Online program Overview Session: MIC-17

Abstract

Carbon-ion radiotherapy enables highly precise tumor treatment, particularly for locations near critical structures such as the brainstem or spinal cord. However, the focused dose distributions that make this modality effective also increase its sensitivity to variations in the beam path. Consequently, accurate monitoring and control of the dose distribution in the patient are essential. Despite this clinical need, radiation-free monitoring approaches are scarce.

In order to investigate use of secondary ions for this purpose, we compare measured ion distributions across treatment fractions. For this approach, a contactless detection system for secondary-ion tracking was developed and clinically implemented at the Heidelberg Ion-Beam Therapy Facility (HIT), Germany. The system enables tracking of individual secondary-ions with high spatial and temporal resolution.

The performance of the developed monitoring approach is currently being assessed within the clinical study “InViMo.” To date, more than 100 patient measurements have been acquired. For the majority of patients, the measured data showed consistency across treatment fractions. However, pronounced inter-fractional variations were observed in several cases. These signals demonstrated clear spatial correlation with the anatomical ground truth derived from CT imaging, including challenging cases involving deep-seated tumors. In addition, the system enabled a worldwide first measurement of a patient treated with helium ions, a promising modality for several pediatric tumor indications. Considerable amount of secondary ion tracks was recorded.

Our results demonstrate that the proposed method can detect clinically relevant anatomical changes in treated patients with high sensitivity and accurate spatial localization.

Abstract

Objective: Online range monitoring is critically important in proton therapy, as range uncertainties arising from patient positioning, anatomical variations, and range calculation algorithms remain a major limitation in precise dose delivery. Prompt gamma-ray imaging (PGI) offers a promising solution for real‑time range verification due to the ultra‑fast emission of prompt gamma rays. However, for the most advanced dose delivery technique—pencil beam scanning—proton beams are delivered in a three‑dimensional (3D) lattice, necessitating 3D online monitoring systems capable of spot‑by‑spot range and dose verification within a single acquisition.
Approach: In this study, a dual‑head 3D PGI system based on multi‑slit collimated gamma‑ray cameras was evaluated for proton beams delivered to 3D lattices. Experiments were conducted in a clinical proton therapy treatment room using a proton beam of typical therapeutic energy incident on a polymethyl methacrylate (PMMA) phantom. The precision and accuracy of both range verification and beam spot positioning were systematically assessed.
Main results: At a typical low proton count level of 1 × 10⁸ protons per scanning spot, the system achieved accuracy and precision better than 1.5 mm for both range verification and beam spot positioning. At proton counts of 3 × 10⁸ or higher, both metrics improved to sub‑millimeter levels (<1 mm).
Significance: These findings demonstrate that the dual‑head 3D PGI system is capable of high‑precision, spot‑by‑spot range and beam spot verification even at low proton counts, highlighting its potential for effective online in vivo monitoring in 3D pencil beam scanning proton therapy.

Abstract

Hadrontherapy is a kind of radiation therapy that delivers highly localized radiation doses to treat tumors spearing healthy tissues. In this context, Prompt Gamma Imaging (PGI) is a promising technique towards real-time monitoring of the particle beam range, thereby enhancing both treatment precision and patient safety. The REALPATH project aims to develop a compact range verification system based on passive collimation and a pixelated gamma camera. The detector utilizes LYSO scintillator crystals coupled to silicon photomultipliers (SiPMs), organized into 64- channel base units that scale up to a 512-channel instrument with a 20 × 10 cm² footprint. The primary objective of this project is to overcome the physical and operational barriers that currently prevent PGI systems from being used during standard treatment workflows. For this reason, the detector and electronics are engineered to maximize detection efficiency, minime acquisition dead time, while reducing the footprint of the system. A novel ”inverted” collimator design significantly reduces the overall instrument weight and allows the camera to be rigidly fixed beneath the patient couch. The experimental results obtained from measurement campaigns at CNAO facility in Pavia, Italy are also reported.

Abstract

Proton therapy provides highly conformal dose delivery and the integration of in-vivo range verification can further enhance treatment safety and efficacy by serving as a trigger for intervention and by decreasing safety margins [1]. The NOVO collaboration [2] investigates a novel hybrid detector concept that combines prompt gamma ray and fast neutron imaging in a compact organic-scintillator-based system to improve proton range verification. This dual-particle approach offers complementary particle information and thus improved localisation capabilities [3]. For the first time, the NOVO detector was operated at a clinical proton beam at the OncoRay proton therapy facility in Dresden, Germany [4]. The system’s detection performance and imaging capability were investigated by irradiating different phantoms with numerous proton energies and beam currents and by varying the phantoms’ position and compositions. The detector array demonstrated stable performance under clinically relevant mixed-field and high-rate conditions and achieved reliable neutron–photon discrimination. Furthermore, images could be reconstructed which provide the first experimental validation of the combined n/gamma approach in proton therapy and highlight its strong potential as a future real-time range verification technique.

Abstract

Biological washout, traditionally considered a source of error in range‑verification PET in particle therapy, is now emerging as a potential new biomarker for tumor diagnosis. At QST, proof‑of‑concept studies using animal irradiation at HIMAC demonstrated a correlation between hypoxia PET maps and washout rate maps derived from range‑verification PET. However, due to facility limitations, including radioisotope regulation constraints, hypoxia PET had to be performed on the day following irradiation. As a result, confounding factors such as tumor growth and delayed irradiation effects could not be fully excluded. In contrast, LMU has developed the Small Animal Proton Irradiator for Research in Molecular Image‑Guided Radiation Oncology (SIRMIO) that includes an in-beam PET scanner, and conducted experiments at DCPT, which offers close integration with a nuclear medicine division. Leveraging this environment, we designed an experimental protocol to perform both proton range‑verification PET (irradiation-PET) and hypoxia PET (FAZA-PET) on the same platform with a shortened interval using the SIRMIO system at DCPT. Considering that the activity level in range‑verification PET is much lower than that in FAZA-PET, ¹⁸F‑FAZA administration was performed after the irradiation-PET. The time interval between the two PET scans was reduced to < 4 hours, which is sufficient for FAZA uptake while minimizing biological changes in the tumor. The first proof‑of‑concept experiment was conducted using mouse models bearing SCCVII tumors. Mouse was positioned in a custom-made holder, and co-registration was ensured by on-board μCBCT. A low washout rate in hypoxic areas was observed, which may be explained by poor blood perfusion. Correlation to in-beam PET data will be analyzed and reported.

Abstract

In carbon ion therapy, positron emission tomography (PET) is one of the most investigated methods for range verification that relies on short half-life β⁺ emitters such as ¹¹C and ¹⁵O. Consequently, in-beam PET or off-beam PET performed immediately after irradiation have been considered mandatory, and little attention has been paid to the existence of longer-lived β⁺ emitters than ¹¹C. With a recent increase in PET system sensitivity, delayed acquisitions targeting longer-lived β⁺ emitters have become increasingly feasible. In this study, therefore, we focused on the feasibility of off-beam detection of an irradiation-induced ¹⁸F component for range verification in carbon ion therapy. Monte Carlo simulations were first performed to estimate the yield of ¹⁸F and the other most important β⁺ emitters induced in a polymethyl methacrylate (PMMA) phantom irradiated by carbon ion beams. The yield of produced ¹⁸F was one-eighth that of the ¹¹C, and the shifts of the dose peak and PET peak were 1.5 mm and 0.5 mm for in- and off-beam PET, respectively. To validate the simulation results, a PMMA phantom and a live tumor-bearing rat model were irradiated with a ¹²C ion beam of 290 MeV/u at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba (HIMAC) to evaluate ¹⁸F production in both simplified and biologically relevant environments. One hour after irradiation, PET scans were carried out for 30 min for both the phantom and the rat. Time-activity curves (TACs) were extracted from the PET images, and they showed the presence and detectability of ¹⁸F. A measured activity profile was obtained from the off-beam PET image of the phantom and compared with the measured dose. The dose peak and PET peak positions were matched, which is consistent with submillimeter (0.5 mm) shift of the peaks for off-beam PET predicted from  the simulation. Our results demonstrate the feasibility of ¹⁸F for range verification in carbon ion therapy using off-beam PET.