Super-resolution of diffusion-weighted images using space-customized learning model
Abstract
BACKGROUND:
Diffusion-weighted imaging (DWI) is a noninvasive method used for investigating the microstructural properties of the brain. However, a tradeoff exists between resolution and scanning time in clinical practice. Super-resolution has been employed to enhance spatial resolution in natural images, but its application on high-dimensional and non-Euclidean DWI remains challenging.
OBJECTIVE:
This study aimed to develop an end-to-end deep learning network for enhancing the spatial resolution of DWI through post-processing.
METHODS:
We proposed a space-customized deep learning approach that leveraged convolutional neural networks (CNNs) for the grid structural domain (x-space) and graph CNNs (GCNNs) for the diffusion gradient domain (q-space). Moreover, we represented the output of CNN as a graph using correlations defined by a Gaussian kernel in q-space to bridge the gap between CNN and GCNN feature formats.
RESULTS:
Our model was evaluated on the Human Connectome Project, demonstrating the effective improvement of DWI quality using our proposed method. Extended experiments also highlighted its advantages in downstream tasks.
CONCLUSION:
The hybrid convolutional neural network exhibited distinct advantages in enhancing the spatial resolution of DWI scans for the feature learning of heterogeneous spatial data.
1.Introduction
As the only noninvasive technique for in vivo examination of white matter tracts, diffusion-weighted imaging (DWI) plays a pivotal role in brain research [1]. However, DWI often encounters challenges in terms of quality due to the tradeoff between resolution, signal-to-noise ratio (SNR), and scanning time [2, 3]. For instance, acquiring higher-resolution DWI scans undesirably prolongs scanning time and lowers SNR. Conversely, low-resolution (LR) DWI can result in significant partial-volume effects and introduce bias into subsequent processing steps, such as diffusion tensor fitting, fiber tractography, and brain connectome construction. The demand for higher imaging spatial and angular resolutions has increased with the advancement of the model’s capability to depict tissue microstructure. The duration of magnetic resonance imaging (MRI) scans varies depending on several factors and typically ranges from 10 min to more than an hour. DWI necessitates longer scan times due to the requirement for a larger number of sequences. Patients must maintain a fixed posture and remain still during scanning to ensure data acquisition quality, which can be particularly challenging for infants. Despite continuous progress in DWI, it has consistently faced the predicament of limited promotion and application in clinical practice. Hence, addressing the urgent technical issue of meeting both high-quality imaging and high-efficiency requirements for the clinical implementation of diffusion MRI has become imperative. Super-resolution (SR) techniques can be employed to enhance the spatial resolution of DWI scans. In fact, SR has been a longstanding topic within the MRI community with various algorithms already developed for the SR of MRI scans [4, 5, 6, 7, 8, 9, 10, 11]. All of these methods aim to map LR images to their high-resolution (HR) counterparts using voxel correlations within an image or between different slice orientations.
The process of image acquisition can be perceived as a form of degradation, which can be mathematically represented as
The DWI scans exist within a combined 6D domain, encompassing both the x-space (spatial domain) and q-space (diffusion wave-vector domain). Within the x-space, diffusion signals are structured as a collection of volumes with a 3D grid arrangement. Tanno et al. assessed the uncertainty of CNNs for Bayesian quality transfer of DWI scans to enhance their spatial resolution [15]. They introduced generative adversarial networks to augment the spatial resolution of DWI scans. Additionally, attempts were made to leverage joint features from both x-space and q-space, represented by a graph, to learn missing information during longitudinal brain studies in infant [3]. Furthermore, efforts were made to optimize memory and computation costs to reduce model parameter capacity while ensuring efficient operation for deeper image quality transfer tasks [16]. Finally, SR generative adversarial network, enhanced deep SR network, and bicubic interpolation were employed in conjunction with each other to generate HR DWI scans for breast tumor detection [17, 18].
The DWI signal is associated with both the three-dimensional (3D) Euclidean space (x-space) and the diffusion gradient angle space (q-space). Its heterogeneous and high-dimensional characteristics pose challenges for effective learning using convolutional neural networks (CNNs). Although significant research progress has been made in DWI SR technology using deep learning (DL), existing methods primarily focus on feature learning in x-space and do not fully exploit the correlation between diffusion gradient directions in q-space. Existing models for image SR in DWI can be broadly classified into two groups. The first group primarily focuses on increasing spatial resolution without considering the impact of q-space, as demonstrated by Alexander et al. [11] and Tanno et al. [15]. The second group pays more attention to a unified framework by integrating both x-space and q-space with compromises induced by heterogeneous domain fusion, as proposed by Chen et al. [3]. For overcoming these limitations, we proposed a two-stage domain-directed (TSDD) learning network that fully exploited correlations in both x-space and q-space to enhance the spatial resolution of DWI scans. In this study, “Domain Directed” refers to the guiding convolution type based on the structure inherent to each domain. Specifically, we relied on CNNs for effective perception in x-space and on graph CNNs (GCNNs) for exploiting correlations in q-space. We designed a cascaded hybrid neural network comprising CNNs and GCNNs to address the aforementioned drawbacks. First, a residual CNN sub-network predicted coarse SR in the x-space. Subsequently, GCNN refined this coarse SR in q-space. Compared with the existing models that operated solely within specific domains, our approach leveraged the strengths of both CNNs in grid-structure domains and GCNNs in non-Euclidean domains. Furthermore, serving as a post-processing method, the approach was independent of scanning protocols. We evaluated our method using data from the Human Connectome Project (HCP), demonstrating satisfactory performance achieved by TSDD.
The structure of our manuscript is outlined as follows. Section 2 provides a comprehensive description of our network architecture. In Section 3, we present the datasets and discuss the obtained results. Section 4 delves into insightful discussions. Finally, in Section 5, we conclude our work.
2.Materials and methods
Existing studies have demonstrated the exceptional learning performance of CNN in domains characterized by a grid structure. However, the effectiveness of CNN is limited when applied to non-Euclidean spaces [19]. We proposed an end-to-end heterogeneous deep neural network that combined both CNN and GCNN in the case of DWI scans where 3D volumes were sampled from q-space (a non-Euclidean and wave-vector domain). Our approach involved using CNN to initially predict HR DWI scans in x-space for each volume, followed by refining these predictions using GCNN to exploit the correlations among diffusion gradients in q-space. The application of GCNN followed ChebNet [19], which was based on graph spectrum analysis [20]. The output of CNN needed to be formatted accordingly to meet the requirements of GCNN. For this purpose, we predefined a fixed graph as the reference for graph learning in this study. The construction details of the reference graph are visualized in Fig. 1 and discussed in Section 2.1. Additionally, Section 2.2 provides an introduction to GCNN, whereas Section 2.3 presents a summary and discussion of our network architecture depicted in Fig. 2. Finally, Section 2.4 outlines the loss function employed for this task.
Figure 1.
2.1Reference graph
In the first stage, a CNN-based sub-network was used to predict a coarse DWI SR in the x-space. However, the coarse SR obtained could not be directly fed into the subsequent GCNN-based sub-network due to the inconsistent data format. Graph-structured samples are essential for GCNN. Therefore, we needed to bridge the format gap and make training feasible in our two-stage network with hybrid convolutions. To achieve this goal, we constructed a reference graph in q-space to leverage correlations among diffusions. This reference graph served as an indispensable component for graph convolution operations in our experiments. The details of reference graph construction are illustrated in Fig. 1.
(1)
where
2.2Graph CNN
In the last decade, DL has demonstrated exceptional performance across various applications. Particularly, CNNs and recurrent neural networks have achieved state-of-the-art results in computer vision and speech recognition tasks. Generally, CNNs are employed for feature extraction from 2D or 3D grid-structured data. However, they cannot be directly applied to high-dimensional or non-Euclidean datasets such as citations and social networks. DWI data possess both high-dimensional and non-Euclidean characteristics due to the dependence of their voxel values on spatial location and diffusion wave-vector. Conventional CNN models also exhibit limited effectiveness when applied to DWI data.
Many approaches have been proposed for the application of DL to non-Euclidean data, including those by Bronstein et al., Lee et al., and Li et al. [21, 22, 23]. Among these, GCNN stands out as a convolutional model based on graph spectrum, which was initially introduced by Bruna et al. [20]. Compared with CNNs, GCNNs offer a more versatile learning framework that leverages frequency domain multiplication to define graph convolutions and allows for the definition of graph filters as follows:
(2)
where
(3)
where
(4)
where
(5)
where
GCNN has displayed outstanding performance in some studies. For instance, Kipf and Welling proposed a semi-supervised learning network based on GCNN for citation network classification [26]. Ktena et al. used GCNN to examine the difference between two functional brain networks [27]. The correlations in q-space were fully exploited in this task based on GCNN to improve the performance of DWI SR. Section 2.3 explains in detail how to build a hybrid neural network, and Section 2.4 describes how to train a hybrid neural network in the DWI SR task.
2.3TSDD neural network
As previously mentioned, DWI data exist in a 6D space, consisting of three dimensions for spatial space and three dimensions for diffusion directions. Each diffusion direction has a DWI scan organized as a volume with a 3D grid structure. Leveraging this prior structural information is advantageous for SR performance. Given the significant advantages of CNNs in learning tasks involving 2D or 3D data, we first employed them for coarse SR prediction. Additionally, we proposed using correlations in diffusion gradients to enhance SR performance because the diffusion signal was influenced by not only spatial position but also diffusion gradient direction.
We referred to our proposed SR method as the TSDD neural network. In the first stage, we developed a 3D version of dense convolutional networks (DenseNet [28]) to generate a coarse SR prediction solely based on the 3D DWI scans. Subsequently, in the second stage, we transformed this coarse prediction into a graph using the approach described in Section 2.1 and enhanced it through GCNN refinement. Thus, we effectively leveraged the strengths of CNNs and GCNNs across distinct data domains for accomplishing the DWI SR task.
Figure 2.
As shown in Fig. 2, our network consisted of two sub-networks: dense CNN and graph CNN. The input of our network was the LR DWI scans, whereas the target output was the SR DWI scans. The whole pipeline could be formulated as follows:
(6)
where
DenseNet has proven to be highly effective in image SR tasks because it promotes feature reuse and alleviates the vanishing gradient problem that can plague deep networks [29, 30, 31]. The output of DenseNet is a coarse SR prediction, which is enhanced in the x-space with a 3D grid structure. The signals of each voxel at all diffusion gradients were organized as a vector, as discussed in Section 2.1. Then, leveraging the reference graph illustrated in Fig. 1, the CSR was represented as a graph and inputted into the sub-network based on GCNN.
The input of GCNN consisted of two parts: graph signal and reference graph. The representation of the graph signal and reference graph is shown in Fig. 1. The specific generation process has been described in detail in Section 2.1. The graph CNN in this study was based on ChebNet [19]. The specific convolution operation definition has been explained in Section 2.2. The graph convolutional layer primarily involved two parameters: the order of the Chebyshev polynomial and the number of filters, also known as channels. These parameters collectively determined the capacity of network parameters. The order of the Chebyshev polynomial determined both the number of parameters in the graph convolution filter and its neighborhood range within the graph. The experimental results demonstrated that an optimal outcome could be achieved when setting the order to 2, with minimal impact on performance, by increasing it further. In this study, all graph convolution filters in GCNN were set to order 2. For our experiments, we configured the number of channels for each graph convolutional layer as follows: 1 channel for input graphs, 64 channels for middle layers, and 1 channel for the final layer. Following this output graph stage, three additional convolutional layers similar to those used at the inception of CNN were employed to strike a balance between smoothing and sharpening.
2.4Loss function
The DWI SR in this task was considered as a regression procedure from LR to HR. Similar to most regression networks, the mean square error (MSE) was used as an objective function in both CNN- and GCNN-based sub-networks. The details of the MSE loss was defined as follows:
(7)
where
According to the graph spectral theory, edge connections between nodes in a graph can be expressed as a Laplacian matrix. To evaluate the similarity between the predicted and target graphs, we defined Laplacian loss as follows:
(8)
where
(9)
where
(10)
where
3.Experiments
3.1Data
The actual brain diffusion MRI data used in this study were acquired by Washington University in Saint Louis and the University of Minnesota [32], and downloaded from the HCP. Scanning was performed on a Siemens 3T Skyra scanner using a 2D spin-echo single-shot multi-band EPI sequence with a multi-band factor of 3 and a monopolar gradient pulse. The spatial resolution was set to 1.25 mm isotropic, with TR
3.2Training setting
The Adam optimizer was employed to train our model, with an initial learning rate of 10-4 and a decay frequency of once every 5000 iterations. Other training settings were as follows: a batch size of 20 and a maximum epoch set to 300. Additionally, we used a nonzero-ratio of 0.1 to discard voxel patches containing excessive zeros. Our network implementation was based on the TensorFlow 1.9 framework. The training process took approximately 12 h using a single GTX 2080Ti GPU.
3.3Evaluation metrics
The computation of three quantitative metrics, such as MSE, peak signal-to-noise ratio (PSNR), and structural similarity (SSIM), was conducted as proposed previously [36]. The mathematical definitions for MSE, PSNR, and SSIM are presented in Eqs (11), (12), and (13), respectively. In this study, we solely evaluated our model using single-shell data while reserving the evaluation on multi-shell data for future investigation. MSE is defined as follows:
(11)
where
(12)
where Max denotes the maximum diffusion value. In our experiment, DWI data were normalized to the value range of (0 1); thus, Max was 1. SSIM is defined as follows:
(13)
where
Figure 3.
Figure 4.
Figure 5.
3.4Results
Comparisons were made on bicubic interpolation citation: CNN-only neural network and GCNN-only neural network with the same capacity of parameters. We also evaluated the quality of derived diffusion features, including fractional anisotropy (FA), fiber orientation distribution functions (fODFs) and fiber tracts. As shown in Fig. 3, the results of our proposed method were closer to the ground truth. We also computed the error maps for DWI and FA values (Figs 4 and 5). These figures show that our proposed method still achieved the best performance. The colored FA images are shown in Fig. 6. We zoomed in on some local regions of DWI scans, as shown in Fig. 7. These results indicated that our model achieved better performance with more structural details. fODFs are visualized in Fig. 8, indicating that the proposed model had coherent and clean fiber distributions close to the ground truth. We further performed tractography to evaluate our method. The fiber tracking results are visualized in Fig. 9, indicating that our model yielded rich fiber tracts extremely similar to the ground truth. All of the source images and their featured mappings were visualized using MRtrix3 [37].
Figure 6.
Table 1
Model | Linear | NLM | CNN | GCNN | TSDD |
---|---|---|---|---|---|
DWI | 29.69 and 0.90 | 30.16 and 0.92 | 30.49 and 0.95 | 28.29 and 0.94 | 33.52 and 0.96 |
FA | 30.11 and 0.92 | 31.24 and 0.93 | 32.46 and 0.96 | 30.35 and 0.93 | 34.32 and 0.98 |
Figure 7.
Figure 8.
Figure 9.
The quantitative results are displayed in Table 1 As shown, the proposed method achieved the best performance in terms of PSNR and SSIM.
4.Discussion
In our experiments, the voxel value in DWI scans was normalized to [0–1], reducing the loss value. So, a smaller regulation coefficient was a reasonable choice in training, for example, 5
5.Conclusions
In this study, we proposed a two-stage and domain-directed convolutional learning model for increasing the spatial resolution of LR DWI scans. In our proposed network, we used CNN and GCNN to extract spatial and angular information from grid structural and diffusion domains, respectively. Extensive experiments using HCP data demonstrated the improved performance of our proposed method in both qualitative and quantitative evaluations. Our model had the potential to be applied to other studies requiring learning from heterogeneous data domains.
Acknowledgments
The data for this study were partially sourced from the HCP, WU-Minn Consortium, led by principal investigators David Van Essen and Kamil Ugurbil (Grant No. 1U54MH091657). Funding for this project was provided by 16 NIH institutes and centers supporting the NIH Blueprint for Neuroscience Research, and by the McDonnell Center for Systems Neuroscience at Washington University. The data collection and sharing were facilitated by the MGH-USC HCP.
Conflict of interest
None to report.
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