Quantitative susceptibility mapping through model-based deep image prior (MoDIP).

The data-driven approach of supervised learning methods has limited applicability in solving dipole inversion in Quantitative Susceptibility Mapping (QSM) with varying scan parameters across different objects. To address this generalization issue in supervised QSM methods, we propose a novel training-free model-based unsupervised method called MoDIP (Model-based Deep Image Prior). MoDIP comprises a small, untrained network and a Data Fidelity Optimization (DFO) module. The network converges to an interim state, acting as an implicit prior for image regularization, while the optimization process enforces the physical model of QSM dipole inversion. Experimental results demonstrate MoDIP's excellent generalizability in solving QSM dipole inversion across different scan parameters. It exhibits robustness against pathological brain QSM, achieving over 32 % accuracy improvement than supervised deep learning methods. It is also 33 % more computationally efficient and runs 4 times faster than conventional DIP-based approaches, enabling 3D high-resolution image reconstruction in under 4.5 min.

Harmonic field extension for QSM with reduced spatial coverage using physics-informed generative adversarial network.

Quantitative susceptibility mapping (QSM) is frequently employed in investigating brain iron related to brain development and diseases within deep gray matter (DGM). Nonetheless, the acquisition of whole-brain QSM data is time-intensive. An alternative approach, focusing the QSM specifically on areas of interest such as the DGM by reducing the field-of-view (FOV), can significantly decrease scan times. However, severe susceptibility value underestimations have been reported during QSM reconstruction with a limited FOV, largely attributable to artifacts from incorrect background field removal in the boundary region. This presents a considerable barrier to the clinical use of QSM with small spatial coverages using conventional methods alone. To mitigate the propagation of these errors, we proposed a harmonic field extension method based on a physics-informed generative adversarial network. Both quantitative and qualitative results demonstrate that our method outperforms conventional methods and delivers results comparable to those obtained with full FOV. Furthermore, we demonstrate the versatility of our method by applying it to data acquired prospectively with limited FOV and to data from patients with Parkinson's disease. The method has shown significant improvements in local field results, with QSM outcomes. In a clear illustration of its feasibility and effectiveness in real clinical environments, our proposed method addresses the prevalent issue of susceptibility underestimation in QSM with small spatial coverage.

Quantitative susceptibility mapping in the brain reflects spatial expression of genes involved in iron homeostasis and myelination.

Quantitative susceptibility mapping (QSM) is an MRI modality used to non-invasively measure iron content in the brain. Iron exhibits a specific anatomically varying pattern of accumulation in the brain across individuals. The highest regions of accumulation are the deep grey nuclei, where iron is stored in paramagnetic molecule ferritin. This form of iron is considered to be what largely contributes to the signal measured by QSM in the deep grey nuclei. It is also known that QSM is affected by diamagnetic myelin contents. Here, we investigate spatial gene expression of iron and myelin related genes, as measured by the Allen Human Brain Atlas, in relation to QSM images of age-matched subjects. We performed multiple linear regressions between gene expression and the average QSM signal within 34 distinct deep grey nuclei regions. Our results show a positive correlation (p < .05, corrected) between expression of ferritin and the QSM signal in deep grey nuclei regions. We repeated the analysis for other genes that encode proteins thought to be involved in the transport and storage of iron in the brain, as well as myelination. In addition to ferritin, our findings demonstrate a positive correlation (p < .05, corrected) between the expression of ferroportin, transferrin, divalent metal transporter 1, several gene markers of myelinating oligodendrocytes, and the QSM signal in deep grey nuclei regions. Our results suggest that the QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.

Whole brain pattern of iron accumulation in REM sleep behavior disorder.

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

Three-dimensional EPI with shot-selective CAIPIRIHANA for rapid high-resolution quantitative susceptibility mapping at 3 T.

PURPOSE: QSM provides insight into healthy brain aging and neuropathologies such as multiple sclerosis (MS), traumatic brain injuries, brain tumors, and neurodegenerative diseases. Phase data for QSM are usually acquired from 3D gradient-echo (3D GRE) scans with long acquisition times that are detrimental to patient comfort and susceptible to patient motion. This is particularly true for scans requiring whole-brain coverage and submillimeter resolutions. In this work, we use a multishot 3D echo plannar imaging (3D EPI) sequence with shot-selective 2D CAIPIRIHANA to acquire high-resolution, whole-brain data for QSM with minimal distortion and blurring. METHODS: To test clinical viability, the 3D EPI sequence was used to image a cohort of MS patients at 1-mm isotropic resolution at 3 T. Additionally, 3D EPI data of healthy subjects were acquired at 1-mm, 0.78-mm, and 0.65-mm isotropic resolution with varying echo train lengths (ETLs) and compared with a reference 3D GRE acquisition. RESULTS: The appearance of the susceptibility maps and the susceptibility values for segmented regions of interest were comparable between 3D EPI and 3D GRE acquisitions for both healthy and MS participants. Additionally, all lesions visible in the MS patients on the 3D GRE susceptibility maps were also visible on the 3D EPI susceptibility maps. The interplay among acquisition time, resolution, echo train length, and the effect of distortion on the calculated susceptibility maps was investigated. CONCLUSION: We demonstrate that the 3D EPI sequence is capable of rapidly acquiring submillimeter resolutions and providing high-quality, clinically relevant susceptibility maps.

Exploiting gradient-echo frequency evolution: Probing white matter microstructure and extracting bulk susceptibility-induced frequency for quantitative susceptibility mapping.

PURPOSE: This work is to investigate the microstructure-induced frequency shift in white matter (WM) with crossing fibers and to separate the microstructure-related frequency shift from the bulk susceptibility-induced frequency shift by model fitting the gradient-echo (GRE) frequency evolution for potentially more accurate quantitative susceptibility mapping (QSM). METHODS: A hollow-cylinder fiber model (HCFM) with two fiber populations was developed to investigate GRE frequency evolutions in WM voxels with microstructural orientation dispersion. The simulated and experimentally measured TE-dependent local frequency shift was then fitted to a simplified frequency evolution model to obtain a microstructure-related frequency difference parameter ( ∆ f $$ \Delta f $$ ) and a TE-independent bulk susceptibility-induced frequency shift ( C f $$ {C}_f $$ ). The obtained C f $$ {C}_f $$ was then used for QSM reconstruction. Reconstruction performances were evaluated using a numerical head phantom and in vivo data and then compared to other multi-echo combination methods. RESULTS: GRE frequency evolutions and ∆ f $$ \Delta f $$ -based tissue parameters in both parallel and crossing fibers determined from our simulations were comparable to those observed in vivo. The TE-dependent frequency fitting method outperformed other multi-echo combination methods in estimating C f $$ {C}_f $$ in simulations. The fitted ∆ f $$ \Delta f $$ , C f $$ {C}_f $$ , and QSM could be improved further by navigator-based B0 fluctuation correction. CONCLUSION: A HCFM with two fiber populations can be used to characterize microstructure-induced frequency shifts in WM regions with crossing fibers. HCFM-based TE-dependent frequency fitting provides tissue contrast related to microstructure ( ∆ f $$ \Delta f $$ ) and in addition may help improve the quantification accuracy of C f $$ {C}_f $$ and the corresponding QSM.

Rapid submillimeter QSM and R2* mapping using interleaved multishot 3D-EPI at 7 and 3 Tesla.

PURPOSE: To explore the high signal-to-noise ratio (SNR) efficiency of interleaved multishot 3D-EPI with standard image reconstruction for fast and robust high-resolution whole-brain quantitative susceptibility (QSM) and R 2 ∗ $$ {R}_2^{\ast } $$ mapping at 7 and 3T. METHODS: Single- and multi-TE segmented 3D-EPI is combined with conventional CAIPIRINHA undersampling for up to 72-fold effective gradient echo (GRE) imaging acceleration. Across multiple averages, scan parameters are varied (e.g., dual-polarity frequency-encoding) to additionally correct for B 0 $$ {\mathrm{B}}_0 $$ -induced artifacts, geometric distortions and motion retrospectively. A comparison to established GRE protocols is made. Resolutions range from 1.4 mm isotropic (1 multi-TE average in 36 s) up to 0.4 mm isotropic (2 single-TE averages in approximately 6 min) with whole-head coverage. RESULTS: Only 1-4 averages are needed for sufficient SNR with 3D-EPI, depending on resolution and field strength. Fast scanning and small voxels together with retrospective corrections result in substantially reduced image artifacts, which improves susceptibility and R 2 ∗ $$ {R}_2^{\ast } $$ mapping. Additionally, much finer details are obtained in susceptibility-weighted image projections through significantly reduced partial voluming. CONCLUSION: Using interleaved multishot 3D-EPI, single-TE and multi-TE data can readily be acquired 10 times faster than with conventional, accelerated GRE imaging. Even 0.4 mm isotropic whole-head QSM within 6 min becomes feasible at 7T. At 3T, motion-robust 0.8 mm isotropic whole-brain QSM and R 2 ∗ $$ {R}_2^{\ast } $$ mapping with no apparent distortion in less than 7 min becomes clinically feasible. Stronger gradient systems may allow for even higher effective acceleration rates through larger EPI factors while maintaining optimal contrast.

Improved test-retest reliability of R 2 * $$ {\mathrm{R}}_2

PURPOSE: This study aimed to evaluate the potential of 3D EPI for improving the reliability of T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted data and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ decay rate and susceptibility (χ) compared with conventional gradient-echo (GRE)-based acquisition. METHODS: Eight healthy subjects in a wide age range were recruited. Each subject received repeated scans for both GRE and EPI acquisitions with an isotropic 1 mm resolution at 3 T. Maps of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ were quantified, and their interscan differences were used to evaluate the test-retest reliability. Interprotocol differences of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ between GRE and EPI were also measured voxel by voxel and in selected regions of interest to test the consistency between the two acquisition methods. RESULTS: The quantifications of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ using EPI protocols showed increased test-retest reliability with higher EPI factors up to 5 as performed in the experiment and were consistent with those based on GRE. CONCLUSION: The result suggests that multishot multi-echo 3D EPI can be a useful alternative acquisition method for T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted MRI and quantification of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ and χ with reduced scan time, improved test-retest reliability, and similar accuracy compared with commonly used 3D GRE.

Quantifying cerebral microbleeds using quantitative susceptibility mapping from magnetization-prepared rapid gradient-echo.

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r2: 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B0 of 3 T or higher with no additional time cost, when standard T2*-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.

Longitudinal Associations of Magnetic Susceptibility with Clinical Severity in Parkinson's Disease.

BACKGROUND: Dementia is common in Parkinson's disease (PD), but there is wide variation in its timing. A critical gap in PD research is the lack of quantifiable markers of progression, and methods to identify early stages of dementia. Atrophy-based magnetic resonance imaging (MRI) has limited sensitivity in detecting or tracking changes relating to PD dementia, but quantitative susceptibility mapping (QSM), sensitive to brain tissue iron, shows potential for these purposes. OBJECTIVE: The objective of the paper is to study, for the first time, the longitudinal relationship between cognition and QSM in PD in detail. METHODS: We present a longitudinal study of clinical severity in PD using QSM, including 59 PD patients (without dementia at study onset), and 22 controls over 3 years. RESULTS: In PD, increased baseline susceptibility in the right temporal cortex, nucleus basalis of Meynert, and putamen was associated with greater cognitive severity after 3 years; and increased baseline susceptibility in basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was associated with greater motor severity after 3 years. Increased follow-up susceptibility in these regions was associated with increased follow-up cognitive and motor severity, with further involvement of hippocampus relating to cognitive severity. However, there were no consistent increases in susceptibility over 3 years. CONCLUSIONS: Our study suggests that QSM may predict changes in cognitive severity many months prior to overt cognitive involvement in PD. However, we did not find robust longitudinal changes in QSM over the course of the study. Additional tissue metrics may be required together with QSM for it to monitor progression in clinical practice and therapeutic trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Characterization of quantitative susceptibility mapping in the left ventricular myocardium.

BACKGROUND: Myocardial quantitative susceptibility mapping (QSM) may offer better specificity to iron than conventional T2* imaging in the assessment of cardiac diseases, including intra-myocardial hemorrhage. However, the precision and repeatability of cardiac QSM have not yet been characterized. The aim of this study is to characterize these key metrics in a healthy volunteer cohort and show the feasibility of the method in patients. METHODS: Free breathing respiratory-navigated multi-echo 3D gradient echo images were acquired, from which QSM maps were reconstructed using the Morphology Enhanced Dipole Inversion toolbox. This technique was first evaluated in a susceptibility phantom containing tubes with known concentrations of gadolinium. In vivo characterization of myocardial QSM was then performed in a cohort of 10 healthy volunteers where each subject was scanned twice. Mean segment susceptibility, precision (standard deviation of voxel magnetic susceptibilities within one segment), and repeatability (absolute difference in segment mean susceptibility between repeats) of QSM were calculated for each American Heart Association (AHA) myocardial segment. Finally, the feasibility of the method was shown in 10 patients, including four with hemorrhagic infarcts. RESULTS: The phantom experiment showed a strong linear relationship between measured and predicted susceptibility shifts (R2 > 0.99). For the healthy volunteer cohort, AHA segment analysis showed the mean segment susceptibility was 0.00 ± 0.02 ppm, the mean precision was 0.05 ± 0.04 ppm, and the mean repeatability was 0.02 ± 0.02 ppm. Cardiac QSM was successfully performed in all patients. Focal iron deposits were successfully visualized in the patients with hemorrhagic myocardial infarctions. CONCLUSION: The precision and repeatability of cardiac QSM were successfully characterized in phantom and in vivo experiments. The feasibility of the technique was also successfully demonstrated in patients. While challenges still remain, further clinical evaluation of the technique is now warranted. TRIAL REGISTRATION: This work does not report on a health care intervention.

Oxygen extraction fraction (OEF) values and applications in neurological diseases.

One of the goals of this systematic review is to provide a meta-analysis-derived mean OEF of healthy volunteers. Another aim of this study is to indicate the OEF ranges of various neurological pathologies. Potential clinical applications of OEF metrics are presented. Peer-reviewed studies reporting OEF metrics derived from computed tomography (CT)/positron emission tomography (PET) and/or magnetic resonance imaging (MRI) were considered. Databases utilized included MEDLINE, PubMed, EMBASE, Web of Science, and Google Scholar. The Newcastle-Ottawa scoring system was used for evaluating studies. R Studio was utilized for the meta-analysis calculations when appropriate. The GRADE framework was utilized to assess additional findings. Of 2267 potential studies, 165 met the inclusion criteria. The healthy volunteer meta-analysis included 339 subjects and found a mean OEF value of 38.87 (37.38, 40.36), with a prediction interval of 32.40-45.34. There were no statistical differences in OEF values derived from PET versus MRI. We provided a GRADE A certainty rating for the use of OEF metrics to predict stroke occurrence in patients with symptomatic carotid or cerebral vessel disease. We provided a GRADE B certainty rating for monitoring treatment response in Moyamoya disease. Use of OEF metrics in diagnosing and/or monitoring other conditions had a GRADE C certainty rating or less. OEF might have a role in diagnosing and monitoring patients with symptomatic carotid or cerebral vessel disease and Moyamoya disease. While we found insufficient evidence to support measuring OEF metrics in other patient populations, in many cases, further studies are warranted.

Affine transformation edited and refined deep neural network for quantitative susceptibility mapping.

Deep neural networks have demonstrated great potential in solving dipole inversion for Quantitative Susceptibility Mapping (QSM). However, the performances of most existing deep learning methods drastically degrade with mismatched sequence parameters such as acquisition orientation and spatial resolution. We propose an end-to-end AFfine Transformation Edited and Refined (AFTER) deep neural network for QSM, which is robust against arbitrary acquisition orientation and spatial resolution up to 0.6 mm isotropic at the finest. The AFTER-QSM neural network starts with a forward affine transformation layer, followed by a Unet for dipole inversion, then an inverse affine transformation layer, followed by a Residual Dense Network (RDN) for QSM refinement. Simulation and in-vivo experiments demonstrated that the proposed AFTER-QSM network architecture had excellent generalizability. It can successfully reconstruct susceptibility maps from highly oblique and anisotropic scans, leading to the best image quality assessments in simulation tests and suppressed streaking artifacts and noise levels for in-vivo experiments compared with other methods. Furthermore, ablation studies showed that the RDN refinement network significantly reduced image blurring and susceptibility underestimation due to affine transformations. In addition, the AFTER-QSM network substantially shortened the reconstruction time from minutes using conventional methods to only a few seconds.

APART-QSM: An improved sub-voxel quantitative susceptibility mapping for susceptibility source separation using an iterative data fitting method.

The brain tissue phase contrast in MRI sequences reflects the spatial distributions of multiple substances, such as iron, myelin, calcium, and proteins. These substances with paramagnetic and diamagnetic susceptibilities often colocalize in one voxel in brain regions. Both opposing susceptibilities play vital roles in brain development and neurodegenerative diseases. Conventional QSM methods only provide voxel-averaged susceptibility value and cannot disentangle intravoxel susceptibilities with opposite signs. Advanced susceptibility imaging methods have been recently developed to distinguish the contributions of opposing susceptibility sources for QSM. The basic concept of separating paramagnetic and diamagnetic susceptibility proportions is to include the relaxation rate R2* with R2' in QSM. The magnitude decay kernel, describing the proportionality coefficient between R2' and susceptibility, is an essential reconstruction coefficient for QSM separation methods. In this study, we proposed a more comprehensive complex signal model that describes the relationship between 3D GRE signal and the contributions of paramagnetic and diamagnetic susceptibility to the frequency shift and R2* relaxation. The algorithm is implemented as a constrained minimization problem in which the voxel-wise magnitude decay kernel and sub-voxel susceptibilities are determined alternately in each iteration until convergence. The calculated voxel-wise magnitude decay kernel could realistically model the relationship between the R2' relaxation and the volume susceptibility. Thus, the proposed method effectively prevents the errors of the magnitude decay kernel from propagating to the final susceptibility separation reconstruction. Phantom studies, ex vivo macaque brain experiments, and in vivo human brain imaging studies were conducted to evaluate the ability of the proposed method to distinguish paramagnetic and diamagnetic susceptibility sources. The results demonstrate that the proposed method provides state-of-the-art performances for quantifying brain iron and myelin compared to previous QSM separation methods. Our results show that the proposed method has the potential to simultaneously quantify whole brain iron and myelin during brain development and aging. The proposed model was also deployed with multiple-orientation complex GRE data input measurements, resulting in high-quality QSM separation maps with more faithful tissue delineation between brain structures compared to those reconstructed by single-orientation QSM separation methods.

Super-resolution QSM in little or no additional time for imaging (NATIve) using 2D EPI imaging in 3 orthogonal planes.

Quantitative Susceptibility Mapping has the potential to provide additional insights into neurological diseases but is typically based on a quite long (5-10 min) 3D gradient-echo scan which is highly sensitive to motion. We propose an ultra-fast acquisition based on three orthogonal (sagittal, coronal and axial) 2D simultaneous multi-slice EPI scans with 1 mm in-plane resolution and 3 mm thick slices. Images in each orientation are corrected for susceptibility-related distortions and co-registered with an iterative non-linear Minimum Deformation Averaging (Volgenmodel) approach to generate a high SNR, super-resolution data set with an isotropic resolution of close to 1 mm. The net acquisition time is 3 times the volume acquisition time of EPI or about 12 s, but the three volumes could also replace "dummy scans" in fMRI, making it feasible to acquire QSM in little or No Additional Time for Imaging (NATIve). NATIve QSM values agreed well with reference 3D GRE QSM in the basal ganglia in healthy subjects. In patients with multiple sclerosis, there was also a good agreement between the susceptibility values within lesions and control ROIs and all lesions which could be seen on 3D GRE QSMs could also be visualized on NATIve QSMs. The approach is faster than conventional 3D GRE by a factor of 25-50 and faster than 3D EPI by a factor of 3-5. As a 2D technique, NATIve QSM was shown to be much more robust to motion than the 3D GRE and 3D EPI, opening up the possibility of studying neurological diseases involving iron accumulation and demyelination in patients who find it difficult to lie still for long enough to acquire QSM data with conventional methods.

Comparison of quantitative susceptibility mapping methods for iron-sensitive susceptibility imaging at 7T: An evaluation in healthy subjects and patients with Huntington's disease.

Quantitative susceptibility mapping (QSM) is a promising tool for investigating iron dysregulation in neurodegenerative diseases, including Huntington's disease (HD). Many diverse methods have been proposed to generate accurate and robust QSM images. In this study, we evaluated the performance of different dipole inversion algorithms for iron-sensitive susceptibility imaging at 7T on healthy subjects of a large age range and patients with HD. We compared an iterative least-squares-based method (iLSQR), iterative methods that use regularization, single-step approaches, and deep learning-based techniques. Their performance was evaluated by comparing: (1) deviations from a multiple-orientation QSM reference; (2) visual appearance of QSM maps and the presence of artifacts; (3) susceptibility in subcortical brain regions with age; (4) regional brain susceptibility with published postmortem brain iron quantification; and (5) susceptibility in HD-affected basal ganglia regions between HD subjects and healthy controls. We found that single-step QSM methods with either total variation or total generalized variation constraints (SSTV/SSTGV) and the single-step deep learning method iQSM generally provided the best performance in terms of correlation with iron deposition and were better at differentiating between healthy controls and premanifest HD individuals, while deep learning QSM methods trained with multiple-orientation susceptibility data created QSM maps that were most similar to the multiple orientation reference and with the best visual scores.

Multimodal comparisons of QSM and PET in neurodegeneration and aging.

Quantitative susceptibility mapping (QSM) has been used to study susceptibility changes that may occur based on tissue composition and mineral deposition. Iron is a primary contributor to changes in magnetic susceptibility and of particular interest in applications of QSM to neurodegeneration and aging. Iron can contribute to neurodegeneration through inflammatory processes and via interaction with aggregation of disease-related proteins. To better understand the local susceptibility changes observed on QSM, its signal has been studied in association with other imaging metrics such as positron emission tomography (PET). The associations of QSM and PET may provide insight into the pathophysiology of disease processes, such as the role of iron in aging and neurodegeneration, and help to determine the diagnostic utility of QSM as an indirect indicator of disease processes typically evaluated with PET. In this review we discuss the proposed mechanisms and summarize prior studies of the associations of QSM and amyloid PET, tau PET, TSPO PET, FDG-PET, 15O-PET, and F-DOPA PET in evaluation of neurologic diseases with a focus on aging and neurodegeneration.

Data adaptive regularization with reference tissue constraints for liver quantitative susceptibility mapping.

PURPOSE: To improve repeatability and reproducibility across acquisition parameters and reduce bias in quantitative susceptibility mapping (QSM) of the liver, through development of an optimized regularized reconstruction algorithm for abdominal QSM. METHODS: An optimized approach to estimation of magnetic susceptibility distribution is formulated as a constrained reconstruction problem that incorporates estimates of the input data reliability and anatomical priors available from chemical shift-encoded imaging. The proposed data-adaptive method was evaluated with respect to bias, repeatability, and reproducibility in a patient population with a wide range of liver iron concentration (LIC). The proposed method was compared to the previously proposed and validated approach in liver QSM for two multi-echo spoiled gradient-recalled echo protocols with different acquisition parameters at 3T. Linear regression was used for evaluation of QSM methods against a reference FDA-approved R 2 $$ {R}_2 $$ -based LIC measure and R 2 ∗ $$ {R}_2^{\ast } $$ measurements; repeatability/reproducibility were assessed by Bland-Altman analysis. RESULTS: The data-adaptive method produced susceptibility maps with higher subjective quality due to reduced shading artifacts. For both acquisition protocols, higher linear correlation with both R 2 $$ {R}_2 $$ - and R 2 ∗ $$ {R}_2^{\ast } $$ -based measurements were observed for the data-adaptive method ( r 2 = 0 . 74 / 0 . 69 $$ {r}^2=0.74/0.69 $$ for R 2 $$ {R}_2 $$ , 0 . 97 / 0 . 95 $$ 0.97/0.95 $$ for R 2 ∗ $$ {R}_2^{\ast } $$ ) than the standard method ( r 2 = 0 . 60 / 0 . 66 $$ {r}^2=0.60/0.66 $$ and 0 . 79 / 0 . 88 $$ 0.79/0.88 $$ ). For both protocols, the data-adaptive method enabled better test-retest repeatability (repeatability coefficients 0.19/0.30 ppm for the data-adaptive method, 0.38/0.47 ppm for the standard method) and reproducibility across protocols (reproducibility coefficient 0.28 vs. 0.53ppm) than the standard method. CONCLUSIONS: The proposed data-adaptive QSM algorithm may enable quantification of LIC with improved repeatability/reproducibility across different acquisition parameters as 3T.

Investigating the effect of oblique image acquisition on the accuracy of QSM and a robust tilt correction method.

PURPOSE: Quantitative susceptibility mapping (QSM) is used increasingly for clinical research where oblique image acquisition is commonplace, but its effects on QSM accuracy are not well understood. THEORY AND METHODS: The QSM processing pipeline involves defining the unit magnetic dipole kernel, which requires knowledge of the direction of the main magnetic field B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ with respect to the acquired image volume axes. The direction of B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ is dependent on the axis and angle of rotation in oblique acquisition. Using both a numerical brain phantom and in vivo acquisitions in 5 healthy volunteers, we analyzed the effects of oblique acquisition on magnetic susceptibility maps. We compared three tilt-correction schemes at each step in the QSM pipeline: phase unwrapping, background field removal and susceptibility calculation, using the RMS error and QSM-tuned structural similarity index. RESULTS: Rotation of wrapped phase images gave severe artifacts. Background field removal with projection onto dipole fields gave the most accurate susceptibilities when the field map was first rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ . Laplacian boundary value and variable-kernel sophisticated harmonic artifact reduction for phase data background field removal methods gave accurate results without tilt correction. For susceptibility calculation, thresholded k-space division, iterative Tikhonov regularization, and weighted linear total variation regularization, all performed most accurately when local field maps were rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ before susceptibility calculation. CONCLUSION: For accurate QSM, oblique acquisition must be taken into account. Rotation of images into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ should be carried out after phase unwrapping and before background-field removal. We provide open-source tilt-correction code to incorporate easily into existing pipelines: https://github.com/o-snow/QSM_TiltCorrection.git.

Thin slab quantitative susceptibility mapping.

PURPOSE: Susceptibility maps reconstructed from thin slabs may suffer underestimation due to background-field removal imperfections near slab boundaries and the increased difficulty of solving a 3D-inversion problem with reduced support, particularly in the direction of the main magnetic field. Reliable QSM reconstruction from thin slabs would enable focal acquisitions in a much-reduced scan time. METHODS: This work proposes using additional rapid low-resolution data of extended spatial coverage to improve background-field estimation and regularize the inversion-to-susceptibility process for high resolution, thin slab data. The new method was tested using simulated and in-vivo brain data of high resolution (0.33 × 0.33 × 0.33 mm3 and 0.54 × 0.54 × 0.65 mm3 , respectively) at 3T, and compared to the standard large volume approach. RESULTS: Using the proposed method, in-vivo high-resolution QSM at 3T was obtained from slabs of width as small as 10.4 mm, aided by a lower-resolution dataset of 24 times coarser voxels. Simulations showed that the proposed method produced more consistent measurements from slabs of at least eight slices. Reducing the mean ROI error to 5% required the low-resolution data to cover ˜60 mm in the direction of the main field, have at least 2-mm isotropic resolution that is not coarser than the high-resolution data by more than four-fold in any direction. CONCLUSION: Applying the proposed method enabled focal QSM acquisitions at sub-millimeter resolution within reasonable acquisition time.