Institute of Anatomy

Research

MikroCT

Research

Prologue/Short Summary

Since 2011, the research activities of Dr. Ruslan Hlushchuk focus on the development of new methods/approaches in (micro)vascular imaging and the quantitative analysis of angiogenesis. Besides the establishment of a new quantitative angiogenesis assay in zebrafish model [3], he managed to acquire financial support from Commission for Technology and Innovation (CTI) for a large project (total budget – over 1.3 million CHF). Two desktop microCT-scanners were acquired within the frame of this CTI-supported project and used since the start of the project in 2013. During this project, the research group of Dr. Ruslan Hlushchuk became a “microCT research group”. This project has finally led to the development and successful patent registration of a novel polymer-based contrast agent called µAngiofil for ex vivo microangiography/microangioCT. The promising results of our first studies with µAngiofil have attracted attention throughout the international research community. The group members have been invited to present the results at international conferences and meetings, and our work has won awards on the national (SNSF Scientific Image Competition 2017, Framing [Science]) as well as international levels, e.g., the Wellcome Image Awards 2017. The gained recognition lead to an increasing amount of requests for cooperation from Switzerland and abroad, including the most prominent opinion leaders in the various fields of research as corroborated by recent publications in Circulation [4], Nature Communications [5] and Science [6].

Our microCT research group believes to have extensive experience and probably unique know-how in analysis and well as imaging of the microvasculature in various tissues including rodent brain, skeletal muscle, heart etc. By now, our microCT infrastructure has been upgraded through acquisition of the multiscale nanoCT laboratory system SkyScan 2214 (March 2021) and the research focus of our projects and collaborations has broadened beyond microangioCT (see below).

 

Research

The aforementioned ex vivo polymer-based contrast agent, µAngiofil, which was developed in our research group, enables superb microCT-based microvascular imaging in various tissues (=microangioCT) and can be combined with subsequent histological investigation for correlative morphology (Fig. 1 & 2) [2, 7].

MicroangioCT of the minipig eye
Fig 1. MicroangioCT of the minipig eye. For details, see Hlushchuk et al, Brain Struct Funct (2020) [2].

 

Correlative imaging approach to visualize vasculature and fiber arrangement by microCT and histology
Fig. 2. Correlative imaging approach to visualize vasculature and fiber arrangement by microCT and histology. A Workflow. B: Contrast-enhanced vasculature of plantaris muscle in 3D. C: Muscle fibers of the same plantaris muscle in 3D. F: Corresponding histological cross-section stained with Masson trichrome. For details, see Hlushchuk et al, Vascul Pharmacol (2019).

 

MicroangioCT of murine brain
Fig. 3

We have a few ongoing collaborations (Prof. Britta Engelhardt, Theodor-Kocher Institute, University of Bern) on the vasculature-related brain research projects, in which we apply microangioCT approach enabling the visualization of the vasculature of the whole murine brain (Fig. 3).

MicroangioCT of the periimplant tissues in the minipig mandibular
Fig 4. MicroangioCT of the periimplant tissues in the minipig mandibular (common project with Institut Straumann AG, Basel, Switzerland). The sample was scanned on SkyScan 2214 at 5µm isotropic voxel size.

Visualization of the vasculature within the soft tissues and organs using microangioCT approach is far less challenging than within the bone tissue or even in the vicinity of the metal or ceramic implants. But even this challenge could be overcome using µAngiofil and higher acceleration voltage range of the newest multiscale nanotomograph. We are proud to say that we can visualize the vascularization of the peri-implant bone as well as soft tissue (in a collaboration project with Institut Straumann AG) Therefore, microangioCT opens new horizons for the implantology research (see Fig. 4).

Three-dimensional visualization of tooth sample and its root canal configuration
Fig 5. Three-dimensional visualization of tooth sample and its root canal configuration [1]

Besides microangioCT-focused projects we also have extensive experience in non-vascular microCT-based imaging of various structures like tooth canals (common project with Dental Medical Clinic, University of Bern) (Fig. 5), zebrafish gills (collaboration with internal groups from the Institute of Anatomy, University of Bern) or even chondrules (collaboratin with Space Research and Planetary Sciences, Institute of Physics, University of Bern).

 

Epilogue

We are open for collaborations especially if the questions addressed are interesting and the imaging is challenging.

For collaboration requests, please, contact Ruslan Hlushchuk.

 

References

1. Haberthur, D., R. Hlushchuk, and T.G. Wolf, Automated segmentation and description of the internal morphology of human permanent teeth by means of micro-CT. BMC Oral Health, 2021. 21(1): p. 185.

2. Hlushchuk, R., et al., Innovative high-resolution microCT imaging of animal brain vasculature. Brain Struct Funct, 2020. 225(9): p. 2885-2895.

3. Hlushchuk, R., et al., Zebrafish Caudal Fin Angiogenesis Assay-Advanced Quantitative Assessment Including 3-Way Correlative Microscopy. PLoS One, 2016. 11(3): p. e0149281.

4. Rasanen, M., et al., VEGF-B Promotes Endocardium-Derived Coronary Vessel Development and Cardiac Regeneration. Circulation, 2021. 143(1): p. 65-77.

5. Nording, H., et al., The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets. Nat Commun, 2021. 12(1): p. 3352.

6. Grunewald, M., et al., Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span. Science, 2021. 373(6554).

7. Hlushchuk, R., D. Haberthur, and V. Djonov, Ex vivo microangioCT: Advances in microvascular imaging. Vascul Pharmacol, 2019. 112: p. 2-7.