Researchers at the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering have presented a new approach to wavefront shaping in the journal Nature Communications. The approach, which has extensive and significant applications, especially in non-invasive biological imaging of deep tissue, is demonstrated in the article on neurons (nerve cells).

Wavefront shaping is a promising approach to deep tissue imaging. Until now, it was possible only via an invasive approach: fluorescent points were manually inserted into the sample, and the tissue was indirectly mapped by imaging them. That process has many disadvantages, and it was clear that direct imaging of the tissue is a better way. However, direct imaging involves various difficulties, including the fact that the radiation emitted from tissues is weak, making its measurement prone to noise, especially when it comes to deep tissue imaging.

The new technology presented by the Technion researchers overcomes these limitations and offers the possibility of direct tissue imaging by illuminating a neuron marked with the fluorescent protein EGFP, which emits light in a different color in response to illumination. This technology is based on dual correction of wavefronts – correction of the wavefront sent to the tissue and correction of the wavefront returning from it. With the help of mathematical calculations that balance the signal-to-noise ratio, the researchers achieved high resolution imaging of the neurons deep inside the tissue.

Doctoral student Dror Aizik, who conducted the research under the guidance of Prof. Anat Levin, explained that “previous demonstrations of wavefront shaping corrected relatively slight distortions and were effective only for very limited tissue depths. Our research demonstrated the technology for the first time in performing deep tissue imaging and correcting very large distortions, which without our correction would have resulted in ‘noise images’ with no visual information.”

The new technology provided high-quality images of the neurons and their axons, even when the neurons were covered by a thick tissue layer. According to the researchers, the technology demonstrated on neurons is also relevant to many other types of tissue.
The research is supported by the European Research Commission (ERC), the US-Israel Binational Science Foundation (BSF), and the Israel Science Foundation (ISF).

Prof. Anat Levin joined the Technion in 2016, after completing her doctorate at the Hebrew University, post-doctorate at the Massachusetts Institute of Technology, and seven years at the Weizmann Institute of Science. She specializes in optics, image processing, and computer vision and has won numerous awards including the Michael Bruno Award, the Blavatnik Award, and the Krill Prize, as well as 3 ERC grants.

For the article in Nature Communications click here.

For photos click here.

In the pictures:
1. Prof. Anat Levin
2. Doctoral student Dror Aizik
3. In the image table: images of neurons that were captured by the system. On the left: a regular image of a neuron deep within the tissue. In the middle: the dramatic improvement provided by the new technology. On the right: a real image of the neuron taken without scattering tissue.
4. In the large diagram: a schematic of the new technology. At the top left: the incoming wave (in blue) arrives from the left and undergoes wavefront correction in the Illumination SLM. It then enters the tissue, hits the neuron, and from there the returning wave (in green) undergoes wavefront correction in the Imaging SLM. At the bottom left, you can see the image obtained before correction (on the right) and after correction (on the left). On the right side, you can see at the top the incoming (blue) and outgoing (green) light before correction (in the top two images) and after correction (in the bottom images).

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