title: Structural and functional effects of metastases in rat brain determined by multimodal MRI.
abstract: Metastasis to the brain results in significant impairment of brain function and poor patient survival. Currently, magnetic resonance imaging (MRI) is under-utilised in monitoring brain metastases and their effects on brain function. Here, we sought to establish a model of focal brain metastasis in the rat that enables serial multimodal structural and functional MRI studies, and to assess the sensitivity of these approaches to metastatic growth. Female Berlin-Druckrey-IX rats were injected intracerebrally with metastatic ENU1564 cells in the ventroposterior medial nucleus (VPM) of the thalamus, a relay node of the whisker-to-barrel cortex pathway. Animals underwent multimodal structural and vascular MRI, as well as functional MRI of the cortical blood oxygenation level dependent (BOLD) responses to whisker pad stimulation. T2 , diffusion, magnetisation transfer and perfusion weighted MRI enabled differentiation between a central area of more advanced metastatic growth and penumbral regions of co-optive perivascular micrometastatic growth, with magnetisation transfer MRI being the most sensitive to micrometastatic growth. Areas of cortical BOLD activation in response to whisker pad stimulation were significantly reduced in the hemisphere containing metastases in the VPM. The reduction in BOLD response correlated with metastatic burden in the thalamus, and was sensitive to the presence of smaller metastases than currently detectable clinically. Our findings suggest that multimodal MRI provides greater sensitivity to tumour heterogeneity and micrometastatic growth than single modality contrast-enhanced MRI. Understanding the relationships between these MRI parameters and the underlying pathology may greatly enhance the utility of MRI in diagnosis, staging and monitoring of brain metastasis.
authors.affiliation: CR-UK/MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United Kingdom.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Serres
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martin
authors.forename: Manuel
authors.initials: M
authors.lastname: Sarmiento Soto
authors.forename: Claire
authors.initials: C
authors.lastname: Bristow
authors.forename: Emma R
authors.initials: ER
authors.lastname: O'Brien
authors.forename: John J
authors.initials: JJ
authors.lastname: Connell
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Khrapitchev
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Sibson
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D064847:Multimodal Imaging; D061206:Neoplasm Micrometastasis; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor
keywords: MRI; brain; fMRI; metastasis; rCBV