Multicenter Repeatability and Reproducibility of MR Fingerprinting in Phantoms and in Prostatic Tissue.

PURPOSE To evaluate multicenter repeatability and reproducibility of T1 and T2 maps generated using MR fingerprinting (MRF) in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom and in prostatic tissues. METHODS MRF experiments were performed on 5 different 3 Tesla MRI scanners at 3 different institutions: University Hospitals Cleveland Medical Center (Cleveland, OH), Brigham and Women's Hospital (Boston, MA) in the United States, and Diagnosticos da America (Rio de Janeiro, RJ) in Brazil. Raw MRF data were reconstructed using a Gadgetron-based MRF online reconstruction pipeline to yield quantitative T1 and T2 maps. The repeatability of T1 and T2 values over 6 measurements in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom was assessed to demonstrate intrascanner variation. The reproducibility between the 4 clinical scanners was assessed to demonstrate interscanner variation. The same-day test-retest normal prostate mean T1 and T2 values from peripheral zone and transitional zone were also compared using the intraclass correlation coefficient and Bland-Altman analysis. RESULTS The intrascanner variation of values measured using MRF was less than 2% for T1 and 4.7% for T2 for relaxation values, within the range of 307.7 to 2360 ms for T1 and 19.1 to 248.5 ms for T2 . Interscanner measurements showed that the T1 variation was less than 4.9%, and T2 variation was less than 8.1% between multicenter scanners. Both T1 and T2 values in in vivo prostatic tissue demonstrated high test-retest reliability (intraclass correlation coefficient > 0.92) and strong linear correlation (R2  > 0.840). CONCLUSION Prostate MRF measurements of T1 and T2 are repeatable and reproducible between MRI scanners at different centers on different continents for the above measurement ranges

Primis : design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.MethodsAdults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint-chosen in conjunction with guidance from the U.S. Food and Drug Administration-is the proportion of patients with >= 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.ConclusionThe phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.Trial Registration: ClinicalTrials.gov NCT03890120; registered 26/03/2019.Peer reviewe

In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study

Fetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.National Institutes of Health (U.S.) (Grant U01 HD087211)National Institutes of Health (U.S.) (Grant R01 EB017337

PRIMIS: design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.MethodsAdults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint-chosen in conjunction with guidance from the U.S. Food and Drug Administration-is the proportion of patients with ≥ 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.ConclusionThe phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.Trial registrationClinicalTrials.gov NCT03890120; registered 26/03/2019