​Looking inside Zebrafish

A novel imaging technique developed in Delft must enable medical researchers to look inside living Zebrafish to study tumours.

Soon there will be no need to cut them up anymore. (Photo: Novartis, creative commons)
Soon there will be no need to cut them up anymore. (Photo: Novartis, creative commons)

Under normal circumstances, the Zebrafish swimming in the aquarium at the office of Dr. Jeroen Kalkman of the Department of Imaging Physics (AS) would end up cut into thin slices that would then be placed one after the other under a microscope. That destiny however is not awaiting these little grey and white creatures of less than a centimetre long, which in many academic hospitals serve as animal models to study disease.

Kalkman and his colleagues are developing a technique called Optical Coherence Computed Tomography enabling them to look into these live fish using infrared light. Rontgen is already being used for this purpose, but these images have a serious drawback; they lack contrast.

“By making high speed 3D images of living fish with good spatial resolution and high contrast, all kinds of physiological developments inside the animal can be studied. Like the growth of tumours for instance”, said Kalkman, who in 2013 received a 800,000 euro grant from the Dutch research financing institute NWO, and is now about to do the first calibration tests with his special microscope.

The technique is based on interferometry and involves a lot of data processing. Before light hits the fish, it is split into a reference and a sample arm.  The sample beam shines light through the fish. After recombination with the reference beam via a serie of mirrors, the difference in path length between the two light paths is used to compute a clear image.

Kalkman collaborates with researchers from the university of Leiden and the Hubrecht Laboratory in Utrecht, (specialized in developmental biology) who have been working a lot with Zebrafish.  Once the technique is finished they will apply the microscope in their research. The idea is to sedate the animal stick it in a narrow tube with oxygenated water flowing through and 3D scan the animal by rotating it in the infrared light beam. In this way the animal stays alive and the same animal can be imaged throughout its entire lifespan.