Characterisation of Fibrosis in Chemically-induced Rat Mammary Carcinomas Using Multi-modal Endogenous Contrast MRI on a 1.5T Clinical Platform

Overview

Journal Eur Radiol

Specialty Radiology

Date 2017 Oct 18

PMID 29038934

Citations 1

Authors

Neil P Jerome

Jessica K R Boult

Matthew R Orton

James A dArcy

Ashutosh Nerurkar

Martin O Leach

Dow-Mu Koh

David J Collins

Simon P Robinson

Affiliations

Soon will be listed here.

Abstract

Objectives: To determine the ability of multi-parametric, endogenous contrast MRI to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma.

Methods: Female Sprague-Dawley rats (n=18) were administered with N-methyl-N-nitrosourea; resulting mammary carcinomas underwent nine-b-value diffusion-weighted (DWI), ultrashort-echo (UTE) and magnetisation transfer (MT) magnetic resonance imaging (MRI) on a clinical 1.5T platform, and associated quantitative MR parameters were calculated. Excised tumours were histologically assessed for degree of necrosis, collagen, hypoxia and microvessel density. Significance level adjusted for multiple comparisons was p=0.0125.

Results: Significant correlations were found between MT parameters and degree of picrosirius red staining (r > 0.85, p < 0.0002 for k and δ, r < -0.75, p < 0.001 for T and T, Pearson), indicating that MT is sensitive to collagen content in mammary carcinoma. Picrosirius red also correlated with the DWI parameter fD* (r=0.801, p=0.0004) and conventional gradient-echo T* (r=-0.660, p=0.0055). Percentage necrosis correlated moderately with ultrashort/conventional-echo signal ratio (r=0.620, p=0.0105). Pimonidazole adduct (hypoxia) and CD31 (microvessel density) staining did not correlate with any MR parameter assessed.

Conclusions: Magnetisation transfer MRI successfully detects collagen content in mammary carcinoma, supporting inclusion of MT imaging to identify fibrosis, a prognostic marker, in clinical breast MRI examinations.

Key Points: • Magnetisation transfer imaging is sensitive to collagen content in mammary carcinoma. • Magnetisation transfer imaging to detect fibrosis in mammary carcinoma fibrosis is feasible. • IVIM diffusion does not correlate with microvessel density in preclinical mammary carcinoma.

Citing Articles

Bimodal magnetic resonance and optical imaging of extracellular matrix remodelling by orthotopic ovarian tumours.

Bochner F, Fellus-Alyagor L, Ketter D, Golani O, Biton I, Neeman M Br J Cancer. 2020; 123(2):216-225.

PMID: 32390007 PMC: 7374547. DOI: 10.1038/s41416-020-0878-7.

References

Jerome N, Papoutsaki M, Orton M, Parkes H, Winfield J, Boss M . Development of a temperature-controlled phantom for magnetic resonance quality assurance of diffusion, dynamic, and relaxometry measurements. Med Phys. 2016; 43(6):2998-3007. DOI: 10.1118/1.4948997. View

Watanabe H, Kanematsu M, Goshima S, Kondo H, Onozuka M, Moriyama N . Staging hepatic fibrosis: comparison of gadoxetate disodium-enhanced and diffusion-weighted MR imaging--preliminary observations. Radiology. 2011; 259(1):142-50. DOI: 10.1148/radiol.10100621. View

Kakkad S, Zhang J, Akhbardeh A, Jacob D, Krishnamachary B, Solaiyappan M . Collagen fibers mediate MRI-detected water diffusion and anisotropy in breast cancers. Neoplasia. 2016; 18(10):585-593. PMC: 5035345. DOI: 10.1016/j.neo.2016.08.004. View

Scholz T, Ceckler T, Balaban R . Magnetization transfer characterization of hypertensive cardiomyopathy: significance of tissue water content. Magn Reson Med. 1993; 29(3):352-7. DOI: 10.1002/mrm.1910290311. View

Goonewardene T, Sowter H, Harris A . Hypoxia-induced pathways in breast cancer. Microsc Res Tech. 2002; 59(1):41-8. DOI: 10.1002/jemt.10175. View

Luciani A, Vignaud A, Cavet M, Tran Van Nhieu J, Mallat A, Ruel L . Liver cirrhosis: intravoxel incoherent motion MR imaging--pilot study. Radiology. 2008; 249(3):891-9. DOI: 10.1148/radiol.2493080080. View

Jerome N, Boult J, Orton M, dArcy J, Collins D, Leach M . Modulation of renal oxygenation and perfusion in rat kidney monitored by quantitative diffusion and blood oxygen level dependent magnetic resonance imaging on a clinical 1.5T platform. BMC Nephrol. 2016; 17(1):142. PMC: 5048450. DOI: 10.1186/s12882-016-0356-x. View

de Jong S, Zwanenburg J, Visser F, van der Nagel R, van Rijen H, Vos M . Direct detection of myocardial fibrosis by MRI. J Mol Cell Cardiol. 2011; 51(6):974-9. DOI: 10.1016/j.yjmcc.2011.08.024. View

Jerome N, dArcy J, Feiweier T, Koh D, Leach M, Collins D . Extended T2-IVIM model for correction of TE dependence of pseudo-diffusion volume fraction in clinical diffusion-weighted magnetic resonance imaging. Phys Med Biol. 2016; 61(24):N667-N680. PMC: 5952260. DOI: 10.1088/1361-6560/61/24/N667. View

10.

Annet L, Peeters F, Abarca-Quinones J, Leclercq I, Moulin P, Van Beers B . Assessment of diffusion-weighted MR imaging in liver fibrosis. J Magn Reson Imaging. 2006; 25(1):122-8. DOI: 10.1002/jmri.20771. View

11.

Bali M, Metens T, Denolin V, Delhaye M, Demetter P, Closset J . Tumoral and nontumoral pancreas: correlation between quantitative dynamic contrast-enhanced MR imaging and histopathologic parameters. Radiology. 2011; 261(2):456-66. DOI: 10.1148/radiol.11103515. View

12.

Hasebe T, Tsuda H, Hirohashi S, Shimosato Y, Iwai M, Imoto S . Fibrotic focus in invasive ductal carcinoma: an indicator of high tumor aggressiveness. Jpn J Cancer Res. 1996; 87(4):385-94. PMC: 5921099. DOI: 10.1111/j.1349-7006.1996.tb00234.x. View

13.

Hammer C, Maduro J, Bantema-Joppe E, van der Schaaf A, van der Laan H, Langendijk J . Radiation-induced fibrosis in the boost area after three-dimensional conformal radiotherapy with a simultaneous integrated boost technique for early-stage breast cancer: A multivariable prediction model. Radiother Oncol. 2016; 122(1):45-49. DOI: 10.1016/j.radonc.2016.10.006. View

14.

Cox T, Erler J . Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis Model Mech. 2011; 4(2):165-78. PMC: 3046088. DOI: 10.1242/dmm.004077. View

15.

Workman P, Aboagye E, Balkwill F, Balmain A, Bruder G, Chaplin D . Guidelines for the welfare and use of animals in cancer research. Br J Cancer. 2010; 102(11):1555-77. PMC: 2883160. DOI: 10.1038/sj.bjc.6605642. View

16.

Cho G, Moy L, Zhang J, Baete S, Lattanzi R, Moccaldi M . Comparison of fitting methods and b-value sampling strategies for intravoxel incoherent motion in breast cancer. Magn Reson Med. 2014; 74(4):1077-85. PMC: 4439397. DOI: 10.1002/mrm.25484. View

17.

Jerome N, Miyazaki K, Collins D, Orton M, dArcy J, Wallace T . Repeatability of derived parameters from histograms following non-Gaussian diffusion modelling of diffusion-weighted imaging in a paediatric oncological cohort. Eur Radiol. 2016; 27(1):345-353. PMC: 5127877. DOI: 10.1007/s00330-016-4318-2. View

18.

Li W, Zhang Z, Nicolai J, Yang G, Omary R, Larson A . Magnetization transfer MRI in pancreatic cancer xenograft models. Magn Reson Med. 2012; 68(4):1291-7. PMC: 3323767. DOI: 10.1002/mrm.24127. View

19.

Jerome N, Hekmatyar S, Kauppinen R . Blood oxygenation level dependent, blood volume, and blood flow responses to carbogen and hypoxic hypoxia in 9L rat gliomas as measured by MRI. J Magn Reson Imaging. 2013; 39(1):110-9. DOI: 10.1002/jmri.24097. View

20.

Egeblad M, Rasch M, Weaver V . Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol. 2010; 22(5):697-706. PMC: 2948601. DOI: 10.1016/j.ceb.2010.08.015. View