Deciphering the dynamics of pathophysiological processes in animal models of age-related brain diseases using MRI
Jan Klohs1
1Bruker, Switzerland

Synopsis

The use of magnetic resonance imaging (MRI) in animal models of brain diseases has opened-up exciting possibilities to non-invasively interrogate pathological changes in the model brain and to monitor the dynamics of these events over the disease course. In my lecture I will showcase recent advances in MRI methodology and discuss their current applications for the research of cerebral ischemia and other age-related brain diseases. Applications span from the assessment of anatomical information of the brain, to quantitative probing of its microstructure and chemical composition, as well as deriving physiological and molecular information using dedicated imaging probes.

Age-related brain diseases such as cerebral ischemia and Alzheimer’s disease come with various unmet medical needs and have large disease burdens. The use of adequate animal models of human disease forms a fundamental part of the research efforts to improve the prevention, diagnosis, understanding and treatment of these neurological disease conditions. The use of magnetic resonance imaging (MRI) in animal models has opened-up novel possibilities to non-invasively interrogate the complex pathological changes in the model brain and to monitor the dynamics of these events over the disease course. Structural MRI exploiting different contrast is suited for assessing anatomical abnormalities such as lesions, calcifications and microhaemorrhages [1, 2]. Computation approaches allow to assess region-specific changes in brain morphology caused by pathology. Quantitative MRI techniques based on advanced sequences and biophysical models can extract detailed information (e.g. water content, magnetic susceptibility, relaxation times et.) of tissues that are related to its microstructural features and chemical composition [3, 4]. Moreover, the advent of newly designed contrast agents and reporter systems enables the direct visualization of cellular and molecular processes that play central roles in the pathophysiology [5]. In my lecture I will showcase recent innovations and current challenges in MRI methodology and discuss novel empirical findings. I will show how MRI based techniques may be particularly suited for the: i) phenotyping of experimental and genetic models of age-related brain diseases; ii) monitoring of neurodegenerative, vascular and immunological processes in the intact animal; iii) development and evaluation of novel treatments; and iv) the deployment and validation of imaging biomarkers that are translatable to the clinics.

Acknowledgements

No acknowledgement found.

References

[1] Klohs J, Deistung A, Schweser F, Grandjean J, Dominietto M, Waschkies C, Nitsch RM, Knuesel I, Reichenbach JR, Rudin M. Detection of cerebral microbleeds with quantitative susceptibility mapping in the ArcAbeta mouse model of cerebral amyloidosis. J Cereb Blood Flow Metab. 2011 Dec;31(12):2282-92.

[2] Ni R, Zarb Y, Kuhn GA, Müller R, Yundung Y, Nitsch RM, Kulic L, Keller A, Klohs J. SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy. MAGMA. 2020 Dec;33(6):769-781.

[3] Vaas M, Deistung A, Reichenbach JR, Keller A, Kipar A, Klohs J. Vascular and Tissue Changes of Magnetic Susceptibility in the Mouse Brain After Transient Cerebral Ischemia. Transl Stroke Res. 2018 Aug;9(4):426-435.

[4] Massalimova A, Ni R, Nitsch RM, Reisert M, von Elverfeldt D, Klohs J. Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy. Neurodegener Dis. 2020;20(5-6):173-184.

[5] Klohs J, Deistung A, Ielacqua GD, Seuwen A, Kindler D, Schweser F, Vaas M, Kipar A, Reichenbach JR, Rudin M. Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI. J Cereb Blood Flow Metab. 2016 Sep;36(9):1614-24.

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)