Abstract
ObjectivesTo determine the ability of multi-parametric, endogenous contrast MRI to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma.MethodsFemale 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.ResultsSignificant correlations were found between MT parameters and degree of picrosirius red staining (r > 0.85, p < 0.0002 for ka and δ, r < -0.75, p < 0.001 for T1 and T1s, 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 T2* (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.ConclusionsMagnetisation 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.
Highlights
Breast cancer development and growth is strongly influenced by the crosstalk of tumour cells with the surrounding extracellular matrix/stroma [1,2,3]
intravoxel incoherent motion (IVIM) diffusion does not correlate with microvessel density in preclinical mammary carcinoma
This study aims to determine the ability of multi-parametric magnetic resonance imaging (MRI) incorporating several endogenous contrast mechanisms, such as DWI, magnetisation transfer (MT)-MRI and ultrashort-echo time (UTE)-MRI, performed on a clinical imaging platform, to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma previously shown to produce heterogeneous tumours with a range of fibrosis severity [18]
Summary
Breast cancer development and growth is strongly influenced by the crosstalk of tumour cells with the surrounding extracellular matrix/stroma [1,2,3]. The stroma can make up a significant proportion of a breast carcinoma [4], and differs from normal stroma, bearing closer resemblance to granulation tissue and wound healing, with a high number of fibroblasts, deposition of type I collagen and fibrin, and the infiltration of inflammatory cells [5]. The presence of a fibrotic focus, a central scar-like area within a carcinoma that represents a focus of exaggerated reactive tumour stromal formation, was first proposed as an indicator of increased tumour aggressiveness in invasive ductal breast cancer by Hasabe et al [6], and has since been linked to early disease relapse, lymph node and osteolytic bone metastasis, and reduced long-term survival [7,8,9]. Imaging biomarkers for assessing tumour pathophysiology require evaluation before being routinely deployed in clinical trials; in particular, imagingpathology correlation, and whether the imaging biomarker reflects underlying pathology is important to establish, but can often only meaningfully be studied in animal models [11]
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