Comparison Between In-Beam and Offline Positron Emission Tomography Imaging of Proton and Carbon Ion Therapeutic Irradiation at Synchrotron- and Cyclotron-Based Facilities

doi:10.1016/j.ijrobp.2008.02.033

International Journal of Radiation OncologyBiologyPhysics

Volume 71, Issue 3, 1 July 2008, Pages 945-956

https://doi.org/10.1016/j.ijrobp.2008.02.033 Get rights and content

Purpose

The benefit of using dedicated in-beam positron emission tomography (PET) detectors in the treatment room instead of commercial tomographs nearby is an open question. This work quantitatively compares the measurable signal for in-beam and offline PET imaging, taking into account realistic acquisition strategies at different ion beam facilities. Both scenarios of pulsed and continuous irradiation from synchrotron and cyclotron accelerators are considered, because of their widespread use in most carbon ion and proton therapy centers.

Methods and Materials

A mathematical framework is introduced to compare the time-dependent amount and spatial distribution of decays from irradiation-induced isotope production. The latter is calculated with Monte Carlo techniques for real proton treatments of head-and-neck and paraspinal tumors. Extrapolation to carbon ion irradiation is based on results of previous phantom experiments. Biologic clearance is modeled taking into account available data from previous animal and clinical studies.

Results

Ratios between the amount of physical decays available for in-beam and offline detection range from 40% to 60% for cyclotron-based facilities, to 65% to 110% (carbon ions) and 94% to 166% (protons) at synchrotron-based facilities, and increase when including biologic clearance. Spatial distributions of decays during irradiation exhibit better correlation with the dose delivery and reduced influence of biologic processes.

Conclusions

In-beam imaging can be advantageous for synchrotron-based facilities, provided that efficient PET systems enabling detection of isotope decays during beam extraction are implemented. For very short (<2 min) irradiation times at cyclotron-based facilities, a few minutes of acquisition time after the end of irradiation are needed for counting statistics, thus affecting patient throughput.

Introduction

Positron emission tomography (PET) has been suggested by several investigators as a valuable tool for in vivo, noninvasive confirmation of the treatment delivery in ion beam therapy 1, 2, 3, 4, 5, 6. The method exploits the β⁺-activity produced in nuclear interactions between the ions and the irradiated tissue. Phantom experiments 7, 8, 9, 10 and clinical trials 11, 12 performed during (in-beam) or shortly after (offline) irradiation with carbon ion and proton beams indicate 1- to 2-mm achievable accuracy for verification of the beam range in rigidly immobilized sites. Use of PET imaging can also enable within-millimeter control of the lateral field position 1, 6, 8, 9, 10 and detection of deviations between planned and applied treatment, e.g., because of minor misalignments or local changes of the patient anatomy or physiology (13). Therefore several institutions are considering the establishment of PET quality assurance at existent or upcoming ion beam therapy facilities worldwide. The optimal implementation is still a topic of debate.

Similar to the first prototype (14), in-beam PET detectors inside the treatment room are the method of choice for acquisition in treatment position—ideally in real-time during irradiation—and for detection of the activity contribution from short-lived emitters such as ¹⁵O (half-life T_1/2=121.8s). This solution is clinically implemented at the Gesellschaft für Schwerioneneforschung (GSI), Darmstadt, Germany, for therapy with stable carbon ion beams 2, 11. A similar experimental installation was developed at the secondary beam course of the Heavy Ion Medical Accelerator in Chiba, Japan, for range verification of implanted radioactive beams (15). A third is under development in Kashiwa, Japan, for verification of proton treatments (9).

As a technical challenge, integration into the treatment environment poses geometric constraints because of the need of an opening for the beam portal (and exit cone of light fragments for heavy ions) and flexible patient positioning, typically resulting in dual-head configurations. Furthermore production of background radiation during beam extraction 2, 3, 16 and sensitivity of PET imaging to the time course of irradiation (especially for dynamic beam application) demand synchronization of the PET data acquisition with the beam control system (11). To date, the former problem restricts usable “in-beam” detection during the pauses of pulsed beam delivery 2, 3, 11 or directly after continuous irradiation 3, 9, although solutions have already been proposed and successfully tested (17).

A technically less demanding alternative is offered by commercial full-ring PET scanners, measuring the activity contribution from long-lived emitters such as ¹¹C (T_1/2=1223s) shortly after treatment (offline). This approach uses resources which are typically located outside the treatment room and can serve other applications besides ion beam quality assurance. The method becomes particularly attractive with devices combining PET and computed tomography (CT) 10, 12. The additional CT enables accurate co-registration between the treatment and imaging position, compensating for unavoidable patient movement caused by transportation and/or repositioning. Moreover it allows detection of morphologic modifications with respect to the planning CT, which is used in in-beam PET imaging for calculation of the attenuation map and co-registration to the patient anatomy.

The imaging performances are mostly conditioned by the geometrical detector arrangement and the severity of limited-angle artifacts (18). The second major factor is counting statistics (18), which, for a given fractionation scheme and detector arrangement, depends on the time course of the beam delivery and PET acquisition. In both in-beam and offline imaging scenarios, prolongation of the measuring time for the sake of statistics is limited. For detectors inside the treatment room, this results from the requirement of efficient patient throughput. For offline imaging at remote sites, major restrictions come from considerations of patient comfort. Finally biologic clearance and/or transport of the produced activity increases with the time after treatment, affecting the spatial distribution and the intensity of the measurable signal.

At the upcoming Heidelberg Ion-Beam Therapy (HIT) Centre in Heidelberg, Germany, we are evaluating the integration of the in-beam PET scanner, which has been developed and operated at the GSI experimental therapy unit by the Forschungszentrum Dresden-Rossendorf (11). In comparison to GSI, the dedicated synchrotron of the new hospital-based facility is designed for more efficient use of its duty cycle in combination with the active beam delivery system. This will result in shorter treatment times with reduced pauses during the pulsed beam delivery, compromising the counting statistics of in-beam PET imaging.

Therefore, this study aims to investigate the advantage of in-beam against offline PET imaging for each individual ion species (¹H, ¹²C) and accelerator system. In addition to the synchrotron-based facilities at GSI and HIT, we include conventional cyclotrons coupled to passive beam shaping systems as widely used in most proton therapy centers. There is, however, no aim to compare, e.g., PET imaging of synchrotron-based carbon ion treatments against protons at cyclotron-based facilities.

Section snippets

Production of β⁺-emitters

Amount and spatial distribution of irradiation-induced β⁺-emitters were obtained from CT-based Monte Carlo (MC) calculations (19) for head-and-neck and paraspinal tumors treated with proton beams at Massachusetts General Hospital (MGH) in Boston, MA (12). This approach provides more accurate isotope identification, at the expense of computing time (19), in comparison to carbon ion modeling as described by Pönisch et al. (20), which adapts β⁺-emitter yield in polymethylmethacrylate (C₅H₈O₂) to

Production of β⁺-emitters

The MC-calculated dose distributions of individual portals are shown in Fig. 2 for clinical cases of skull-base and paraspinal tumors treated with multi-field irradiation at the proton therapy unit at MGH. The selected fields were chosen because they do not necessarily require a beam gantry, which, for example, is not available at GSI. The data were normalized to the delivery of a typical field dose of 1 Gy.

The corresponding spatial distributions of the most abundant positron emitters are

Discussion

Despite the simplified assumption of constant irradiation parameters and the approximate extrapolation to carbon ions, this study can offer a valuable insight on the available signal for in-beam and offline PET imaging at different ion beam facilities. In particular it shows that, for very short (<2 min) irradiation at conventional cyclotron-based facilities, suppression of random coincidences during beam delivery, and a few minutes of acquisition time immediately after irradiation are

Conclusions

We have presented a comparison of the measurable in-beam and offline PET signal for single treatment fields of head-and-neck and paraspinal tumor sites, considering different beam delivery and imaging approaches at cyclotron- and synchrotron-based ion beam facilities. These data can assist other institutions in evaluating the optimal implementation of PET quality assurance in ion therapy. The values must be interpreted taking into account the specific fractionation scheme and the properties of

Acknowledgments

The authors acknowledge Harald Paganetti from Massachusetts General Hospital for providing the phase-space of the proton treatments. The authors also thank Jürgen Debus (Heidelberg University Clinic, Heidelberg, Germany) and Wolfgang Enghardt (Oncoray and Forschungszentrum Rossendorf, Dresden, Germany), for fruitful discussions.

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: Conflict of interest: none.

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Physics ContributionComparison Between In-Beam and Offline Positron Emission Tomography Imaging of Proton and Carbon Ion Therapeutic Irradiation at Synchrotron- and Cyclotron-Based Facilities

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Production of β+-emitters

Production of β+-emitters

Discussion

Conclusions

Acknowledgments

Nucl Instrum Methods A

Int J Radiat Oncol Biol Phys

Radiother Oncol

Nucl Instrum Methods A

Nucl Instrum Methods A

Proton dose monitoring with PET: Quantitative studies in Lucite

Phys Med Biol

In-beam PET imaging for the control of heavy-ion tumor therapy

IEEE Trans Nucl Sci

On-line monitoring of radiotherapy beams: Experimental results with proton beams

Med Phys

Potential application of PET in quality assurance of proton therapy

Phys Med Biol

In-beam PET measurements of β+-radioactivity induced by proton beams

Phys Med Biol

Distributions of β+ decayed nuclei generated in the CH2 and H2O targets by target nuclear fragment reaction using therapeutic MONO and SOBP proton beam

Med Phys

Beiträge zur Einführung der Positronen-Emissions-Tomographie bei der Schwerionen-Tumortherapie

Forschungszentrum Rossendorf Wiss Techn Ber

Experimental study on the feasibility of in-beam PET for accurate monitoring of proton therapy

IEEE Trans Nucl Sci

Physics Contribution
Comparison Between In-Beam and Offline Positron Emission Tomography Imaging of Proton and Carbon Ion Therapeutic Irradiation at Synchrotron- and Cyclotron-Based Facilities

Production of β⁺-emitters

Production of β⁺-emitters

In-beam PET measurements of β⁺-radioactivity induced by proton beams

Distributions of β⁺ decayed nuclei generated in the CH₂ and H₂O targets by target nuclear fragment reaction using therapeutic MONO and SOBP proton beam