Imaging standardisation in metastatic colorectal cancer: A joint EORTC-ESOI-ESGAR expert consensus recommendation.

BACKGROUND: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points. PATIENTS AND METHODS: Acknowledging the recently highlighted potential of radiomics and artificial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. RESULTS: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. CONCLUSION: This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centres.

Imaging features for the prediction of clinical endpoints in chronic liver disease: a scoping review protocol.

INTRODUCTION: Chronic liver disease is a growing cause of morbidity and mortality in the UK. Acute presentation with advanced disease is common and prioritisation of resources to those at highest risk at earlier disease stages is essential to improving patient outcomes. Existing prognostic tools are of limited accuracy and to date no imaging-based tools are used in clinical practice, despite multiple anatomical imaging features that worsen with disease severity.In this paper, we outline our scoping review protocol that aims to provide an overview of existing prognostic factors and models that link anatomical imaging features with clinical endpoints in chronic liver disease. This will provide a summary of the number, type and methods used by existing imaging feature-based prognostic studies and indicate if there are sufficient studies to justify future systematic reviews. METHODS AND ANALYSIS: The protocol was developed in accordance with existing scoping review guidelines. Searches of MEDLINE and Embase will be conducted using titles, abstracts and Medical Subject Headings restricted to publications after 1980 to ensure imaging method relevance on OvidSP. Initial screening will be undertaken by two independent reviewers. Full-text data extraction will be undertaken by three pretrained reviewers who have participated in a group data extraction session to ensure reviewer consensus and reduce inter-rater variability. Where needed, data extraction queries will be resolved by reviewer team discussion. Reporting of results will be based on grouping of related factors and their cumulative frequencies. Prognostic anatomical imaging features and clinical endpoints will be reported using descriptive statistics to summarise the number of studies, study characteristics and the statistical methods used. ETHICS AND DISSEMINATION: Ethical approval is not required as this study is based on previously published work. Findings will be disseminated by peer-reviewed publication and/or conference presentations.

Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial.

OBJECTIVE: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). DESIGN: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. RESULTS: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. CONCLUSIONS: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG. TRIAL REGISTRATION NUMBER: NCT02879383.

Current Applications and Future Development of Magnetic Resonance Fingerprinting in Diagnosis, Characterization, and Response Monitoring in Cancer.

Magnetic resonance imaging (MRI) has enabled non-invasive cancer diagnosis, monitoring, and management in common clinical settings. However, inadequate quantitative analyses in MRI continue to limit its full potential and these often have an impact on clinicians' judgments. Magnetic resonance fingerprinting (MRF) has recently been introduced to acquire multiple quantitative parameters simultaneously in a reasonable timeframe. Initial retrospective studies have demonstrated the feasibility of using MRF for various cancer characterizations. Further trials with larger cohorts are still needed to explore the repeatability and reproducibility of the data acquired by MRF. At the moment, technical difficulties such as undesirable processing time or lack of motion robustness are limiting further implementations of MRF in clinical oncology. This review summarises the latest findings and technology developments for the use of MRF in cancer management and suggests possible future implications of MRF in characterizing tumour heterogeneity and response assessment.

Haemodynamic changes in cirrhosis following terlipressin and induction of sepsis-a preclinical study using caval subtraction phase-contrast and cardiac MRI.

OBJECTIVES: Effects of liver disease on portal venous (PV), hepatic arterial (HA), total liver blood flow (TLBF), and cardiac function are poorly understood. Terlipressin modulates PV flow but effects on HA, TLBF, and sepsis/acute-on-chronic liver failure (ACLF)-induced haemodynamic changes are poorly characterised. In this study, we investigated the effects of terlipressin and sepsis/ACLF on hepatic haemodynamics and cardiac function in a rodent cirrhosis model using caval subtraction phase-contrast (PC) MRI and cardiac cine MRI. METHODS: Sprague-Dawley rats (n = 18 bile duct-ligated (BDL), n = 16 sham surgery controls) underwent caval subtraction PCMRI to estimate TLBF and HA flow and short-axis cardiac cine MRI for systolic function at baseline, following terlipressin and lipopolysaccharide (LPS) infusion, to model ACLF. RESULTS: All baseline hepatic haemodynamic/cardiac systolic function parameters (except heart rate and LV mass) were significantly different in BDL rats. Following terlipressin, baseline PV flow (sham 181.4 ± 12.1 ml/min/100 g; BDL 68.5 ± 10.1 ml/min/100 g) reduced (sham - 90.3 ± 11.1 ml/min/100 g, p < 0.0001; BDL - 31.0 ± 8.0 ml/min/100 g, p = 0.02), sham baseline HA flow (33.0 ± 11.3 ml/min/100 g) increased (+ 92.8 ± 21.3 ml/min/100 g, p = 0.0003), but BDL baseline HA flow (83.8 ml/min/100 g) decreased (- 34.4 ± 7.5 ml/min/100 g, p = 0.11). Sham baseline TLBF (214.3 ± 16.7 ml/min/100 g) was maintained (+ 2.5 ± 14.0 ml/min/100 g, p > 0.99) but BDL baseline TLBF (152.3 ± 18.7 ml/min/100 g) declined (- 65.5 ± 8.5 ml/min/100 g, p = 0.0004). Following LPS, there were significant differences between cohort and change in HA fraction (p = 0.03) and TLBF (p = 0.01) with BDL baseline HA fraction (46.2 ± 4.6%) reducing (- 20.9 ± 7.5%, p = 0.03) but sham baseline HA fraction (38.2 ± 2.0%) remaining unchanged (+ 2.9 ± 6.1%, p > 0.99). Animal cohort and change in systolic function interactions were significant only for heart rate (p = 0.01) and end-diastolic volume (p = 0.03). CONCLUSIONS: Caval subtraction PCMRI and cardiac MRI in a rodent model of cirrhosis demonstrate significant baseline hepatic haemodynamic/cardiac differences, failure of the HA buffer response post-terlipressin and an altered HA fraction response in sepsis, informing potential translation to ACLF patients. KEY POINTS: Caval subtraction phase-contrast and cardiac MRI demonstrate: • Significant differences between cirrhotic/non-cirrhotic rodent hepatic blood flow and cardiac systolic function at baseline. • Failure of the hepatic arterial buffer response in cirrhotic rodents in response to terlipressin. • Reductions in hepatic arterial flow fraction in the setting of acute-on-chronic liver failure.

Serum Scoring and Quantitative Magnetic Resonance Imaging in Intestinal Failure-Associated Liver Disease: A Feasibility Study.

(1) Background: Intestinal failure-associated liver disease (IFALD) in adults is characterized by steatosis with variable progression to fibrosis/cirrhosis. Reference standard liver biopsy is not feasible for all patients, but non-invasive serological and quantitative MRI markers for diagnosis/monitoring have not been previously validated. Here, we examine the potential of serum scores and feasibility of quantitative MRI used in non-IFALD liver diseases for the diagnosis of IFALD steatosis; (2) Methods: Clinical and biochemical parameters were used to calculate serum scores in patients on home parenteral nutrition (HPN) with/without IFALD steatosis. A sub-group underwent multiparameter quantitative MRI measurements of liver fat fraction, iron content, tissue T1, liver blood flow and small bowel motility; (3) Results: Compared to non-IFALD (n = 12), patients with IFALD steatosis (n = 8) demonstrated serum score elevations in Enhanced Liver Fibrosis (p = 0.032), Aspartate transaminase-to-Platelet Ratio Index (p < 0.001), Fibrosis-4 Index (p = 0.010), Forns Index (p = 0.001), Gamma-glutamyl transferase-to-Platelet Ratio Index (p = 0.002) and Fibrosis Index (p = 0.001). Quantitative MRI scanning was feasible in all 10 sub-group patients. Median liver fat fraction was higher in IFALD steatosis patients (10.9% vs 2.1%, p = 0.032); other parameter differences were non-significant; (4) Conclusion: Serum scores used for non-IFALD liver diseases may be useful in IFALD steatosis. Multiparameter MRI is feasible in patients on HPN.

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer.

BACKGROUND: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. METHODS/DESIGN: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. DISCUSSION: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. TRIAL REGISTRATION: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

Super-resolution for upper abdominal MRI: Acquisition and post-processing protocol optimization using brain MRI control data and expert reader validation.

PURPOSE: Magnetic resonance (MR) cholangiopancreatography (MRCP) is an established specialist method for imaging the upper abdomen and biliary/pancreatic ducts. Due to limitations of either MR image contrast or low through-plane resolution, patients may require further evaluation with contrast-enhanced computed tomography (CT) images. However, CT fails to offer the high tissue-ductal-vessel contrast-to-noise ratio available on T2-weighted MR imaging. METHODS: MR super-resolution reconstruction (SRR) frameworks have the potential to provide high-resolution visualizations from multiple low through-plane resolution single-shot T2-weighted (SST2W) images as currently used during MRCP studies. Here, we (i) optimize the source image acquisition protocols by establishing the ideal number and orientation of SST2W series for MRCP SRR generation, (ii) optimize post-processing protocols for two motion correction candidate frameworks for MRCP SRR, and (iii) perform an extensive validation of the overall potential of upper abdominal SRR, using four expert readers with subspeciality interest in hepato-pancreatico-biliary imaging. RESULTS: Obtained SRRs show demonstrable advantages over traditional SST2W MRCP data in terms of anatomical clarity and subjective radiologists' preference scores for a range of anatomical regions that are especially critical for the management of cancer patients. CONCLUSIONS: Our results underline the potential of using SRR alongside traditional MRCP data for improved clinical diagnosis.

Quantitative pancreatic MRI: a pathology-based review.

MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences capturing pancreatic structure can however be adapted to yield quantitative measures which provide more diagnostic information, with a view to increasing diagnostic accuracy, improving patient stratification, providing robust non-invasive outcome measures for therapeutic trials and ultimately personalizing patient care. In this review, we evaluate the use of established techniques such as secretin-enhanced MR cholangiopancreatography, diffusion-weighted imaging, T 1, T 2* and fat fraction mapping, but also more experimental methods such as MR elastography and arterial spin labelling, and their application to the assessment of diffuse pancreatic disease (including chronic, acute and autoimmune pancreatitis/IgG4 disease, metabolic disease and iron deposition disorders) and cystic/solid focal pancreatic masses. Finally, we explore some of the broader challenges to their implementation and future directions in this promising area.

Fat fraction mapping using magnetic resonance imaging: insight into pathophysiology.

Adipose cells have traditionally been viewed as a simple, passive energy storage depot for triglycerides. However, in recent years it has become clear that adipose cells are highly physiologically active and have a multitude of endocrine, metabolic, haematological and immune functions. Changes in the number or size of adipose cells may be directly implicated in disease (e.g. in the metabolic syndrome), but may also be linked to other pathological processes such as inflammation, malignant infiltration or infarction. MRI is ideally suited to the quantification of fat, since most of the acquired signal comes from water and fat protons. Fat fraction (FF, the proportion of the acquired signal derived from fat protons) has, therefore, emerged as an objective, image-based biomarker of disease. Methods for FF quantification are becoming increasingly available in both research and clinical settings, but these methods vary depending on the scanner, manufacturer, imaging sequence and reconstruction software being used. Careful selection of the imaging method-and correct interpretation-can improve the accuracy of FF measurements, minimize potential confounding factors and maximize clinical utility. Here, we review methods for fat quantification and their strengths and weaknesses, before considering how they can be tailored to specific applications, particularly in the gastrointestinal and musculoskeletal systems. FF quantification is becoming established as a clinical and research tool, and understanding the underlying principles will be helpful to both imaging scientists and clinicians.

Improved hepatic arterial fraction estimation using cardiac output correction of arterial input functions for liver DCE MRI.

Liver dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling could be useful in the assessment of diffuse liver disease and focal liver lesions, but is compromised by errors in arterial input function (AIF) sampling. In this study, we apply cardiac output correction to arterial input functions (AIFs) for liver DCE MRI and investigate the effect on dual-input single compartment hepatic perfusion parameter estimation and reproducibility. Thirteen healthy volunteers (28.7 ± 1.94 years, seven males) underwent liver DCE MRI and cardiac output measurement using aortic root phase contrast MRI (PCMRI), with reproducibility (n = 9) measured at 7 d. Cardiac output AIF correction was undertaken by constraining the first pass AIF enhancement curve using the indicator-dilution principle. Hepatic perfusion parameters with and without cardiac output AIF correction were compared and 7 d reproducibility assessed. Differences between cardiac output corrected and uncorrected liver DCE MRI portal venous (PV) perfusion (p = 0.066), total liver blood flow (TLBF) (p = 0.101), hepatic arterial (HA) fraction (p = 0.895), mean transit time (MTT) (p = 0.646), distribution volume (DV) (p = 0.890) were not significantly different. Seven day corrected HA fraction reproducibility was improved (mean difference 0.3%, Bland-Altman 95% limits-of-agreement (BA95%LoA) ±27.9%, coefficient of variation (CoV) 61.4% versus 9.3%, ±35.5%, 81.7% respectively without correction). Seven day uncorrected PV perfusion was also improved (mean difference 9.3 ml min-1/100 g, BA95%LoA ±506.1 ml min-1/100 g, CoV 64.1% versus 0.9 ml min-1/100 g, ±562.8 ml min-1/100 g, 65.1% respectively with correction) as was uncorrected TLBF (mean difference 43.8 ml min-1/100 g, BA95%LoA ±586.7 ml min-1/ 100 g, CoV 58.3% versus 13.3 ml min-1/100 g, ±661.5 ml min-1/100 g, 60.9% respectively with correction). Reproducibility of uncorrected MTT was similar (uncorrected mean difference 2.4 s, BA95%LoA ±26.7 s, CoV 60.8% uncorrected versus 3.7 s, ±27.8 s, 62.0% respectively with correction), as was and DV (uncorrected mean difference 14.1%, BA95%LoA ±48.2%, CoV 24.7% versus 10.3%, ±46.0%, 23.9% respectively with correction). Cardiac output AIF correction does not significantly affect the estimation of hepatic perfusion parameters but demonstrates improvements in normal volunteer 7 d HA fraction reproducibility, but deterioration in PV perfusion and TLBF reproducibility. Improved HA fraction reproducibility maybe important as arterialisation of liver perfusion is increased in chronic liver disease and within malignant liver lesions.