Liver https://www.imi-tristan.eu/ en PBPK Modelling of PV in Rats https://www.imi-tristan.eu/node/406 <span>PBPK Modelling of PV in Rats</span> <span><span lang="" about="/user/276" typeof="schema:Person" property="schema:name" datatype="">gunnar.schuetz</span></span> <span>19.08.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2021-07-20T12:00:00Z">20.07.2021</time> </div> <div> <div> <article about="/taxonomy/term/131"> <div> <div class="coh-container ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-style-article-teaser---type-1---sgm ssa-instance-2481043932 coh-ce-cpt_article_teaser_type_1-7c69df1" > <div class="coh-container text-wrapper" > <h4 class="coh-heading headline "> <b>Article Title and Summary</b> </h4> <div class="coh-wysiwyg description"> <p>Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat.</p> </div> <a href="/#" class="coh-link ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 read-more enable-basic-hover ssa-instance-664298994 coh-ce-cpt_read_more_button-34304a6b" title="Read more" target="_self" data-analytics-layer="[{&quot;trigger&quot;:&quot;click&quot;,&quot;value&quot;:&quot;gaGenericEvent&quot;,&quot;key&quot;:&quot;event&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventCategory&quot;,&quot;value&quot;:&quot;CTA&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventLabel&quot;,&quot;value&quot;:&quot;www.imi-tristan.eu/#&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventAction&quot;,&quot;value&quot;:&quot;Read more&quot;}]" > <span class="coh-inline-element">Read more</span> </a> </div> </div> </div> </article> </div> </div> <div><p><strong>Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats</strong></p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">123</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-d7fdd183-d060-49c1-910f-30793d71e1ea coh-component-instance-d7fdd183-d060-49c1-910f-30793d71e1ea ssa-instance-1532798025 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-f1e15723-e76e-47ba-bffa-c072af8b8f74 coh-component-instance-f1e15723-e76e-47ba-bffa-c072af8b8f74 ssa-instance-769564607 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>PBPK Modelling of gadoxetate in rat liver</h2> <p><strong>Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats</strong></p> <p><em>Daniel Scotcher, Nicola Melillo, Sirisha Tadimalla, Adam S. Darwich, Sabina Ziemian, Kayode Ogungbenro, Gunnar Schütz, Steven Sourbron, and Aleksandra Galetin</em></p> <p><br /> ACS Mol. Pharmaceutics 2021, 18, 8, 2997-3009; <a href="https://doi.org/10.1021/acs.molpharmaceut.1c00206">doi:10.1021/acs.molpharmaceut.1c00206</a></p> <p>Abstract</p> <p>Physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development to simulate changes in both systemic and tissue exposures that arise as a result of changes in enzyme and/or transporter activity. Verification of these model-based simulations of tissue exposure is challenging in the case of transporter-mediated drug–drug interactions (tDDI), in particular as these may lead to differential effects on substrate exposure in plasma and tissues/organs of interest. Gadoxetate, a promising magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 (OATP1B1) and multidrug resistance-associated protein 2 (MRP2). In this study, we developed a gadoxetate PBPK model and explored the use of liver-imaging data to achieve and refine in vitro–in vivo extrapolation (IVIVE) of gadoxetate hepatic transporter kinetic data. In addition, PBPK modeling was used to investigate gadoxetate hepatic tDDI with rifampicin i.v. 10 mg/kg. In vivo dynamic contrast-enhanced (DCE) MRI data of gadoxetate in rat blood, spleen, and liver were used in this analysis. Gadoxetate in vitro uptake kinetic data were generated in plated rat hepatocytes. Mean (%CV) in vitro hepatocyte uptake unbound Michaelis–Menten constant (<i>K</i><sub>m,u</sub>) of gadoxetate was 106 μM (17%) (<i>n</i> = 4 rats), and active saturable uptake accounted for 94% of total uptake into hepatocytes. PBPK–IVIVE of these data (bottom-up approach) captured reasonably systemic exposure, but underestimated the in vivo gadoxetate DCE–MRI profiles and elimination from the liver. Therefore, in vivo rat DCE–MRI liver data were subsequently used to refine gadoxetate transporter kinetic parameters in the PBPK model (top-down approach). Active uptake into the hepatocytes refined by the liver-imaging data was one order of magnitude higher than the one predicted by the IVIVE approach. Finally, the PBPK model was fitted to the gadoxetate DCE–MRI data (blood, spleen, and liver) obtained with and without coadministered rifampicin. Rifampicin was estimated to inhibit active uptake transport of gadoxetate into the liver by 96%. The current analysis highlighted the importance of gadoxetate liver data for PBPK model refinement, which was not feasible when using the blood data alone, as is common in PBPK modeling applications. The results of our study demonstrate the utility of organ-imaging data in evaluating and refining PBPK transporter IVIVE to support the subsequent model use for quantitative evaluation of hepatic tDDI.</p> <div></div> </div> </div> </div> </div> </div> </div> </div> </div> <div>PBPK Modelling of Gadoxetate in Rat Liver</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> </div> </div> Thu, 19 Aug 2021 07:24:38 +0000 gunnar.schuetz 406 at https://www.imi-tristan.eu Liver T1 Mapping with vFA https://www.imi-tristan.eu/node/396 <span>Liver T1 Mapping with vFA</span> <span><span lang="" about="/user/276" typeof="schema:Person" property="schema:name" datatype="">gunnar.schuetz</span></span> <span>22.06.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2021-05-15T12:00:00Z">15.05.2021</time> </div> <div> <div> <article about="/taxonomy/term/131"> <div> <div class="coh-container ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-style-article-teaser---type-1---sgm ssa-instance-2481043932 coh-ce-cpt_article_teaser_type_1-7c69df1" > <div class="coh-container text-wrapper" > <h4 class="coh-heading headline "> <b>Article Title and Summary</b> </h4> <div class="coh-wysiwyg description"> <p>Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat.</p> </div> <a href="/#" class="coh-link ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 read-more enable-basic-hover ssa-instance-664298994 coh-ce-cpt_read_more_button-34304a6b" title="Read more" target="_self" data-analytics-layer="[{&quot;trigger&quot;:&quot;click&quot;,&quot;value&quot;:&quot;gaGenericEvent&quot;,&quot;key&quot;:&quot;event&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventCategory&quot;,&quot;value&quot;:&quot;CTA&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventLabel&quot;,&quot;value&quot;:&quot;www.imi-tristan.eu/#&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventAction&quot;,&quot;value&quot;:&quot;Read more&quot;}]" > <span class="coh-inline-element">Read more</span> </a> </div> </div> </div> </article> </div> </div> <div><p><strong>Bias, repeatability and reproducibility of liver T1 mapping with variable flip angles</strong></p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">123</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-a5f92d00-8fc3-446c-9a2f-d7d6be976580 coh-component-instance-a5f92d00-8fc3-446c-9a2f-d7d6be976580 ssa-instance-2910546535 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-382c3026-cf9e-4466-9dcd-c0e19a73f282 coh-component-instance-382c3026-cf9e-4466-9dcd-c0e19a73f282 ssa-instance-4203109745 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>Liver T1 Mapping with vFA</h2> <div class="page-head"> <p><strong>Bias, repeatability and reproducibility of liver T1 mapping with variable flip angles</strong></p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>Sirisha Tadimalla, Daniel Wilson, David Shelley, Gavin Bainbridge, Margaret Saysell, Iosif A Mendichovszky, Martin Graves, Geoff JM Parker, Steven Sourbron</em></p> <p><br /> ISMRM Conference 2021</p> <p>Abstract</p> <p>A multi-centre, multi-vendor study in 8 travelling healthy volunteers was conducted for technical validation of variable flip angle (VFA) T1 mapping in the liver across 6 scanners (3 vendors and 2 field strengths). The 95% CI was 28 ± 8% for the bias in liver T1, 10 ± 3% for the intra-scanner repeatability CV and 28 ± 6% for the inter-scanner reproducibility CV. These values are comparable to literature values for B1+-corrected VFA T1 in prostate, brain, breast, and phantoms. Any proposed refinement of the VFA method in the liver should demonstrate a significant improvement on those benchmarks before it can be recommended as a future standard.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>Liver T1 Mapping with vFA</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Tue, 22 Jun 2021 19:22:30 +0000 gunnar.schuetz 396 at https://www.imi-tristan.eu Gadoxetate MRI to assess rifampicin effect https://www.imi-tristan.eu/node/386 <span>Gadoxetate MRI to assess rifampicin effect</span> <span><span lang="" about="/user/276" typeof="schema:Person" property="schema:name" datatype="">gunnar.schuetz</span></span> <span>22.06.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2021-03-15T12:00:00Z">15.03.2021</time> </div> <div> <div> <article about="/taxonomy/term/131"> <div> <div class="coh-container ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-style-article-teaser---type-1---sgm ssa-instance-2481043932 coh-ce-cpt_article_teaser_type_1-7c69df1" > <div class="coh-container text-wrapper" > <h4 class="coh-heading headline "> <b>Article Title and Summary</b> </h4> <div class="coh-wysiwyg description"> <p>Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat.</p> </div> <a href="/#" class="coh-link ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 read-more enable-basic-hover ssa-instance-664298994 coh-ce-cpt_read_more_button-34304a6b" title="Read more" target="_self" data-analytics-layer="[{&quot;trigger&quot;:&quot;click&quot;,&quot;value&quot;:&quot;gaGenericEvent&quot;,&quot;key&quot;:&quot;event&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventCategory&quot;,&quot;value&quot;:&quot;CTA&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventLabel&quot;,&quot;value&quot;:&quot;www.imi-tristan.eu/#&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventAction&quot;,&quot;value&quot;:&quot;Read more&quot;}]" > <span class="coh-inline-element">Read more</span> </a> </div> </div> </div> </article> </div> </div> <div><p><strong>Acute and chronic rifampicin effect on gadoxetate uptake in rats using gadoxetate DCE-MRI</strong></p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">123</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-ea814786-f1b7-49d4-a54c-4ea6770631b6 coh-component-instance-ea814786-f1b7-49d4-a54c-4ea6770631b6 ssa-instance-2051510954 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-f85090e4-eb46-4e9c-94b2-c39b069a6ea7 coh-component-instance-f85090e4-eb46-4e9c-94b2-c39b069a6ea7 ssa-instance-4185094668 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>Gadoxetate MRI to assess rifampicin effect</h2> <div class="page-head"> <p><strong>Acute and chronic rifampicin effect on gadoxetate uptake in rats using gadoxetate DCE-MRI</strong></p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>Mikael Montelius, Steven Sourbron, Nicola Melillo, Daniel Scotcher, Aleksandra Galetin, Gunnar Schuetz, Claudia Green, Edvin Johansson, John Waterton, Paul D. Hockings</em></p> <p><br /> ISMRM Conference 2021</p> <p>Abstract</p> <p>Non-invasive biomarkers for Drug Induced Liver Injury, which cause liver failure and impede drug development, and Drug-Drug Interactions affecting pharmacokinetics of drugs when combined are needed. We used gadoxetate DCE-MRI to measure clinical and high dose rifampicin effects on hepatocellular uptake in acute and chronic settings in rats. At high dose, uptake was significantly reduced after acute dosing, and returned to baseline after chronic dosing. Similar but non-significant effects was seen at clinical dose levels. We thus demonstrated the potential of gadoxetate DCE-MRI to non-invasively assess drug-induced inhibition of hepatocellular transport and DDIs. <br /> .</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>Gadoxetate MRI to assess rifampicin effect</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Tue, 22 Jun 2021 19:11:14 +0000 gunnar.schuetz 386 at https://www.imi-tristan.eu Assess Liver Transporter Kinetics and DDI from Imaging Data https://www.imi-tristan.eu/node/381 <span>Assess Liver Transporter Kinetics and DDI from Imaging Data</span> <span><span lang="" about="/user/276" typeof="schema:Person" property="schema:name" datatype="">gunnar.schuetz</span></span> <span>22.06.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2021-01-19T12:00:00Z">19.01.2021</time> </div> <div> <div> <article about="/taxonomy/term/131"> <div> <div class="coh-container ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-style-article-teaser---type-1---sgm ssa-instance-2481043932 coh-ce-cpt_article_teaser_type_1-7c69df1" > <div class="coh-container text-wrapper" > <h4 class="coh-heading headline "> <b>Article Title and Summary</b> </h4> <div class="coh-wysiwyg description"> <p>Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat.</p> </div> <a href="/#" class="coh-link ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 read-more enable-basic-hover ssa-instance-664298994 coh-ce-cpt_read_more_button-34304a6b" title="Read more" target="_self" data-analytics-layer="[{&quot;trigger&quot;:&quot;click&quot;,&quot;value&quot;:&quot;gaGenericEvent&quot;,&quot;key&quot;:&quot;event&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventCategory&quot;,&quot;value&quot;:&quot;CTA&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventLabel&quot;,&quot;value&quot;:&quot;www.imi-tristan.eu/#&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventAction&quot;,&quot;value&quot;:&quot;Read more&quot;}]" > <span class="coh-inline-element">Read more</span> </a> </div> </div> </div> </article> </div> </div> <div><p><strong>Insights on hepatobiliary transporter kinetics and DDIs from tissue imaging data: Lessons from PBPK modelling of gadoxetate</strong></p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">123</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-0c6ca766-d990-445d-8f62-241964f07efd coh-component-instance-0c6ca766-d990-445d-8f62-241964f07efd ssa-instance-4151809505 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-71a71283-918d-4c29-8cc5-a3cb4f98a94c coh-component-instance-71a71283-918d-4c29-8cc5-a3cb4f98a94c ssa-instance-4228699789 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>Assess Liver Transporter Kinetics and DDI from Imaging Data</h2> <div class="page-head"> <p><strong>Insights on hepatobiliary transporter kinetics and DDIs from tissue imaging data: Lessons from PBPK modelling of gadoxetate</strong></p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>Daniel Scotcher</em></p> <p>2021 Drug Metabolism Discussion Group and Swedish Academy of Pharmaceutical Sciences Online Joint Meeting</p> <p>Abstract</p> <p>Physiologically-based pharmacokinetic (PBPK) modelling provides a framework for in vitro-in vivo extrapolation (IVIVE) of drug disposition. Quantitative prediction of transporter-mediated processes and tissue permeation remains challenging due to the lack of available in vivo tissue data for model validation. Gadoxetate is a magnetic resonance imaging (MRI) contrast agent and substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and multidrug resistance-associated protein 2 (MRP2). Gadoxetate is being explored as a novel imaging biomarker for hepatic transporter function in context of evaluation of drug-drug interactions and drug induced liver injury. The in vitro uptake kinetics of gadoxetate in plated rat hepatocytes were assessed, and transporter kinetic parameters derived using a mechanistic cell model. Subsequently, a novel PBPK model was developed for gadoxetate in rat, where liver uptake and cellular binding were informed by IVIVE. Gadoxetate in vivo blood, spleen and liver data obtained in the presence and absence of a single 10 mg/kg intravenous dose of rifampicin were used for PBPK model refinement. The PBPK model successfully predicted gadoxetate concentrations in systemic blood and spleen and corresponding increase in gadoxetate systemic exposure in the presence of rifampicin, whereas liver concentrations were under-predicted. Refinement of the PBPK model using the dynamic contrast agent enhanced (DCE)-MRI data enabled recovery of the liver profile. The current study demonstrates utility of tissue imaging data in validating and refining PBPK models for prediction of transporter-mediated disposition.<br />  </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>Assess Liver Transporter Kinetics and DDI from Imaging Data</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Tue, 22 Jun 2021 19:04:24 +0000 gunnar.schuetz 381 at https://www.imi-tristan.eu Imaging of DDI risk with liver transporters https://www.imi-tristan.eu/node/376 <span>Imaging of DDI risk with liver transporters</span> <span><span lang="" about="/user/276" typeof="schema:Person" property="schema:name" datatype="">gunnar.schuetz</span></span> <span>22.06.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2021-03-12T12:00:00Z">12.03.2021</time> </div> <div> <div> <article about="/taxonomy/term/131"> <div> <div class="coh-container ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-style-article-teaser---type-1---sgm ssa-instance-2481043932 coh-ce-cpt_article_teaser_type_1-7c69df1" > <div class="coh-container text-wrapper" > <h4 class="coh-heading headline "> <b>Article Title and Summary</b> </h4> <div class="coh-wysiwyg description"> <p>Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat.</p> </div> <a href="/#" class="coh-link ssa-component coh-component ssa-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 coh-component-instance-f0598579-1399-4f64-8cf9-8ba150a93307 read-more enable-basic-hover ssa-instance-664298994 coh-ce-cpt_read_more_button-34304a6b" title="Read more" target="_self" data-analytics-layer="[{&quot;trigger&quot;:&quot;click&quot;,&quot;value&quot;:&quot;gaGenericEvent&quot;,&quot;key&quot;:&quot;event&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventCategory&quot;,&quot;value&quot;:&quot;CTA&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventLabel&quot;,&quot;value&quot;:&quot;www.imi-tristan.eu/#&quot;},{&quot;trigger&quot;:&quot;click&quot;,&quot;key&quot;:&quot;eventAction&quot;,&quot;value&quot;:&quot;Read more&quot;}]" > <span class="coh-inline-element">Read more</span> </a> </div> </div> </div> </article> </div> </div> <div><p><strong>In vivo imaging and evaluation of drug-drug interaction risk arising via hepatobiliary transporters</strong></p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">123</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-99d6b889-6dda-4cd6-b156-26133c37caab coh-component-instance-99d6b889-6dda-4cd6-b156-26133c37caab ssa-instance-1136428565 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-bcd61b80-82c3-4e43-9900-74b37cc4e9a3 coh-component-instance-bcd61b80-82c3-4e43-9900-74b37cc4e9a3 ssa-instance-2654790208 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <h2>Imaging of DDI risk with liver transporters</h2> <div class="page-head"> <p><strong>In vivo imaging and evaluation of drug-drug interaction risk arising via hepatobiliary transporters</strong></p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>J. Gerry Kenna, Claudia Green, Catherine D. G. Hines Iina Laitinen, Aleksandra Galetin, Paul D. Hockings,  Nicola Melillo, Mikael Montelius,  Daniel Scotcher, Steven Sourbron, John C. Watertone, Gunnar Schütz</em><br />  </p> <p>Virtual 2021 Annual Meeting of the US Society of Toxicology and ToxExpo</p> <p>Abstract</p> <p>Inhibition of transporters that mediate hepatic drug uptake and/or biliary excretion may cause clinically relevant drug-drug interactions (DDIs) leading to potentiated or reduced efficacy, and/or increased or reduced toxicity to liver or other tissues. These DDIs are difficult to assess, since accurate prediction of changes in tissue exposure in vivo based on in vitro transport interaction data is challenging. Dynamic contract enhanced magnetic resonance imaging (DCE-MRI) enables in vivo visualisation of hepatic transporter mediated uptake and efflux of the contrast agent gadoxetate. When analysed using a compartmental kinetic model of gadoxetate disposition, gadoxetate DCE-MRI studies provide quantitative rate constants for hepatic gadoxetate uptake (khe) and biliary excretion (kbh). These processes are mediated primarily by Organic Anion Transport Polypeptides (OATPs) and Multidrug Resistance Protein Type 2 (MRP2), respectively. To evaluate drug effects on hepatic gadoxetate khe and kbh, DCE-MRI studies were undertaken in adult male Wistar rats (approx. 250g body weight) dosed intravenously (iv) with single doses of <br /> drugs (rifampicin, asunaprevir, bosentan, cyclosporin, ketoconazole, pioglitazone) that inhibited rat oatp, and human OATP, activities in vitro. Drug doses were selected, via pharmacokinetic modelling and simulation, to achieve rat peripheral blood plasma concentrations following iv administration that were equivalent to steady-state human blood plasma concentrations. Simulations predicted that the selected doses of rifampicin and cyclosporin reduced liver gadoxetate exposure in vivo, whereas the other tested drugs did not. Gadoxetate khe values were determined 20 min after iv administration of dose vehicle and then, in the same animals, after a minimum 48 hr washout interval and following drug administration (n=6 per group). Gadoxetate khe (min-1) was reduced (p &lt; 0.01) following administration of rifampicin at 2 mg/kg (mean +SD, dose: 0.44+0.06; vehicle: 0.92+0.17) or cyclosporin at 5 mg/kg (mean+SD, dose: 0.08+0.02; vehicle: 1.00+0.24); but not after dosing of asunaprevir at 5 mg/kg, bosentan at 2 mg/kg, ketoconazole at 3 mg/kg or pioglitazone at 0.4 mg/kg. These results indicate that gadoxetate DCE-MRI may aid assessment of hepatic transporter-mediated DDI risk.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>Imaging of DDI risk with liver transporters</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Tue, 22 Jun 2021 18:57:26 +0000 gunnar.schuetz 376 at https://www.imi-tristan.eu Proton relaxation in liver https://www.imi-tristan.eu/node/336 <span>Proton relaxation in liver</span> <span><span lang="" about="/user/276" typeof="schema:Person" property="schema:name" datatype="">gunnar.schuetz</span></span> <span>12.05.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2021-05-12T00:00:00Z">12.05.2021</time> </div> <div><p><strong>Survey of Water Proton Longitudinal Relaxation in Liver in vivo</strong></p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">150</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-3659a715-e554-4ba7-9bb1-85233b37fcd4 coh-component-instance-3659a715-e554-4ba7-9bb1-85233b37fcd4 ssa-instance-2558277698 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-56617d53-af97-4467-a5b9-73481f1ef773 coh-component-instance-56617d53-af97-4467-a5b9-73481f1ef773 ssa-instance-1998107534 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>Liver longitudinal relaxation in-vivo</h2> <div class="page-head"> <p class="coh-style-text-bold"><strong>Survey of water proton longitudinal relaxation in liver in vivo</strong></p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>by John Charles Waterton</em></p> <p><br /><i>Magn Reson Mater Phy</i> (2021). <a href="https://doi.org/10.1007/s10334-021-00928-x">doi: 10.1007/s10334-021-00928-x</a></p> <p>Abstract</p> <p>Objective: To determine the variability, and preferred values, for normal liver longitudinal water proton relaxation rate <i>R</i><sub>1</sub> in the published literature.</p> <p>Methods: Values of mean <i>R</i><sub>1</sub> and between-subject variance were obtained from literature searching. Weighted means were fitted to a heuristic and to a model.</p> <p>Results: After exclusions, 116 publications (143 studies) remained, representing apparently normal liver in 3392 humans, 99 mice and 249 rats. Seventeen field strengths were included between 0.04 T and 9.4 T. Older studies tended to report higher between-subject coefficients of variation (CoV), but for studies published since 1992, the median between-subject CoV was 7.4%, and in half of those studies, measured <i>R</i><sub>1</sub> deviated from model by 8.0% or less.</p> <p>Discussion: The within-study between-subject CoV incorporates repeatability error and true between-subject variation. Between-study variation also incorporates between-population variation, together with bias from interactions between methodology and physiology. While quantitative relaxometry ultimately requires validation with phantoms and analysis of propagation of errors, this survey allows investigators to compare their own <i>R</i><sub>1</sub> and variability values with the range of existing literature.</p> <p>.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>LIVER LONGITUDINAL RELAXATION IN VIVO</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Wed, 12 May 2021 16:46:50 +0000 gunnar.schuetz 336 at https://www.imi-tristan.eu Noninvasive Preclinical and Clinical Imaging of Liver https://www.imi-tristan.eu/node/291 <span>Noninvasive Preclinical and Clinical Imaging of Liver</span> <span><span lang="" about="/user/236" typeof="schema:Person" property="schema:name" datatype="" content="iris.gebhart.ext@bayer.com">iris.gebhart.e…</span></span> <span>12.01.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2018-03-21T08:00:00Z">21.03.2018</time> </div> <div><p><strong>Noninvasive Preclinical and Clinical Imaging of Liver Transporter Function Relevant to Drug-Induced Liver Injury</strong></p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">151</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-e143c718-b654-488a-9206-0e86bf6d3bb8 coh-component-instance-e143c718-b654-488a-9206-0e86bf6d3bb8 ssa-instance-341555623 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-47bda8d2-4cfd-40d7-8383-2c1a2ec8588b coh-component-instance-47bda8d2-4cfd-40d7-8383-2c1a2ec8588b ssa-instance-1863457652 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>DILI Book Chapter</h2> <div class="page-head"> <p><strong>Noninvasive Preclinical and Clinical Imaging of Liver Transporter Function Relevant to Drug-Induced Liver Injury</strong></p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>J. Gerry Kenna, John C. Waterton, Andreas Baudy, Aleksandra Galetin, Catherine D. G. Hines, Paul Hockings, Manishkumar Patel, Daniel Scotcher, Steven Sourbron, Sabina Ziemian and Gunnar Schuetz</em></p> <p><br /> In: Chen M., Will Y. (eds) Drug-Induced Liver Toxicity. Methods in Pharmacology and Toxicology. Humana Press, New York, NY <a href="https://rd.springer.com/protocol/10.1007%2F978-1-4939-7677-5_30#citeas" target="_blank" rel="noreferrer noopener">doi: 10.1007/978-1-4939-7677-5_30.</a></p> <p> </p> <p>Abstract</p> <p>Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and drug-induced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug−drug interactions mediated via hepatobiliary transporter perturbation.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>DILI BOOK CHAPTER</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Tue, 12 Jan 2021 07:11:23 +0000 iris.gebhart.ext@bayer.com 291 at https://www.imi-tristan.eu Gadoxetate relaxivities increase significantly after hepatic https://www.imi-tristan.eu/node/281 <span>Gadoxetate relaxivities increase significantly after hepatic</span> <span><span lang="" about="/user/236" typeof="schema:Person" property="schema:name" datatype="" content="iris.gebhart.ext@bayer.com">iris.gebhart.e…</span></span> <span>12.01.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2018-06-16T08:00:00Z">16.06.2018</time> </div> <div><p><strong>Gadoxetate relaxivities increase significantly after hepatic uptake at clinical field strength impacting kinetic modelling for liver function analysis</strong> (Conference Abstract)</p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">149</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-e1a10b61-64f9-49f0-b754-d5ddcc0f51c1 coh-component-instance-e1a10b61-64f9-49f0-b754-d5ddcc0f51c1 ssa-instance-987921898 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-c209af56-b265-4cf6-89f7-f99bc1491943 coh-component-instance-c209af56-b265-4cf6-89f7-f99bc1491943 ssa-instance-2988312463 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>Conference Abstract: Gadoxetate relaxivity in liver</h2> <div class="page-head"> <p><strong>Gadoxetate relaxivities increase significantly after hepatic uptake at clinical field strength impacting kinetic modelling for liver function analysis</strong> (Conference Abstract)</p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>Gregor Jost, Gunnar Schuetz, Hubertus Pietsch</em></p> <p><br /> ISMRM Annual Meeting 2018, 16-21 June 2018,Paris, France</p> <p> </p> <p>Abstract</p> <p>Gadoxetate has been clinically approved for detection and characterization of focal liver lesions by MRI. It exhibits moderate protein binding and is excreted from the body partially through the kidneys and partially by a hepatobiliary pathway. Hepatocytes take up gadoxetate mainly via OAPT and NTCP transporters and excrete it into the bile mainly utilizing Mrp2. By means of dynamic acquisition of gadoxetate signal intensity during liver uptake and excretion followed by application of a suitable kinetic model, the activity of the aforementioned liver transporters can be estimated. For kinetic modelling the gadoxetate concentration for each time point is needed which can be calculated from the signal intensity if r1 in tissue is known. In 1992 Schuhmann-Giampieri et al. reported r1 of gadoxetate to be significantly higher in liver tissue compared to blood at 0.47T. This effect has been attributed to gadoxetate’s protein binding which leads to an increased rotational correlation time. Gadoxetate relaxivities at 1.5T, 3T and 4.7T have since then been reported for water and plasma, but not for hepatocytes. We here present relaxivities for gadoxetate in hepatocytes at 1.5T and 3T to complement the original Schuhmann-Giampieri data. Measurements at 7T are in progress. Interestingly, r1 of gadoxetate after uptake into hepatocytes is about 2x higher compared to plasma and does not decrease with increasing field strength as has been shown for high relaxivity Gd based contrast agents exhibiting high protein binding e.g. gadofosveset. Gadoxetate’s higher r1 in hepatocytes has to be taken into account for pharmacokinetic modelling of dynamic gadoxetate MRI at clinical field strength, which has not been done so far.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>CONFERENCE ABSTRACT: GADOXETATE RELAXIVITY IN LIVER</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Tue, 12 Jan 2021 07:00:55 +0000 iris.gebhart.ext@bayer.com 281 at https://www.imi-tristan.eu Overview of the TRanslational Imaging in Drug SafeTy https://www.imi-tristan.eu/node/276 <span>Overview of the TRanslational Imaging in Drug SafeTy</span> <span><span lang="" about="/user/236" typeof="schema:Person" property="schema:name" datatype="" content="iris.gebhart.ext@bayer.com">iris.gebhart.e…</span></span> <span>12.01.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2018-07-15T08:00:00Z">15.07.2018</time> </div> <div><p><strong>Overview of the TRanslational Imaging in Drug SafeTy AssessmeNt (TRISTAN) IMI Consortium and Progress towards Standardization of MR Biomarkers of Liver Injury and Drug-Drug Interactions</strong> (Conference Abstract)</p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">148</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-9d99993c-91d8-4fc5-845d-aa4f20270ed0 coh-component-instance-9d99993c-91d8-4fc5-845d-aa4f20270ed0 ssa-instance-1988773789 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-5b8d6dd7-8dea-49fd-b474-f3695b20346c coh-component-instance-5b8d6dd7-8dea-49fd-b474-f3695b20346c ssa-instance-4054989001 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>Conference Abstract: DILI imaging biomarkers</h2> <div class="page-head"> <p><strong>Overview of the TRanslational Imaging in Drug SafeTy AssessmeNt (TRISTAN) IMI Consortium and Progress towards Standardization of MR Biomarkers of Liver Injury and Drug-Drug Interactions</strong> (Conference Abstract)</p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>Aleksandra Galetin, Claudia Green, Catherine Hines, Paul Hockings, Lisa Jarl, Gerry Kenna, Sascha Koehler, Iina Laitinen, Xiangjun Meng, Corin Miller, Kayode Ogungbenro, Geoff Parker, Ian Rowe, Gunnar Schuetz, Daniel Scotcher, Steven Sourbron, Klaus Strobel, Sirisha Tadimalla, Ekaterina Tankisheva, John Waterton, Sabina Ziemian</em></p> <p><br /> In Vivo MR Gordon Research Conference, 15-20 July 2018, Andover, NH, USA</p> <p> </p> <p>Abstract</p> <p>In 2017, the TRanslational Imaging in Drug SafeTy AssesmeNt (TRISTAN) Innovative Medicines Initiative (IMI) consortium commenced to leverage the potential of imaging techniques to improve drug safety analysis and translatability of findings by validating and making available imaging procedures as assays to provide biomarkers for widespread use. As such, hepatobiliary transporter assessment is being undertaken using gadoxetate-enhanced MRI-derived biomarkers. Gadoxetate is known to be a substrate for the human influx transporters OATP1B1, OATP1B3, and NTCP, and the efflux transporters MRP2 and MRP3, and their rat orthologues. These transporters contribute to relevant transporter-mediated drug-drug interactions and mediate hepatobiliary clearance of numerous drugs which cause drug-induced liver injury. In addition, inhibition of bile acid excretion by drugs is an important mechanism by which drug-induced liver injury can be initiated. In view of this, the authors seek to validate influx and efflux rates of gadoxetate as an imaging biomarker assay for in vivo liver transporter assessment.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>CONFERENCE ABSTRACT: DILI IMAGING BIOMARKERS</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Tue, 12 Jan 2021 06:56:22 +0000 iris.gebhart.ext@bayer.com 276 at https://www.imi-tristan.eu Slow infusion improves precision of liver function https://www.imi-tristan.eu/node/261 <span>Slow infusion improves precision of liver function</span> <span><span lang="" about="/user/236" typeof="schema:Person" property="schema:name" datatype="" content="iris.gebhart.ext@bayer.com">iris.gebhart.e…</span></span> <span>11.01.2021</span> <div> <div>Private</div> <div>Public</div> </div> <div><time datetime="2018-09-24T07:00:00Z">24.09.2018</time> </div> <div><p><strong>Slow infusion improves precision of liver function measurements by DCE-MRI </strong>(Conference Abstract)</p> </div> <div><ul class="coh-style-approval-code-list"><li class="coh-approval-code coh-page-approval-code">145</li></ul></div> <div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-46119713-73b2-485a-85aa-e6814ef4acdd coh-component-instance-46119713-73b2-485a-85aa-e6814ef4acdd ssa-instance-617885799 coh-ce-cpt_text_component-109d695a"> <div id="head-box"><div class="container head-box sub" title="Publication" style="background-image:url(&quot;/sites/g/files/vrxlpx12716/files/2020-12/background-header-publications.jpg&quot;);"><div class="row"><div class="headline transparent-box-black"><h1 class="hind-light p-md-5"><span class="green-font hind-semibold">Publications</span><br />Take a look</h1></div></div></div></div> </div> <div class="coh-wysiwyg ssa-component coh-component ssa-component-instance-d43e215c-6474-45f8-9bca-78b1b2f70b95 coh-component-instance-d43e215c-6474-45f8-9bca-78b1b2f70b95 ssa-instance-2739091032 coh-ce-cpt_text_component-109d695a"> <div class="container publication-section"> <div class="spacer"> <div class="row"> <div class="col-sm-12 col-lg-12 p-md-5"> <div class="blog-post"> <div> <h2>Conference Abstract: Slow infusion dce-mri</h2> <div class="page-head"> <p><strong>Slow infusion improves precision of liver function measurements by DCE-MRI</strong> (Conference Abstract)</p> </div> <div> <div class="paragraph" style="clear:both;"> <div class="paragraph-box-text"> <p><em>Sirisha Tadimalla and Steven Sourbron</em></p> <p><br /> The British Chapter of ISMRM Annual Meeting, 24-26 September 2018, Somerville College, Oxford</p> <p> </p> <p>Background</p> <p>Quantitative dynamic contrast-enhanced (DCE) MRI with a rapidly injected bolus of gadoxetate can be used to quantify liver perfusion and transporter function [1,2]. Measuring these rapid changes requires high temporal resolution, and this involves compromises in spatial resolution, coverage or SNR. However, when the aim is to measure hepatocellular function (a slow process), rather than perfusion (a fast process), there is no rationale for a rapid injection.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div>CONFERENCE ABSTRACT: SLOW INFUSION DCE-MRI</div> <div> <div>Article categories</div> <div> <div><a href="/taxonomy/term/126" hreflang="en">Publications</a></div> <div><a href="/taxonomy/term/121" hreflang="en">Liver</a></div> </div> </div> Mon, 11 Jan 2021 14:04:55 +0000 iris.gebhart.ext@bayer.com 261 at https://www.imi-tristan.eu