Quantitative MRCP and metrics of bile duct disease over time in patients with primary sclerosing cholangitis: A prospective study.

BACKGROUND: Imaging markers of biliary disease in primary sclerosing cholangitis (PSC) have potential for use in clinical and trial disease monitoring. Herein, we evaluate how quantitative magnetic resonance cholangiopancreatography (MRCP) metrics change over time, as per the natural history of disease. METHODS: Individuals with PSC were prospectively scanned using non-contrast MRCP. Quantitative metrics were calculated using MRCP+ post-processing software to assess duct diameters and dilated and strictured regions. Additionally, a hepatopancreatobiliary radiologist (blinded to clinical details, biochemistry and quantitative biliary metrics) reported each scan, including ductal disease assessment according to the modified Amsterdam Cholangiographic Score (MAS). RESULTS: At baseline, 14 quantitative MRCP+ metrics were found to be significantly different in patients with PSC (N = 55) compared to those with primary biliary cholangitis (N = 55), autoimmune hepatitis (N = 57) and healthy controls (N = 18). In PSC specifically, baseline metrics quantifying the number of strictures and the number and length of bile ducts correlated with the MAS, transient elastography and serum ALP values (p < 0.01 for all correlations). Over a median 371-day follow-up (range: 364-462), 29 patients with PSC underwent repeat MRCP, of whom 15 exhibited quantitative changes in MRCP+ metrics. Compared to baseline, quantitative MRCP+ identified an increasing number of strictures over time (p < 0.05). Comparatively, no significant differences in biochemistry, elastography or the MAS were observed between timepoints. Quantitative MRCP+ metrics remained stable in non-PSC liver disease. CONCLUSION: Quantitative MRCP+ identifies changes in ductal disease over time in PSC, despite stability in biochemistry, liver stiffness and radiologist-derived cholangiographic assessment (trial registration: ISRCTN39463479).

Novel multiparametric MRI detects improved future liver remnant quality post-dual vein embolization.

BACKGROUND: Optimisation of the future liver remnant (FLR) is crucial to outcomes of extended liver resections. This study aimed to assess the quality of the FLR before and after dual vein embolization (DVE) by quantitative multiparametric MRI. METHODS: Of 100 patients with liver metastases recruited in a clinical trial (Precision1:NCT04597710), ten consecutive patients with insufficient FLR underwent quantitative multiparametric MRI pre- and post-DVE (right portal and hepatic vein). FLR volume, liver fibro-inflammation (corrected T1) scores and fat percentage (proton density fat fraction, PDFF) were determined. Patient metrics were compared by Wilcoxon signed-rank test and statistical analysis done using R software. RESULTS: All patients underwent uncomplicated DVE with improvement in liver remnant health, median 37 days after DVE: cT1 scores reduced from median (interquartile range) 790 ms (753-833 ms) to 741 ms (708-760 ms) p = 0.014 [healthy range <795 ms], as did PDFF from 11% (4-21%), to 3% (2-12%) p = 0.017 [healthy range <5.6%]. There was a significant increase in median (interquartile range) FLR volume from 33% (30-37%)% to 49% (44-52%), p = 0.002. CONCLUSION: This non-invasive and reproducible MRI technique showed improvement in volume and quality of the FLR after DVE. This is a significant advance in our understanding of how to prevent liver failure in patients undergoing major liver surgery.

Collision Tumour Comprising Desmoplastic Ameloblastoma and Squamous Odontogenic Tumour in the Anterior Maxilla: A Case Report.

Collision tumours, characterized by the simultaneous occurrence of two distinct neoplasms within the same anatomical site, are exceedingly rare in oral pathology. This case report presents an uncommon collision tumour involving desmoplastic ameloblastoma and squamous odontogenic tumour in the anterior maxilla of a 52-year-old male from the Indian population. Desmoplastic ameloblastoma is a variant of ameloblastoma known for its unique histopathological features, while squamous odontogenic tumour is a benign epithelial odontogenic tumour with distinctive clinical behaviour. The rarity of this occurrence emphasizes the need for accurate diagnosis and effective treatment strategies. This report discusses the clinical presentation, radiographic findings, and histopathological characteristics of this collision tumour. Through the presentation of this case, we aim to contribute to the understanding of these rare entities and their management considerations.

Quantitative digital pathology enables automated and quantitative assessment of inflammatory activity in patients with autoimmune hepatitis.

Background: Chronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component. Methods: Whole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC). Results: ID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation. Conclusion: Quantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.

Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study.

Background: Sex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses. Methods: The observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.5 years). We conducted linear regression analysis to investigate the sex-specific associations of sex hormones and SHBG with liver fat, estimated by fatty liver index (FLI). For MR analyses, we selected genetic variants associated with sex hormones and SHBG and extracted their associations with magnetic resonance imaging measured liver fat from the largest up to date European genome-wide associations studies. Results: In the observational analysis, T, dihydrotestosterone (DHT), progesterone and 17α-hydroxyprogesterone (17-OHP) were inversely associated with FLI in men, with beta estimates ranging from -4.23 to -2.30 [p-value <0.001 to 0.003]. Whereas in women, a positive association of free T with FLI (ß = 4.17, 95%CI: 1.35, 6.98) was observed. SHBG was inversely associated with FLI across sexes [men: -3.45 (-5.13, -1.78); women: -9.23 (-12.19, -6.28)]. No causal association was found between genetically determined sex hormones and liver fat, but higher genetically determined SHBG was associated with lower liver fat in women (ß = -0.36, 95% CI: -0.61, -0.12). Conclusion: Our results provide suggestive evidence for a causal association between SHBG and liver fat in women, implicating the protective role of SHBG against liver fat accumulation.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

Ideal plasticity and shape memory of nanolamellar high-entropy alloys.

Understanding the relationship among elemental compositions, nanolamellar microstructures, and mechanical properties enables the rational design of high-entropy alloys (HEAs). Here, we construct nanolamellar AlxCoCuFeNi HEAs with alternating high- and low-Al concentration layers and explore their mechanical properties using a combination of molecular dynamic simulation and density functional theory calculation. Our results show that the HEAs with nanolamellar structures exhibit ideal plastic behavior during uniaxial tensile loading, a feature not observed in homogeneous HEAs. This remarkable ideal plasticity is attributed to the unique deformation mechanisms of phase transformation coupled with dislocation nucleation and propagation in the high-Al concentration layers and the confinement and slip-blocking effect of the low-Al concentration layers. Unexpectedly, this ideal plasticity is fully reversible upon unloading, leading to a remarkable shape memory effect. Our work highlights the importance of nanolamellar structures in controlling the mechanical and functional properties of HEAs and presents a fascinating route for the design of HEAs for both functional and structural applications.

Plasma Amino Acids in NAFLD Patients with Obesity Are Associated with Steatosis and Fibrosis: Results from the MAST4HEALTH Study.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been linked to changes in amino acid (AA) levels. The objective of the current study was to examine the relationship between MRI parameters that reflect inflammation and fibrosis and plasma AA concentrations in NAFLD patients. Plasma AA levels of 97 NAFLD patients from the MAST4HEALTH study were quantified with liquid chromatography. Medical, anthropometric and lifestyle characteristics were collected and biochemical parameters, as well as inflammatory and oxidative stress biomarkers, were measured. In total, subjects with a higher MRI-proton density fat fraction (MRI-PDFF) exhibited higher plasma AA levels compared to subjects with lower PDFF. The concentrations of BCAAs (p-Value: 0.03), AAAs (p-Value: 0.039), L-valine (p-Value: 0.029), L-tyrosine (p-Value: 0.039) and L-isoleucine (p-Value: 0.032) were found to be significantly higher in the higher PDFF group compared to lower group. Plasma AA levels varied according to MRI-PDFF. Significant associations were also demonstrated between AAs and MRI-PDFF and MRI-cT1, showing the potential utility of circulating AAs as diagnostic markers of NAFLD.

Underlying factors determining grain morphologies in high-strength titanium alloys processed by additive manufacturing.

In recent research, additions of solute to Ti and some Ti-based alloys have been employed to produce equiaxed microstructures when processing these materials using additive manufacturing. The present study develops a computational scheme for guiding the selection of such alloying additions, and the minimum amounts required, to effect the columnar to equiaxed microstructural transition. We put forward two physical mechanisms that may produce this transition; the first and more commonly discussed is based on growth restriction factors, and the second on the increased freezing range effected by the alloying addition coupled with the imposed rapid cooling rates associated with AM techniques. We show in the research described here, involving a number of model binary as well as complex multi-component Ti alloys, and the use of two different AM approaches, that the latter mechanism is more reliable regarding prediction of the grain morphology resulting from given solute additions.

Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.

BACKGROUND & AIMS: Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events. METHODS: Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c). RESULTS: A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001). CONCLUSION: Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat. IMPACT AND IMPLICATIONS: Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.

Exceptional enhancement of mechanical properties in high-entropy alloys via thermodynamically guided local chemical ordering.

Understanding the local chemical ordering propensity in random solid solutions, and tailoring its strength, can guide the design and discovery of complex, paradigm-shifting multicomponent alloys. First, we present a simple thermodynamic framework, based solely on binary enthalpies of mixing, to select optimal alloying elements to control the nature and extent of chemical ordering in high-entropy alloys (HEAs). Next, we couple high-resolution electron microscopy, atom probe tomography, hybrid Monte-Carlo, special quasirandom structures, and density functional theory calculations to demonstrate how controlled additions of Al and Ti and subsequent annealing drive chemical ordering in nearly random equiatomic face-centered cubic CoFeNi solid solution. We establish that short-range ordered domains, the precursors of long-range ordered precipitates, inform mechanical properties. Specifically, a progressively increasing local order boosts the tensile yield strengths of the parent CoFeNi alloy by a factor of four while also substantially improving ductility, which breaks the so-called strength-ductility paradox. Finally, we validate the generality of our approach by predicting and demonstrating that controlled additions of Al, which has large negative enthalpies of mixing with the constituent elements of another nearly random body-centered cubic refractory NbTaTi HEA, also introduces chemical ordering and enhances mechanical properties.

Clonal haematopoiesis and risk of chronic liver disease.

Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response.

Machine learning based de-noising of electron back scatter patterns of various crystallographic metallic materials fabricated using laser directed energy deposition.

A novel machine learning (ML) method of refining noisy Electron Back Scatter Patterns (EBSP) is proposed. For this, conditional generative adversarial networks (c-GAN) have been employed. The problem of de-noising the EBSPs was formulated as an image translation task conditioned on the input images to get refined/denoised output of EBSPs which can be indexed using conventional Hough transform based indexing algorithms. The ML model was trained using 10,000 EBSPs acquired under different settings for additively manufactured FCC, BCC and HCP alloy samples ensuring enough diversity and complexity in training data set. Pairs of noisy and corresponding optimal EBSPs were acquired by suitable tweaking of the EBSP acquisition parameters such as beam defocus, pattern binning and EBSD camera exposure duration. The trained model has brought out significant improvement in EBSD indexing success rate on test data, accompanied by betterment of indexing accuracy, quantified through 'pattern fit'. Complete automation of the EBSP refinement was demonstrated where in entire EBSD scan data can be fed to the model to get the refined EBSPs from which high quality EBSD data can be obtained.

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection.

BACKGROUND: Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID. OBJECTIVES: To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection. METHODS: 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls. RESULTS: Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months. CONCLUSION: CMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID. TRIAL REGISTRATION NUMBER: NCT04369807.

Multi-organ impairment and long COVID: a 1-year prospective, longitudinal cohort study.

OBJECTIVES: To determine the prevalence of organ impairment in long COVID patients at 6 and 12 months after initial symptoms and to explore links to clinical presentation. DESIGN: Prospective cohort study. PARTICIPANTS: Individuals. METHODS: In individuals recovered from acute COVID-19, we assessed symptoms, health status, and multi-organ tissue characterisation and function. SETTING: Two non-acute healthcare settings (Oxford and London). Physiological and biochemical investigations were performed at baseline on all individuals, and those with organ impairment were reassessed. MAIN OUTCOME MEASURES: Primary outcome was prevalence of single- and multi-organ impairment at 6 and 12 months post COVID-19. RESULTS: A total of 536 individuals (mean age 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post COVID-19); 331 (62%) with organ impairment or incidental findings had follow-up, with reduced symptom burden from baseline (median number of symptoms 10 and 3, at 6 and 12 months, respectively). Extreme breathlessness (38% and 30%), cognitive dysfunction (48% and 38%) and poor health-related quality of life (EQ-5D-5L < 0.7; 57% and 45%) were common at 6 and 12 months, and associated with female gender, younger age and single-organ impairment. Single- and multi-organ impairment were present in 69% and 23% at baseline, persisting in 59% and 27% at follow-up, respectively. CONCLUSIONS: Organ impairment persisted in 59% of 331 individuals followed up at 1 year post COVID-19, with implications for symptoms, quality of life and longer-term health, signalling the need for prevention and integrated care of long COVID.Trial Registration: ClinicalTrials.gov Identifier: NCT04369807.

STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol.

INTRODUCTION: Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. METHODS AND ANALYSIS: This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as "standard of care" in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately. ETHICS AND DISSEMINATION: The protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. TRIAL REGISTRATION NUMBER: ISRCTN10665760.

A quantitative MRCP-derived score for medium-term outcome prediction in primary sclerosing cholangitis.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is the gold standard for diagnosis of patients with primary sclerosing cholangitis (PSC). The semi-quantitative MRCP-derived Anali scores proposed for risk stratification, have poor-to-moderate inter-reader agreement. AIMS: To evaluate the prognostic performance of quantitative MRCP metrics in PSC. METHODS: This is a retrospective study of PSC patients undergoing MRCP. Images were processed using MRCP+ software (Perspectum Ltd, Oxford) that provides quantitative biliary features, semi-automatically extracted by artificial intelligence-driven analysis of MRCP-3D images. The prognostic value of biliary features has been assessed for all hepato-biliary complications. RESULTS: 87 PSC patients have been included in the analysis. Median follow-up from MRCP to event/censoring of 30.9 months (Q1-Q3=13.6-46.6). An adverse outcome occurred in 27 (31.0%) patients. The number of biliary strictures (HR=1.05 per unit, 95%CI 1.02-1.08, p < 0.0001), spleen length (HR=1.16 per cm, 95%CI 1.01-1.34, p = 0.039), adjusted for height, age at MRCP, and time from diagnosis to MRCP predicted higher risk of hepatobiliary complications. These were incorporated into a the quantitative MRCP-derived PSC (qMRCP-PSC) score (C-statistic=0.80). After 3-fold cross-validation, qMRCP-PSC outperformed the Anali score in our cohort (C-statistic of 0.78 vs 0.64) and enabled the discrimination of survival of PSC patients (log-rank p < 0.0001). CONCLUSIONS: The qMRCP-PSC score identified patients at higher risk of hepatobiliary complications and outperformed the available radiological scores. It represents a novel quantitative biomarker for disease monitoring and a potential surrogate endpoint for clinical trials.