Tissue Characterization of Acute Myocardial Infarction and Myocarditis by Cardiac Magnetic Resonance

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1 JACC: CARDIOVASCULAR IMAGING VOL. 1, NO. 5, BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN X/08/$34.00 PUBLISHED BY ELSEVIER INC. DOI: /j.jcmg FROM PICTURES TO PRACTICE PARADIGMS Tissue Characterization of Acute Myocardial Infarction and Myocarditis by Cardiac Magnetic Resonance Matthias G., MD, FESC Calgary, Alberta, Canada Electrocardiograms, biomarkers, and ventricular function studies are diagnostic tools that are currently used to assess patients with acute myocardial disease. These tools are limited in their diagnostic accuracy and scope. Thus, for informed therapeutic decision making, tissue characterization may serve as a very important source of information in these initially regional diseases. Cardiac magnetic resonance (CMR) is becoming an important tool for phenotyping cardiac patients in vivo. Recent advances of CMR hardware and software as well as protocols have allowed for accurately visualizing tissue changes in patients with acute myocardial diseases. This is of special interest for acute myocardial infarction and acute myocarditis, because these entities may have a very similar clinical presentation and require immediate therapeutic decision making. Several CMR approaches can be combined in a comprehensive CMR examination, which provides information not only on ventricular size, morphology, and function, but also on the stage, degree, and extent of reversible and irreversible myocardial injury. Streamlined protocols allow such a CMR examination to be a time- and cost-efficient diagnostic tool, even in patients with acute disease. Current CMR approaches for visualizing tissue pathology in vivo are reviewed, examples are presented, and the potential role of CMR tissue characterization in patients with acute myocardial disease is discussed. The specific role of imaging the extent and regional distribution of myocardial edema and necrosis is discussed. (J Am Coll Cardiol Img 2008;1:652 62) 2008 by the American College of Cardiology Foundation Current Diagnostic Tools in Acute Myocardial Disease Patients with acute heart disease require immediate care. To make informed, timely therapeutic decisions, physicians need fast, accurate, and reliable diagnostic tools. This is especially true for acute myocardial infarction and acute myocarditis, with their often dramatic and sometimes apparently life-threatening clinical presentation. In patients with a clinical history, symptoms, and physical findings that suggest acute myocardial disease, a combination of ECG and seromarkers such as troponins is used to determine acuity, extent, and location of the injury. Current diagnostic approaches, however, have significant limitations. The diagnostic accuracy of ECGs to detect myocardial ischemia often is inadequately low, which may result in inappropriate treatment (1). Even in controlled trials, more than 4% of patients with acute coronary From the Departments of Cardiac Sciences and Radiology, Stephenson Cardiovascular MR Centre at the Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada. Manuscript received July 17, 2008; accepted July 21, 2008.

2 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, syndrome may be discharged with missed acute coronary syndrome or acute infarction (2). Echocardiographic studies of left ventricular function are helpful, but also have a moderate diagnostic accuracy (3) and often cannot distinguish between acute and chronic myocardial injury. Troponins accurately identify acute myocardial injury. The sensitivity of any seromarker, however, is limited during the first hours of and late after the onset of the injury. The diagnostic accuracy of these diagnostic tools is even lower when applied to patients with acute myocarditis (4). Whereas the pathophysiological and pathological features of both acute diseases offer several diagnostic targets (Table 1), each of these routinely used diagnostic tools typically addresses just 1 aspect, providing limited information for clinical decision making. Given the primarily regional nature of the acute injury, tissue abnormalities appear to be the prime candidate for diagnosing acute myocardial disease and estimating its severity. Endomyocardial biopsy, though the gold standard for tissue pathology, does not have a clinical role in acute myocardial infarction and clinical indications in acute myocarditis are limited to patients with otherwise unexplained heart failure (5). Therefore, at least in the acute clinical settings, in vivo imaging appears be the most promising approach to retrieve tissuerelated diagnostic information. Imaging Tissue Pathology Current clinical imaging modalities include echocardiography, nuclear cardiology techniques (NCT), computed tomography (CT), and cardiac magnetic resonance (CMR). Each of these modalities is characterized by specific strengths and weaknesses (Fig. 1), with Echocardiography being the most accessible, NCT being the most powerful on a molecular level, and CT providing the most detailed anatomical information. Although CMR appears to be a very versatile modality, its main strength lies in its unique ability to directly visualize tissue characteristics. Unlike all other imaging techniques, CMR uses a signal that is emitted by molecules in the region of interest and that reflects genuine physical (i.e., magnetic) properties. Thus, the contrast-generating mechanism does not depend on reflection (echocardiography), transmission (CT), or radiation of injected radioactive tracers (NCT). Instead, in MR images, molecular properties themselves determine the appearance of Table 1. Potential Diagnostic Targets in Acute MI and Acute Myocarditis Acute MI Coronary artery occlusion Hypoperfusion Ischemia Breakdown of membrane potential Dysfunction Leakage of intracellular components Edema Necrosis MI myocardial infarction. Acute Myocarditis Presence of infective or toxic agent Hyperperfusion Direct/toxic cell injury Breakdown of membrane potential Dysfunction Leakage of intracellular components Edema Necrosis the tissue. Furthermore, a large variety of highfrequency pulse sequences ( sequences ) allow for specific signal intensity characteristics, which can be used to selectively visualize certain molecular environments. In so-called T 1 -weighted sequences, for example, water will appear with a very low signal intensity, whereas fat will appear brightly. In contrast, so-called T 2 -weighted images will show water with high signal intensity. AND The typical relative signal intensity of any tissue is predictable and any significant abnormality may serve as a diagnostic marker for, often disease-specific, tissue changes. Thus, CMR has unique features, making it the imaging tool of choice for in vivo tissue characterization for disease entities such as ABBREVIATIONS ACRONYMS CMR cardiac magnetic resonance CT computed tomography NCT nuclear cardiology techniques Figure 1. Strengths of Currently Used Cardiac Imaging Tools Diagnostic power of cardiac imaging techniques at different levels of pathophysiology. CMR cardiac magnetic resonance; CT computed tomography; Echo echocardiography; Nuclear nuclear cardiology techniques.

3 654 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, 2008 Table 2. Appearance of Acute MIs in CMR Sequences Typically Used in a Comprehensive Examination T 2 T 1 /Late Enhancement Acute MI, early reperfusion Transmural high SI Nontransmural high SI with broad subendocardial base, area is smaller than area with high SI in T 2 images Acute MI, late reperfusion Transmural high SI Largely transmural high SI Acute MI, late reperfusion, no reflow Transmural high SI, small core with low SI may be seen Largely transmural high SI, core with low SI Acute MI, not reperfused Transmural high SI Largely transmural high SI, extent matches the area of high SI in T 2 images CMR cardiac magnetic resonance; SI signal intensity; other abbreviation as in Table 1. myocarditis (6). Because CMR also allows the assessment of ventricular morphology, contractile function, and blood flow during the same session, tissue characteristics can be integrated into a comprehensive all in one imaging examination. CMR of the heart is quite different from magnetic resonance imaging of other organs. CMR requires a set of techniques to reduce or eliminate artifacts caused by blood flow, breathing and cardiac motion, and conditions such as arrhythmia (e.g., atrial fibrillation) or breathing during the image acquisition may impair image quality. Significant technical advances, however, allow for a success rate of clinical scans in almost 100% of patients. These Figure 2. CMR of Acute, Nontransmural Infarction (Upper panels) Diastolic (left) and systolic (right) frames in a short-axis view. (Lower panels) T 2 -weighted (left) and post-contrast T 1 -weighted (late enhancement) (right) images showing infarction-related transmural edema but only subendocardial necrosis (see Online Video 1). advances include hardware components such as high-speed gradient systems, cardiac coils, and improved ECG triggering devices as well as software developments such as parallel data acquisition and ultrafast sequences. Currently, comprehensive scans including assessment of left ventricular function and tissue characterization can be performed in far less than 30 min. This is often faster and cheaper than using other combined approaches to achieve a similarly wide scope of diagnostic information that includes tissue characterization. CMR Techniques to Assess Tissue Pathology Hypoperfusion (acute myocardial infarction). In patients, CMR perfusion studies with adenosine accurately identify coronary artery stenosis (7) with an outstanding negative predictive value (8,9). In a protocol combining adenosine with late enhancement, Laissy et al. (10) have shown that CMR discriminates acute myocardial infarction from acute myocarditis. The clinical role of perfusion imaging in acute myocardial disease, however, remains to be defined. Edema. In myocardial edema, the predominant magnetic properties of the affected tissue and thus its appearance in applied MR images differ from that of normal myocardium, because protons now are more frequently bound to free water and have a longer transversal relaxation time (T 2 ). So-called T 2 -weighted sequences, that is, sequences specified to retrieve most of the signal from tissue components with a long T 2, will display the edematous area with a higher signal intensity than it displays the remote myocardium (with its still-normal proton binding and hence normal T 2 ). This principle is used in the entire body to visualize water or high tissue water content. This has been shown in acute myocardial infarction (11).

4 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, Although T 2 -weighted CMR has been previously used to assess myocardial infarction, its clinical use has been limited until recently by inconsistent image quality. Because T 2 -weighted images have relatively low signal-to-noise ratios, they are susceptible to motion artifacts and confounders such as repetition time between repeated data acquisition, motion, and flow. In addition, other tissue components may affect signal intensity, and it is important that hardware and software are optimized for application in the heart. The use of a cardiac coil provides a higher signal-to-noise ratio, but can be problematic, because inferolateral regions may have a lower signal due to the longer distance to the surface coil and thus should only be used if an efficient coil intensity correction algorithm is implemented. Prescription of thicker slices is helpful to increase the signal-to-noise ratio. Sequences should have a repetition time of at least 2 R-R intervals to ensure adequate T 2 weighting. Several sequence types are available for T2- weighted imaging of the heart. Whereas most published data have been acquired using a flow- and fat-suppressed spin echocardiography sequence, newer protocols may offer a higher signal-to-noise ratio and a more consistent image quality (12,13). Recently, methods have been developed to reproducibly measure and map myocardial T 2 times (14). Clinical data using this promising technique, however, are not yet available. A detailed review of the techniques and clinical role of T 2 -weighted CMR can be found elsewhere (15). Hyperemia (myocarditis). Any tissue inflammation with preserved vasculature is associated with an increased regional blood flow and volume. In acute myocarditis, this has been used as a diagnostic criterion by using contrast-enhanced CMR images obtained early after administration of gadolinium with its initial vascular and brief interstitial steady state (16,17). In these early enhancement images, inflamed regions appear with higher signal intensity. Because cardiac output, renal clearance, artifacts, and internal signal post-processing may alter absolute signal intensity, published studies successfully used values normalized to skeletal muscle (16,18). In the case of suspected skeletal muscle involvement, however, the contrast agent-induced relative signal intensity increase was found to be more sensitive without normalization (17). Necrosis. Acute, irreversible myocardial injury is best visualized on T 1 -weighted images acquired late (i.e., at least 5 to 10 min) after the administration of interstitial contrast agents such as gadolinium- Figure 3. CMR of Ischemic Cardiomyopathy With Chronic, Transmural Inferior Infarction (Upper panels) Diastolic (left) and systolic (right) frames in a short axis view with akinesis of the inferoseptal and inferior segments. (Lower panels) T 2 -weighted (left) and post-contrast T 1 -weighted (late enhancement) (right) images showing no edema, but transmural fibrosis (arrows) within the akinetic region (see Online Video 2). Figure 4. CMR in a Patient With Acute Myocarditis (Upper panels) Diastolic (left) and systolic (right) frames of a cine study showing pericardial effusion (bright signal) and largely preserved systolic function. (Lower panels) T 2 -weighted (left) and post-contrast T 1 -weighted (late enhancement) (right) images showing lateral edema (arrows) and focal fibrosis typical for the nonischemic injury pattern of myocarditis (arrows) (see Online Video 3).

5 656 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, 2008 Figure 5. CMR of Acute, Transmural Infarction (Upper panels) Diastolic (left) and systolic (right) frames in a short-axis view. (Lower panels) T 2 -weighted (left) and post-contrast T 1 -weighted (late enhancement) (right) images showing infarct-related transmural edema with transmural necrosis of the same size (see Online Video 4). diethylenetriaminepentaacetic acid. The delayed washout of these agents is specific to irreversibly injured myocardium (19). Optimized sequence parameter settings allow for selective nulling of signal intensity of myocardium without significant gadolinium accumulation and thus for very sensitive detection of necrotic tissue. This method, dubbed late gadolinium enhancement, is regarded as the noninvasive gold standard for visualizing myocardial infarctions in vivo (20,21). Its sensitivity is outstanding and allows for detecting scars of less than1g(22). Late gadolinium enhancement can be used to visualize acute and chronic infarctions; however, it does not allow for discriminating 1 infarction type from the other (20). No reflow. Late reperfusion of a large infarction is often associated with a phenomenon called no reflow, which is currently understood as a complex reperfusion injury that results in an interruption of blood flow to the infarction core despite normalized blood flow in the epicardial portions of the coronary artery system ( microvascular obstruction ) (23). Capillary injury, mechanical obstruction of capillaries, and intramyocardial hemorrhage have been observed as pathologic features associated with no reflow. CMR Tissue Characterization in Myocardial Infarction Figure 6. CMR of Acute, Transmural Infarction With No-Reflow in a Patient With Reperfused Lateral Infarction, Who Presented Late After Onset of Symptoms (Upper panels) Diastolic (left) and systolic (right) frames in a short-axis view showing preserved wall thickness of the lateral wall but regional akinesis of the anterolateral and inferolateral segments. (Lower panels) T 2 -weighted (left) and post-contrast T 1 -weighted (late enhancement) (right) images showing infarction-related transmural edema and matching necrosis in the dysfunctional segments. Both, T 2 -weighted and late enhancement images show a core with reduced signal intensity reflecting no-reflow (arrowheads) (see Online Video 5). The acute, typically thrombotic, occlusion of an epicardial coronary artery and the subsequent regional ischemia initiate a cascade of regional events that sequentially affect metabolism, function, and tissue composition. The acute lack of oxygen in the perfusion bed (area at risk) initially leads to a breakdown of membrane integrity, which within 15 min of no-flow ischemia begets intracellular sodium accumulation with subsequent intracellular edema (24,25). This is followed by leakage of osmotically relevant components into the interstitial space resulting in extracellular/interstitial edema. A wave of violent cell death (necrosis) spreads from the subendocardial layer of the area at risk through the entire myocardial wall, which if not revascularized spontaneously or by therapeutic intervention eventually will be irreversibly injured. Necrosis and accompanying inflammation are followed by the fibrotic mesh of the scar, which remains in place as the long-term sequela of the event. The T 2 -weighted CMR visualizes acute reperfused infarctions and allows for discriminating acute from chronic infarctions (26). It can also be used to determine the area at risk in reperfused and nonreperfused infarctions. When T 2 -weighted CMR is combined with contrast-enhanced imaging of irreversible injury ( late enhancement ), the salvaged area at risk can be quantified and thus the success of

6 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, Table 3. Appearance of Acute Myocarditis and Sarcoidosis in CMR Sequences Typically Used in a Comprehensive Examination T 2 T 1 /Early Enhancement T 1 /Late Enhancement Viral myocarditis Sarcoidosis Areas with high SI (mostly intramural or subepicardial), global SI typically increased* Areas with high SI (mostly intramural or subepicardial), global SI typically increased* Several areas with high SI may be visually apparent, post-gd global SI typically increased* Mostly singular areas with high SI may be visually apparent, post- Gd global SI typically increased* Areas with high SI, mostly intramural or subepicardial; rarely involving the subendocardium Focal, often transmural areas with high SI may be seen, no broad subendocardial base *Normalized to skeletal muscle. Gd gadolinium; other abbreviations as in Table 2. revascularization or adjunctive treatment on limiting infarctions size can be assessed (27 29). Appearance of acute infarctions. Table 2 summarizes the appearance of acute infarctions in CMR sequences typically used as part of a comprehensive CMR examination. Whereas necrosis may be almost prevented by early reperfusion, for example, by spontaneous recanalization or immediate revascularization, myocardial edema is an invariable feature of acute infarctions. Although the diagnostic utility of T 2 - weighted imaging in assessing nonreperfused infarctions has not been tested yet, there are experimental data indicating its clinical potential in this setting (30). The size of the edematous region reflects the perfusion bed, which represents the area at risk (27). Thus, in a clinical setting of reperfused myocardial infarction, edema as defined by high T 2 signal intensity is transmural, even if the acute irreversible injury (i.e., the necrosis) is not (Fig. 2) (26,29). In contrast to acute infarctions, T 2 is abnormally short in fibrotic tissue (31). Therefore, in T 2 - weighted images, fibrotic scars in the absence of inflammation or other acute pathology typically have a lower signal intensity than normal myocardium does (Fig. 3), and the lack of high signal intensity differentiates acute from chronic myocardial infarction (26). There is a lack of systematic data on the appearance of no reflow areas in T 2 -weighted images. In most of the cases, however, this region will appear as an intramural area of low signal intensity, which Figure 7. CMR of a Patient With Acute Myocarditis (Left panel) Diastolic (upper) and systolic (lower) frames of a cine study showing hyperdynamic systolic function. (Middle panel) Nonbreath-hold T 1 -weighted images acquired before (upper) and over the first minutes after gadolinium indicating significant myocardial gadolinium uptake. The uptake ratio (early enhancement) was increased. (Right upper panel) T 2 -weighted image with high signal intensity of the anterior wall. (Right lower panel) Post-contrast T 1 -weighted (late enhancement) image showing possible diffuse necrosis but lack of regional injury (see Online Video 6).

7 658 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, 2008 Figure 8. CMR of a Patient With Acute Myocarditis and Chronic Scarring (Left panel) Diastolic (upper) and systolic (lower) frames of a cine study showing grossly systolic function with mild septal hypokinesis. (Middle panel) Non-breath-hold T 1 -weighted images acquired before (upper) and over the first minutes after gadolinium indicating significant myocardial gadolinium uptake. The uptake ratio (early enhancement) was increased. (Right upper panel) T 2 -weighted image with high signal intensity of the septum (arrow). (Right lower panel) Post-contrast T 1 -weighted (late enhancement) image showing a focal scar in the lateral wall but no necrosis in the septal region (see Online Video 7). is embedded in a high signal intensity rim of edema (Fig. 4). Late enhancement images show necrotic myocardium as a region of very bright signal intensity (Figs. 2 to 5). In reperfused infarctions, the subendocardial portion is usually broader than the subepicardial portion. This reflects the termination of the wave front-like expansion of the injury, which spans across the perfusion bed starting in the subendocardium, which is more susceptible to ischemia. In nonreperfusion infarctions, especially those caused by proximal coronary lesions, necrosis most often is transmural (Figs. 3 to 5). It is important to emphasize that wall thickness is preserved in acute infarctions. In fact, injury-related edema leads to regional swelling (i.e., an increased wall thickness of the infarcted segments) (Figs. 2 and 5). Because blood flow is interrupted in areas with no reflow, interstitial compounds such as gadolinium can enter only through inward diffusion from the peripheral border of the no-reflow zone. If this region is sufficiently large and thus a long time is needed for gadolinium to diffuse into its center, the latter will not appear enhanced during the first minutes after administration (Fig. 6). This should not be confused with viable myocardium. Figure 9. CMR of a Patient With Remote Myocarditis This CMR image of a patient with remote myocarditis shows chronic multifocal, partially subendocardial scarring in a T 1 -weighted (late enhancement) image. CMR Tissue Characterization in Myocarditis Viral agents or other triggers, such as toxins initiating inflammation, will cause cell injury

8 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, Figure 10. CMR of an Elderly Patient With Acute Anterior Infarction and Invasive Exclusion of Relevant Coronary Artery Stenosis (A) The CMR images taken at admission of an elderly woman who presented with acute anterior infarction and invasive exclusion of relevant coronary artery stenosis. (Left panel) Diastolic (upper) and systolic (lower) frames of a breath-hold cine study, showing typical extensive mid-ventricular and apical dyskinesia ( ballooning ). (Right upper panel) T 2 -weighted image showing diffuse intraventricular high signal intensity due to slow flowing blood as well as an increased signal intensity of the mid-ventricular and apical myocardium, presumably reflecting myocardial edema. (Right lower panel) Late gadolinium enhancement study showing no subendocardial high signal intensity but some diffuse late enhancement of the dysfunctional segments. The final diagnosis in this patient was acute stress-induced cardiomyopathy (see Online Video 8). (B) Follow-up study of the same patient after 4weeks. (Left panel) Diastolic (upper) and systolic (lower) frames of a breath-hold cine study, showing normalization of systolic function. (Right upper panel) T 2 -weighted image showing homogeneous signal intensity. (Right lower panel) Late gadolinium enhancement study showing persisting diffuse late enhancement of the dysfunctional segments (see Online Video 9). with edema, necrosis, and, if sufficiently large, macroscopic scarring. Although these basic tissue responses show similarities to ischemic injury, its evolution and spatial distribution are substantially different from infarctions. Whereas acute infarctions are characterized by a lack of perfu-

9 660 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, 2008 sion, tissue inflammation is usually associated with peripheral vasodilation and thus increased blood volume in the affected region. Furthermore, instead of an outward wave front of reversible and irreversible damage, spreading of myocardial inflammation shows a disseminated, focal or global myocardial involvement. Thus, in contrast to acute infarctions, the injury with few exceptions does not show the pattern of infarctions, which again are characterized by predominantly subendocardial or transmural involvement. The CMR techniques used to visualize tissue pathology of myocarditis are very similar to those for imaging infarctions. Appearance of acute myocarditis. The regional distribution of inflammation-induced tissue characteristics is distinct from that of acute myocardial infarction (Table 3). Edema, as defined by high signal intensity in T 2 -weighted images, may be absent in very early stages of myocarditis (32), but if present it is easily identified in subepicardial or intramural layers of the myocardium (Figs. 4 to 8). Global involvement of the heart can be detected by quantifying the signal intensity ratio between the myocardium and skeletal muscles (18,33). In early enhancement images, the myocardium typically reveals a focal and/or global signal intensity increase (Figs. 7 and 8). The normalized enhancement ratio (compared with that for skeletal muscle) is increased. Early enhancement image quality depends on scanner settings and the patient s breathing pattern. Table 4. Clinical Scenarios for CMR Tissue Characterization Acute chest pain Recent or current viral disease, low risk of coronary artery disease Absence of both, ST-segment elevation and seromarker elevation Angiographic exclusion of relevant coronary artery stenosis Persisting ST-segment elevation, absence of seromarker elevation Presentation more than 8 h after onset of infarctiontypical symptoms Acute or worsened heart failure Atypical or mild symptoms such as pleuritic pain Abbreviation as in Table 2. Absence of both, ST-segment elevation and marked seromarker elevation Nonspecific ECG abnormalities or mild seromarker elevation Table 5. Current Limitations of CMR Tissue Characterization in Acute Heart Disease Lack of widely used standardized scanner protocols Availability of CMR-capable MRI systems Lack of experienced CMR imagers/readers Limited specificity regarding virus presence and species Contraindications to MRI (implanted devices, orthopnea, unstable hemodynamics) MRI magnetic resonance imaging; other abbreviation as in Table 2. Late enhancement images in patients with acute myocarditis often show multifocal areas with high signal intensity in predominantly intramural or subepicardial regions (Figs. 4, 8, and 9). Although a recent study linked subendocardial scars to myocarditis-induced coronary spasm induced by parvovirus B-19 (34), the injury pattern found in myocarditis does not predominantly involve the subendocardial layer. Interestingly, the inferolateral wall appears to be affected most often (16,35). There is preliminary evidence that the regional distribution may also depend on the viral species, with parvovirus B-19 predominantly affecting the inferolateral wall and the herpes virus preferring the septum (36). Further studies are needed to confirm these findings and better understand their clinical implications. Combined CMR protocols assessing accompanying pericardial effusion and ventricular function in addition to tissue markers for inflammation and irreversible injury have been found to have the highest diagnostic accuracy in myocarditis (18,33). Clinical Scenarios for Tissue Characterization Patients with a high clinical suspicion of acute infarction (i.e., high risk profile, diagnostic ECG changes with positive biomarkers) need no further diagnostic workup as this would only delay appropriate revascularization. If, however, the story does not fit, for example, because the patient is very young or coronary artery stenosis has been ruled out, tissue characterization adds important additional information. Myocarditis is the most frequent diagnosis in patients presenting clinically acute infarctions but with normal coronary arteries on angiograms (37). Myocarditis can be reliably detected in such patients by CMR tissue characterization (38). An important differential diagnosis in patients presenting with acute chest pain, functional abnormality, ECG changes, and positive seromarkers is stress-induced cardiomyopathy (takot-

10 JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 5, subo). The CMR tissue characterization has beenmost significant limitation may be with logistics of shown to be very useful for verifying the disease patient transport, setup, and uninterrupted cardiac using tissue characterization. Mid and apicalmonitoring during transportation. dyskinesis in combination with edema and a lack of infarction-like subendocardial necrosis allow for establishing this diagnosis 39,40). ( Diffuse, Conclusions spotty regions of high signal intensity, however, may be observed Fig. ( 10). Because scars shrink Myocardial tissue characterization provides very over time, these findings may be reversibleimportant additional information in many patients through follow-up. with acute myocardial disease. Although further Table 4 lists several clinical scenarios of acutestandardization and streamlining of protocols are heart disease in which CMR tissue characterization can provide important information upon required, CMR has unique features, making it the diagnostic tool of choice for this purpose, particularly when applied as part of a single, fast and which to base further therapeutic decisions. Tissue characterization using late enhancement is efficient scan of morphology, function, and tissue considered highly appropriate for the evaluation pathology. of infarction and myocarditis 41) ( and standard protocols have been recently proposed 42). ( Limitations of CMR Tissue Characterization Reprint requests and correspondence: Dr. Matthias G., Suite 700-SSB, Foothills Medical Centre. Table 5 lists current limitations of CMR tissue char-140acterization. In clinical settings of acute disease, the Canada. 29th Street NW, Calgary, Alberta T2N 2T9, matthias.friedrich@ucalgary.ca. 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APPENDIX For an accompanying slide set, and Videos 1 to 9 that correspond to Figures 2 to 10, please see the online version of this article.