The mouse model of spontaneous developing glioblastoma was sourced from a colony at the Queensland Brain Institute, University of Queensland. Materials and Methods Animal Model and Preparation This was demonstrated using a selection of mice with glioblastoma tumours at different stages of progression. The aim of this study was to demonstrate independent measurement of MR derived vascular delivery and tissue uptake simultaneously with the PET tracer DPA-714 in a mouse model of glioblastoma. This allows parallel changes in vascular delivery and tissue uptake to be determined, which was not possible previously. Therefore, we move from acquiring separate T 1 or T 2* contrast images to simultaneously calculating T 1 and T 2* images from gradient echo image pairs with TE = 3 and 6 ms. Dual echo gradient echo MRI enables T 1 and T 2* changes to be calculated simultaneously. Typically, imaging sequences are optimised for only one contrast, T 1 or T 2*, dependent on the type of perfusion regime being investigated. For higher Gd concentrations, T 2 and T 2* shortening dominate, decreasing the signal, ultimately nulling at high concentrations, as exploited in dynamic susceptibility (DSC) MRI. Lower concentrations of Gd produces T 1 shortening resulting in signal enhancement in T 1 weighted images, as used in dynamic contrast enhanced (DCE) MRI. For comparison, in nuclear imaging methods like PET, the image intensity observed is in units of radioactivity that are directly related to the activity of tracer present. The change in MR image intensity during contrast-enhanced magnetic resonance imaging (MRI) is not linearly related to the Gadolinium (Gd) concentration over a large concentration range, particularly when the image contrast is a mix of T1, T2 and/or T2* weighting. The higher spatial and temporal resolution of magnetic resonance imaging (MRI) has potential to allow MR image derived arterial input function (AIF) for PET pharmacokinetic modelling. This is challenging in rodents, particularly mice, as methods often require blood sampling and/or surgical procedures, and imaging methods are limited by the low resolution of PET. Kinetic analysis of PET tracers requires determination of the time dependent change in tracer activity in the blood (input function). These effects can dramatically change the transport of candidate diagnostics and therapeutics and contribute to the effectiveness of new treatments, with recent data demonstrating that nanomedicine accumulation is related to vascular leakiness, rather than tumour volume alone. Tumour growth is accompanied by neovascular development and compromised BBB integrity. The measured activity of a diagnostic or therapeutic positron emission tomography (PET) tracer can be modulated by vascular delivery, transport into and out of the tissue, specific and non-specific binding of the radiotracer and metabolism, particularly in the brain where the blood brain barrier (BBB) strongly regulates transport from the vasculature to the neural tissue. The dramatic changes in the MR-derived vascular delivery and tissue uptake estimates may improve the understanding of the alteration of delivery and uptake of new theranostic agents. Changes in the PET activity curves were seen in tumours and normal tissue, reflecting changes in the MR derived dynamic curves. Separate T 2*- and T 1-derived gadolinium concentrations curves were derived in a selection of tumours and normal tissue, reflecting vascular delivery and tissue uptake. Relaxivity values then enabled determination of independent T 2*- and T 1-derived gadolinium concentrations simultaneously with measurement of DPA-714 neuroinflammation radiotracer delivery. Simultaneous dynamic gadolinium MR-PET enables independent assessment of vascular delivery and blood brain barrier integrity in a brain tumour animal model in the presence of a PET tracer.ĭual echo dynamic gadolinium enhanced gradient echo imaging allows simultaneous calculation of T 2* and T 1 images from the TE image pairs. 3Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Convergent BioNano Science and Technology and ARC Training Centre in Biomedical Imaging Technology, University of Queensland, Brisbane, QLD, AustraliaĮfficacy of diagnostics and therapeutics for brain tumours can be modulated by vascular delivery and blood brain barrier permeability.2Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.1National Imaging Facility, Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.Gary J Cowin 1*, Karine Mardon 1, Zachary H.
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