Solid state NMR/Biophysical Organic Chemistr

Alia, A.

Braakman, N.

Buchem, M.A. van

Groot, H.J.M. de

Kara, F.

Ravensbergen, J.

Schliebs, R.

Leiden University Scholary Publications

MRI assessment of blood flow artifacts in a transgenic mouse model ofAlzheimer’s diseaseKara, F.; Ravensbergen, J.; Braakman, N.; Buchem, M.A. van; Schliebs, R.; Groot, H.J.M. de;Alia, A.CitationKara, F., Ravensbergen, J., Braakman, N., Buchem, M. A. van, Schliebs, R., Groot, H. J. M. de,& Alia, A. (2009). MRI assessment of blood flow artifacts in a transgenic mouse model ofAlzheimer’s disease. Proceedings Of The International Society For Magnetic Resonance InMedicine, 17, 1331. Retrieved from https://hdl.handle.net/1887/3454657 Version: Publisher's VersionLicense: Licensed under Article 25fa Copyright Act/Law (Amendment Taverne)Downloaded from: https://hdl.handle.net/1887/3454657 Note: To cite this publication please use the final published version (if applicable).See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/330857031MRI assessment of blood flow artifacts in a transgenic mouse model ofAlzheimer's diseaseConference Paper · January 2009CITATIONS0READS537 authors, including:Some of the authors of this publication are also working on these related projects:Leiden University View projectFree Heme at Alzheimers Disease View projectFirat KaraMayo Clinic38 PUBLICATIONS   197 CITATIONS   SEE PROFILEJanneke RavensbergenVrije Universiteit Amsterdam15 PUBLICATIONS   253 CITATIONS   SEE PROFILENiels BraakmanHaaglanden Medisch Centrum19 PUBLICATIONS   136 CITATIONS   SEE PROFILEHuub De GrootLeiden University359 PUBLICATIONS   9,797 CITATIONS   SEE PROFILEAll content following this page was uploaded by Alia Alia on 04 February 2019.The user has requested enhancement of the downloaded file.MRI assessment of blood flow artifacts in a transgenic mouse model of Alzheimer’s disease  F. Kara1, J. Ravensbergen1, N. Braakman1, M. A. van Buchem2, R. Schliebs3, H. J. de Groot1, and A. Alia1 1Leiden Institute of Chemistry, Leiden University, Leiden, P.O. Box 9502, Netherlands, 2Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, 3Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany  Introduction Alzheimer’s disease (AD) is the most common form of dementia in the elderly with no effective treatment or definitive antemortem diagnostic test. The neuropathologic features of AD include the occurrence of amyloid β (Aβ) containing plaques, neurofibrillary tangles, decreased synaptic density, and loss of neurons. In AD, the deposition of Aβ peptide in the cerebral vessel walls, known as cerebral amyloid angiopathy (CAA) is frequently observed, leading to blood flow abnormalities. However, its contribution to the onset and progression of dementia is unknown. The evidence for blood flow disturbance during AD comes mainly from postmortem studies. Direct non-invasive in vivo methods to probe blood flow disturbance during AD are highly challenging.  A previous study [1] has shown that magnetic resonance angiography (MRA) is a useful method to identify changes of vascular function in APP23 mice model of AD.  In this study we optimized high resolution MRA at 9.4T in combination with strong gradients to monitor morphological changes in cerebral arteries in APPTg2576 transgenic mice which is one of the most widely used mouse model of AD.  Our preliminary data showed significant morphological changes in large and medium sized arteries in APPTg2576 mice.   Methods The transgenic mice used in this study (Tg2576) contain as transgene the Swedish double mutation of the human amyloid precursor protein (APP695), as developed and described previously by Hsiao et al [2]. The transgene is expressed in C57B6 breeders. The N2 generation mice of both genders were studied at ages between 8 and 23 months. Age-matched non-transgenic littermates served as controls (WT). MRA measurements were conducted at 9.4-T vertical wide-bore imaging systems equipped with a Bruker Avance console and 1000-mT/m gradients. The imaging coil used was a 25-mm volume coil. Time-of-flight (TOF) angiograms were obtained using a 3D gradient echo sequence. The parameters used were TEeff = 1.9 ms, TR =15 ms, flip angle 30° and average = 1.  A resolution of 78x78x78 μm was achieved within an acquisition time of ~16 minutes. A three-dimensional view was obtained by generating maximum-intensity projections (MIP’s).  Results and Discussion It is well known that vascular abnormalities coexist with other pathological features of AD.  Recent vascular corrosion casts studies in APP23 transgenic AD mice have shown significant alteration of the microvasculature [3]. Small to medium-sized arteries and arterioles are most frequently affected vessels by CAA in AD [4]. To compare the vascular architecture of living APPTg2576 transgenic and WT mice, we applied high resolution MRA at 9.4T.  With 3D TOF sequence, which is sensitive to fast-flowing blood, cerebral arterial structures of living mice can be selectively probed (Fig. 1). Due to high field strength and use of strong gradients, the large and medium sized arteries were very clearly imaged upto the level of the pial vessels. Overall decrease in the brightness of the arteries was observed in transgenic mice as compared to wild-type suggesting an overall decrease in cerebral blood flow. Flow voids were observed at different places such as in superior cerebral artery, anterior cerebral arteries as well as in pterygopalatine arteries (Fig. 2). However, these voids were not restricted to only these locations in transgenic mice. The presence of plaques and CAA in the brain of same APPTg2576 was confirmed by histology (Fig. 3).  Our results suggest that MRA at high magnetic field is useful method to monitor CAA-related structural changes in cererbral arteries and arterioles in mouse models, providing a powerful tool to study the contribution of CAA to AD in vivo in animal models.  References:  [1] Beckmann N, Schuler A, Mueggler T, et al.  J. Neurosci. 2003;23:8453-8459; [2] Hsiao K, Chapman P, Nilsen S, et al. Science 1996;274(5284):99-103; [3] Meyer EP, Ulmann-Schuler A, Staufenbiel M, Krucker T. Proc. Nat. Acad. Sci. 2008;105:3587-3592; [4] Herzig MC. Inaugural dissertation, Universität Basel 2004.          Fig. 1. MIP of 3D TOF MRA of 23-month- old wild type mouse.  The arteries are identified as: 1, posterior cerebral artery;  2, superior cerebellar artery;  3,  caudal cellebellar artery;  4, basilar artery;  5, middle cerebral artery;  6, anterior cerebral artery;  7, facial artery;  8, palatine portion of pterygopalatine;  9, maxillary artery;  10,  pterygo portion of pterygopalatine;  11, external carotid artery;  12, internal carotid artery;  14, vertebral artery;  15, common carotid artery.  123134567891011121415 Fig. 2. Angiogram of 23-month-old transgenic mice showing severe flow voids at the pterygo portion of the pterygopalatine artery (a,c) and missing bifurcation of one of the anterior cerebral arteries (b, d). Such changes were not observed in wild-type mice.    Fig. 3. CAA detected in the brain sections of 23-month old transgenic mice stained with Aβ40 a b c d Proc. Intl. Soc. Mag. Reson. Med. 17 (2009) 1331View publication stats

MRI assessment of blood flow artifacts in a transgenic mouse model of Alzheimer’s disease

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MRI assessment of blood flow artifacts in a transgenic mouse model of Alzheimer’s disease

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