Brain age identification from diffusion MRI synergistically predicts neurodegenerative disease

Estimated brain age from magnetic resonance image (MRI) and its deviation from chronological age can provide early insights into potential neurodegenerative diseases, supporting early detection and implementation of prevention strategies. Diffusion MRI (dMRI), a widely used modality for brain age estimation, presents an opportunity to build an earlier biomarker for neurodegenerative disease prediction because it captures subtle microstructural changes that precede more perceptible macrostructural changes. However, the coexistence of macro- and micro-structural information in dMRI raises the question of whether current dMRI-based brain age estimation models are leveraging the intended microstructural information or if they inadvertently rely on the macrostructural information. To develop a microstructure-specific brain age, we propose a method for brain age identification from dMRI that minimizes the model's use of macrostructural information by non-rigidly registering all images to a standard template. Imaging data from 13,398 participants across 12 datasets were used for the training and evaluation. We compare our brain age models, trained with and without macrostructural information minimized, with an architecturally similar T1-weighted (T1w) MRI-based brain age model and two state-of-the-art T1w MRI-based brain age models that primarily use macrostructural information. We observe difference between our dMRI-based brain age and T1w MRI-based brain age across stages of neurodegeneration, with dMRI-based brain age being older than T1w MRI-based brain age in participants transitioning from cognitively normal (CN) to mild cognitive impairment (MCI), but younger in participants already diagnosed with Alzheimer's disease (AD). Approximately 4 years before MCI diagnosis, dMRI-based brain age yields better performance than T1w MRI-based brain ages in predicting transition from CN to MCI.

Bi-Directional MS Lesion Filling and Synthesis Using Denoising Diffusion Implicit Model-based Lesion Repainting

Automatic magnetic resonance (MR) image processing pipelines are widely used to study people with multiple sclerosis (PwMS), encompassing tasks such as lesion segmentation and brain parcellation. However, the presence of lesion often complicates these analysis, particularly in brain parcellation. Lesion filling is commonly used to mitigate this issue, but existing lesion filling algorithms often fall short in accurately reconstructing realistic lesion-free images, which are vital for consistent downstream analysis. Additionally, the performance of lesion segmentation algorithms is often limited by insufficient data with lesion delineation as training labels. In this paper, we propose a novel approach leveraging Denoising Diffusion Implicit Models (DDIMs) for both MS lesion filling and synthesis based on image inpainting. Our modified DDIM architecture, once trained, enables both MS lesion filing and synthesis. Specifically, it can generate lesion-free T1-weighted or FLAIR images from those containing lesions; Or it can add lesions to T1-weighted or FLAIR images of healthy subjects. The former is essential for downstream analyses that require lesion-free images, while the latter is valuable for augmenting training datasets for lesion segmentation tasks. We validate our approach through initial experiments in this paper and demonstrate promising results in both lesion filling and synthesis, paving the way for future work.

Multi-Modality Conditioned Variational U-Net for Field-of-View Extension in Brain Diffusion MRI

An incomplete field-of-view (FOV) in diffusion magnetic resonance imaging (dMRI) can severely hinder the volumetric and bundle analyses of whole-brain white matter connectivity. Although existing works have investigated imputing the missing regions using deep generative models, it remains unclear how to specifically utilize additional information from paired multi-modality data and whether this can enhance the imputation quality and be useful for downstream tractography. To fill this gap, we propose a novel framework for imputing dMRI scans in the incomplete part of the FOV by integrating the learned diffusion features in the acquired part of the FOV to the complete brain anatomical structure. We hypothesize that by this design the proposed framework can enhance the imputation performance of the dMRI scans and therefore be useful for repairing whole-brain tractography in corrupted dMRI scans with incomplete FOV. We tested our framework on two cohorts from different sites with a total of 96 subjects and compared it with a baseline imputation method that treats the information from T1w and dMRI scans equally. The proposed framework achieved significant improvements in imputation performance, as demonstrated by angular correlation coefficient (p < 1E-5), and in downstream tractography accuracy, as demonstrated by Dice score (p < 0.01). Results suggest that the proposed framework improved imputation performance in dMRI scans by specifically utilizing additional information from paired multi-modality data, compared with the baseline method. The imputation achieved by the proposed framework enhances whole brain tractography, and therefore reduces the uncertainty when analyzing bundles associated with neurodegenerative.

Influence of Early through Late Fusion on Pancreas Segmentation from Imperfectly Registered Multimodal MRI

Multimodal fusion promises better pancreas segmentation. However, where to perform fusion in models is still an open question. It is unclear if there is a best location to fuse information when analyzing pairs of imperfectly aligned images. Two main alignment challenges in this pancreas segmentation study are 1) the pancreas is deformable and 2) breathing deforms the abdomen. Even after image registration, relevant deformations are often not corrected. We examine how early through late fusion impacts pancreas segmentation. We used 353 pairs of T2-weighted (T2w) and T1-weighted (T1w) abdominal MR images from 163 subjects with accompanying pancreas labels. We used image registration (deeds) to align the image pairs. We trained a collection of basic UNets with different fusion points, spanning from early to late, to assess how early through late fusion influenced segmentation performance on imperfectly aligned images. We assessed generalization of fusion points on nnUNet. The single-modality T2w baseline using a basic UNet model had a Dice score of 0.73, while the same baseline on the nnUNet model achieved 0.80. For the basic UNet, the best fusion approach occurred in the middle of the encoder (early/mid fusion), which led to a statistically significant improvement of 0.0125 on Dice score compared to the baseline. For the nnUNet, the best fusion approach was na\"ive image concatenation before the model (early fusion), which resulted in a statistically significant Dice score increase of 0.0021 compared to baseline. Fusion in specific blocks can improve performance, but the best blocks for fusion are model specific, and the gains are small. In imperfectly registered datasets, fusion is a nuanced problem, with the art of design remaining vital for uncovering potential insights. Future innovation is needed to better address fusion in cases of imperfect alignment of abdominal image pairs.

Beyond MR Image Harmonization: Resolution Matters Too

Magnetic resonance (MR) imaging is commonly used in the clinical setting to non-invasively monitor the body. There exists a large variability in MR imaging due to differences in scanner hardware, software, and protocol design. Ideally, a processing algorithm should perform robustly to this variability, but that is not always the case in reality. This introduces a need for image harmonization to overcome issues of domain shift when performing downstream analysis such as segmentation. Most image harmonization models focus on acquisition parameters such as inversion time or repetition time, but they ignore an important aspect in MR imaging -- resolution. In this paper, we evaluate the impact of image resolution on harmonization using a pretrained harmonization algorithm. We simulate 2D acquisitions of various slice thicknesses and gaps from 3D acquired, 1mm3 isotropic MR images and demonstrate how the performance of a state-of-the-art image harmonization algorithm varies as resolution changes. We discuss the most ideal scenarios for image resolution including acquisition orientation when 3D imaging is not available, which is common for many clinical scanners. Our results show that harmonization on low-resolution images does not account for acquisition resolution and orientation variations. Super-resolution can be used to alleviate resolution variations but it is not always used. Our methodology can generalize to help evaluate the impact of image acquisition resolution for multiple tasks. Determining the limits of a pretrained algorithm is important when considering preprocessing steps and trust in the results.

Vector Field Attention for Deformable Image Registration

Deformable image registration establishes non-linear spatial correspondences between fixed and moving images. Deep learning-based deformable registration methods have been widely studied in recent years due to their speed advantage over traditional algorithms as well as their better accuracy. Most existing deep learning-based methods require neural networks to encode location information in their feature maps and predict displacement or deformation fields though convolutional or fully connected layers from these high-dimensional feature maps. In this work, we present Vector Field Attention (VFA), a novel framework that enhances the efficiency of the existing network design by enabling direct retrieval of location correspondences. VFA uses neural networks to extract multi-resolution feature maps from the fixed and moving images and then retrieves pixel-level correspondences based on feature similarity. The retrieval is achieved with a novel attention module without the need of learnable parameters. VFA is trained end-to-end in either a supervised or unsupervised manner. We evaluated VFA for intra- and inter-modality registration and for unsupervised and semi-supervised registration using public datasets, and we also evaluated it on the Learn2Reg challenge. Experimental results demonstrate the superior performance of VFA compared to existing methods. The source code of VFA is publicly available at https://github.com/yihao6/vfa/.

Revisiting registration-based synthesis: A focus on unsupervised MR image synthesis

Deep learning (DL) has led to significant improvements in medical image synthesis, enabling advanced image-to-image translation to generate synthetic images. However, DL methods face challenges such as domain shift and high demands for training data, limiting their generalizability and applicability. Historically, image synthesis was also carried out using deformable image registration (DIR), a method that warps moving images of a desired modality to match the anatomy of a fixed image. However, concerns about its speed and accuracy led to its decline in popularity. With the recent advances of DL-based DIR, we now revisit and reinvigorate this line of research. In this paper, we propose a fast and accurate synthesis method based on DIR. We use the task of synthesizing a rare magnetic resonance (MR) sequence, white matter nulled (WMn) T1-weighted (T1-w) images, to demonstrate the potential of our approach. During training, our method learns a DIR model based on the widely available MPRAGE sequence, which is a cerebrospinal fluid nulled (CSFn) T1-w inversion recovery gradient echo pulse sequence. During testing, the trained DIR model is first applied to estimate the deformation between moving and fixed CSFn images. Subsequently, this estimated deformation is applied to align the paired WMn counterpart of the moving CSFn image, yielding a synthetic WMn image for the fixed CSFn image. Our experiments demonstrate promising results for unsupervised image synthesis using DIR. These findings highlight the potential of our technique in contexts where supervised synthesis methods are constrained by limited training data.

Towards an accurate and generalizable multiple sclerosis lesion segmentation model using self-ensembled lesion fusion

Automatic multiple sclerosis (MS) lesion segmentation using multi-contrast magnetic resonance (MR) images provides improved efficiency and reproducibility compared to manual delineation. Current state-of-the-art automatic MS lesion segmentation methods utilize modified U-Net-like architectures. However, in the literature, dedicated architecture modifications were always required to maximize their performance. In addition, the best-performing methods have not proven to be generalizable to diverse test datasets with contrast variations and image artifacts. In this work, we developed an accurate and generalizable MS lesion segmentation model using the well-known U-Net architecture without further modification. A novel test-time self-ensembled lesion fusion strategy is proposed that not only achieved the best performance using the ISBI 2015 MS segmentation challenge data but also demonstrated robustness across various self-ensemble parameter choices. Moreover, equipped with instance normalization rather than batch normalization widely used in literature, the model trained on the ISBI challenge data generalized well on clinical test datasets from different scanners.

Harmonization-enriched domain adaptation with light fine-tuning for multiple sclerosis lesion segmentation

Deep learning algorithms utilizing magnetic resonance (MR) images have demonstrated cutting-edge proficiency in autonomously segmenting multiple sclerosis (MS) lesions. Despite their achievements, these algorithms may struggle to extend their performance across various sites or scanners, leading to domain generalization errors. While few-shot or one-shot domain adaptation emerges as a potential solution to mitigate generalization errors, its efficacy might be hindered by the scarcity of labeled data in the target domain. This paper seeks to tackle this challenge by integrating one-shot adaptation data with harmonized training data that incorporates labels. Our approach involves synthesizing new training data with a contrast akin to that of the test domain, a process we refer to as "contrast harmonization" in MRI. Our experiments illustrate that the amalgamation of one-shot adaptation data with harmonized training data surpasses the performance of utilizing either data source in isolation. Notably, domain adaptation using exclusively harmonized training data achieved comparable or even superior performance compared to one-shot adaptation. Moreover, all adaptations required only minimal fine-tuning, ranging from 2 to 5 epochs for convergence.

Rapid Brain Meninges Surface Reconstruction with Layer Topology Guarantee

The meninges, located between the skull and brain, are composed of three membrane layers: the pia, the arachnoid, and the dura. Reconstruction of these layers can aid in studying volume differences between patients with neurodegenerative diseases and normal aging subjects. In this work, we use convolutional neural networks (CNNs) to reconstruct surfaces representing meningeal layer boundaries from magnetic resonance (MR) images. We first use the CNNs to predict the signed distance functions (SDFs) representing these surfaces while preserving their anatomical ordering. The marching cubes algorithm is then used to generate continuous surface representations; both the subarachnoid space (SAS) and the intracranial volume (ICV) are computed from these surfaces. The proposed method is compared to a state-of-the-art deformable model-based reconstruction method, and we show that our method can reconstruct smoother and more accurate surfaces using less computation time. Finally, we conduct experiments with volumetric analysis on both subjects with multiple sclerosis and healthy controls. For healthy and MS subjects, ICVs and SAS volumes are found to be significantly correlated to sex (p<0.01) and age (p<0.03) changes, respectively.