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PURPOSE: Imaging carotid artery plaques to identify features of vulnerability typically requires a multicontrast MRI protocol. The identification of regions of inflammation with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles requires separate pre- and postcontrast scans. We propose a method of joint water-fat separation and quantitative susceptibility mapping (QSM) to aid classification of atherosclerotic plaques and offer a positive contrast mechanism in USPIO-imaging. METHODS: Ten healthy volunteers (3 women and 7 men; aged, 30.7 ± 10.7 years) were imaged at 1.5T to develop an acquisition and postprocessing protocol. Five patients (1 woman and 4 men; mean age, 71 ± 7.5 years) with moderate to severe luminal stenosis were imaged pre- and postadministration of a USPIO contrast agent. We used a multiecho gradient echo acquisition to perform water/fat separation and subsequently QSM. The results were compared with a conventional multicontrast MRI protocol, CT images, and histopathology data. RESULTS: In the volunteer scans, a multiecho gradient echo acquisition with bipolar readout gradients demonstrated to be a reliable acquisition methodology to produce high-quality susceptibility maps in conjunction with the proposed postprocessing methodology. In the patient study, water/fat separation provided a tool to identify lipid-rich necrotic cores and QSM provided a qualitative and quantitative evaluation of plaque features and positive contrast when evaluating USPIO uptake. Plaque calcification could be identified by strong diamagnetism (-1.27 ± 0.71 ppm), while USPIO uptake demonstrated a strong paramagnetism (1.32 ± 0.61 ppm). CONCLUSION: QSM was able to identify multiple plaque features in a single acquisition, providing positive contrast for plaques demonstrating USPIO uptake and negative contrast for calcification.

Multiparametric magnetic resonance imaging (MRI) can be used to characterize many cancer subtypes including ovarian cancer. Quantitative mapping of MRI relaxation values, such as T 1 and T 2 mapping, is promising for improving tumor assessment beyond conventional qualitative T 1- and T 2-weighted images. However, quantitative MRI relaxation mapping methods often involve long scan times due to sequentially measuring many parameters. Magnetic resonance fingerprinting (MRF) is a new method that enables fast quantitative MRI by exploiting the transient signals caused by the variation of pseudorandom sequence parameters. These transient signals are then matched to a simulated dictionary of T 1 and T 2 values to create quantitative maps. The ability of MRF to simultaneously measure multiple parameters, could represent a new approach to characterizing cancer and assessing treatment response. This feasibility study investigates MRF for simultaneous T 1, T 2, and relative proton density (rPD) mapping using ovarian cancer as a model system.

Purpose: While the aetiology of rheumatoid arthritis (RA) remains unclear, many of the inflammatory components are well characterised. For diagnosis and therapy evaluation, in vivo insight into these processes would be valuable. Various imaging probes have shown value including dynamic contrast-enhanced (DCE) MRI and PET/CT using 18F-fluorodeoxyglucose (18F-FDG) or tracers targeting the translocator protein (TSPO). To evaluate 18F-GE-180, a novel TSPO PET tracer, for detecting and quantifying disease activity in RA, we compared 18F-GE-180 uptake with that of 18F-FDG and DCE-MRI measures of inflammation. Methods: Eight RA patients with moderate-to-high, stable disease activity and active disease in at least one wrist were included in this study (NCT02350426). Participants underwent PET/CT examinations with 18F-GE-180 and 18F-FDG on separate visits, covering the shoulders and from the pelvis to the feet, including hands and wrists. DCE-MRI was performed on one affected hand. Uptake was compared visually between tracers as judged by an experienced radiologist and quantitatively using the maximum standardised uptake value (SUVmax). Uptake for both tracers was correlated with DCE-MRI parameters of inflammation, including the volume transfer coefficient Ktrans using Pearson correlation (r). Results: PET/CT imaging with 18F-GE-180 in RA patients showed marked extra-synovial uptake around the affected joints. Overall sensitivity for detecting clinically affected joints was low (14%). 18F-GE-180 uptake did not or only weakly correlate with DCE-MRI parameters in the wrist (r = 0.09–0.31). 18F-FDG showed higher sensitivity for detecting symptomatic joints (34%), as well as strong positive correlation with DCE-MRI parameters (SUVmax vs. Ktrans: r = 0.92 for wrist; r = 0.68 for metacarpophalangeal joints). Conclusions: The correlations between DCE-MRI parameters and 18F-FDG uptake support use of this PET tracer for quantification of inflammatory burden in RA. The TSPO tracer 18F-GE-180, however, has shown limited use for the investigation of RA due to its poor sensitivity and ability to quantify disease activity in RA.

BACKGROUND: Sodium MRI (23 Na-MRI)-derived biomarkers such as total sodium concentration (TSC) have the potential to provide information on tumor cellularity and the changes in tumor microstructure that occur following therapy. PURPOSE: To evaluate the repeatability and reproducibility of TSC measurements in the brains of healthy volunteers, providing evidence for the technical validation of 23 Na-MRI-derived biomarkers. STUDY TYPE: Prospective multicenter study. SUBJECTS: Eleven volunteers (32 ± 6 years; eight males, three females) were scanned twice at each of two sites. FIELD STRENGTH/SEQUENCE: Comparable 3D-cones 23 Na-MRI ultrashort echo time acquisitions at 3T. ASSESSMENT: TSC values, quantified from calibration phantoms placed in the field of view, were obtained from white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), based on automated segmentation of coregistered 1 H T1 -weighted images and hand-drawn regions of interest by two readers. STATISTICAL TESTS: Coefficients of variation (CoVs) from mean TSC values were used to assess intrasite repeatability and intersite reproducibility. RESULTS: Mean GM TSC concentrations (52.1 ± 7.1 mM) were ∼20% higher than for WM (41.8 ± 6.7 mM). Measurements were highly repeatable at both sites with mean scan-rescan CoVs between volunteers and regions of 2% and 4%, respectively. Mean intersite reproducibility CoVs were 3%, 3%, and 6% for WM, GM, and CSF, respectively. DATA CONCLUSION: These results demonstrate technical validation of sodium MRI-derived biomarkers in healthy volunteers. We also show that comparable 23 Na imaging of the brain can be implemented across different sites and scanners with excellent repeatability and reproducibility. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1278-1284.

BACKGROUND: There has been recent interest in nonproton MRI including hyperpolarized carbon-13 (13 C) imaging. Prostate cancer has been shown to have a higher tissue sodium concentration (TSC) than normal tissue. Sodium (23 Na) and 13 C nuclei have a frequency difference of only 1.66 MHz at 3T, potentially enabling 23 Na imaging with a 13 C-tuned coil and maximizing the metabolic information obtained from a single study. PURPOSE: To compare TSC measurements from a 13 C-tuned endorectal coil to those quantified with a dedicated 23 Na-tuned coil. STUDY TYPE: Prospective. POPULATION: Eight patients with biopsy-proven, intermediate/high risk prostate cancer imaged prior to prostatectomy. SEQUENCE: 3T MRI with separate dual-tuned 1 H/23 Na and 1 H/13 C endorectal receive coils to quantify TSC. ASSESSMENT: Regions-of-interest for TSC quantification were defined for normal peripheral zone (PZ), normal transition zone (TZ), and tumor, with reference to histopathology maps. STATISTICAL TESTS: Two-sided Wilcoxon rank sum with additional measures of correlation, coefficient of variation, and Bland-Altman plots to assess for between-test differences. RESULTS: Mean TSC for normal PZ and TZ were 39.2 and 33.9 mM, respectively, with the 23 Na coil and 40.1 and 36.3 mM, respectively, with the 13 C coil (P = 0.22 and P = 0.11 for the intercoil comparison, respectively). For tumor tissue, there was no statistical difference between the overall mean tumor TSC measured with the 23 Na coil (41.8 mM) and with the 13 C coil (46.6 mM; P = 0.38). Bland-Altman plots showed good repeatability for tumor TSC measurements between coils, with a reproducibility coefficient of 9 mM; the coefficient of variation between the coils was 12%. The Pearson correlation coefficient for TSC between coils for all measurements was r = 0.71 (r2 = 0.51), indicating a strong positive linear relationship. The mean TSC within PZ tumors was significantly higher compared with normal PZ for both the 23 Na coil (45.4 mM; P = 0.02) and the 13 C coil (49.4 mM; P = 0.002). DATA CONCLUSION: We demonstrated the feasibility of using a carbon-tuned coil to quantify TSC, enabling dual metabolic information from a single coil. This approach could make the acquisition of both 23 Na-MRI and 13 C-MRI feasible in a single clinical imaging session. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:90-97.

The tumor microenvironment is characteristically acidic and this extracellular acidosis is known to play a role in carcinogenesis and metastasis and can affect tumor chemosensitivity and radiosensitivity. Intracellular pH has been used as a possible biomarker of salvageable tissue in ischemic stroke. A non-invasive MRI-based approach for the determination and imaging of cerebral pH would be a powerful tool in cancer diagnosis and monitoring, as well as stroke treatment planning. Several pH-based MRI imaging approaches have been proposed but for these to be useful, disentangling the effects of pH from other parameters which may affect the measured MRI signal is crucial to ensure accuracy and specificity. R1 relaxation in the rotating frame (R1ρ) is an example of a method that has been proposed to probe pH in vivo using MRI. In this study, we have investigated the relationship between R1ρ, pH, and macromolecular density in vitro using phantoms and in human volunteers. Here we show that the rate of R1ρ relaxation (=1/T1ρ) varies with pH but only in the presence of macromolecules. At constant pH, phantom macromolecular density inversely correlated with R1ρ. R1ρ imaging of the normal human brain demonstrated regional heterogeneity with significant differences between structurally distinct regions, which are likely to be independent of pH. For example, R1ρ was higher in the basal ganglia compared to grey matter and higher in grey matter compared to white matter. We conclude that R1ρ cannot be reliably used to image tissue pH without deconvolution from the effects of local tissue macromolecular composition.