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).

A composite score using quantitative magnetic resonance cholangiopancreatography predicts clinical outcomes in primary sclerosing cholangitis.

Background & Aims: Magnetic resonance cholangiopancreatography (MRCP) for evaluation of biliary disease currently relies on subjective assessment with limited prognostic value because of the lack of quantitative metrics. Artificial intelligence-enabled quantitative MRCP (MRCP+) is a novel technique that segments biliary anatomy and provides quantitative biliary tree metrics. This study investigated the utility of MRCP+ as a prognostic tool for the prediction of clinical outcomes in primary sclerosing cholangitis (PSC). Methods: MRCP images of patients with PSC were post-processed using MRCP+ software. The duration between the MRCP and clinical event (liver transplantation or death) was calculated. Survival analysis and stepwise Cox regression were performed to investigate the optimal combination of MRCP+ metrics for the prediction of clinical outcomes. The resulting risk score was validated in a separate validation cohort and compared with an existing prognostic score (Mayo risk score). Results: In this retrospective study, 102 patients were included in a training cohort and a separate 50 patients formed a validation cohort. Between the two cohorts, 34 patients developed clinical outcomes over a median duration of 3 years (23 liver transplantations and 11 deaths). The proportion of bile ducts with diameter 3-5 mm, total bilirubin, and aspartate aminotransferase were independently associated with transplant-free survival. Combined as a risk score, the overall discriminative performance of the MRCP+ risk score (M+BA) was excellent; area under the receiver operator curve 0.86 (95% CI: 0.77, 0.95) at predicting clinical outcomes in the validation cohort with a hazard ratio 5.8 (95% CI: 1.5, 22.1). This was superior to the Mayo risk score. Conclusions: A composite score combining MRCP+ with total bilirubin and aspartate aminotransferase (M+BA) identified PSC patients at high risk of liver transplantation or death. Prospective studies are warranted to evaluate the clinical utility of this novel prognostic tool. Impact and Implications: Primary sclerosis cholangitis (PSC) is a disease of the biliary tree where inflammation and fibrosis cause areas of narrowing (strictures) and expansion (dilatations) within the biliary ducts leading to liver failure and/or cancer (cholangiocarcinoma). In this study, we demonstrate that quantitative assessment of the biliary tree can better identify patients with PSC who are at high risk of either death or liver transplantation than a current blood-based risk score (Mayo risk score).

Determination of oxygen relaxivity in oxygen nanobubbles at 3 and 7 Tesla.

OBJECTIVE: Oxygen-loaded nanobubbles have shown potential for reducing tumour hypoxia and improving treatment outcomes, however, it remains difficult to noninvasively measure the changes in partial pressure of oxygen (PO2) in vivo. The linear relationship between PO2 and longitudinal relaxation rate (R1) has been used to noninvasively infer PO2 in vitreous and cerebrospinal fluid, and therefore, this experiment aimed to investigate whether R1 is a suitable measurement to study oxygen delivery from such oxygen carriers. METHODS: T1 mapping was used to measure R1 in phantoms containing nanobubbles with varied PO2 to measure the relaxivity of oxygen (r1Ox) in the phantoms at 7 and 3 T. These measurements were used to estimate the limit of detection (LOD) in two experimental settings: preclinical 7 T and clinical 3 T MRI. RESULTS: The r1Ox in the nanobubble solution was 0.00057 and 0.000235 s-1/mmHg, corresponding to a LOD of 111 and 103 mmHg with 95% confidence at 7 and 3 T, respectively. CONCLUSION: This suggests that T1 mapping could provide a noninvasive method of measuring a > 100 mmHg oxygen delivery from therapeutic nanobubbles.

Promoting high T2 contrast in Dy-doped MSNs through Curie effects.

Contrast agents retaining high relaxivities at ultrahigh magnetic fields underpin an enhanced image sensitivity within derived MRI scans. By varying the Dy3+ loading density inside a mesoporous silica architecture the dominant Curie effect can be effectively tuned so as to optimise T2 contrast at magnetic fields as high as 11.7 T.

Noninvasive assessment of steatosis and viability of cold-stored human liver grafts by MRI.

PURPOSE: A shortage of suitable donor livers is driving increased use of higher risk livers for transplantation. However, current biomarkers are not sensitive and specific enough to predict posttransplant liver function. This is limiting the expansion of the donor pool. Therefore, better noninvasive tests are required to determine which livers will function following implantation and hence can be safely transplanted. This study assesses the temperature sensitivity of proton density fat fraction and relaxometry parameters and examines their potential for assessment of liver function ex vivo. METHODS: Six ex vivo human livers were scanned during static cold storage following normothermic machine perfusion. Proton density fat fraction, T1 , T2 , and T2∗ were measured repeatedly during cooling on ice. Temperature corrections were derived from these measurements for the parameters that showed significant variation with temperature. RESULTS: Strong linear temperature sensitivities were observed for proton density fat fraction (R2 = 0.61, P < .001) and T1 (R2 = 0.78, P < .001). Temperature correction according to a linear model reduced the coefficient of repeatability in these measurements by 41% and 36%, respectively. No temperature dependence was observed in T2 or T2∗ measurements. Comparing livers deemed functional and nonfunctional during normothermic machine perfusion by hemodynamic and biochemical criteria, T1 differed significantly: 516 ± 50 ms for functional versus 679 ± 60 ms for nonfunctional, P = .02. CONCLUSION: Temperature correction is essential for robust measurement of proton density fat fraction and T1 in cold-stored human livers. These parameters may provide a noninvasive measure of viability for transplantation.

Ischemia-Reperfusion Injuries Assessment during Pancreas Preservation.

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.

Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH). METHODS: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model. RESULTS: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs. CONCLUSIONS: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking. LAY SUMMARY: Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

Using a whole-body 31P birdcage transmit coil and 16-element receive array for human cardiac metabolic imaging at 7T.

PURPOSE: Cardiac phosphorus magnetic resonance spectroscopy (31P-MRS) provides unique insight into the mechanisms of heart failure. Yet, clinical applications have been hindered by the restricted sensitivity of the surface radiofrequency-coils normally used. These permit the analysis of spectra only from the interventricular septum, or large volumes of myocardium, which may not be meaningful in focal disease. Löring et al. recently presented a prototype whole-body (52 cm diameter) transmit/receive birdcage coil for 31P at 7T. We now present a new, easily-removable, whole-body 31P transmit radiofrequency-coil built into a patient-bed extension combined with a 16-element receive array for cardiac 31P-MRS. MATERIALS AND METHODS: A fully-removable (55 cm diameter) birdcage transmit coil was combined with a 16-element receive array on a Magnetom 7T scanner (Siemens, Germany). Electro-magnetic field simulations and phantom tests of the setup were performed. In vivo maps of B1+, metabolite signals, and saturation-band efficiency were acquired across the torsos of eight volunteers. RESULTS: The combined (volume-transmit, local receive array) setup increased signal-to-noise ratio 2.6-fold 10 cm below the array (depth of the interventricular septum) compared to using the birdcage coil in transceiver mode. The simulated coefficient of variation for B1+ of the whole-body coil across the heart was 46.7% (surface coil 129.0%); and the in vivo measured value was 38.4%. Metabolite images of 2,3-diphosphoglycerate clearly resolved the ventricular blood pools, and muscle tissue was visible in phosphocreatine (PCr) maps. Amplitude-modulated saturation bands achieved 71±4% suppression of phosphocreatine PCr in chest-wall muscles. Subjects reported they were comfortable. CONCLUSION: This easy-to-assemble, volume-transmit, local receive array coil combination significantly improves the homogeneity and field-of-view for metabolic imaging of the human heart at 7T.