DeepEMC-T2 mapping: Deep learning-enabled T2 mapping based on echo modulation curve modeling.

PURPOSE: Echo modulation curve (EMC) modeling enables accurate quantification of T2 relaxation times in multi-echo spin-echo (MESE) imaging. The standard EMC-T2 mapping framework, however, requires sufficient echoes and cumbersome pixel-wise dictionary-matching steps. This work proposes a deep learning version of EMC-T2 mapping, called DeepEMC-T2 mapping, to efficiently estimate accurate T2 maps from fewer echoes. METHODS: DeepEMC-T2 mapping was developed using a modified U-Net to estimate both T2 and proton density (PD) maps directly from MESE images. The network implements several new features to improve the accuracy of T2/PD estimation. A total of 67 MESE datasets acquired in axial orientation were used for network training and evaluation. An additional 57 datasets acquired in coronal orientation with different scan parameters were used to evaluate the generalizability of the framework. The performance of DeepEMC-T2 mapping was evaluated in seven experiments. RESULTS: Compared to the reference, DeepEMC-T2 mapping achieved T2 estimation errors from 1% to 11% and PD estimation errors from 0.4% to 1.5% with ten/seven/five/three echoes, which are more accurate than standard EMC-T2 mapping. By incorporating datasets acquired with different scan parameters and orientations for joint training, DeepEMC-T2 exhibits robust generalizability across varying imaging protocols. Increasing the echo spacing and including longer echoes improve the accuracy of parameter estimation. The new features proposed in DeepEMC-T2 mapping all enabled more accurate T2 estimation. CONCLUSIONS: DeepEMC-T2 mapping enables simplified, efficient, and accurate T2 quantification directly from MESE images without dictionary matching. Accurate T2 estimation from fewer echoes allows for increased volumetric coverage and/or higher slice resolution without prolonging total scan times.

Multiband accelerated 2D EPI for multi-echo brain QSM at 3 T.

PURPOSE: Data for QSM are typically acquired using multi-echo 3D gradient echo (GRE), but EPI can be used to accelerate QSM and provide shorter acquisition times. So far, EPI-QSM has been limited to single-echo acquisitions, which, for 3D GRE, are known to be less accurate than multi-echo sequences. Therefore, we compared single-echo and multi-echo EPI-QSM reconstructions across a range of parallel imaging and multiband acceleration factors. METHODS: Using 2D single-shot EPI in the brain, we compared QSM from single-echo and multi-echo acquisitions across combined parallel-imaging and multiband acceleration factors ranging from 2 to 16, with volume pulse TRs from 21.7 to 3.2 s, respectively. For single-echo versus multi-echo reconstructions, we investigated the effect of acceleration factors on regional susceptibility values, temporal noise, and image quality. We introduce a novel masking method based on thresholding the magnitude of the local field gradients to improve brain masking in challenging regions. RESULTS: At 1.6-mm isotropic resolution, high-quality QSM was achieved using multi-echo 2D EPI with a combined acceleration factor of 16 and a TR of 3.2 s, which enables functional applications. With these high acceleration factors, single-echo reconstructions are inaccurate and artefacted, rendering them unusable. Multi-echo acquisitions greatly improve QSM quality, particularly at higher acceleration factors, provide more consistent regional susceptibility values across acceleration factors, and decrease temporal noise compared with single-echo QSM reconstructions. CONCLUSION: Multi-echo acquisition is more robust for EPI-QSM across parallel imaging and multiband acceleration factors than single-echo acquisition. Multi-echo EPI can be used for highly accelerated acquisition while preserving QSM accuracy and quality relative to gold-standard 3D-GRE QSM.

Quantification of Cardiac Iron Overload at 3 T MRI in a Rabbit Model Utilizing ME-GRE T2* Sequence.

BACKGROUND: Myocardial iron overload can lead to myocardial dysfunction, muscle cell injury, and end-stage heart failure. The enhanced signal-to-noise ratio and technical advancements have made 3 T magnetic resonance imaging (MRI) more accessible in clinical settings. However, 3 T assessments for early diagnosis of myocardial iron overload are scarce. PURPOSE: To evaluate the feasibility of myocardial iron quantification using 3 T MRI in a rabbit model of iron overload. STUDY TYPE: Animal model. ANIMAL MODEL: Overall, 40 male New Zealand white rabbits were categorized into control (N = 8; no treatment) and experimental (N = 32; weekly 200 mg/kg iron dextran injections) groups. SEQUENCE: 3 T MRI with multi-echo gradient echo (ME-GRE) T2* sequence. ASSESSMENT: Each week, two experimental rabbits were randomly selected for blood collection to determine serum iron (SI) levels; their tissue was harvested to assess myocardial and hepatic iron deposition. STATISTICAL TESTS: Spearman's rank correlation tests were used to evaluate the correlations among R2*, cardiac iron concentration (CIC), liver iron concentration (LIC), total amount of iron injected, and SI levels. P ≤ 0.05 was considered statistically significant. RESULTS: The myocardial T2* value in the experimental group was significantly lower than that of the control group. An excellent correlation was observed between R2* values and CIC (r = 0.854). CIC moderately correlated with LIC (r = 0.712) and the total amount of iron injected (r = 0.698). A strong correlation was observed between the total amount of iron injected and LIC (r = 0.866). SI levels poorly correlated with the total amount of iron injected (r = 0.205, P = 0.277) and LIC (r = 0.170, P = 0.370) but fairly correlated with CIC (r = 0.415, P = 0.022). DATA CONCLUSION: A 3 T MRI with an ME-GRE sequence may serve as a noninvasive method for evaluating cardiac iron content. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 1.

Precision mapping of the default network reveals common and distinct (inter) activity for autobiographical memory and theory of mind.

The default network is widely implicated as a common neural substrate for self-generated thought, such as remembering one's past (autobiographical memory) and imagining the thoughts and feelings of others (theory of mind). Findings that the default network comprises subnetworks of regions, some commonly and some distinctly involved across processes, suggest that one's own experiences inform their understanding of others. With the advent of precision functional MRI (fMRI) methods, however, it is unclear if this shared substrate is observed instead due to traditional group analysis methods. We investigated this possibility using a novel combination of methodological strategies. Twenty-three participants underwent multi-echo resting-state and task fMRI. We used their resting-state scans to conduct cortical parcellation sensitive to individual variation while preserving our ability to conduct group analysis. Using multivariate analyses, we assessed the functional activation and connectivity profiles of default network regions while participants engaged in autobiographical memory, theory of mind, or a sensorimotor control condition. Across the default network, we observed stronger activity associated with both autobiographical memory and theory of mind compared to the control condition. Nonetheless, we also observed that some regions showed preferential activity to either experimental condition, in line with past work. The connectivity results similarly indicated shared and distinct functional profiles. Our results support that autobiographical memory and theory of mind, two theoretically important and widely studied domains of social cognition, evoke common and distinct aspects of the default network even when ensuring high fidelity to individual-specific characteristics.NEW & NOTEWORTHY We used cutting-edge precision functional MRI (fMRI) methods such as multi-echo fMRI acquisition and denoising, a robust experimental paradigm, and individualized cortical parcellation across 23 participants to provide evidence that remembering one's past experiences and imagining the thoughts and feelings of others share a common neural substrate. Evidence from activation and connectivity analyses indicate overlapping and distinct functional profiles of these widely studied episodic and social processes.

Rapid simultaneous estimation of relaxation rates using multi-echo, multi-contrast MRI.

PURPOSE: Multi-echo, multi-contrast methods are increasingly used in dynamic imaging studies to simultaneously quantify R2∗ and R2. To overcome the computational challenges associated with nonlinear least squares (NLSQ) fitting, we propose a generalized linear least squares (LLSQ) solution to rapidly fit R2∗ and R2. METHODS: Spin- and gradient-echo (SAGE) data were simulated across T2∗ and T2 values at high (200) and low (20) SNR. Full (four-parameter) and reduced (three-parameter) parameter fits were implemented and compared with both LLSQ and NLSQ fitting. Fit data were compared to ground truth using concordance correlation coefficient (CCC) and coefficient of variation (CV). In vivo SAGE perfusion data were acquired in 20 subjects with relapsing-remitting multiple sclerosis. LLSQ R2∗ and R2, as well as cerebral blood volume (CBV), were compared with the standard NLSQ approach. RESULTS: Across all fitting methods, T2∗ was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.87, CV ≤ 0.08) SNR. Except for short T2∗ values (5-15 ms), T2 was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.99, CV ≤ 0.03) SNR. In vivo, LLSQ R2∗ and R2 estimates were similar to NLSQ, and there were no differences in R2∗ across fitting methods at high SNR. However, there were some differences at low SNR and for R2 at high and low SNR. In vivo NLSQ and LLSQ three parameter fits performed similarly, as did NLSQ and LLSQ four-parameter fits. LLSQ CBV nearly matched the standard NLSQ method for R2∗- (0.97 ratio) and R2-CBV (0.98 ratio). Voxel-wise whole-brain fitting was faster for LLSQ (3-4 min) than NLSQ (16-18 h). CONCLUSIONS: LLSQ reliably fit for R2∗ and R2 in simulated and in vivo data. Use of LLSQ methods reduced the computational demand, enabling rapid estimation of R2∗ and R2.

Accelerated 3D multi-echo spin-echo sequence with a subspace constrained reconstruction for whole mouse brain T 2 mapping.

PURPOSE: To accelerate whole-brain quantitative T 2 $$ {\mathrm{T}}_2 $$ mapping in preclinical imaging setting. METHODS: A three-dimensional (3D) multi-echo spin echo sequence was highly undersampled with a variable density Poisson distribution to reduce the acquisition time. Advanced iterative reconstruction based on linear subspace constraints was employed to recover high-quality raw images. Different subspaces, generated using exponential or extended-phase graph (EPG) simulations or from low-resolution calibration images, were compared. The subspace dimension was investigated in terms of T 2 $$ {\mathrm{T}}_2 $$ precision. The method was validated on a phantom containing a wide range of T 2 $$ {\mathrm{T}}_2 $$ and was then applied to monitor metastasis growth in the mouse brain at 4.7T. Image quality and T 2 $$ {\mathrm{T}}_2 $$ estimation were assessed for 3 acceleration factors (6/8/10). RESULTS: The EPG-based dictionary gave robust estimations of a large range of T 2 $$ {\mathrm{T}}_2 $$ . A subspace dimension of 6 was the best compromise between T 2 $$ {\mathrm{T}}_2 $$ precision and image quality. Combining the subspace constrained reconstruction with a highly undersampled dataset enabled the acquisition of whole-brain T 2 $$ {\mathrm{T}}_2 $$ maps, the detection and the monitoring of metastasis growth of less than 500 µ m 3 $$ \mu {\mathrm{m}}^3 $$ . CONCLUSION: Subspace-based reconstruction is suitable for 3D T 2 $$ {\mathrm{T}}_2 $$ mapping. This method can be used to reach an acceleration factor up to 8, corresponding to an acquisition time of 25 min for an isotropic 3D acquisition of 156 µ $$ \mu $$ m on the mouse brain, used here for monitoring metastases growth.

Fast and High-Resolution T2 Mapping Based on Echo Merging Plus k-t Undersampling with Reduced Refocusing Flip Angles (TEMPURA) as Methods for Human Renal MRI.

PURPOSE: To develop a highly accelerated multi-echo spin-echo method, TEMPURA, for reducing the acquisition time and/or increasing spatial resolution for kidney T2 mapping. METHODS: TEMPURA merges several adjacent echoes into one k-space by either combining independent echoes or sharing one echo between k-spaces. The combined k-space is reconstructed based on compressed sensing theory. Reduced flip angles are used for the refocusing pulses, and the extended phase graph algorithm is used to correct the effects of indirect echoes. Two sequences were developed: a fast breath-hold sequence; and a high-resolution sequence. The performance was evaluated prospectively on a phantom, 16 healthy subjects, and two patients with different types of renal tumors. RESULTS: The fast TEMPURA method reduced the acquisition time from 3-5 min to one breath-hold (18 s). Phantom measurements showed that fast TEMPURA had a mean absolute percentage error (MAPE) of 8.2%, which was comparable to a standardized respiratory-triggered sequence (7.4%), but much lower than a sequence accelerated by purely k-t undersampling (21.8%). High-resolution TEMPURA reduced the in-plane voxel size from 3 × 3 to 1 × 1 mm2, resulting in improved visualization of the detailed anatomical structure. In vivo T2 measurements demonstrated good agreement (fast: MAPE = 1.3%-2.5%; high-resolution: MAPE = 2.8%-3.3%) and high correlation coefficients (fast: R = 0.85-0.98; high-resolution: 0.82-0.96) with the standardized method, outperforming k-t undersampling alone (MAPE = 3.3-4.5%, R = 0.57-0.59). CONCLUSION: TEMPURA provides fast and high-resolution renal T2 measurements. It has the potential to improve clinical throughput and delineate intratumoral heterogeneity and tissue habitats at unprecedented spatial resolution.

Experience transforms crossmodal object representations in the anterior temporal lobes.

Combining information from multiple senses is essential to object recognition, core to the ability to learn concepts, make new inferences, and generalize across distinct entities. Yet how the mind combines sensory input into coherent crossmodal representations - the crossmodal binding problem - remains poorly understood. Here, we applied multi-echo fMRI across a 4-day paradigm, in which participants learned three-dimensional crossmodal representations created from well-characterized unimodal visual shape and sound features. Our novel paradigm decoupled the learned crossmodal object representations from their baseline unimodal shapes and sounds, thus allowing us to track the emergence of crossmodal object representations as they were learned by healthy adults. Critically, we found that two anterior temporal lobe structures - temporal pole and perirhinal cortex - differentiated learned from non-learned crossmodal objects, even when controlling for the unimodal features that composed those objects. These results provide evidence for integrated crossmodal object representations in the anterior temporal lobes that were different from the representations for the unimodal features. Furthermore, we found that perirhinal cortex representations were by default biased toward visual shape, but this initial visual bias was attenuated by crossmodal learning. Thus, crossmodal learning transformed perirhinal representations such that they were no longer predominantly grounded in the visual modality, which may be a mechanism by which object concepts gain their abstraction.

Improved clinical outcome prediction in depression using neurodynamics in an emotional face-matching functional MRI task.

Introduction: Approximately one in six people will experience an episode of major depressive disorder (MDD) in their lifetime. Effective treatment is hindered by subjective clinical decision-making and a lack of objective prognostic biomarkers. Functional MRI (fMRI) could provide such an objective measure but the majority of MDD studies has focused on static approaches, disregarding the rapidly changing nature of the brain. In this study, we aim to predict depression severity changes at 3 and 6 months using dynamic fMRI features. Methods: For our research, we acquired a longitudinal dataset of 32 MDD patients with fMRI scans acquired at baseline and clinical follow-ups 3 and 6 months later. Several measures were derived from an emotion face-matching fMRI dataset: activity in brain regions, static and dynamic functional connectivity between functional brain networks (FBNs) and two measures from a wavelet coherence analysis approach. All fMRI features were evaluated independently, with and without demographic and clinical parameters. Patients were divided into two classes based on changes in depression severity at both follow-ups. Results: The number of coherence clusters (nCC) between FBNs, reflecting the total number of interactions (either synchronous, anti-synchronous or causal), resulted in the highest predictive performance. The nCC-based classifier achieved 87.5% and 77.4% accuracy for the 3- and 6-months change in severity, respectively. Furthermore, regression analyses supported the potential of nCC for predicting depression severity on a continuous scale. The posterior default mode network (DMN), dorsal attention network (DAN) and two visual networks were the most important networks in the optimal nCC models. Reduced nCC was associated with a poorer depression course, suggesting deficits in sustained attention to and coping with emotion-related faces. An ensemble of classifiers with demographic, clinical and lead coherence features, a measure of dynamic causality, resulted in a 3-months clinical outcome prediction accuracy of 81.2%. Discussion: The dynamic wavelet features demonstrated high accuracy in predicting individual depression severity change. Features describing brain dynamics could enhance understanding of depression and support clinical decision-making. Further studies are required to evaluate their robustness and replicability in larger cohorts.

JUST-Net: Jointly unrolled cross-domain optimization based spatio-temporal reconstruction network for accelerated 3D myelin water imaging.

PURPOSE: We introduced a novel reconstruction network, jointly unrolled cross-domain optimization-based spatio-temporal reconstruction network (JUST-Net), aimed at accelerating 3D multi-echo gradient-echo (mGRE) data acquisition and improving the quality of resulting myelin water imaging (MWI) maps. METHOD: An unrolled cross-domain spatio-temporal reconstruction network was designed. The main idea is to combine frequency and spatio-temporal image feature representations and to sequentially implement convolution layers in both domains. The k-space subnetwork utilizes shared information from adjacent frames, whereas the image subnetwork applies separate convolutions in both spatial and temporal dimensions. The proposed reconstruction network was evaluated for both retrospectively and prospectively accelerated acquisition. Furthermore, it was assessed in simulation studies and real-world cases with k-space corruptions to evaluate its potential for motion artifact reduction. RESULTS: The proposed JUST-Net enabled highly reproducible and accelerated 3D mGRE acquisition for whole-brain MWI, reducing the acquisition time from fully sampled 15:23 to 2:22 min within a 3-min reconstruction time. The normalized root mean squared error of the reconstructed mGRE images increased by less than 4.0%, and the correlation coefficients for MWI showed a value of over 0.68 when compared to the fully sampled reference. Additionally, the proposed method demonstrated a mitigating effect on both simulated and clinical motion-corrupted cases. CONCLUSION: The proposed JUST-Net has demonstrated the capability to achieve high acceleration factors for 3D mGRE-based MWI, which is expected to facilitate widespread clinical applications of MWI.

Multi-Echo Complex Quantitative Susceptibility Mapping and Quantitative Blood Oxygen Level-Dependent Magnitude (mcQSM + qBOLD or mcQQ) for Oxygen Extraction Fraction (OEF) Mapping.

Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an essential biomarker used to directly assess tissue viability and function in neurologic disorders. In ischemic stroke, for example, increased OEF can indicate the presence of penumbra-tissue with low perfusion yet intact cellular integrity-making it a primary therapeutic target. However, practical OEF mapping methods are not currently available in clinical settings, owing to the impractical data acquisitions in positron emission tomography (PET) and the limitations of existing MRI techniques. Recently, a novel MRI-based OEF mapping technique, termed QQ, was proposed. It shows high potential for clinical use by utilizing a routine sequence and removing the need for impractical multiple gas inhalations. However, QQ relies on the assumptions of Gaussian noise in susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low signal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic Gaussian noise in mGRE complex signals. We implemented mcQQ using a deep learning framework (mcQQ-NET) and compared it with the existing QQ-NET in simulations, ischemic stroke patients, and healthy subjects, using identical training and testing datasets and schemes. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the subacute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaffected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR, such as SNR ≤ 15 (dB). Therefore, mcQQ-NET improves OEF accuracy by more accurately reflecting realistic Gaussian noise in complex mGRE signals. Its enhanced sensitivity to OEF abnormalities, based on more realistic biophysics modeling, suggests that mcQQ-NET has potential for investigating tissue variability in neurologic disorders.

Single-shot Echo Planar Time-resolved Imaging for multi-echo functional MRI and distortion-free diffusion imaging.

Purpose: To develop EPTI, a multi-shot distortion-free multi-echo imaging technique, into a single-shot acquisition to achieve improved robustness to motion and physiological noise, increased temporal resolution, and high SNR efficiency for dynamic imaging applications. Methods: A new spatiotemporal encoding was developed to achieve single-shot EPTI by enhancing spatiotemporal correlation in k-t space. The proposed single-shot encoding improves reconstruction conditioning and sampling efficiency, with additional optimization under various accelerations to achieve optimized performance. To achieve high SNR efficiency, continuous readout with minimized deadtime was employed that begins immediately after excitation and extends for an SNR-optimized length. Moreover, k-t partial Fourier and simultaneous multi-slice acquisition were integrated to further accelerate the acquisition and achieve high spatial and temporal resolution. Results: We demonstrated that ss-EPTI achieves higher tSNR efficiency than multi-shot EPTI, and provides distortion-free imaging with densely-sampled multi-echo images at resolutions ~1.25-3 mm at 3T and 7T-with high SNR efficiency and with comparable temporal resolutions to ss-EPI. The ability of ss-EPTI to eliminate dynamic distortions common in EPI also further improves temporal stability. For fMRI, ss-EPTI also provides early-TE images (e.g., 2.9ms) to recover signal-intensity and functional-sensitivity dropout in challenging regions. The multi-echo images provide TE-dependent information about functional fluctuations, successfully distinguishing noise-components from BOLD signals and further improving tSNR. For diffusion MRI, ss-EPTI provides high-quality distortion-free diffusion images and multi-echo diffusion metrics. Conclusion: ss-EPTI provides distortion-free imaging with high image quality, rich multi-echo information, and enhanced efficiency within comparable temporal resolution to ss-EPI, offering a robust and efficient acquisition for dynamic imaging.

Dynamic T 2 * relaxometry of hyperpolarized [1-13 C]pyruvate MRI in the human brain and kidneys.

PURPOSE: This study aimed to quantify T 2 * $$ {T}_2^{\ast } $$ for hyperpolarized [1-13 C]pyruvate and metabolites in the healthy human brain and renal cell carcinoma (RCC) patients at 3 T. METHODS: Dynamic T 2 * $$ {T}_2^{\ast } $$ values were measured with a metabolite-specific multi-echo spiral sequence. The dynamic T 2 * $$ {T}_2^{\ast } $$ of [1-13 C]pyruvate, [1-13 C]lactate, and 13 C-bicarbonate was estimated in regions of interest in the whole brain, sinus vein, gray matter, and white matter in healthy volunteers, as well as in kidney tumors and the contralateral healthy kidneys in a separate group of RCC patients. T 2 * $$ {T}_2^{\ast } $$ was fit using a mono-exponential function; and metabolism was quantified using pyruvate-to-lactate conversion rate maps and lactate-to-pyruvate ratio maps, which were compared with and without an estimated T 2 * $$ {T}_2^{\ast } $$ correction. RESULTS: The T 2 * $$ {T}_2^{\ast } $$ of pyruvate was shown to vary during the acquisition, whereas the T 2 * $$ {T}_2^{\ast } $$ of lactate and bicarbonate were relatively constant through time and across the organs studied. The T 2 * $$ {T}_2^{\ast } $$ of lactate was similar in gray matter (29.75 ± 1.04 ms), white matter (32.89 ± 0.9 ms), healthy kidney (34.61 ± 4.07 ms), and kidney tumor (33.01 ± 2.31 ms); and the T 2 * $$ {T}_2^{\ast } $$ of bicarbonate was different between whole-brain (108.17 ± 14.05 ms) and healthy kidney (58.45 ± 6.63 ms). The T 2 * $$ {T}_2^{\ast } $$ of pyruvate had similar trends in both brain and RCC studies, reducing from 75.56 ± 2.23 ms to 22.24 ± 1.24 ms in the brain and reducing from 122.72 ± 9.86 ms to 57.38 ± 7.65 ms in the kidneys. CONCLUSION: Multi-echo dynamic imaging can quantify T 2 * $$ {T}_2^{\ast } $$ and metabolism in a single integrated acquisition. Clear differences were observed in the T 2 * $$ {T}_2^{\ast } $$ of metabolites and in their behavior throughout the timecourse.

Whole-brain multivariate hemodynamic deconvolution for functional MRI with stability selection.

Conventionally, analysis of functional MRI (fMRI) data relies on available information about the experimental paradigm to establish hypothesized models of brain activity. However, this information can be inaccurate, incomplete or unavailable in multiple scenarios such as resting-state, naturalistic paradigms or clinical conditions. In these cases, blind estimates of neuronal-related activity can be obtained with paradigm-free analysis methods such as hemodynamic deconvolution. Yet, current formulations of the hemodynamic deconvolution problem have three important limitations: (1) their efficacy strongly depends on the appropriate selection of regularization parameters, (2) being univariate, they do not take advantage of the information present across the brain, and (3) they do not provide any measure of statistical certainty associated with each detected event. Here we propose a novel approach that addresses all these limitations. Specifically, we introduce multivariate sparse paradigm free mapping (Mv-SPFM), a novel hemodynamic deconvolution algorithm that operates at the whole brain level and adds spatial information via a mixed-norm regularization term over all voxels. Additionally, Mv-SPFM employs a stability selection procedure that removes the need to select regularization parameters and also lets us obtain an estimate of the true probability of having a neuronal-related BOLD event at each voxel and time-point based on the area under the curve (AUC) of the stability paths. Besides, we present a formulation tailored for multi-echo fMRI acquisitions (MvME-SPFM), which allows us to better isolate fluctuations of BOLD origin on the basis of their linear dependence with the echo time (TE) and to assign physiologically interpretable units (i.e., changes in the apparent transverse relaxation ΔR2∗) to the resulting deconvolved events. Remarkably, we demonstrate that Mv-SPFM achieves comparable performance even when using a single-echo formulation. We demonstrate that this algorithm outperforms existing state-of-the-art deconvolution approaches, and shows higher spatial and temporal agreement with the activation maps and BOLD signals obtained with a standard model-based linear regression approach, even at the level of individual neuronal events. Furthermore, we show that by employing stability selection, the performance of the algorithm depends less on the selection of temporal and spatial regularization parameters λ and ρ. Consequently, the proposed algorithm provides more reliable estimates of neuronal-related activity, here in terms of ΔR2∗, for the study of the dynamics of brain activity when no information about the timings of the BOLD events is available. This algorithm will be made publicly available as part of the splora Python package.

Framewise multi-echo distortion correction for superior functional MRI.

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities which currently must be corrected using separately acquired field map data. However, changes in the head position of a scanning participant across fMRI frames can cause changes in the B0 field, preventing accurate correction of geometric distortions. Additionally, field maps can be corrupted by movement during their acquisition, preventing distortion correction altogether. In this study, we use phase information from multi-echo (ME) fMRI data to dynamically sample distortion due to fluctuating B0 field inhomogeneity across frames by acquiring multiple echoes during a single EPI readout. Our distortion correction approach, MEDIC (Multi-Echo DIstortion Correction), accurately estimates B0 related distortions for each frame of multi-echo fMRI data. Here, we demonstrate that MEDIC's framewise distortion correction produces improved alignment to anatomy and decreases the impact of head motion on resting-state functional connectivity (RSFC) maps, in higher motion data, when compared to the prior gold standard approach (i.e., TOPUP). Enhanced framewise distortion correction with MEDIC, without the requirement for field map collection, furthers the advantage of multi-echo over single-echo fMRI.

Multi-echo Acquisition and Thermal Denoising Advances Infant Precision Functional Imaging.

The characterization of individual functional brain organization with Precision Functional Mapping has provided important insights in recent years in adults. However, little is known about the ontogeny of inter-individual differences in brain functional organization during human development, but precise characterization of systems organization during periods of high plasticity might be most influential towards discoveries promoting lifelong health. Collecting and analyzing precision fMRI data during early development has unique challenges and emphasizes the importance of novel methods to improve data acquisition, processing, and analysis strategies in infant samples. Here, we investigate the applicability of two such methods from adult MRI research, multi-echo (ME) data acquisition and thermal noise removal with Noise reduction with distribution corrected principal component analysis (NORDIC), in precision fMRI data from three newborn infants. Compared to an adult example subject, T2* relaxation times calculated from ME data in infants were longer and more variable across the brain, pointing towards ME acquisition being a promising tool for optimizing developmental fMRI. The application of thermal denoising via NORDIC increased tSNR and the overall strength of functional connections as well as the split-half reliability of functional connectivity matrices in infant ME data. While our findings related to NORDIC denoising are coherent with the adult literature and ME data acquisition showed high promise, its application in developmental samples needs further investigation. The present work reveals gaps in our understanding of the best techniques for developmental brain imaging and highlights the need for further developmentally-specific methodological advances and optimizations, towards precision functional imaging in infants.

Optimization of Gradient-Echo Echo-Planar Imaging for T2* Contrast in the Brain at 0.5 T.

Gradient-recalled echo (GRE) echo-planar imaging (EPI) is an efficient MRI pulse sequence that is commonly used for several enticing applications, including functional MRI (fMRI), susceptibility-weighted imaging (SWI), and proton resonance frequency (PRF) thermometry. These applications are typically not performed in the mid-field (<1 T) as longer T2* and lower polarization present significant challenges. However, recent developments of mid-field scanners equipped with high-performance gradient sets offer the possibility to re-evaluate the feasibility of these applications. The paper introduces a metric "T2* contrast efficiency" for this evaluation, which minimizes dead time in the EPI sequence while maximizing T2* contrast so that the temporal and pseudo signal-to-noise ratios (SNRs) can be attained, which could be used to quantify experimental parameters for future fMRI experiments in the mid-field. To guide the optimization, T2* measurements of the cortical gray matter are conducted, focusing on specific regions of interest (ROIs). Temporal and pseudo SNR are calculated with the measured time-series EPI data to observe the echo times at which the maximum T2* contrast efficiency is achieved. T2* for a specific cortical ROI is reported at 0.5 T. The results suggest the optimized echo time for the EPI protocols is shorter than the effective T2* of that region. The effective reduction of dead time prior to the echo train is feasible with an optimized EPI protocol, which will increase the overall scan efficiency for several EPI-based applications at 0.5 T.

Comparing the efficacy of data-driven denoising methods for a multi-echo fMRI acquisition at 7T.

In functional magnetic resonance imaging (fMRI) of the brain the measured signal is corrupted by several (e.g. physiological, motion, and thermal) noise sources and depends on the image acquisition. Imaging at ultrahigh field strength is becoming increasingly popular as it offers increased spatial accuracy. The latter is of particular benefit in brainstem neuroimaging given the small cross-sectional area of most nuclei. However, physiological noise scales with field strength in fMRI acquisitions. Although this problem is in part solved by decreasing voxel size, it is clear that adequate physiological denoising is of utmost importance in brainstem-focused fMRI experiments. Multi-echo sequences have been reported to facilitate highly effective denoising through TE-dependence of Blood Oxygen Level Dependent (BOLD) signals, in a denoising method referred to as multi-echo independent component analysis (ME-ICA). It has not been explored previously how ME-ICA compares to other data-driven denoising approaches at ultrahigh field strength. In the current study, we compared the efficacy of several denoising methods, including anatomical component based correction (aCompCor), Automatic Removal of Motion Artifacts (ICA-AROMA) aggressive and non-aggressive options, ME-ICA, and a combination of ME-ICA and aCompCor. We assessed several data quality metrics, including temporal signal-to-noise ratio (tSNR), delta variation signal (DVARS), spectral density of the global signal, functional connectivity and Shannon spectral entropy. Moreover, we looked at the ability of each method to uncouple the global signal and respiration. In line with previous reports at lower field strengths, we demonstrate that after applying ME-ICA, the data is best post-processed in order to remove spatially diffuse noise with a method such as aCompCor. Our findings indicate that ME-ICA combined with aCompCor and the aggressive option of ICA-AROMA are highly effective denoising approaches for multi-echo data acquired at 7T. ME-ICA combined with aCompCor potentially preserves more signal-of-interest as compared to the aggressive option of ICA-AROMA.

Fiber-orientation independent component of R2* obtained from single-orientation MRI measurements in simulations and a post-mortem human optic chiasm.

The effective transverse relaxation rate (R2*) is sensitive to the microstructure of the human brain like the g-ratio which characterises the relative myelination of axons. However, the fibre-orientation dependence of R2* degrades its reproducibility and any microstructural derivative measure. To estimate its orientation-independent part (R2,iso*) from single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientations, a second-order polynomial in time model (hereafter M2) can be used. Its linear time-dependent parameter, ß1, can be biophysically related to R2,iso* when neglecting the myelin water (MW) signal in the hollow cylinder fibre model (HCFM). Here, we examined the performance of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We found that the fitted ß1 can estimate R2,iso* using meGRE with long maximum-echo time (TEmax ≈ 54 ms), but not accurately captures its microscopic dependence on the g-ratio (error 84%). We proposed a new heuristic expression for ß1 that reduced the error to 12% for ex vivo compartmental R2 values. Using the new expression, we could estimate an MW fraction of 0.14 for fibres with negligible dispersion in a fixed human optic chiasm for the ex vivo compartmental R2 values but not for the in vivo values. M2 and the HCFM-based simulations failed to explain the measured R2*-orientation-dependence around the magic angle for a typical in vivo meGRE protocol (with TEmax ≈ 18 ms). In conclusion, further validation and the development of movement-robust in vivo meGRE protocols with TEmax ≈ 54 ms are required before M2 can be used to estimate R2,iso* in subjects.

Free-breathing high isotropic resolution quantitative susceptibility mapping (QSM) of liver using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction.

PURPOSE: To enable free-breathing and high isotropic resolution liver quantitative susceptibility mapping (QSM) using 3D multi-echo UTE cones acquisition and respiratory motion-resolved image reconstruction. METHODS: Using 3D multi-echo UTE cones MRI, a respiratory motion was estimated from the k-space center of the imaging data. After sorting the k-space data with estimated motion, respiratory motion state-resolved reconstruction was performed for multi-echo data followed by nonlinear least-squares fitting for proton density fat fraction (PDFF), R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , and fat-corrected B0 field maps. PDFF and B0 field maps were subsequently used for QSM reconstruction. The proposed method was compared with motion-averaged (gridding) reconstruction and conventional 3D multi-echo Cartesian MRI in moving gadolinium phantom and in vivo studies. Region of interest (ROI)-based linear regression analysis was performed on these methods to investigate correlations between gadolinium concentration and QSM in the phantom study and between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM in in vivo study. RESULTS: Cones with motion-resolved reconstruction showed sharper image quality compared to motion-averaged reconstruction with a substantial reduction of motion artifacts in both moving phantom and in vivo studies. For ROI-based linear regression analysis of the phantom study, susceptibility values from cones with motion-resolved reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.31 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.05, R 2 $$ {R}^2 $$ = 0.999) and Cartesian without motion ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.32 × gadolinium mM + $$ \times {\mathrm{gadolinium}}_{\mathrm{mM}}+ $$ 0.04, R 2 $$ {R}^2 $$ = 1.000) showed linear relationships with gadolinium concentrations and showed good agreement with each other. For in vivo, motion-resolved reconstruction showed higher goodness of fit ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.00261 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.524, R 2 $$ {R}^2 $$ = 0.977) compared to motion-averaged reconstruction ( QSM ppm $$ {\mathrm{QSM}}_{\mathrm{ppm}} $$ = 0.0021 × R 2 s - 1 * - $$ \times {\mathrm{R}}_{2_{{\mathrm{s}}^{-1}}}^{\ast }- $$ 0.572, R 2 $$ {R}^2 $$ = 0.723) in ROI-based linear regression analysis between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and QSM. CONCLUSION: Feasibility of free-breathing liver QSM was demonstrated with motion-resolved 3D multi-echo UTE cones MRI, achieving high isotropic resolution currently unachievable in conventional Cartesian MRI.