PIBS: Proton and ion beam spectroscopy for in vivo measurements of oxygen, carbon, and calcium concentrations in the human body

Abstract

Proton and ion beam therapy has proven to benefit tumour control with lower side-effects, mostly in paediatrics. Here we demonstrate a feasible technique for proton and ion beam spectroscopy (PIBS) capable of determining the elemental compositions of the irradiated tissues during particle therapy. This follows the developments in prompt gamma imaging for online range verification and the inheritance from prompt gamma neutron activation analysis. Samples of water solutions were prepared to emulate varying oxygen and carbon concentrations. the irradiation of those samples and other tissue surrogate inserts by protons and ion beams under clinical conditions clearly showed a logarithmic relationship between the target elemental composition and the prompt gamma production. This finding is in line with the known logarithmic dependence of the pH with the proton molar concentration. Elemental concentration changes of 1% for calcium and 2% for oxygen in adipose, brain, breast, liver, muscle and bone-related tissue surrogates were clearly identified. Real-time in vivo measurements of oxygen, carbon and calcium concentrations will be evaluated in a pre-clinical and clinical environment. This technique should have an important impact in the assessment of tumour hypoxia over the course of several treatment fractions and the tracking of calcifications in brain metastases. The analysis of the elemental compositions of the human body by means of irradiated particles was first described by Anderson et al. in 1964 1,2. That technique was coined as in vivo neutron activation analysis 1. That breakthrough gave rise to the measurements of total body hydrogen 3,4 , carbon 5 , nitrogen 6 , calcium and sodium 7,8 , and localized measurements of chlorine 9 and cadmium 6,10. The activated elements were identified because of their decay at different rates or because they emitted gamma-rays of different energy 1. The latter was further developed and nominated as prompt gamma in vivo neutron analysis (PGIVNA or IVNAA). The evaluation of total body protein by IVNAA 11 had a major impact in intensive care patients 12 , thus saving several billions of dollars annually round the World 13. A comprehensive review of in vivo experimental methods to determine the composition of the human body has been carried out by Sutcliffe 14 and Ellis & Eastman 15. The IVNAA relied either on high energy resolution germanium detectors (HPGe) for tracking calcium, cadmium and chlorine or by thick sodium iodide NaI(Tl) detectors for determining total body hydrogen and nitrogen. This technique was developed close to nuclear reactors, particle accelerators or radioisotope neutron sources. Many facilities, such as the ones at Birmingham 16 and Brookhaven 4,17 , were fully designed with the purpose of studying the prompt activation for the spectroscopy of neutron activated elements. More recently, new techniques have emerged for the detection of heavier elements in human organs 18-20. However, neutron therapy, although popular in the 70 s and 80 s, still offers low mar...

GEANT4 simulation of a range verification method using delayed γ spectroscopy of a 92Mo marker

“…Prompt γ (PG) RV makes use of the multitude of prompt characteristic γ rays which are emitted from nuclear interactions between the proton beam and tissue along the beam path (Martins et al 2020). Due to the short time scale in which they are emitted, the acquisition time for this method is much shorter than that of PET, so the PG method has the potential to provide immediate feedback on treatment quality.…”

Towards real-time PGS range monitoring in proton therapy of prostate cancer

“…Prompt gamma spectroscopy (PGS) is currently one of the most promising techniques for particle range monitoring and measurements of the elemental composition of irradiated targets in particle therapy 6 , 13 , 55 , 61 . This technique facilitates absolute range measurements with millimetre precision due to accurate knowledge of the nuclear reaction cross-sections between the irradiated particles and the types of atoms in the patient.…”

A triple-imaging-modality system for simultaneous measurements of prompt gamma photons, prompt x-rays, and induced positrons during proton beam irradiation

“…Several methods have been extensively studied in attempts to measure the range of a particle ion beam from outside the subject. In these trials, one of the major approaches is the imaging of prompt gamma photons (Smeets et al 2012, Perali et al 2014, Richter et al 2016, Taya et al 2017, Koide et al 2018, Krimmer et al 2018, Martins et al 2020 for the SiFi-CC group 2020, Zhang et al 2020, Pennazio et al 2022, Wang et al 2022, Cheon et al 2023. Imaging the prompt secondary electron bremsstrahlung x-rays (hereinafter, simply prompt x-rays) (Yamaguchi et al 2012, Ando et al 2017, Yamamoto et al 2020, Yamaguchi et al 2020a during particle ions irradiation to a subject is also a possible approach.…”