Biomedical imaging techniques are often limited by the loss of resolution with depth due to light scattering in biological tissue. Beyond a few millimeters in depth, diffuse transport dominates and makes high resolution imaging impossible using conventional techniques. In this work, light sheet imaging using x-ray photons was developed with a keV x-ray source. This partially overcomes this scattering by generating light within tissue at depth. The light excites fluorescent probes that can be used for tumor tracking based upon molecular targeting. Most of the fluorescent probes have a lifetime in the nanosecond range. In this study, the use of a portable linear accelerator delivering 30-ns x-ray pulses was explored. Using x-ray excitable fluorophores, light was generated within a tissue phantom. Image stacks were acquired using an intensified camera (PiMAX4 – Princeton Instrument – USA) placed perpendicularly to the slicing direction of the sample. A solid-state silicon photomultiplier was used to gate acquisition. Although this delayed acquisition slightly, it improved the fluorescence signal-to-noise ratio (SNR). A deconvolution algorithm counteracted the blurring effects of tissue, and image stacks were converted to 3D reconstructions. In summary, nanosecond x-ray pulses can be used to excite fluorophores through radioluminescence phenomenon. Combined with slice imaging, this approach shows promise for time-resolved x-ray luminescence.
During radiotherapy, X-ray beams induce Cherenkov light emission in tissue as part of the dose delivery. This light can be used for dosimetry, in order to track and image the dose as it happens. The Cherenkov light levels are in the range of 10−6 to 10−9 W∕cm2, which makes it challenging to detect in a clinical environment. However, because the radiation is pulsed in 4 microsecond bursts, time-gated acquisition of the signal allows for robust detection, even in the presence of ambient room lighting. Thus, imaging sensors for this application must be highly sensitive and must be able to time gate faster than a microsecond.
In this study, the use of a solid-state detector composed of 64×32 single photon avalanche diodes (SPADs) was examined. The advantages of this technology were intra-chip amplification, high dynamic range, superior X-ray noise rejection and fast temporal gating of the acquisition. The results show that the SPAD camera was sensitive enough to detect Cherenkov radiation despite the 3% fill factor. 2D oversampling (×25) was also used to increase final image resolution to 320×160. In this work we demonstrate the SPAD camera performance in imaging Cherenkov emission from a tissue optical phantom and one patient undergoing radiotherapy. The results show that the SPAD camera was sensitive enough to detect Cherenkov radiation emitted from patient’s surface with signal-to-noise ratio of 14 after 6s acquisition.
The SPAD camera sensors could be a viable alternative for Cherenkov imaging, as compared to current imaging methods that are mostly focused around image intensifier-based cameras and so have a range of non-linearities and instabilities which could be solved by an all solid-state camera sensor.