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Or Perlman

Publications and source records attributed to Or Perlman.

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Pre-CAT: A web-based, graphical user-interface toolbox for preclinical CEST-MRI data processing and analysis

Purpose: As interest in CEST-MRI grows, particularly in the preclinical setting, the necessity for standardized and easy-to-use acquisition and data analysis pipelines has become apparent. While vendors have increasingly introduced support for CEST acquisitions on both clinical and preclinical hardware, image post-processing and analysis pipelines remain siloed based on privately developed code. We aim to develop an easy-to-use, open-source graphical user interface toolbox for preclinical CEST-MRI data analysis (Preclinical CEST-MRI Analysis Tool; Pre-CAT), supporting multiple acquisition types, organ systems, and CEST contrast mechanisms. Methods: Pre-CAT was developed in Python and utilizes the Numpy, Scipy, and Matplotlib libraries for data analysis and plotting. Inbuilt data processing steps include image loading, reconstruction, post-processing, and segmentation. Pre-CAT also supports data analysis for QUESP, CEST-MRF, and field mapping experiments using consensus protocols and methods. Pre-CAT's web interface and GUI were developed using Streamlit, an open-source Python framework. Pre-CAT is hosted and accessible online and can be downloaded for local installation to complete the data analysis pipeline in roughly one minute using modern hardware. Results: Pre-CAT analysis pipelines for Z-spectroscopy, CEST-MRF, and quantitative CEST (QUESP/QUEST) are demonstrated. Conclusion: With the introduction of Pre-CAT, we aim to standardize the preclinical CEST-MRI data analysis pipeline, fostering collaboration across research sites and reducing methodological redundancy. Pre-CAT is open-source and relatively modular, encouraging the addition of new methods and protocols.

physics.med-ph

Multiparameter Uncertainty Mapping in Quantitative Molecular MRI using a Physics-Structured Variational Autoencoder (PS-VAE)

Quantitative imaging methods, such as magnetic resonance fingerprinting (MRF), aim to extract interpretable pathology biomarkers by estimating biophysical tissue parameters from signal evolutions. However, the pattern-matching algorithms or neural networks used in such inverse problems often lack principled uncertainty quantification, which limits the trustworthiness and transparency, required for clinical acceptance. Here, we describe a physics-structured variational autoencoder (PS-VAE) designed for rapid extraction of voxelwise multi-parameter posterior distributions. Our approach integrates a differentiable spin physics simulator with self-supervised learning, and provides a full covariance that captures the inter-parameter correlations of the latent biophysical space. The method was validated in a multi-proton pool chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) molecular MRF study, across in-vitro phantoms, tumor-bearing mice, healthy human volunteers, and a subject with glioblastoma. The resulting multi-parametric posteriors are in good agreement with those calculated using a brute-force Bayesian analysis, while providing an orders-of-magnitude acceleration in whole brain quantification. In addition, we demonstrate how monitoring the multi-parameter posterior dynamics across progressively acquired signals provides practical insights for protocol optimization and may facilitate real-time adaptive acquisition.

stat.ML

Quantitative multi-metabolite imaging of Parkinson's disease using AI boosted molecular MRI

Traditional approaches for molecular imaging of Parkinson's disease (PD) in vivo require radioactive isotopes, lengthy scan times, or deliver only low spatial resolution. Recent advances in saturation transfer-based PD magnetic resonance imaging (MRI) have provided biochemical insights, although the image contrast is semi-quantitative and nonspecific. Here, we combined a rapid molecular MRI acquisition paradigm with deep learning based reconstruction for multi-metabolite quantification of glutamate, mobile proteins, semisolid, and mobile macromolecules in an acute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The quantitative parameter maps are in general agreement with the histology and MR spectroscopy, and demonstrate that semisolid magnetization transfer (MT), amide, and aliphatic relayed nuclear Overhauser effect (rNOE) proton volume fractions may serve as PD biomarkers.

physics.med-ph

Optimization of pulsed saturation transfer MR fingerprinting (ST MRF) acquisition using the Cram\'er-Rao bound and sequential quadratic programming

Purpose: To develop a method for optimizing pulsed saturation transfer MR fingerprinting (ST MRF) acquisition. Methods: The Cram\'er-Rao bound (CRB) for variance assessment was employed on Bloch-McConnell-based simulated signals, followed by a numerical sequential quadratic programming optimization and basin-hopping avoidance of local minima. Validation was performed using L-arginine phantoms and healthy human volunteers (n=4) at 3T while restricting the scan time to be less than 40 s. Results: The proposed optimization approach resulted in a significantly improved agreement with reference gold standard values in vivo, compared to baseline non-optimized protocols (8$\%$ lower NRMSE, 7$\%$ higher SSIM, and 15$\%$ higher Pearson's r value, p<0.001). Conclusion: The combination of the CRB with sequential quadratic programming and a rapid Bloch-McConnell simulator offers a means for optimizing and accelerating pulsed CEST and semisolid magnetization transfer (MT) MRF acquisition.

physics.med-ph

Multi-Parameter Molecular MRI Quantification using Physics-Informed Self-Supervised Learning

Biophysical model fitting plays a key role in obtaining quantitative parameters from physiological signals and images. However, the model complexity for molecular magnetic resonance imaging (MRI) often translates into excessive computation time, which makes clinical use impractical. Here, we present a generic computational approach for solving the parameter extraction inverse problem posed by ordinary differential equation (ODE) modeling coupled with experimental measurement of the system dynamics. This is achieved by formulating a numerical ODE solver to function as a step-wise analytical one, thereby making it compatible with automatic differentiation-based optimization. This enables efficient gradient-based model fitting, and provides a new approach to parameter quantification based on self-supervised learning from a single data observation. The neural-network-based train-by-fit pipeline was used to quantify semisolid magnetization transfer (MT) and chemical exchange saturation transfer (CEST) amide proton exchange parameters in the human brain, in an in-vivo molecular MRI study (n = 4). The entire pipeline of the first whole brain quantification was completed in 18.3 $\pm$ 8.3 minutes. Reusing the single-subject-trained network for inference in new subjects took 1.0 $\pm$ 0.2 s, to provide results in agreement with literature values and scan-specific fit results.

physics.med-ph

Decoding the human brain tissue response to radiofrequency excitation using a biophysical-model-free deep MRI on a chip framework

Magnetic resonance imaging (MRI) relies on radiofrequency (RF) excitation of proton spin. Clinical diagnosis requires a comprehensive collation of biophysical data via multiple MRI contrasts, acquired using a series of RF sequences that lead to lengthy examinations. Here, we developed a vision transformer-based framework that captures the spatiotemporal magnetic signal evolution and decodes the brain tissue response to RF excitation, constituting an MRI on a chip. Following a per-subject rapid calibration scan (28.2 s), a wide variety of image contrasts including fully quantitative molecular, water relaxation, and magnetic field maps can be generated automatically. The method was validated across healthy subjects and a cancer patient in two different imaging sites, and proved to be 94% faster than alternative protocols. The deep MRI on a chip (DeepMonC) framework may reveal the molecular composition of the human brain tissue in a wide range of pathologies, while offering clinically attractive scan times.

physics.med-ph

Deep Learning for Accelerated and Robust MRI Reconstruction: a Review

Deep learning (DL) has recently emerged as a pivotal technology for enhancing magnetic resonance imaging (MRI), a critical tool in diagnostic radiology. This review paper provides a comprehensive overview of recent advances in DL for MRI reconstruction. It focuses on DL approaches and architectures designed to improve image quality, accelerate scans, and address data-related challenges. These include end-to-end neural networks, pre-trained networks, generative models, and self-supervised methods. The paper also discusses the role of DL in optimizing acquisition protocols, enhancing robustness against distribution shifts, and tackling subtle bias. Drawing on the extensive literature and practical insights, it outlines current successes, limitations, and future directions for leveraging DL in MRI reconstruction, while emphasizing the potential of DL to significantly impact clinical imaging practices.

cs.LG

Molecular MRI-Based Monitoring of Cancer Immunotherapy Treatment Response

Immunotherapy constitutes a paradigm shift in cancer treatment. Its FDA approval for several indications has yielded improved prognosis for cases where traditional therapy has shown limited efficiencey. However, many patients still fail to benefit from this treatment modality, and the exact mechanisms responsible for tumor response are unknown. Noninvasive treatment monitoring is crucial for longitudinal tumor characterization and the early detection of non-responders. While various medical imaging techniques can provide a morphological picture of the lesion and its surrounding tissue, a molecular-oriented imaging approach holds the key to unraveling biological effects that occur much earlier in the immunotherapy timeline. Magnetic resonance imaging (MRI) is a highly versatile imaging modality, where the image contrast can be tailored to emphasize a particular biophysical property of interest using advanced engineering of the imaging pipeline. In this review, recent advances in molecular-MRI based cancer immunotherapy monitoring are described. Next, the presentation of the underlying physics, computational, and biological features are complemented by a critical analysis of the results obtained in preclinical and clinical studies. Finally, emerging artificial intelligence (AI)-based strategies to further distill, quantify, and interpret the image-based molecular MRI information are discussed in terms of perspectives for the future.

physics.med-ph

Dynamic and Rapid Deep Synthesis of Molecular MRI Signals

Model-driven analysis of biophysical phenomena is gaining increased attention and utility for medical imaging applications. In magnetic resonance imaging (MRI), the availability of well-established models for describing the relations between the nuclear magnetization, tissue properties, and the externally applied magnetic fields has enabled the prediction of image contrast and served as a powerful tool for designing the imaging protocols that are now routinely used in the clinic. Recently, various advanced imaging techniques have relied on these models for image reconstruction, quantitative tissue parameter extraction, and automatic optimization of acquisition protocols. In molecular MRI, however, the increased complexity of the imaging scenario, where the signals from various chemical compounds and multiple proton pools must be accounted for, results in exceedingly long model simulation times, severely hindering the progress of this approach and its dissemination for various clinical applications. Here, we show that a deep-learning-based system can capture the nonlinear relations embedded in the molecular MRI Bloch-McConnell model, enabling a rapid and accurate generation of biologically realistic synthetic data. The applicability of this simulated data for in-silico, in-vitro, and in-vivo imaging applications is then demonstrated for chemical exchange saturation transfer (CEST) and semisolid macromolecule magnetization transfer (MT) analysis and quantification. The proposed approach yielded 78%-99% acceleration in data synthesis time while retaining excellent agreement with the ground truth (Pearson's r$>$0.99, p$<$0.0001, normalized root mean square error $<$3%).

physics.med-ph

Accelerated and Quantitative 3D Semisolid MT/CEST Imaging using a Generative Adversarial Network (GAN-CEST)

Purpose: To substantially shorten the acquisition time required for quantitative 3D chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction. Methods: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at 3 different sites, using 3 different scanner models and coils. A generative adversarial network supervised framework (GAN-CEST) was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content. Results: The GAN-CEST 3D acquisition time was 42-52 seconds, 70% shorter than CEST-MRF. The quantitative reconstruction of the entire brain took 0.8 seconds. An excellent agreement was observed between the ground truth and GAN-based L-arginine concentration and pH values (Pearson's r > 0.97, NRMSE < 1.5%). GAN-CEST images from a brain-tumor subject yielded a semi-solid volume fraction and exchange rate NRMSE of 3.8$\pm$1.3% and 4.6$\pm$1.3%, respectively, and SSIM of 96.3$\pm$1.6% and 95.0$\pm$2.4%, respectively. The mapping of the calf-muscle exchange parameters in a cardiac patient, yielded NRMSE < 7% and SSIM > 94% for the semi-solid exchange parameters. In regions with large susceptibility artifacts, GAN-CEST has demonstrated improved performance and reduced noise compared to MRF. Conclusion: GAN-CEST can substantially reduce the acquisition time for quantitative semisolid MT/CEST mapping, while retaining performance even when facing pathologies and scanner models that were not available during training.

physics.med-ph

CEST MR fingerprinting (CEST-MRF) for Brain Tumor Quantification Using EPI Readout and Deep Learning Reconstruction

$\textbf{Purpose}$: To develop a clinical CEST MR fingerprinting (CEST-MRF) method for brain tumor quantification using EPI acquisition and deep learning reconstruction. $\textbf{Methods}$: A CEST-MRF pulse sequence originally designed for animal imaging was modified to conform to hardware limits on clinical scanners while keeping scan time $\leq$ 2 minutes. Quantitative MRF reconstruction was performed using a deep reconstruction network (DRONE) to yield the water relaxation and chemical exchange parameters. The feasibility of the 6 parameter DRONE reconstruction was tested in simulations in a digital brain phantom. A healthy subject was scanned with the CEST-MRF sequence, conventional MRF and CEST sequences for comparison. Reproducibility was assessed via test-retest experiments and the concordance correlation coefficient (CCC) calculated for white matter (WM) and grey matter (GM). The clinical utility of CEST-MRF was demonstrated in 4 patients with brain metastases in comparison to standard clinical imaging sequences. Tumors were segmented into edema, solid core and necrotic core regions and the CEST-MRF values compared to the contra-lateral side. $\textbf{Results}$: The DRONE reconstruction of the digital phantom yielded a normalized RMS error of $\leq$ 7% for all parameters. The CEST-MRF parameters were in good agreement with those from conventional MRF and CEST sequences and previous studies. The mean CCC for all 6 parameters was 0.98$\pm$0.01 in WM and 0.98$\pm$0.02 in GM. The CEST-MRF values in nearly all tumor regions were significantly different (P=0.05) from each other and the contra-lateral side. $\textbf{Conclusion}$: Combination of EPI readout and deep learning reconstruction enabled fast, accurate and reproducible CEST-MRF in brain tumors.

physics.med-ph

An End-to-End AI-Based Framework for Automated Discovery of CEST/MT MR Fingerprinting Acquisition Protocols and Quantitative Deep Reconstruction (AutoCEST)

Purpose: To develop an automated machine-learning-based method for the discovery of rapid and quantitative chemical exchange saturation transfer (CEST) MR fingerprinting acquisition and reconstruction protocols. Methods: An MR physics governed AI system was trained to generate optimized acquisition schedules and the corresponding quantitative reconstruction neural-network. The system (termed AutoCEST) is composed of a CEST saturation block, a spin dynamics module, and a deep reconstruction network, all differentiable and jointly connected. The method was validated using a variety of chemical exchange phantoms and an in-vivo mouse brain at 9.4T. Results: The acquisition times for AutoCEST optimized schedules ranged from 35-71s, with a quantitative image reconstruction time of only 29 ms. The resulting exchangeable proton concentration maps for the phantoms were in good agreement with the known solute concentrations for AutoCEST sequences (mean absolute error = 2.42 mM; Pearson's r=0.992 , p$<$0.0001), but not for an unoptimized sequence (mean absolute error = 65.19 mM; Pearson's r=-0.161, p=0.522). Similarly, improved exchange rate agreement was observed between AutoCEST and quantification of exchange using saturation power (QUESP) methods (mean absolute error: 35.8 Hz, Pearson's r=0.971, p$<$0.0001) compared to an unoptimized schedule and QUESP (mean absolute error = 58.2 Hz; Pearson's r=0.959, p$<$0.0001). The AutoCEST in-vivo mouse brain semi-solid proton volume-fractions were lower in the cortex (12.21$\pm$1.37%) compared to the white-matter (19.73 $\pm$ 3.30%), as expected, and the amide proton volume-fraction and exchange rates agreed with previous reports. Conclusion: AutoCEST can automatically generate optimized CEST/MT acquisition protocols that can be rapidly reconstructed into quantitative exchange parameter maps.

physics.med-ph

CEST MR-Fingerprinting: practical considerations and insights for acquisition schedule design and improved reconstruction

Purpose: To understand the influence of various acquisition parameters on the ability of CEST MR-Fingerprinting (MRF) to discriminate different chemical exchange parameters and to provide tools for optimal acquisition schedule design and parameter map reconstruction. Methods: Numerical simulations were conducted using a parallel-computing implementation of the Bloch-McConnell equations, examining the effect of TR, TE, flip-angle, water T$_{1}$ and T$_{2}$, saturation-pulse duration, power, and frequency on the discrimination ability of CEST-MRF. A modified Euclidean-distance matching metric was evaluated and compared to traditional dot-product matching. L-Arginine phantoms of various concentrations and pH were scanned at 4.7T and the results compared to numerical findings. Results: Simulations for dot-product matching demonstrated that the optimal flip-angle and saturation times are 30$^{\circ}$ and 1100 ms, respectively. The optimal maximal saturation power was 3.4 $\mu$T for concentrated solutes with a slow exchange-rate, and 5.2 $\mu$T for dilute solutes with medium-to-fast exchange-rates. Using the Euclidean-distance matching metric, much lower maximum saturation powers were required (1.6 and 2.4 $\mu$T, respectively), with a slightly longer saturation time (1500 ms) and 90$^{\circ}$ flip-angle. For both matching metrics, the discrimination ability increased with the repetition time. The experimental results were in agreement with simulations, demonstrating that more than a 50% reduction in scan-time can be achieved by Euclidean-distance-based matching. Conclusion: Optimization of the CEST-MRF acquisition schedule is critical for obtaining the best exchange parameter accuracy. The use of Euclidean-distance-based matching of signal trajectories simultaneously improved the discrimination ability and reduced the scan time and maximal saturation power required.

physics.med-ph