2012 Proceedings - International Tissue Elasticity Conference

030 SENSITIVITY OF MAGNETIC RESONANCE ELASTOGRAPHY TO DETECT BRAIN
DEVELOPMENT AND MATURATION.
Katharina Schregel 1,2 , Julie Le Faouder 2,3 , Eva Würfel 4 , Simon Chatelin 2 , Pierre Bedossa 2,5 ,
Jens Wüerfel 1 , Ralph Sinkus 2 .
1 Institute of Neuroradiology, University Luebeck, Luebeck, GERMANY; 2 Université Paris Diderot,
Sorbonne Paris Cité, INSERM, CRB3 U773, Paris, FRANCE; 3 Institut Fédératif de Recherche
Claude Bernard, Université Paris-Diderot, Paris, FRANCE; 4 Neuropediatrics Department,
University Goettingen, Goettingen, GERMANY; 5 Pathology Department, Beaujon Hospital,
Assistance Publique–Hôpitaux de Paris and Université Paris-Diderot, Paris, FRANCE.
Background: Cerebral tissue structure is altered in many neurodegenerative diseases but also during
physiological processes like maturation or aging. It is reasonable to assume that structural changes
directly affect the mechanical tissue properties. Magnetic Resonance Elastography (MRE) is an imaging
technique capable of assessing biomechanical brain parenchymal properties non–invasively [1].
Viscoelasticity can be quantified by analyzing the propagation of mechanically elicited shear waves in the
investigated tissue. Thus, MRE could be a helpful tool to detect physiological or pathological processes
influencing the cerebral tissue integrity.
Aims: As previously demonstrated, cerebral viscoelastic properties change during ongoing brain
maturation in adolescent mice [2]. However, the underlying cellular or molecular mechanisms responsible
for the observed changes have not been elucidated so far. In the present study, we combine full 3D–MRE
with MALDI–IMS (Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry) in order to (1)
prove an age–dependent behavior of cerebral biomechanics and (2) identify the underlying process.
Methods: 20 healthy 4–week-old female C57/BL6 mice were investigated 3–weekly. They were studied for
12 weeks, corresponding to a final age of 16 weeks. High resolution T2–weighted scans in addition to full
3D–MRE were performed on a 7 Tesla rodent scanner. The value of the complex–valued shear modulus
|G*| was calculated in a region of interest (ROI) covering the corpus callosum, rendering information on
its viscoelasticity. After each scanning period, 5 mice were sacrificed and brains were harvested for
further analyses. One part was investigated by MALDI–IMS, the remaining part by
immunohistochemistry.
Results: Viscoelasticity shows a triphasic course, matching the time course already observed in former
experiments [2]: it decreases from week 0 to 3, then increases up to week 9 and stabilizes afterwards.
MALDI–IMS renders matching spectra for all time points. Protein distribution correlates well with
anatomical features and peak intensity differs age–dependently.
Conclusions: Viscoelasticity developed during adolescence and reached a plateau at a mean age of 16
weeks, corresponding to the adulthood of the animals. Protein expression assessed with MALDI–IMS
seems to be age related as well. As volume fraction of the extra–cellular matrix (ECM) is described to
decrease during maturation [3], yet to perform protein identification and immunohistochemistry may help
to identify the exact mechanism responsible for the alterations of brain biomechanics during maturation.
Figure: (A) Quantitative analysis of viscoelasticity |G*| in the
corpus callosum (cc). Triphasic timecourse with
decrease, then increase and plateau of viscoelasticity.
(B) Optical image of the mouse brain with superposed
MALDI–MS image (pink). ROI covers the cc. Protein
distribution correlates with anatomy. (C) Superposed
spectra from different time points. Inlet shows
exemplary that peak intensity changes with age.
References:
[1] Green MA et al.: NMR Biomed, 21, pp, 755–764, 2008.
[2] Schregel K et al.: PNAS, 109, pp. 6650–6655, 2012.
[3] Sykova E, Mazel T, Simonova Z: Exp Gerontol., 33, pp. 837–851 1998.
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