Comparison Study on Different Quantification Methods of Diffuse Myocardial Fibrosis of Dilated Cardiomyopathy Using Myocardial T1 Value

doi:10.4236/ojrad.2013.33019

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Open Journal of Radiology, 2013, 3, 117-123

http://dx.doi.org/10.4236/ojrad.2013.33019 Published Online September 2013 (http://www.scirp.org/journal/ojrad)

Comparison Study on Different Quantification Methods of

Diffuse Myocardial Fibrosis of Dilated Cardiomyopathy

Using Myocardial T1 Value*

Takeshi Hayashida, Eijun Sueyoshi#, Hiroki Nagayama, Ichiro Sakamoto, Masataka Uetani

Department of Radiology, Nagasaki University School of Medicine, Nagasaki, Japan

Email: #[email protected]

Received June 26, 2013; revised July 26, 2013; accepted August 3, 2013

cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Purpose: The purpose is to compare several quantification methods and clarify which quantification method is reliable

to estimate diffuse myocardial fibrosis with cardiac MRI in patients with dilated cardiomyopathy (DCM) using myo-

cardial T1 value. Methods and Results: Delayed enhancement imaging was performed in 52 patients with DCM and

10 control subjects to identify fibrosis using an inversion time scout sequence. The mean contrast-enhanced myocardial

(M) T1 values of the pre and post contrast-enhanced myocardial and left ventricular lumen (L) of control and dilated

cardiomyopathy cases were compared. The calculated post M T1 value, pre M T1 value-post M T1 value, and (pre M TI

value-post M T1 value)/(pre L T1 value-post L T1 value) were significantly different between the patient group and the

control group (344.5 ± 31.6 vs. 390.4 ± 19.3 msec, 239.9 ± 64.2 msec vs. 134.0 ± 28.9 msec, and 0.50 ± 0.11 vs. 0.30 ±

0.60, respectively). (Pre M T1 value-post M T1 value)/(pre L T1 value-post L T1 value) was significantly the most re-

lated to the left ventricular ejection fraction (r = 0.66, p < 0.0001). Conclusion: (Pre M T1 value-post M T1 value)/(pre

L T1 value-post L T1 value) was the most reliable quantification method to estimate the severity of DCM.

Keywords: Inversion Time; Quantification Methods; Myocardial Fibrosis; Dilated Cardiomyopathy

1. Introduction

Recently, the importance of myocardial fibrosis in the

development and progression of systolic and diastolic

cardiac failure has been highlighted in cardiomyopathy

[1-3]. Central to the diagnostic utility of cardiovascular

magnetic resonance is its almost unique capacity to re-

veal myocardial fibrosis through the use of delayed ga-

dolinium enhancement imaging [4].

In patients with cardiac infarction, infarcted regions in

the myocardium, having undergone scar formation with

collagen deposition, have a much slower washout rate of

gadolinium-based contrast material than healthy myocar-

dium, leading to markedly increased signal intensity on

T1-weighted imaging [5]. On the other hand, because

60% of dilated cardiomyopathy (DCM) patients have

diffuse myocardial fibrosis, the technique of delayed

contrast enhancement often shows no regional scarring

[5]. Previous study suggested that the mean contrast-

enhanced myocardial inversion time at the null point (T1

value) was significantly shorter in a patient group than in

a control group [5]. T1 value can be easily obtained, but

this technique does not consider the influence of the con-

trast medium in the blood pool, and thus may not evalu-

ate the enhancement of myocardium precisely.

The purpose of this study was to compare several

quantification methods and clarify which quantification

method is reliable to evaluate diffuse myocardial fibrosis

of DCM using T1 value.

2. Materials and Methods

2.1. Patients

Fifty-two patients (33 men, 19 women; mean age ± SD,

53.3 ± 13.6 y; age range, 18 - 77 y) with DCM and 10

control subjects (5 men, 5 women; mean age ± SD, 54.8

± 12.4 y; age range, 55 - 74 y) underwent MRI at our

institution between June 2008 and July 2011. There was

no statistically significant difference in mean age (P =

0.763) between the two groups. The diagnosis of non-

ischemic DCM was made according to World Health

Organization and International Society and Federation of

*Conflict of interest: This work was supported by JSPS KAKENHI

Grant Number 24591776.

#Corresponding author.

T. HAYASHIDA ET AL.

118

Cardiology criteria [6]. None of the subjects had clinical

symptoms or signs of ongoing myocarditis. By the use of

coronary angiography, cases of significant coronary ar-

tery disease (>50% diameter luminal stenosis in any

coronary artery) were excluded from this study. Other

exclusion criteria were the presence of any contraindica-

tions for cardiac MRI, significant valvular disease, or any

evidence of infiltrative heart disease by clinical symp-

toms or signs and sonographic findings. In addition, all

patients with DCM underwent myocardial biopsy. The

specimens showed disarray, with varying degrees of in-

terstitial fibrosis of the myocardium, which were consis-

tent with DCM.

On the other hand, all control subjects (n = 10) under-

went cardiac MRI because of arrhythmia; however, no

subjects had abnormalities according to coronary an-

giography, laboratory testing, echocardiography, nuclear

medicine scan, or myocardial biopsy, which were per-

formed to rule out various myocardial diseases.

All subjects gave written informed consent, and the

protocol was approved by a medical ethics committee.

2.2. Cardiac MRI

All subjects were studied in the supine position using a

1.5-T cardiac MRI system (Avanto, Siemens Healthcare)

with an eight-channel body coil. The data acquisition was

blinded to diagnosis. The cardiac MRI study included

cine steady-state free-precision imaging (TR/TE, 3.4/1.2;

in-plane spatial resolution, 1.6 × 2 mm) of left ventricular

function. Cine images were acquired with ECG gating

and breath-holding. Cine images were obtained in 8 - 14

short axis (8-mm thickness with 0-mm spacing) from the

base to the apex of the left ventricle. Vertical long axis

images were also obtained. In all subjects (n = 62), in-

version time scout images were obtained before en-

hancement and 15 minutes from the beginning of bolus

injection of gadopentetate dimeglumine (0.2 mmol/kg;

Magnevist, Bayer Schering Pharma) to identify regional

fibrosis using a 2D inversion recovery gradient-echo

technique (inversion time scout sequence: TR/TE, 20.8/1.3;

flip angle, 25˚; acquisition matrix, 192 × 78; field of view,

34 × 27 cm; slice thickness, 8 mm; inversion time, indi-

vidually determined to null the myocardial and left ven-

tricular lumen signal). Forty-two images per single mid-

ventricular slice were acquired at various inversion times

during breath-holding as long as possible (Figures 1(a)

and (b)). This single midventricular slice was selected on

the basis of long axis scout images of the left ventricle

be- fore inversion time scout images were obtained.

These inversion time scout images were then processed

with a curve-fitting technique to generate T1 maps (Fig-

ures 1(c) and (d)). After the inversion time scout se-

quence was performed, ordinary delayed enhanced im-

ages were obtained.

2.3. Data Analysis

All MRI post-processing was performed by a single ob-

server with more than 10 years of experience in cardiac

MRI. The left ventricular ejection fraction was derived

from cine images using a workstation for analysis (Syngo,

Siemens Healthcare). A T1 mapping sequence was used

to calculate the pre and post contrast-enhanced myocar-

dial and left ventricular lumen T1 times of a single mid-

ventricular slice as an index of diffuse fibrosis. After

image acquisition, short-axis images of varying inversion

times were transferred to a workstation for analysis

(Syngo, Siemens Healthcare). For each image, a region

of interest was drawn in the left ventricular lumen and

around the entire myocardium to calculate the pre and

post contrast-enhanced myocardial and left ventricular

lumen TI0 values for each subject (Figures 1(a) and (b)).

This allowed us to analyze regions of interest to find the

average T1 time for that area, as well as a pixel-by-pixel

determination of T1, by fitting data acquired at various

preparation times to the exponential curve.

We then determined pre and post contrast-enhanced

myocardial (M) and left ventricular lumen (L) T1 values

(pre contrast-enhanced myocardial T1 value; pre M T1

value, pre contrast-enhanced left ventricular lumen T1

value; pre L T1 value, post contrast-enhanced myocardial

T1 value; post M T1 value, post contrast-enhanced left

ventricular lumen T1 value; post L T1 value) [1,7,8]

(Figures 1(c) and (d)). We compared the several quanti-

fication methods as follows: 1) post M T1 value, 2) pre

M T1 value-post M T1 value, 3) post M T1 value/post L

T1 value, and 4) (pre M T1 value-post M T1 value)/(pre

L T1 value-post L T1 value).

2.4. Statistical Analysis

All values are expressed as the mean ± SD. Statistical

analysis was performed on clinical and morphologic

variables with the paired Student’s t test and Mann-

Whitney U test for continuous variables. Pearson’s cor-

relation coefficients were used to examine the correlation

of left ventricular ejection fraction with all TI0 values.

Correlation coefficient values of 0.4 - 1.0 were consid-

ered to indicate a correlation [9]. In all tests, p < 0.05 was

considered significant (SPSS, release 11.5; SPSS).

3. Results

The results are summarized in Table 1. In patients in the

DCM group, the mean pre M T1 value, post M T1 value,

pre L T1 value, and post L T1 value were 581.3 ± 58.3

msec, 344.5 ± 31.6 msec, 741.2 ± 92.5 msec, and 257.5 ±

46.1 msec, respectively. In the control group, the mean

pre M T1 value, post M T1 value, pre L T1 value, and

post L T1 value were 519.7 ± 30.4 msec, 390.4 ± 19.3

msec, 731.4 ± 64.4 msec, and 299.3 ± 35.5 msec,

T. HAYASHIDA ET AL.

119

(a) (b)

Figure 1. A 63-year-old woman with dilated cardiomyopathy. (a) Epicardial and endocardial borders were manually traced,

and a region of interest was placed in a single midventricular slice to obtain signal intensity of left ventricular myocardium.

(b) Region of interest was manually placed in the left ventricular lumen in a single midventricular slice to obtain signal inten-

sity of left ventricular myocardium. (c) We analyzed regions of interest to find the average T1 for that area by fitting data

acquired at various preparation times to an exponential curve. We determined pre contrast-enhanced myocardial T1 value

(vertical line). SI = signal intensity. (d) We analyzed regions of interest to find the average T1 for that area by fitting data

acquired at various preparation times to an exponential curve. We determined post contrast-enhanced myocardial T1 value

(vertical line). SI = signal intensity.

respectively (Table 2). There were statistically signifi-

cant differences between the patient and control groups

in pre M T1 values, post M T1 values, and post L T1

values (P = 0.0052, P < 0.0001, P = 0.002, respectively).

However, there was no significant difference between the

patient and control groups in pre L T1 value (P = 0.559).

In patients in the DCM group, post M T1 value, pre M

T1 value-post M T1 value, post M T1 value/post L T1

value, and (pre M T1 value-post M T1 value)/(pre L T1

value-post L T1 value) were 344.5 ± 31.6 msec, 239.9 ±

64.2 msec, 1.37 ± 0.21, and 0.50 ± 0.11, respectively. In

the control group, post M T1 value, pre M T1 value-post

M T1 value, post M T1 value/post T1 value, and (pre M

T1 value-post M T1 value)/(pre L T1 value-post L T1

value) were 390.4 ± 19.3 msec, 134.0 ± 28.9 msec, 1.31

± 0.13, and 0.30 ± 0.60, respectively (Table 3). There

were statistically significant differences between the pa-

tient and control groups in post M T1 value, pre M T1

value-post M T1 value, and (pre M T1 value-post M T1

value)/(pre L T1 value-post L T1 value) (P < 0.0001, P <

0.0001, P < 0.0001, respectively). However, there was no

significant difference between the patient and control

T. HAYASHIDA ET AL.

120

Table 1. Summary of results in patient and control groups.

Characteristic Control Subjects

(n = 10)

Patients

(n = 52) P

Age(Y) 54.8 ± 12.4 53.3 ± 13.6 NS

Sex(no.) NS

Male 5 33

Female 5 19

LVEF (%) 62.5 ± 7.0 37.2 ± 14.1 <0.0001

Note: LVEF = Left ventricular ejection fraction, NS = not significant.

Table 2. Comparison of pre and post contrast-enhanced

myocardial and left ventricular lumen T1 values between

control and DCM groups.

Control DCM P

Pre M T1 value

(msec) 519.7 ± 30.4 581.3 ± 58.3 0.005

Post M T1

value (msec) 390.4 ± 19.3 344.5 ± 31.6 <0.0001

Pre L T1 value

(msec) 731.4 ± 64.4 741.2 ± 92.5 NS

Post L T1 value

(msec) 299.3 ± 35.5 257.5 ± 46.1 0.002

Note: NS = not significant.

Table 3. Comparison of four quantification methods of T1

value between control and DCM groups.

Control DCM P

Post M T1 value (msec) 390.4 ± 19.3 344.5 ± 31.6 <0.0001

Pre M T1 value - post M

TI value (msec) 134.0 ± 28.9 239.9 ± 64.2 <0.0001

Post M T1 value/post L

T1 value 1.31 ± 0.13 1.37 ± 0.21 0.3422

(pre M T1 value - post

M T1 value)/(pre L T1

value - post L T1 value)

0.30 ± 0.60 0.50 ± 0.11 <0.0001

Note: M = myocardial, L = left ventricular lumen, DCM = dilated cardio-

myopathy.

groups in post M T1 value/post T1 value.

In the DCM groups, (pre M T1 value-post M T1

value)/(pre L T1 value-post L T1 value) was the most

significantly related to the left ventricular ejection frac-

tion (r = 0.66; P < 0.0001) (Figure 2). The other quanti-

fication methods (post M T1 value, pre M T1 value-post

M T1 value, and post M T1 value/post L T1 value) had

smaller positive correlations than (pre M T1 value-post

M T1 value)/(pre L T1 value-post L T1 value) with the

left ventricular ejection fraction (post M T1 value; r =

0.53; P < 0.0001) (Figure 3), pre M T1 value-post M T1

value (r = −0.47; P < 0.0001) (Figure 4), and post M T1

value/post L T1 value (r = 0.10; P = 0.43) (Figure 5).

Figure 2. Scatterplot shows correlation between left ven-

tricular ejection fraction and (pre M T1 value-post M T1

value)/(pre L T1 value-post L T1 value) in patients with

DCM. (Pre M T1 value-post M T1 value)/(pre L T1

value-post L T1 value) was most significantly related to left

ventricular ejection fraction (r = 0.66; P < 0.0001).

Figure 3. Scatterplot shows correlation between left ven-

tricular ejection fraction and post M T1 value in patients

with DCM. Post M T1value was significantly related to left

ventricular ejection fraction (r = 0.53; P < 0.0001).

Figure 4. Scatterplot shows correlation between left ven-

tricular ejection fraction and pre M T1 value-post M T1

value in patients with DCM. Pre M T1 value-post M T1

value was significantly related to left ventricular ejection

fraction (r = −0.47; P < 0.0001).

T. HAYASHIDA ET AL. 121

Figure 5. Scatterplot shows correlation between left ven-

tricular ejection fraction and post M T1 value/post L T1

value in patients with DCM. Post M T1 value/post L T1

value was not significantly related to left ventricular ejec-

tion fraction (r = 0.10; P =0.43).

4. Discussion

In patients with DCM, an important mechanism for the

occurrence of arrhythmias and failure to respond to treat-

ment is the presence of myocardial fibrosis [10-13]. There-

fore, in patients with DCM, fibrosis is one of the most

important risk factors for mortality.

Delayed enhanced MRI has enabled depiction of

myocardial damage with high spatial resolution in vari-

ous myocardial diseases. Delayed enhanced cardiac MRI

has been used to evaluate focal myocardial fibrosis, but it

is difficult to evaluate diffuse fibrosis of the myocardium.

Prior studies have identified pathologic findings of myo-

cardial fibrosis and disarray can show enhancement on

delayed enhanced images, but delayed enhancement re-

lated to disarray is usually faint. Measurement of con-

trast-enhanced myocardial T1 value can provide an esti-

mate of diffuse fibrosis of the myocardium [1,5,7]. There-

fore, the prior studies used contrast-enhanced myocardial

T1 value, which is easily calculated on a workstation

[14-16]. In addition, T1 value was used as the optimal

inversion time when delayed enhanced MR images were

acquired.

According to previous study, the T1 values were 273 -

420 msec, 15 minutes after administration of contrast

material in patients with DCM [5]. This quantification

method has been postulated to be useful as this contrast-

enhanced myocardial T1 value was significantly shorter

in the patient group than in the control group. However,

this quantification method does not consider the influ-

ence of the contrast medium of the blood pool and thus

this quantification method might not enable precise de-

termination of the enhancement of myocardium. Another

prior study identified quantification methods such as post

M T1 value/post L T1 value, which considered the in-

fluence of the contrast medium of the blood pool [17],

but this quantification method did not measure the dif-

ference between post M T1 value and pre M T1 value, or

between post L T1 value and pre L T1 value. For these

reasons, this quantification method might not evaluate

the enhancement of myocardium precisely.

To our knowledge, this is the first study to determine

pre and post contrast-enhanced myocardial and left ven-

tricular lumen T1 values. This study compared several

quantification methods.

In this study, post M T1 value, pre M T1 value-post M

T1 value, and (pre M T1 value-post M T1 value)/(pre L

T1 value-post L T1 value) showed statistically significant

differences between patient and control groups. These

methods could be useful diagnostic tools for DCM. How-

ever, because the quantification method of post M T1

value did not measure a difference between post M T1

value and pre M T1 value, this quantification method

may not evaluate the enhancement of myocardium pre-

cisely. Moreover, because this quantification method

may not measure the difference between post L T1 value

and pre L T1 value, this quantification method did not

consider the influence of the contrast medium of the

blood pool.

The quantification method of pre M T1 value-post M

T1 value may not measure the difference between post L

T1 value and pre L T1 value. Because this quantification

method did not consider the influence of the contrast

medium of the blood pool, this quantification method

may not evaluate the enhancement of myocardium pre-

cisely.

The quantification method of post M T1 value/post L

T1 value did not show a significant difference between

the patient and control groups, although this quantifica-

tion method considers the influence of the contrast me-

dium of the blood pool.

The quantification method of (pre M T1 value-post M

T1 value)/(pre L T1 value-post L T1 value) measured the

difference between post M T1 value and pre M T1 value,

and between post L T1 value and pre L T1 value. Be-

cause this quantification method considers the influence

of the contrast medium of the blood pool, this method

may evaluate the enhancement of myocardium most pre-

cisely among the four methods.

In prior studies, left ventricular ejection fraction was

suggested to be associated with serious clinical symp-

toms [18-20]. According to our results, (pre M T1

value-post M T1 value)/(pre L T1 value-post L T1 value)

was the most significantly related to the left ventricular

ejection fraction (r = 0.66; P < 0.0001) in the DCM

group. Our study shows that the quantification method of

(pre M T1 value-post M T1 value)/(pre L T1 value-post

L T1 value) considers the influence of the contrast me-

dium of the blood pool and evaluates the enhancement of

myocardium. Therefore, this method may be the most re-

liable diagnostic method to evaluate the extent of myo-

T. HAYASHIDA ET AL.

122

cardial fibrosis non-invasively.

There were several limitations to this study. First, we

used inversion times to measure a single slice. Ideally,

measurement of the whole myocardium is needed to

evaluate diffuse fibrosis. Therefore, further studies re-

garding markers of fibrosis are needed. In addition, it is

not easy to draw a myocardial boundary. This process

may potentially bias the results.

Second, this study lacked a comparison of severity of

myocardial fibrosis, histologically. However, it may be

impossible to correlate the areas of fibrosis on biopsy

with the areas seen on MRI.

Third, we evaluated only four quantification methods

and we must carry out further examination to find a more

useful quantification method.

5. Conclusion

In conclusion, (pre M T1 value-post M T1 value)/(pre L

T1 value-post L T1 value), which considered the influ-

ence of the contrast medium of the blood pool, evaluated

the enhancement of myocardium precisely. This method

was the most significantly related to the left ventricular

ejection fraction. These data suggest that (pre M T1

value-post M T1 value)/(pre L T1 value-post L T1 value)

is the most reliable quantification method to estimate the

severity of DCM.

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