Outline
1. Rationale
Contributing authors’ characteristics | Count (%); Median(IQR) |
---|---|
MR Vendors | |
Siemens | 26 (53) |
Philips | 17(35) |
General Electrics | 6(12) |
Field Strength | |
1.5 Tesla | 37(76) |
3.0 Tesla | 17(35) |
Both | 15(31) |
Specialty | |
Cardiology | 25(51) |
Radiology | 18(38) |
Other | 5(10) |
Number of previously co-authored Societal consensus papers (any) | 3(1–4.5) |
Number of previously co-authored SCMR Consensus papers | 2(1–3) |
aNumber of previously co-authored papers in the CMR field | 86(57–141) |
bNumber of previously co-authored papers in the author’s themed field | 44(23–68) |
Number of studies | Total number of subjects | ||
---|---|---|---|
Ventricular volumes and function | |||
CMR is the reference standard for quantification of LV and RV volumes, function and mass. CMR should be considered as the first line technique in clinical trials requiring one of these parameters for in- or exclusion or as an endpoint. The evidence for the use of quantification of cardiac function and volumes is favourable. | |||
Analytical validation | Excellent validation of LV mass and volumes | 7 | 121 |
Precision | Large body of evidence on interstudy, inter- and intraobserver reproducibility | 2* | 32 |
Normal values | Available for various field strengths, imaging sequences, post-processing approaches, age-, sex- and ethnicity groups | 9 | 6895 |
Qualification/Utilisation | The original evidence base by transthoracic echocardiography has been revalidated and expanded upon by CMR | 7 | 14,711 |
Regional wall motion, deformation and dyssynchrony | |||
CMR-based strain-imaging techniques seem similarly suited as echocardiographic techniques for assessing longitudinal motion and strain. The evidence for the use of CMR-based strain imaging techniques is promising. | |||
Analytical validation | CMR tagging techniques have been well validated. Other MR based strain imaging techniques have been either directly compared with tagging or indirectly against a technique originally compared to tagging. | 11 | 600 |
Precision | Limited data on inter-study reproducibility | 9 | 168 |
Normal values | Normal values are available, but show considerable regional variation as well as variation between different studies | 11 | 3191 |
Qualification/Utilisation | Outcome data suggest utility in addition to standard measures of care in clinical management. | 5 | 2462 |
Diastolic function | |||
CMR may have advantages over other techniques by direct assessment of myocardial tissue. The evidence for the use of CMR-based assessment of diastolic function is promising. | |||
Analytical validation | Reasonably well validated versus PV loops and echocardiography for diastolic filling, atrial volumes and function and transmitral and pulmonary venous flow | 4 | 212 |
Late gadolinium enhancement | |||
CMR based LGE should be used as the first line technique in clinical trials requiring the assessment of regional scar or fibrosis for inclusion or exclusion or as an endpoint. CMR should also be employed for optimal risk-classification of trial subjects with ischemic or non-ischemic cardiomyopathies. The evidence for the use of LGE imaging for visual detection of regional myocardial fibrosis and quantification of ischaemic scar is favourable. The quantification of non-ischaemic scar remains promising. | |||
Analytical validation | Extensively validated as a marker of irreversible damage post myocardial infarction in animals as well as versus biopsies, in explanted hearts and versus other imaging techniques | 8 | 406 |
Precision | Strong data on inter-study reproducibility | 7 | 200 |
Qualification/Utilisation | Strong parameter to predict outcome, superior to volumes and function. | 37 | 12,562 |
T2-weighted imaging | |||
Due to the availability of many different sequences no generally accepted standard has been defined. For clinical trials, it is important to use a validated and standardized approach amongst different centres and vendors and use normal values and effect sizes specifically for these sequences. The evidence for the use of T2W imaging of AAR is promising. | |||
Analytical validation | Well validated in animals, phantoms and humans | 15 | 817 |
Precision | Scarce data on inter-study reproducibility in acute myocardial infarction. Lack of reproducibility data and outcome studies for T2W-oedema imaging in inflammatory cardiac conditions | 4 | 234 |
Qualification/Utilisation | Small number of outcome studies using AAR | 17 | 1509 |
T1 mapping | |||
Due to the availability of many different sequences, no generally accepted standard has been defined. To employ T1 mapping in clinical trials, the use of validated (well understood sequence) and standardized approach amongst different centres and vendors is mandatory, due to the different normal values and effect sizes between various sequences. CMR T1-mapping may be considered as a standard for adequate risk-assessment of patients with non-ischemic dilated cardiomyopathy in clinical trials. The evidence for the use of T1 mapping is promising. | |||
Analytical validation | Well validated in phantoms, animal models, human biopsies and explanted hearts. | 15 | 267 |
Precision | Evidence on interstudy, inter- and intraobserver variability | 10 | 270 |
Normal values | Sequence-specific normal values available | 4 | 1735 |
Qualification/Utilisation | Strong predictors of outcome in non-ischaemic dilated cardiomyopathies, superior to volumes, function and LGE. | 37 | 6153 |
T2 mapping | |||
Due to the availability of many different sequences no generally accepted standard has been defined. The use a validated and standardized approaches amongst different centres and vendors is mandatory for the use in clinical trials, due to the different normal values and effect sizes specifically for these sequences. The timing of imaging after an acute event must be highly standardized. The evidence for the use of T2 mapping is promising. | |||
Analytical validation | Well validated against phantoms, animal models, human biopsies and other imaging biomarkers | 11 | 340 |
Precision | Evidence on interstudy, inter- and intraobserver variability | 1* | 73 |
Normal values | Sequence-specific normal values available | 3 | 205 |
Qualification/Utilisation | Useful in detecting myocardial oedema and inflammation | 12 | 680 |
T2* mapping | |||
T2* can be regarded as the clinical reference standard in thalassemia and provide superior outcome data if used for therapy guidance. T2* measurements during or shortly after an acute coronary or vascular event provides important prognostic information in terms of short-term LV remodelling. The evidence for the use of T2* mapping is favourable. | |||
Analytical validation | Excellently validated and standardized in iron-overload | 17 | 1728 |
Precision | Evidence on interscanner, intercenter, interstudy, inter- and intraobserver variability | 4* | 59 |
Normal values | Normal values and established clinically relevant cut-offs available | 5 | 100 |
Qualification/Utilisation | Outcome data in thalassaemia major. Prognostic information after a coronary event | 19 | 1778 |
Stress myocardial perfusion | |||
Perfusion imaging should be considered as a first line technique for assessing the presence, extent and localization of inducible ischemia. Its use for full quantification requires locally validated and standardized sequences with specific normal values. The evidence for the use of myocardial perfusion imaging for visual detection of ischaemia is favourable. The quantification remains promising. | |||
Analytical validation | Well-validated against animal models and alternative techniques | 63 | 10,916 |
Precision | Limited evidence on interstudy, inter- and intraobserver reproducibility due to need of stress and contrast injection | 5* | 73 |
Normal values | Limited data on normal values due to lack of standardization of image acquisition and post-processing | 3 | 42 |
Qualification/Utilisation | Large body of evidence showing significant predictive association for the presence/severity of myocardial ischemia with outcome | 14 | 26,494 |
Vascular | |||
CMR vascular imaging is well suited to assess vascular anatomy and function. Aortic and carotid vessel wall imaging, are robust markers of atherosclerotic burden in these vessels and can be used in clinical trials. | |||
Analytical validation | Validation of PWV against alternative techniques and T2 mapping against histology | 7 | 237 |
Precision | Limited evidence on interstudy reproducibility of anatomical and tissue measurements. Excellent evidence for PWV | 6 | 95 |
Normal values | Available for different anatomical and functional measurements | 7 | 4112 |
Qualification/Utilisation | Aortic wall imaging and PWV serve robust biomarkers of cardiovascular risk | 2 | 5797 |
2. Imaging parameters as biomarkers and endpoints
3. Executive statements - SCMR Clinical Trial Writing Group
Ventricular volumes and function
i. Regional wall motion, deformation and dyssynchrony
Diastolic function
Late gadolinium enhancement (LGE)
T2-weighted imaging
T1-mapping
T2-mapping
T2* -mapping
Perfusion imaging
Vascular imaging
4. Ventricular volumes and mass
i. Global volumes, thickness and function
-
Cine imaging (bSSFP sequences)
-
Acquisition defined in SCMR Standardized Protocols [1]:
○
complete LV and RV coverage using short axis (SAX) stack of slices○
long axis LV views. -
Older approaches of cine imaging based on fast gradient recalled echo (GRE) sequences: compared to bSSFP sequences, GRE sequences lead to larger LV mass and smaller LV volumes.
-
Standardised approach defined in SCMR Standardized Post-processing recommendations [2]
○
LV mass measurement: inclusion of papillary muscles into LV cavity reduces accuracy compared to autopsy, but results in higher precision (smaller observer variability);○
LV dimensions and wall thickness: most reproducible in 3-chamber view [4];○
An early study showed higher reproducibility of RV volumes; measured in a transverse (TRA) stack [5], a later study reaffirmed that both SAX and TRA are similarly reproducible, as long as both ventricles acquired in entirety [6, 7].○
TRA stack does not support reproducible RV mass measurements [2, 7]. No data available for SAX stack.○
The accuracy and reproducibility of novel post-processing algorithms based on signal intensity thresholding is unknown
-
There is moderate variability in normal ranges depending on the population studied and method of quantification.
-
SCMR CT WG members recommend the use of normal values that correspond the mode of acquisition and postprocessing (as per SCMR recommendations for acquisition and postprocessing (1,2).
-
Diagnostic interpretation and clinical decision making underlying practice guidelines is based on evidence derived with echocardiography. The cut-off values (most notably for LV ejection fraction) have been adopted by other imaging modalities, including CMR. The original evidence base by transthoracic echocardiography has been revalidated and expanded upon by CMR (Additional file 1: Table 3ai.4).
-
Abnormal changes in cardiac volumes, function and LV mass indicate the presence of disease and relate to worse outcome. LV volumes and function by echocardiography have been described as the strongest predictor of survival in heart failure (HF) [17‐20]. Recent data with CMR LGE (Additional file 2: Table 3b-i.4) and T1-mapping indices (Additional file 3: Table 3c-i.6) show consistently better prognostic predictive value in HF and non-ischemic cardiomyopathy (NICM).
ii. Regional wall motion and deformation
-
○
Visual segmental analysis [2] -
○
Regional wall motion score -
○
Deformation/strain analysis (tagging, feature tracking [25]) -
○
Dyssynchrony [26] -
Results may be presented either segmental (provided for 17 segments as per AHA/ACC) or global (deformation components: longitudinal, radial, circumferential, torsion) values.
iii. Diastolic function
-
2- and 4-chamber cine views for measurement of left atrial (LA) volume
-
Phase-contrast gradient echo sequence acquisitions:
-
○
Through-plane flow measurement across mitral valve, pulmonary venous inflow (velocity encoding 130 cm/sec) -
○
Basal SAX slice measurement of mitral flow and annulus velocities (velocity encoding < 30 cm/sec)
-
-
Tagging [50]
-
Transmitral E and A waves
-
Pulmonary venous inflow S, D and A waves
-
Mitral annulus velocity e’
-
LA size
-
Peak early diastolic strain rate (PEDSR)
-
Normal values available for early diastolic velocities
5. Tissue characterisation
i. Late gadolinium enhancement
-
Inversion recovery (IR) prepared T1 weighted gradient echo sequences with either individually adapted prepulse delay (‘to achieve myocardial signal nulling’) and/or inline Phase-Sensitive Inversion-Recovery (PSIR)-based reconstruction algorithm [1]
-
Acquired as in full LV coverage in short axis and long axis views during mid-diastole
-
~ 10 min delay time from administration of GBCA [1]
-
GBCAs lead to:
-
○
shortening of T1 - > increased signal intensity in areas of intense GBCA accumulation compared to areas with quick wash-out, such as normal myocardium; -
○
differential distribution between myocardial regions with intact myocardial cells (membranes) and expanded extracellular space due to necrosis, fibrosis or scar; -
○
in amyloidosis, there is commonly poor contrast difference between the blood and myocardium due to expansion of the extracellular volume throughout the myocardium, resulting in lower gradient in GBCA concentration between these two tissues, save for the bright endocardial border;
-
-
Evidence of LGE is a marker of expanded extracellular space, most commonly seen due to necrotic myocardium or scar tissue
-
Methods to assess microvascular obstruction (MVO) (and IMH) include [55‐57]:
-
○
first pass perfusion imaging, -
○
early IR-TFE imaging (app. 1 min, no ‘nulling’, long prepulse delay > 400 msec) -
○
LGE (app. 10–20 min) -
○
native T1 -
○
Contrast-enhanced cine-bSSFP -
○
First pass and early hypoenhancement less strongly related to remodelling and clinical outcomes than LGE
-
-
Alternative ways to IMH imaging by T2* (see section Mapping) [58].
-
Visual assessment reporting on the presence, type (ischemic/non-ischemic), location, and transmurality [2]
-
Quantitative assessment (i.e. LGE extent) can be based on several approaches:
-
○
Manual approach (i.e. visual delineation) -
○
full width half maximum (FHWM) -
○
The “n”-SD approach (standard deviations, SD): 2SD (for nonischaemic scar)/5SD of the noise (for infarction) above the signal intensity of normal myocardium [2]. -
○
LGE extent is reported as % of LV mass
-
-
MVO can be measured manually or by SD-thresholds. The strong contrast between scar and MVO results in a highly reproducible delineation [59].
-
Excellent validation of LGE imaging for the presence, extent and transmurality of LGE against reference standard for ischemic scar and non-ischemic fibrosis (animal experiments, human endomyocardial biopsies (EMB), explanted hearts) (Additional file 2: Tables 3b-i.1 and 3b-i.2)
-
○
In acute myocardial infarction, LGE overestimates infarct size (see T2 imaging section) reviewed in [60]. -
○
CMR favourably compares to alternative techniques (SPECT, PET) due to its higher sensitivity and spatial resolution to resolve infarct transmurality (based on better spatial resolution) (Additional file 2: Table 3b-i.3)
-
-
Large body of evidence on interstudy, inter- and intraobserver variability in acute and chronic ischemic scar as well as in NICMs (Additional file 2: Table 3b-i.2)
-
No comparison of precision to SPECT/PET due to the poor interstudy reproducibility of the later methods
-
No benchmarking datasets available
-
Normal reference defined as absence of LGE
-
Interpretation by pattern (ischemic, non-ischemic, patchy, diffuse), localization (typical coronary artery territory, mid-wall, epicardial, septal, lateral), transmurality (% of wall thickness).
-
Excellent diagnostic tool for the determination of chronic myocardial infarction and regional fibrosis in cardiomyopathies.
-
Stronger predictor of outcome than LVejection fraction (EF) and LV volumes in chronic stable disease (HF, chronic CAD)
-
Stronger predictor of outcome than LV-EF and LV volumes in acute myocardial infarction
-
Stronger predictor of malignant ventricular arrhythmia, sudden death and lower likelihood of improvement with medical therapy in various patient groups with cardiomyopathy
-
LGE transmurality able to inform on reversibility of underlying regional wall motion abnormality
-
Standardization of acquisition methods and nulling approaches to achieve similar relative signal-to-noise ratios of fibrotic tissue versus normal myocardium (currently dependent on contrast agent type, dose and time after injection, field strength, type of sequence and other variables including the underlying injury itself).
-
Improved definition of transmurality and segmental allocation for visual interpretation
-
Standardization of quantification methods for LGE. Studies used the FWHM and the SD-based methods, however, this remains suboptimally standardized in terms of
-
○
To determine the cut-off value, the method with the best prognostic/ diagnostic value. -
○
The different data acquisition techniques and post-processing algorithms may require different post-processing approaches.
-
ii. T2 weighted imaging
-
○
T2W black-blood turbo spin echo (T2W-TSE) -
○
T2W short tau inversion recovery (STIR), -
○
T2-prepared SSFP -
○
Emerging new approach for AAR using contrast-enhanced SSFP (based on T2 and T1 contrast) for AAR assessment based on the acquisition of the cine LV stack [63]
-
Technical limitations of T2W CMR pulse sequences are susceptible to various influences causing some limitations as endpoints and in clinical practice:
-
○
long acquisition time over 2 heart beats result in long breath-holds and artefacts due to cardiorespiratory motion; -
○
variations in phase array coil sensitivity -
○
high signal from slow moving blood (e.g. at the subendocardium and in the ventricular apex) -
○
low contrast-noise ratio in differentiating oedematous vs. normal tissue
-
-
T2W imaging of AAR/myocardial salvage ((Additional file 4: Tables 3b-ii.1–2):
-
○
MSI is calculated by dividing the salvage area by the AAR. -
○
Post processing is subjective (based on ‘n’-SD threshold approaches or visual delineation) -
○
Optimal imaging time for AAR assessment is ideally 4–7 days after acute MI [62].
-
T2W imaging in myocarditis (LLC) [66]:
-
○
Visually determined areas of hyperintensity in T2W images -
○
Global oedema ratio: semi-quantitative analysis by normalizing the signal intensity of the myocardium to that of skeletal muscle: values of more than 1.9 indicate myocarditis
-
-
Hyperintense signal on T2W CMR has been shown to indicate increased myocardial water content, whereas hypointense signal within the hyperintense injured zone indicates IMH (Additional file 4: Table 3b-ii.1)
-
Phantom and Tissue studies
-
○
Proton transverse (T2) relaxation times reflect tissue hydration. -
○
Alterations in T2 signal enable visualisation of regional myocardial oedema as area of hyperintense signal
-
-
Animal models
-
○
The ischemic AAR consists of oedema and is typically greater than infarct size - > T2W imaging represents a non-invasive approach to AAR estimation. -
○
T2W imaging enables retrospective determination of the ischaemic area-at-risk -
○
Comparison of contrast-enhanced bSSFP with myocardial perfusion SPECT
-
-
Comparison of T2W vs. T2 mapping for AAR reveals T2 mapping to be more reproducible [71];
-
Comparison of seven post-processing approaches for quantifying oedema in T2W imaging in acute MI (2 SD, 3 SD, 5 SD, Otsu, FWHM, manual threshold, and manual contouring) revealed that manual contouring provided the lowest inter, intraobserver, and interstudy variability for both infarct size and oedema quantification [72].
-
The FWHM method for infarct size quantification and the Otsu method for myocardial oedema quantification are acceptable alternatives [72].
-
No data available for contrast-enhanced bSSFP
-
No data available for oedema ratio in myocarditis
-
Normal reference = absence of hyperintense signal (poor negative predictive value)
-
In myocarditis: semiquantitative ‘oedema ratio’ of < 1.9 (SI of myocardium/SI of skeletal muscle) [66]
-
○
Detection of myocardial damage in patients with acute coronary syndrome (ACS) [73] -
○
Determination of salvaged myocardium in STEMI patients, prediction of higher revascularisation rate and adverse prognosis (Additional file 4: Table 3b-ii.4). -
○
T2-oedema ratio variable sensitivity across inflammatory cardiomyopathies with moderate positive and poor negative predictive value (Additional file 4: Table 3b-ii.3) -
○
No prognostic or therapeutic studies
-
Native T2 mapping methods enable quantification of T2 relaxation times and are less susceptible to artefacts (see chapter on T2 mapping)
-
The utility of T2W-imaging in excluding ACS in the emergency room has become less prominent since the advent of high-sensitivity troponin assays.
6. Quantitative tissue characterisation
i. T1 mapping
-
Acquisition in mid-diastole (owing to a lengthy image acquisition time, systolic acquisition window less robust)
-
Magnetisation preparation by inversion (180°) or saturation (90°) prepulses
-
Several imaging schemes with differences in number of images, pauses for magnetization recovery (which can be defined as either beats or seconds), flip angles, use of adiabatic prepulses, acceleration techniques (half-scan, partial Fourier)
-
○
resulting in differences in T1 accuracy (with consequences for precision and diagnostic accuracy, see below).
-
-
Native (without GBCA) and post-contrast T1 mapping (typically ~ 10–15 min after administration of GBCA, dose and type of GBCA not standardized)
-
Single (midventricular) short axis slice (− > diffuse myocardial disease) or three short axis slices (apical, midventricular, basal) (− > regional myocardial disease)
-
Heart-rate dependency:
-
○
for myocardial T1 with most sequences not relevant within physiological heart rates < 80 bpm; -
○
less important for post-contrast images, more relevant for long T1 values such as native blood, or in very severe myocardial disease (amyloidosis, severe oedema), as more time needed for full relaxation; -
○
every other beat acquisition (2RR intervals) may be used in tachycardia
-
-
Extracellular volume fraction (ECV) calculation based on pre- and postcontrast T1 mapping acquisitions and blood values which requires standardization and heart rate correction for each component (unclear: identical sequences/ different schemes for pre/postcontrast acquisitions)
-
Pixel-wise image reconstruction and exponential curve-fitting of signal intensity values (3-parameter fitting model):
-
○
magnitude image detection: SMAG(t) = abs(A – B exp.(−t/T1*) -
○
phase sensitive inversion recovery (PSIR) detection : SPSIR(t) = A – B exp.(−t/T1*).
-
-
T1 value equates with the time at 63% recovery of longitudinal magnetisation
-
Post-processing affected by the regional variation due to variable sensitivity of phase array coils and artefacts in the lateral wall (septal region of interest (ROI) more precise compared to SAX ROI, segmental values difficult to normalise)
-
Myocardial ROI placement:
-
○
regional myocardial T1 values:-
▪ Segmental ROI placement [79]:
-
▪ Significant regional differences in T1 values - > difficulty in normalising segmental T1 values
-
▪ No significant differences between septal values for basal and midventricular slice, however considerable overestimation in apical slice (due to partial volume)
-
-
Blood ROI placed in the centre of the blood pool using same acquisition as above, avoiding papillary muscles
-
Post-contrast T1 blood: less in-flow effect compared to native T1
-
T1 indices (Additional file 3: Table 3c-i.1):
-
○
direct measurements: native T1, post-contrast T1 -
○
calculated indices based on pre- and post-contrast T1 mapping acquisitions:-
▪ lambda (partition coefficient of contrast agent distribution between blood and myocardium) = (R1myocardiumnative-R1myocardiumpost-contrast)/ (R1bloodnative- R1bloodpost-contrast), where R1 = 1/T1
-
▪ ECV is partition coefficient lambda, which relates to the extracellular space only, by accounting for intracellular space of blood by haematocrit (requires contemporaneous blood sampling): =(1-Ht)x lambda
-
-
-
Phantom sequence characterisation (T1 accuracy and precision)
-
Histological correlation with collagen volume fraction (Additional file 3: Table 3c-i.2)
-
○
Correlations vary between reports -
○
Differences in staining techniques, inclusion/exclusion of areas of LGE -
○
Differences in sequence parameters, type/dose/timing of GBCA, different sequences used in pre/postcontrast acquisitions, post-processing (ROI placement)
-
-
Several components of the measured values do not occur in phantoms, such as magnetisation transfer, water-exchange, T2 sensitivity, inflow effects, making a full validation in phantoms or ex-vivo impossible
-
Evidence on interstudy, inter- and intraobserver variability (Additional file 3: Table 3c-i.3)
-
No benchmarking datasets available as variability seems mainly dependent on data acquisition
-
Some sequences have established normal values (Additional file 3: Table 3c-i.4). Of note, every specific implementation may yield slightly different values and requires standardization.
-
Disease models: myocarditis, non-ischaemic dilated cardiomyopathy, amyloidosis, ischaemic cardiomyopathy, hypertrophic cardiomyopathy (Additional file 3: Table 3c-i.5)
-
Outcome data (Additional file 3: Table 3c-i.6): T1 values are stronger predictor of outcome than LV function, volumes and LGE:
-
○
Amyloidosis -
○
Non-ischaemic dilated cardiomyopathy -
○
Mixed patient cohorts
-
-
Sequence and vendor specific standardization of acquisition, normal values and calibration of values in health and disease
-
Outcome data
-
Data on guiding management
-
Pre- and post-contrast T1 mapping acquisitions
-
○
unclear whether identical sequences or different schemes for pre/post-contrast acquisitions amount to a justifiable counterpart of pre/post-contrast acquisition, but rather a mix of poorly related diagnostic tests.
-
ii. T2 mapping
-
Sequences acquiring separate images during the evolution of the transverse relaxation in diastolic standstill
-
T2 prepared spin echo sequences with several different schemes with differences in number of image acquisitions, flip angles, accelerating techniques, single-shot vs. multiecho
-
○
T2-prepared bSSFP sequence -
○
T2-hybrid gradient echo and spin echo (GraSE) sequence
-
-
Native acquisition (no contrast agent)
-
Single (midventricular) short axis slice (− > diffuse myocardial disease) or three short axis slices (apical, midventricular, basal) (− > regional myocardial disease)
-
No regional variation due to variable sensitivity of phase array coil
-
Pixel-wise image reconstruction and exponential curve fitting
-
T2 value equates with the time at 63% decay of transverse magnetisation, direct myocardial measurement
-
ROI placement:
-
○
Myocardial septal ROI or SAX ROI (in case of diffuse myocardial disease) -
○
Segmental ROI placement (in case regional T2 values are desired)
-
-
No significant difference in segmental values for basal and midventricular slice, overestimation in apical slice (partial volume)
-
Phantom sequence characterisation (T2 accuracy and precision)
-
Histological validation (Additional file 5: Table 3c-ii.1).
-
in animal models
-
○
AAR -
○
AMI reperfused and non-reperfused-
▪ Detection of AAR (comparison with T2W/LGE approach as reference standard)
-
-
-
Model diseases: AMI, myocarditis, transplant rejection
-
Validation of water component difficult in animals and biopsies
-
Has been shown to be superior to T2W imaging and Lake-Louise Criteria for the diagnosis of acute myocarditis (Additional file 5: Table 3c-ii.2)
-
Interstudy, inter- and intraobserver variability (Additional file 5: Table 3c-ii.3)
-
No benchmarking datasets available as variability seems mainly due to data acquisition
-
Several sequences have established normal values (Additional file 5: Table 3c-ii.4)
-
T2 mapping useful in detecting myocardial oedema and inflammation (Additional file 5: Table 3c-ii.5)
-
○
Acute myocardial infarction -
○
Myocarditis, inflammatory cardiomyopathies, including cardiac involvement in systemic inflammatory diseases, tako-tsubo cardiomyopathy -
○
Early detection of ongoing inflammation with the possibility of reversal of myocardial damage using anti-inflammatory intervention may be feasible.
-
iii. T2* mapping
-
As per SCMR protocols:
-
○
single breath-hold multiecho T2* gradient echo sequences (black-blood prepulse) [1] -
○
a single midventricular SAX slice - > septal T2*measurement -
○
3 short axis slices - > global T2* measurement
-
-
Each sequence yields sequence specific “absolute” T2* values (in ms)
-
Each sequence requires standardisation (validation, normal values, clinically relevant cut-off values) prior to clinical use
-
As per SCMR standardised image interpretation and post-processing [2]
-
T2* values = the time delay taken for decay of the myocardial signal by 63%
-
ROI placement:
-
○
Myocardial septal ROI in midventricular slice encompassing both epicardial and endocardial borders, to prevent the epicardium-endocardium heterogeneity of iron deposition (informs on global myocardial iron content) -
○
Segmental ROI placement (− > regional T2* values) -
○
Complete SAX coverage in basal, midventricular and apical slice generates a global T2* value, however, this is less frequently used.
-
-
Significant differences in segmental values reported. Regional variation most likely due to variable sensitivity of phase array coils to different regions.
-
Validation against myocardial and liver iron content (Additional file 6: Table 3c-iii.1 and 2)
-
○
Ex vivo histological validation - > good correlation of T2* measurements versus chemically assayed iron -
○
Biopsy not useful as reference standard -
○
Therapy guidance by T2* imaging is superior to other tests – as such T2* in thalassemia can be regarded as the clinical reference standard
-
-
Evidence on interscanner, intercenter, interstudy, inter- and intraobserver variability (Additional file 6: Table 3c-iii.3)
-
Iron loading:
-
○
Normal values for 1.5 T (Additional file 6: Table 3c-iii.4) -
○
Established clinically relevant cut-offs of significant myocardial iron loading (septal ROI):-
▪ T2* < 20 ms: clinically relevant myocardial iron loading
-
▪ T2* < 10 ms: severe myocardial iron loading
-
-
-
IMH - intramyocardial hemorrhage
-
○
A myocardial region of interest with a T2* < 20 ms is taken to represent haemorrhage -
○
T2* (< 20 ms) is highly discriminative of haemorrhagic transformation within the infarct zone vs. infarct zone without haemorrhage or the remote zone
-
-
T2* useful in detecting relevant cardiac iron overload involvement in thalassemia major – > at T2* < 20 msec
-
In cardiac iron loading T2* correlates closely with
-
Comparison with historical data indicate improve survival of patients at risk of iron overload due to cardiac T2* mapping guided iron-depletion therapy [87]
-
Interdisciplinary consensus statements recommend surveillance of patients at risk of cardiac iron overload using cardiac T2* mapping [88]
-
Serial changes in myocardial oedema and haemorrhage in ischaemic and remote zone after reperfusion [62]
-
IMH detection by T2* core is independently associated with adverse LV remodelling, major adverse cardiac events and mortality [89]
7. Stress myocardial perfusion with CMR
-
Acquisition as per SCMR Standardized Protocols [1]
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Dynamic acquisition during the passage of the contrast agent bolus (dose 0.05–0.1 mmol/kg body weight) through the left ventricular cavity and the myocardium; -
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First pass acquisition during pharmacological stress; -
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Repeat pass acquisition at rest (may be omitted for qualitative assessment, if LGE is available to determine infarction) -
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3 short axis slices (basal, midventricular and apical) every heart beat for a minimum of 40–50 heart beats→ a minimum of 40–50 dynamic measurements); -
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3D whole heart acquisition methods available, currently no demonstrated diagnostic advantage over 2D 3-SAX slice acquisition [90];
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Sequences: various sequences available based on saturation prepulse for preparation of magnetization and acquisition of data with either:
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spoiled fast gradient echo (GrE); -
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bSSFP pulse sequences; -
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typically combined with acceleration techniques:-
▪ echo planar imaging (GrE-EPI);
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▪ spatial undersampling (e.g. sensitivity encoding (SENSE)
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▪ generalized autocalibrating partially parallel acquisitions (GRAPPA),
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▪ spatio-temporal undersampling (e.g. k-t Broad Linear Speed up Technique, k-t BLAST or k-t SENSE);
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differing in the acquired spatial (3x3x8 mm to 1.3 × 1.3x8mm) resolution.
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Diagnostically relevant is the stress acquisition.
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The rest acquisition is used to:
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discern possible artefacts -
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to support calculation of parameters based on the change of stress and rest perfusion (e.g. myocardial perfusion reserve index - MPRI or myocardial blood flow – MBF - reserve).
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Pharmacological stress is the standard approach (adenosine, regadenosone, dobutamine); exercise stress has shown feasibility in research settings.
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as per SCMR Standardized Postprocessing [2]
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Visual interpretation is the standard clinical approach: -
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Hypoperfusion is defined as segmentally reduced contrast agent uptake at peak stress persisting for 5 consecutive heart beats-
▪ not present at rest,
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▪ outside the enhanced myocardium on LGE images.
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several diagnostic standards of test positivity proposed demonstrating a reduced increase of flow or reduced peak flow in areas subtended by vessels with significant coronary stenosis (see below)
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The benefits of quantitative and semi-quantitative over qualitative interpretation remain at present investigational. Quantitative and semi-quantitative evaluation require:
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stress and rest acquisition to calculate perfusion reserve or perfusion reserve indices; peak perfusion can be determined from stress images only -
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dual bolus, dual contrast sequences or other algorithms to correct for the non-linearity of signal intensity and contrast agent at higher doses -
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correction for baseline signal differences -
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efficient motion correction -
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a myocardial perfusion reserve index (MPRI) can be calculated from various parameters, usually using the relative upslope between rest and stress (corrected for changes of upslope of the contrast bolus in the left ventricle) -
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full quantification can be achieved with various mathematical algorithms (e.g. Fermi deconvolution, Patlak plot).
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Excellent validation of technique (Additional file 7: Table 3d.1 and 2):
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Flow in phantoms and microspheres in animals; -
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Comparative effectiveness diagnostic studies and meta-analyses studies of CMR to PET, SPECT, invasive coronary angiography and invasive flow measurements (fractional flow reserve – FFR; Additional file 7: Table 3d.1). Favorable results in comparison to SPECT due to higher spatial resolution. [91, 92] -
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Outcome studies of stress myocardial perfusion CMR imaging validating predictive association of positive and negative outcome (Additional file 7: Table 3d.3), similar results to SPECT. -
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Quantitative perfusion imaging: many approaches require more validation, especially as large outcome studies have been performed with visual analysis
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Limited evidence on interstudy, inter- and intraobserver reproducibility due to need of stress and contrast injection (Additional file 7: Table 3d.2)
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Limited data on normal values due to lack of standardization of image acquisition and post-processing
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Visual assessment: several diagnostic standards on the interpretation of the presence/severity/prognostic relevance of myocardial hypoperfusion based on number of affected segments:
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ESC guidelines on stable CAD (16 segment ACC/AHA segmentation) [93]:-
▪ ≤2/16 segments indicate a good prognosis with optimal medical therapy (OMT) (negative test)
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▪ ≥ 3/16 segments defined as prognostically relevant (warrants attempt to revascularize on prognostic grounds (positive test)
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Subsegmentation into 32 segments (with endo- and epicardial division):-
▪ ≤ 3/32 segments indicate a good prognosis with OMT
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▪ ≥4/32 segments defined as prognostically relevant [94]
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MR-INFORM: prognostically relevant ischaemia [95]:-
▪ Either transmural hypoperfusion defect or perfusion defect affecting 2 slices or > 60% in basal and midventricular slice, > 90% in apical slice.
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-
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(Semi-) quantitative assessment of MBF, MPR or MPRI: experimental data available for different field strengths
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Data from prospective observational studies using stress myocardial perfusion CMR have shown significant predictive association for the presence/severity of myocardial ischemia with outcome (Additional file 7: Table 3d.3):
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Effective cardiac risk reclassification in patients with known or suspected stable CAD [96]. -
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Excellent negative predictive value - > low event rate in patients with a negative test -
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Excellent positive predictive value substantiating the role for revascularisation following positive test to improve prognosis -
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Improvement of MPR after percutaneous coronary intervention (PCI)
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Standardization of post processing methods (semi quantitative and quantitative) to allow definition of normal values, effect sizes and improvement of reproducibility. Different post processing methods may apply for different data acquisition techniques.
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Improvement of spatial resolution / coverage based on faster acquisition techniques (e.g. compressed sensing)
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Quantitative perfusion imaging is increasingly becoming available. At this stage the various approaches require more validation, especially as large outcome studies have been performed with visual analysis.
8. Vascular endpoints
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Anatomy and dimensions:
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cardiac triggered-contrast enhanced CMR angiography -
○
free-breathing 3D balanced acquisition.
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Wall thickness and wall volume by black blood CMR
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Distensibility and strain: balanced (cine) image acquisitions orthogonal to the vessel of interest;
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PWV: measurement of pulse wave travel time/path between ascending and descending aorta
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‘through plane’ flow acquisitions in ascending or descending aorta and an anatomical image of thoracic aorta. -
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‘inplane’ velocity acquisition of thoracic aortic candy-cane
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Wall tissue characterisation by:
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T2 weighted sequences -
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T1 inversion recovery GRE sequences (vessel wall gadolinium enhancement)
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Inner-vessel diameters, cross-sectional areas
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PWV: travelled path divided by time delay.
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Foot-to-foot -
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Upslope measurements
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Tissue characterisation
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Visual assessment -
○
Contrast-to-noise (CNR) measurements
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-
Comparative studies for aortic PWV and distensibility with alternative techniques, including invasive and tonometric PWV measurements (Additional file 8: Table 3e.1)
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T2 mapping vs. histology of carotid specimens showing accurate quantification of plaque lipid content and the different plaque composition despite similar grade of stenosis (Additional file 8: Table 3e.1).
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Limited evidence on interstudy reproducibility of anatomical and tissue measurements
-
Excellent evidence for PWV: measurements highly reproducible
-
CMR data from large healthy populations are available for different anatomical and functional measurements adjusted by age, sex and body mass index (BMI) (Additional file 8: Table 3e2).
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Guiding management in aortic dilatation and aortic valve replacement (Additional file 8: Table 3e2)
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Aortic wall imaging and PWV serve robust biomarkers of cardiovascular risk