Guidelines for Cardiovascular Magnetic Resonance Imaging from the Korean Society of Cardiovascular ImagingPart 3: Perfusion, Delayed Enhancement, and T1- and T2 Mapping



## Myocardial perfusion imaging

## Visual assessment
I. What-to-See . Intramural coronary artery disease (CAD), which is pathologically characterized by smooth muscle thickening and luminal narrowing, may be attributable to an ischemia in HCM. The fact that fibrosis is present within the area of an ischemia, and is smaller than the area of an ischemia, supports this speculation (7). 5. Delayed perfusion in a patient who is post bypass graft: A delayed perfusion due to long graft pathway in a post bypass graft can mimic a true perfusion defect on myocardial stress MRI (8). The differential points are extent and duration: delayed perfusion kjronline.org from a long bypass graft pathway is transmural, while in true perfusion defects, hypoenhancement is non-transmural in most cases, and true perfusion defects tend to last longer. Additionally, a delayed perfusion from a long bypass graft pathway appears on both stress and rest images. Semi-quantitative and quantitative measurements are helpful to differentiate between them, because perfusion parameters of a delayed perfusion from a long graft are not deteriorated, and like those of the normal myocardium , Supplementary Movie 5). 6. Overcalling of inducible ischemia: Certain conditions, such as microvascular obstruction (MVO) in acute myocardial infarction, infarcted tissue, thrombus, and tumor, can appear as a hypo-signal on stress perfusion imaging. Evaluating them with LGE images is important to prevent misinterpretation as inducible ischemia. 7. Inadequate effect of vasodilator stress: Caffeine is a nonspecific competitive antagonist of all adenosine receptor subtypes; therefore, it may hamper the coronary vasodilatory effects of adenosine agonists. Despite the conflicting and limited published data, current guidelines recommend that caffeine be withheld for 12 hours prior to vasodilator stress myocardial perfusion imaging (10).

## Semi-quantitative assessment
I. What-to-See 1. Analysis methods of the signal intensity (SI) profile of myocardial dynamic perfusion CMR data, without estimating the absolute myocardial blood flow (11) . 2. Maximal up-slope: May be normalized to LV upslope. 3. Time to peak SI of the myocardial SI profile.. The up-slope integral: Area under the SI-time curve until arterial input function (AIF) peak, also insertion point). 6. Generate time-intensity curve from myocardial segments and LV blood pool. 7. Make sure to substrate baseline signal in the timeintensity curve. 8. Time window for calculation starts from the contrast arrival in the LV. 9. Some MR vendors provide inline post-processing of up-slope mapping after automatic motion correction and registration at each perfusion imaging. 10. Dedicated software provides regional values for myocardial segments, and LV blood pool, according to American Heart Association classification. 11. Consider separate calculation of endocardial and epicardial layers, and repeat analysis. III. Pitfalls 1. SI may vary according to the distance from coil. 2. No absolute measurement of myocardial blood flow derived. 3. Confounding effect of the quantity in the denominator, which serves the role of normalization, causes unreliable results. For example, in patients with hypertension, resting blood flow may be abnormally elevated in proportion to the ratepressure product. Evaluating the myocardial perfusion reserve from a ratio in this situation would be inaccurate. kjronline.org

## Quantitative assessment
I. What-to-See 1. Estimation of absolute myocardial blood flow (unit: mL/min/g) by analyzing the SI profile of myocardial dynamic perfusion CMR data. II. How-To 1. Quantitative analysis is performed in the same manner as the semi-quantitative analysis. 2. AIF to analyze absolute myocardial blood flow is required, and can be derived from the ROI in the LV blood pool. 3. Generally, there are two approaches that can be used to quantify myocardial blood flow using contrastenhanced CMR perfusion data: model-based (16) and model-independent methods (17). III. Pitfalls 1. Use of an adequate pulse sequence and contrast regime is the prerequisite for reliable quantification. 2. Correction of the AIF for saturation effects, resulting in the nonlinearity of the relationship between SI and contrast concentration. 3. Dual-bolus injection method that uses diluted contrast agent as pre-bolus before the main bolus: an initial minibolus (i.e., 0.0025 mmol/ kg) to maintain blood pool linearity followed by a high dose (i.e., 0.05 or 0.10 mmol/kg) to maximize myocardial signal-to-noise ratio (SNR) 10 or 20 seconds later. Low doses of contrast to minimize saturation effects: 0.025-0.050 mmol/kg for quantification is usually used, strictly less than 0.03 mmol/kg. 4. Dual-T1 sensitivity method with high dose, single injection (20): This method uses a low-resolution sequence with a short saturation-recovery time to measure AIF and a high-resolution sequence with a long saturation-recovery time to assess myocardial output within each R-R interval. 5. The optimal solution to the nonlinearity of the myocardium has not been defined yet because of more complex challenges. 6. Use of an intravascular contrast agent instead of an extracellular agent can simplify the estimation of blood flow, due to absence of leakage into the interstitial space (zero permeability surface area product), and it can improve the accuracy of blood flow estimates (21). 7. Baseline correction: Background signal should be subtracted before contrast enhancement. 8. At least 10 minutes interval after contrast injection to minimize the influence of the first perfusion scans. Determine the optimal inversion time (TI) using initial TI scout imaging, to obtain a good-quality LGE image. The optimal TI differs depending on the contrast material clearance from the normal myocardium. In general, a slightly too long TI is preferred over a slightly too short TI (22).

## Use phase-sensitive inversion recovery (psir)
imaging. PSIR imaging is less sensitive to TI, and shows infarct tissue as bright, and always shows the normal myocardium as dark, regardless of the TI. 3. Adjust window width and level to avoid noise, and to prevent the LGE regions to be cut-off. 4. Determine the presence of LGE. If high SI is as bright as the LV blood pool, it is considered as LGE. 5. Assess the pattern of LGE. CAD type is typically seen as subendocardial involvement that corresponds to a coronary artery perfusion territory . Non-CAD type is usually described as subendocardial sparing and myocardial enhancement restricted to the mid-wall or epicardium . 6. Evaluate the average transmural extent of LGE. In each of 17 standardized myocardial segments, the Left image (A) shows wrong nulling of normal myocardium that is shown to be darkest at border with higher SI centrally. These findings signify that degree of LGE may be underestimated if TI is too short. Right image (B) shows optimal nulling of myocardium with repeated image taken at longer TI and demonstrates larger LGE area in inferior wall (arrows A. MVO is shown as a central hypo-enhanced region within an avidly hyper-enhanced region of infarcted myocardium on LGE image.
Although the appearance of MVO on first-pass perfusion and early and LGE sequences is similar,
LGE is a more accurate predictor of adverse ventricular remodeling and future major adverse cardiovascular eventsinterpretation of additional sequences may be required. The contrast between the infarcted myocardium, and blood in the inversion recovery image relies on variables such as blood velocity, dosage of contrast material, time from gadolinium administration, clearance rate of contrast media, and imaging parameters. The solution to these problems includes using multiple contrasts, such as T1 and T2, or using blood suppression techniques.

## Semi-quantitative assessment
I. What-to-See 1. Semi-automated analyses that measure the LGE extent and/or "gray-zone" extent under the premise of subjective visual assessment that is still needed to identify poor nulling, no-reflow zones, artifacts, etc. and to delineate endocardial and epicardial borders. II. How-To LGE weight, and the ratio of LGE to normal myocardium can be calculated. 3. The "n"-SD technique: The rule of thumb is to select the reference myocardium and an appropriate threshold method that produces the results matched to "radiologist's eye." A. Outline endocardial and epicardial borders to draw the myocardial ROI. B. Select a normal "remote" (dark) ROI in the myocardium for the reference SI (mean and SD). C. The software will distinguish the areas within the myocardial ROI with a SI greater than a certain mean  SD threshold, which is defined by the operator. D. Select a threshold between the normal myocardium and the area of LGE. 1) The relative SNR between scar tissue and normal myocardium varies according to the type and dose of contrast agent, time after injection, type of sequence, field strength, and the underlying injury itself. 2) There is no fixed cut-off value. Recommended semi-automatic thresholding: n + 5 SD in infarction and n + 3 SD in myocarditis (33, 34).
3) The LGE area within the myocardium is determined automatically. 4) Automated thresholding may provide better reproducibility after appropriate standardization. 5) Manually modify to include no-reflow zones, except for artifacts and LV blood pool, which are kjronline.org caused by an error in drawing the endocardial contour. 6) It is receptive to spatial variations of the radiofrequency (RF) field, generated by the surface coil. 4. The FWHM technique: The rule of thumb is to appropriately determine both, the reference and LGE myocardium, so that the results match with those of the "radiologist's eye." The location and size of ROI for the reference and LGE myocardium can be adjusted to match the results with those of the "radiologist's eye."
A. Outline the endocardial and epicardial borders to draw the myocardial ROI. B. Evaluate whether the LGE is present. If there is an LGE lesion, choose an ROI that contains the "maximum" signal. 1) Threshold is set at half of the maximal SI within the scar.
2) The FWHM technique is less receptive to spatial variations of the RF field generated by the surface coil than the "n"-SD technique.
3) The FWHM technique is more reproducible compared to the "n"-SD technique. kjronline.org

## 4) the accuracy of the fwhm technique may be reduced compared to the "n"-sd technique if
LGE is patchy or gray, because the technique presumes a bright LGE core. C. Manually modify to include no-reflow zones except for artifacts and LV blood pool, which are caused by an error in drawing the endocardial contour.

## T1-weighted imaging
Quantitative Assessment I. What-to-See 1. Native T1 A. 'Native T1' means tissue longitudinal relaxation time (T1) values, without using contrast agent. B. T1 is affected by water (edema), proteins, and other T1-altering substances (lipid, iron). T1 is sensitive to change of composition, and structure of myocardial tissue. C. It may also be used with terms such as "native myocardial T1," "pre-contrast T1," or "non-contrast T1." "Native T1" or simply "T1" is used in this paper. D. Native T1 mapping is one of the CMR techniques that provides a parametric map in which each pixel is encoded with a native T1 value (43).

## Post-contrast t1
A. "Post-contrast T1" means tissue longitudinal relaxation time values with the use of a contrast agent. B. Post-contrast T1 mapping is a CMR technique that provides a parametric map in which each pixel is encoded with a post-contrast T1 value (40).

## Extracellular volume (ecv) fraction or myocardial ecv
A. ECV reflects the fraction of the volume occupied by extracellular space of heart tissues. It can be altered by diseases involving the myocardium. B. Measurements of ECV are obtained by measuring the native and post-contrast T1 of the myocardium and blood. C. Using the relationship between the fraction of plasma and the change in T1 relaxation rate of blood before and after contrast agent administration, the change in T1 relaxation rate in myocardial tissue can be used to estimate ECV. This can be expressed as follows:
 Using the relationship between the fraction of plasma and the change in T1 relaxation rate of blood before and after contrast agent administration, the change in T1 relaxation rate in myocardial tissue can be used to estimate ECV. This can be expressed as follows:
[formula] ECV = (1 -hematocrit)  1 Postcontrast T1 myocardium - 1 Native T1 myocardium 1 [/formula]
Postcontrast T1 blood -1 Native T1 blood  ECV map can be formed by encoding the ECV value at each pixel.
 ECV measures and predicts the space occupied by the extracellular matrix, which is also associated with the collagen volume fraction.
 Unless there is infiltrative disease or myocardial edema, it is associated with myocardial fibrosis, and myocardial remodeling.
 How-To  Preparation  Because normal values may vary due to various causes (sex/age, D. ECV map can be formed by encoding the ECV value at each pixel. E. ECV measures and predicts the space occupied by the extracellular matrix, which is also associated with the collagen volume fractionkjronline.org the septum or measure the total myocardium on the short axis and, then, find the mean value. However, if the ROI does not match the pathologic lesion, the disease may be missed.
2) The 16 segments approach: This measures the total myocardium. However, there can be problems with off resonance or partial volume error (53) .

## T2-weighted imaging
Visual Assessment I. What-to-See 1. The aim is to detect the increased SI area, indicating increased free water content. 2. Indications are acute coronary syndromes, including myocardial infarction, acute myocarditis kjronline.org and heart transplantation rejection. 3. Cleary-detectable high SI area following anatomical borders, and expected regional distribution pattern is suggestive of myocardial edema. II. How-To 1. Identify appropriate images. 2. Modify image contrast and brightness to minimize SI in the background, and reduce maximal SI in the highest SI area, to remove the "over-shining" effect. 3. Check for artifacts, such as surface coil reception field inhomogeneity, low SI artifacts due to arrhythmia or myocardial motion, and high SI artifacts due to slow flowing blood, especially in dark-blood triple-inversion recovery spine echo (short tau inversion recovery, turbo inversion recovery magnitude) images.

## Semi-quantitative assessment
I. What-to-See 1. It is a method of SI quantification with reference region that can reduce the impact of artifacts. II. How-To 1. Draw the largest ROI for short-axis views in the serratus anterior muscle (global SI), and the ROI in the affected myocardial area (regional SI). 2. Divide the regional SI by global SI. 3. Cut-off value of SI ratio is 1.9 in dark-blood tripleinversion recovery spine echo images.

## Quantitative assessment
I. What-to-See 1. It is a parametric map, in which each pixel is encoded with a T2 value.

## T2* imaging
Quantitative Assessment I. What-to-See 1. The aim is to detect myocardial hemorrhage or iron deposition. 2. If iron burden is increasing, rapid signal loss develops along with increasing echo time (TE). II. How-To 1. Draw the ROI of the ventricular septum with avoidance of blood pool, and proximal blood vessels (full-thickness ROI). 2. Calculate mean myocardial SI from the ROI. 3. Check SI with changes of TE, and get a mono-exponential curve. 4. Truncate the curve by removing later TEs, to avoid underestimating T2* in patients with heavy iron overload (55). 5. Cut-off value of T2* at 1.5 tesla is 40 ms (56). 6. T2* < 20 ms indicates cardiac iron overload, and T2* < 10 ms indicates increased risk of developing heart failure (57, 58). 7. T2* evaluation at 3 tesla is not recommended.

## Sample report
These sample reports are written from examples of diseases that are often clinically encountered. Each report was written by committee members in consensus. These reports are just an example, not a guideline. It can be applied differently depending on the clinical situation of75-100% transmural infarct at LV mid anterior and septal wall, apical anterior, septal, and inferior wall, and apex Associated with large amount of no reflow zone  suggesting acute myocardial infarction of left anterior descending artery territory C. Regional wall motion abnormality (+)-see findings D. Pericardial effusion 2.