Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

Decreased brain iron deposition based on quantitative susceptibility mapping correlates with reduced neurodevelopmental status in children with autism spectrum disorder.

To investigate potential correlations between the susceptibility values of certain brain regions and the severity of disease or neurodevelopmental status in children with autism spectrum disorder (ASD), 18 ASD children and 15 healthy controls (HCs) were recruited. The neurodevelopmental status was assessed by the Gesell Developmental Schedules (GDS) and the severity of the disease was evaluated by the Autism Behavior Checklist (ABC). Eleven brain regions were selected as regions of interest and the susceptibility values were measured by quantitative susceptibility mapping. To evaluate the diagnostic capacity of susceptibility values in distinguishing ASD and HC, the receiver operating characteristic (ROC) curve was computed. Pearson and Spearman partial correlation analysis were used to depict the correlations between the susceptibility values, the ABC scores, and the GDS scores in the ASD group. ROC curves showed that the susceptibility values of the left and right frontal white matter had a larger area under the curve in the ASD group. The susceptibility value of the right globus pallidus was positively correlated with the GDS-fine motor scale score. These findings indicated that the susceptibility value of the right globus pallidus might be a viable imaging biomarker for evaluating the neurodevelopmental status of ASD children.

Direct comparison between 18F-Flortaucipir tau PET and quantitative susceptibility mapping in progressive supranuclear palsy.

PURPOSE: The pattern of flortaucipir tau PET uptake is topographically similar to the pattern of magnetic susceptibility in progressive supranuclear palsy (PSP); both with increased signal in subcortical structures such as the basal ganglia and midbrain, suggesting that they may be closely related. However, their relationship remains unknown since no studies have directly compared these two modalities in the same PSP cohort. We hypothesized that some flortaucipir uptake in PSP is associated with magnetic susceptibility, and hence iron deposition. The aim of this study was to evaluate the regional relationship between flortaucipir uptake and magnetic susceptibility and to examine the effects of susceptibility on flortaucipir uptake in PSP. METHODS: Fifty PSP patients and 67 cognitively normal controls were prospectively recruited and underwent three Tesla MRI and flortaucipir tau PET scans. Quantitative susceptibility maps were reconstructed from multi-echo gradient-echo MRI images. Region of interest (ROI) analysis was performed to obtain flortaucipir and susceptibility values in the subcortical regions. Relationships between flortaucipir and susceptibility signals were evaluated using partial correlation analysis in the subcortical ROIs and voxel-based analysis in the whole brain. The effects of susceptibility on flortaucipir uptake were examined by using the framework of mediation analysis. RESULTS: Both flortaucipir and susceptibility were greater in PSP compared to controls in the putamen, pallidum, subthalamic nucleus, red nucleus, and cerebellar dentate (p<0.05). The ROI-based and voxel-based analyses showed that these two signals were positively correlated in these five regions (r = 0.36-0.59, p<0.05). Mediation analysis showed that greater flortaucipir uptake was partially explained by susceptibility in the putamen, pallidum, subthalamic nucleus, and red nucleus, and fully explained in the cerebellar dentate. CONCLUSIONS: These results suggest that some of the flortaucipir uptake in subcortical regions in PSP is related to iron deposition. These findings will contribute to our understanding of the mechanisms underlying flortaucipir tau PET findings in PSP and other neurodegenerative diseases.

Neuroimaging of Parkinson's disease by quantitative susceptibility mapping.

Parkinson's disease (PD) is a common neurodegenerative disease, and apart from a few rare genetic causes, its pathogenesis remains largely unclear. Recent scientific interest has been captured by the involvement of iron biochemistry and the disruption of iron homeostasis, particularly within the brain regions specifically affected in PD. The advent of Quantitative Susceptibility Mapping (QSM) has enabled non-invasive quantification of brain iron in vivo by MRI, which has contributed to the understanding of iron-associated pathogenesis and has the potential for the development of iron-based biomarkers in PD. This review elucidates the biochemical underpinnings of brain iron accumulation, details advancements in iron-sensitive MRI technologies, and discusses the role of QSM as a biomarker of iron deposition in PD. Despite considerable progress, several challenges impede its clinical application after a decade of QSM studies. The initiation of multi-site research is warranted for developing robust, interpretable, and disease-specific biomarkers for monitoring PD disease progression.

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.

SIPAS: A comprehensive susceptibility imaging process and analysis studio.

Quantitative susceptibility mapping (QSM) is a rising MRI-based technology and quite a few QSM-related algorithms have been proposed to reconstruct maps of tissue susceptibility distribution from phase images. In this paper, we develop a comprehensive susceptibility imaging process and analysis studio (SIPAS) that can accomplish reliable QSM processing and offer a standardized evaluation system. Specifically, SIPAS integrates multiple methods for each step, enabling users to select algorithm combinations according to data conditions, and QSM maps could be evaluated by two aspects, including image quality indicators within all voxels and region-of-interest (ROI) analysis. Through a sophisticated design of user-friendly interfaces, the results of each procedure are able to be exhibited in axial, coronal, and sagittal views in real-time, meanwhile ROIs can be displayed in 3D rendering visualization. The accuracy and compatibility of SIPAS are demonstrated by experiments on multiple in vivo human brain datasets acquired from 3T, 5T, and 7T MRI scanners of different manufacturers. We also validate the QSM maps obtained by various algorithm combinations in SIPAS, among which the combination of iRSHARP and SFCR achieves the best results on its evaluation system. SIPAS is a comprehensive, sophisticated, and reliable toolkit that may prompt the QSM application in scientific research and clinical practice.

Quantitative susceptibility mapping for susceptibility source separation with adaptive relaxometric constant estimation (QSM-ARCS) from solely gradient-echo data.

To separate the contributions of paramagnetic and diamagnetic sources within a voxel, a magnetic susceptibility source separation method based solely on gradient-echo data has been developed. To measure the opposing susceptibility sources more accurately, we propose a novel single-orientation quantitative susceptibility mapping method with adaptive relaxometric constant estimation (QSM-ARCS) for susceptibility source separation. Moreover, opposing susceptibilities and their anisotropic effects were determined in healthy volunteers in the white matter. Multiple spoiled gradient echo and diffusion tensor imaging of ten healthy volunteers was obtained using a 3 T magnetic resonance scanner. After the opposing susceptibility and fractional anisotropy (FA) maps had been reconstructed, the parametric maps were spatially normalized. To evaluate the agreements of QSM-ARCS against the susceptibility source separation method using R2 and R2* maps (χ-separation) by Bland-Altman plots, the opposing susceptibility values were measured using white and deep gray matter atlases. We then evaluated the relationships between the opposing susceptibilities and FAs in the white matter and used a field-to-fiber angle to assess the fiber orientation dependencies of the opposing susceptibilities. The susceptibility maps in QSM-ARCS were successfully reconstructed without large artifacts. In the Bland-Altman analyses, the opposing QSM-ARCS susceptibility values excellently agreed with the χ-separation maps. Significant inverse and proportional correlations were observed between FA and the negative and positive susceptibilities estimated by QSM-ARCS. The fiber orientation dependencies of the negative susceptibility represented a nonmonotonic feature. Conversely, the positive susceptibility increased linearly with the fiber angle with respect to the B0 field. The QSM-ARCS could accurately estimate the opposing susceptibilities, which were identical values of χ-separation, even using gradient echo alone. The opposing susceptibilities might offer direct biomarkers for assessment of the myelin and iron content in glial cells and, through the underlying magnetic sources, provide biologic insights toward clinical transition.

Exploring cognitive related microstructural alterations in normal appearing white matter and deep grey matter for small vessel disease: A quantitative susceptibility mapping study.

Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.

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.

Associations of quantitative susceptibility mapping with cortical atrophy and brain connectome in Alzheimer's disease: A multi-parametric study.

Aberrant susceptibility due to iron level abnormality and brain network disconnections are observed in Alzheimer's disease (AD), with disrupted iron homeostasis hypothesized to be linked to AD pathology and neuronal loss. However, whether associations exist between abnormal quantitative susceptibility mapping (QSM), brain atrophy, and altered brain connectome in AD remains unclear. Based on multi-parametric brain imaging data from 30 AD patients and 26 healthy controls enrolled at the China-Japan Friendship Hospital, we investigated the abnormality of the QSM signal and volumetric measure across 246 brain regions in AD patients. The structural and functional connectomes were constructed based on diffusion MRI tractography and functional connectivity, respectively. The network topology was quantified using graph theory analyses. We identified seven brain regions with both reduced cortical thickness and abnormal QSM (p < 0.05) in AD, including the right superior frontal gyrus, left superior temporal gyrus, right fusiform gyrus, left superior parietal lobule, right superior parietal lobule, left inferior parietal lobule, and left precuneus. Correlations between cortical thickness and network topology computed across patients in the AD group resulted in statistically significant correlations in five of these regions, with higher correlations in functional compared to structural topology. We computed the correlation between network topological metrics, QSM value and cortical thickness across regions at both individual and group-averaged levels, resulting in a measure we call spatial correlations. We found a decrease in the spatial correlation of QSM and the global efficiency of the structural network in AD patients at the individual level. These findings may provide insights into the complex relationships among QSM, brain atrophy, and brain connectome in AD.

Quantitative susceptibility mapping of multiple system atrophy and Parkinson's disease correlates with neurotransmitter reference maps.

BACKGROUND: Multiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and impaired neurochemical transmission. Considering the critical role of iron in neurotransmitter synthesis and transport, our study aims to identify distinct patterns of whole-brain iron accumulation in MSA and PD, and to elucidate the corresponding neurochemical substrates. METHODS: A total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity. RESULTS: MSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits. CONCLUSIONS: Our findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspires research on potential targets for pharmacotherapy.

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.

Maximum spherical mean value filtering for whole-brain QSM.

PURPOSE: To develop a tissue field-filtering algorithm, called maximum spherical mean value (mSMV), for reducing shadow artifacts in QSM of the brain without requiring brain-tissue erosion. THEORY AND METHODS: Residual background field is a major source of shadow artifacts in QSM. The mSMV algorithm filters large field-magnitude values near the border, where the maximum value of the harmonic background field is located. The effectiveness of mSMV for artifact removal was evaluated by comparing existing QSM algorithms in numerical brain simulation as well as using in vivo human data acquired from 11 healthy volunteers and 93 patients. RESULTS: Numerical simulation showed that mSMV reduces shadow artifacts and improves QSM accuracy. Better shadow reduction, as demonstrated by lower QSM variation in the gray matter and higher QSM image quality score, was also observed in healthy subjects and in patients with hemorrhages, stroke, and multiple sclerosis. CONCLUSION: The mSMV algorithm allows QSM maps that are substantially equivalent to those obtained using SMV-filtered dipole inversion without eroding the volume of interest.

Recommended implementation of quantitative susceptibility mapping for clinical research in the brain: A consensus of the ISMRM electro-magnetic tissue properties study group.

This article provides recommendations for implementing QSM for clinical brain research. It is a consensus of the International Society of Magnetic Resonance in Medicine, Electro-Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available have generated a need in the neuroimaging community for guidelines on implementation. This article outlines considerations and implementation recommendations for QSM data acquisition, processing, analysis, and publication. We recommend that data be acquired using a monopolar 3D multi-echo gradient echo (GRE) sequence and that phase images be saved and exported in Digital Imaging and Communications in Medicine (DICOM) format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background field removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields within the brain mask should be removed using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity-based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of the whole brain as a region of interest in the analysis. The minimum acquisition and processing details required when reporting QSM results are also provided. These recommendations should facilitate clinical QSM research and promote harmonized data acquisition, analysis, and reporting.

Assessment for Carotid Atherosclerotic Plaque Using Vessel Wall Magnetic Resonance Imaging: A Multireader ROC Study to Determine Optimal Sequence for Detecting Vessel Wall Calcification.

INTRODUCTION: We aimed to compare conventional vessel wall MR imaging techniques and quantitative susceptibility mapping (QSM) to determine the optimal sequence for detecting carotid artery calcification. METHODS: Twenty-two patients who underwent carotid vessel wall MR imaging and neck CT were enrolled. Four slices of 6-mm sections from the bilateral internal carotid bifurcation were subdivided into 4 segments according to clock position (0-3, 3-6, 6-9, and 9-12) and assessed for calcification. Two blinded radiologists independently reviewed a total of 704 segments and scored the likelihood of calcification using a 5-point scale on spin-echo imaging, FLASH, and QSM. The observer performance for detecting calcification was evaluated by a multireader, multiple-case receiver operating characteristic study. Weighted κ statistics were calculated to assess interobserver agreement. RESULTS: QSM had a mean area under the receiver operating characteristic curve of 0.85, which was significantly higher than that of any other sequence (p < 0.01) and showed substantial interreader agreement (κ = 0.68). A segment with a score of 3-5 was defined as positive, and a segment with a score of 1-2 was defined as negative; the sensitivity and specificity of QSM were 0.75 and 0.87, respectively. CONCLUSION: QSM was the most reliable MR sequence for the detection of plaque calcification.

ComBating inter-site differences in field strength: harmonizing preclinical traumatic brain injury MRI data.

Integrating datasets from multiple sites and scanners can increase statistical power for neuroimaging studies but can also introduce significant inter-site confounds. We evaluated the effectiveness of ComBat, an empirical Bayes approach, to combine longitudinal preclinical MRI data acquired at 4.7 or 9.4 T at two different sites in Australia. Male Sprague Dawley rats underwent MRI on Days 2, 9, 28, and 150 following moderate/severe traumatic brain injury (TBI) or sham injury as part of Project 1 of the NIH/NINDS-funded Centre Without Walls EpiBioS4Rx project. Diffusion-weighted and multiple-gradient-echo images were acquired, and outcomes included QSM, FA, and ADC. Acute injury measures including apnea and self-righting reflex were consistent between sites. Mixed-effect analysis of ipsilateral and contralateral corpus callosum (CC) summary values revealed a significant effect of site on FA and ADC values, which was removed following ComBat harmonization. Bland-Altman plots for each metric showed reduced variability across sites following ComBat harmonization, including for QSM, despite appearing to be largely unaffected by inter-site differences and no effect of site observed. Following harmonization, the combined inter-site data revealed significant differences in the imaging metrics consistent with previously reported outcomes. TBI resulted in significantly reduced FA and increased susceptibility in the ipsilateral CC, and significantly reduced FA in the contralateral CC compared with sham-injured rats. Additionally, TBI rats also exhibited a reversal in ipsilateral CC ADC values over time with significantly reduced ADC at Day 9, followed by increased ADC 150 days after injury. Our findings demonstrate the need for harmonizing multi-site preclinical MRI data and show that this can be successfully achieved using ComBat while preserving phenotypical changes due to TBI.

Simultaneous time-of-flight MR angiography and quantitative susceptibility mapping with key time-of-flight features.

A technique for combined time-of-flight (TOF) MR angiography (MRA) and quantitative susceptibility mapping (QSM) was developed with key features of standard three-dimensional (3D) TOF acquisitions, including multiple overlapping thin slab acquisition (MOTSA), ramped RF excitation, and venous saturation. The developed triple-echo 3D TOF-QSM sequence enabled TOF-MRA, susceptibility-weighted imaging (SWI), QSM, and R2* mapping. The effects of ramped RF, resolution, flip angle, venous saturation, and MOTSA were studied on QSM. Six volunteers were scanned at 3 T with the developed sequence, conventional TOF-MRA, and conventional SWI. Quantitative comparison of susceptibility values on QSM and normalized arterial and venous vessel-to-background contrasts on TOF and SWI were performed. The ramped RF excitation created an inherent phase variation in the raw phase. A generic correction factor was computed to remove the phase variation to obtain QSM without artifacts from the TOF-QSM sequence. No statistically significant difference was observed between the developed and standard QSM sequence for susceptibility values. However, maintaining standard TOF features led to compromises in signal-to-noise ratio for QSM and SWI, arising from the use of MOTSA rather than one large 3D slab, higher TOF spatial resolution, increased TOF background suppression due to larger flip angles, and reduced venous signal from venous saturation. In terms of vessel contrast, veins showed higher normalized contrast on SWI derived from TOF-QSM than the standard SWI sequence. While fast flowing arteries had reduced contrast compared with standard TOF-MRA, no statistical difference was observed for slow flowing arteries. Arterial contrast differences largely arise from the longer TR used in TOF-QSM over standard TOF-MRA to accommodate additional later echoes for SWI. In conclusion, although the sequence has a longer TR and slightly lower arterial contrast, provided an adequate correction is made for ramped RF excitation effects on phase, QSM may be performed from a multiecho sequence that includes all key TOF features, thus enabling simultaneous TOF-MRA, SWI, QSM, and R2* map computation.

Comparison of three magnetic resonance imaging measures of brain iron in healthy and cocaine use disorder participants.

Several magnetic resonance imaging (MRI) measures for quantifying endogenous nonheme brain iron have been proposed. These correspond to distinct physical properties with varying sensitivities and specificities to iron. Moreover, they may depend not only on tissue iron concentration, but also on the intravoxel spatial pattern of iron deposition, which is complex in many brain regions. Here, the three MRI brain iron measures of R 2 * , magnetic field correlation (MFC), and magnetic susceptibility are compared in several deep gray matter regions for both healthy participants (HPs) and individuals with cocaine use disorder (CUD). Their concordance is assessed from their correlations with each other and their relative dependencies on age. In addition, associations between the iron measures and microstructure in adjacent white matter regions are investigated by calculating their correlations with diffusion MRI measures from the internal capsule, and associations with cognition are determined by using results from a battery of standardized tests relevant to CUD. It is found that all three iron measures are strongly correlated with each other for the considered gray matter regions, but with correlation coefficients substantially less than one indicating important differences. The age dependencies of all three measures are qualitatively similar in most regions, except for the red nucleus, where the susceptibility has a significantly stronger correlation with age than R 2 * . Weak to moderate correlations are seen for the iron measures with several of the diffusion and cognitive measures, with the strongest correlations being obtained for R 2 * . The iron measures differ little between the HP and CUD groups, although susceptibility is significantly lower in the red nucleus for the CUD group. For the comparisons made, the iron measures behave similarly in most respects, but with notable quantitative differences. It is suggested that these differences may be, in part, attributable to a higher sensitivity to the spatial pattern of iron deposition for R 2 * and MFC than for susceptibility. This is supported most strongly by a sharp contrast between the values of the iron measures in the globus pallidus relative to those in the red nucleus. The observed correlations of the iron measures with diffusion and cognitive scores point to possible connections between gray matter iron, white matter microstructure, and cognition.

Evaluation of gadolinium deposition in cortical bone using three-dimensional ultrashort echo time quantitative susceptibility mapping: A preliminary study.

The aim of the current study was to investigate the feasibility of three-dimensional ultrashort echo time quantitative susceptibility mapping (3D UTE-QSM) for the assessment of gadolinium (Gd) deposition in cortical bone. To this end, 40 tibial bovine cortical bone specimens were divided into five groups then soaked in phosphate-buffered saline (PBS) solutions with five different Gd concentrations of 0, 0.4, 0.8, 1.2, and 1.6 mmol/L for 48 h. Additionally, eight rabbits were randomly allocated into three groups, consisting of a normal-dose macrocyclic gadolinium-based contrast agent (GBCA) group (n = 3), a high-dose macrocyclic GBCA group (n = 3), and a control group (n = 2). All bovine and rabbit tibial bone samples underwent magnetic resonance imaging (MRI) on a 3-T clinical MR system. A 3D UTE-Cones sequence was utilized to acquire images with five different echo times (i.e., 0.032, 0.2, 0.4, 0.8, and 1.2 ms). The UTE images were subsequently processed with the morphology-enabled dipole inversion algorithm to yield a susceptibility map. The average susceptibility was calculated in three regions of interest in the middle of each specimen, and the Pearson's correlation between the estimated susceptibility and Gd concentration was calculated. The bone samples soaked in PBS with higher Gd concentrations exhibited elevated susceptibility values. A mean susceptibility value of -2.47 ± 0.23 ppm was observed for bovine bone soaked in regular PBS, while the mean QSM value increased to -1.75 ± 0.24 ppm for bone soaked in PBS with the highest Gd concentration of 1.6 mmol/L. A strong positive correlation was observed between Gd concentrations and QSM values. The mean susceptibility values of rabbit tibial specimens in the control group, normal-dose GBCA group, and high-dose GBCA group were -4.11 ± 1.52, -3.85 ± 1.33, and -3.39 ± 1.35 ppm, respectively. In conclusion, a significant linear correlation between Gd in cortical bone and QSM values was observed. The preliminary results suggest that 3D UTE-QSM may provide sensitive noninvasive assessment of Gd deposition in cortical bone.

The Larmor frequency shift of a white matter magnetic microstructure model with multiple sources.

Magnetic susceptibility imaging may provide valuable information about chemical composition and microstructural organization of tissue. However, its estimation from the MRI signal phase is particularly difficult as it is sensitive to magnetic tissue properties ranging from the molecular to the macroscopic scale. The MRI Larmor frequency shift measured in white matter (WM) tissue depends on the myelinated axons and other magnetizable sources such as iron-filled ferritin. We have previously derived the Larmor frequency shift arising from a dense medium of cylinders with scalar susceptibility and arbitrary orientation dispersion. Here, we extend our model to include microscopic WM susceptibility anisotropy as well as spherical inclusions with scalar susceptibility to represent subcellular structures, biologically stored iron, and so forth. We validate our analytical results with computer simulations and investigate the feasibility of estimating susceptibility using simple iterative linear least squares without regularization or preconditioning. This is done in a digital brain phantom synthesized from diffusion MRI measurements of an ex vivo mouse brain at ultra-high field.