X-ray-excited nanoparticle imaging - a new hybrid modality for deep, in-vivo imaging in preclinical research

Modern medicine relies heavily on the ability of scientists to study the ways in which living tissue and organisms respond to pathogens or other agents that cause damage, and to assess the effectiveness of potential treatments. Imaging is a major tool in biomedical research, revealing the structure and function of tissue in healthy and diseased states.

While microscopy can provide impressive, detailed images at subcellular levels, in most cases it is restricted to studying relatively isolated cells or extracted tissue samples which do not fully represent the state of cells in living, whole-body environments. That instead is the domain of biomedical imaging, where images are acquired that can reveal the state of biomedical processes in a complete living subject. Biomedical imaging techniques exploit a wide range of capabilities, from X-ray and gamma-ray cameras, to infrared detectors and radio-frequency signals. Each such modality has its advantages and shortcomings. For example, visible and near-infrared light can provide very detailed images, but do not penetrate deeply into tissues, whereas X-rays can pass through almost unattenuated.

Xstrahl Ltd is a British medical technology company that designs clinical and research systems to help eradicate cancer. Its systems are in operation at more than 700 treatment and research facilities worldwide, utilising X-ray techniques to study and treat cancer. One of its most valued research instruments is the SARRP - its Small Animal Radiation Research Platform - which is used in the development of methods for diagnosing and treating cancer. The SARRP delivers targeted radiation in pre-clinical studies of research animals which model human disease, such as tumour-bearing mice.

In this project, we aim to implement a new, hybrid biomedical imaging approach that utilises the best characteristics of X-rays, which undergo little scattering in their passage through living material, and engineered nanomaterials that convert X-rays into near-infrared light that can be manipulated and detected outside the body. We have so far determined that a range of nanoparticles respond favourably to X-ray irradiation, and that they can be excited and detected in the internal organs of mice, which are commonly used to model human disease, so our next step is to integrate this imaging capability with the Xstrahl SARRP instrument. The SARRP is ideally suited to this imaging modality because it already provides complete support for X-ray planning, delivery and monitoring, and for animal welfare during imaging procedures, while having the flexibility needed by the developmental nature of this translational research. Our ultimate goal is to elevate this technique from being a bespoke, emerging technology, to one that is readily available to thousands of biomedical researchers through the Xstrahl SARRP.

Medical research relies on imaging to study the ways in which tissue responds to pathogens and other agents that cause damage, and the effectiveness of potential treatments in live, whole-body environments. The near-infrared (NIR) transmission window from 700-900 nm allows NIR light to escape from mammalian tissue with relatively low absorption, albeit highly scattered. X-rays, on the other hand, experience much less absorption or scattering. We are developing a hybrid imaging modality for preclinical research that exploits the ability of X-rays to traverse mammalian tissue relatively undeviated, and therein to excite NIR emission that can be detected outside the body. This enables us to trace the distribution of NIR emitters in deeper-lying organs and other physiological structures, and to probe physiological function through the sequestering of the NIR emitters in localised regions of the body. To date we have demonstrated this capability using NIR emitting quantum dots, nanometre-sized particles in aqueous suspension, which we have excited at depth in whole mouse using clinical X-ray sources.

Our aim is to develop this hybrid imaging technique further using Xstrahl's Small Animal Radiation Research Platform - SARRP - which is in operation at more than 700 treatment and research facilities worldwide, and delivers targeted radiation in pre-clinical studies of animals bearing human disease models, such as tumour-bearing mice. The SARRP is ideally suited to this hybrid imaging modality because it already provides complete support for X-ray planning, delivery and monitoring, with integrated CT and bioluminescent imaging capabilities, alongside animal welfare infrastructure. It also provides the flexibility needed by the developmental nature of this translational research. Our ultimate goal is to elevate this technique from being a bespoke, emerging technology, to one that is readily available to thousands of biomedical researchers through the Xstrahl SARRP.