Cardiac Functional Assessment by Magnetic Resonance Imaging

Abstract

The assessment of cardiac function using echocardiography has gained a strong foothold in clinical practice. Cardiac magnetic resonance (CMR) imaging harbors distinct advantages over echocardiography, as it is not affected by limitations of acoustic windows and operator dependence. CMR is also designed to non-invasively assess cardiac morphology, ventricular geometry, myocardial wall motion, and intra-cardiac flow quantification without the use of ionizing radiation. These inherent features make CMR appropriate for diagnosing cardiovascular diseases, monitoring patients after treatment, and providing longitudinal follow-up. In this paper, the state-of-the-art work that has demonstrated the aspects of cardiac function by CMR is reviewed, and acquisition techniques and clinical applications are covered.

1. Introduction

The quantification of cardiac morphology and function is pivotal in cardiac imaging, in that it plays a significant role in the prediction, diagnosis, and treatment of patients with almost all types of cardiovascular disease including cardiomyopathies, coronary artery disease, valvular heart disease, congenital heart disease, and heart failure. The unique ability of echocardiography to provide real-time images of the cardiac cycle, coupled with its cost-effectiveness, portability, and widespread availability, makes it the most extensively employed modality for non-invasive assessment of cardiac function.^[1] However, operator dependence and a limited acoustic window are some of the well-known technical limitations of echocardiography in clinical applications. To fill these gaps, other imaging modalities such as computed tomography, nuclear medicine, and cardiac magnetic resonance (CMR) are utilized. Nuclear medicine and computed tomography are known to provide accurate assessments of cardiac function with good reproducibility despite their relatively low spatial and temporal resolution, respectively.^[2,3] Additionally, repeated measurements resulting in exposure to ionizing radiation make them unsuitable alternatives.

Owing to its excellent tissue characterization and endocardium definition, CMR imaging is widely acknowledged as the gold standard for evaluating cardiac function.^[4] There have been numerous recent advances in the CMR assessment of cardiac function that warrant review. We will begin with the most applied and impactful cine technology, namely a traditional method to investigate ventricular and atrial geometry. Next, techniques to detect myocardial stiffness by strain CMR are discussed, given their value for detecting subtle deformations in the underlying substrate. This will be followed by an exploration of phase-contrast CMR imaging of blood flow, which is a relatively new technique but holds promise for a better understanding of blood-tissue interaction. Finally, we will elucidate their utility in diverse clinical scenarios where CMR imaging could prove valuable for cardiovascular diseases, encompassing diagnosis, risk stratification, therapy management, and monitoring [Figure 1].

Figure 1.

Representation and application of function parameters that can be obtained by cardiac magnetic resonance.

2. Conventional cardiac function assessment

2.1. Acquisition methods

Considering that the anatomical evaluation of the heart depends on high spatial resolution, while its functional evaluation requires sufficient temporal resolution, CMR cine imaging usually employs a balanced, steady-state, free precession technique combined with breath holding and electrocardiography gating. With the emergence of new technologies like compressed sensing which overcomes the constraints of traditional Nyquist sampling theorem, the acquisition time for cine imaging would be drastically shortened. It operates on the assumption that the k-space data is randomly undersampled, the image has a sparse representation in some pre-defined basis or dictionary, and a non-linear reconstruction is performed to enforce the sparsity of the image and consistency with the acquired MR data. Thus, the compressed sensing technique offers the advantage of acquiring functional information in at least one plane for patients who are unable to maintain breath-holding for multiple heartbeats or those with arrhythmias. Cine imaging is referred to as “bright blood imaging” because it produces images where the blood pool exhibits a higher brightness than the intermediate signal intensity observed in the adjacent myocardial region. By combining improved edge definition between intraventricular blood and the endocardium with its highly reproducible metrics and larger field of view than 2-dimensional (2D) echocardiography, cine imaging is considered a standard reference for evaluating chamber volumes and function against which other modalities are validated.^[4] Nevertheless, there are some challenges in distinguishing certain pathologies or subtle tissue variations using this technique.

2.2. Quantification of chamber volume and function

The application of CMR has demonstrated its accuracy and reproducibility in the estimation of left ventricular volumes, mass, and ejection fraction [Table 1].^[5,6] The technique provides a precise and easily traceable volume calculation by offering a spatially defined 3D dataset at multiple levels and phases, with excellent myocardium-to-blood contrast and without geometric assumptions. Distinct from echocardiography, which relies on the biplane method of disks summation (modified Simpson’s rule),^[7] CMR is not limited by the assumption about left ventricular shape in deformed hearts. Therefore, CMR provides more accurate and reliable left ventricular volume measurements than transthoracic echocardiography.^[8] Left ventricular ejection fraction (LVEF) is derived from volumetric data and calculated as the ratio of stroke volume (the difference between end-systolic and end-diastolic cavity volumes) to the end-diastolic volume (EDV). Despite its limitations, LVEF remains a well-established measure of systolic function given its simplicity and extensive validation. The calculation of left ventricular mass involves multiplying the total volume of the myocardium by the myocardial density which is taken as 1.05 g/mL.^[9] High spatial-resolution imaging allows for accurate delineation of wall thickness in all segments, including improved recognition of the crista supraventricularis muscle, which may lead to an overestimation of left ventricular wall thickness. Furthermore, most volumetric and functional parameters used to assess the left ventricle can also be applied to the other chambers. For example, left atrial volume and emptying fraction assessed by CMR are markers of subclinical atrial fibrillation as detected by continuous monitoring; right ventricular ejection fraction is an important determinant of outcomes in heart failure cohorts.

Table 1.

Parameters of biventricular and bi-atrial size and function in healthy Chinese adults according to sex based on CMR.^[5,6]

Items	Men	Women	P
LV
LVEDVi (mL/m2)*	77.7 (53.8, 101.6)	72.7 (52.4, 93.0)	<0.001
LVESVi (mL/m2)*	30.0 (17.8, 42.2)	26.8 (16.3, 37.3)	<0.001
LVMi (g/m2)*	49.1 (35.0, 63.2)	41.8 (30.7, 52.9)	<0.001
LVEF (%)*	61.4 (52.1, 70.7)	63.2 (54.0, 72.4)	<0.001
RV
RVEDVi (mL/m2)*	79.8 (53.1, 106.5)	71.2 (49.4, 93.0)	<0.001
RVESVi (mL/m2)*	31.3 (18.2, 44.3)	26.3 (15.5, 37.2)	<0.001
RVEF (%)*	60.9 (51.8, 69.9)	63.2 (54.1, 72.3)	<0.001
LA
LAV total (mL)	39.1 (20.9–57.3)	37.7 (23.2–52.2)	0.109
LAV passive (mL)	23.2 (8.7–37.7)	21.8 (10.2–33.4)	0.041
LAV active (mL)	15.9 (5.1–26.7)	15.9 (5.9–25.9)	0.404
LAEF total (%)	60.0 (47.9–72.2)	62.5 (50.9–74.1)	<0.001
LAEF passive (%)	35.6 (19.1–52.1)	36.3 (20.2–52.4)	0.968
LAEF active (%)	37.6 (22.1–53.1)	40.9 (26.0–55.8)	<0.001
RA
RAV total (mL)	29.9 (11.5–48.3)	27.5 (10.1–44.9)	0.008
RAV passive (mL)	13.9 (1.8–26.1)	13.3 (1.2–25.5)	0.368
RAV active (mL)	16.1 (2.6–29.6)	14.2 (1.5–26.9)	0.005
RAEF total (%)	47.2 (30.7–63.7)	52.6 (34.4–70.8)	<0.001
RAEF passive (%)	21.9 (5.4–38.4)	25.6 (5.6–45.6)	<0.001
RAEF active (%)	32.3 (14.5–50.1)	36.0 (15.2–56.8)	0.001

Data are presented as mean (95% confidence interval). ^*Data are presented as mean (mean–2SD, mean+2SD). CMR: Cardiac magnetic resonance; LA: Left atrium; LAEF/RAEF: Left/right atrial ejection fraction; LAV/RAV: Left/right atrial volume; LV: Left ventricle; LVEDVi/RVEDVi: Left/right ventricular end-diastolic index; LVEF/RVEF: Left/right ventricular ejection fraction; LVESVi/RVESVi: Left/right ventricular end-systolic index; LVMi: Left ventricular mass index; RA: Right atrium; RV: Right ventricle; SD: Standard deviation.

2.3. Clinical applications

2.3.1. Left ventricle

The presence of left ventricular diastolic dysfunction is closely associated with left ventricular hypertrophy, which can be accurately quantified by precise measurements of the left ventricular wall thickness. Notably, compared to 2D echocardiography, CMR has demonstrated superior precision in assessing left ventricular wall thickness in some patients with hypertrophic cardiomyopathy, such as when 64.5% apical aneurysm detected by CMR was not reliably identifiable using 2D echocardiography.^[10] Thus, the European Society of Cardiology has recommended performing CMR for the diagnosis of hypertrophic cardiomyopathy when acoustic windows are suboptimal or certain regions are poorly visualized—such as the anterolateral wall, left ventricular apex, or right ventricle.^[11] This further solidifies the role of CMR as an indispensable adjunct to echocardiography.

After an acute myocardial infarction, increased pressure and volume load can lead to asymmetrical hypertrophy of the non-infarcted myocardium to preserve cardiac function. Over time, this causes significant increase in left ventricular wall tension, EDV and end-systolic volume, eventually impairing cardiac function by causing mitral or tricuspid regurgitation as well as reducing LVEF. In a contemporary cohort of patients presenting with ST-elevation myocardial infarction (STEMI), CMR imaging observations strongly suggested that an increase in left ventricular EDV index ≥12% might be considered an “adverse” phenomenon linked to decreased LVEF; an increase in end-systolic volume index ≥12% might not necessarily indicate an “adverse” outcome, rather a “compensatory” response associated with improved LVEF at the follow-up.^[12] Another study showed that ≥10% EDV reduction at 4 months is strongly correlated with clinical outcome in the same cohort.^[13] While the adverse remodeling, defined as a combination >15% increase in EDV with >3% ejection fraction reduction at 6 months, could be the best predictor of 6-year cardiovascular events.^[14] Given the variations in the baseline and the period of follow-up, studies on left ventricular remodeling cut-off values have yielded diverse results, indicating a lack of consensus regarding volume thresholds for defining adverse left ventricular remodeling. However, it is widely acknowledged that the degree of structural remodeling observed through CMR is useful to guide therapeutic interventions or assess treatment response.^{[15,16,17,18]} Moreover, the left atrioventricular coupling index has demonstrated incremental prognostic value in predicting incident heart failure, new onset atrial fibrillation, and cardiovascular death beyond traditional risk factors by measuring the ratio of left atrial to left ventricular volumes at left ventricular end-diastole.^[19,20,21] Still, it remains unclear whether this index can be incorporated into algorithms to assess left ventricular diastolic function owing to a lack of studies linking it with invasive measurements of left ventricular filling pressure (LVFP) to establish a cut-off value. Thus, LVEF is still widely accepted as a functional surrogate for evaluation of disease progression, therapy response, cardiovascular outcome prediction, or determination of the next step in the treatment algorithm. In patients post-myocardial infarction and those with heart failure, accurate and reliable assessment of LVEF is crucial, because once it exceeds 45%, ejection fraction no longer contributes significantly to cardiovascular risk assessment.^[22] Meanwhile, it is recognized that there may be some discrepancy between LVEF derived from CMR and echocardiography.^[8] If a specific cut-off value for ejection fraction is used to stratify risk or guide treatment decisions, the diverse techniques will have considerable impact on who is treated, with both clinical and financial consequences. Therefore, caution should be exercised when interpreting LVEF findings in light of locally available techniques.

Although LVEF has been the primary metric to assess systolic left ventricular dysfunction, it is influenced by cardiac load and therefore may be insensitive to detect subtle changes in contractile reserve. As a result, this measure can significantly underestimate or misdiagnose asymptomatic patients with slowly progressing myocardial disorders. To address this limitation, novel parameters based on volume data have been proposed which may play a promising role in quantifying or predicting left ventricular dysfunction. For example, simultaneous measurements of volume from cine imaging and invasive left ventricular pressures could be used to quantitatively evaluate contractility and compliance through pressure-volume loops during dynamic preload reduction.^[23]

2.3.2. Left atrium

The left atrial performance can be divided into 3 distinct phases throughout the cardiac cycle: an atrial systole filling phase, an early diastolic rapid ventricular filling conduit phase, and a late diastole active contraction phase. These phases serve 3 functions, namely reservoir, conduit, and pumping that can be evaluated by utilizing CMR-based volumes at different stages. Total emptying, assessed as a cyclic change, refers to the disparity between the maximum and minimum volumes of the left atrium. Passive emptying, represented as left atrial passive volume, can be quantified by calculating the difference between maximum left atrial and pre-atrial contraction volumes. Active left atrial emptying, indicated by left atrial stroke volume, is defined as the difference between pre-atrial contraction and the minimum left atrial volume. The filling function can be further represented by an ejection fraction in each distinct phase, encompassing total left atrial ejection fraction (LAEF), passive LAEF, and active LAEF. Reference values for phasic left atrial volumes and ejection fraction according to sex are shown in Table 1. Left atrial dilation is a compensatory mechanism in response to elevated LVFP resulting from left ventricular diastolic dysfunction. Garg et al^[24] proved the diagnostic accuracy of CMR-modeled LVFP estimated from left atrial volume and left ventricular mass. In patients with suspected heart failure, this method can correctly reclassify cases where echocardiology is inconclusive and identify individuals at an elevated risk of mortality. In addition, its predictive accuracy for survival prognosis is comparable to, if not non-inferior to, that of pulmonary capillary wedge pressure derived from right heart catheterizationd. Furthermore, superior to left atrial size enlargement, LAEF may also be a classifier for left ventricular dysfunction as it deteriorates before atrial volumes are measurably affected.^[13,25] In patients diagnosed with systemic light-chain amyloidosis, CMR-assessed LAEF shows association with Mayo Clinic stage, New York Heart Association functional class, myocardial late gadolinium enhancement (LGE), and 2-year mortality.^[26]

Traditionally, left atrial dysfunction has been regarded as an indicator or consequence of other cardiac conditions rather than the primary etiological factor itself, but recent evidence has indicated that left atrial failure may be an early driver or a crucial pathogenic factor in cardiac dysfunction. For example, LAEF and left atrial volume are strongly linked to prevalent and incident cardiovascular outcomes, regardless of left ventricular metrics.^[27] Furthermore, up to 45% patients presenting with heart failure with preserved ejection fraction (HFpEF) onset have underlying left atrial dysfunction as the mechanism.^[28] Therefore, gaining a comprehensive understanding of left atrial mechanics is imperative.

2.3.3. Right atrium and ventricle

The use of CMR is particularly advantageous for assessing the morphology and function of the right ventricle and right atrium, overcoming the challenges posed by the unique anatomy of the right chamber and anterior location beneath the sternum within the chest. For example, one of the diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy is severe dilation of the right ventricle and a reduction in its ejection fraction, which can be assessed using CMR.^[29] Reference values for right atrial and ventricular volumes and ejection fraction according to sex are shown in Table 1. Given the independent association between right ventricular ejection fraction and heart failure hospitalization as well as mortality, it serves as a valuable tool for selecting candidates for transcatheter aortic valve replacement,^[30] or revising the stratification of prognostic assessment in patients with heart failure.^[31]

Although there is a scarcity of data on right atrial remodeling and shape alterations, recent advance of artificial intelligence has enabled automated analysis of right atrial size and function with high efficiency and moderate associations compared to invasive hemodynamics.^[32] Men demonstrate greater right atrial volume, while women have higher right atrial ejection fraction; for both sexes, aging is associated with decreased right atrial ejection fraction.^[5] Although recent studies have suggested a frequent occurrence of bi-atrial remodeling in atrial fibrillation, an interesting finding was that the presence of right atrial remodeling does not predict atrial fibrillation recurrence after atrial fibrillation ablation.^[33]

Overall, while CMR cine imaging allows for a comprehensive evaluation of cardiac morphology and function, the measurable indices like ejection fraction or volume primarily reflect manifestations of advanced disease progression. However, it is important to undertake the arduous task of identifying early disease development indicators or subtle regional information, thereby shifting the emphasis from LVEF to an alternative metric such as strain.

3. Advanced myocardial deformation imaging with strain

Myocardial deformation is considered complementary to standard measures of ejection fraction and is sometimes more effective in detecting alterations in left ventricular function, which can be precursors to overt structural and functional deficits. To gain a comprehensive understanding of deformation, it is imperative to possess a profound comprehension of myocardial architecture and the distinct contributions made by various layers of the myocardium to left ventricular strain. The myocytes are arranged in planes that run parallel to the longitudinal axis of the heart, forming local average “fiber” direction. In proximity to the midwall of the ventricle, this orientation becomes predominantly circumferential (resembling a “hoop”). However, it undergoes clockwise rotation resulting in a left-handed helix with an angle greater than or equal to 60° in the subepicardium and counterclockwise rotation leading to a right-handed helix with an angle less than or equal to 60° in the subendocardium. Contraction induces strains and corresponding shears across these layers with varying orientations. Radial strain arises from the contraction of fibers occurring in all layers, accompanied by thickening and inward displacement of the myocardium. Longitudinal strain refers to the contraction of myocardial fibers from the base toward the apex, whereas circumferential strain signifies fiber shortening along the circular perimeter [Figure 2].^[34] The intricate architecture of the left ventricle enables only 15% fiber shortening to translate into a substantial 60% alteration in the left ventricular volume.

Figure 2.

Components of LV myocardial deformation. (A) Myocardial strain can be projected into a cylindrical system of reference centered around the left ventricle. A longitudinal strain curve (B) is derived from the long-axis four chamber cine image, while the short-axis image is utilized for calculating radial (C) and circumferential strain (D) curves in a healthy volunteer. AR: Apical rotation; BR: Basal rotation; GCS: Global circumferential strain; GLS: Global longitudinal strain; GRS: Global radial strain; LV: Left ventricular.

3.1. Acquisition methods

Speckle-tracking echocardiography is well established as a modality for assessing myocardial stiffness,^[35] but its reproducibility is heavily dependent on image quality.^[36] Strain imaging using CMR has generated considerable attention as a promising development in this field. It can provide valuable clinical contributions to the appraisement of myocardial deformation through either tailored image acquisition or post-processing software [Table 2].

Table 2.

Characteristics of CMR techniques to assess myocardial strain with main advantages and disadvantages.

CMR technique	How to work	Advantages	Disadvantages
Dedicated acquisition
CMR tagging	Track planes of saturated myocardial magnetization tags	•Good tags tracking •Higher reproducibility of plane acquisitions •Extensive validation	•Low spatial and temporal resolution •Fading tags •Long post-processing and acquisition time
DENSE	Encode tissue displacement with intrinsic phase correction	•High spatial resolution •Good-quality strain in short acquisition time	•Low signal-to-noise ratio •Fading tags •Modest clinical experience
SENC	Use magnetization tags parallelly overlaid on the myocardium	•High spatial resolution •Fast post-processing •Better reproducibility	•Measures only through plane strain •No radial strain •Fading tags •Modest clinical experience
PVM	Encode myocardial velocity in 3 directions	•High spatial resolution	•Low temporal resolution •Time-consuming and cumbersome
Post-processing method
FT-CMR	Track features along the myocardial wall detailing endocardial and epicardial contour	•Regional and global strain measurements •No additional image acquisition	•Low spatial and temporal resolution •Less performance for regional strain •No standardization •Inter-vendor differences •No rotation/twist

CMR: Cardiac magnetic resonance; DENSE: Displacement encoding with stimulated echoes; FT-CMR: Feature-tracking CMR; PVM: Phase-velocity mapping; SENC: Strain-encoded imaging.

The CMR tagging technique, initially introduced by Zerhouni et al,^[37] has been extensively employed in numerous clinical studies and is widely acknowledged as the gold standard for validating other strain measurement techniques including speckle-tracking echocardiography.^[38,39] This methodology entails an initial pre-acquisition phase wherein magnetic labels (black lines, tags) are precisely positioned over the myocardium. Subsequently, by tracking the motion of these tags that move simultaneously with the myocardium, a direct quantification of myocardial relaxation and strain throughout the cardiac cycle can be obtained.^[40] Despite being the most extensively validated CMR technique for assessing myocardial strain, tagging is limited in terms of low spatial resolution and its ability to evaluate thin myocardial layers. Furthermore, dedicated acquisition and long post-processing time are what mainly limit its use as predominant research tools. Subsequent methods based on the principles of tagging have been introduced for strain evaluation, including displacement encoding with stimulated echoes and strain-encoded imaging.^[41,42] These techniques enable rapid examination through a single-shot acquisition in one heartbeat, facilitating faster post-processing and ensuring excellent reproducibility. However, similar to tags, displacement encoding with stimulated echoes is unable to fully assess the entire cardiac cycle because of the tendency for encoding to disappear. The main limitation of strain-encoded imaging is its inability to evaluate radial deformation; whereas, longitudinal strain on short-axis images and circumferential strain on long-axis images can be assessed. Likewise, phase-velocity mapping CMR offers an alternative approach for evaluating myocardial deformation by allowing calculations of myocardial velocities in 3 directions with enhanced spatial resolution, albeit at the expense of reduced temporal resolution.^[43] Feature-tracking CMR is a post-processing technique that can be applied to routinely acquired cine images.^[44,45] The endocardium features are tracked over time in successive imaging frames, allowing for the measurement of deformation. Specifically, this method entails the delineation of a small patch surrounding the pixel within a single frame, followed by an extensive search for a corresponding patch of pixels in the subsequent image frame. The distance between these 2 identified regions determines the local tissue displacement, providing measurements independent of ventricular size or shape and without requiring dedicated acquisition.^[44,45] However, it should be noted that cine images used in feature-tracking CMR exhibit significantly reduced spatial and temporal resolution when compared to tagging.^[45]

Despite the presence of various strain techniques based on CMR, standardization remains a distant objective considering their research progress, technological challenges, or variations in clinical practices. The reported normal ranges exhibit significant variabilities attributed to multiple factors, including those associated with the imaging modality, software and vendor used, operator expertise, patient demographics, and hemodynamic characteristics.^[46,47,48] As shown in Table 3, longitudinal and circumferential strains demonstrate negative values indicating shortening, thinning, and/or contraction; whereas, radial strain shows positive values suggesting lengthening, thickening, and/or relaxation. An abnormality is determined by a mathematically higher threshold for negative-strain variables and a lower threshold for positive-strain variables. Longitudinal strain is among the most frequently utilized deformation components given its (almost) uniform distribution along the wall and its ability to evaluate the entire left ventricle in an easy and reliable manner.

Table 3.

Comparison of reference global strain values by CMR techniques. ^[46,47,48]

CMR technique	LVGLS	LVGCS	LVGRS	RVGLS	LAtotal	RAtotal
CMR tagging	−14.6 (−16.2 to −12.9)	−19.9 (−21.1 to −17.7)	16.2 (11.2–21.2)	ND	ND	ND
DENSE	ND	−19.0 (−19.7 to −18.3)	24.3 (16.2–32.2)	ND	ND	ND
SENC	−20.0 (−22.5 to −17.4)	−20.9 (−22.4 to −19.3)	ND	−18.7 (−19.5 to −17.9)	ND	ND
FT-CMR	−18.4 (−19.2 to −17.6)	−21.4 (−22.3 to −20.6)	43.7 (40–47.4)	−24.0 (−25.8 to −22.1)	34.9 (29.6–40.2)	36.3 (15.5–57.0)

Data are presented as mean (95% confidence interval). CMR: Cardiac magnetic resonance; DENSE: Displacement encoding with stimulated echoes; FT-CMR: Feature-tracking CMR; GCS: Global circumferential strain; GLS: Global longitudinal strain; GRS: Global radial strain; LA: Left atrium; LV: Left ventricle; ND: No data; RA: Right atrium; RV: Right ventricle; SENC: Strain-encoded imaging.

3.2. Strain parameters and factors affecting strain values

The normal motion of the heart wall and its associated strain patterns are influenced by a complex interplay of forces among various structures. Myocardial deformation, as a compensatory mechanism, develops in response to changes in various conditions within the cardiac muscle. Previous studies have confirmed that preload positively affects strain through the Frank-Starling mechanism when contractile function is preserved.^[49] In patients with acute volume overload caused by mitral or aortic regurgitation, early-stage disease is characterized by increased deformation while maintaining intact myocardial contractility.^[50,51] The impact of chronic increases in afterload, such as systemic hypertension, pulmonary hypertension, and aortic stenosis, has been consistently observed to result in the reduction of left ventricular global longitudinal strain (GLS) according to several studies.^[52,53] In addition, the afterload on myofibers is determined by the pressure within the cavity, while ventricular geometry (such as diameter and wall thickness) determines how cavity pressure translates into the relevant parameter of “wall stress.” For example, in later stages of severe regurgitation, prolonged volume overload leads to progressive chamber enlargement accompanied by escalating wall stress and ultimately irreversible contractile dysfunction characterized by reduced strain values.^[51] To account for abnormal volume compensation, it might be worth considering correcting strain values based on left ventricular volumes in future analyses. Furthermore, for a given pre- and afterload, in addition to intrinsic contractility, the shortening of myofibers can be further influenced by various other tissue characteristics. One such characteristic is fibrosis and depositions within the myocardium that can alter the contractile properties of the muscle fibers. The heterogeneity of myocardial function, either regionally or temporally, as well as alterations in passive properties of the myocardium can also affect myofiber shortening. Illustrative examples include ischemic disease, which leads to reduced contractility due to scar formation following inadequate blood supply over a prolonged period; various infiltrative and storage diseases such as amyloidosis or hemochromatosis; toxic effects resulting from chemotherapy; and other conditions that induce irreversible damage to myocytes. Finally, pathologic interactions occur between the left ventricular walls owing to conduction delays like left bundle branch block, resulting in heterogeneous myocardial activation.^[54]

3.3. Clinical applications

Strain measurements have been recommended as essential functional parameters in routine echocardiography guidelines. Thanks to ongoing technological advancements, strain derived from CMR is poised to offer valuable supplementary insights in the domains of diagnosis, pathophysiology, and risk stratification [Table 4]. Given these advantages, the incorporation of CMR-based strain analysis into routine clinical evaluations is eagerly anticipated and expected to become a standard practice in the near future.

Table 4.

Clinical application of LV myocardial strain by cardiac disease.

Disease	Factors affecting strain	Recent clinical application
Ischemic disease	•Regional inhomogeneity in contractility	•Predict outcomes and stratify risks in ischemic cardiomyopathy •Monitor cardiac function and validate novel therapies •Identify infarct tissue and segments that will recover function
Cardiomyopathy	•Chamber geometry •Myocardial deposits and fibrosis •Reduced contractility •Regionally inhomogeneous function	•Understand the pathophysiology of non-ischemic cardiomyopathies •Distinguish cardiac amyloidosis from other forms of LV hypertrophy •Detect early cardiac dysfunction before LVEF •Predict outcomes in DCM, HCM, amyloidosis, and myocarditis
Valvular heart diseases and congenital heart disease	•Preload and afterload •Chamber geometry (remodeling) •Contractility	•Identify asymptomatic patients who may benefit from surgery •Select optimal surgical time and approach •Identify early dysfunction after surgery
Cardiotoxicity	•Globally impaired contractility	•Identify and monitor for subclinical cardiac dysfunction after cancer treatment
Cardiac resynchronization therapy	•Inhomogeneous timing of contraction •Inhomogeneous regional remodeling	•Deliver insights into the complexities of cardiac mechanical dyssynchrony •Guide LV lead deployment •Identify responders for cardiac resynchronization therapy

DCM: Dilated cardiomyopathy; HCM: Hypertrophic cardiomyopathy; LV: Left ventricle; LVEF: Left ventricular ejection fraction.

3.3.1. Left ventricular strain

3.3.1.1. Ischemic heart disease

The subendocardially located longitudinally orientated fibers are particularly vulnerable to ischemia, making GLS a more sensitive metric for risk stratification and an independent and superior predictor of outcomes compared to well-known risk markers such as LVEF, severity of infarction, or microvascular obstruction in ischemic heart disease.^[55] When it comes to monitoring cardiac function and validating novel therapies among STEMI patients, both GLS and global circumferential strain (GCS) have shown robustness and potential accuracy.^[56] Aditionally, deterioration of GCS has discriminative value between normal and stenotic segments as well as between stenotic and neighboring segments.^[57] However, the impact of most pathologies on the heart is not uniform, necessitating the identification of regional dysfunction which may be concealed by seemingly “normal” values of global function. For instance, the circumferential strain in regions of infarcted tissue, as highlighted by LGE, is markedly different from that of healthy myocardium. This distinction provides clinically valuable insights into the contractile function and its potential for recovery in patients with myocardial infarction.^[58]

3.3.1.2. Non-ischemic heart disease

Strain analysis offers valuable insights into the pathophysiology of various non-ischemic heart diseases. Specifically, in isolated left ventricular non-compaction, the apical subendocardium is predominantly affected because of the compaction process occurring from the basal segment to the apex and from the epicardium to the endocardium.^[59] This phenomenon accounts for why middle and apical longitudinal strain decrease more prominently in left ventricular non-compaction than in dilated cardiomyopathy, which primarily affects disordered myocardial fibers in the midwall layer, that is circumferentially arranged myocardium.^[60] “Apical sparing” is a phenomenon observed in patients with cardiac amyloidosis, where the apex of the heart is preserved or relatively spared from significant strain and thickening compared to other regions. The coexistence of a base-to-apex gradient in quantitative LGE burden among these patients suggests that apex sparing may be partially attributed to the extent of amyloid deposition and fibrosis. Therefore, one potential significance of strain measurements lies in their ability to eliminate the need for intravenous contrast material if a strong linear correlation between impaired strain and the presence of LGE is observed.^[61] Meanwhile, several studies have utilized CMR to differentiate cardiac amyloidosis from hypertensive heart disease and hypertrophic cardiomyopathy by examining the presence of apical sparing.^[62,63] Overall, strain measurement sheds lights on the pathophysiology of various non-ischemic heart diseases and thus provides a new approach for differential diagnosis; however, further research in these directions is still needed.

CMR strain imaging has demonstrated its significance across a broad spectrum of cardiovascular diseases, not only allowing for early detection of cardiac dysfunction before changes in LVEF occur,^[64,65] but also contributing to improved risk stratification and provides incremental/independent prognostic value. For instance, impaired GLS demonstrated significant independent predictive value for mortality or major adverse cardiac events (MACE) in patients with dilated cardiomyopathy, surpassing routine and dedicated functional parameters such as ejection fraction and LGE.^[66,67] In patients with hypertrophic cardiomyopathy, reduced longitudinal deformation among strains in 3 directions remains a significant independent predictor of MACE, including sudden cardiac death, resuscitated cardiac arrest due to ventricular fibrillation or hemodynamically unstable ventricular tachycardia, and hospitalization for heart failure.^[68] Strain as an independent predictor of adverse outcomes is similarly validated against in myocarditis.^[69,70]

3.3.1.3. Valvular heart disease and congenital heart disease

Strain may potentially contribute to patient selection for surgery in valvular heart disease. For example, patients with severe aortic stenosis who are asymptomatic or have only mild symptoms demonstrate a significant reduction in both circumferential and longitudinal strain, comparable to those with pronounced symptoms necessitating aortic valve replacement.^[71] Strain is also a valuable tool for clinicians and researchers to understand and compare the immediate effects of different treatments after aortic valve replacement: transcatheter aortic valve implantation leads to an immediate improvement in GLS, and early after surgical aortic valve replacement, there is a notable worsening of GLS. In the longer-term follow-up, both interventions are found to be associated with an improvement in left ventricular myocardial deformation and a reduction in left ventricular hypertrophy.^[72] Additionally, several pieces of evidence have provided further information, paving the way toward validating strain as an indicator for early identification of dysfunction after surgery in several congenital heart disease and asymptomatic heart transplant patients.^[73]

3.3.1.4. Cardiotoxicity

The advantage of strain measurement, which exhibits less dependency compared to ejection fraction, is particularly valuable in clinical scenarios where subtle changes in myocardial function are of critical importance, such as the detection of chemotherapy-induced cardiotoxicity. The American Society of Echocardiography and the European Society of Cardiology recommend a relative drop in GLS exceeding 15% compared to baseline as clinically significant.^[74] Although fairly under developed, clinical trials are currently underway to evaluate the efficacy of initiating cardioprotective medication based on CMR strain parameters. CMR has shown that LVEF and GCS exhibit early deterioration and persistently abnormal levels even after 6 months of initiating low-to-moderate doses of anthracyclines.^[75] Breast cancer patients undergoing trastuzumab treatment exhibit a significant decrease in GLS and GCS, which corresponds with a decline in LVEF at 6 months and 12 months.^[76] Previous studies have demonstrated that left ventricular diastolic impairment precedes the reduction of LVEF in the context of anthracycline-related cardiotoxicity.^[77] However, it appears that systolic strain rates may be more pertinent than diastolic strain rates in monitoring subclinical trastuzumab-related myocardial impairment, as evidenced by the sustained stability of diastolic strain rates for 18 months following therapy initiation in a study involving cancer patients receiving trastuzumab.^[78] Therefore, investigating whether strain-guided therapy could provide enhanced cardiac protection to survivors of potentially cardiotoxic chemotherapy is an area of research interest.^[79,80]

3.3.1.5. Cardiac resynchronization therapy

Considerable efforts have been made to the imaging-based identification of dyssynchrony to select optimal candidates for cardiac resynchronization therapy. More recently, the feasibility of feature-tracking CMR has been demonstrated for evaluating left ventricular dyssynchrony.^[81,82] In patients undergoing cardiac resynchronization therapy implantation, deploying a lead over non-scarred segments with the latest mechanical activation has demonstrated significant reverse remodeling and improved clinical outcomes compared to deploying the lead over scarred and/or earlier activated segments.^[83] Emerging evidence suggests that identifying specific patterns of mechanical dyssynchrony can greatly increase the response rates to cardiac resynchronization therapy, while relying solely on simplistic measures such as time to peak strain or peak velocity differences may lead to suboptimal patient selection for cardiac resynchronization therapy.^[81,84]

3.3.2. Left atrial strain

Atrial strain, which indirectly reflects left ventricular relaxation ability and compliance, has increasingly played a significant role in cardiac performance. Given the unique orientations of fibers and the thinness of the atrial wall, only longitudinal strain is typically assessed at the atrial level. Left atrium strain comprises 3 components, namely passive strain (ε_E, corresponding to conduit function), active strain (ε_A, related to booster pump function), and total strain (ε_S, representing reservoir function). Normal values for left atrium-global strain are 34.9% (29.6%–40.2%) for the reservoir function, 21.3% (16.6%–26.1%) for the conduit function, and 14.3% (11.8%–16.8%) for the booster pump phases, respectively. The left atrial strain can vary with age, sex, and ethnicity. Female patients tend to have higher values of left atrial strain parameters than male patients. As individuals age, the active strain and strain rate gradually increase, while passive strain gradually decreases. This phenomenon may serve as a compensatory mechanism in response to impaired ventricular diastolic function. The variation in active strain was influenced by the regional distribution of the population, with Asian subjects exhibiting the highest strain values. Other factors also include post-processing vendors.

Dysfunction of the left atrium is commonly observed in patients with atrial fibrillation. The strain on the left atrial reservoir and conduit is significantly reduced in patients with atrial fibrillation who exhibit extensive atrial fibrosis.^[85] Therefore, apart from predicting the onset of new atrial fibrillation, left atrial strain can also serve as a predictor for atrial fibrillation recurrence after ablation.^[86,87] Left atrial remodeling, characterized by decreased peak reservoir strain even in the presence of normal left atrial size, has been observed in cardiometabolic conditions such as diabetes.^[88] These patients exhibited a heightened risk of MACE in the presence of elevated filling pressure and diastolic dysfunction diseases such as STEMI and heart failure.^[89,90] In patients with hypertrophic cardiomyopathy, impairments of both left atrial reservoir and conduit precede the enlargement of the left atrium,^[91] suggesting that left atrial strain is a more sensitive indicator than left atrial volume for detecting involvement of the left atrium in hypertrophic cardiomyopathy. While they are both strongly associated with outcomes,^[92] left atrial conduit strain appears to be a stronger predictor of outcome than reservoir strain. It outperforms left ventricular GLS, LVEF, and left atrial volume index in predicting all-cause mortality and hospitalization due to heart failure.^[93] In summary, the utilization of left atrial strain analysis holds significant potential in various clinical scenarios primarily involving the left atrium, including atrial fibrillation prediction, post-ablation atrial fibrillation recurrence evaluation, and risk stratification in cardiomyopathy.

3.3.3. Right atrial and ventricular strain

Similarly, extensive research has been conducted on right ventricular free wall strain and right atrial strain. In contrast to the observed left ventricular strain patterns, the right ventricular myofibers exhibit a predominant inner longitudinal and outer oblique orientation.^[94] As a result, right ventricular strain and strain rates demonstrate a more heterogeneous distribution compared to the left ventricle, displaying a reverse base-apical gradient. However, there is currently a relative lack of validation in large samples for reference ranges of right ventricular strain [Table 3].

The latest research findings have demonstrated that in healthy volunteers, right ventricular longitudinal shortening plays a more significant role in determining right ventricular systolic function than circumferential shortening. Moreover, right ventricular free wall longitudinal strain provides prognostic insights for patients with severe functional tricuspid regurgitation beyond common clinical and CMR risk factors such as right ventricular function, size, and the presence of LGE.^[95] However, in patients with pulmonary hypertension, the rate of GCS was superior than GLS in identifying patients at heightened risk of combined events of death, lung transplantation, or functional class deterioration.^[96] In addition to its diagnostic value in cases of arrhythmogenic right ventricular cardiomyopathy,^[97] biventricular myocardial deformation represents a significant advancement in risk stratification over traditional measures such as right ventricle size and clinical variables when assessing prognosis in patients with repaired tetralogy of Fallot.^[98] Interestingly enough, right ventricular longitudinal strain emerges as an independent predictor of ventricular tachycardia in hypertrophic cardiomyopathy^[99]; however, its diagnostic value is limited in the context of myocarditis.^[100] Taken together, recent studies have suggested that CMR-derived right ventricular strain could serve as a reliable prognostic indicator for patients with tricuspid regurgitation, hypertensive heart disease, arrhythmogenic right ventricular cardiomyopathy, tetralogy of Fallot, or certain types of cardiomyopathy.

The right atrium is now being recognized as more than a passive chamber and can be divided, similar to the left atrial strain, into 3 phases (reservoir, conduit, and booster). However, accurately assessing right atrial deformation using speckle-tracking echocardiography poses significant challenges due to its extremely thin atrial wall, the retrosternal location, and the presence of the caval venous system. Many studies have focused on the crucial role of right atrial strain in pulmonary hypertension.^[101,102] Moreover, it is interesting to note that altered phasic function of the right atrium in response to chronic right ventricular pressure overload highlights the importance of paying attention to right atrial function when managing patients with pulmonary hypertension and systemic congestion caused by backward venous flow.^[103] While the incremental deterioration of bi-atrium strain indicates bi-atrial dysfunction caused by increasing left ventricular diastolic dysfunction and atrial fibrillation,^[104] it has been found that right atrial parameters could not predict atrial fibrillation recurrence after atrial fibrillation ablation.^[33] Furthermore, analysis of right atrial strain may also have clinical utility and prognostic value in conditions such as dilated cardiomyopathy,^[105] HFpEF,^[106] and myocardial infarction.^[107]

4. Flow imaging

To maintain efficient cardiac output, the intra-cardiac blood flow should be adjusted in response to structural changes in the heart. Hence, flow analysis may likely unveil preclinical manifestations of disease or physiologically unstable conditions that may initiate progressive left ventricular remodeling and eventually lead to clinically overt heart failure. While wall motion abnormalities like hypokinesia or asynchrony directly indicate the presence of overt clinical disease, abnormal flow patterns could suggest maladaptive function even prior to detectable structural changes. The utilization of phase-contrast imaging techniques or cine imaging techniques has provided valuable clinical insights particularly into physiological and pathophysiological processes of cardiovascular diseases, otherwise unachievable with conventional cardiovascular imaging.

4.1. The utilization of phase-contrast imaging

4.1.1. 2D CMR phase-contrast imaging

Although Doppler echocardiography is commonly selected as the initial test for assessing flow in valvular heart disease, its precision heavily relies on the operator. Challenges such as poor acoustic windows, inappropriate probe placement, and misalignment of the left ventricle often compromise its reliability. In contrast, the 2D CMR phase-contrast imaging overcomes many limitations associated with echocardiography by utilizing its inherent flow sensitivity to generate phase images, in addition to acquiring magnitude images similar to conventional cardiac gated cine MR.^[108] This technique operates on the principle of velocity-encoding, where 2 opposing gradient pulses are added to the imaging sequence. In pixels with stationary tissue, the effects of the 2 pulses cancel each other out. However, if there is tissue motion between the pulses, a phase shift proportional to the velocity along the gradient’s direction is observed in that pixel. Typically, single-direction (through-plane) velocity encoding is used for image acquisition during breath-holding, as it is less affected by motion outside of the imaging plane. Consequently, if flow is required at different locations, it is necessary to repeat the acquisition process at each site to ensure perpendicular intersection with the vessel of interest. However, this technical and time-consuming procedure may pose difficulties for patients, particularly those with complex congenital heart disease. In addition, precise setting of the sensitivity of velocity encoding (Venc) before image acquisition is crucial to phase-contrast imaging, and it is determined by the disparity in flow sensitivities between the 2 acquisitions. High Venc causes a decreased velocity-to-noise ratio, while low Venc leads to aliasing artifacts. After acquiring the image data, the resulting phase is calculated and subtracted from 2 separate images to generate a velocity image, in which the gray scale of each pixel represents the velocity of blood flow. Generally, the stationary tissue appears as mid-gray, while forward (positive) and reverse (negative) velocities are indicated by higher and lower pixel intensities, respectively. Phase-contrast imaging can assess various aspects of complex blood flow in the heart and vessels: volume flow, peak blood and pulse-wave velocity, patterns and timings of velocity waveforms, and wall shear stress (mainly in the great vessels). The current clinical applications of phase-contrast imaging in cardiac assessment will be discussed later. More comprehensive applications pertaining to the great vessels are beyond the scope of this review, but have been covered elsewhere.^[109]

In patients with valvular heart disease, it is important to identify valvular stenosis and/or regurgitation, assess their severity, as well as any associated anatomical abnormalities. Historically, the severity of aortic stenosis has been assessed by evaluating the transvalvular pressure gradient and valve area calculated through phase-contrast-derived measures that have demonstrated excellent concordance with color Doppler echocardiography measurements.^[110,111] However, there is often disagreement between Doppler echocardiography and CMR in grading the severity of regurgitation, which affects intervention timing and surgical planning in patients with aortic regurgitation.^[112] The slight superiority (difference) of CMR over echocardiography can be attributed to its direct measurement of valve flow, including regurgitant volume, as opposed to relying on secondary estimates like vena contracta or proximal isovelocity surface area, which compromise the reliability of echocardiography. In the evaluation of left-to-right shunts, 2D phase-contrast imaging not only provides precise characterization of the defect in terms of its presence, location, and size but also enables simultaneous computation of the pulmonary-to-systemic ratio by evaluating both the pulmonary trunk and ascending aorta. This approach exhibits substantial concordance when compared to catheter oximetry.^[113] Therefore, phase-contrast-CMR is highly suitable for the pre- and post-surgical evaluation of patients with congenital heart disease owing to its capability in providing reliable evaluation of intricate cardiac and vascular anatomy as well as hemodynamics. This enables distinct management approaches and facilitates routine follow-up tests.^[114] However, before its practical clinical usefulness can be confirmed, further studies involving larger populations are needed.

4.1.2. 4D flow CMR

4D flow CMR encodes the velocity in all 3 directions within a defined volume over time. This technique provides a time-resolved, three-directional phase-contrast imaging where “4D” denotes the combination of 3D plus time, thereby overcoming previous limitations in capturing multi-dimensional and multi-directional flow characteristics. Just as in 2D phase-contrast CMR, Venc sensitivity is required for optimal control, which is usually close to the maximum velocity (<25% above), but this value must be adjusted as guidance when stenosis or abnormal structure is suspected.^[115] Similar to 2D phase-contrast imaging, variations in gradient fields give rise to spatial and temporal phase offsets, leading to inaccuracies in velocity measurements. The primary sources of errors that necessitate correction prior to flow visualization and quantification include Maxwell terms, Eddy current effects, gradient field distortions, and phase wraps. Optimal corrections for background phase offsets may differ depending on CMR systems, sequences, protocols, and regions of interest.

Despite the time-consuming and intricate nature of data processing, the utilization of diverse visualization modalities offers unparalleled capabilities to present distinct and complementary representations of the same flow field. Visualization techniques commonly employed in 4D flow CMR encompass velocity-based color coding, instantaneous streamlines, and pathlines [Figure 3]. The magnitude of velocity can be visually depicted through color coding or by adjusting vector sizes, or a combination thereof. Instantaneous streamlines are traces that run parallel to velocity vectors at all spatial points along their length in a 3D velocity field, rendering them suitable for illustrating a specific moment within an evolving flow field. This enables characterization of blood flow patterns such as laminar flow, helical flow, and vortical flow. In contrast to streamlines, pathlines illustrate the trajectory of a particle (ie, voxel) over time by performing backward/forward particle tracing using time integration methods for displacement calculation based on velocity data.

Figure 3.

Visualization of blood flow using 4-dimensional flow cardiac magnetic resonance. The blood flow in panel (A) is visualized using a color-coded vector glyph representation, which accurately depicts both the direction and magnitude of velocity. In contrast, panel (B) utilizes a pathline representation, while panel (C) employs a streamline representation.

The quantification of flow volume using CMR is commonly employed in numerous institutions for the estimation of mean/peak velocity and flow volume, among other parameters.^[116] The 4D flow measurements of blood flow exhibit strong agreement with those obtained in 2D CMR and demonstrate excellent scan-rescan repeatability.^[117] In addition to the above-mentioned conventional intra-cardiac flow parameters, an increasing number of novel hemodynamic parameters are being investigated, including kinetic energy, turbulent kinetic energy (TKE), pressure gradient, and differential flow analysis. With significant advancements in CMR acceleration, 4D flow CMR has transitioned from being solely a research tool to becoming an essential resource for clinicians. Consequently, there has been an exponential increase in the number of publications on this topic in recent years.

4.1.2.1. 4D flow CMR vs. 4D color Doppler echocardiography

To enhance the clinical assessment of cardiac function by incorporating flow-mediated hemodynamic forces (HDFs), the application of 4D color Doppler echocardiography has been extensively investigated in clinical research, such as the direct quantification of mitral regurgitant flow volume using dealiasing of color Doppler flow at the vena contracta or imaging the mitral annulus and the left ventricular outflow tract to quantify mitral inflow and aortic stroke volumes within the same cardiac cycle.^[118,119] However, several challenges such as the difficulty in configuring echo window settings remain unresolved, making it impractical for cases involving complex 3D flow or high-velocity jets. In comparison, besides offering a comprehensive evaluation of flow in any direction within the acquired volume of interest, 4D flow CMR also enables the generation of numerous novel hemodynamic parameters that have the potential to unlock new avenues for managing cardiovascular diseases. Given the significance of ensuring consistency, reliability, and comparability across different clinical settings, it is imperative to establish standardized protocols for integrating sophisticated 4D CMR techniques into clinical practice.

4.1.3. Advanced hemodynamic analysis based on 4D flow

4.1.3.1. Kinetic energy

Kinetic energy is transferred to the blood as the left ventricle actively expands during diastole and draws blood in from the left atrium, which can be calculated based on local velocity and rate of blood flow. In normal hearts, there are 3 kinetic energy peaks corresponding to the velocity peaks observed on trans-mitral Doppler echocardiography, occurring in mid-systole, early diastole (also known as the “E wave”), and end/late diastole (also known as the “A wave”). Within the left ventricle, the highest kinetic energy peak generated in early diastole serves as a reminder that ventricular relaxation is an active process. Reportedly, early diastolic peak kinetic energy declines with aging. It can be attributed to age-associated increases in cardiac stiffness which are believed to contribute to HFpEF.^[120] Therefore, diastolic kinetic energy could serve as a surrogate marker for ventricular compliance, and applying this technique to patients with HFpEF could provide further insights into the underlying pathophysiological mechanisms. A significant reduction in peak E wave kinetic energy is inversely associated with adverse remodeling observed in patients with STEMI, providing new hemodynamic insights for left ventricular remodeling.^[121]

4.1.3.2. TKE and viscous energy loss

A portion of the blood flow’s kinetic energy is converted into TKE when standard cardiovascular blood flow transitions from laminar to turbulent due to high-velocity fluctuations caused by conditions such as valvular stenosis. Energy loss is considered a novel indicator of flow inefficiency, resulting from friction between blood and the ventricular wall.

In the normal, healthy heart, TKE ranges from 0 to 5 mJ. However, in patients with dilated cardiomyopathy and valve diseases, the left ventricular TKE is significantly higher than that in a normal heart.^[122,123] Nevertheless, there is no current consensus on whether significant turbulence exists within the normal heart. Therefore, TKE is recommended as a complementary tool to echocardiography to provide new information about the pattern of blood flow. Similarly, the clinical implications of elevated levels of energy loss in the left ventricle require further investigation.

4.1.3.3. Flow component analysis

Quantification of 3D blood flow within the left ventricle has enabled separation into different functional flow components [Figure 4]: direct flow, the most efficient component that transits the heart in one cardiac cycle; retained inflow, which enters during diastole but does not leave until at least 1 cycle; delayed ejection flow, which resides inside the left ventricle during diastole and leaves during systole; and residual volume, which remains in the left ventricle for at least 2 cycles.

Figure 4.

Components of the left ventricular flow in a 50-year-old male patient with hypertrophic cardiomyopathy. The schematic representation in panel (A) illustrates the 4 components of left ventricular flow. Green: direct flow; Blue: delayed ejection; Yellow: retained inflow; Red: residual volume. Three time-points in the cardiac cycle are represented: diastole in panel (B), end diastole in panel (C), and systole in panel (D). AO: Aorta; LA: Left atrium; LV: Left ventricle.

The relative volumes and kinetic energy of each flow mentioned above can also be calculated to provide enhanced insights into left ventricular hemodynamics, alterations in which have been shown between normal left ventricles and under certain myopathic left ventricles.^[124] Several studies have showed a direct correlation between the volume and diastolic kinetic energy of the flow component.^[125] This is not surprising given that mass (where mass = mean density of blood × voxel volume) is a central component of kinetic energy. However, research on assessing left ventricular diastolic function using 4D flow CMR has so far been limited to small single-center studies.^{[124,125,126]} To comprehensively assess cardiac conditions involving left ventricular diastolic dysfunction and make definitive comparisons of novel 4D parameters with contemporary diagnostic markers requires larger multicenter and multimodality studies. Furthermore, despite no change in flow component volume, patients with left bundle branch block exhibit lower pre-systolic kinetic energy of direct flow component than those without it. This intriguing research proposes that 4D flow can serve as markers of response to cardiac resynchronization therapy.^[126]

4.1.3.4. Vortex flow analysis

A vortex is formed during diastole as blood flows into the left ventricle through the mitral valve, causing a redirection toward the left ventricular outflows. This process exhibits significant responsiveness to subsequent left ventricular maladaptation by amplifying even minor modifications in surrounding conditions like differences in energetic or dynamic properties. Relevant studies in echocardiography have previously characterized the phenomenon of vortex formation and its correlation with energy dissipation and impairment of diastolic function. Compared with echocardiography, vortex assessment based on 4D flow CMR, although relatively newer, can adequately detail vortex structures, dimensions, vorticity, and kinetic energy. The shape of mitral inflow to a significant extent determines the vortex shape and is hence of importance to vortex formation and energy efficiency of blood flow. This may explain why several groups have reported that advancements in blood flow analysis can be applied to regurgitant or stenotic valves. Vortex flow visualization techniques provide new options to quantify flow in atrioventricular septal defect and ischemic heart disease with reasonable accuracy.^[127,128]

4.1.3.5. Cardiac fluid dynamic forces

HDFs represent the force exchange between ventricular blood and the endocardium, serving as a global measure of the interventricular pressure gradient (IVPG) integrated over the left ventricular volume.^[129] HDFs changes have shown potential to assess cardiac function when volumetric and deformation cardiac measures remain intact^[130] making them a promising candidate for detecting early alterations in cardiac function and predicting disease outcomes.

HDFs occur along 3 planes within the left ventricle: basal-apical, septal-lateral, and inferior-anterior; among these, the basal-apical force has emerged as the most reproducible and detectable force across all patients. Normalized with respect to left ventricular volume, HDFs are expressed as a percentage of gravity acceleration, encompassing amplitude, timing, and orientation parameters.

In the 1990s, non-invasive estimation of IVPG was investigated by the spatial-temporal velocity distribution derived from 4D flow CMR. This approach deviated from the need for invasive assessments by utilizing either the simplified Bernoulli equation or the Navier-Stokes equation.^[131] The present literature provides characteristics for healthy subjects,^[132] against which the distribution of HDFs in left ventricles of dilated cardiomyopathy patients is altered.^[133] It has been reported that diastolic force patterns can differentiate between healthy individuals and patients with clinically compensated heart failure but dyssynchrony, thus indicating a potential role for this new approach in guiding cardiac resynchronization therapy treatment for patients with heart failure.^[134] However, recent research suggests that base-to-apical HDFs derived from HDF analysis (see below) are not consistently abnormal,^[135] implying that left ventricle HDFs are not yet ready for clinical trials assessing HFpEF.

4.2. The utilization of cine imaging

HDF analysis is an emerging technique that exploits endocardial edge tracking technology, requiring only manual drawing of valve diameters and endocardial contours on conventional 2-, 3-, and 4-chamber cine images [Figure 5].^[136] HDFs can be estimated using a validated mathematical model based on feature tracking, which has shown high accuracy when compared to 4D flow MRI for both instantaneous values (mean correlation coefficient r = 0.77) and global values (r = 0.88).^[137] Its straightforward application in existing datasets within minutes provides an opportunity to enhance the detection of early myocardial dysfunction beyond ejection fraction. Therefore, HDF assessment shifts the focus from wall mechanics to intracavitary fluid dynamics, which play a crucial role in inducing left ventricular remodeling during the early phase of myocardial infarction.^[138] In patients with HFpEF compared to controls, progressive reduction of HDFs revealed impairment of left ventricular systolic function prior to ejection fraction and deformation parameters such as GLS,^[135] and were superior to GLS in prediction of cardiovascular hospitalization.^[139] Recently, 2 visually distinctive IVPG patterns have been introduced in the dilated cardiomyopathy population, of which the pressure reversal pattern was negatively affecting diastolic filling, independently associated with worse outcome.^[140] Despite being considered a valuable novel tool for quantitative cardiac function assessment, further larger-scale studies are needed to validate the proposed techniques and explore the clinical advantages offered by HDF analysis over standard practices.

Figure 5.

Procedure of hemodynamic forces analysis based on cine imaging. 2C/3C/4C: 2/3/4 chambers; HDF: Hemodynamic force; RMS: Root mean square.

5. Limitations

Over the past decade, advances in CMR have rendered this imaging modality indispensable for managing patients with cardiovascular disease. However, it does possess certain limitations and contraindications that need to be considered. CMR requires a dedicated cardiac scanner and local expertise, along with longer acquisition times and higher costs than echocardiography. Other limitations include unreliable measurements in patients with tachyarrhythmias or breathing artifacts, while claustrophobia and commonly contraindicated magnetic devices such as left ventricular assist devices are important contraindications.

6. Conclusions

Although non-invasive volumetric estimation from cine imaging is the cornerstone of cardiac function assessment, contemporary CMR moves far beyond the simplistic evaluation of LVEF to encompass the intricate mechanics and pathophysiological changes of the ventricles. Strain imaging progressively and firmly integrates into daily clinical practice, providing an additional layer of knowledge on cardiac mechanics. Differently, flow imaging has evolved to provide novel physiological insights and the potential to detect functional alterations before evident or irreversible tissue modifications occur. Incorporating emerging cardiac imaging modalities into routine practice will significantly enhance cardiac function assessment. Despite gaps in knowledge, the future remains brimming with newer opportunities.

Funding

This work was supported by National Natural Science Foundation of China (Grant 81971588), Construction Research Project of Key Laboratory of Chinese Academy of Medical Sciences (2019PT310025), Youth Key Program of High-level Hospital Clinical Research (2022-GSPQZ-5), and Undergraduate Education Reform Project of Peking Union Medical College (2023zlgl 026).

Author contributions

Mengdi Jiang drafted the manuscript. Minjie Lu and Shihua Zhao read and edited the manuscript. All authors read and approved the final manuscript.

Conflicts of interest

None.

Editor note: Shihua Zhao is an Editorial Board Member of Cardiology Discovery. The article was subject to the journal’s standard procedures, with peer review handled independently of this editor and his research group.