Quantitative susceptibility mapping (QSM), one of the advanced MRI techniques for evaluating magnetic susceptibility, offers precise quantitative measurements of spatial distributions of magnetic susceptibility. Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and is a substance-specific value. Recently, QSM has been widely used to estimate various levels of substances in the brain, including iron, hemosiderin, and deoxyhemoglobin (paramagnetism), as well as calcification (diamagnetism). By visualizing iron distribution in the brain, it is possible to identify anatomic structures that are not evident on conventional images and to evaluate various neurodegenerative diseases. It has been challenging to apply QSM in areas outside the brain because of motion artifacts from respiration and heartbeats, as well as the presence of fat, which has a different frequency to the proton. In this review, the authors provide a brief overview of the theoretical background and analyze methods of converting MRI phase images to QSM. Moreover, we provide an overview of the current clinical applications of QSM. Online supplemental material is available for this article. ©RSNA, 2022.

Quantitative Susceptibility Mapping: Basic Methods and Clinical Applications.

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.

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

Purpose To develop a nonlinear preconditioned total field-inversion algorithm using the MEDI toolbox (MEDInpt) for robust QSM of carotid plaques and evaluate its performance in comparison with a local field-inversion algorithm (STI Suite) previously applied to carotid QSM. Methods Numerical simulation and in vivo carotid QSM were performed to compare the MEDInpt and STI Suite algorithms. Multicontrast MRI was used as the reference standard for detecting calcified plaque and intraplaque hemorrhage (IPH). A total of 5 healthy volunteers and 11 patients with at least one significant carotid artery stenosis were enrolled in this study. Results In the numerical carotid phantom, the relative susceptibility errors for calcified plaque and IPH were reduced from -63.2% and -56.5% with STI Suite to -13.0% and -24.2% with MEDInpt, respectively. In humans, MEDInpt provided a higher QSM quality score and better detection of calcification and IPH than STI Suite. Although all calcifications and IPHs detected on multicontrast MRI could be seen on QSM obtained with MEDInpt, only 50% of calcified plaques and 83% of IPHs could be captured on QSM obtained with STI Suite. Conclusion MEDInpt can resolve calcification and IPH in advanced atherosclerotic carotid plaques. Compared with STI Suite, MEDInpt provided better QSM quality and has the potential to improve the detection of these plaque components.

Quantitative susceptibility mapping of carotid plaques using nonlinear total field inversion: Initial experience in patients with significant carotid stenosis.

OBJECTIVES The aim of this study was to assess the accuracy, reliability, and cerebral microbleed (CMB) detection performance of 2-minute quantitative susceptibility mapping (QSM) from 3-dimensional echo-planar imaging (3D-EPI). MATERIALS AND METHODS Gadolinium phantom study was conducted using 3D-EPI, single-echo time (TE), and multi-TE gradient-recalled echo (GRE) sequences on two 3-T magnetic resonance (MR) scanners to assess the accuracy between measured and theoretical susceptibility values. The institutional review board approved this prospective study, and 40 healthy volunteers were enrolled with written consent between April 2018 and October 2019. Each underwent 3D-EPI, single-TE, and multi-TE GRE sequences consecutively on one 3-T MR scanner, and QSMs were calculated to assess the reliability of 3D-EPI QSM. Intraclass correlation coefficient (ICC), linear regression, and Bland-Altman plots were calculated. Patients with CMB who underwent both 3D-EPI and GRE QSM scans were retrospectively enrolled. Two radiologists evaluated images independently, and Cohen κ coefficients were calculated to compare CMB detection performance. RESULTS Phantom study showed excellent validity of 3D-EPI QSM on both MR scanners: Skyra, R2 = 0.996, P < 0.001, ICC = 0.997, mean difference, -2 ppb (95% confidence interval [CI], -45 to 40 ppb); Prisma, R2 = 0.992, P < 0.001, ICC = 0.988, mean difference, 15 ppb (95% CI, -67 to 97 ppb). A human study of 40 healthy volunteers (59 ± 13 years, 25 women) showed excellent reliability with 3D-EPI QSM for both single-TE and multi-TE GRE (R2 = 0.981, P < 0.001, ICC = 0.988; R2 = 0.983, P < 0.001, ICC = 0.990, respectively), supported by a Bland-Altman mean difference of 4 ppb (95% CI, -15 to 23 ppb) for single-TE GRE and 3 ppb (95% CI, -15 to 20 ppb) for multi-TE GRE. The CMB detection performance evaluation from 38 patients (51 ± 20 years, 20 women) showed almost perfect agreement between 3D-EPI and GRE QSM for both raters (κ = 0.923 and 0.942, P < 0.001). CONCLUSIONS Faster QSM from 3D-EPI demonstrated excellent accuracy, reliability, and CMB detection performance.

Two-Minute Quantitative Susceptibility Mapping From Three-Dimensional Echo-Planar Imaging: Accuracy, Reliability, and Detection Performance in Patients With Cerebral Microbleeds.

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.

NeuroImaging of Parkinson's disease by Quantitative Susceptibility Mapping

Quantitative susceptibility-weighted imaging in presence of strong susceptibility sources: Application to hemorrhage.

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.

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

T2 Mapping in Hemorrhagic and Ischemic Stroke using Standard Clinical Images

Background: Quantitative susceptibility mapping (QSM) offers a means to track iron evolution in hemorrhage. However, standard QSM sequences have long acquisition times and are prone to motion artifact in hemorrhagic patients. Purpose: To minimize motion artifact and acquisition time by performing rapid QSM in intracerebral hemorrhage (ICH) using single-shot echo planar imaging (EPI). Study Type: Prospective method evaluation. Population/Subjects: Forty-five hemorrhages were analyzed from 35 MRI exams obtained between February 2016 and March 2019 from 27 patients (14 male / 13 female, age: 71 ± 12 years) with confirmed primary ICH. Field Strength/Sequence: 3T; susceptibility-weighted imaging (SWI) with 4.54-minute acquisition and 2D single-shot gradient EPI with 0.45-minute acquisition. Assessment: Susceptibility maps were constructed from both methods. Measurement of ICH area and mean magnetic susceptibility were made manually by three independent observers. Motion artifacts were quantified using the magnitude signal ratio of artifact-to-brain tissue to classify into three categories: mild or no artifact, moderate artifact, or severe artifact. The cutoff for each category was determined by four observers. Statistical Tests: Pearson's correlation coefficient and paired t-test using α = 0.05 were used to compare results. Inter- and intraclass correlation was used to assess observer variability. Results: Using 45 hemorrhages, the ICH regions measured on susceptibility maps obtained from EPI and SWI sequences had high correlation coefficients for area (R ≥ 0.97) and mean magnetic susceptibility (R ≥ 0.93) for all observers. The artifact-to-tissue ratio was significantly higher (P < 0.01) for SWI vs. EPI, and the standard deviation for the SWI method (SD = 0.05) was much larger than EPI (SD = 0.01). All observers' measurements showed high agreement. Data Conclusion: Single-shot EPI-QSM enabled rapid measurement of ICH area and mean magnetic susceptibility, with reduced motion as compared with more standard SWI. EPI-QSM requires minimal additional acquisition time and could be incorporated into iron tracking studies in ICH. Level of Evidence: 2. Technical Efficacy Stage: 1. J. Magn. Reson. Imaging 2019.

Rapid quantitative susceptibility mapping of intracerebral hemorrhage.

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Quantitative susceptibility-weighted imaging in presence of strong susceptibility sources: Application to hemorrhage.

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

T2 Mapping in Hemorrhagic and Ischemic Stroke using Standard Clinical Images

Rapid quantitative susceptibility mapping of intracerebral hemorrhage.