Vascular and Tissue Changes of Magnetic Susceptibility in the Mouse Brain After Transient Cerebral Ischemia

Translational Stroke Research https://doi.org/10.1007/s12975-017-0591-x ORIGINAL ARTICLE Vascular and Tissue Changes of Magnetic Susceptibility in the Mouse Brain After Transient Cerebral Ischemia Markus Vaas 1,2 & Andreas Deistung 3,4,5 & Jürgen R. Reichenbach 3,6 & Annika Keller 7 & Anja Kipar 8 & Jan Klohs 1,2 Received: 6 November 2017 / Accepted: 17 November 2017 # The Author(s) 2017. This article is an open access publication Abstract Quantitative susceptibility mapping (QSM) has been recently introduced as a novel MRI post-processing technique of gradient recalled echo (GRE) data. QSM is useful in depicting both brain anatomy and for detecting abnormalities. Its utility in the context of ischemic stroke has, however, not been extensively characterized so far. In this study, we explored the potential of QSM to characterize vascular and tissue changes in the transient middle cerebral artery occlusion (tMCAO) mouse model of cerebral ischemia. We acquired GRE data of mice brains at different time points after tMCAO, from which we computed QSM and MR frequency maps, and compared these maps with diffusion imaging and multi-slice multi-echo imaging data acquired in the same animals. Prominent vessels with increased magnetic susceptibility were visible surrounding the lesion on both frequency and magnetic susceptibility maps at all time points (mostly visible at > 12 h after reperfusion). Immunohistochemistry revealed the presence of compressed capillaries and dilated larger vessels, suggesting that the appearance of prominent vessels after reestablishment of reperfusion may serve compensatory purposes. In addition, on both contrast maps, tissue regions of decreased magnetic susceptibility were observed at 24 and 48 h after reperfusion that were distinctly different from the lesions seen on maps of the apparent diffusion coefficient and T2 relaxation time constant. Since QSM can be extracted as an add-on from GRE data and thus requires no additional acquisition time in the course of acute stroke MRI examination, it may provide unique and complementary information during the course of acute stroke MRI examinations. Keywords Quantitative susceptibility mapping . MR frequency . Magnetic resonance imaging . Mice . Middle cerebral artery occlusion . Ischemia Introduction * Jan Klohs 1 Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland 2 Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland 3 Medical Physics Group, Institute of Diagnostic and Interventional Radiology, University Hospital Jena, 07743 Jena, Germany 4 Section of Experimental Neurology, Department of Neurology, Essen University Hospital, 45147 Essen, Germany 5 Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, 45141 Essen, Germany 6 Michael Stifel Center for Data-driven and Simulation Science Jena, Friedrich Schiller University Jena, 07743 Jena, Germany 7 Division of Neurosurgery, University Hospital Zurich, 8091 Zurich, Switzerland 8 Institute of Veterinary Pathology, University of Zurich, 8057 Zurich, Switzerland Magnetic resonance imaging (MRI) is an important aid for physicians in the diagnosis and management of patients with acute stroke [1], providing multiple useful contrasts for assessing hemodynamic function as well as extent and severity of brain injury. In case of ischemic stroke, magnetic resonance angiography, for instance, can identify occlusion of a parent artery [2], whereas perfusion-weighted imaging (PWI) informs about regional disturbances of cerebral blood supply in hyperacute and acute ischemic stroke [3]. Diffusion-weighted imaging (DWI) has been shown to depict the ischemic lesion in the hyperacute, acute, and subacute stage after an ischemic insult [4–7]. Analyzing T1 and T2 relaxation times has also been used to assess ischemic damage [8, 9]. Bulk magnetic susceptibility is a fundamental physical property representing a materials’ tendency to interact with and distort an applied magnetic field. By applying gradient (recalled) echo (GRE) magnetic resonance-based techniques, Transl. Stroke Res. such as T2*-weighted imaging [10, 11], phase imaging [12, 13], and susceptibility-weighted imaging (SWI) [14, 15], it is possible to assess qualitatively magnetic susceptibility variations in the brain. Regarding acute stroke MRI, T2*-weighted imaging and SWI are used to detect cerebral microbleeds and hemorrhages [16], where SWI is also used to identify areas of hypoperfusion and to detect acute intravascular emboli [1]. Furthermore, asymmetrical veins between ischemic and normal brain tissues have been demonstrated with SWI, which may add information about local oxygen metabolism [17–19]. More recently, quantitative susceptibility mapping (QSM) has been introduced as a promising post-processing technique based on GRE data. QSM utilizes the small magnetic field variations arising from the underlying tissue magnetic susceptibility distribution to compute quantitative maps. It provides complementary anatomical contrast of the brain [20, 21], supports identification and characterization of brain lesions [22, 23], but also enables quantification of tissue iron content [24, 25], assessment of functional changes [26], and quantification of contrast agent concentration [27]. Concerning acute stroke QSM has been shown to be able to assess vessel function and oxygen metabolism in patients with acute stroke [18, 28] as well as in animal models of the disease [29]. In the present study, we investigated the potential of QSM and MR frequency mapping to assess the evolution of vascular and tissue changes in the mouse brain after transient middle cerebral artery occlusion (tMCAO). We acquired highresolution GRE, DWI, and multi-slice multi-echo imaging data of mice brains at different time points after reperfusion. On the post-processed QSM and MR frequency maps, magnetic susceptibility and frequency were quantified in prominent vessels and brain tissues in both the ischemic and contralateral hemisphere side. We also evaluated the time courses of the occurrence of regional contrast changes on the frequency, magnetic susceptibility, apparent diffusion coefficient (ADC), and T 2 relaxation time constant maps. Immunohistochemical analyses were performed to assess underlying vascular pathology. Methods Animals All procedures conformed to the national guidelines of the Swiss Federal act on animal protection and were approved by the Cantonal Veterinary Office Zurich (Permit Number: 18-2014 and 49-2011). All procedures fulfilled the ARRIVE guidelines on reporting animal experiments. Animals were housed in a temperature-controlled room in individually ventilated cages, containing up to five animals per cage, under a 12-h dark/light cycle. Paper tissue was given as environmental enrichment. Access to pelleted food (3437PXL15, CARGILL) and water was provided ad libit (...truncated)