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

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

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 RCT, 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 (HbA1c 59–86mmol/mol, BMI ≥24 and ≤40kg/m2, fasting insulin >48.6pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver magnetic resonance imaging 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 (NAFLD), particularly in patients with high FPG

Imaging standardization 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 tumor burden. Response Evaluation Criteria in Solid Tumors (RECIST) provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardized imaging protocol tailored to mCRC patients. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging endpoints and is an obstacle for research on novel imaging endpoints. Patients and methods: Acknowledging the recently highlighted potential of radiomics and artificial intelligence (AI) 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 standardization and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardization will increase reproducibility of radiomics and AI studies and serve as a catalyst for future research on imaging endpoints. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centers.peer-reviewe

Hepatocyte labeling with ⁹⁹mTc-GSA:a potential non-invasive technique for tracking cell transplantation

Background: Hepatocyte transplantation is a promising alternative to orthotopic liver transplantation, however, the fate of transplanted hepatocytes is not well defined. 99mTc-galactosyl-serum albumin (99mTc-GSA) is a clinical scintigraphic agent which is specifically taken up by the hepatocyte asialoglycoprotein receptor (ASGPR). Aims: To investigate labeling of fresh and cryopreserved human hepatocytes and fresh rat hepatocytes in vitro using 99mTc-GSA Methods: Human and rat hepatocytes were isolated from liver tissue by collagenase perfusion. The ASGPR were characterized using immunohistochemistry and RT-PCR. Hepatocytes were incubated with 99mTc-GSA in suspension at 4°C and 37°C. Cell viability and function was determined using cell mitochondrial dehydrogenase (MTS) and sulphorhodamine B (SRB) assays. Results: Fresh and cryopreserved human hepatocytes expressed the ASGPR. Incubation of hepatocytes in suspension with 99mTc-GSA reduced the viability of hepatocytes, but this was similar to unlabeled control cells. Greater loss of viability was seen on incubation at 37°C compared to 4°C, but there was a significantly greater uptake of 99mTc-GSA at the physiological temperature (6.6 ± SE 0.6-fold increase, p&lt;0.05) consistent with ASGPR-mediated endocytosis. MTS and SRB assays were not significantly affected by labeling with 99mTc-GSA in all three cell types. A mean of 18.5% of the radioactivity was released over 120 min when 99mTc-GSA - labeled hepatocytes were shaken in vitro at 37°C. Conclusions: Human and rat hepatocytes can be labeled with 99mTc-GSA, which may have potential application for in vivo imaging after hepatocyte transplantation. </jats:sec

Deep learning-based detection of liver disease using MRI

Traditional approaches to MRI detection of liver disease require specialist hardware, sequences and post-processing. Here we propose a deep learning (DL) based model for the detection of liver disease using standard T2-weighted anatomical sequences, as an early feasibility study for the potential of DL-based classification of liver disease severity. Our DL model achieved a diagnostic accuracy of 0.92 on unseen data and achieved a test accuracy of 0.75 when trained with relevant anatomical segmentation masks without images, demonstrating potential scanner/sequence independence. Lastly, we used DL interpretability techniques to analyse failure cases

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