Matthew S. Rosen

Aryan Kalluvila, Neha Koonjoo, Danyal Bhutto et al.

Low-field (LF) MRI scanners have the power to revolutionize medical imaging by providing a portable and cheaper alternative to high-field MRI scanners. However, such scanners are usually significantly noisier and lower quality than their high-field counterparts. The aim of this paper is to improve the SNR and overall image quality of low-field MRI scans to improve diagnostic capability. To address this issue, we propose a Nested U-Net neural network architecture super-resolution algorithm that outperforms previously suggested deep learning methods with an average PSNR of 78.83 and SSIM of 0.9551. We tested our network on artificial noisy downsampled synthetic data from a major T1 weighted MRI image dataset called the T1-mix dataset. One board-certified radiologist scored 25 images on the Likert scale (1-5) assessing overall image quality, anatomical structure, and diagnostic confidence across our architecture and other published works (SR DenseNet, Generator Block, SRCNN, etc.). We also introduce a new type of loss function called natural log mean squared error (NLMSE). In conclusion, we present a more accurate deep learning method for single image super-resolution applied to synthetic low-field MRI via a Nested U-Net architecture.

Karthik Gopinath, Annabel Sorby-Adams, Jonathan W. Ramirez et al.

Three-dimensional reconstruction of cortical surfaces from MRI for morphometric analysis is fundamental for understanding brain structure. While high-field MRI (HF-MRI) is standard in research and clinical settings, its limited availability hinders widespread use. Low-field MRI (LF-MRI), particularly portable systems, offers a cost-effective and accessible alternative. However, existing cortical surface analysis tools are optimized for high-resolution HF-MRI and struggle with the lower signal-to-noise ratio and resolution of LF-MRI. In this work, we present a machine learning method for 3D reconstruction and analysis of portable LF-MRI across a range of contrasts and resolutions. Our method works "out of the box" without retraining. It uses a 3D U-Net trained on synthetic LF-MRI to predict signed distance functions of cortical surfaces, followed by geometric processing to ensure topological accuracy. We evaluate our method using paired HF/LF-MRI scans of the same subjects, showing that LF-MRI surface reconstruction accuracy depends on acquisition parameters, including contrast type (T1 vs T2), orientation (axial vs isotropic), and resolution. A 3mm isotropic T2-weighted scan acquired in under 4 minutes, yields strong agreement with HF-derived surfaces: surface area correlates at r=0.96, cortical parcellations reach Dice=0.98, and gray matter volume achieves r=0.93. Cortical thickness remains more challenging with correlations up to r=0.70, reflecting the difficulty of sub-mm precision with 3mm voxels. We further validate our method on challenging postmortem LF-MRI, demonstrating its robustness. Our method represents a step toward enabling cortical surface analysis on portable LF-MRI. Code is available at https://surfer.nmr.mgh.harvard.edu/fswiki/ReconAny

Lin Tian, Sean I. Young, Jonathan Williams Ramirez et al. · harvard

Correlation of neuropathology with MRI has the potential to transfer microscopic signatures of pathology to invivo scans. Recently, a classical registration method has been proposed, to build these correlations from 3D reconstructed stacks of dissection photographs, which are routinely taken at brain banks. These photographs bypass the need for exvivo MRI, which is not widely accessible. However, this method requires a full stack of brain slabs and a reference mask (e.g., acquired with a surface scanner), which severely limits the applicability of the technique. Here we propose RefFree, a dissection photograph reconstruction method without external reference. RefFree is a learning approach that estimates the 3D coordinates in the atlas space for every pixel in every photograph; simple least-squares fitting can then be used to compute the 3D reconstruction. As a by-product, RefFree also produces an atlas-based segmentation of the reconstructed stack. RefFree is trained on synthetic photographs generated from digitally sliced 3D MRI data, with randomized appearance for enhanced generalization ability. Experiments on simulated and real data show that RefFree achieves performance comparable to the baseline method without an explicit reference while also enabling reconstruction of partial stacks. Our code is available at https://github.com/lintian-a/reffree.

Hongwei Bran Li, Matthew S. Rosen, Shahin Nasr et al.

High-resolution fMRI provides a window into the brain's mesoscale organization. Yet, higher spatial resolution increases scan times, to compensate for the low signal and contrast-to-noise ratio. This work introduces a deep learning-based 3D super-resolution (SR) method for fMRI. By incorporating a resolution-agnostic image augmentation framework, our method adapts to varying voxel sizes without retraining. We apply this innovative technique to localize fine-scale motion-selective sites in the early visual areas. Detection of these sites typically requires a resolution higher than 1 mm isotropic, whereas here, we visualize them based on lower resolution (2-3mm isotropic) fMRI data. Remarkably, the super-resolved fMRI is able to recover high-frequency detail of the interdigitated organization of these sites (relative to the color-selective sites), even with training data sourced from different subjects and experimental paradigms -- including non-visual resting-state fMRI, underscoring its robustness and versatility. Quantitative and qualitative results indicate that our method has the potential to enhance the spatial resolution of fMRI, leading to a drastic reduction in acquisition time.

Mark D. Olchanyi, Annabel Sorby-Adams, John Kirsch et al.

Portable, ultra-low-field (ULF) magnetic resonance imaging has the potential to expand access to neuroimaging but currently suffers from coarse spatial and angular resolutions and low signal-to-noise ratios. Diffusion tensor imaging (DTI), a sequence tailored to detect and reconstruct white matter tracts within the brain, is particularly prone to such imaging degradation due to inherent sequence design coupled with prolonged scan times. In addition, ULF DTI scans exhibit artifacting that spans both the space and angular domains, requiring a custom modelling algorithm for subsequent correction. We introduce a nine-direction, single-shell ULF DTI sequence, as well as a companion Bayesian bias field correction algorithm that possesses angular dependence and convolutional neural network-based superresolution algorithm that is generalizable across DTI datasets and does not require re-training (''DiffSR''). We show through a synthetic downsampling experiment and white matter assessment in real, matched ULF and high-field DTI scans that these algorithms can recover microstructural and volumetric white matter information at ULF. We also show that DiffSR can be directly applied to white matter-based Alzheimers disease classification in synthetically degraded scans, with notable improvements in agreement between DTI metrics, as compared to un-degraded scans. We freely disseminate the Bayesian bias correction algorithm and DiffSR with the goal of furthering progress on both ULF reconstruction methods and general DTI sequence harmonization. We release all code related to DiffSR for $\href{https://github.com/markolchanyi/DiffSR}{public \space use}$.

Pablo Laso, Stefano Cerri, Annabel Sorby-Adams et al.

Brain atrophy and white matter hyperintensity (WMH) are critical neuroimaging features for ascertaining brain injury in cerebrovascular disease and multiple sclerosis. Automated segmentation and quantification is desirable but existing methods require high-resolution MRI with good signal-to-noise ratio (SNR). This precludes application to clinical and low-field portable MRI (pMRI) scans, thus hampering large-scale tracking of atrophy and WMH progression, especially in underserved areas where pMRI has huge potential. Here we present a method that segments white matter hyperintensity and 36 brain regions from scans of any resolution and contrast (including pMRI) without retraining. We show results on eight public datasets and on a private dataset with paired high- and low-field scans (3T and 64mT), where we attain strong correlation between the WMH ($ρ$=.85) and hippocampal volumes (r=.89) estimated at both fields. Our method is publicly available as part of FreeSurfer, at: http://surfer.nmr.mgh.harvard.edu/fswiki/WMH-SynthSeg.

John D. Mayfield, Matthew S. Rosen

We propose a novel method of understanding disease transformation from a healthy baseline with biomarker-level explainability. By modeling the biomarker covariance matrices of healthy controls and disease states, the perturbation can be individually characterized to accomplish mechanistic explanations of disease trajectories, both at a molecular level and for individual patients. Given a cohort of n patients each measured on p biomarkers, we define the biomarker "Hamiltonian" H = X^T X / n \in R^{p \times p}, where X \in R^{n \times p} is the covariant biomarker matrix. The eigenvectors of H define a set of normal modes of biomarker coordination, and the eigenvalues quantify the energy carried by each mode. In the healthy state, the reference Hamiltonian H_0 governs this structure where disease perturbs H_0 by an additive operator ΔH, thus shifting eigenvalues and rotating eigenvectors in proportion to the severity of pathological disruption. We formalize this framework, derive the spectral change given a disease perturbation, and demonstrate that the projection of a newly diagnosed patient's cumulative biomarker covariance structure onto disease-discriminant eigenmodes constitutes an optimal prognostic statistic for greater precision in disease prognosis. This work serves as a veritable white paper with application across a panoply of disease frameworks from cancer to neurodegenerative disorders.

Tal Oved, Beatrice Lena, Chloé F. Najac et al.

Magnetic resonance imaging (MRI) offers superb-quality images, but its accessibility is limited by high costs, posing challenges for patients requiring longitudinal care. Low-field MRI provides affordable imaging with low-cost devices but is hindered by long scans and degraded image quality, including low signal-to-noise ratio (SNR) and tissue contrast. We propose a novel healthcare paradigm: using deep learning to extract personalized features from past standard high-field MRI scans and harnessing them to enable accelerated, enhanced-quality follow-up scans with low-cost systems. To overcome the SNR and contrast differences, we introduce ViT-Fuser, a feature-fusion vision transformer that learns features from past scans, e.g. those stored in standard DICOM CDs. We show that \textit{a single prior scan is sufficient}, and this scan can come from various MRI vendors, field strengths, and pulse sequences. Experiments with four datasets, including glioblastoma data, low-field ($50mT$), and ultra-low-field ($6.5mT$) data, demonstrate that ViT-Fuser outperforms state-of-the-art methods, providing enhanced-quality images from accelerated low-field scans, with robustness to out-of-distribution data. Our freely available framework thus enables rapid, diagnostic-quality, low-cost imaging for wide healthcare applications.

Danyal F. Bhutto, Bo Zhu, Jeremiah Z. Liu et al.

Accurate image reconstruction is at the heart of diagnostics in medical imaging. Supervised deep learning-based approaches have been investigated for solving inverse problems including image reconstruction. However, these trained models encounter unseen data distributions that are widely shifted from training data during deployment. Therefore, it is essential to assess whether a given input falls within the training data distribution for diagnostic purposes. Uncertainty estimation approaches exist but focus on providing an uncertainty map to radiologists, rather than assessing the training distribution fit. In this work, we propose a method based on the local Lipschitz-based metric to distinguish out-of-distribution images from in-distribution with an area under the curve of 99.94%. Empirically, we demonstrate a very strong relationship between the local Lipschitz value and mean absolute error (MAE), supported by a high Spearman's rank correlation coefficient of 0.8475, which determines the uncertainty estimation threshold for optimal model performance. Through the identification of false positives, the local Lipschitz and MAE relationship was used to guide data augmentation and reduce model uncertainty. Our study was validated using the AUTOMAP architecture for sensor-to-image Magnetic Resonance Imaging (MRI) reconstruction. We compare our proposed approach with baseline methods: Monte-Carlo dropout and deep ensembles, and further analysis included MRI denoising and Computed Tomography (CT) sparse-to-full view reconstruction using UNET architectures. We show that our approach is applicable to various architectures and learned functions, especially in the realm of medical image reconstruction, where preserving the diagnostic accuracy of reconstructed images remains paramount.

David E. J. Waddington, Nicholas Hindley, Neha Koonjoo et al.

MRI-guidance techniques that dynamically adapt radiation beams to follow tumor motion in real-time will lead to more accurate cancer treatments and reduced collateral healthy tissue damage. The gold-standard for reconstruction of undersampled MR data is compressed sensing (CS) which is computationally slow and limits the rate that images can be available for real-time adaptation. Here, we demonstrate the use of automated transform by manifold approximation (AUTOMAP), a generalized framework that maps raw MR signal to the target image domain, to rapidly reconstruct images from undersampled radial k-space data. The AUTOMAP neural network was trained to reconstruct images from a golden-angle radial acquisition, a benchmark for motion-sensitive imaging, on lung cancer patient data and generic images from ImageNet. Model training was subsequently augmented with motion-encoded k-space data derived from videos in the YouTube-8M dataset to encourage motion robust reconstruction. We find that AUTOMAP-reconstructed radial k-space has equivalent accuracy to CS but with much shorter processing times after initial fine-tuning on retrospectively acquired lung cancer patient data. Validation of motion-trained models with a virtual dynamic lung tumor phantom showed that the generalized motion properties learned from YouTube lead to improved target tracking accuracy. Our work shows that AUTOMAP can achieve real-time, accurate reconstruction of radial data. These findings imply that neural-network-based reconstruction is potentially superior to existing approaches for real-time image guidance applications.

Juan Eugenio Iglesias, Riana Schleicher, Sonia Laguna et al.

The recent introduction of portable, low-field MRI (LF-MRI) into the clinical setting has the potential to transform neuroimaging. However, LF-MRI is limited by lower resolution and signal-to-noise ratio, leading to incomplete characterization of brain regions. To address this challenge, recent advances in machine learning facilitate the synthesis of higher resolution images derived from one or multiple lower resolution scans. Here, we report the extension of a machine learning super-resolution (SR) algorithm to synthesize 1 mm isotropic MPRAGE-like scans from LF-MRI T1-weighted and T2-weighted sequences. Our initial results on a paired dataset of LF and high-field (HF, 1.5T-3T) clinical scans show that: (i) application of available automated segmentation tools directly to LF-MRI images falters; but (ii) segmentation tools succeed when applied to SR images with high correlation to gold standard measurements from HF-MRI (e.g., r = 0.85 for hippocampal volume, r = 0.84 for the thalamus, r = 0.92 for the whole cerebrum). This work demonstrates proof-of-principle post-processing image enhancement from lower resolution LF-MRI sequences. These results lay the foundation for future work to enhance the detection of normal and abnormal image findings at LF and ultimately improve the diagnostic performance of LF-MRI. Our tools are publicly available on FreeSurfer (surfer.nmr.mgh.harvard.edu/).

Ouri Cohen, Bo Zhu, Matthew S. Rosen

PURPOSE: Demonstrate a novel fast method for reconstruction of multi-dimensional MR Fingerprinting (MRF) data using Deep Learning methods. METHODS: A neural network (NN) is defined using the TensorFlow framework and trained on simulated MRF data computed using the Bloch equations. The accuracy of the NN reconstruction of noisy data is compared to conventional MRF template matching as a function of training data size, and quantified in a both simulated numerical brain phantom data and acquired data from the ISMRM/NIST phantom. The utility of the method is demonstrated in a healthy subject in vivo at 1.5 T. RESULTS: Network training required 10 minutes and once trained, data reconstruction required approximately 10 ms. Reconstruction of simulated brain data using the NN resulted in a root-mean-square error (RMSE) of 3.5 ms for T1 and 7.8 ms for T2. The RMSE for the NN trained on sparse dictionaries was approximately 6 fold lower for T1 and 2 fold lower for T2 than conventional MRF dot-product dictionary matching on the same dictionaries. Phantom measurements yielded good agreement (R2=0.99) between the T1 and T2 estimated by the NN and reference values from the ISMRM/NIST phantom. CONCLUSION: Reconstruction of MRF data with a NN is accurate, 300 fold faster and more robust to noise and undersampling than conventional MRF dictionary matching.

Bo Zhu, Jeremiah Z. Liu, Bruce R. Rosen et al.

Image reconstruction plays a critical role in the implementation of all contemporary imaging modalities across the physical and life sciences including optical, MRI, CT, PET, and radio astronomy. During an image acquisition, the sensor encodes an intermediate representation of an object in the sensor domain, which is subsequently reconstructed into an image by an inversion of the encoding function. Image reconstruction is challenging because analytic knowledge of the inverse transform may not exist a priori, especially in the presence of sensor non-idealities and noise. Thus, the standard reconstruction approach involves approximating the inverse function with multiple ad hoc stages in a signal processing chain whose composition depends on the details of each acquisition strategy, and often requires expert parameter tuning to optimize reconstruction performance. We present here a unified framework for image reconstruction, AUtomated TransfOrm by Manifold APproximation (AUTOMAP), which recasts image reconstruction as a data-driven, supervised learning task that allows a mapping between sensor and image domain to emerge from an appropriate corpus of training data. We implement AUTOMAP with a deep neural network and exhibit its flexibility in learning reconstruction transforms for a variety of MRI acquisition strategies, using the same network architecture and hyperparameters. We further demonstrate its efficiency in sparsely representing transforms along low-dimensional manifolds, resulting in superior immunity to noise and reconstruction artifacts compared with conventional handcrafted reconstruction methods. In addition to improving the reconstruction performance of existing acquisition methodologies, we anticipate accelerating the discovery of new acquisition strategies across modalities as the burden of reconstruction becomes lifted by AUTOMAP and learned-reconstruction approaches.