Fast DTI @ 11.7 T: Ready for Cohort Studies

Abstract: The application of the cryogenically cooled resonator enables rapid DTI acquisitions as basis for cohort studies in mice.

Hans-Peter Müller¹ , Ina Vernikouskaya^2,3, Albert C. Ludolph¹ , Jan Kassubek¹ , Detlef Stiller⁴, Volker Rasche^2,3

¹ Department of Neurology, University Hospital Ulm, Ulm, Germany

² Department of Internal Medicine II, University Hospital of Ulm, Ulm, Germany

3 Small Animal MRI, Medical Faculty, University of Ulm, Ulm, Germany

⁴ Target Discovery Research, Boehringer Ingelheim Pharma GmbH&Co. KG, Biberach, Germany

⁵ Aggarwal M, Mori S, Shimogori T, Blackshaw S, Zhang J (2010) Threedimensional diffusion tensor microimaging for anatomical characterization of the mouse brain. Magn Reson Med 64: 249-261

Introduction: in vivo high resolution diffusion tensor imaging (DTI) of the mouse brain has proven promising application for a variety of pathologies. Its application to large cohort studies, however, is often limited by the intrinsic low signal to noise ratio (SNR) causing long acquisition times. Cryogenically cooled resonators (CCR) have demonstrated the potential for significantly increasing SNR and appear attractive for reducing scan times in DTI imaging thus enabling cohort studies. This contribution describes the DTI acquisition optimization using CCRs and presents the outcome of an initial cohort study at the group level to β-amyloid precursor protein (APP) transgenic mice.

Methods: A DTI sequence providing 156² x 250 µm³ spatial resolution with 30 diffusion encoding directions was optimized for using CCR at ultrahigh field (11.7 T), resulting in a total acquisition time of 35 minutes. The quality was directly compared with a standardized 110 minutes acquisition protocol published earlier. Fractional anisotropy (FA) and fiber tracking (FT) results including quantitative tractwise fractional anisotropy statistics (TFAS) were qualitatively and quantitatively compared. The optimized sequence was then applied to 5 wild type and 7 APP transgenic (tg2576) mice for investigation of its potential for cohort studies. Fractional anisotropy (FA) maps were statistically compared by whole brain-based spatial statistics (WBSS) at the group level vs. wild type controls.

Results: With the optimized protocol no remarkable differences were observed for the qualitative and quantitative assessment of the calculated fractional anisotropy maps and fibre tracking results. Coefficients of variation for ROI-based FA-comparison as well as for TFAS revealed comparable results for the investigated scanning protocols. At the group level, differences were observed between the WT and the transgenic animals at locations associated with Alzheimer’s disease in humans, such as the hippocampus, the entorhinal cortex, and the caudoputamen.

Conclusion: DTI of the mouse brain at 11.7 T can be performed within approximately 30 minutes, which renders cohort studies feasible. With the fast protocol reliable and reproducible FA-values and FT reconstructions could be achieved. The application of the fast protocol to cohort studies revealed changes identified by WBSS of the FA maps in regions associated with amyloid-β deposition for the transgenic mice, thus proving the potential of rapid DTI for cohort studies.