Unveiling the Exquisite Microstructural Details in Zebrafish Brain Non-invasively using Magnetic Resonance Imaging at 28.2 T

Preprints.org

Abstract

Zebrafish (Danio rerio) is an important animal model for a wide range of neurodegenerative diseases. However, obtaining the cellular resolution that is essential for studying the zebrafish brain remains challenging as it requires high-spatial resolution and signal-to-noise ratios (SNR). In the current study, we present the first MRI results of the zebrafish brain at the state-of-the-art magnetic field strength of 28.2 T. The performance of MRI at 28.2 T was compared to 17.6 T. A 20% improvement in SNR was observed at 28.2 T as compared to 17.6 T. Excellent contrast, resolution, and SNR allowed the identification of several brain structures. The normative T1 and T2 relaxation values were established over different zebrafish brain structures at 28.2 T. To zoom into the white matter structures, we applied diffusion tensor imaging (DTI) and obtained axial, radial, and mean diffusivity, as well as fractional anisotropy at a very high spatial resolution. Visualization of white matter structures was achieved by short-track track-density imaging by applying the constrained spherical deconvolution method (stTDI CSD). For the first time, an algorithm for stTDI with multi-shell multi-tissue (msmt) CSD was tested on zebrafish brain data. A significant reduction of false-positive tracks from grey matter signals was observed compared to stTDI with single-shell single-tissue (ssst) CSD. This allowed the non-invasive identification of white matter structures at high resolution and contrast. Our results show that ultra-high field DTI and tractography provide reproducible and quantitative maps of fibre organization from tiny zebrafish brains, which can be implemented in the future for a mechanistic understanding of disease-related microstructural changes in zebrafish models of various brain diseases.

Authors 8

1. Rico Singer Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2301 RA Leiden, The Netherlands

2. Ina Oganezova Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2301 RA Leiden, The Netherlands

3. Wanbin Hu Aachen Institute of Biology, Leiden University

   Leiden University

   Affiliation as printed

   Institute of Biology, Leiden University, Einsteinweg 55, 2301 RA Leiden, The Netherlands

4. Yi Ding Aachen Institute of Biology, Leiden University

   Leiden University

   Affiliation as printed

   Institute of Biology, Leiden University, Einsteinweg 55, 2301 RA Leiden, The Netherlands

5. Antonios Papaioannou

   Bruker (Germany)

   Affiliation as printed

   Bruker BioSpin GmbH, NMR Microscopy, Rheinstetten, Germany

6. Huub J. M. de Groot Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2301 RA Leiden, The Netherlands

7. Herman P. Spaink Aachen Institute of Biology, Leiden University

   Leiden University

   Affiliation as printed

   Institute of Biology, Leiden University, Einsteinweg 55, 2301 RA Leiden, The Netherlands

8. A. Alia corresponding Aachen

   Leiden University · Leipzig University

   Affiliation as printed

   Institut für Medizinische Physik und Biophysik, Universität Leipzig, Härtelstr. 16-18, D-04107 Leipzig, Germany

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2301 RA Leiden, The Netherlands