Mitigating the impact of flip angle and orientation dependence in single compartment R2* estimates via 2-pool modeling.

PURPOSE: The effective transverse relaxation rate ( R 2 * $$ {\mathrm{R}}_2^{\ast } $$ ) is influenced by biological features that make it a useful means of probing brain microstructure. However, confounding factors such as dependence on flip angle (α) and fiber orientation with respect to the main field ( θ $$ \uptheta $$ ) complicate interpretation. The α- and θ $$ \uptheta $$ -dependence stem from the existence of multiple sub-voxel micro-environments (e.g., myelin and non-myelin water compartments). Ordinarily, it is challenging to quantify these sub-compartments; therefore, neuroscientific studies commonly make the simplifying assumption of a mono-exponential decay obtaining a single R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimate per voxel. In this work, we investigated how the multi-compartment nature of tissue microstructure affects single compartment R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimates. METHODS: We used 2-pool (myelin and non-myelin water) simulations to characterize the bias in single compartment R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimates. Based on our numeric observations, we introduced a linear model that partitions R 2 * $$ {\mathrm{R}}_2^{\ast } $$ into α-dependent and α-independent components and validated this in vivo at 7T. We investigated the dependence of both components on the sub-compartment properties and assessed their robustness, orientation dependence, and reproducibility empirically. RESULTS: R 2 * $$ {\mathrm{R}}_2^{\ast } $$ increased with myelin water fraction and residency time leading to a linear dependence on α. We observed excellent agreement between our numeric and empirical results. Furthermore, the α-independent component of the proposed linear model was robust to the choice of α and reduced dependence on fiber orientation, although it suffered from marginally higher noise sensitivity. CONCLUSION: We have demonstrated and validated a simple approach that mitigates flip angle and orientation biases in single-compartment R 2 * $$ {\mathrm{R}}_2^{\ast } $$ estimates.

Lung parenchyma transverse relaxation rates at 0.55 T.

PURPOSE: To determine R2 and R 2 ' $$ {R}_2^{\prime } $$ transverse relaxation rates in healthy lung parenchyma at 0.55 T. This is important in that it informs the design and optimization of new imaging methods for 0.55T lung MRI. METHODS: Experiments were performed in 3 healthy adult volunteers on a prototype whole-body 0.55T MRI, using a custom free-breathing electrocardiogram-triggered, single-slice echo-shifted multi-echo spin echo (ES-MCSE) pulse sequence with respiratory navigation. Transverse relaxation rates R2 and R 2 ' $$ {R}_2^{\prime } $$ and off-resonance ∆f were jointly estimated using nonlinear least-squares estimation. These measurements were compared against R2 estimates from T2 -prepared balanced SSFP (T2 -Prep bSSFP) and R 2 * $$ {R}_2^{\ast } $$ estimates from multi-echo gradient echo, which are used widely but prone to error due to different subvoxel weighting. RESULTS: The mean R2 and R 2 ' $$ {R}_2^{\prime } $$ values of lung parenchyma obtained from ES-MCSE were 17.3 ± 0.7 Hz and 127.5 ± 16.4 Hz (T2  = 61.6 ± 1.7 ms; T 2 ' $$ {\mathrm{T}}_2^{\prime } $$  = 9.5 ms ± 1.6 ms), respectively. The off-resonance estimates ranged from -60 to 30 Hz. The R2 from T2 -Prep bSSFP was 15.7 ± 1.7 Hz (T2  = 68.6 ± 8.6 ms) and R 2 * $$ {R}_2^{\ast } $$ from multi-echo gradient echo was 131.2 ± 30.4 Hz ( T 2 * $$ {\mathrm{T}}_2^{\ast } $$  = 8.0 ± 2.5 ms). Paired t-test indicated that there is a significant difference between the proposed and reference methods (p < 0.05). The mean R2 estimate from T2 -Prep bSSFP was slightly smaller than that from ES-MCSE, whereas the mean R 2 ' $$ {R}_2^{\prime } $$ and R 2 * $$ {R}_2^{\ast } $$ estimates from ES-MCSE and multi-echo gradient echo were similar to each other across all subjects. CONCLUSIONS: Joint estimation of transverse relaxation rates and off-resonance is feasible at 0.55 T with a free-breathing electrocardiogram-gated and navigator-gated ES-MCSE sequence. At 0.55 T, the mean R2 of 17.3 Hz is similar to the reported mean R2 of 16.7 Hz at 1.5 T, but the mean R 2 ' $$ {R}_2^{\prime } $$ of 127.5 Hz is about 5-10 times smaller than that reported at 1.5 T.

Multisite reproducibility of quantitative susceptibility mapping and effective transverse relaxation rate in deep gray matter at 3 T using locally optimized sequences in 24 traveling heads.

Iron concentration in the human brain plays a crucial role in several neurodegenerative diseases and can be monitored noninvasively using quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2 *) mapping from multiecho T2 *-weighted images. Large population studies enable better understanding of pathologies and can benefit from pooling multisite data. However, reproducibility may be compromised between sites and studies using different hardware and sequence protocols. This work investigates QSM and R2 * reproducibility at 3 T using locally optimized sequences from three centers and two vendors, and investigates possible reduction of cross-site variability through postprocessing approaches. Twenty-four healthy subjects traveled between three sites and were scanned twice at each site. Scan-rescan measurements from seven deep gray matter regions were used for assessing within-site and cross-site reproducibility using intraclass correlation coefficient (ICC) and within-subject standard deviation (SDw) measures. In addition, multiple QSM and R2 * postprocessing options were investigated with the aim to minimize cross-site sequence-related variations, including: mask generation approach, echo-timing selection, harmonizing spatial resolution, field map estimation, susceptibility inversion method, and linear field correction for magnitude images. The same-subject cross-site region of interest measurements for QSM and R2 * were highly correlated (R2 ≥ 0.94) and reproducible (mean ICC of 0.89 and 0.82 for QSM and R2 *, respectively). The mean cross-site SDw was 4.16 parts per billion (ppb) for QSM and 1.27 s-1 for R2 *. For within-site measurements of QSM and R2 *, the mean ICC was 0.97 and 0.87 and mean SDw was 2.36 ppb and 0.97 s-1 , respectively. The precision level is regionally dependent and is reduced in the frontal lobe, near brain edges, and in white matter regions. Cross-site QSM variability (mean SDw) was reduced up to 46% through postprocessing approaches, such as masking out less reliable regions, matching available echo timings and spatial resolution, avoiding the use of the nonconsistent magnitude contrast between scans in field estimation, and minimizing streaking artifacts.

Application of Multiparametric Magnetic Resonance Imaging to Monitor the Early Antitumor Effect of CuS@GOD Nanoparticles in a 4 T1 Breast Cancer Xenograft Model.

BACKGROUND: We have developed hybrid nanoparticles (NPs) by co-loading copper sulfide (CuS) NPs and glucose oxidase (GOD) (CuS@GOD NPs) to explore their antitumor properties. PURPOSE: To investigate the feasibility of using multiparametric magnetic resonance imaging (MRI) including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and R2 * mapping to quantitatively assess the early antitumor effect of CuS@GOD NPs. STUDY TYPE: Prospective. ANIMAL MODEL: The orthotopic BALB/c mice 4 T1 breast cancer model. The 4 T1 xenografts in group 1 mice received normal saline, group 2 received CuS@GOD NPs, group 3 received CuS NPs plus laser, and group 4 received CuS@GOD NPs plus laser (n = 28 for each group). FIELD STRENGTH/SEQUENCE: A 3.0 T/IVIM-DWI MRI single-shot echo-planar imaging, R2 * mapping spoiled gradient recalled echo (SPGR) sequence, T2-weighted images (T2WI) and T1-weighted images (T1WI) fast spin echo (FSE) sequence. ASSESSMENT: The IVIM-DWI and R2 * mapping were performed before and after treatment at 0 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, and 24 hours in four groups and the MRI parameters were obtained. Correlation analysis between the MRI parameters and histological analyses was conducted. STATISTICAL TESTS: One-way ANOVA, Pearson's correlation analysis, two independent samples t test, intraclass correlation coefficient. P < 0.05 was considered to be statistically significant. RESULTS: In group 4, the tumoral D value was significantly higher than that of group 2 at 24 hours (0.541 ± 0.065 vs. 0.492 ± 0.051). The f value of group 4 was significantly lower than that of groups 1 and 2 at 2 hours (10.83 ± 2.16 vs. 14.28 ± 1.86, 16.67 ± 3.53, respectively). The R2 * value was significantly increased at 0 hour in group 4 compared to that of groups 1 and 2 (64.552 ± 4.663 vs. 42.441 ± 1.516, 43.165 ± 1.709, respectively). D, f, and R2 * were correlated with the histological staining results (r = 0.695-0.970). DATA CONCLUSION: The IVIM-DWI-derived D and f and R2 * mapping-derived R2 * could monitor early response to CuS@GOD NPs treatment in vivo. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Can R2 ' mapping evaluate hypoxia in renal ischemia reperfusion injury quantitatively? An experimental study.

PURPOSE: To explore if R2 ' mapping can assess renal hypoxia in rabbits with ischemia reperfusion injury (IRI). METHODS: Forty rabbits were randomly divided into 4 groups according to the clipping time: the sham group and 45 min, 60 min, and 75 min for the mild, moderate, and severe groups (with n = 10 each group), respectively. Intravenous furosemide (FU) was administered 24 h after IRI. All rabbits were performed 5 times (IRIpre , IRI24h , FU5min , FU12min , and FU24min ) with a 3.0 Tesla MR. The R2 ' values and the hypoxic scores were then recorded. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. RESULTS: Compared to the baseline, the medullary R2 ' values increased significantly 24 h after the IRI (baseline 19.31 ± 1.21 s-1 , mild group 20.05 ± 1.26 s-1 , moderate group 25.38 ± 1.38 s-1 , and severe group 25.79 ± 1.10 s-1 ; each P < .001). FU led to a significant decrease in the medullary R2 ' value (sham group 11.17 ± 4.33 s-1 , mild group 7.80 ± 0.74 s-1 , moderate group 3.92 ± 0.28 s-1 , and severe group 3.82 ± 0.23 s-1 ; each P < .05). Quantitative hypoxic scores revealed significant differences among the 4 groups in the outer medulla (P < .001 each). The medullary R2 ' differences (before and after intravenous FU) were significantly correlated with the hypoxic scores, respectively (P < .001). CONCLUSION: R2 ' mapping can evaluate the renal hypoxia in the procession of IRI in rabbits and might serve as a quantitative biomarker for IRI.

Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T applied to amyotrophic lateral sclerosis.

Susceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology. Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices. Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex. Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.

Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: Results from the UK7T study.

INTRODUCTION: We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's "Travelling Heads" study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5-3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. METHODS: Ten healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each "home" site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. RESULTS AND DISCUSSION: Mean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001-0.005 ppm (χ) and 0.0005-0.001 ms-1 (R2*). For χ this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. CONCLUSION: The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

Quantitative Measurement of Metal Accumulation in Brain of Patients With Wilson's Disease.

BACKGROUND: Currently, no study has evaluated metal accumulation in the brains of patients with Wilson's disease by using quantitative susceptibility mapping at 3T MRI. The objectives of this study were to qualitatively and quantitatively evaluate changes in magnetic susceptibility and R2* maps in deep gray matter nuclei to discriminate Wilson's disease patients from healthy controls and to evaluate their sensitivities in diagnosing Wilson's disease. METHODS: Magnetic susceptibility and R2* maps and conventional T1-weighted, T2-weighted, and T2-weighted fluid-attenuated inversion recovery images were obtained from 17 Wilson's disease patients and 14 age-matched healthy controls on a 3T MRI scanner. Differences between Wilson's disease and healthy control groups in susceptibility and R2* values in multiple deep nuclei were evaluated using a Mann-Whitney U test and receiver operating characteristic curves. The correlations of susceptibility and R2* values with Unified Wilson's Disease Rating Scale score were also performed. RESULTS: Magnetic susceptibility and R2* can effectively distinguish different types of signal abnormalities. Magnetic susceptibility and R2* values in multiple deep nuclei of Wilson's disease patients were significantly higher than those in healthy controls. Magnetic susceptibility value in the substantia nigra had the highest area under the curve (0.888). There were positive correlations of the Unified Wilson's Disease Rating Scale score with susceptibility values in the caudate nucleus (r = 0.757, P = 0.011), putamen (r = 0.679, P = 0.031), and red nucleus (r = 0.638, P = 0.047), as well as R2* values in the caudate nucleus (r = 0.754, P = 0.012). CONCLUSIONS: Quantitative susceptibility mapping at 3T could be a useful tool to evaluate metal accumulation in deep gray matter nuclei of Wilson's disease patients. © 2020 International Parkinson and Movement Disorder Society.

Cell density quantification with TurboSPI: R2* mapping with compensation for off-resonance fat modulation.

OBJECTIVE: Tracking the migration of superparamagnetic iron oxide (SPIO)-labeled immune cells in vivo is valuable for understanding the immunogenic response to cancer and therapies. Quantitative cell tracking using TurboSPI-based R2* mapping is a promising development to improve accuracy in longitudinal studies on immune recruitment. However, off-resonance fat signal isochromats lead to modulations in the signal time-course that can be erroneously fit as R2* signal decay, overestimating the density of labeled cells, while excluding voxels with fat-typical modulations results in underestimation of cell density in voxels with mixed content. Approaches capable of accurate R2* estimation in the presence of fat are needed. METHODS: We propose a dual-decay (separate R2f* and R2w* for fat and water) Dixon-based signal model that accounts for the presence of fat in a voxel to provide better estimates of SPIO-induced dephasing. This model was tested in silico, in phantoms with varying quantities of fat and SPIO-labeled cells, and in 5 mice injected with SPIO-labeled CD8+ T cells. RESULTS: In silico single voxel simulations illustrate how the proposed dual-decay model provides stable R2w* estimates that are invariant to fat content. The proposed model outperforms previous methods when applied to in vitro samples of SPIO-labeled cells and oil prepared with oil content ≥ 15%. Preliminary in vivo results show that, compared to previous methods, the dual-decay model improves the balance of R2* mapping in fat-dense areas, which will yield more reliable analysis in future cell tracking studies. DISCUSSION: The proposed model is a promising tool for quantitative TurboSPI R2* cell tracking, with further refinements offering the possibility of better specificity and sensitivity.

Prospective Evaluation of an R2* Method for Assessing Liver Iron Concentration (LIC) Against FerriScan: Derivation of the Calibration Curve and Characterization of the Nature and Source of Uncertainty in the Relationship.

BACKGROUND: FerriScan is the method-of-choice for noninvasive liver iron concentration (LIC) quantification. However, it has a number of drawbacks including cost and expediency. PURPOSE/HYPOTHESIS: To characterize an R2*-based MRI technique that may potentially be used as an alternative to FerriScan. This was accomplished through the derivation of a calibration curve that characterized the relationship between FerriScan-derived LIC and R2*. The nature and source of uncertainty in this curve were investigated. It was hypothesized that the source of uncertainty is heterogeneity of LIC across the liver. STUDY TYPE: Prospective. SUBJECTS: In all, 125 patients (69 women, 56 men) undergoing chelation treatment for iron overload prospectively underwent FerriScan and R2* MRI during the same exam. FIELD STRENGTH/SEQUENCE: Pulse sequences included 2D multislice spin-echo pulse for FerriScan, and a prototype 3D 6-echo gradient echo acquisition for R2* mapping at 1.5T. ASSESSMENT: A linear calibration curve was derived from the relationship between FerriScan-derived LIC estimates and R2* through least-squares fitting. STATISTICAL TESTS: The nature of the uncertainty in the curve was characterized through tests of normality and homoscedasticity. The source of uncertainty was tested by comparing the magnitude of LIC variation over the FerriScan ROI to the observed uncertainty in the R2*-derived LIC estimates. RESULTS: A linear relationship between logarithmically transformed FerriScan-derived LIC and R2* (log{FerriScan-derived LIC} = 1.029 log{R2*} - 3.822) was confirmed. Uncertainty was random, with a behaviour that was normal and homoscedastic. The source of uncertainty was confirmed as iron heterogeneity across the liver. The nontransformed calibration curve was: FerriScan-derived LIC = 0.0266⋅R2*, with a constant coefficient-of-variation of 0.32. DATA CONCLUSION: FerriScan and R2* techniques were found to provide equivalent quantification of LIC in this study. Any difference in accuracy or precision was at a level lower than the uncertainty caused by variation in LIC over the liver. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1467-1474.

Detection of Hyperacute Reactions of Desacetylvinblastine Monohydrazide in a Xenograft Model Using Intravoxel Incoherent Motion DWI and R2* Mapping.

OBJECTIVE: This study aimed to investigate the feasibility of intravoxel incoherent motion (IVIM) DWI and R2* (transverse relaxation rate) mapping to monitor the hyperacute therapeutic efficacy of desacetylvinblastine monohydrazide (DAVLBH) on an experimental hepatocellular carcinoma mouse model within 24 hours. MATERIALS AND METHODS: Forty-four mice were implanted with hepatocellular carcinoma and divided into three random groups. A treatment group and a control group underwent IVIM-DWI and R2* mapping examinations before and after a single injection of DAVLBH or saline at 1, 2, 4, and 24 hours. The pathology group was set for pathologic analysis, including H and E staining and CD31 and hypoxia-inducible factor (HIF)-1α immunohistochemical staining. RESULTS: DAVLBH caused hyperacute disruptions on the tumor capillaries in the treatment group. Water molecule diffusion (D), microcirculation perfusion (D*), and perfusion fraction (f) decreased initially but then gradually recovered to the baseline level by 24 hours after the first injection of DAVLBH. In contrast, R2* increased dramatically at 1 hour and then gradually decreased from 1 hour to 24 hours after treatment. D*, f, and D showed similar trends and were positively correlated with CD31 expression (r = 0.868, 0.721, and 0.730, respectively), but were negatively correlated with HIF-1α expression (r = -0.784, -0.737, and -0.673, respectively). R2* showed a negative correlation with CD31 expression (r = -0.823) and a positive correlation with HIF-1α expression (r = 0.791). CONCLUSION: Both IVIM-DWI and R2* mapping can adequately detect the vascular-disrupting effect of DAVLBH as early as 1 hour after injection in a mouse xenograft model. Moreover, D* and R2* are the two most sensitive hemodynamic parameters and can monitor the hyperacute changes associated with DAVLBH treatment in vivo.

The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging (MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin. In this study, we assessed the extent to which QSM and R2* reflect iron concentration as well as histological iron and myelin intensities. Six unfixed human post-mortem brains were imaged in situ with a 7 T MRI scanner. After formalin fixation, the brains were sliced axially and punched. 671 tissue punches were subjected to ferrozine iron quantification. Subsequently, brain slices were embedded in paraffin, and histological double-hemispheric axial brain slices were stained for Luxol fast blue (myelin) and diaminobenzidine (DAB)-enhanced Turnbull blue (iron). 3331 regions of interest (ROIs) were drawn on the histological stainings to assess myelin and iron intensities, which were compared with MRI data in corresponding ROIs. QSM more closely reflected quantitative ferrozine iron values (r = 0.755 vs. 0.738), whereas R2* correlated better with iron staining intensities (r = 0.619 vs. 0.445). Myelin intensities correlated negatively with QSM (r = -0.352), indicating a diamagnetic effect of myelin on susceptibility. Myelin intensities were higher in the thalamus than in the basal ganglia. A significant relationship was nonetheless observed between quantitative iron values and QSM, confirming the applicability of the latter in this brain region for iron quantification.

Improved liver R2* mapping by pixel-wise curve fitting with adaptive neighborhood regularization.

PURPOSE: To improve liver R2* mapping by incorporating adaptive neighborhood regularization into pixel-wise curve fitting. METHODS: Magnetic resonance imaging R2* mapping remains challenging because of the serial images with low signal-to-noise ratio. In this study, we proposed to exploit the neighboring pixels as regularization terms and adaptively determine the regularization parameters according to the interpixel signal similarity. The proposed algorithm, called the pixel-wise curve fitting with adaptive neighborhood regularization (PCANR), was compared with the conventional nonlinear least squares (NLS) and nonlocal means filter-based NLS algorithms on simulated, phantom, and in vivo data. RESULTS: Visually, the PCANR algorithm generates R2* maps with significantly reduced noise and well-preserved tiny structures. Quantitatively, the PCANR algorithm produces R2* maps with lower root mean square errors at varying R2* values and signal-to-noise-ratio levels compared with the NLS and nonlocal means filter-based NLS algorithms. For the high R2* values under low signal-to-noise-ratio levels, the PCANR algorithm outperforms the NLS and nonlocal means filter-based NLS algorithms in the accuracy and precision, in terms of mean and standard deviation of R2* measurements in selected region of interests, respectively. CONCLUSIONS: The PCANR algorithm can reduce the effect of noise on liver R2* mapping, and the improved measurement precision will benefit the assessment of hepatic iron in clinical practice. Magn Reson Med 80:792-801, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Assessment of MR-based R2* and quantitative susceptibility mapping for the quantification of liver iron concentration in a mouse model at 7T.

PURPOSE: To assess the feasibility of quantifying liver iron concentration (LIC) using R2* and quantitative susceptibility mapping (QSM) at a high field strength of 7 Tesla (T). METHODS: Five different concentrations of Fe-dextran were injected into 12 mice to produce various degrees of liver iron overload. After mice were sacrificed, blood and liver samples were harvested. Ferritin enzyme-linked immunosorbent assay (ELISA) and inductively coupled plasma mass spectrometry were performed to quantify serum ferritin concentration and LIC. Multiecho gradient echo MRI was conducted to estimate R2* and the magnetic susceptibility of each liver sample through complex nonlinear least squares fitting and a morphology enabled dipole inversion method, respectively. RESULTS: Average estimates of serum ferritin concentration, LIC, R2*, and susceptibility all show good linear correlations with injected Fe-dextran concentration; however, the standard deviations in the estimates of R2* and susceptibility increase with injected Fe-dextran concentration. Both R2* and susceptibility measurements also show good linear correlations with LIC (R2 = 0.78 and R2 = 0.91, respectively), and a susceptibility-to-LIC conversion factor of 0.829 ppm/(mg/g wet) is derived. CONCLUSION: The feasibility of quantifying LIC using MR-based  R2* and QSM at a high field strength of 7T is demonstrated. Susceptibility quantification, which is an intrinsic property of tissues and benefits from being field-strength independent, is more robust than R2* quantification in this ex vivo study. A susceptibility-to-LIC conversion factor is presented that agrees relatively well with previously published QSM derived results obtained at 1.5T and 3T.

Discriminative analysis of regional evolution of iron and myelin/calcium in deep gray matter of multiple sclerosis and healthy subjects.

BACKGROUND: Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. PURPOSE: We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. STUDY TYPE: Longitudinal (baseline and 2-year follow-up) retrospective study. SUBJECTS: Twenty-seven relapsing-remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age-matched healthy subjects. FIELD STRENGTH/SEQUENCE: 4.7T 10-echo gradient-echo acquisition. ASSESSMENT: Automatically segmented caudate nucleus (CN), thalamus (TH), putamen (PU), globus pallidus, red nucleus (RN), substantia nigra, and dentate nucleus were retrospectively analyzed to quantify regional volumes, bulk mean R2*, and bulk mean QS. DARE utilized combined R2* and QS localized changes to compute spatial extent, mean intensity, and total changes of DGM iron and myelin/calcium over 2 years. STATISTICAL TESTS: We used mixed factorial analysis for bulk analysis, nonparametric tests for DARE (α = 0.05), and multiple regression analysis using backward elimination of DGM structures (α = 0.05, P = 0.1) to regress bulk and DARE measures with the follow-up Multiple Sclerosis Severity Score (MSSS). False detection rate correction was applied to all tests. RESULTS: Bulk analysis only detected significant (Q ≤ 0.05) interaction effects in RRMS CN QS (η = 0.45; Q = 0.004) and PU volume (η = 0.38; Q = 0.034). DARE demonstrated significant group differences in all RRMS structures, and in all PMS structures except the RN. The largest RRMS effect size was CN total R2* iron decrease (r = 0.74; Q = 0.00002), and TH mean QS myelin/calcium decrease for PMS (r = 0.70; Q = 0.002). DARE iron increase using total QS demonstrated the highest correlation with MSSS (r = 0.68; Q = 0.0005). DATA CONCLUSION: DARE enabled discriminative assessment of specific DGM changes over 2 years, where iron and myelin/calcium changes were the primary drivers in RRMS and PMS compared to age-matched controls, respectively. Specific DARE measures of MS DGM correlated with follow-up MSSS, and may reflect complex disease pathology. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

MRI-based quantitative susceptibility mapping (QSM) and R2* mapping of liver iron overload: Comparison with SQUID-based biomagnetic liver susceptometry.

PURPOSE: We aimed to determine the agreement between quantitative susceptibility mapping (QSM)-based biomagnetic liver susceptometry (BLS) and confounder-corrected R2* mapping with superconducting quantum interference device (SQUID)-based biomagnetic liver susceptometry in patients with liver iron overload. METHODS: Data were acquired from two healthy controls and 22 patients undergoing MRI and SQUID-BLS as part of routine monitoring for iron overload. Magnetic resonance imaging was performed on a 3T system using a three-dimensional multi-echo gradient-echo acquisition. Both magnetic susceptibility and R2* of the liver were estimated from this acquisition. Linear regression was used to compare estimates of QSM-BLS and R2* to SQUID-BLS. RESULTS: Both QSM-BLS and confounder-corrected R2* were sensitive to the presence of iron in the liver. Linear regression between QSM-BLS and SQUID-BLS demonstrated the following relationship: QSM-BLS = (-0.22 ± 0.11) + (0.49 ± 0.05) · SQUID-BLS with r2 = 0.88. The coefficient of determination between liver R2* and SQUID-BLS was also r2 = 0.88. CONCLUSION: We determined a strong correlation between both QSM-BLS and confounder-corrected R2* to SQUID-BLS. This study demonstrates the feasibility of QSM-BLS and confounder-corrected R2* for assessing liver iron overload, particularly when SQUID systems are not accessible. Magn Reson Med 78:264-270, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7T.

Quantitative susceptibility mapping (QSM) has recently emerged as a novel magnetic resonance imaging (MRI) method to detect non-haem iron deposition, calcifications, demyelination and vascular lesions in the brain. It has been suggested that QSM is more sensitive than the more conventional quantifiable MRI measure, namely the transverse relaxation rate, R2*. Here, we conducted the first high-resolution, whole-brain, simultaneously acquired, comparative study of the two techniques using 7Tesla MRI. We asked which of the two techniques would be more sensitive to explore global differences in tissue composition in elderly adults relative to young subjects. Both QSM and R2* revealed strong age-related differences in subcortical regions, hippocampus and cortical grey matter, particularly in superior frontal regions, motor/premotor cortices, insula and cerebellar regions. Within the basal ganglia system-but also hippocampus and cerebellar dentate nucleus-, QSM was largely in agreement with R2* with the exception of the globus pallidus. QSM, however, provided superior anatomical contrast and revealed age-related differences in the thalamus and in white matter, which were otherwise largely undetected by R2* measurements. In contrast, in occipital cortex, age-related differences were much greater with R2* compared to QSM. The present study, therefore, demonstrated that in vivo QSM using ultra-high field MRI provides a novel means to characterise age-related differences in the human brain, but also combining QSM and R2* using multi-gradient recalled echo imaging can potentially provide a more complete picture of mineralisation, demyelination and/or vascular alterations in aging and disease.

Quantitative susceptibility mapping in patients with systemic lupus erythematosus: detection of abnormalities in normal-appearing basal ganglia.

OBJECTIVES: To evaluate whether quantitative susceptibility mapping (QSM) can be employed to detect abnormalities within normal-appearing basal ganglia on conventional MRI in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: For 33 SLE patients (13 NPSLE and 20 non-NPSLE patients) and 23 age/sex-matched controls, two radiologists independently measured the mean QSM and R2* values in various brain structures that appeared to be normal on conventional MR images. These values in each brain structure were compared among the two SLE groups and controls. RESULTS: Regarding the putamen, the NPSLE patients showed significantly higher QSM values than the non-NPSLE patients and controls (p < 0.05). For the lateral globus pallidus, both SLE groups showed significantly higher QSM values than the controls (p < 0.05). The R2* values were not significantly different between both SLE groups. The NPSLE patients showed a significant correlation between the mean QSM values in putamen and the disease duration (r = 0.63, p < 0.05). For the interobserver agreement, the QSM value was superior to the R2* value (0.690 vs. 0.446, Kendall W value). CONCLUSIONS: QSM can be used to identify increased susceptibility of the basal ganglia appearing to be normal on conventional MR images in NPSLE patients. KEY POINTS: • QSM values in the putamen are significantly higher in NPSLE than non-NPSLE. • NPSLE patients show correlation between QSM values in the putamen and disease duration. • QSM is more sensitive than R2* mapping for detecting subtle changes.

Validation of quantitative susceptibility mapping with Perls' iron staining for subcortical gray matter.

Quantitative susceptibility mapping (QSM) measures bulk susceptibilities in the brain, which can arise from many sources. In iron-rich subcortical gray matter (GM), non-heme iron is a dominant susceptibility source. We evaluated the use of QSM for iron mapping in subcortical GM by direct comparison to tissue iron staining. We performed in situ or in vivo QSM at 4.7 T combined with Perls' ferric iron staining on the corresponding extracted subcortical GM regions. This histochemical process enabled examination of ferric iron in complete slices that could be related to susceptibility measurements. Correlation analyses were performed on an individual-by-individual basis and high linear correlations between susceptibility and Perls' iron stain were found for the three multiple sclerosis (MS) subjects studied (R(2) = 0.75, 0.62, 0.86). In addition, high linear correlations between susceptibility and transverse relaxation rate (R2*) were found (R(2) = 0.88, 0.88, 0.87) which matched in vivo healthy subjects (R(2) = 0.87). This work validates the accuracy of QSM for brain iron mapping and also confirms ferric iron as the dominant susceptibility source in subcortical GM, by demonstrating high linear correlation of QSM to Perls' ferric iron staining.

Volumetric R2 * mapping using z-shim multi-echo gradient echo imaging.

PURPOSE: To introduce macroscopic B0 field inhomogeneity-compensated volumetric R2 * mapping method with a three-dimensional (3D) z-shim multi-echo acquisition. METHODS: The proposed z-shim sequence acquired conventional and z-shimmed echoes alternately with bipolar readout gradients. A constant-valued z-shim gradient was applied prior to each negative readout gradient lobe. A phase combination algorithm was also proposed based on this pulse sequence, which acquires a B0 inhomogeneity-compensated field map that was shown to play a critical role for accurate R2 * mapping. A modified signal model based on recently suggested model for 3D acquisition was proposed for R2 * quantification. RESULTS: To validate the performance of the proposed method, phantom and in vivo experiments were performed and compared with other methods. An increase in the range of field inhomogeneity correction was shown in the phantom results. For in vivo studies, the proposed method showed enhanced R2 * map quality for the different subjects. CONCLUSION: The proposed method improves R2 * estimation, especially in the frontal and temporal regions.