Successful Serial Imaging of the Mouse Cerebral Arteries Using Conventional 3-T Magnetic Resonance Imaging

Abstract

Serial imaging studies can be useful in characterizing the pathologic and physiologic remodeling of cerebral arteries in various mouse models. We tested the feasibility of using a readily available, conventional 3-T magnetic resonance imaging (MRI) to serially image cerebrovascular remodeling in mice. We utilized a mouse model of intracranial aneurysm as a mouse model of the dynamic, pathologic remodeling of cerebral arteries. Aneurysms were induced by hypertension and a single elastase injection into the cerebrospinal fluid. For the mouse cerebrovascular imaging, we used a conventional 3-T MRI system and a 40-mm saddle coil. We used non-enhanced magnetic resonance angiography (MRA) to detect intracranial aneurysm formation and T2-weighted imaging to detect aneurysmal subarachnoid hemorrhage. A serial MRI was conducted every 2 to 3 days. MRI detection of aneurysm formation and subarachnoid hemorrhage was compared against the postmortem inspection of the brain that was perfused with dye. The imaging times for the MRA and T2-weighted imaging were 3.7 ± 0.5 minutes and 4.8 ± 0.0 minutes, respectively. All aneurysms and subarachnoid hemorrhages were correctly identified by two masked observers on MRI. This MRI-based serial imaging technique was useful in detecting intracranial aneurysm formation and subarachnoid hemorrhage in mice. 1 There are a number of mouse models of the physiologic or pathologic remodeling of cerebral arteries. Journal of Cerebral Blood2-5 To study the remodeling of cerebral arteries, a noninvasive, serial imaging technique that can visualize the cerebral arteries is an extremely useful tool.We report on the feasibility of using a readily available, conventional 3-T clinical magnetic resonance imaging (MRI) system to serially image cerebral arteries in mice. As a test case, we utilized a mouse model of an intracranial aneurysm that shows dynamic changes in the cerebral arteries. 2,6,7 In this model, intracranial aneurysms were induced by a combination of systemic hypertension and a single injection of elastase into the cerebrospinal fluid.

Imaging of intracranial aneurysms in animals: a systematic review of modalities

“…Therefore, few studies using endogenous IA animal models used MRA (Table 1 ). In 2015, using MRA, Makino et al [ 143 ] were able to detect a large aneurysm induced in a mouse cerebral artery after elastase injection in the cerebrospinal fluid. However, because of their small size, most endogenous IAs are impossible to image with MRA despite huge improvement in MRI technology with the development of 7 T or even 9.4 T MRI.…”

“…This less invasive imaging modality makes MRA an optimal instrument for serial imaging in long-term studies. Indeed, safe serial imaging in long-term studies using MRA was performed in dogs [113], mouse [143,156,174], rats [96,136,137,181], and rabbit elastase IA models [18,169]. Several studies in human suggest that MRA could be considered equivalent to DSA to detect IAs [7].…”

Extra- and Intraluminal Elastase Induce Morphologically Distinct Abdominal Aortic Aneurysms in Mice and Thus Represent Specific Subtypes of Human Disease

“…We, therefore, suggest an acute neutrophil-driven inflammation with destruction of the adventitia and consecutive medial macrophage homing with establishment of the macrophage/MMP-driven elastolysis as responsible mechanism for aneurysm growth in EPA. This is emphasized by the possibility of aneurysm induction also in low elastin-containing murine femoral arteries by external elastase application (data not shown) or cerebral arteries [9]. …”

“…The concept of extraluminal elastase has since gained some attention in murine models of vascular disease, e.g. in cerebral or thoracic aortic aneurysms [9,10]. …”

Protective Effect of Mesenchymal Stem Cells Against the Development of Intracranial Aneurysm Rupture in Mice

“…17 Our previous studies, including a study utilizing serial magnetic resonance imaging, found that aneurysm formation occurs during the first 6 to 7 d in this model; aneurysmal rupture begins approximately ∼7 d after aneurysm induction. 6,[17][18][19] Therefore, experimental treatments starting from 6 d after aneurysm induction can be used to test whether the experimental agents reduce the rupture rate. 5,17,18 In the current study, MSCs (1×10 6 cells per 150 μL PBS) were injected intravenously 6 and 9 d after aneurysm induction, as shown in the experimental protocol ( Figure 1A).…”