Deep Optical Imaging of Tissue (DOIT)

Optical tissue imaging can provide biomolecular contrast that is not readily reachable with other imaging modalities. The investigators focus on developing a technique for instantaneous measurements of blood oxygenation which have significant influence in many areas like tumour detection, myocardial infarction, or stroke. However, the technique can in addition to tissue oxygenation also in general measure the optical absorption and scattering properties of tissue, and this is what the investigators will develop and further capitalize on in this project.

In general, the spatial resolution of tissue diagnostics using optical techniques is limited to a few cm due to the strong scattering properties of tissue. Using quantum designed filter structures with large acceptance angle that are many orders of magnitude narrower than any other large acceptance angle filters, this technique can image deeper into tissue with significantly better contrast-to-noise than other optical techniques.

By analyzing the frequency shifted light only, a spatial resolution equal to the ultrasound focus can be obtained. This technique is called Ultrasound Optical Tomography (UOT). A critical factor in UOT is the ability to discriminate between the light frequency-shifted by the ultrasound and the much stronger non-frequency-shifted light.

The absorption of ultrasound in tissue increases with increasing ultrasound frequency, and therefore the ultrasound frequency preferably should be just a few MHz. The small frequency shift is why previous attempts to develop UOT techniques have had limited success: conventional filtering techniques are either not narrow enough to suppress only the carrier or has a very small acceptance angle - a serious drawback as light exiting tissue propagates in all directions.

The Quantum Information Group at the Division of Atomic Physics, Department of Physics at Lund University, has world leading experience in creating narrowband (1 MHz) filters with high (~50 dB) suppression as well as a large acceptance angle. These so-called Slow Light Filters are created in inorganic crystals doped by rare-earth ions, where laser light is used to semi-permanently transfer ions to non-absorbing states. The filters are created by "burning" a spectral hole in the absorption profile of the crystal at the frequency fS so that it transmits this frequency but absorbs the unwanted background light at the frequency fL. An added and important effect of these filters is that light propagating at the transmitted frequency, fS, will be slowed down by several orders of magnitude. In this way, any remaining background from the carrier frequency after the filter can be suppressed using time gating.

In terms of combined suppression of non-frequency shifted light and acceptance angle for the frequency shifted light, slow-light filters outperform currently existing filters by several orders of magnitude, in turn enabling orders of magnitude better contrast for tissue imaging.

In summary, UOT is an emerging technology which is predicted to reach much deeper than previous optical imaging techniques and to have an order of magnitude better signal-to noise or contras-to-noise already at 1 cm depth and 2 orders of magnitude stronger signal at 2 cm depth. It is unique in the sense of being an optical imaging technique expected to be able to utilize light transmitted through 10 cm of tissue, a feature not present in any other optical imaging technique. In this first proof-of-concept project the investigators will primarily assess the imaging depth and imaging quality in muscle and breast tissue to be able to adapt the system to better performance before moving to early clinical trials. Muscle tissue oxygenation is well studied using optical techniques and is therefore suitable for validation of UOT measurements. Breast is expected to be an excellent first clinical performance test model since the organ has a rather superficial and accessible anatomical position and offer many conventional techniques for cross-referencing. If UOT is successful in breast, it may be further developed for applications in other parts of the body and organs.

Inclusion criteria

• Healthy individuals without systemic or skin-related conditions.
• Ability to provide informed consent.

Exclusion criteria

• Pregnancy: Although the risk that laser illumination on the skin may affect the fetus is minimal, we will exclude pregnant research subjects for safety.
• Skin diseases: Certain skin conditions can increase the risk of damage or complications when exposed to laser light, such as active rosacea, eczema, skin infections, or tattoos.
• Medication: Some medications can increase the sensitivity of the skin to laser light or increase the risk of side effects. It is important to consider the person's medical history and any ongoing treatments.
• Sunburn: Recent sun exposure of the skin may lead to increased sensitivity to laser light and can be more likely to experience discomfort or skin irritation/damage. This can both affect the reliability of the study and increase the risk of injury to the research subjects.
• History of keloid formation or scarring: People who have a history of excessive scarring may be more likely to react with greater skin irritation from the laser light.
• For breast measurements only: History of breast cancer or surgery. In this project, we aim to map the UOT signal only in healthy breast tissue.