MIMOSA: Multi-parametric Imaging using Multiple-echoes with Optimized Simultaneous Acquisition for highly-efficient quantitative MRI

Purpose: To develop a new sequence, MIMOSA, for highly-efficient T1, T2, T2*, proton density (PD), and source separation quantitative susceptibility mapping (QSM). Methods: MIMOSA was developed based on 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) by combining 3D turbo Fast Low Angle Shot (FLASH) and multi-echo gradient echo acquisition modules with a spiral-like Cartesian trajectory to facilitate highly-efficient acquisition. Simulations were performed to optimize the sequence. Multi-contrast/-slice zero-shot self-supervised learning algorithm was employed for reconstruction. The accuracy of quantitative mapping was assessed by comparing MIMOSA with 3D-QALAS and reference techniques in both ISMRM/NIST phantom and in-vivo experiments. MIMOSA's acceleration capability was assessed at R = 3.3, 6.5, and 11.8 in in-vivo experiments, with repeatability assessed through scan-rescan studies. Beyond the 3T experiments, mesoscale quantitative mapping was performed at 750 um isotropic resolution at 7T. Results: Simulations demonstrated that MIMOSA achieved improved parameter estimation accuracy compared to 3D-QALAS. Phantom experiments indicated that MIMOSA exhibited better agreement with the reference techniques than 3D-QALAS. In-vivo experiments demonstrated that an acceleration factor of up to R = 11.8-fold can be achieved while preserving parameter estimation accuracy, with intra-class correlation coefficients of 0.998 (T1), 0.973 (T2), 0.947 (T2*), 0.992 (QSM), 0.987 (paramagnetic susceptibility), and 0.977 (diamagnetic susceptibility) in scan-rescan studies. Whole-brain T1, T2, T2*, PD, source separation QSM were obtained with 1 mm isotropic resolution in 3 min at 3T and 750 um isotropic resolution in 13 min at 7T. Conclusion: MIMOSA demonstrated potential for highly-efficient multi-parametric mapping.

A Tutorial on MRI Reconstruction: From Modern Methods to Clinical Implications

MRI is an indispensable clinical tool, offering a rich variety of tissue contrasts to support broad diagnostic and research applications. Clinical exams routinely acquire multiple structural sequences that provide complementary information for differential diagnosis, while research protocols often incorporate advanced functional, diffusion, spectroscopic, and relaxometry sequences to capture multidimensional insights into tissue structure and composition. However, these capabilities come at the cost of prolonged scan times, which reduce patient throughput, increase susceptibility to motion artifacts, and may require trade-offs in image quality or diagnostic scope. Over the last two decades, advances in image reconstruction algorithms--alongside improvements in hardware and pulse sequence design--have made it possible to accelerate acquisitions while preserving diagnostic quality. Central to this progress is the ability to incorporate prior information to regularize the solutions to the reconstruction problem. In this tutorial, we overview the basics of MRI reconstruction and highlight state-of-the-art approaches, beginning with classical methods that rely on explicit hand-crafted priors, and then turning to deep learning methods that leverage a combination of learned and crafted priors to further push the performance envelope. We also explore the translational aspects and eventual clinical implications of these methods. We conclude by discussing future directions to address remaining challenges in MRI reconstruction. The tutorial is accompanied by a Python toolbox (https://github.com/tutorial-MRI-recon/tutorial) to demonstrate select methods discussed in the article.

Rapid Whole Brain Mesoscale In-vivo MR Imaging using Multi-scale Implicit Neural Representation

Purpose: To develop and validate a novel image reconstruction technique using implicit neural representations (INR) for multi-view thick-slice acquisitions while reducing the scan time but maintaining high signal-to-noise ratio (SNR). Methods: We propose Rotating-view super-resolution (ROVER)-MRI, an unsupervised neural network-based algorithm designed to reconstruct MRI data from multi-view thick slices, effectively reducing scan time by 2-fold while maintaining fine anatomical details. We compare our method to both bicubic interpolation and the current state-of-the-art regularized least-squares super-resolution reconstruction (LS-SRR) technique. Validation is performed using ground-truth ex-vivo monkey brain data, and we demonstrate superior reconstruction quality across several in-vivo human datasets. Notably, we achieve the reconstruction of a whole human brain in-vivo T2-weighted image with an unprecedented 180{\mu}m isotropic spatial resolution, accomplished in just 17 minutes of scan time on a 7T MRI scanner. Results: ROVER-MRI outperformed LS-SRR method in terms of reconstruction quality with 22.4% lower relative error (RE) and 7.5% lower full-width half maximum (FWHM) indicating better preservation of fine structural details in nearly half the scan time. Conclusion: ROVER-MRI offers an efficient and robust approach for mesoscale MR imaging, enabling rapid, high-resolution whole-brain scans. Its versatility holds great promise for research applications requiring anatomical details and time-efficient imaging.

$χ$-sepnet: Deep neural network for magnetic susceptibility source separation

Magnetic susceptibility source separation ($\chi$-separation), an advanced quantitative susceptibility mapping (QSM) method, enables the separate estimation of para- and diamagnetic susceptibility source distributions in the brain. The method utilizes reversible transverse relaxation (R2'=R2*-R2) to complement frequency shift information for estimating susceptibility source concentrations, requiring time-consuming data acquisition for R2 in addition R2*. To address this challenge, we develop a new deep learning network, $\chi$-sepnet, and propose two deep learning-based susceptibility source separation pipelines, $\chi$-sepnet-R2' for inputs with multi-echo GRE and multi-echo spin-echo, and $\chi$-sepnet-R2* for input with multi-echo GRE only. $\chi$-sepnet is trained using multiple head orientation data that provide streaking artifact-free labels, generating high-quality $\chi$-separation maps. The evaluation of the pipelines encompasses both qualitative and quantitative assessments in healthy subjects, and visual inspection of lesion characteristics in multiple sclerosis patients. The susceptibility source-separated maps of the proposed pipelines delineate detailed brain structures with substantially reduced artifacts compared to those from conventional regularization-based reconstruction methods. In quantitative analysis, $\chi$-sepnet-R2' achieves the best outcomes followed by $\chi$-sepnet-R2*, outperforming the conventional methods. When the lesions of multiple sclerosis patients are assessed, both pipelines report identical lesion characteristics in most lesions ($\chi$para: 99.6% and $\chi$dia: 98.4% out of 250 lesions). The $\chi$-sepnet-R2* pipeline, which only requires multi-echo GRE data, has demonstrated its potential to offer broad clinical and scientific applications, although further evaluations for various diseases and pathological conditions are necessary.

PRIME: Phase Reversed Interleaved Multi-Echo acquisition enables highly accelerated distortion-free diffusion MRI

Purpose: To develop and evaluate a new pulse sequence for highly accelerated distortion-free diffusion MRI (dMRI) by inserting an additional echo without prolonging TR, when generalized slice dithered enhanced resolution (gSlider) radiofrequency encoding is used for volumetric acquisition. Methods: A phase-reversed interleaved multi-echo acquisition (PRIME) was developed for rapid, high-resolution, and distortion-free dMRI, which includes two echoes where the first echo is for target diffusion-weighted imaging (DWI) acquisition with high-resolution and the second echo is acquired with either 1) lower-resolution for high-fidelity field map estimation, or 2) matching resolution to enable efficient diffusion relaxometry acquisitions. The sequence was evaluated on in vivo data acquired from healthy volunteers on clinical and Connectome 2.0 scanners. Results: In vivo experiments demonstrated that 1) high in-plane acceleration (Rin-plane of 5-fold with 2D partial Fourier) was achieved using the high-fidelity field maps estimated from the second echo, which was made at a lower resolution/acceleration to increase its SNR while matching the effective echo spacing of the first readout, 2) high-resolution diffusion relaxometry parameters were estimated from dual-echo PRIME data using a white matter model of multi-TE spherical mean technique (MTE-SMT), and 3) high-fidelity mesoscale DWI at 550 um isotropic resolution could be obtained in vivo by capitalizing on the high-performance gradients of the Connectome 2.0 scanner. Conclusion: The proposed PRIME sequence enabled highly accelerated, high-resolution, and distortion-free dMRI using an additional echo without prolonging scan time when gSlider encoding is utilized.

NLCG-Net: A Model-Based Zero-Shot Learning Framework for Undersampled Quantitative MRI Reconstruction

Typical quantitative MRI (qMRI) methods estimate parameter maps after image reconstructing, which is prone to biases and error propagation. We propose a Nonlinear Conjugate Gradient (NLCG) optimizer for model-based T2/T1 estimation, which incorporates U-Net regularization trained in a scan-specific manner. This end-to-end method directly estimates qMRI maps from undersampled k-space data using mono-exponential signal modeling with zero-shot scan-specific neural network regularization to enable high fidelity T1 and T2 mapping. T2 and T1 mapping results demonstrate the ability of the proposed NLCG-Net to improve estimation quality compared to subspace reconstruction at high accelerations.

SubZero: Subspace Zero-Shot MRI Reconstruction

Recently introduced zero-shot self-supervised learning (ZS-SSL) has shown potential in accelerated MRI in a scan-specific scenario, which enabled high-quality reconstructions without access to a large training dataset. ZS-SSL has been further combined with the subspace model to accelerate 2D T2-shuffling acquisitions. In this work, we propose a parallel network framework and introduce an attention mechanism to improve subspace-based zero-shot self-supervised learning and enable higher acceleration factors. We name our method SubZero and demonstrate that it can achieve improved performance compared with current methods in T1 and T2 mapping acquisitions.

Chaos and COSMOS -- Considerations on QSM methods with multiple and single orientations and effects from local anisotropy

Purpose: Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more object orientations. Calculation Of Susceptibility through Multiple Orientations Sampling (COSMOS) is an established oversampling approach and regarded as QSM gold standard. It achieves a well-conditioned inverse problem, requiring rotations by 0{\deg}, 60{\deg} and 120{\deg} in the yz-plane. However, this is impractical in vivo, where head rotations are typically restricted to a range of +-25{\deg}. Non-ideal sampling degrades the conditioning with residual streaking artifacts whose mitigation needs further regularization. Moreover, susceptibility anisotropy in white matter is not considered in the COSMOS model, which may introduce additional bias. The current work presents a thorough investigation of these effects in primate brain. Methods: Gradient-recalled echo (GRE) data of an entire fixed chimpanzee brain were acquired at 7 T (350 microns resolution, 10 orientations) including ideal COSMOS sampling and realistic rotations in vivo. Comparisons of the results included ideal COSMOS, in-vivo feasible acquisitions with 3-8 orientations and single-orientation iLSQR QSM. Results: In-vivo feasible and optimal COSMOS yielded high-quality susceptibility maps with increased SNR resulting from averaging multiple acquisitions. COSMOS reconstructions from non-ideal rotations about a single axis required additional L2-regularization to mitigate residual streaking artifacts. Conclusion: In view of unconsidered anisotropy effects, added complexity of the reconstruction, and the general challenge of multi-orientation acquisitions, advantages of sub-optimal COSMOS schemes over regularized single-orientation QSM appear limited in in-vivo settings.

Improved Multi-Shot Diffusion-Weighted MRI with Zero-Shot Self-Supervised Learning Reconstruction

Diffusion MRI is commonly performed using echo-planar imaging (EPI) due to its rapid acquisition time. However, the resolution of diffusion-weighted images is often limited by magnetic field inhomogeneity-related artifacts and blurring induced by T2- and T2*-relaxation effects. To address these limitations, multi-shot EPI (msEPI) combined with parallel imaging techniques is frequently employed. Nevertheless, reconstructing msEPI can be challenging due to phase variation between multiple shots. In this study, we introduce a novel msEPI reconstruction approach called zero-MIRID (zero-shot self-supervised learning of Multi-shot Image Reconstruction for Improved Diffusion MRI). This method jointly reconstructs msEPI data by incorporating deep learning-based image regularization techniques. The network incorporates CNN denoisers in both k- and image-spaces, while leveraging virtual coils to enhance image reconstruction conditioning. By employing a self-supervised learning technique and dividing sampled data into three groups, the proposed approach achieves superior results compared to the state-of-the-art parallel imaging method, as demonstrated in an in-vivo experiment.

Zero-DeepSub: Zero-Shot Deep Subspace Reconstruction for Rapid Multiparametric Quantitative MRI Using 3D-QALAS

Purpose: To develop and evaluate methods for 1) reconstructing 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) time-series images using a low-rank subspace method, which enables accurate and rapid T1 and T2 mapping, and 2) improving the fidelity of subspace QALAS by combining scan-specific deep-learning-based reconstruction and subspace modeling. Methods: A low-rank subspace method for 3D-QALAS (i.e., subspace QALAS) and zero-shot deep-learning subspace method (i.e., Zero-DeepSub) were proposed for rapid and high fidelity T1 and T2 mapping and time-resolved imaging using 3D-QALAS. Using an ISMRM/NIST system phantom, the accuracy of the T1 and T2 maps estimated using the proposed methods was evaluated by comparing them with reference techniques. The reconstruction performance of the proposed subspace QALAS using Zero-DeepSub was evaluated in vivo and compared with conventional QALAS at high reduction factors of up to 9-fold. Results: Phantom experiments showed that subspace QALAS had good linearity with respect to the reference methods while reducing biases compared to conventional QALAS, especially for T2 maps. Moreover, in vivo results demonstrated that subspace QALAS had better g-factor maps and could reduce voxel blurring, noise, and artifacts compared to conventional QALAS and showed robust performance at up to 9-fold acceleration with Zero-DeepSub, which enabled whole-brain T1, T2, and PD mapping at 1 mm isotropic resolution within 2 min of scan time. Conclusion: The proposed subspace QALAS along with Zero-DeepSub enabled high fidelity and rapid whole-brain multiparametric quantification and time-resolved imaging.