Susie Y. Huang

Joshua K. Marchant, Hong-Hsi Lee, Elizabeth R. Gerstner et al.

The lack of analytical models describing diffusion time dependence at intermediate time scales in complex tissue microstructure limits the accurate quantification of extracellular diffusivity and tissue microstructure. We introduce TRACED, a biophysical model that incorporates diffusion time dependence in cell distributions to quantify pathologically-relevant properties in solid tumors. Neural networks were trained on Monte Carlo diffusion simulations using sphere distribution-based geometries to enable the rapid computation of time-dependent diffusion MRI signals in cell populations of variable cell size. Model sensitivity and fit performance were assessed via simulation. Diffusion data from eight mixed-grade glioma patients was fitted using the TRACED model. Data fitting was performed using a novel physics-informed transfer learning pipeline, Sim2PINN. In two patients, cell size measurements were compared directly with image-localized histology. Simulation results indicate improved parameter estimation compared to the simple two-compartment model. TRACED enabled the simultaneous in vivo quantification of intracellular volume fraction, cell size distribution, extracellular intrinsic diffusivity, and tortuosity in glioma patients. Neural network implementations of diffusion time-dependence and tortuosity showed behavior consistent with coarse-graining and effective medium theory, respectively. Future work will explore the clinical utility of TRACED parameters in additional patients.

Kwok-Shing Chan, Hansol Lee, Yixin Ma et al.

Quantitative MRI (qMRI) offers tissue-specific biomarkers that can be tracked over time or compared across populations; however, its adoption in clinical research is hindered by significant computational demands of parameter estimation. Images acquired at high spatial resolution or requiring fitting multiple parameters often require lengthy processing time, constraining their use in routine pipelines and slowing methodological innovation and clinical translation. We present GACELLE, an open source, GPU-accelerated framework for high-throughput qMRI analysis. GACELLE provides a stochastic gradient descent optimiser and a stochastic sampler in MATLAB, enabling fast parameter mapping, improved estimation robustness via spatial regularisation, and uncertainty quantification. GACELLE prioritises accessibility: users only need to provide a forward signal model, while GACELLE's backend manages computational parallelisation, automatic parameter updates, and memory-batching. The stochastic solver performs fully vectorised Markov chain Monte Carlo with identical likelihood on CPU and GPU, ensuring reproducibility across hardware. Benchmarking demonstrates up to 451-fold acceleration for the stochastic gradient descent solver and 14,380-fold acceleration for stochastic sampling compared to CPU-based estimation, without compromising accuracy. We demonstrated GACELLE's versatility on three representative qMRI models and on an image reconstruction task. Across these applications, GACELLE improves parameter precision, enhances test-retest reproducibility, and reduces noise in quantitative maps. By combining speed, usability and flexibility, GACELLE provides a generalisable optimisation framework for medical image analysis. It lowers the computational barrier for qMRI, paving the way for reproducible biomarker development, large-scale imaging studies, and clinical translation.

Mehmet Yigit Avci, Ziyu Li, Qiuyun Fan et al.

Dropout is conventionally used during the training phase as regularization method and for quantifying uncertainty in deep learning. We propose to use dropout during training as well as inference steps, and average multiple predictions to improve the accuracy, while reducing and quantifying the uncertainty. The results are evaluated for fractional anisotropy (FA) and mean diffusivity (MD) maps which are obtained from only 3 direction scans. With our method, accuracy can be improved significantly compared to network outputs without dropout, especially when the training dataset is small. Moreover, confidence maps are generated which may aid in diagnosis of unseen pathology or artifacts.

Qiyuan Tian, Ziyu Li, Qiuyun Fan et al.

The noise in diffusion-weighted images (DWIs) decreases the accuracy and precision of diffusion tensor magnetic resonance imaging (DTI) derived microstructural parameters and leads to prolonged acquisition time for achieving improved signal-to-noise ratio (SNR). Deep learning-based image denoising using convolutional neural networks (CNNs) has superior performance but often requires additional high-SNR data for supervising the training of CNNs, which reduces the practical feasibility. We develop a self-supervised deep learning-based method entitled "SDnDTI" for denoising DTI data, which does not require additional high-SNR data for training. Specifically, SDnDTI divides multi-directional DTI data into many subsets, each consisting of six DWI volumes along optimally chosen diffusion-encoding directions that are robust to noise for the tensor fitting, and then synthesizes DWI volumes along all acquired directions from the diffusion tensors fitted using each subset of the data as the input data of CNNs. On the other hand, SDnDTI synthesizes DWI volumes along acquired diffusion-encoding directions with higher SNR from the diffusion tensors fitted using all acquired data as the training target. SDnDTI removes noise from each subset of synthesized DWI volumes using a deep 3-dimensional CNN to match the quality of the cleaner target DWI volumes and achieves even higher SNR by averaging all subsets of denoised data. The denoising efficacy of SDnDTI is demonstrated on two datasets provided by the Human Connectome Project (HCP) and the Lifespan HCP in Aging. The SDnDTI results preserve image sharpness and textural details and substantially improve upon those from the raw data. The results of SDnDTI are comparable to those from supervised learning-based denoising and outperform those from state-of-the-art conventional denoising algorithms including BM4D, AONLM and MPPCA.

Qiyuan Tian, Ziyu Li, Qiuyun Fan et al.

High-resolution diffusion tensor imaging (DTI) is beneficial for probing tissue microstructure in fine neuroanatomical structures, but long scan times and limited signal-to-noise ratio pose significant barriers to acquiring DTI at sub-millimeter resolution. To address this challenge, we propose a deep learning-based super-resolution method entitled "SRDTI" to synthesize high-resolution diffusion-weighted images (DWIs) from low-resolution DWIs. SRDTI employs a deep convolutional neural network (CNN), residual learning and multi-contrast imaging, and generates high-quality results with rich textural details and microstructural information, which are more similar to high-resolution ground truth than those from trilinear and cubic spline interpolation.

Berkin Bilgic, Itthi Chatnuntawech, Mary Kate Manhard et al.

Purpose: To introduce a combined machine learning (ML) and physics-based image reconstruction framework that enables navigator-free, highly accelerated multishot echo planar imaging (msEPI), and demonstrate its application in high-resolution structural and diffusion imaging. Methods: Singleshot EPI is an efficient encoding technique, but does not lend itself well to high-resolution imaging due to severe distortion artifacts and blurring. While msEPI can mitigate these artifacts, high-quality msEPI has been elusive because of phase mismatch arising from shot-to-shot variations which preclude the combination of the multiple-shot data into a single image. We employ deep learning to obtain an interim image with minimal artifacts, which permits estimation of image phase variations due to shot-to-shot changes. These variations are then included in a Joint Virtual Coil Sensitivity Encoding (JVC-SENSE) reconstruction to utilize data from all shots and improve upon the ML solution. Results: Our combined ML + physics approach enabled Rinplane x MultiBand (MB) = 8x2-fold acceleration using 2 EPI-shots for multi-echo imaging, so that whole-brain T2 and T2* parameter maps could be derived from an 8.3 sec acquisition at 1x1x3mm3 resolution. This has also allowed high-resolution diffusion imaging with high geometric fidelity using 5-shots at Rinplane x MB = 9x2-fold acceleration. To make these possible, we extended the state-of-the-art MUSSELS reconstruction technique to Simultaneous MultiSlice (SMS) encoding and used it as an input to our ML network. Conclusion: Combination of ML and JVC-SENSE enabled navigator-free msEPI at higher accelerations than previously possible while using fewer shots, with reduced vulnerability to poor generalizability and poor acceptance of end-to-end ML approaches.