CrossrefMedlineGoogle Scholar
  • 12. Mahrholdt H., Goedecke C., Wagner A.et al. : "Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology". Circulation 2004; 109: 1250.

    CrossrefMedlineGoogle Scholar
  • 13. Abdel-Aty H., Boye P., Zagrosek A.et al. : "Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches". J Am Coll Cardiol 2005; 45: 1815.

    View ArticleGoogle Scholar
  • 14. Caforio A.L., Calabrese F., Angelini A.et al. : "A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis". Eur Heart J 2007; 28: 1326.

    CrossrefMedlineGoogle Scholar
  • 15. Morgera T., Di Lenarda A., Dreas L.et al. : "Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes". Am Heart J 1992; 124: 455.

    CrossrefMedlineGoogle Scholar
  • 16. Lauer B., Niederau C., Kuhl U.et al. : "Cardiac troponin T in patients with clinically suspected myocarditis". J Am Coll Cardiol 1997; 30: 1354.

    View ArticleGoogle Scholar
  • 17. Cooper L.T., Baughman K.L., Feldman A.M.et al. : "The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology: Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology". J Am Coll Cardiol 2007; 50: 1914.

    View ArticleGoogle Scholar
  • 18. Chow L.H., Radio S.J., Sears T.D. and McManus B.M. : "Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis". J Am Coll Cardiol 1989; 14: 915.

    View ArticleGoogle Scholar
  • 19. Hauck A.J., Kearney D.L. and Edwards W.D. : "Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error". Mayo Clin Proc 1989; 64: 1235.

    CrossrefMedlineGoogle Scholar
  • 20. Shirani J., Freant L.J. and Roberts W.C. : "Gross and semiquantitative histologic findings in mononuclear cell myocarditis causing sudden death, and implications for endomyocardial biopsy". Am J Cardiol 1993; 72: 952.

    CrossrefMedlineGoogle Scholar
  • 21. Feldman A.M. and McNamara D. : "Medical progress: myocarditis". N Engl J Med 2000; 343: 1388.

    CrossrefMedlineGoogle Scholar
  • 22. Baughman K.L. : "Diagnosis of myocarditis: death of Dallas criteria". Circulation 2006; 113: 593.

    CrossrefMedlineGoogle Scholar
  • 23. Aretz H.T., Billingham M.E., Edwards W.D.et al. : "Myocarditis: A histopathologic definition and classification". Am J Cardiovasc Pathol 1987; 1: 3.

    MedlineGoogle Scholar
  • 24. Hahn E.A., Hartz V.L., Moon T.E.et al. : "The Myocarditis Treatment Trial: design, methods and patients enrollment". Eur Heart J 1995; 16: 162.

    CrossrefMedlineGoogle Scholar
  • 25. Shanes J.G., Ghali J., Billingham M.E.et al. : "Interobserver variability in the pathologic interpretation of endomyocardial biopsy results". Circulation 1987; 75: 401.

    CrossrefMedlineGoogle Scholar
  • 26. Herskowitz A., Ahmed-Ansari A., Neumann D.A.et al. : "Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: a nonhistologic marker of myocarditis". J Am Coll Cardiol 1990; 15: 624.

    View ArticleGoogle Scholar
  • 27. Angelini A., Crosato M., Boffa G.M.et al. : "Active versus borderline myocarditis: clinicopathological correlates and prognostic implications". Heart 2002; 87: 210.

    CrossrefMedlineGoogle Scholar
  • 28. Richardson P., McKenna W., Bristow M.et al. : "Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies". Circulation 1996; 93: 841.

    CrossrefMedlineGoogle Scholar
  • 29. Skouri H.N., Dec G.W., Friedrich M.G. and Cooper L.T. : "Noninvasive imaging in myocarditis". J Am Coll Cardiol 2006; 48: 2085.

    View ArticleGoogle Scholar
  • 30. Felker G.M., Boehmer J.P., Hruban R.H.et al. : "Echocardiographic findings in fulminant and acute myocarditis". J Am Coll Cardiol 2000; 36: 227.

    View ArticleGoogle Scholar
  • 31. Sarda L., Colin P., Boccara F.et al. : "Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms". J Am Coll Cardiol 2001; 37: 786.

    View ArticleGoogle Scholar
  • 32. Dec G.W., Palacios I., Yasuda T.et al. : "Antimyosin antibody cardiac imaging: its role in the diagnosis of myocarditis". J Am Coll Cardiol 1990; 16: 97.

    View ArticleGoogle Scholar
  • 33. Gagliardi M.G., Bevilacqua M., Di Renzi P., Picardo S., Passariello R. and Marcelletti C. : "Usefulness of magnetic resonance imaging for diagnosis of acute myocarditis in infants and children, and comparison with endomyocardial biopsy". Am J Cardiol 1991; 68: 1089.

    CrossrefMedlineGoogle Scholar
  • 34. Gutberlet M., Spors B., Thoma T.et al. : "Suspected chronic myocarditis at cardiac MR: diagnostic accuracy and association with immunohistologically detected inflammation and viral persistence". Radiology 2008; 246: 401.

    CrossrefMedlineGoogle Scholar
  • 35. Roditi G.H., Hartnell G.C. and Cohen M.C. : "MRI changes in myocarditis—evaluation with spin echo, cine MR angiography and contrast enhanced spin echo imaging". Clin Radiol 2000; 55: 752.

    CrossrefMedlineGoogle Scholar
  • 36. Rieker O., Mohrs O., Oberholzer K., Kreitner K.F. and Thelen M. : "Cardiac MRI in suspected myocarditis". Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2002; 174: 1530.

    CrossrefGoogle Scholar
  • 37. Laissy J.P., Hyafil F., Feldman L.J.et al. : "Differentiating acute myocardial infarction from myocarditis: diagnostic value of early- and delayed-perfusion cardiac MR imaging". Radiology 2005; 237: 75.

    CrossrefMedlineGoogle Scholar
  • 38. Ingkanisorn W.P., Paterson D.I., Calvo K.R.et al. : "Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: similarities to community-acquired myocarditis". J Cardiovasc Magn Reson 2006; 8: 353.

    CrossrefMedlineGoogle Scholar
  • 39. De Cobelli F., Pieroni M., Esposito A.et al. : "Delayed gadolinium-enhanced cardiac magnetic resonance in patients with chronic myocarditis presenting with heart failure or recurrent arrhythmias". J Am Coll Cardiol 2006; 47: 1649.

    View ArticleGoogle Scholar
  • 40. Mahrholdt H., Wagner A., Deluigi C.C.et al. : "Presentation, patterns of myocardial damage, and clinical course of viral myocarditis". Circulation 2006; 114: 1581.

    CrossrefMedlineGoogle Scholar
  • 41. Schulz-Menger J., Wassmuth R., Abdel-Aty H.et al. : "Patterns of myocardial inflammation and scarring in sarcoidosis as assessed by cardiovascular magnetic resonance". Heart 2006; 92: 399.

    CrossrefMedlineGoogle Scholar
  • 42. Yelgec N.S., Dymarkowski S., Ganame J. and Bogaert J. : "Value of MRI in patients with a clinical suspicion of acute myocarditis". Eur Radiol 2007; 17: 2211.

    CrossrefMedlineGoogle Scholar
  • 43. Yilmaz A., Mahrholdt H., Athanasiadis A.et al. : "Coronary vasospasm as the underlying cause for chest pain in patients with PVB19-myocarditis". Heart 2008; 94: 1456.

    CrossrefMedlineGoogle Scholar
  • 44. Wagner A., Schulz-Menger J., Dietz R. and Friedrich M.G. : "Longterm follow-up of patients with acute myocarditis by magnetic resonance imaging". Magma 2003; 16: 17.

    CrossrefMedlineGoogle Scholar
  • 45. Ammann P., Naegeli B., Schuiki E.et al. : "Long-term outcome of acute myocarditis is independent of cardiac enzyme release". Int J Cardiol 2003; 89: 217.

    CrossrefMedlineGoogle Scholar
  • 46. Carniel E., Sinagra G., Bussani R.et al. : "Fatal myocarditis: morphologic and clinical features". Ital Heart J 2004; 5: 702.

    MedlineGoogle Scholar
  • 47. Karjalainen J. and Heikkila J. : "“Acute pericarditis”: myocardial enzyme release as evidence for myocarditis". Am Heart J 1986; 111: 546.

    CrossrefMedlineGoogle Scholar
  • 48. Hiramitsu S., Morimoto S., Kato S.et al. : "Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study". Jpn Circ J 2001; 65: 863.

    CrossrefMedlineGoogle Scholar
  • 49. Zagrosek A., Wassmuth R., Abdel-Aty H., Rudolph A., Dietz R. and Schulz-Menger J. : "Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis—a CMR study". J Cardiovasc Magn Reson 2008; 10: 19.

    CrossrefMedlineGoogle Scholar
  • 50. Kishimoto C. and Hiraoka Y. : "Clinical and experimental studies in myocarditis". Curr Opin Cardiol 1994; 9: 349.

    CrossrefMedlineGoogle Scholar
  • 51. Simonetti O.P., Kim R.J., Fieno D.S.et al. : "An improved MR imaging technique for the visualization of myocardial infarction". Radiology 2001; 218: 215.

    CrossrefMedlineGoogle Scholar
  • 52. Abdel-Aty H., Zagrosek A., Schulz-Menger J.et al. : "Delayed enhancement and T2-weighted cardiovascular magnetic resonance imaging differentiate acute from chronic myocardial infarction". Circulation 2004; 109: 2411.

    CrossrefMedlineGoogle Scholar
  • 53. Kellman P., Aletras A.H., Mancini C., McVeigh E.R. and Arai A.E. : "T2-prepared SSFP improves diagnostic confidence in edema imaging in acute myocardial infarction compared to turbo spin echo". Magn Reson Med 2007; 57: 891.

    CrossrefMedlineGoogle Scholar
  • 54. Aletras A.H., Kellman P., Derbyshire J.A. and Arai A.E. : "ACUT2E TSE-SSFP: a hybrid method for T2-weighted imaging of edema in the heart". Magn Reson Med 2008; 59: 229.

    CrossrefMedlineGoogle Scholar
  • 55. Miller D.D., Holmvang G., Gill J.B.et al. : "MRI detection of myocardial perfusion changes by gadolinium-DTPA infusion during dipyridamole hyperemia". Magn Reson Med 1989; 10: 246.

    CrossrefMedlineGoogle Scholar
  • 56. Paajanen H., Brasch R.C., Schmiedl U. and Ogan M. : "Magnetic resonance imaging of local soft tissue inflammation using gadolinium-DTPA". Acta Radiol 1987; 28: 79.

    CrossrefMedlineGoogle Scholar
  • 57. Rehwald W.G., Fieno D.S., Chen E.L., Kim R.J. and Judd R.M. : "Myocardial magnetic resonance imaging contrast agent concentrations after reversible and irreversible ischemic injury". Circulation 2002; 105: 224.

    CrossrefMedlineGoogle Scholar
  • 58. Kim R.J., Fieno D.S., Parrish T.B.et al. : "Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function". Circulation 1999; 100: 1992.

    CrossrefMedlineGoogle Scholar
  • 59. Kim R.J., Wu E., Rafael A.et al. : "The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction". N Engl J Med 2000; 343: 1445.

    CrossrefMedlineGoogle Scholar
  • 60. Codreanu A., Djaballah W., Angioi M.et al. : "Detection of myocarditis by contrast-enhanced MRI in patients presenting with acute coronary syndrome but no coronary stenosis". J Magn Reson Imaging 2007; 25: 957.

    CrossrefMedlineGoogle Scholar
  • 61. Mahrholdt H., Wagner A., Judd R.M., Sechtem U. and Kim R.J. : "Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies". Eur Heart J 2005; 26: 1461.

    CrossrefMedlineGoogle Scholar
  • 62. Assomull R.G., Lyne J.C., Keenan N.et al. : "The role of cardiovascular magnetic resonance in patients presenting with chest pain, raised troponin, and unobstructed coronary arteries". Eur Heart J 2007; 28: 1242.

    CrossrefMedlineGoogle Scholar
  • 63. Cerqueira M.D., Weissman N.J., 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: 539.

    CrossrefMedlineGoogle Scholar
  • 64. Aletras A.H., Tilak G.S., Natanzon A.et al. : "Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations". Circulation 2006; 113: 1865.

    CrossrefMedlineGoogle Scholar
  • 65. Friedrich M.G., Strohm O., Schulz-Menger J., Marciniak H., Luft F.C. and Dietz R. : "Noninvasive diagnosis of acute myocarditis by contrast-enhanced magnetic resonance imaging—response to the author". Circulation 1999; 99: 459.

    MedlineGoogle Scholar

Footnotes

Dr. Friedrich is a shareholder and advisor for Circle Cardiovascular Imaging, Inc., Calgary, Alberta, Canada. One of the meetings of the Consensus Group was in part supported by nonrestricted grants from Siemens Medical Solutions Canada and from Berlex Canada Inc. None of the sponsors was involved in the writing process.