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Objective To develop a phantom system which can be integrated with an automated injection system, eliminating the experimental variability that arises with manual injection; for the purposes of pulse sequence testing and metric derivation in hyperpolarised 13C-MR. Methods The custom dynamic phantom was machined from Ultem and filled with a nicotinamide adenine dinucleotide and lactate dehydrogenase mixture dissolved in phosphate buffered saline. Hyperpolarised [1-13C]-pyruvate was then injected into the phantom (n = 8) via an automated syringe pump and the conversion of pyruvate to lactate monitored through a 13C imaging sequence. Results The phantom showed low coefficient of variation for the lactate to pyruvate peak signal heights (11.6%) and dynamic area-under curve ratios (11.0%). The variance for the lactate dehydrogenase enzyme rate constant (kP) was also seen to be low at 15.6%. Conclusion The dynamic phantom demonstrates high reproducibility for quantification of 13C-hyperpolarised MR-derived metrics. Establishing such a phantom is needed to facilitate development of hyperpolarsed 13C-MR pulse sequenced; and moreover, to enable multisite hyperpolarised 13C-MR clinical trials where assessment of metric variability across sites is critical. Advances in knowledge The dynamic phantom developed during the course of this study will be a useful tool in testing new pulse sequences and standardisation in future hyperpolarised work.

IntroductionMultiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and a high false-positive rate, especially in men with mpMRI scored as indeterminate (3/5) or likely (4/5) to have clinically significant cancer (csPCa) (Gleason ≥3+4). Advanced MRI techniques have emerged which seek to improve this characterisation and could predict biopsy results non-invasively. Before these techniques are translated clinically, robust histological and clinical validation is required.Methods and analysisThis study aims to clinically validate two advanced MRI techniques in a prospectively recruited cohort of men suspected of prostate cancer. Histological analysis of men undergoing biopsy or prostatectomy will be used for biological validation of biomarkers derived from Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours and Luminal Water imaging. In particular, prostatectomy specimens will be processed using three-dimension printed patient-specific moulds to allow for accurate MRI and histology mapping. The index tests will be compared with the histological reference standard to derive false positive rate and true positive rate for men with mpMRI scores which are indeterminate (3/5) or likely (4/5) to have clinically significant prostate cancer (csPCa). Histopathological validation from both biopsy and prostatectomy samples will provide the best ground truth in validating promising MRI techniques which could predict biopsy results and help avoid unnecessary biopsies in men suspected of prostate cancer.Ethics and disseminationEthical approval was granted by the London—Queen Square Research Ethics Committee (19/LO/1803) on 23 January 2020. Results from the study will be presented at conferences and submitted to peer-reviewed journals for publication. Results will also be available on ClinicalTrials.gov.Trial registration numberNCT04792138.

Hyperpolarised 13C MRI (HP-MRI) is a novel imaging technique that allows real-time analysis of metabolic pathways in vivo. 1 The technology to conduct HP-MRI in humans has recently become available and is starting to be clinically applied. As knowledge of molecular biology advances, it is increasingly apparent that cancer cell metabolism is related to disease outcomes, with lactate attracting specific attention. 2 Recent reviews of breast cancer screening programs have raised concerns and increased public awareness of over treatment. The scientific community needs to shift focus from improving cancer detection alone to pursuing novel methods of distinguishing aggressive breast cancers from those which will remain indolent. HP-MRI offers the opportunity to identify aggressive tumour phenotypes and help monitor/predict therapeutic response. Here we report one of the first cases of breast cancer imaged using HP-MRI alongside correlative conventional imaging, including breast MRI.

Purpose: Diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (MRI) are increasingly applied for the assessment of functional tissue biomarkers for diagnosis, lesion characterization, or for monitoring of treatment response. However, these techniques are vulnerable to the influence of various factors, so there is a necessity for a standardized MR quality assurance procedure utilizing a phantom to facilitate the reliable estimation of repeatability of these quantitative biomarkers arising from technical factors (e.g., B 1 variation) affecting acquisition on scanners of different vendors and field strengths. The purpose of this study is to present a novel phantom designed for use in quality assurance for multicenter trials, and the associated repeatability measurements of functional and quantitative imaging protocols across different MR vendors and field strengths. Methods: A cylindrical acrylic phantom was manufactured containing 7 vials of polyvinylpyrrolidone (PVP) solutions of different concentrations, ranging from 0% (distilled water) to 25% w/w, to create a range of different MR contrast parameters. Temperature control was achieved by equilibration with ice-water. Repeated MR imaging measurements of the phantom were performed on four clinical scanners (two at 1.5 T, two at 3.0 T; two vendors) using the same scanning protocol to assess the long-term and short-term repeatability. The scanning protocol consisted of DW measurements, inversion recovery (IR) T 1 measurements, multiecho T 2 measurement, and dynamic T 1-weighted sequence allowing multiple variable flip angle (VFA) estimation of T 1 values over time. For each measurement, the corresponding calculated parameter maps were produced. On each calculated map, regions of interest (ROIs) were drawn within each vial and the median value of these voxels was assessed. For the dynamic data, the autocorrelation function and their variance were calculated; for the assessment of the repeatability, the coefficients of variation (CoV) were calculated. Results: For both field strengths across the available vendors, the apparent diffusion coefficient (ADC) at 0 °C ranged from (1.12 ± 0.01) × 10−3 mm2/s for pure water to (0.48 ± 0.02) × 10−3 mm2/s for the 25% w/w PVP concentration, presenting a minor variability between the vendors and the field strengths. T 2 and IR-T 1 relaxation time results demonstrated variability between the field strengths and the vendors across the different acquisitions. Moreover, the T 1 values derived from the VFA method exhibited a large variation compared with the IR-T 1 values across all the scanners for all repeated measurements, although the calculation of the standard deviation of the VFA-T 1 estimate across each ROI and the autocorrelation showed a stability of the signal for three scanners, with autocorrelation of the signal over the dynamic series revealing a periodic variation in one scanner. Finally, the ADC, the T 2, and the IR-T 1 values exhibited an excellent repeatability across the scanners, whereas for the dynamic data, the CoVs were higher. Conclusions: The combination of a novel PVP phantom, with multiple compartments to give a physiologically relevant range of ADC and T 1 values, together with ice-water as a temperature-controlled medium, allows reliable quality assurance measurements that can be used to measure agreement between MRI scanners, critical in multicenter functional and quantitative imaging studies.

The aim of this study is to dosimetrically characterize a new MRI based polymer gel system and to evaluate its usefulness in clinical practice just in terms of beam profile measurements. Normoxic N-vinylpyrrolidone based polymer gel (VIPET) phantoms were produced and used in order to perform three main sets of experiments: a) dose-response evaluation and reproducibility experiments, b) experiments for the evaluation of sensitivity of dose characteristics on 'gel manufacture - irradiation' time interval and c) experiments for the evaluation of sensitivity of dose characteristics on 'irradiation - MRscanning' time interval. It has been shown that this gel system can be used in a wide dose-range of 0-60 Gy. It exhibits a linear dose-response in the dose-range of 2-35 Gy. Following the proposed manufacturing method the dose-response characteristics are reproducible. Moreover, it seems that the optimum 'gel manufacturing - irradiation' time interval is 1 day. However, a 'gel manufacturing - irradiation' time interval up to ∼1 week can be safely used. The optimum 'irradiation - MRscanning' time interval in terms of dose-response sensitivity and dose resolution can be reliably ranged from 1 day to 3 weeks. Finally, X-ray beam profile gel-measurements were performed and found to be in satisfying agreement with corresponding small sensitive volume ion chamber measurements. VIPET gel dosimeters preserved the spatial integrity of the dose distribution during a time period of 50 days post-irradiation. The studied gel system can be safely used in clinical practice within the practical limitations found and described in this work.

Purpose: To determine the test-retest repeatability of Apparent Diffusion Coefficient (ADC) measurements across institutions and MRI vendors, plus investigate the effect of post-processing methodology on measurement precision. Methods: Thirty malignant lung lesions >2 cm in size (23 patients) were scanned on two occasions, using echo-planar-Diffusion-Weighted (DW)-MRI to derive whole-tumour ADC (b = 100, 500 and 800smm-2). Scanning was performed at 4 institutions (3 MRI vendors). Whole-tumour volumes-of-interest were copied from first visit onto second visit images and from one post-processing platform to an open-source platform, to assess ADC repeatability and cross-platform reproducibility. Results: Whole-tumour ADC values ranged from 0.66-1.94x10-3mm2s-1 (mean = 1.14). Within-patient coefficient-of-variation (wCV) was 7.1% (95% CI 5.7–9.6%), limits-of-agreement (LoA) -18.0 to 21.9%. Lesions >3 cm had improved repeatability: wCV 3.9% (95% CI 2.9–5.9%); and LoA -10.2 to 11.4%. Variability for lesions 2 = 0.99; CoV 2.8% (95% CI 2.3-3.4%); and LoA -7.4 to 8.0%. Conclusion: A free-breathing DW-MRI protocol for imaging malignant lung tumours achieved satisfactory within-patient repeatability and was robust to changes in post-processing software, justifying its use in multi-centre trials. For response evaluation in individual patients, a change in ADC >21.9% will reflect treatment-related change. Key Points: • In lung cancer, free-breathing DWI-MRI produces acceptable images with evaluable ADC measurement. • ADC repeatability coefficient-of-variation is 7.1% for lung tumours >2 cm. • ADC repeatability coefficient-of-variation is 3.9% for lung tumours >3 cm. • ADC measurement precision is unaffected by the post-processing software used. • In multicentre trials, 22% increase in ADC indicates positive treatment response.