Towards a novel small animal quantitative perfusion MRI reference standard

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Perfusion MRI is a clinically important imaging technique in the management of e.g. stroke, cardiac ischemia or tumors. Absolute quantification of perfusion parameters is highly desirable to take treatment decisions most objectively. Small animal perfusion MRI falls far behind from clinical scanning in terms of quantification. This insufficiency limits the translation of preclinical perfusion experiments into clinical studies. The lack of quantification mainly derives from the inability to precisely measure the dynamic arterial blood concentration - the so-called arterial input function (AIF) – a critical prerequisite for quantitative perfusion MRI. Especially in mice, given the image resolution, e.g. intracranial arterial vessels are typically too small to measure signals from pure blood. In previous preliminary work, we developed a novel technique for measuring AIFs in small animals: The animals’ blood is shunted and lead through an extracorporeal circulation to generate an artificial perfused blood reservoir that can be positioned inside the imaging plane. We could demonstrate the potential of the novel setup to gather AIFs in perfusion MRI in mice with previously unmet quality and quantitative robustness. Moreover, the setup allows to simultaneously measure radiotracer blood concentrations allowing unique multimodal validation approaches. In this project, we aim (1) to demonstrate that our experimental setup can serve as a quantitative ground truth to evaluate conventional methods of AIF measurements. (2) We will establish a specific reference dataset of AIFs and perfusion parameters serving as a quantitative standard for future studies. (3) We will compare the quantitative potential of the two most common perfusion MRI methods: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC)-MRI. (4) We will validate the quantitative potential of recently published rapid MR imaging techniques of perfusion MRI.To fulfill these objectives, we perform DCE and DSC perfusion MRI using our novel extracorporeal circulation setup in mouse brains bearing intracranial glioblastoma, a frequent preclinical and clinical scenario to study perfusion. We will target our objectives by extensive multimodal validation of the MR-derived contrast agent concentration and perfusion parameters including: (1) A co-Injected radioactive labelled variant of a standard Gadolinium contrast agent will be simultaneously measured to validate the whole dynamic range of the AIF. (2) Laser-ablation ionizing coupled plasma mass spectrometry (LA-ICP-MS) will serve to evaluate contrast agent concentration in tissue. (3) [99mTc]-labeled radiotracers will be co-injected for quantitatively mapping cerebral blood volume and flow by SPECT/CT and autoradiography.We thereby expect a significant advance for quantitative preclinical perfusion MRI to catch up with the quantitative abilities of clinical scanning finally improving preclinical and translational studies.