Original contributionEffect of B-value in revealing postinfarct myocardial microstructural remodeling using MR diffusion tensor imaging
Introduction
Magnetic resonance diffusion tensor imaging (DTI) has been regarded as a powerful tool to nondestructively characterize myocardial microstructure [1], [2], [3], [4], [5]. In normal hearts, left ventricular (LV) myocardial fiber orientation changes smoothly from left-handed in epicardium to right-handed in endocardium when viewed from apex [1], [2], [3], [4], which is well validated with histological measurements [6], [7], [8]. This double-helical myocardial fiber architecture is essential for dispersing strain uniformly and conserving energy expenditure [9], and has been widely observed in humans [10] and other mammalian species [11]. Besides fiber orientation, other intrinsic myocardial characteristics, including fiber directional integrity and water molecule mobility [12], can be represented by derived DTI indices, such as fractional anisotropy (FA), mean diffusivity (MD), and directional diffusivities along myofiber axial (λ∥) and radial (λ⊥) directions. Recently, these DTI indices together with fiber architecture have been extensively utilized to monitor microstructural alterations of hearts with myocardium infarction (MI) [13], [14], [15], [16], [17], [18], [19]. The double-helical structure was reported to be reorganized with shifting towards more left-hand orientation in both infarcted and non-infarcted myocardium [13], [14], [15], [17] with increase of local angular dispersion compared to normal hearts [13], [16]. As contribution of myofiber to cardiac contraction was heterogeneous across myocardial wall [20] and related with fiber orientation, alteration of the fiber architecture would subsequently impair heart function. During the acute phase of MI, decrease of MD and increase of FA were observed in the infarcted myocardium, indicating myocyte swelling and lengthening [16], [21]. Gradually with infarct formation, MD was found to increase and FA decrease, reflecting the appearance of myocyte necrosis and fibrosis [13], [14], [15], [16], [17]. All these experimental and clinical studies have demonstrated the powerful ability of DTI in probing myocardial remodeling process.
In recent years, in vivo cardiac DTI is becoming feasible for animal [22], [23] and human [14], [18], [24] studies by alleviating motion artifacts with incorporating motion-compensation methods, such as ECG triggering, respiratory navigation, or breath-holding. Quantitative DTI index maps and 3D myocardial fiber tractography were successfully achieved in beating hearts, demonstrating the feasibility of the technique in description of in vivo heart microstructure. Such imaging approach provides a novel way for longitudinally tracing and evaluating the remodeling evolution of diseased hearts at microscopic level, which may benefit the development of specific therapeutic strategies.
It is noteworthy that most of the previous cardiac DTI studies assumed free water diffusion mode inside of myocardium, and the diffusion-weighted (DW) signal was of monoexponential dependence on the diffusion sensitivity of b-value, which therefore had no impact on DTI index quantification. However, nonmonoexponential diffusion decay at high diffusion strengths (> 1000 s/mm2) has been observed in perfused rabbit [25] and rat [26] hearts, which uncovered the complicate diffusion behavior in myocardium and implied the possible effect of b-value on conventional DTI index characterization. Despite of this potential limitation, the conventional DTI method is still widely accepted as a fast, robust and reliable protocol to explore water diffusion characteristics in routine research and clinical settings. Especially, its ability in detecting microstructural alterations may be greatly strengthened with b-value optimization. Recently, b-value dependence of DTI measurement in monitoring biological tissue changes has been explored in normal developing brains [27] and some abdomen organs with ischemia reperfusion injury [28], [29] in rat models. Quantifications and abilities of specific DTI indices in exploring tissue structural alterations were found to vary with b-values. These experimental results not only demonstrated the crucial role of b-value in DTI index measurement, but also confirmed the necessity of optimizing it for better detecting structural changes when using conventional DTI analysis. These important findings then prompt us to make the present endeavors to determine if such b-value dependence of DTI index characterization exists in ex vivo heart samples.
The current study was conducted on a rabbit model due to its advantages of intermediate body size, easy handling, favorable cost effectiveness and pertinent outcomes to human patients with similar cardiovascular conditions [30]. Fixed heart samples of normal and infarcted rabbits at 1, 3, 5, and 7 days after MI surgery underwent ex vivo DTI scans. B-value impact on DTI index quantification was explored, and optimal b-values to achieve the most sensitive detection of microstructural degradation were identified. To our knowledge, this is the first study that documents the influence and optimization of b-value in investigating remodeling of infarcted hearts, and may provide useful information for optimizing cardiac DTI protocols for beating hearts in the future.
Section snippets
Sample preparation
The animal experiments were approved by the local institutional ethics committee for animal research. Twenty-four adult New Zealand rabbits (≈ 2200 g, 12 males and 12 females) were anesthetized, and the proximal left circumflex (LCX) coronary artery was permanently occluded with a surgical suture to create MI approximately at lateral myocardial wall [31]. Animals were randomly classified into 4 groups, each of which was composed of equal male and female subjects to reduce the bias arising from
Results
Maps of FA, color-coded FA, λ∥, and λ⊥ computed from DW images using different two b-value sets (i.e., 0 versus 5 representative non-zero b-values of 500, 1000, 1500, 2000, and 2500 s/mm2) as well as using all ten b-values via ME fitting were illustrated in Fig. 2. Each type of DTI index maps was displayed in the same grayscale for all groups. Myocardial fiber orientation, with red-green-blue colors representing the directions of left-right, up-down, and in-out, respectively, were observed to be
Discussion
“Slow” and “fast” diffusion pools were reported to coexist in complex biological tissues. Specifically, the slow diffusion pool comprises water that interacts by electrostatic forces with the proteins, cytoskeleton, and membranes of the cell, and the fast one consists of the remaining water in the intracellular or extracellular space [37]. It was generally accepted that small b-values tended to reveal information of fast diffusion pool, and large b-values helped slow diffusing to dominate the
Conclusion
Nonmonoexponential diffusion behavior in myocardium was confirmed. DTI indices were observed to decrease gradually with b-values in all regions and groups. Optimal b-value range for sensitive detection of microstructural alteration varied with targeted DTI indices. Specifically, FA showed the most sensitive detection of fiber integrity degradation at moderate b-values (≈ 1500 to 2000 s/mm2), and the strongest ability of mean and directional diffusivities in monitoring diffusivity alteration
Acknowledgments
The study was supported by National Natural Science Foundation of China (30900387), National Basic Research 973 Program of China (No. 2011CB707903), Hong Kong Research Grant Council (GRF HKU7826/10M), Introduction of Innovative R&D Team Program of Guangdong Province (LCHT and 201001S0104811217), and Basic Research Program of Shenzhen (JC201005270311A).
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