While spatial dose conformity delivered to a target volume has been pushed to its practical limits with advanced treatment planning and delivery, investigations in novel temporal dose delivery are unfolding new mechanisms. Recent advances in ultra-high dose radiotherapy, abbreviated as FLASH, indicate the potential for reduction in healthy tissue damage while preserving tumor control. FLASH therapy relies on very high dose rate of > 40Gy/s with sub-second temporal beam modulation, taking a seemingly opposite direction from the conventional paradigm of fractionated therapy. FLASH brings unique challenges to dosimetry, beam control, and verification, as well as complexity of radiobiological effective dose through altered tissue response. In this review, we compare the dosimetric methods capable of operating under high dose rate environments. Due to excellent dose-rate independence, superior spatial (∼ <1 mm) and temporal (∼ns) resolution achievable with Cherenkov and scintillation-based detectors, we show that luminescent detectors have a key role to play in the development of FLASH, as the field rapidly progresses toward clinical adaptation. Additionally, we show that the unique ability of certain luminescence-based methods to provide tumor oxygenation maps in real-time with submillimeter resolution can elucidate the radiobiological mechanisms behind the FLASH effect. In particular, such techniques will be crucial for understanding the role of oxygen in mediating the FLASH effect.
The physics and chemistry of liquid solutions play a central role in science, and our understanding of life on Earth. Unfortunately, key tools for interrogating aqueous systems, such as infrared and soft X-ray spectroscopy, cannot readily be applied because of strong absorption in water. Here we use gas-dynamic forces to generate free-flowing, sub-micron, liquid sheets which are two orders of magnitude thinner than anything previously reported. Optical, infrared, and X-ray spectroscopies are used to characterize the sheets, which are found to be tunable in thickness from over 1 μm down to less than 20 nm, which corresponds to fewer than 100 water molecules thick. At this thickness, aqueous sheets can readily transmit photons across the spectrum, leading to potentially transformative applications in infrared, X-ray, electron spectroscopies and beyond. The ultrathin sheets are stable for days in vacuum, and we demonstrate their use at free-electron laser and synchrotron light sources.
Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO 2) between the capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a noninvasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO 2 responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO 2 distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.
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