SiMix: A domain generalization method for cross-site brain MRI harmonization via site mixing.

Brain magnetic resonance imaging (MRI) is widely used in clinical practice for disease diagnosis. However, MRI scans acquired at different sites can have different appearances due to the difference in the hardware, pulse sequence, and imaging parameter. It is important to reduce or eliminate such cross-site variations with brain MRI harmonization so that downstream image processing and analysis is performed consistently. Previous works on the harmonization problem require the data acquired from the sites of interest for model training. But in real-world scenarios there can be test data from a new site of interest after the model is trained, and training data from the new site is unavailable when the model is trained. In this case, previous methods cannot optimally handle the test data from the new unseen site. To address the problem, in this work we explore domain generalization for brain MRI harmonization and propose Site Mix (SiMix). We assume that images of travelling subjects are acquired at a few existing sites for model training. To allow the training data to better represent the test data from unseen sites, we first propose to mix the training images belonging to different sites stochastically, which substantially increases the diversity of the training data while preserving the authenticity of the mixed training images. Second, at test time, when a test image from an unseen site is given, we propose a multiview strategy that perturbs the test image with preserved authenticity and ensembles the harmonization results of the perturbed images for improved harmonization quality. To validate SiMix, we performed experiments on the publicly available SRPBS dataset and MUSHAC dataset that comprised brain MRI acquired at nine and two different sites, respectively. The results indicate that SiMix improves brain MRI harmonization for unseen sites, and it is also beneficial to the harmonization of existing sites.

Deep learning enables accurate brain tissue microstructure analysis based on clinically feasible diffusion magnetic resonance imaging.

Diffusion magnetic resonance imaging (dMRI) allows non-invasive assessment of brain tissue microstructure. Current model-based tissue microstructure reconstruction techniques require a large number of diffusion gradients, which is not clinically feasible due to imaging time constraints, and this has limited the use of tissue microstructure information in clinical settings. Recently, approaches based on deep learning (DL) have achieved promising tissue microstructure reconstruction results using clinically feasible dMRI. However, it remains unclear whether the subtle tissue changes associated with disease or age are properly preserved with DL approaches and whether DL reconstruction results can benefit clinical applications. Here, we provide the first evidence that DL approaches to tissue microstructure reconstruction yield reliable brain tissue microstructure analysis based on clinically feasible dMRI scans. Specifically, we reconstructed tissue microstructure from four different brain dMRI datasets with only 12 diffusion gradients, a clinically feasible protocol, and the neurite orientation dispersion and density imaging (NODDI) and spherical mean technique (SMT) models were considered. With these results we show that disease-related and age-dependent alterations of brain tissue were accurately identified. These findings demonstrate that DL tissue microstructure reconstruction can accurately quantify microstructural alterations in the brain based on clinically feasible dMRI.

Brain network dynamics in patients with single- and multiple-domain amnestic mild cognitive impairment.

INTRODUCTION: Brain network dynamics have been extensively explored in patients with amnestic mild cognitive impairment (aMCI); however, differences in single- and multiple-domain aMCI (SD-aMCI and MD-aMCI) remain unclear. METHODS: Using multicenter datasets, coactivation patterns (CAPs) were constructed and compared among normal control (NC), SD-aMCI, MD-aMCI, and Alzheimer's disease (AD) patients based on individual high-order cognitive network (HOCN) and primary sensory network (PSN) parcellations. Correlations between spatiotemporal characteristics and neuropsychological scores were analyzed. RESULTS: Compared to NC, SD-aMCI showed temporal alterations in HOCN-dominant CAPs, while MD-aMCI showed alterations in PSN-dominant CAPs. In addition, transitions from SD-aMCI to AD may involve PSN, while MD-aMCI to AD involves both PSN and HOCN. Results were generally consistent across datasets from Chinese and White populations. DISCUSSION: The HOCN and PSN are distinctively involved in aMCI subtypes and in the transformation between aMCI subtypes and AD, highlighting the necessity of aMCI subtype classification in AD studies. HIGHLIGHTS: Individual functional network parcellations and coactivation pattern (CAP) analysis were performed to characterize spatiotemporal differences between single- and multiple-domain amnestic mild cognitive impairment (SD-aMCI and MD-aMCI), and between distinct aMCI subtypes and Alzheimer's disease (AD). The analysis of multicenter datasets converged on four pairs of recurrent CAPs, including primary sensory networks (PSN)-dominant CAPs, high-order cognitive networks (HOCN)-dominant CAPs, and PSN-HOCN-interacting CAPs. The HOCN and PSN are distinctively involved in aMCI subtypes and in the transformation between distinct aMCI subtypes and AD.

CarveMix: A simple data augmentation method for brain lesion segmentation.

Brain lesion segmentation provides a valuable tool for clinical diagnosis and research, and convolutional neural networks (CNNs) have achieved unprecedented success in the segmentation task. Data augmentation is a widely used strategy to improve the training of CNNs. In particular, data augmentation approaches that mix pairs of annotated training images have been developed. These methods are easy to implement and have achieved promising results in various image processing tasks. However, existing data augmentation approaches based on image mixing are not designed for brain lesions and may not perform well for brain lesion segmentation. Thus, the design of this type of simple data augmentation method for brain lesion segmentation is still an open problem. In this work, we propose a simple yet effective data augmentation approach, dubbed as CarveMix, for CNN-based brain lesion segmentation. Like other mixing-based methods, CarveMix stochastically combines two existing annotated images (annotated for brain lesions only) to obtain new labeled samples. To make our method more suitable for brain lesion segmentation, CarveMix is lesion-aware, where the image combination is performed with a focus on the lesions and preserves the lesion information. Specifically, from one annotated image we carve a region of interest (ROI) according to the lesion location and geometry with a variable ROI size. The carved ROI then replaces the corresponding voxels in a second annotated image to synthesize new labeled images for network training, and additional harmonization steps are applied for heterogeneous data where the two annotated images can originate from different sources. Besides, we further propose to model the mass effect that is unique to whole brain tumor segmentation during image mixing. To evaluate the proposed method, experiments were performed on multiple publicly available or private datasets, and the results show that our method improves the accuracy of brain lesion segmentation. The code of the proposed method is available at https://github.com/ZhangxinruBIT/CarveMix.git.

Prediction of H3K27M Alteration Status in Brainstem Glioma Using Multi-Shell Diffusion MRI Metrics.

BACKGROUND: Multi-shell diffusion characteristics may help characterize brainstem gliomas (BSGs) and predict H3K27M status. PURPOSE: To identify the diffusion characteristics of BSG patients and investigate the predictive values of various diffusion metrics for H3K27M status in BSG. STUDY TYPE: Prospective. POPULATION: Eighty-four BSG patients (median age 10.5 years [IQR 6.8-30.0 years]) were included, of whom 56 were pediatric and 28 were adult patients. FIELD STRENGTH/SEQUENCE: 3 T, multi-shell diffusion imaging. ASSESSMENT: Diffusion kurtosis imaging and neurite orientation dispersion and density imaging analyses were performed. Age, gender, and diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, radial diffusivity (RD), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis, intracellular volume fraction (ICVF), orientation dispersion index, and isotropic volume fraction (ISOVF), were compared between H3K27M-altered and wildtype BSG patients. STATISTICAL TESTS: Chi-square test, Mann-Whitney U test, multivariate analysis of variance (MANOVA), step-wise multivariable logistic regression. P-values <0.05 were considered significant. RESULTS: 82.4% pediatric and 57.1% adult patients carried H3K27M alteration. In the whole group, the H3K27M-altered BSGs demonstrated higher FA, AK and lower RD, ISOVF. The combination of age and median ISOVF showed fair performance for H3K27M prediction (AUC = 0.78). In the pediatric group, H3K27M-altered BSGs showed higher FA, AK, MK, ICVF and lower RD, MD, ISOVF. The combinations of median ISOVF, 5th percentile of FA, median MK and median MD showed excellent predictive power (AUC = 0.91). In the adult group, H3K27M-altered BSGs showed higher ICVF and lower RD, MD. The 75th percentile of RD demonstrated fair performance for H3K27M status prediction (AUC = 0.75). DATA CONCLUSION: Different alteration patterns of diffusion measures were identified between H3K27M-altered and wildtype BSGs, which collectively had fair to excellent predictive value for H3K27M alteration status, especially in pediatric patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Deep Learning for Noninvasive Assessment of H3 K27M Mutation Status in Diffuse Midline Gliomas Using MR Imaging.

BACKGROUND: Determination of H3 K27M mutation in diffuse midline glioma (DMG) is key for prognostic assessment and stratifying patient subgroups for clinical trials. MRI can noninvasively depict morphological and metabolic characteristics of H3 K27M mutant DMG. PURPOSE: This study aimed to develop a deep learning (DL) approach to noninvasively predict H3 K27M mutation in DMG using T2-weighted images. STUDY TYPE: Retrospective and prospective. POPULATION: For diffuse midline brain gliomas, 341 patients from Center-1 (27 ± 19 years, 184 males), 42 patients from Center-2 (33 ± 19 years, 27 males) and 35 patients (37 ± 18 years, 24 males). For diffuse spinal cord gliomas, 133 patients from Center-1 (30 ± 15 years, 80 males). FIELD STRENGTH/SEQUENCE: 5T and 3T, T2-weighted turbo spin echo imaging. ASSESSMENT: Conventional radiological features were independently reviewed by two neuroradiologists. H3 K27M status was determined by histopathological examination. The Dice coefficient was used to evaluate segmentation performance. Classification performance was evaluated using accuracy, sensitivity, specificity, and area under the curve. STATISTICAL TESTS: Pearson's Chi-squared test, Fisher's exact test, two-sample Student's t-test and Mann-Whitney U test. A two-sided P value <0.05 was considered statistically significant. RESULTS: In the testing cohort, Dice coefficients of tumor segmentation using DL were 0.87 for diffuse midline brain and 0.81 for spinal cord gliomas. In the internal prospective testing dataset, the predictive accuracies, sensitivities, and specificities of H3 K27M mutation status were 92.1%, 98.2%, 82.9% in diffuse midline brain gliomas and 85.4%, 88.9%, 82.6% in spinal cord gliomas. Furthermore, this study showed that the performance generalizes to external institutions, with predictive accuracies of 85.7%-90.5%, sensitivities of 90.9%-96.0%, and specificities of 82.4%-83.3%. DATA CONCLUSION: In this study, an automatic DL framework was developed and validated for accurately predicting H3 K27M mutation using T2-weighted images, which could contribute to the noninvasive determination of H3 K27M status for clinical decision-making. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.

Volumetric segmentation of white matter tracts with label embedding.

Convolutional neural networks have achieved state-of-the-art performance for white matter (WM) tract segmentation based on diffusion magnetic resonance imaging (dMRI). However, the segmentation can still be difficult for challenging WM tracts with thin bodies or complicated shapes; the segmentation is even more problematic in challenging scenarios with reduced data quality or domain shift between training and test data, which can be easily encountered in clinical settings. In this work, we seek to improve the segmentation of WM tracts, especially for challenging WM tracts in challenging scenarios. In particular, our method is based on volumetric WM tract segmentation, where voxels are directly labeled without performing tractography. To improve the segmentation, we exploit the characteristics of WM tracts that different tracts can cross or overlap and revise the network design accordingly. Specifically, because multiple tracts can co-exist in a voxel, we hypothesize that the different tract labels can be correlated. The tract labels at a single voxel are concatenated as a label vector, the length of which is the number of tract labels. Due to the tract correlation, this label vector can be projected into a lower-dimensional space-referred to as the embedded space-for each voxel, which allows the segmentation network to solve a simpler problem. By predicting the coordinate in the embedded space for the tracts at each voxel and subsequently mapping the coordinate to the label vector with a reconstruction module, the segmentation result can be achieved. To facilitate the learning of the embedded space, an auxiliary label reconstruction loss is integrated with the segmentation accuracy loss during network training, and network training and inference are end-to-end. Our method was validated on two dMRI datasets under various settings. The results show that the proposed method improves the accuracy of WM tract segmentation, and the improvement is more prominent for challenging tracts in challenging scenarios.

Cerebellar Contributions to Motor and Cognitive Control in Multiple Sclerosis✰✰✰.

OBJECTIVE: To evaluate relationships between specific cerebellar regions and common clinical measures of motor and cognitive function in persons with multiple sclerosis (PwMS). DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS: Twenty-nine PwMS and 28 age- and sex-matched controls without multiple sclerosis (MS) (N=57). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Both diffusion and lobule magnetic resonance imaging analyses and common clinical measures of motor and cognitive function were used to examine structure-function relationships in the cerebellum. RESULTS: PwMS demonstrate significantly worse motor and cognitive function than controls, including weaker strength, slower walking, and poorer performance on the Symbol Digit Modalities Test, but demonstrate no differences in cerebellar volume. However, PwMS demonstrate significantly worse diffusivity (mean diffusivity: P=.0003; axial diffusivity: P=.0015; radial diffusivity: P=.0005; fractional anisotropy: P=.016) of the superior cerebellar peduncle, the primary output of the cerebellum. Increased volume of the motor lobules (I-V, VIII) was significantly related to better motor (P<.022) and cognitive (P=.046) performance, and increased volume of the cognitive lobules (VI-VII) was also related to better motor (P<.032) and cognitive (P=.008) performance, supporting the role of the cerebellum in both motor and cognitive functioning. CONCLUSIONS: These data highlight the contributions of the cerebellum to both motor and cognitive function in PwMS. Using novel neuroimaging techniques to examine structure-function relationships in PwMS improves our understanding of individualized differences in this heterogeneous group and may provide an avenue for targeted, individualized rehabilitation aimed at improving cerebellar dysfunction in MS.

Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease.

The cerebellum plays an important role in both motor control and cognitive function. Cerebellar function is topographically organized and diseases that affect specific parts of the cerebellum are associated with specific patterns of symptoms. Accordingly, delineation and quantification of cerebellar sub-regions from magnetic resonance images are important in the study of cerebellar atrophy and associated functional losses. This paper describes an automated cerebellar lobule segmentation method based on a graph cut segmentation framework. Results from multi-atlas labeling and tissue classification contribute to the region terms in the graph cut energy function and boundary classification contributes to the boundary term in the energy function. A cerebellar parcellation is achieved by minimizing the energy function using the α-expansion technique. The proposed method was evaluated using a leave-one-out cross-validation on 15 subjects including both healthy controls and patients with cerebellar diseases. Based on reported Dice coefficients, the proposed method outperforms two state-of-the-art methods. The proposed method was then applied to 77 subjects to study the region-specific cerebellar structural differences in three spinocerebellar ataxia (SCA) genetic subtypes. Quantitative analysis of the lobule volumes shows distinct patterns of volume changes associated with different SCA subtypes consistent with known patterns of atrophy in these genetic subtypes.

Reconstruction of the human cerebral cortex robust to white matter lesions: method and validation.

Cortical atrophy has been reported in a number of diseases, such as multiple sclerosis and Alzheimer's disease, that are also associated with white matter (WM) lesions. However, most cortical reconstruction techniques do not account for these pathologies, thereby requiring additional processing to correct for the effect of WM lesions. In this work, we introduce CRUISE(+), an automated process for cortical reconstruction from magnetic resonance brain images with WM lesions. The process extends previously well validated methods to allow for multichannel input images and to accommodate for the presence of WM lesions. We provide new validation data and tools for measuring the accuracy of cortical reconstruction methods on healthy brains as well as brains with multiple sclerosis lesions. Using this data, we validate the accuracy of CRUISE(+) and compare it to another state-of-the-art cortical reconstruction tool. Our results demonstrate that CRUISE(+) has superior performance in the cortical regions near WM lesions, and similar performance in other regions.

Multi-Task Collaborative Pre-Training and Adaptive Token Selection: A Unified Framework for Brain Representation Learning.

Structural magnetic resonance imaging (sMRI) reveals the structural organization of the brain. Learning general brain representations from sMRI is an enduring topic in neuroscience. Previous deep learning models neglect that the brain, as the core of cognition, is distinct from other organs whose primary attribute is anatomy. Capturing the high-level representation associated with inter-individual cognitive variability is key to appropriately represent the brain. Given that this cognition-related information is subtle, mixed, and distributed in the brain structure, sMRI-based models need to both capture fine-grained details and understand how they relate to the overall global structure. Additionally, it is also necessary to explicitly express the cognitive information that implicitly embedded in local-global image features. Therefore, we propose MCPATS, a brain representation learning framework that combines Multi-task Collaborative Pre-training (MCP) and Adaptive Token Selection (ATS). First, we develop MCP, including mask-reconstruction to understand global context, distort-restoration to capture fine-grained local details, adversarial learning to integrate features at different granularities, and age-prediction, using age as a surrogate for cognition to explicitly encode cognition-related information from local-global image features. This co-training allows progressive learning of implicit and explicit cognition-related representations. Then, we develop ATS based on mutual attention for downstream use of the learned representation. During fine-tuning, the ATS highlights discriminative features and reduces the impact of irrelevant information. MCPATS was validated on three different public datasets for brain disease diagnosis, outperforming competing methods and achieving accurate diagnosis. Further, we performed detailed analysis to confirm that the MCPATS-learned representation captures cognition-related information.

HMDA: A Hybrid Model with Multi-scale Deformable Attention for Medical Image Segmentation.

Transformers have been applied to medical image segmentation tasks owing to their excellent longrange modeling capability, compensating for the failure of Convolutional Neural Networks (CNNs) to extract global features. However, the standardized self-attention modules in Transformers, characterized by a uniform and inflexible pattern of attention distribution, frequently lead to unnecessary computational redundancy with high-dimensional data, consequently impeding the model's capacity for precise concentration on salient image regions. Additionally, achieving effective explicit interaction between the spatially detailed features captured by CNNs and the long-range contextual features provided by Transformers remains challenging. In this architecture, we propose a Hybrid Transformer and CNN architecture with Multi-scale Deformable Attention(HMDA), designed to address the aforementioned issues effectively. Specifically, we introduce a Multi-scale Spatially Adaptive Deformable Attention (MSADA) mechanism, which attends to a small set of key sampling points around a reference within the multi-scale features, to achieve better performance. In addition, we propose the Cross Attention Bridge (CAB) module, which integrates multi-scale transformer and local features through channelwise cross attention enriching feature synthesis. HMDA is validated on multiple datasets, and the results demonstrate the effectiveness of our approach, which achieves competitive results compared to the previous methods.

Attention-based q-space Deep Learning Generalized for Accelerated Diffusion Magnetic Resonance Imaging.

Diffusion magnetic resonance imaging (dMRI) is a non-invasive method for capturing the microanatomical information of tissues by measuring the diffusion weighted signals along multiple directions, which is widely used in the quantification of microstructures. Obtaining microscopic parameters requires dense sampling in the q space, leading to significant time consumption. The most popular approach to accelerating dMRI acquisition is to undersample the q-space data, along with applying deep learning methods to reconstruct quantitative diffusion parameters. However, the reliance on a predetermined q-space sampling strategy often constrains traditional deep learning-based reconstructions. The present study proposed a novel deep learning model, named attention-based q-space deep learning (aqDL), to implement the reconstruction with variable q-space sampling strategies. The aqDL maps dMRI data from different scanning strategies onto a common feature space by using a series of Transformer encoders. The latent features are employed to reconstruct dMRI parameters via a multilayer perceptron. The performance of the aqDL model was assessed utilizing the Human Connectome Project datasets at varying undersampling numbers. To validate its generalizability, the model was further tested on two additional independent datasets. Our results showed that aqDL consistently achieves the highest reconstruction accuracy at various undersampling numbers, regardless of whether variable or predetermined q-space scanning strategies are employed. These findings suggest that aqDL has the potential to be used on general clinical dMRI datasets.

Generating synthetic computed tomography for radiotherapy: SynthRAD2023 challenge report.

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information, while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: (1) MRI-to-CT and (2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (≥0.87/0.90) and gamma pass rates for photon (≥98.1%/99.0%) and proton (≥97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy. It showcased the growing capacity of deep learning to produce high-quality sCT, reducing reliance on conventional CT for treatment planning.

One-shot segmentation of novel white matter tracts via extensive data augmentation and adaptive knowledge transfer.

The use of convolutional neural networks (CNNs) has allowed accurate white matter (WM) tract segmentation on diffusion magnetic resonance imaging (dMRI). To train the CNN-based segmentation models, a large number of scans on which WM tracts are annotated need to be collected, and these annotated scans can be accumulated over a long period of time. However, when novel WM tracts that are different from existing annotated WM tracts are of interest, additional annotations are required for their segmentation. Due to the cost of manual annotations, methods have been developed for few-shot segmentation of novel WM tracts, where the segmentation knowledge is transferred from existing WM tracts to novel WM tracts and the amount of annotated data for novel WM tracts is reduced. Despite these developments, it is desirable to further reduce the amount of annotated data to the one-shot setting with a single annotated image. To address this problem, we develop an approach to one-shot segmentation of novel WM tracts. Our method follows the existing pretraining/fine-tuning framework that transfers segmentation knowledge from existing to novel WM tracts. First, as there is extremely scarce annotated data in the one-shot setting, we design several different data augmentation strategies so that extensive data augmentation can be performed to obtain extra synthetic training data. The data augmentation strategies are based on image masking and thus applicable to the one-shot setting. Second, to address overfitting and knowledge forgetting in the fine-tuning stage that can be more severe given limited training data, we propose an adaptive knowledge transfer strategy that selects the network weights to be updated. The data augmentation and adaptive knowledge transfer strategies are combined to train the segmentation model. Considering that the different data augmentation strategies can generate synthetic data that contain potentially conflicting information, we apply the data augmentation strategies separately, each leading to a different segmentation model. The results predicted by the different models are fused to produce the final segmentation. We validated our method on two brain dMRI datasets, including a public dataset and an in-house dataset. Different settings were considered for the validation, and the results show that the proposed method improves the one-shot segmentation of novel WM tracts.

A microstructure estimation Transformer inspired by sparse representation for diffusion MRI.

Diffusion magnetic resonance imaging (dMRI) is an important tool in characterizing tissue microstructure based on biophysical models, which are typically multi-compartmental models with mathematically complex and highly non-linear forms. Resolving microstructures from these models with conventional optimization techniques is prone to estimation errors and requires dense sampling in the q-space with a long scan time. Deep learning based approaches have been proposed to overcome these limitations. Motivated by the superior performance of the Transformer in feature extraction than the convolutional structure, in this work, we present a learning-based framework based on Transformer, namely, a Microstructure Estimation Transformer with Sparse Coding (METSC) for dMRI-based microstructural parameter estimation. To take advantage of the Transformer while addressing its limitation in large training data requirement, we explicitly introduce an inductive bias-model bias into the Transformer using a sparse coding technique to facilitate the training process. Thus, the METSC is composed with three stages, an embedding stage, a sparse representation stage, and a mapping stage. The embedding stage is a Transformer-based structure that encodes the signal in a high-level space to ensure the core voxel of a patch is represented effectively. In the sparse representation stage, a dictionary is constructed by solving a sparse reconstruction problem that unfolds the Iterative Hard Thresholding (IHT) process. The mapping stage is essentially a decoder that computes the microstructural parameters from the output of the second stage, based on the weighted sum of normalized dictionary coefficients where the weights are also learned. We tested our framework on two dMRI models with downsampled q-space data, including the intravoxel incoherent motion (IVIM) model and the neurite orientation dispersion and density imaging (NODDI) model. The proposed method achieved up to 11.25 folds of acceleration while retaining high fitting accuracy for NODDI fitting, reducing the mean squared error (MSE) up to 70% compared with the previous q-space learning approach. METSC outperformed the other state-of-the-art learning-based methods, including the model-free and model-based methods. The network also showed robustness against noise and generalizability across different datasets. The superior performance of METSC indicates its potential to improve dMRI acquisition and model fitting in clinical applications.

The combination of HT-ac and HBET improves the cognitive and learning abilities of heat-stressed mice by maintaining mitochondrial function through the PKA-CREB-BDNF pathway.

The aim was to investigate whether the combination of hydroxytyrosol acetate (HT-ac) and ethyl ß-hydroxybutyrate (HBET) can improve the cognition of heat-stressed mice, meanwhile exploring the mechanism of action. Mice were divided into 5 groups: control, heat-stressed, HT-ac, HBET, and HT-ac + HBET. Mice were gavaged for 21 days and exposed to heat (42.5 ± 0.5 °C, RH 60 ± 10%, 1 h day-1) on days 15-21, except for the control group. Results showed that the combination of HT-ac + HBET improved the cognitive and learning abilities of heat-stressed mice, which were tested by Morris water maze, shuttle box, and jumping stage tests. The combination of HT-ac + HBET maintained the integrity of neurons and mitochondria of heat-stressed mice. Likewise, this combination increased the mitochondrial membrane potential, the ATP content, the expression of phosphorylated PKA, BDNF, phosphorylated CREB and Bcl-2, and decreased the expression of Bax, caspase-3, and intracytoplasmic Cyt C in heat-stressed mice.

Nutritional supplements formulated to prevent cognitive impairment in animals.

Heat stress will cause a series of response in the living system and the most significant impact is on brain functions. The aim of this article is to develop nutritional supplements that can alleviate cognitive decline caused by heat stress. In this article, we screen functional food factors which can prevent or relieve effects on heat stress injury based on bioinformatics. 129 function factors related to the crossover targets were obtained, and a food database related to the prevention of high-temperature impairment was constructed. After a series of scoring standards combined with food classification, two formulas-nutrition fortifier formula (tyrosine and multivitamin B) and plant compound formula (quercetin, proanthocyanidin, and naringin) were investigated using animal experiments to determine their ability to prevent cognitive impairment of heat-stressed animals. Our results demonstrated that certain functional food factors and our two designed formulations significantly prevent cognitive impairment of heat-stressed animals. Further mechanism was carried out by cell viability assay, reactive oxygen species assay, real-time quantitative PCR and Western blot. The results showed that the plant compound formula diluted 4000 times had the best relieving effect on HT22 after heat stress, and this concentration formula can significantly alleviate the elevated levels of reactive oxygen species caused by heat stress. This formula also can significantly down-regulate IL-1ß, IL-6, TNF-α, IL-10, iNOS and COX-2 expression. Likewise, Western blot results showed that the formula could activate the cAMP pathway and increase the expression of phosphorylated PKA and BDNF in hippocampal cells.

A transfer learning approach to few-shot segmentation of novel white matter tracts.

Convolutional neural networks (CNNs) have achieved state-of-the-art performance for white matter (WM) tract segmentation based on diffusion magnetic resonance imaging (dMRI). The training of the CNN-based segmentation model generally requires a large number of manual delineations of WM tracts, which can be expensive and time-consuming. Although it is possible to carefully curate abundant training data for a set of WM tracts of interest, there can also be novel WM tracts-i.e., WM tracts that are not included in the existing annotated WM tracts-that are specific to a new scientific problem, and it is desired that the novel WM tracts can be segmented without repeating the laborious collection of a large number of manual delineations for these tracts. One possible solution to the problem is to transfer the knowledge learned for segmenting existing WM tracts to the segmentation of novel WM tracts with a fine-tuning strategy, where a CNN pretrained for segmenting existing WM tracts is fine-tuned with only a few annotated scans to segment the novel WM tracts. However, in classic fine-tuning, the information in the last task-specific layer for segmenting existing WM tracts is completely discarded. In this work, based on the pretraining and fine-tuning framework, we propose an improved transfer learning approach to the segmentation of novel WM tracts in the few-shot setting, where all knowledge in the pretrained model is incorporated into the fine-tuning procedure. Specifically, from the weights of the pretrained task-specific layer for segmenting existing WM tracts, we derive a better initialization of the last task-specific layer for the target model that segments novel WM tracts. In addition, to allow further improvement of the initialization of the last layer and thus the segmentation performance in the few-shot setting, we develop a simple yet effective data augmentation strategy that generates synthetic annotated images with tract-aware image mixing. To validate the proposed method, we performed experiments on brain dMRI scans from public and private datasets under various experimental settings, and the results indicate that our method improves the performance of few-shot segmentation of novel WM tracts.