Rata, M., Collins, D. J., Darcy, J., Messiou, C., Tunariu, N., Desouza, N., Young, H., Leach, M. O., Orton, M. R. (2016) Assessment of repeatability and treatment response in early phase clinical trials using DCE-MRI: comparison of parametric analysis using MR- and CT-derived arterial input functions. EUROPEAN RADIOLOGY, 26 (7). pp. 1991-1998. ISSN 0938-7994

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Abstract

Pharmacokinetic (PK) modelling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data requires a reliable measure of the arterial input function (AIF) to robustly characterise tumour vascular properties. This study compared repeatability and treatment-response effects of DCE-MRI-derived PK parameters using a population-averaged AIF and three patient-specific AIFs derived from pre-bolus MRI, DCE-MRI and dynamic contrast computed tomography (DC-CT) data. The four approaches were compared in 13 patients with abdominal metastases. Baseline repeatability [Bland-Altman statistics; coefficient of variation (CoV)], cohort percentage change and p value (paired t test) and number of patients with significant DCE-MRI parameter change post-treatment (limits of agreement) were assessed. Individual AIFs were obtained for all 13 patients with pre-bolus MRI and DC-CT-derived AIFs, but only 10/13 patients had AIFs measurable from DCE-MRI data. The best CoV (7.5 %) of the transfer coefficient between blood plasma and extravascular extracellular space (K (trans)) was obtained using a population-averaged AIF. All four AIF methods detected significant treatment changes: the most significant was the DC-CT-derived AIF. The population-based AIF was similar to or better than the pre-bolus and DCE-MRI-derived AIFs. A population-based AIF is the recommended approach for measuring cohort and individual effects since it has the best repeatability and none of the PK parameters derived using measured AIFs demonstrated an improvement in treatment sensitivity. aEuro cent Pharmacokinetic modelling of DCE-MRI data requires a reliable measure of AIF. aEuro cent Individual MRI-DCE-derived AIFs cannot reliably be extracted from patients. aEuro cent All four AIF methods detected significant K (trans) changes after treatment. aEuro cent A population-based AIF can be recommended for measuring cohort treatment responses in trials.

Item Type:	Article
Authors (ICR Faculty only):	Desouza, Nandita and Leach, Martin
All Authors:	Rata, M., Collins, D. J., Darcy, J., Messiou, C., Tunariu, N., Desouza, N., Young, H., Leach, M. O., Orton, M. R.
Additional Information:	ISI Document Delivery No.: DO7XK Times Cited: 0 Cited Reference Count: 22 Rata, Mihaela Collins, David J. Darcy, James Messiou, Christina Tunariu, Nina Desouza, Nandita Young, Helen Leach, Martin O. Orton, Matthew R. CRUK; EPSRC; MRC; Department of Health [C1060/A10334, C1060/A16464]; NHS; Clinical Research Facility in Imaging; UK Department of Health [C51/A7401, C12540/A15573]; AstraZeneca; EPSRC Platform Grant [EP/H046526/1] The scientific guarantor of this publication is Prof Martin Leach. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. This work was supported by funding from CRUK and EPSRC support to the Cancer Imaging Centre at ICR and RMH in association with MRC and the Department of Health C1060/A10334, C1060/A16464 and NHS funding to the NIHR Biomedical Research Centre and the Clinical Research Facility in Imaging. An Experimental Cancer Medicine Centre Network award (joint initiative, CRUK and UK Department of Health) [grants C51/A7401 & C12540/A15573]). This work was also supported by AstraZeneca. Support was also received from EPSRC Platform Grant EP/H046526/1. MOL is an NIHR senior investigator. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was obtained from all patients. Some study patients or cohorts were previously reported in Messiou C, Orton M, Ang JE, et al. (2012) Advanced solid tumors treated with Cediranib: comparison of dynamic contrast-enhanced MR imaging and CT as markers of vascular activity. Radiology 265(2): 426-436. 0 SPRINGER NEW YORK EUR RADIOL
Uncontrolled Keywords:	Magnetic resonance imaging Computed tomography Drug evaluation Clinical trials, phase 1 Comparative study CONTRAST-ENHANCED MRI SOLID TUMORS PERFUSION
Research teams:	ICR divisions > Radiotherapy and Imaging > Magnetic Resonance
Depositing User:	Barry Jenkins
Date Deposited:	02 Aug 2016 08:16
Last Modified:	02 Aug 2016 08:27
URI:	http://publications.icr.ac.uk/id/eprint/15199

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