Quantitative susceptibility mapping (QSM) has enabled MRI of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols.

Purpose To assess the reproducibility of brain quantitative susceptibility mapping (QSM) in healthy subjects and in patients with multiple sclerosis (MS) on 1.5 and 3T scanners from two vendors. Materials and Methods Ten healthy volunteers and 10 patients were scanned twice on a 3T scanner from one vendor. The healthy volunteers were also scanned on a 1.5T scanner from the same vendor and on a 3T scanner from a second vendor. Similar imaging parameters were used for all scans. QSM images were reconstructed using a recently developed nonlinear morphology-enabled dipole inversion (MEDI) algorithm with L1 regularization. Region-of-interest (ROI) measurements were obtained for 20 major brain structures. Reproducibility was evaluated with voxel-wise and ROI-based Bland–Altman plots and linear correlation analysis. Results ROI-based QSM measurements showed excellent correlation between all repeated scans (correlation coefficient R ≥ 0.97), with a mean difference of less than 1.24 ppb (healthy subjects) and 4.15 ppb (patients), and 95% limits of agreements of within −25.5 to 25.0 ppb (healthy subjects) and −35.8 to 27.6 ppb (patients). Voxel-based QSM measurements had a good correlation (0.64 ≤ R ≤ 0.88) and limits of agreements of −60 to 60 ppb or less. Conclusion Brain QSM measurements have good interscanner and same-scanner reproducibility for healthy and MS subjects, respectively, on the systems evaluated in this study.

Purpose To develop and measure the reproducibility of 4-min whole brain myelin water fraction (MWF) mapping using fast acquisition with spiral trajectory and T2prep (FAST-T2) sequence at 3T. Methods Experiments were performed on phantoms, 13 volunteers, and 16 patients with multiple sclerosis. MWF maps were extracted using a spatially constrained non-linear algorithm. The proposed adiabatic modified BIR-4 (mBIR-4) T2prep was compared with the conventional composite T2prep (COMP). The effect of reducing the number of echo times (TEs) from 15 to 6 (reducing scan time from 10 to 4 min) was evaluated. Reproducibility was assessed using correlation analysis, coefficient of variation (COV), and Bland–Altman plots. Results Compared with COMP, mBIR-4 provided more accurate T2 in phantoms and better MWF maps in human brains. Reducing the number of TEs had a negligible effect on MWF map quality, with a regional MWF difference of <0.8%. Regional MWFs obtained by repeated scans showed excellent correlation (R = 0.99), low COV (1.3%–2.4%), and negligible bias within ±1% limits of agreement. On a voxel-wise basis, the agreement remained strong (correlation R = 0.89 ± 0.03, bias = 0.01% ± 0.29%, limits of agreement = [−3.35% ± 0.73%, 3.33% ± 0.61%]). Conclusion Whole brain MWF mapping with adiabatic FAST-T2 is feasible in 4 min and provides good intrasite reproducibility.

SUMMARY Prostate cancer (PC) is the most common non-cutaneous malignancy affecting men in North America. Despite significant efforts, conventional imaging of PC does not contribute to patient management as much as imaging performed for other common cancers. Given the lack of specificity in conventional imaging techniques, one possible solution is to screen for PC specific antigenic targets and generate agents able to specifically bind. Prostate specific membrane antigen (PSMA) is over-expressed in PC tissue, with low levels of expression in the small intestine, renal tubular cells and salivary gland. The first clinical agent for targeting PSMA was 111In-capromab, involving an antibody recognizing the internal domain of PSMA. The second- and third-generation humanized PSMA binding antibodies have the potential to overcome some of the limitations inherent to capromab pendetide i.e. inability to bind to live PC cells. One example is the humanized monoclonal antibody J591 (Hu mAb J591) that was developed primarily for therapeutic purposes but also has interesting imaging characteristics including the identification of bone metastases in PC. The major disadvantage of use of mAb for imaging is slow target recognition and background clearance in an appropriate timeframe for diagnostic imaging. Urea-based compounds such as small molecule inhibitors may also present promising agents for PC imaging with SPECT and PET. Two such small-molecule inhibitors targeting PSMA, MIP-1072 and MIP-1095, have exhibited high affinity for PSMA. The uptake of 123I-MIP-1072 and 123I-MIP-1095 in PC xenografts have imaged successfully with favorable properties amenable to human trials. While advances in conventional imaging will continue, Ab and small molecule imaging exemplified by PSMA targeting have the greatest potential to improve diagnostic sensitivity and specificity.

Purpose To demonstrate the phase and QSM patterns created by solid and shell spatial distributions of magnetic susceptibility in MS lesions. Materials and Methods Numerical simulations and experimental phantoms of solid- and shell-shaped magnetic susceptibility sources were used to generate magnitude, phase, and QSM images. Imaging of 20 consecutive MS patients was also reviewed for this IRB-approved MRI study to identify appearance of solid and shell lesions on phase and QSM images. Results Solid and shell susceptibility sources were correctly reconstructed in QSM images, while the corresponding phase images depicted both geometries with shell-like patterns, making the underlying susceptibility distribution difficult to determine using phase alone. In MS patients, of the 60 largest lesions identified on T2, 30 lesions were detected on both QSM and phase, of which 83% were solid and 17% were shells on QSM, and of which 30% were solid and 70% were shell on phase. Of the 21 shell-like lesions on phase, 76% appeared solid on QSM, 24% appeared shell on QSM. Of the five shell-like lesions on QSM, all were shell-like on phase. Conclusion QSM accurately depicts both solid and shell patterns of magnetic susceptibility, while phase imaging fails to distinguish them.

Background: Accurate measurement of the liver iron concentration (LIC) is needed to guide iron-chelating therapy for patients with transfusional iron overload. In this work, we investigate the feasibility of automated quantitative susceptibility mapping (QSM) to measure the LIC. Purpose: To develop a rapid, robust and automated liver QSM for clinical practice. Study Type: Prospective Population: 13 healthy subjects and 22 patients. Field strength/Sequences 1.5T and 3T / 3D multi-echo gradient-recalled echo (GRE) sequence. Assessment: Data were acquired using a 3D GRE sequence with an out-of-phase echo spacing with respect to each other. All odd echoes that were in-phase (IP) were used to initialize the fat-water separation and field estimation (T2*-IDEAL) before performing QSM. Liver QSM was generated through an automated pipeline without manual intervention. This IP echo-based initialization method was compared with an existing graph cuts initialization method (SPURS) in healthy subjects (n=5). Reproducibility was assessed over 4 scanners at 2 field strengths from 2 manufacturers using healthy subjects (n=8). Clinical feasibility was evaluated in patients (n=22). Statistical Tests: IP and SPURS initialization methods in both healthy subjects and patients were compared using paired t-test and linear regression analysis to assess processing time and ROI measurements. Reproducibility of QSM, R2*, and proton density fat fraction (PDFF) among the four different scanners was assessed using linear regression, Bland-Altman analysis, and the intraclass correlation coefficient (ICC). Results: Liver QSM using the IP method was found to be approximately 5.5 times faster than SPURS (P< 0.05) in initializing T2*-IDEAL with similar outputs. Liver QSM using the IP method were reproducibly generated in all four scanners (average coefficient of determination 0.95, average slope 0.90, average bias 0.002 ppm, 95% limits of agreement between −0.06 to 0.07 ppm, ICC 0.97). Conclusion: Use of IP echo-based initialization, enables robust water/fat separation and field estimation for automated, rapid and reproducible liver QSM for clinical applications.

1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1281-1287.

Purpose To determine the reproducibility of quantitative susceptibility mapping at multiple sites on clinical and preclinical scanners (1.5 T, 3 T, 7 T, and 9.4 T) from different vendors (Siemens, GE, Philips, and Bruker) for standardization of multicenter studies. Methods Seven phantoms distributed from the core site, each containing 5 compartments with gadolinium solutions with fixed concentrations between 0.625 mM and 10 mM. Multi‐echo gradient echo scans were performed at 1.5 T, 3 T, 7 T, and 9.4 T on 12 clinical and 3 preclinical scanners. DICOM images from the scans were processed into quantitative susceptibility maps using the Laplacian boundary value (LBV) and MEDI+0 automatic uniform reference algorithm. Region of interest (ROI) analyses were performed by a physicist to determine agreement between results from all sites. Measurement reproducibility was assessed using regression, Bland‐Altman plots, and the intra‐class correlation coefficient (ICC). Results Quantitative susceptibility mapping (QSM) from all scanners had similar, artifact‐free visual appearance. Regression analysis showed a linear relationship between gadolinium concentrations and average QSM measurements for all phantoms (y = 350x – 0.0346, r2>0.99). The SD of measurements increased almost linearly from 32 ppb to 230 ppb as the measured susceptibility increased from 0.26 ppm to 3.56 ppm. A Bland‐Altman plot showed the bias, upper, and lower limits of agreement for all comparisons were −10, −210, and 200 ppb, respectively. The ICC was 0.991 with a 95% CI (0.973, 0.99). Conclusions QSM shows excellent multicenter reproducibility for a large range of susceptibility values encountered in cranial and extra‐cranial applications on a diverse set of scanner platforms.