Advanced Cardiac MR Imaging for Myocardial Characterization and Quantification: T1 Mapping

Post-contrast T1 mapping

Although the gadolinium as extracellular contrast agent is not a specific marker, the distribution concentration and dynamic kinetics of contrast agent into extracellular space can be used to describe myocardial fibrosis, inflammation, and edema related to an increase in the extracellular volume. Therefore, some helpful patterns of late gadolinium enhancement have been identified in different myocardial diseases; therefore, LGE CMR is now routinely used as a first-line examination to evaluate the etiology of newly identified heart failure.19-21)

However, measurement of signal intensity of enhancement by LGE is arbitrary and unsuitable for quantification in inter-individual comparison or longitudinal comparison in an individual. No universally accepted cut-off value of signal intensity has been reported to differentiate between normal and affected myocardium in the area of heterogeneity within the myocardial infarct periphery. In addition, the sensitivity of LGE is quite limited for detecting diffuse myocardial pathology because image contrast by LGE depends on the difference between normal and abnormal myocardium, and such difference may not be detected in the absence of normal myocardium if the myocardial disease involves diffusely.9), 10)

In contrast with LGE, T1 mapping with MOLLI sequence directly measures the specific T1 value with a standardized scale. Although post-contrast T1 mapping with the gadolinium appears to be promising for myocardial assessment, its accuracy can be affected by various confounding characteristics of the gadolinium. The physical properties of gadolinium (dose, concentration, and water exchange rate) are all closely related to measuring an accurate T1 value of the myocardium. Because T1 value is exponentially correlated with the concentration of gadolinium, considering consistent wash-out of gadolinium from the myocardium after an administration of gadolinium, the waiting time for imaging acquisition is a significant parameter, changing the measured T1 value.16) Therefore, in clinical practice of post-contrast T1 mapping, the acquisition time of T1 map image should be carefully monitored and considered for correction before further analyses.22)

Extracellular volume fraction by post-contrast T1 mapping

To resolve the problem due to the dynamic kinetics of gadolinium in myocardium, the standardization to non-cardiac tissue or measurement of myocardial T1 value has been studied. Maceira et al.23) proposed a model for the correction of myocardial T1 value compared to the blood T1 value. ECV is another useful and stable index that is related to the myocardial interstitial status or fibrosis. It can be calculated with myocardial R1 (1/T1 value) change, blood R1 change, and hematocrit.10), 24), 25) Ugander et al.10) showed that ECV by pre- and post-T1 mapping could characterize and quantify infarcted myocardium, diffuse fibrosis, and mild myocardial abnormalities, which were not obvious on LGE images.

To achieve accurate ECV, equilibrium state of gadolinium between the blood and myocardium must be secured during imaging acquisition. Although gadolinium is continuously excreted via renal clearance, the ratio of contrast agent concentrations between myocardial tissue and plasma usually reach a dynamic equilibrium state over a certain period of time after contrast administration.26) Lee et al.11) suggested that the gadolinium concentration could achieve dynamic equilibrium between blood and myocardial tissue, as early as 8.5 minutes after injection of the gadolinium, and between 8.5 to 23.5 minutes, the ECV differences at 3.0T between consecutive time points were not significant.

Magnetic field strength for T1 mapping

In clinical practice, CMR imaging is performed typically with the use of 1.5T or 3.0T scanners. Although CMR imaging with 3.0T scanner has some obstacles to overcome, with recent technological developments27) 3.0T scanners are getting used more in cardiac imaging mainly for benefit of increased SNR.

At a given magnetic field strength, a tissue has a certain range for T1 value.1) When the same T1 mapping sequences are used, pre-contrast T1 value is longer at 3.0T than at 1.5T, which requires more time to fully recover. Kawel et al.12) also reported that myocardial ECV is similar at field strengths of 1.5T and 3.0T. In contrast, Lee et al.11) showed that myocardial ECV of normal volunteers at 3.0T slightly higher than that at 1.5T because of an effect of relatively stronger shortening of the longer pre-contrast blood T1 at 3.0T, as compared to that at 1.5T.

Image acquisition phase and location of T1 mapping

Since the myocardium is thicker during systolic phase of the cardiac cycle and can be visualized with a good image quality, it may be advantageous to measure myocardial T1 value at systolic phase.12) Myocardial T1 value and ECV vary significantly during a cardiac cycle depending on the changes in the myocardial blood volume.12) In the left ventricular free wall of rat hearts, Judd and Levy.28) demonstrated a decrease in myocardial blood volume by 42% from diastole to systole. Wansapura et al.29) described a decrease in T1 time from diastole to systole of 70% in the septum, and 43% in the lateral wall. Although myocardial blood volume changes significantly depending on the cardiac cycle, in the animal study, the blood volume accounts for a small fraction of the entire myocardial volume.28) In addition, although absolute variation of myocardial T1 value and ECV in human subjects over the cardiac cycle was significant, absolute changes were small (<2%) and might not be clinically relevant.12) In contrary to the general option and despite the acquisition window of about 200 msec of the MOLLI sequence, images acquired at the early systole may result in a constantly good image quality.12) The regional differences in myocardial motion or perfusion might cause variation in T1 value by post-contrast T1 mapping.12), 29) Messroghli et al.16) compared pre-contrast T1 values of the base, middle, and apical level of the left ventricle (LV) and did not find regional differences.

For practical reasons, most previous studies reported the post-contrast T1 mapping results only at a single location of the LV, commonly at the middle ventricle level. However, even if T1 values are the same between basal, middle, and apical myocardium of the LV, it is not clear whether all locations of the LV are equally affected by diffuse fibrosis. Assessment of post-contrast T1 value and ECV is a sensitive method that requires rigorous conditions, such as considering the target region and cardiac cycle in order to enhance its accuracy to characterize the myocardium.

Acute myocardial injury

The presence of myocardial edema can be a useful finding to differentiate acute from chronic myocardial infarction (Fig. 1),30) assessment of the area-at-risk,31) myocarditis32) and increasingly as a surrogate end-point in clinical trial.33) T1 and T2 values track closely together such myocardial edema, which prolongs T1 and T2 reflecting free water contents in ischemic tissue.33) Especially, following prolonged ischemia, T1 values may increase above the expected increase in water content because of release of intracellular contents into the extracellular interstitium, according to the severity of cellular injury.34)

In the study of patients with acute myocardial infarction, T1 value by pre-contrast T1 mapping showed a significantly lower variability than T2-weighted image (T2WI) and accurately detected acutely injured myocardium.35) Ferreira et al.36) suggested that pre-contrast T1 mapping at 1.5T may be a more sensitive technique in detecting acute myocardial changes in both global and regional pathologies by using the diagnostic criteria of greater than 990 msec T1 value, with a sensitivity and specificity of 92%. In addition, Dall'Armellina et al.35) reported the likelihood of improvement of myocardial function at 6 months after injury decreased progressively with incremental increase of myocardial T1 values.

Myocardial fibrosis

Although the pathophysiological mechanisms of myocardial fibrosis are various, myocardial fibrosis, an increase of the collagen composition has been reported as an independent predictor of major adverse cardiac events.37-39)

Post-contrast T1 values in myocardial fibrosis are much smaller than those of normal myocardium due to the retention of more gadolinium in the expanded extracellular space in the fibrotic tissue. Messroghli et al.40) reported that post-contrast T1 values were approximately 390 msec in chronic infarction scar and 483 msec in normal myocardium by T1 mapping with MOLLI sequence at 1.5T. Kehr et al.41) also showed that post-contrast T1 values for both diffuse and replacement fibrosis were significantly shorter than those for normal myocardium. In addition, myocardial ECV obtained by combining pre- and post-contrast T1 mapping may be useful to detect mild or diffuse abnormalities. Ugander et al.10) reported that the ECV obtained by T1 mapping at 1.5T of "normal appearing" myocardium without LGE was 26±3%, and increased with age. Mild ECV abnormalities were consistent with fibrosis according to age in the remote myocardium from infarction. A recent study reported that extracellular volume expansion measured by CMR might predict both mortality and other composite end points, including death, cardiac transplantation, and left ventricular assist device implantation.42) The investigators enrolled 793 patients and 9 volunteers, and measured ECV in non-infarcted myocardium. The ECV in patients ranged from 21.0% to 45.8%, while that in volunteers ranged from 21.7% to 26.2%. After the cohort was followed for 0.8 year, ECV was related to all-cause mortality and the other composite end points (hazard ratio, 1.5 and 1.48 for every 3% increase in ECV, respectively). Myocardial infiltrative diseases, such as amyloidosis and sarcoidosis usually reveal LGE at the diseased myocardium. Cardiac amyloidosis is characterized by a deposition of amyloid fibrils mainly in the endocardial myocardium, where LGE can be seen with an expanded extracellular space.23) Diffuse subendocardial enhancement is a hallmark of cardiac amyloidosis. T1 mapping can be a useful method to detect and quantify diffuse infiltrative pathology in the myocardium (Fig. 2).

Fig. 2
Late gadolinium enhancement (LGE) (A), pre- and post-contrast (B and C) T1 map images using 3-T MR system in a patient with secondary myocardial amyloidosis from multiple myeloma. LGE-MR image shows diffuse subendocardial gadolinium enhancement, which is a typical finding of myocardial amyloidosis deposition. Post-contrast T1 map image shows decrease of T1 value in the myocardium which enables quantification of extracellular volume fraction.

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Myocarditis

Although myocarditis is represented by myocardial inflammation, temporary pathologic status, according to disease progression or severity varies from edema to necrosis or fibrosis. T2WI of CMR is quite sensitive to detect regional myocardial edema in active myocarditis. LGE is a standard noninvasive imaging technique to evaluate irreversible myocardial injury related to myocarditis. However, diffuse or mild regional myocarditis typically in early or borderline disease may not be detected with T2-weighted imaging or LGE. Recently, a study reported that pre-contrast T1 mapping was sensitive to diagnose acute myocarditis that was CMR diagnosis based on T2-weighted imaging and LGE.43) With combination of pre-contrast and post-contrast T1 mapping, early detection and quantification of water contents or extracellular space will be feasible in myocarditis (Fig. 3).

Fig. 3
Late gadolinium enhancement (LGE) (A), pre- and post-contrast (B and C) T1 map images using 3-T MR system in a patient with esoniophilic myocarditis diagnosed by the biopsy. LGE-MR image shows no remarkable late gadolinium enhancement in the myocardium. Pre-contrast T1 map image shows the prolongation of T1 value in the focal area of mid ventricular septum, compared to the lateral wall. It can suggest the probable edema in the myocardium. Post-contrast T1 mapping show diffusely low T1 value (mean±standard deviation, 410.4±34.4 msec) from gadolinium-induced T1 shortening in the myocardium. Myocardial extracellular volume fraction calculated by the T1 mapping results is 33.5% which is higher than that in normal control in the literature.

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