In vivo range verification in particle therapy

Abstract

Exploitation of the full potential offered by ion beams in clinical practice is still hampered by several sources of treatment uncertainties, particularly related to the limitations of our ability to locate the position of the Bragg peak in the tumor. To this end, several efforts are ongoing to improve the characterization of patient position, anatomy, and tissue stopping power properties prior to treatment as well as to enable in vivo verification of the actual dose delivery, or at least beam range, during or shortly after treatment. This contribution critically reviews methods under development or clinical testing for verification of ion therapy, based on pretreatment range and tissue probing as well as the detection of secondary emissions or physiological changes during and after treatment, trying to disentangle approaches of general applicability from those more specific to certain anatomical locations. Moreover, it discusses future directions, which could benefit from an integration of multiple modalities or address novel exploitation of the measurable signals for biologically adapted therapy.

Keywords: in vivo range verification; ion transmission imaging; particle therapy.

Figure 1

Example of instrumentation for proton/ion radiography and tomography, featuring (a) silicon‐based trackers followed by a multi‐stage calorimeter for single proton imaging of a passively scattered monoenergetic broad beam, (b) a range telescope made by large area plane‐parallel ionization chambers interleaved with plastic degraders for imaging of scanned carbon ion beams and (c) a matrix of diodes combined with a passively energy modulated broad proton beam. Adapted with permission.

Figure 2

Reconstructed proton computed tomography images from experimental (a) and simulated (b) projections acquired for a pediatric head phantom with the prototype scanner shown in Fig. 1(a). The selected slice is approximately taken at the same anatomical position. Figure from Giacometti et al., with permission.

Figure 3

Example of PET instrumentation already used for clinical studies, featuring (a) an onboard planar system integrated in a proton gantry for imaging immediately after end of treatment, (b) a neurological PET scanner on‐wheel for in‐room imaging few minutes after end of treatment,, and (c) a commercial PET/CT scanner for offline imaging several minutes after end of treatment, with permission.

Figure 4

Example of PET monitoring of passively scattered proton therapy with fraction doses of 1.8–2.5 GyE (RBE 1.1) and imaging starting 140 s (top) and immediately after (bottom) irradiation for a scan time of 1200 s and 200 s, respectively (with permission). Top panel: comparison between simulated (a) and measured (b) activity using the in‐room PET scanner shown in Fig. 3(b). Bottom panel: comparison between the planned dose distribution for the considered second port (left) and the activity measured with the on‐board planar detector of Fig. 3(a) at two different treatment fractions, corresponding to the total delivery of a biologically weighted dose of 5 GyE (middle) and 35 GyE (right). The arrow marks regions of disagreement, indicating a later radiologically confirmed anatomical change.

Figure 5

(a) The clinical slit camera used for patient range verification (adapted from Richter et al.85) as well as (b) a schematic drawing of the slit‐collimator imaging concept in which the originating position of the PG is derived from the vector connecting its point of detection in the camera and the opening of the collimator (adapted from Perali et al.80), with permission.

Figure 6

Range shift maps for individual beam spots for a single treatment field delivered for six different fractions measured with a clinical slit camera. Each map shows the deviation of the measured range from the planned range for each spot in each energy layer of the treatment field (from Xie et al. with permission).

Figure 7

Schematic drawing of (a) an energy‐time resolved prompt gamma spectroscopy system containing a collimated scintillator enclosed within a Compton scattered suppression shield (adapted from Verburg et al. with permission). (b) A schematic of the prompt gamma timing concept in which the beam range is derived from the measurement of the time elapsed between the start a proton beam pulse and the arrival of a prompt gamma ray at the scintillation detector (adapted from Hueso‐Gonzalez et al. in accordance with CC BY license agreement).

Figure 8

Schematic drawing of (a) a clinical Compton camera‐based range verification system with the CC mounted on a rail system attached to the patient treatment couch for setup and positioning. (b) Schematic of a CC showing multiple PG scatters used to create the “cone‐of‐origin” (adapted from Mackin et al. with permission).

Figure 9

Illustration of spectroscopic PG imaging in proton or heavy ion therapy. The image is reconstructed from PGs emitted during the delivery of a daily treatment fraction. The PG spectra formed within a specific region of interest (ROI) can then be constructed. Comparison of changes in the relative intensity of PG emission lines from specific elements (6.12 MeV emission from¹⁶O highlighted) in the ROI spectra over the course of treatment could potentially be used to infer how the concentration of different elements are changing in response to the treatment (adapted from Polf et al. with permission).