Search

Hyperpolarized carbon-13 MRI has shown promise for non-invasive assessment of the cerebral metabolism of [1-13C]pyruvate in both healthy volunteers and in patients. Exchange of pyruvate to lactate catalyzed by lactate dehydrogenase (LDH), and pyruvate flux to bicarbonate through pyruvate dehydrogenase (PDH), are the most widely studied reactionsin vivo. Here we show the potential of the technique to probe other metabolic reactions in the human brain. Approximately 50 s after intravenous injection of hyperpolarized pyruvate, high flip angle pulses were used to detect cerebral13C-labelled carbon dioxide (13CO2), in addition to the13C-bicarbonate (H13CO2-) subsequently formed by carbonic anhydrase. Brain pH weighted towards the extracellular compartment was calculated from the ratio of H13CO3-to13CO2in seven volunteers using the Henderson-Hasselbalch equation, demonstrating an average pH ± S.D. of 7.40 ± 0.02, with inter-observer reproducibility of 0.04. In addition, hyperpolarized [1-13C]aspartate was also detected in four of nine volunteers demonstrating irreversible pyruvate carboxylation to oxaloacetate by pyruvate carboxylase (PC), and subsequent transamination by aspartate aminotransferase (AST), with this flux being approximately 6% of that through PDH. Hyperpolarized [1-13C]alanine signal was also detected within the head but this was localized to muscle tissue in keeping with skeletal alanine aminotransferase (ALT) activity. The results demonstrate the potential of hyperpolarized carbon-13 MRI to assess cerebral and extracerebral [1-13C]pyruvate metabolism in addition to LDH and PDH activity. Non-invasive measurements of brain pH could be particularly important in assessing cerebral pathology given the wide range of disease processes that alter acid-base balance.

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site’s data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare. Federated learning, a method for training artificial intelligence algorithms that protects data privacy, was used to predict future oxygen requirements of symptomatic patients with COVID-19 using data from 20 different institutes across the globe.

Background Breast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium (23Na) MRI in preclinical models of breast cancer. Methods Female Rag2−/−Il2rg−/− and Balb/c mice bearing orthotopic breast tumours (MDA-MB-231, EMT6 and 4T1) underwent MRI as part of a randomised, controlled, interventional study. Tumour biology was probed using ex vivo fluorescence microscopy and electrophysiology. Results 23Na MRI revealed elevated sodium concentration ([Na+]) in tumours vs non-tumour regions. Complementary proton-based diffusion-weighted imaging (DWI) linked elevated tumour [Na+] to increased cellularity. Combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared with either parameter alone. Ex vivo assessment of isolated tumour slices confirmed elevated intracellular [Na+] ([Na+]i); extracellular [Na+] ([Na+]e) remained unchanged. Treatment with specific inward Na+ conductance inhibitors (cariporide, eslicarbazepine acetate) did not affect tumour [Na+]. Nonetheless, effective treatment with docetaxel reduced tumour [Na+], whereas DWI measures were unchanged. Conclusions Orthotopic breast cancer models exhibit elevated tumour [Na+] that is driven by aberrantly elevated [Na+]i. Moreover, 23Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone.

PURPOSE An unmet need in carbon-13 (13 C)-MRI is a transmit system that provides uniform excitation across a large FOV and can accommodate patients of wide-ranging body habitus. Due to the small difference between the resonant frequencies, sodium-23 (23 Na) coil developments can inform 13 C coil design while being simpler to assess due to the higher naturally abundant 23 Na signal. Here we present a removable 23 Na birdcage, which also allows operation as a 13 C abdominal coil. METHODS We demonstrate a quadrature-driven 4-rung 23 Na birdcage coil of 50 cm in length for both 23 Na and 13 C abdominal imaging. The coil transmit efficiencies and B1+ maps were compared to a linearly driven 13 C Helmholtz-based (clamshell) coil. SNR was investigated with 23 Na and 13 C data using an 8-channel 13 C receive array within the 23 Na birdcage. RESULTS The 23 Na birdcage longitudinal FOV was > 40 cm, whereas the 13 C clamshell was < 32 cm. The transmit efficiency of the birdcage at the 23 Na frequency was 0.65 µT/sqrt(W), similar to the clamshell for 13 C. However, the coefficient of variation of 23 Na- B1+ was 16%, nearly half that with the 13 C clamshell. The 8-channel 13 C receive array combined with the 23 Na birdcage coil generated a greater than twofold increase in 23 Na-SNR from the central abdomen compared with the birdcage alone. DISCUSSION This 23 Na birdcage coil has a larger FOV and improved B1+ uniformity when compared to the widely used clamshell coil design while also providing similar transmit efficiency. The coil has the potential to be used for both 23 Na and 13 C imaging.

Artificial intelligence (AI) is an overarching term for a multitude of technologies which are currently being discussed and introduced in several areas of medicine and in medical imaging specifically. There is, however, limited literature and information about how AI techniques can be integrated into the design of clinical imaging trials. This article will present several aspects of AI being used in trials today and how imaging departments and especially nuclear medicine departments can prepare themselves to be at the forefront of AI-driven clinical trials. Beginning with some basic explanation on AI techniques currently being used and existing challenges of its implementation, it will also cover the logistical prerequisites which have to be in place in nuclear medicine departments to participate successfully in AI-driven clinical trials.

Purpose The aim of the study was to investigate whether incorrectly compensated eddy currents are the source of persistent X-nuclear spectroscopy and imaging artifacts, as well as methods to correct this. Methods Pulse-acquire spectra were collected for 1 H and X-nuclei (23 Na or 31 P) using the minimum TR permitted on a 3T clinical MRI system. Data were collected in 3 orientations (axial, sagittal, and coronal) with the spoiler gradient at the end of the TR applied along the slice direction for each. Modifications to system calibration files to tailor eddy current compensation for each X-nucleus were developed and applied, and data were compared with and without these corrections for: slice-selective MRS (for 23 Na and 31 P), 2D spiral trajectories (for 13 C), and 3D cones trajectories (for 23 Na). Results Line-shape distortions characteristic of eddy currents were demonstrated for X-nuclei, which were not seen for 1 H. The severity of these correlated with the amplitude of the eddy current frequency compensation term applied by the system along the axis of the applied spoiler gradient. A proposed correction to eddy current compensation, taking account of the gyromagnetic ratio, was shown to dramatically reduce these distortions. The same correction was also shown to improve data quality of non-Cartesian imaging (2D spiral and 3D cones trajectories). Conclusion A simple adaptation of the default compensation for eddy currents was shown to eliminate a range of artifacts detected on X-nuclear spectroscopy and imaging.

BACKGROUND: Determining the compositional response of articular cartilage to dynamic joint-loading using MRI may be a more sensitive assessment of cartilage status than conventional static imaging. However, distinguishing the effects of joint-loading vs. inherent measurement variability remains difficult, as the repeatability of these quantitative methods is often not assessed or reported. PURPOSE: To assess exercise-induced changes in femoral, tibial, and patellar articular cartilage composition and compare these against measurement repeatability. STUDY TYPE: Prospective observational study. POPULATION: Phantom and 19 healthy participants. FIELD STRENGTH/SEQUENCE: 3T; 3D fat-saturated spoiled gradient recalled-echo; T1ρ - and T2 -prepared pseudosteady-state 3D fast spin echo. ASSESSMENT: The intrasessional repeatability of T1ρ and T2 relaxation mapping, with and without knee repositioning between two successive measurements, was determined in 10 knees. T1ρ and T2 relaxation mapping of nine knees was performed before and at multiple timepoints after a 5-minute repeated, joint-loading stepping activity. 3D surface models were created from patellar, femoral, and tibial articular cartilage. STATISTICAL TESTS: Repeatability was assessed using root-mean-squared-CV (RMS-CV). Using Bland-Altman analysis, thresholds defined as the smallest detectable difference (SDD) were determined from the repeatability data with knee repositioning. RESULTS: Without knee repositioning, both surface-averaged T1ρ and T2 were very repeatable on all cartilage surfaces, with RMS-CV SDD) average exercise-induced in T1ρ and T2 of femoral (-8.0% and -5.3%), lateral tibial (-6.9% and -5.9%), medial tibial (+5.8% and +2.9%), and patellar (-7.9% and +2.8%) cartilage were observed. DATA CONCLUSION: Joint-loading with a stepping activity resulted in T1ρ and T2 changes above background measurement error. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1753-1764.

Background: Traditional quantitative analysis of cartilage with MRI averages measurements (eg, thickness) across regions-of-interest (ROIs) which may reduce responsiveness. Purpose: To validate and describe clinical application of a semiautomated surface-based method for analyzing cartilage relaxation times (“composition”) and morphology on MRI, 3D cartilage surface mapping (3D-CaSM). Study Type: Validation study in cadaveric knees and prospective observational (cohort) study in human participants. Population: Four cadaveric knees and 14 participants aged 40–60 with mild–moderate knee osteoarthritis (OA) and 6 age-matched healthy volunteers, imaged at baseline, 1, and 6 months. Field Strength/Sequence: 3D spoiled gradient echo, T 1rho/T 2 magnetization-prepared 3D fast spin echo for mapping of T 1rho/T 2 relaxation times and delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using variable flip angle T 1 relaxation time mapping at 3T. Assessment: 3D-CaSM was validated against high-resolution peripheral quantitative computed tomography (HRpQCT) in cadaveric knees, with comparison to expert manual segmentation. The clinical study assessed test–retest repeatability and sensitivity to change over 6 months for cartilage thickness and relaxation times. Statistical Tests: Bland–Altman analysis was performed for the validation study and evaluation of test–retest repeatability. Six-month changes were assessed via calculation of the percentage of each cartilage surface affected by areas of significant change (%SC), defined using thresholds based on area and smallest detectable difference (SDD). Results: Bias and precision (0.06 ± 0.25 mm) of 3D-CaSM against reference HRpQCT data were comparable to expert manual segmentation (−0.13 ± 0.26 mm). 3D-CaSM demonstrated significant (>SDD) 6-month changes in cartilage thickness and relaxation times in both OA participants and healthy controls. The parameter demonstrating the greatest 6-month change was T 2 relaxation time (OA median %SC [IQR] = 8.8% [5.5 to 12.6]). Data Conclusion: This study demonstrates the construct validity and potential clinical utility of 3D-CaSM, which may offer advantages to conventional ROI-based methods. Level of Evidence: 2. Technical Efficacy Stage: 2. J. Magn. Reson. Imaging 2020;52:1139–1151.

Sodium magnetic resonance imaging (MRI) is a powerful, non-invasive technique to assess sodium distribution within the kidney. Here we undertook pre-clinical and clinical studies to quantify the corticomedullary sodium gradient in healthy individuals and in a porcine model of diuresis. The results demonstrated that sodium MRI could detect spatial differences in sodium biodistribution across the kidney. The sodium gradient of the kidney changed significantly after diuresis in the pig model and was independent of blood electrolyte measurements. Thus, rapid sodium MRI can be used to dynamically quantify sodium biodistribution in the porcine and human kidney., Graphical abstract

Deuterium metabolic imaging (DMI) and hyperpolarized 13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications for cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans, and how they simultaneously probe both glycolytic and oxidative metabolism. DMI was undertaken 1-2 hours after oral administration of [6,6’-2H2]glucose, and 13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm. DMI provided maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine. 13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. There was clear spectral separation in the spectroscopic imaging data with both DMI and 13C-HPMRI at 3 T. The ratio of 13C-lactate/13C-bicarbonate (mean = 3.7 ± 1.2) acquired with 13C-HPMRI was higher than the equivalent 2H-lactate/2H-Glx ratio (mean = 0.18 ± 0.09) acquired with DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and glycolytic metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) methods such as T1rho and T2 mapping are sensitive to changes in tissue composition, however their use in cruciate ligament assessment has been limited to studies of asymptomatic populations or patients with posterior cruciate ligament tears only. The aim of this preliminary study was to compare T1rho and T2 relaxation times of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) between subjects with mild-to-moderate knee osteoarthritis (OA) and healthy controls. METHODS: A single knee of 15 patients with mild-to-moderate knee OA (Kellgren-Lawrence grades 2-3) and of 6 age-matched controls was imaged using a 3.0 T MRI. Three-dimensional (3D) fat-saturated spoiled gradient recalled-echo images were acquired for morphological assessment and T1��- and T2-prepared pseudo-steady-state 3D fast spin echo images for compositional assessment of the cruciate ligaments. Manual segmentation of whole ACL and PCL, as well as proximal / middle / distal thirds of both ligaments was carried out by two readers using ITK-SNAP and mean relaxation times were recorded. Variation between thirds of the ligament were assessed using repeated measures ANOVAs and differences in these variations between groups using a Kruskal-Wallis test. Inter- and intra-rater reliability were assessed using intraclass correlation coefficients (ICCs). RESULTS: In OA knees, both T1rho and T2 values were significantly higher in the distal ACL when compared to the rest of the ligament with the greatest differences in T1rho (e.g. distal mean = 54.5 ms, proximal = 47.0 ms, p, Declarations Ethics approval and consent to participate This study was approved by the East of England Cambridge Central Research Ethics Committee and written informed consent was given by all subjects included in the study. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication Not Applicable Availability of data and materials The datasets generated and analysed during the current study are not publicly available due to unattained permission from participants and research ethics committee but could be made available from JWM (email: jw.mackay@gmail.com). Competing interests JWM, DAK and JDK acknowledge funding support from GlaxoSmithKline for their studentships and fellowships, respectively. JWM is an employee of AstraZeneca. CDSR, VAC and SMM have no competing interests to declare. Acknowledgements The Addenbrooke's Hospital Magnetic Resonance Imaging and Spectroscopy (MRIS) staff are thanked for their help with arranging and conducting the study MRI examinations. We also acknowledge the support of the Addenbrooke's Charitable Trust and the National Institute for Health Research Cambridge Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Funding The study was funded by an Experimental Medicine Initiative PhD studentship from the University of Cambridge [grant number RG81329] and by GlaxoSmithKline [grant number RG87552]. Authors' contributions Writing of original draft manuscript: CDSR. Study design and coordination: CDSR, JWM, JDK and SMM. Data acquisition: JWM and JDK. Data curation, analysis and interpretation: CDSR, JWM, VAC, JDK, DAK and SMM. Statistical analysis: CDSR and JWM. Review and editing of manuscript: JWM, VAC, JDK, DAK and SMM. All authors read and approved the final manuscript.

Breast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium (Female Rag2Orthotopic breast cancer models exhibit elevated tumour [Na

BackgroundImmune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI.MethodsFifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year.ResultsDifferential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (papp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (pConclusionsMultiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.

Hyperpolarised magnetic resonance imaging (HP

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.

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 aim of this study was to assess the feasibility of rapid sodium MRI (23Na-MRI) for the imaging of peritoneal cancer deposits in high grade serous ovarian cancer (HGSOC) and to evaluate the relationship of 23Na-MRI with tumour cellularity. 23Na-MRI was performed at 3 T on twelve HGSOC patients using a 3D-cones acquisition technique. Tumour biopsies specimens were collected after imaging and cellularity was measured from histology. Total 23Na-MRI scan time for each patient was approximately 11 min. At an isotropic resolution of 5.6 mm, signal-to-noise ratios (SNRs) of 82.2 ± 15.3 and 15.1 ± 7.1 (mean ± standard deviation) were achieved for imaging of tumour tissue sodium concentration (TSC) and intracellular weighted sodium concentration (IWS) respectively. Tumour TSC and IWS concentrations were: 56.8 ± 19.1 mM and 30.8 ± 9.2 mM respectively and skeletal muscle TSC and IWS concentrations were 33.2 ± 16.3 mM and 20.5 ± 9.9 mM respectively. There were significant sodium concentration differences between cancer and skeletal muscle, Wilcoxon signed-rank test, P

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1–13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7–11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5–6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. Significance: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7–11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

Objectives Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. Methods Fourteen individuals aged 40–60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. Results Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. Conclusions Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. Key Points • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktransdemonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies.

An unmet need in carbon-13 (We demonstrate a quadrature-driven 4-rungTheThis

Facilitating clinical translation of quantitative imaging techniques has been suggested as means of improving interobserver agreement and diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) of the prostate. One such technique, magnetic resonance fingerprinting (MRF), has significant competitive advantages over conventional mapping techniques in terms of its multi-site reproducibility, short scanning time and inherent robustness to motion. It has also been shown to improve the detection of clinically significant prostate cancer when added to standard mpMRI sequences, however, the existing studies have all been conducted on 3.0 T MRI systems, limiting the technique’s use on 1.5 T MRI scanners that are still more widely used for prostate imaging across the globe. The aim of this proof-of-concept study was, therefore, to evaluate the cross-system reproducibility of prostate MRF T1 in healthy volunteers (HVs) using 1.5 and 3.0 T MRI systems. The initial validation of MRF T1 against gold standard inversion recovery fast spin echo (IR-FSE) T1 in the ISMRM/NIST MRI system revealed a strong linear correlation between phantom-derived MRF and IR-FSE T1 values was observed at both field strengths (R2 = 0.998 at 1.5T and R2 = 0.993 at 3T; p = < 0.0001 for both). In young HVs, inter-scanner CVs demonstrated marginal differences across all tissues with the highest difference of 3% observed in fat (2% at 1.5T vs 5% at 3T). At both field strengths, MRF T1 could confidently differentiate prostate peripheral zone from transition zone, which highlights the high quantitative potential of the technique given the known difficulty of tissue differentiation in this age group. The high cross-system reproducibility of MRF T1 relaxometry of the healthy prostate observed in this preliminary study, therefore, supports the technique’s prospective clinical validation as part of larger trials employing 1.5 T MRI systems, which are still widely used clinically for routine mpMRI of the prostate.

Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7–1.3% for T1, 2.0–7.8% for T2, 1.4–2.5% for normalized PD) and reproducibility (CVs of 2.0–5.8% for T1, 7.4–10.2% for T2, 5.2–9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.

The Erlenmeyer flask deformity is a common skeletal modeling deformity, but current classification systems are binary and may restrict its utility as a predictor of associated skeletal conditions. A quantifiable 3-point system of severity classification could improve its predictive potential in disease. Ratios were derived from volumes of regions of interests drawn in 50 Gaucher’s disease patients. ROIs were drawn from the distal physis to 2 cm proximal, 2 cm to 4 cm, and 4 cm to 6 cm. Width was also measured at each of these boundaries. Two readers rated these 100 femurs using a 3-point scale of severity classification. Weighted kappa indicated reliability and one-way analysis of variance characterized ratio differences across the severity scale. Accuracy analyses allowed determination of clinical cutoffs for each ratio. Pearson’s correlations assessed the associations of volume and width with a shape-based concavity metric of the femur. The volume ratio incorporating the metaphyseal region from 0 to 2 cm and the diametaphyseal region at 4–6 cm was most accurate at distinguishing femurs on the 3-point scale. Receiver operating characteristic curves for this ratio indicated areas of 0.95 to distinguish normal and mild femurs and 0.93 to distinguish mild and severe femurs. Volume was moderately associated with the degree of femur concavity. The proposed volume ratio method is an objective, proficient method at distinguishing severities of the Erlenmeyer flask deformity with the potential for automation. This may have application across diseases associated with the deformity and deficient osteoclast-mediated modeling of growing bone. Electronic supplementary material The online version of this article (10.1007/s00256-020-03561-2) contains supplementary material, which is available to authorized users.

Magnetic resonance fingerprinting (MRF) is a rapidly developing fast quantitative mapping technique able to produce multiple property maps with reduced sensitivity to motion. MRF has shown promise in improving the diagnosis of clinically significant prostate cancer but requires further validation as part of a prostate multiparametric (mp) MRI protocol. mpMRI protocol mandates the inclusion of dynamic contrast enhanced (DCE) imaging, known for its significant T1 shortening effect. MRF could be used to measure both pre- and post-contrast T1 values, but its utility must be assessed. In this proof-of-concept study, we sought to evaluate the variation in MRF T1 measurements post gadolinium-based contrast agent (GBCA) injection and the utility of such T1 measurements to differentiate peripheral and transition zone tumours from normal prostatic tissue. We found that the T1 variation in all tissues increased considerably post-GBCA following the expected significant T1 shortening effect, compromising the ability of MRF T1 to identify transition zone lesions. We, therefore, recommend performing MRF T1 prior to DCE imaging to maintain its benefit for improving detection of both peripheral and transition zone lesions while reducing additional scanning time. Demonstrating the effect of GBCA on MRF T1 relaxometry in patients also paves the way for future clinical studies investigating the added value of post-GBCA MRF in PCa, including its dynamic analysis as in DCE-MRF.

Purpose: Calibration of hyperpolarized 13C-MRI is limited by the low signal from endogenous carbon-containing molecules and consequently requires 13C-enriched external phantoms. This study investigated the feasibility of using either 23Na-MRI or 1H-MRI to calibrate the 13C excitation. Methods: Commercial 13C-coils were used to estimate the transmit gain and center frequency for 13C and 23Na resonances. Simulations of the transmit B1 profile of a Helmholtz loop were performed. Noise correlation was measured for both nuclei. A retrospective analysis of human data assessing the use of the 1H resonance to predict [1-13C]pyruvate center frequency was also performed. In vivo experiments were undertaken in the lower limbs of 6 pigs following injection of hyperpolarized 13C-pyruvate. Results: The difference in center frequencies and transmit gain between tissue 23Na and [1-13C]pyruvate was reproducible, with a mean scale factor of 1.05179 ± 0.00001 and 10.4 ± 0.2 dB, respectively. Utilizing the 1H water peak, it was possible to retrospectively predict the 13C-pyruvate center frequency with a standard deviation of only 11 Hz sufficient for spectral–spatial excitation-based studies. Conclusion: We demonstrate the feasibility of using the 23Na and 1H resonances to calibrate the 13C transmit B1 using commercially available 13C-coils. The method provides a simple approach for in vivo calibration and could improve clinical workflow.

Multipotent Mesenchymal Stem/Stromal Cells (MSCs) are widely used in cellular therapy for joint repair. However, the use of MSC therapies is complicated by a lack of understanding of the behaviour of cells and repair within the joint. Current methods of MSC tracking include labelling the cells with Super Paramagnetic Iron Oxide nanoparticles (SPIOs). However, standard acquisition sequences (T

Multiparametric magnetic resonance imaging (MRI) can be used to characterize many cancer subtypes including ovarian cancer. Quantitative mapping of MRI relaxation values, such as T1 and T2 mapping, is promising for improving tumor assessment beyond conventional qualitative T1- and T2-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 T1 and T2 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 T1, T2, and relative proton density (rPD) mapping using ovarian cancer as a model system.

Significance Carbon-13 MRI was used to assess exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and the endogenous tumor lactate pool in breast cancer patients. Higher levels of 13C label exchange were observed in more-aggressive tumors, including all triple-negative cancers. The 13C label exchange correlated significantly with the expression of the transmembrane transporter mediating uptake of pyruvate into tumor cells and hypoxia inducible factor 1 (HIF1α), but no significant correlation with the expression of lactate dehydrogenase, the enzyme that catalyzes the exchange. The study has shown that 13C MRI can be used for metabolic imaging of breast cancer patients in the clinic, creating possibilities for noninvasive cancer monitoring in this patient group., Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Purpose To obtain a fast and robust fat-water separation with simultaneous estimation of water T1 , fat T1 , and fat fraction maps. Methods We modified an MR fingerprinting (MRF) framework to use a single dictionary combination of a water and fat dictionary. A variable TE acquisition pattern with maximum TE = 4.8 ms was used to increase the fat-water separability. Radiofrequency (RF) spoiling was used to reduce the size of the dictionary by reducing T2 sensitivity. The technique was compared both in vitro and in vivo to an MRF method that incorporated 3-point Dixon (DIXON MRF), as well as Cartesian IDEAL with different acquisition parameters. Results The proposed dictionary-based fat-water separation technique (DBFW MRF) successfully provided fat fraction, water, and fat T1 , B0 , and B1+ maps both in vitro and in vivo. The fat fraction and water T1 values obtained with DBFW MRF show excellent agreement with DIXON MRF as well as with the reference values obtained using a Cartesian IDEAL with a long TR (concordance correlation coefficient: 0.97/0.99 for fat fraction-water T1 ). Whereas fat fraction values with Cartesian IDEAL were degraded in the presence of T1 saturation, MRF methods successfully estimated and accounted for T1 in the fat fraction estimates. Conclusion The DBFW MRF technique can successfully provide T1 and fat fraction quantification in under 20 s per slice, intrinsically correcting T1 biases typical of fast Dixon techniques. These features could improve the diagnostic quality and use of images in presence of fat.

The concentration of sodium ions (Na(+)) is raised in solid tumours and can be measured at the cellular, tissue and patient levels. At the cellular level, the Na(+) gradient across the membrane powers the transport of H(+) ions and essential nutrients for normal activity. The maintenance of the Na(+) gradient requires a large proportion of the cell's ATP. Na(+) is a major contributor to the osmolarity of the tumour microenvironment, which affects cell volume and metabolism as well as immune function. Here, we review evidence indicating that Na(+) handling is altered in tumours, explore our current understanding of the mechanisms that may underlie these alterations and consider the potential consequences for cancer progression. Dysregulated Na(+) balance in tumours may open opportunities for new imaging biomarkers and re-purposing of drugs for treatment.

There has been recent interest in nonproton MRI including hyperpolarized carbon-13 (To compare TSC measurements from aProspective.Eight patients with biopsy-proven, intermediate/high risk prostate cancer imaged prior to prostatectomy.3T MRI with separate dual-tunedRegions-of-interest for TSC quantification were defined for normal peripheral zone (PZ), normal transition zone (TZ), and tumor, with reference to histopathology maps.Two-sided Wilcoxon rank sum with additional measures of correlation, coefficient of variation, and Bland-Altman plots to assess for between-test differences.Mean TSC for normal PZ and TZ were 39.2 and 33.9 mM, respectively, with theWe 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 both2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:90-97.

Fully-quantitative MR imaging methods are useful for longitudinal characterization of disease and assessment of treatment efficacy. However, current quantitative MRI protocols have not been widely adopted in the clinic, mostly due to lengthy scan times. Magnetic Resonance Fingerprinting (MRF) is a new technique that can reconstruct multiple parametric maps from a single fast acquisition in the transient state of the MR signal. Due to the relative novelty of this technique, the repeatability and reproducibility of quantitative measurements obtained using MRF has not been extensively studied. Our study acquired test/retest data from the brains of nine healthy volunteers, each scanned on five MRI systems (two at 3.0 T and three at 1.5 T, all from a single vendor) located at two different centers. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived M0, T1 and T2 maps to an anatomical atlas, coefficients-of-variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated an excellent repeatability (CVs of 2–3% for T1, 5–8% for T2, 3% for normalized-M0) and a good reproducibility (CVs of 3–8% for T1, 8–14% for T2, 5% for normalized-M0) in grey and white matter.

Sodium magnetic resonance imaging (MRI), or imaging of the 23Na nucleus, has been under exploration for several decades, and holds promise for potentially revealing additional biochemical information about the health of tissues that cannot currently be obtained from conventional hydrogen (or proton) MRI. This additional information could serve as an important complement to conventional MRI for many applications. However, despite these exciting possibilities, sodium MRI is not yet used routinely in clinical practice, and will likely remain strictly in the domain of exploratory research for the coming decade. This paper begins with a technical overview of sodium MRI, including the nuclear magnetic resonance (NMR) signal characteristics of the sodium nucleus, the challenges associated with sodium MRI, and the specialized pulse sequences, hardware, and reconstruction techniques required. Various applications of sodium MRI for quantitative analysis of the musculoskeletal system are then reviewed, including the non-invasive assessment of cartilage degeneration in vivo, imaging of tendinopathy, applications in the assessment of various muscular pathologies, and assessment of muscle response to exercise.

PURPOSE To demonstrate that concomitant magnetic fields can cause significant spatially dependent biases in T2* relaxometry measurements with implications for clinical applications such as BOLD and dynamic susceptibility contrast-enhanced MRI. THEORY AND METHODS After developing a theoretical framework for intravoxel dephasing and signal loss from concomitant magnetic fields, this framework and the effect of concomitant fields on T2* are validated with phantom experiments and numerical simulation. In lower leg and renal T2* mapping, we quantify measurement bias for imaging protocols with high gradient amplitude multiecho readouts, comparable to those used in clinical applications. RESULTS Concordance between phantom experiment and numerical simulation validate the theoretical framework. Changes in T2* measured in the lower leg and kidney varied by up to 15% and 35%, respectively, as a result of concomitant gradient effects when compared with the control measurements. CONCLUSION Concomitant magnetic fields produced by imaging gradient coils can cause clinically significant T2* mapping errors when high amplitude, long duration gradient waveforms are used. While we have shown that measurement biases can be quite large, modification of imaging parameters can potentially reduce concomitant field-induced measurement errors to acceptable levels. Magn Reson Med 77:1562-1572, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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.