Introduction
Diagnostic criteria in the pre-mapping era: lights and shadows
CMR technique | Information provided | Imaging features |
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Cine-SSFP | Regional and global biventricular function, ventricular mass, and parietal wall thickness | - Normal or mildly dilated left or biventricular cavities |
- Ejection fraction depending on clinical presentation, usually mildly depressed (45–50 %) | ||
- Parietal wall thickness normal or slightly increased (>10 mm) | ||
- Pericardial effusion in 30–50 % of cases | ||
T2w-STIR | Increased myocardial free water content | - Subepicardial or patchy areas of high signal intensity following LGE distribution |
- Global hyperintensity compared to skeletal muscle (T2 ratio > 1.9 according to LLc) | ||
Pre- and post-Gd T1w FSE | Myocardial hyperemia and expansion of extracellular compartment | - Sequences frequently affected by severe artefacts |
- Myocardial hyper-enhancement compared to skeletal muscle (EGEr > 4 according to LLc) | ||
Delayed enhancement | Myocardial necrosis, scars | - No enhancement |
- Focal subepicardial enhancement typically involving inferolateral LV wall | ||
- Patchy or longitudinal striae of mid-wall enhancement | ||
Native T1 mapping | Pixel-by-pixel assessment of T1-rt revealing myocardial changes, first of all oedema | - T1-rt prolongation: proposed cut-off > 990 ms (59) |
Pre- and post-Gd T1 mapping | ECV expansion due to enhanced diffusion of free water and cardiomyocyte apoptosis | - ECV increase: proposed cut-off ≥ 27 %; still few published data (34) |
T2 mapping | Pixel-by-pixel assessment of T2-rt revealing myocardial oedema | - T2-rt prolongation; still few published data (64) |
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Current diagnostic criterion:
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Definition:
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T2w-STIR sequences must be performed using the same prescription of SSFP images in short-axis views and in three long-axis planes (two-, three-, and four-chamber views). However, a body coil is recommended to avoid signal heterogeneity as compared to SSFP.
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The presence of tissue oedema may be detected visually or, as suggested in the LLc, using a semiquantitative method. Regional oedema is defined as region of at least 10 adjacent pixels with signal intensity more than 2 standard deviations above the mean value of normal tissue, evident in two orthogonal planes [11].
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Diffuse oedema is quantified as the ratio of myocardial to skeletal muscle (T2 ratio) by drawing two distinct regions of interest in the same slice; a ratio ≥ 1.9 is considered positive and reflective of global myocardial oedema [16]. An example of posterolateral left ventricle oedema is showed in Fig. 1.
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Limitations:
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T2w-STIR images usually allow reliable visual identification of oedema in patients with a focal pattern of myocardial involvement, although the limited contrast-to-noise ratio (CNR) may impede the detection of subtle tissue changes in a significant minority of patients.
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Other weaknesses may prevent the interpretation of T2w-STIR images under certain conditions. First, signal heterogeneity related to coil sensitivity profiles can produce both false-negative and false-positive results, and thus the use of reliable surface coil intensity correction filters or body coils is of pivotal importance. Second, the dark blood preparation pulse may introduce regional signal loss in the LV wall, especially in the posterior and posterolateral wall, caused by through-plane cardiac motion. Third, incomplete dark blood preparation may lead to bright rim blood artefacts along the endocardium, especially in patients with impaired ventricular function [20].
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Another limitation is the qualitative nature of T2w-STIR images, which implies the need for reference tissue for interpretation. In the case of suspected diffuse oedema, the reference tissue is the skeletal muscle, although a concomitant signal change within skeletal muscles, such as that in patients with coexisting myositis, may adversely affect diagnostic performance [21, 22].
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Finally, a cut-off value of 1.9 was defined using clinical criteria (symptoms, ECG and serologic evidence of myocardial injury, and angiographic exclusion of coronary artery disease) as a reference standard for establishing a diagnosis, without histological validation [16].
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Current diagnostic criterion:
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Definition:
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The technique used to assess myocardial hyperemia in the context of LLc was originally proposed by Abdel-Aty et al. in 2005. A free-breathing black blood fast spin echo (FSE) T1w sequence with an acquisition time of 3–4 min is acquired in four identical axial slices, both before and after (without any change in the parameters in between) intravascular injection of 0.1 mmol of gadopentetate dimeglumine (Gd-DTPA) [11].
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Sequence parameters should be adjusted to maximize T1 weighting; in particular, an echo train length of less than 4 is desirable. According to LLc, diffuse hyperemia can be detected by calculating the early gadolinium enhancement ratio (EGEr): endocardial and epicardial contours should be traced on both pre- and post-contrast images, and a reference region of interest (ROI) should be placed on the skeletal muscle located within the same slice. The myocardial enhancement should be normalized on the skeletal muscle enhancement, and an EGEr ≥ 4 is considered positive for myocardial inflammation [11].
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Limitations:
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EGE imaging is generally considered the least robust of the three components of the LLc, as FSE sequences originally proposed [11] are limited by inconsistent image quality in many patients [21]. In particular, this sequence is highly prone to severe respiratory artefacts caused by free breathing during acquisition.
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Second, the acquisition of only 3–4 subsequent slices limits anatomic coverage of the left ventricle, impeding a panoramic assessment of the myocardial wall.
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Third, the cut-off value is validated with one standard-relaxivity contrast medium (Gd-DTPA) and may be not acceptable if higher relaxivity agents are used (e.g., Gd-BOPTA and gadobutrol). Therefore, a redefinition of thresholds is needed for agents with higher relaxivity, as has already been reported in a similar model of breast MRI [23].
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Fourth, signal normalization may be hampered by coexisting skeletal muscles disease. Hence, in patients with an increase in skeletal muscle signal intensity ≥ 20 %, as well as in patients with a recent history of muscular pain, an increase of > 45 % in absolute myocardial signal intensity between pre- and post-gadolinium images is suggested as a threshold consistent with myocarditis, rather than normalized EGEr [11].
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An interesting alternative method for fast assessment of myocardial hyperemia in AM was recently reported, which relies on SSFP sequences acquired soon after contrast administration (ceSSFP) [24]. This approach overcomes most of the drawbacks of original FSE sequences and seems to be effective for the identification of areas of regional hyperemia, although it is not yet validated in patients with EMB-proven AM. However, the ceSSFP technique has not yet been implemented in the assessment of diffuse changes involving the entire LV wall, and this is its main limitation.
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Current diagnostic criterion:
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Definition:
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LGE is considered positive if at least one focal area of high signal intensity with non-ischemic pattern of distribution is outlined in at least two orthogonal planes [11].
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Suggested LLc protocol recommends the application of conventional segmented two-dimensional breath-hold IR-GRE pulse sequence.
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Application of a fat-saturation pre-pulse may also be helpful for discriminating epicardial fat from pathological subepicardial LGE foci.
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Any quantitative approach for LGE quantification was recommended in the LLc, although semi-automated standard deviation (SD)-based thresholding techniques are commonly used today in different clinical settings, primarily in the assessment of acute myocardial infarction (AMI) [28].
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Limitations:
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However, LGE detection relies on differences in gadolinium concentration between pathological and “normal” segments. Such differences may not exist if the process is diffuse, or may be insufficient to create contrast in the presence of mild focal involvement.
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Recent data have demonstrated a limited sensitivity of the LGE technique, mainly in patients with less common disease onset such as arrhythmic or cardiomyopathic presentations [31]. These results, correlated with histology, better demonstrate that LGE may be less sensitive for the detection of myocarditis with limited or non-focal myocyte injury.
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Diagnostic performance of LLc
First author (reference) | Year | N | EGEr | T2 ratio | LGE | 2/3 Positive criteria (LLc) | Reference standard |
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Abdel-Aty [16] | 2005 | 48 | Se 80 | Se 84 | Se 44 | Se 76 | Clinical/coronary angiography |
Spec 68 | Spec 74 | Spec 100 | Spec 95 | ||||
Acc 74 | Acc 79 | Acc 71 | Acc 85 | ||||
Röttgen [33] | 2011 | 131 | Se 49 | Se 58 | Se 31 | / | EMB |
Spec 74 | Spec 57 | Spec 88 | |||||
Acc 57 | Acc 58 | Acc 50 | |||||
Stensaeth [32] | 2012 | 42 | Se 31 | Se 57 | Se 64 | Se 76 | Clinical/coronary angiography |
Spec - | Spec - | Spec - | Spec - | ||||
Acc - | Acc - | Acc - | Acc - | ||||
Lurz [30] | 2012 | 70 | Se 76 | Se 64 | Se 74 | Se 81 | EMB |
Spe 53 | Sp 65 | Spec 65 | Spec 71 | ||||
Acc 70 | Acc 63 | Acc 71 | Acc 79 | ||||
Šramko [36] | 2013 | 42 | Se 40 | Se 7 | Se 87 | Se 53 | EMB |
Spec 96 | Spec 100 | Spec 44 | Spec 93 | ||||
Acc 76 | Acc 66 | Acc 60 | Acc 78 | ||||
Chu [13] | 2013 | 45 | Se 66 | Se 69 | Se 77 | Se 80 | Clinical/coronary angiography |
Spec 90 | Spec 100 | Spec 60 | Spec 90 | ||||
Acc 72 | Acc 76 | Acc 73 | Acc 82 | ||||
Francone [31] | 2014 | 57 | Se 61 | Se 47 | Se 60 | Se 61 | EMB |
Spec - | Spec - | Spec - | Spec - | ||||
Acc - | Acc - | Acc - | Acc - | ||||
Radunski [34] | 2014 | 125 | Se 63 | Se 76 | Se 61 | Se 84 | Clinical/coronary angiography |
Spec 71 | Spec 42 | Spec 100 | Spec 57 | ||||
Acc 59 | Acc 70 | Acc 67 | Acc 79 | ||||
Luetkens [21] | 2014 | 66 | Se 83 | Se 79 | Se 75 | Se 92 | Clinical/coronary angiography |
Spec 42 | Spec 61 | Spec 100 | Spec 80 | ||||
Acc 60 | Acc 68 | Acc 91 | Acc 85 | ||||
Pooled data | Se 60 | Se 63 | Se 59 | Se 77 | |||
Spec 68 | Spec 64 | Spec 85 | Spec 81 | ||||
Acc 63 | Acc 63 | Acc 71 | Acc 78 |