Use of FCC-NMRD relaxometry for early detection and characterization of ex-vivo murine breast cancer

Enza Di Gregorio,Giuseppe Ferrauto,Eliana Gianolio,Stefania Lanzardo,Silvio Aime

doi:10.1038/s41598-019-41154-9

Enza Di Gregorio, Giuseppe Ferrauto + Show 3 more

Open Access

https://doi.org/10.1038/s41598-019-41154-9

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Journal: Scientific Reports	Publication Date: Mar 15, 2019
Citations: 8	License type: open-access

Affiliation: University of Turin

Abstract

Breast Cancer is the most diffuse cancer among women and the treatment outcome is largely determined by its early detection. MRI at fixed magnetic field is already widely used for cancer detection. Herein it is shown that the acquisition of proton T1 at different magnetic fields adds further advantages. In fact, Fast Field Cycling Nuclear Magnetic Resonance Dispersion (FFC-NMRD) profiles have been shown to act as a high –sensitivity tool for cancer detection and staging in ex vivo murine breast tissues collected from Balb/NeuT mice. From NMRD profiles it was possible to extract two new cancer biomarkers, namely: (i) the appearance of 14N-quadrupolar peaks (QPs) reporting on tumor onset and (ii) the slope of the NMRD profile reporting on the progression of the tumor. By this approach it was possible to detect the presence of tumor in transgenic NeuT mice at a very early stage (5–7 weeks), when the disease is not yet detectable by using conventional high field (7 T) MRI and only minimal abnormalities are present in histological assays. These results show that, NMRD profiles may represent a useful tool for early breast cancer detection and for getting more insight into an accurate tumor phenotyping, highlighting changes in composition of the mammary gland tissue (lipids/proteins/water) occurring during the development of the neoplasia.

Highlights

Breast Cancer is a multifactorial disease, considered a major public-health issue worldwide and the second cause of cancer-associated death among women[1,2]
Balb-NeuT mice have been investigated at different stage of their growth, i.e.at the age of (i) 5–7w, (ii) 15w, (iii) 21w and (iv) 30w, respectively
The detection threshold by a typical Magnetic Resonance Imaging (MRI)-T2 scan may be set at 15 weeks

Summary

Introduction

Breast Cancer is a multifactorial disease, considered a major public-health issue worldwide and the second cause of cancer-associated death among women[1,2]. Relevant information may be obtained by exploiting the T1 dependence of protons tissue from the applied magnetic field strength (B0) This task cannot be yet accomplished on the available MRI scanners, because they work at fixed B0. The acquisition of the so called Fast Field Cycling–Nuclear Magnetic Dispersion (FFC-NMRD) profiles[17,18,19] on ex vivo tissues can provide useful insights into the potential diagnostic value of Field-dependent T1-based approach[20]. These profiles report about 1H water relaxation rate, R1 (where R1 = 1/T1), over an extended range of magnetic fields. Their analysis can provide useful information about tissue water dynamics and the presence of lipids, protein and paramagnetic species as well as the interaction of water with proteins and other macromolecules[14,15,16,19,20,21]

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