Physics Contribution
Prompt Gamma Imaging for In Vivo Range Verification of Pencil Beam Scanning Proton Therapy

https://doi.org/10.1016/j.ijrobp.2017.04.027Get rights and content

Purpose

To report the first clinical results and value assessment of prompt gamma imaging for in vivo proton range verification in pencil beam scanning mode.

Methods and Materials

A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan.

Results

In 6 treatment fractions recorded over 3 weeks, the mean (± standard deviation) range shifts aggregated over all spots in 9 energy layers were −0.8 ± 1.3 mm for the lateral field, 1.7 ± 0.7 mm for the right-superior-oblique field, and −0.4 ± 0.9 mm for the vertex field.

Conclusions

This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for in vivo proton range verification and quantification of range uncertainties.

Introduction

Although proton therapy may offer superior dosimetric properties compared with photon therapy, it is necessary to account for range uncertainties (1) to avoid any risk of over- or under-ranging with respect to the tumor volume and organs at risk. Contributions to range errors originate not only from uncertainties in treatment preparation (eg, conversion of planning CT Hounsfield units into proton stopping power ratios relative to water, dose calculation approximations) but also from differences between preparation and delivery (eg, patient misalignment, organ motion, anatomic changes). Consequently, a distal margin recipe is included in treatment protocols (eg, 3.5% of range + 1 mm at our institution), which necessitates additional dose imparted to healthy tissue.

To validate proton range and potentially reduce margins in patients, several imaging methods have been investigated for in vivo verification of beam penetration depth (2), 2 of which have subsequently been demonstrated clinically. The use of Positron Emission Tomography (PET) to image nuclear activated β+ emitters during and/or just after treatment delivery for various tumor locations has been described by several groups 3, 4, 5. Two groups have used MRI to image changes in the spine after completion of craniospinal irradiations 6, 7. In the present article we report on a third approach, prompt gamma imaging (PGI), now mature enough for initial characterization in patients.

Prompt gamma imaging was first proposed by Jongen and Stichelbaut in 2003 (8) and experimentally demonstrated 3 years later by Min et al in 2006 (9). More recently, the first PGI patient study was performed in double scattering mode at the Universitäts Protonen Therapie Dresden at OncoRay (10). Recent studies have shown that spectroscopic analysis can be performed simultaneously with range verification using a collimated prompt gamma detector system (11). The characteristic prompt gamma spectral lines from individual elements were used to determine the oxygen and carbon concentrations for the target with unknown composition. A prototype Compton camera has been investigated and used to demonstrate the feasibility to measure the prompt gamma rays. The Compton camera has the advantage of reconstructing 2-dimensional images of the prompt gamma emission, although further improvements are needed for clinical usage (12). In contrast, the present study reports on the first patient application of the PGI technique in pencil beam scanning (PBS) mode, for which the emission profiles are used for range verification on a spot by spot basis.

The PGI method utilizes a dedicated gamma camera to produce an image of the proton tracks by measuring a 1-dimensional (1D) profile of multi-MeV prompt gamma rays transmitted through the patient after emission by excited nuclei along the proton beam path. Because of the limited field of view (FOV) of the camera, only the distal region of the gamma profile was recorded for each proton beam. The detected gamma signal would be too low for use in a low-dose pretreatment range probe strategy, such as the in vivo diode dosimetry approach for tumor volumes abutting a natural cavity (13). However, sufficient signal has been demonstrated for range verification of the high-weighted spots of a typical 2-Gy PBS treatment fraction (14). In this context, the prompt nature of the gamma emission (i.e., less than 1 nanosecond after excitation) means that each gamma photon in the signal can be associated with a particular pencil beam spot so that the beam range can be verified for each individual spot. Compared with PET imaging, PGI offers favorable time-resolved acquisition from multiple spots, layers, and fields without complex signal overlap from sequential fields, signal decay, or wash-out effects from well-perfused soft tissues.

Section snippets

Methods and Materials

The camera evaluated in this study relies on 504 cm3 of lutetium-yttrium oxyorthosilicate scintillating crystals distributed over 2 rows of 20 slabs (15) vertically aligned one on top of the other. Each slab is 31.5 mm thick, 100 mm high, 4 mm in width along the beam axis, and together with its mirror slab in the other row, constitutes one of the 20 bins of the 1D detection profile. A reversed projection of the prompt gamma depth emission profile is produced on the crystals through a 6-mm-wide

Results

For all spots of layers 2 to 9 of the 3 fields, the median precision in shift estimation after spot aggregation with a kernel of 7 mm sigma was 2.1 mm, and the median interfraction variation was 1.8 mm, as shown in Figure 2. Without spot aggregation, the precision in shift retrieval was better than 2 mm for only 1% of the analyzed spots (59 of 5801). The interfraction variability in shift retrieval was smaller than 2 mm for 4% of the spots. Aggregating the spots with a kernel of 4 mm and 7 mm

Discussion

In this study the absolute amplitude of the average shift is 1 to 2 mm, which is smaller than the fixed distal margin of 5 mm applied clinically. From Figure 5 (d-j), the average shift variation of 1.9 mm at 2 sigma over 6 days for the 3 fields is essentially attributable to the uncertainty on the camera positioning, given that the variation is larger between fractions than between layers within a given acquisition. The retrieved shift is sensitive to the camera positioning, which is performed

Conclusions

The first clinical application of PGI for in vivo proton range verification in PBS mode on a spot by spot, layer by layer, field by field basis has been demonstrated. The precision of the shift retrieval depends on the number of protons in each spot, but with spot aggregation, shift retrieval precision of 2 mm can be achieved. The current system is limited by the accuracy of the camera positioning, but the results motivate extension of this study toward other tumor locations and continued

Acknowledgment

The authors would like to thank the UPENN and IBA colleagues at the Roberts Proton Therapy Center for their support and to gratefully acknowledge Michele Manotti and Luca Bombelli from XGLab for the camera hardware, Benjamin Thiebaut, Philippe Raynaud and Olivier Petit from RSI Concept for the camera firmware, as well as Alexandre Van Braeken and Marc André from WOW Technology for the camera trolley.

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Conflict of interest: J. Smeets and D. Prieels have a patent on apparatus for particle therapy verification issued. D. Prieels has a patent Method and apparatus for particle beam range verification issued. Dr. Lin reports personal fees from Ion Beam Applications (IBA), outside the submitted work.

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