Table 1.

Conventional imaging modalities for the assessment of established myocardial fibrosis and its surrogates

Conventional imaging modalities
Modality	Method	Focus of assessment	Advantages	Disadvantages	Next steps
Echocardiography •LVEF •GLS •Diastolic dysfunction	Ultrasound waves directed via probe to detect cardiac structures	LV systolic and diastolic dysfunction and structural change resulting from fibrosis	Cheap, portable, no radiation exposure Available on routine echocardiograms Correlates with CMR fibrosis assessments	Images surrogates of fibrosis rather than direct assessment Less sensitive to detecting smaller or more subtle structural/functional consequences of scar	Establishing clear thresholds to guide patient management and clinical decision-making (GLS)
Nuclear •18F-FDG PET	Determines viability of myocytes by visualizing uptake of radiolabelled glucose analogue therefore inferring normal glucose utilization	Detection of viable myocardium	High sensitivity of PET	Ionizing radiation Availability of scanners for cardiovascular imaging Expensive scans Images viable myocardium rather than fibrosis directly	Development of tracers targeting fibrosis more directly
ȃ•SPECT	Single-photon emission CT at rest and during stress to detect fixed and reversible perfusion deficits	Detection of irreversible perfusion deficits indicates scar	Widely available imaging technique with well-established protocols and image analysis software Exercise or pharmacological stress options available so suitable for all levels of mobility	Ionizing radiation Caffeine restriction Limited spatial resolution—unable to detect small areas of fibrosis nor to differentiate the different patterns of scarring	Improvements in hardware capability and sensitivity: multiple detectors, high-sensitivity collimation Improvements in software processing: iterative construction, attenuation correction Use of reduced radiation dosage protocols
CMR •Native T1	Maps time course taken by tissues recovering from longitudinal magnetization	Interstitial fibrosis	No GBCA required Well-suited to widespread and diffuse changes Provides prognostic information in several conditions	Lack of consistency in values across scanners and magnetic field strengths Overlap in values between disease states, and with normal myocardium	Standardization of T1 values across scanners Establishment of normal ranges and ranges for specific disease states Further prognostic data
ȃ•ECV%	Informs about the percentage of the myocardium comprised by extracellular matrix Uses haematocrit to calculate cell fraction in blood pool and myocardium pre- and post-contrast	Interstitial fibrosis (ECV expansion)	More sensitive in detecting diffuse fibrosis than native T1 Comparable across scanners and magnetic field strengths Prognostic information in several conditions	Requires GBCA Dependent on blood flow and renal clearance Overlap in values between different diseases and with normal myocardium (less so than for native T1) ECV expansion is not synonymous with fibrosis	Establishment of normal ranges and ranges for specific disease states Further prognostic data Multicentre studies
ȃ•iECV	Represents the burden of established fibrosis in the LV. Calculated by multiplying indexed LV volume by ECV%	Interstitial fibrosis (ECV expansion)	Tracks progression and regression of fibrosis Good discrimination between disease states Comparable across scanners and magnetic field strengths Prognostic information in AS	Requires GBCA Limited prognostic information ECV expansion is not synonymous with fibrosis	Investigation of prognostic utility in other myocardial disease states Studies investigating change in iECV with anti-fibrotic therapy
ȃ•LGE	Slowed GBCA clearance from damaged tissue ECM	Replacement fibrosis	Detection of focal scar tissue Strong prognostic predictor across a wide range of conditions	Requires GBCA Not suited to detecting diffuse interstitial fibrosis Difficulty in detecting fibrosis outside the left ventricle Not specific to fibrosis (increased signal with oedema, infiltration etc.)	Developments to improve detection of atrial and right ventricular fibrosis Clinical trials demonstrating the clinical efficacy of LGE assessments in guiding clinical practice
CT •ECV	Uses X-rays to provide cross-sectional imaging. Fibrosis is detected using IV contrast	Interstitial fibrosis (ECV expansion)	Agreement with CMR T1 mapping-derived ECV CT often performed for other clinical indications (e.g. TAVR work up, coronary artery disease)	Requires IV contrast Ionizing radiation Lower contrast intensity compared with CMR	Further comparison with established CMR methods Investigate clinical utility in patients with coronary disease, and patients being considered for TAVR with suspected amyloidosis

A range of methods are currently available to assess myocardial fibrosis each with different benefits and considerations. CMR, cardiovascular magnetic imaging; LGE, late gadolinium enhancement; ECV, extracellular volume; ECV%, percentage of extracellular volume; iECV, indexed extracellular volume; LV, left ventricular; GBCA, gadolinium-based contrast agent; ECM, extracellular matrix; LVEF, left ventricular ejection fraction; GLS, global longitudinal strain; CT, computed tomography; IV, intravenous; TAVR, transcatheter aortic valve replacement; AS, aortic stenosis; SPECT, single photon emission computed tomography; ¹⁸F-FDG, ¹⁸F-fluorodeoxyglucose; PET, positron emission tomography.