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Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI): Validation of different quantitative pharmacokinetic models in monitoring neo-adjuvant treatment in advanced rectal cancer Poster No.: C-1547 Congress: ECR 2010 Type: Scientific Exhibit Topic: GI Tract Authors: A. Petrillo, M. Petrillo, M. Sansone, R. Fusco, U. Bracale, A. Siani; Naples/IT Keywords: DCE-MRI, Rectal cancer, Neoadjiuvant treatment DOI: 10.1594/ecr2010/C-1547 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. 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Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myESR.org Page 1 of 7 Purpose Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) is an concrete functional technique to evaluate in vivo tumor vascular assessment, now essential to monitor the response of rectal cancer before and after neo-adjuvant treatment [1-3]. Time intensity (TIC-I/T) curves do not provide a sufficient range of information to understand all patho-physiological processes that in vivo involve vascular development during tumor overgrowth [4]. Analyzing data obtained performing multiple T-1w (T-1 Weighted) acquisitions after Gadolinium (Gd-DTPA) injection and applying pharmacokinetic models on retrieved values, we evaluated a tumor perfusion approach more capable to summarize contrast enhancement in terms of quantitative parameters, in order to study rectal cancer affected patients before and after the neo adjuvant treatment. Aim of this study was the comparison of multiple quantitative parameters strictly related to vascular anatomy and essential to establish a possible relationship among DCE-MRI perfusion data and patient TNM staging or CRM , assessed during rectal cancer neoadjuvant treatments, CEA and CA 19-9 markers. Methods and Materials Patients selection and MRI examination technique We studied eleven (11) rectal cancer affected patients (55-70 y.o.), 5 females and 6 males. All patients were histologically proven. All patients underwent an MRI study that was performed using a 1,5T scanner and phased-array coils. A superparamagnetic iron oxide (SPIO) contrast enema was employed to distend the rectal lumen and achieve maximal tumor-to-lumen contrast gradient followed by T2-w tse2D axial, sagittal (TE 98, TR 4980, matrix 464x512, slice thickness 3mm,fixed flip angle 150°) and T1-w tse2D coronal images (TE 14, TR 500, matrix 512x512, slice thickness 3mm, fixed flip angle 150°). The IV administration of 2mL/Kg Gadolinium (Gd-DTPA) was performed and eleven (11) axial T1-w fl3D acquisitions (TE 4,5, TR 9,8, matrix 512x384, slice thickness 3mm, fixed flip angle 25°) were obtained. Sagittal and coronal T1-w TSE (TE 14, TR 500, matrix 512x448, slice thickness 3mm, fixed flip angle 150°)images, post-contrast injection were acquired, to complete an accurate TNM staging. Image analysis In order to avoid the influence of motion artifacts on data analysis, images were accurately visually selected and only adequate acquisitions were included in the study. Page 2 of 7 All images were evaluated by two blinded expert radiologists, each one with almost 5 years of training in gastronterology imaging. A region of interest (ROI) was drawn on suspected lesions (5x5 pixels matrix, Fig.1) before and after neo adjuvant treatments and a TNM patient evaluation followed every MRI session. Obtained data were analyzed applying multiple pharmacokinetic models developed by Brix et al., Tofts and Kermode,Larsson et al., Simpson et al. [5-8], on values retrieved from ROI drawn on tumor affected tissues followed by comparison among used quantitative models on same considered ROI. (Fig.2) For each patient were collected data concerning TNM staging, before and after neoadjuvant treatment. Statistical analysis A statistical analysis was made applying t-test and one-way table analysis of variance (ANOVA), in order to explore the existing relationships among quantitative resulting parameters and clinical evaluated factors as above. Images for this section: Fig. 1: TIC of three ROI selected by an expert radiologist (ROI1,ROI2,ROI3) Page 3 of 7 Fig. 2: Comparison among all models. Page 4 of 7 Results We were able to perform a statistical analysis based on data retrieved from calculated quantitative parameters and TNM. A significant (p<0.05) difference was found in terms of quantitative DCE-MRI assessment before and after neo adjuvant treatment corresponding in patients with different TNM that were shown as afferent to different subsets of population. Data processed throw models developed by Brix, Tofts and Simpson were able to distinguish patients with a T2 staging from those with a T3 staging. Pharmacokinetics models developed by Brix, Larsson, Lawrence made a distinction between patients with a T2 or a T3 staging from those with a T4 staging.(Fig.1) Images for this section: Fig. 1: The null hypothesis is that the two samples belong to the same population. The tests return the p-value or the probability that the null hypothesis is true. If p-value is > 0.05 the null hypothesis is accepted; if p-value is < 0.05 the null hypothesis is rejected. Page 5 of 7 Conclusion Preliminary results show that not all pharmacokinetic models have the same performances in characterizing TNM staging in monitoring rectal cancer affected patients during neo-adjuvant treatments. Statistically quantitative DCE-MRI measurements made applying Brix model (Ktrans, Kep and Ve parameters) seem to give superior capabilities in discriminate patients TNM subset of pertinence, especially in characterizing patients with a T2 staging from those with a T3 staging. This observation, if verified on a bigger sample could adequately support in deciding how functional DCE-MRI can implement clinical decisions. Its advantages could be relevant in monitoring rectal cancer affected patient during neoadjuvant treatments, opening new perspectives in getting over the limits that actually affect MRI examinations with more data able to better calibrate the expected response to administered therapies. References [1] M. A. Zahra, K. G. Hollingsworth, E. Sala, D. J. Lomas, L. T. Tan (2007) Dynamic contrast-enhanced MRI as a predictor of tumour response to radiotherapy. Lancet Oncol 8:63-74. [2] L. Bacharach, M. Thomasson (2005) Imaging approaches for monitoring chemotherapy. Drug Discovery Today: Technologies 2:329-334. [3] G. De Lussanet, m. R. Padhani, A. van Baardwijk, P. Lambin, L. Beets, A. Van Engelshoven, H. Beets (2005) Dynamic Contrast-Enhanced Magnetic Resonance Imaging Of Radiation Therapy-Induced Microcirculation Changes In Rectal Cancer. Int. J. Radiation Oncology Biol. Phys 63:1309-1315. [4] Atkin G, Taylor NJ, Daley FM, Stirling JJ, Richman P, Glynne-Jones R, d'Arcy JA, Collins DJ, Padhani AR (2006) Dynamic contrast-enhanced magnetic resonance imaging is a poor measure of rectal cancer angiogenesis. Br J Surg. 93(:992-1000. [5] P. S. Tofts (1997) Modeling Tracer Kinetics in Dynamic Gd-DTPA MR Imaging. J Magn Reson Imaging 7:91-101 [6] Larsson et al (1996) Myocardial perfusion modeling using MRI. Magn Reson Med 35:716-726. [7] G. Brix, W. Semmler, R. Port, et al (1991) Pharmacokinetic Parameters in CNS GdDTPA enhanced MR imaging. J. Comput Assist Tomogr 15:621-628 Page 6 of 7 [8] Simpson NE, He Z, Evelhoch JL (1999) Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods. Magnetic Resonance Med 42:42 - 52. Personal Information Dr. Antonella Petrillo, M.D. Date of birth: Dec 3, 1956; Place of birth: Caserta Degree in Medicine and Surgery on July, 24, 1985, "cum laude"; Specialty Degrees: Nuclear Medicine (Dec. 6, 1988); Diagnostic Radiology (Oct. 10, 1994) All degrees administered by the University of Naples "Federico II", Faculty of Medicine and Surgery. Position held: 1992-2001: Medical Radiologist, National Cancer Institute of Naples "Fondazione G. Pascale", with special interest in Magnetic Resonance Imaging; 2003: Encharged of the High Specialty Degree in MRI imaging, with special reference to Angio-RMI, Cholangio-RMI, Mammo-RMI, Dynamic studies and interventional RMI. 2007: Nomination as President of a Humanitarian Association for patients "Sinergie Salute Onlus ", Via Cisterna dell'Olio 10, 80136 Naples. April 16, 2006. Head of the Simple Operative Structure of Breast Pathology, National Cancer Institute of Naples. Page 7 of 7