Introduction/Background Can Prompt Gamma Emission During Proton Therapy Provide in situ Range Verification? J Styczynski 1/2 , K Riley 3,4 , P Binns 4* , T Bortfeld 2 , H Paganetti 2 1 Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 2 Department of Radiation Oncology, MGH and Harvard Medical School, Boston, MA 3 Radiation Monitoring Devices, Inc. Watertown, MA 4 Nuclear Reactor Laboratory, Massachusetts Institute of Technology, Cambridge, MA * Current address: Department of Radiation Oncology, Mount Auburn Hospital, Cambridge, MA Measurements References:  R. Ramaty, et al. Nuclear gamma-rays from energetic particle interactions. Astrophys. J. Suppl. S. 40 (1979) 487-526.  C. Min, et al ., “Prompt gamma measurement for locating the dose falloff region in the proton therapy,” Applied Physics Letters 89 , 183517 (2006)  Min CH, Kim JW Youn MY and Kim CH (2007). Determination of distal dose edge location by measuring right-angled prompt-gamma rays from a 38 MeV proton beam Nucl. Instrum. Methods A 580 562-565.  B. Kang, et al. , “Monte Carlo Design Study of a Gamma Detector System to Locate Distal Dose Falloff in Proton Therapy,” IEEE Transactions on Nuclear Science, vol 56, no 1, 2009  J. Polf, et al., “Prompt gamma-ray emission from biological tissues during proton irradiation: a preliminary study,” Phys Med Biol 54 731-743 (2009) Contacts: John Styczynski, email: firstname.lastname@example.org, phone: +1 518 229 6586 Kent Riley, email: KRiley@rmdinc.com, phone: +1 617 668 6934 Peter Binns, email: email@example.com Thomas Bortfeld, email: firstname.lastname@example.org, phone: +1 617 724 1180 Harald Paganetti, email: email@example.com, phone: +1 617 726 5847 The use of protons as a source for radiotherapy offers significant advantages over more traditional high energy photon sources, most importantly the increased achievable tumor conformity. Proton’s depth dose distribution allows clinicians to deliver a higher dose to the tumor volume while delivering less integral dose to surrounding tissues. While there is much to applaud about proton therapy, there remain important problems which have yet to be addressed. One such problem is the inability to monitor the depth dose characteristics (namely, the proton range) in vivo . Patient specific uncertainties, including setup errors, motion, and anatomical changes, and dosimetric uncertainties, including errors in the dose calculation algorithm, artifacts in the planning CT, and uncertainties in the Hounsfield Units lead to discrepancies between the planned and actual delivered dose. As a result, the clinical advantage afforded by the depth dose profile can not be fully exploited. An accurate method of monitoring the distal edge of the falloff in administered fields would allow clinicians to tighten constraints on treatment planning – supplying the required dose to the tumor volume while decreasing overall treatment volume necessary to compensate for patient specific uncertainties, as well as monitor treatment to ensure that the delivered dose mimics the treatment plan as closely as possible. We aim to address this problem of proton dose delivery by measuring the gamma rays emitted during therapy via inelastic scattering, or a (p, p’ ) reaction, from carbon, oxygen, and nitrogen, among others. For example, the reaction with oxygen is: p+ 16 O p’+ 16* O 16* O 16 O+ γ 6.129MeV The impetus for developing this technique was a study conducted by Min et al . at the Korean National Cancer Center , in which they successfully revealed a correlation between the gamma ray emission fluence orthogonal to the proton beam and the proton depth dose profile in the water tank. The computational and experimental results both yielded a gamma emission peak slightly proximal (~2cm) to the Bragg peak. (Figure 6) Calculated spectrographic data revealed that the most abundant gamma emission near the Bragg peak was the 4.44MeV peak from 12 C.(Figure 4) Arbitrary integration of the photon data about this energy (4-5MeV and 4-8MeV) was conducted – both sets of data yielded a peak 1cm proximal to the Bragg peak, with the 4-5MeV data displaying a lower plateau relative to the peak.(Figure 5) Narrower energy binning, however, did result in lower overall count rates. Implanted seed geometries displayed the same 4.44MeV peak abundant near the Bragg peak. Significant low energy (<2.0MeV) gamma emission was calculated at the position of the metallic implant due to gammas created in the seed. While this caused the total emission peak to move to the location of the seed, energy binning strategies filtered out these lower energy photons, yielding a 4-5MeV and 4-8MeV emission peak 1cm proximal to the Bragg peak. The 4-5MeV binning technique was used for the heterogeneous phantom in which the proton beam enters lung and stops in bone, yielding a gamma emission peak 1.5cm proximal to the Bragg peak.(Figure 8) Gamma emission was significantly lower in the lung equivalent material than the bone equivalent material, mostly due to the lower density of the lung (0.30g/cc) compared to the bone (1.82g/cc). MCNP Simulations Methods and Materials The Monte Carlo code MCNPX (v2.6.0) was used to simulate a modified model of the Lucite phantom, which consisted of the cylindrical phantom (30x10.2cm, length x dia.), an annular array of NaI photon fluence (25.1cm radius) with thin, ideal collimators extending from the phantom to the tallies in order to register only gammas emitted orthogonal to the proton beam central axis. Tally bins were in increments of 100keV from 0-20MeV, and detector response was not modeled. A 147.5MeV proton beam was used. Modified geometries were also included in order to examine the effect of material inhomogeneities on signal. One simulation included a W seed implant inside the Lucite phantom in order to simulate metallic surgical implants. Other simulations used a heterogeneous phantom consisting of PMMA and bone and lung equivalent slabs.  All simulations used the same tallying scheme as the Lucite phantom. Results p + beam Phantom Annular Tallies PMMA Bone Lung Figures: 3D diagram of the Lucite phantom and annular tallies (collimators not included) (L), and 3D diagram of the heterogeneous phantom Figures: Calculated spectrographic data from Lucite phantom (Left), gamma emission and proton depth-dose profile in Lucite phantom (Center), and calculated gamma emission and proton depth-dose profile for heterogeneous phantom in which beam enters lung and stops in bone (Right) Conclusions The results are promising, and indicate the feasibility of prompt gamma emission detection as a means of characterizing proton beam range in situ . By determining a correlation of the Bragg peak and the gamma emission peak in the homogeneous and heterogeneous phantom, we have shown that this range verification technique works not only with a perfect laboratory target, but also a complex target of varying composition – a step necessary to demonstrate clinical potential. This study has examined many measurement and computational tools, including assessing advantages afforded by energy binning and the effects of elemental composition on the gamma spectrum, and along with studies conducted by Min et al , Kang et al , and Polf et al , is establishing the tools necessary to develop this technique further. Figure: Proton inelastic scattering cross section for two different characteristic gamma ray lines, 6.13 and 2.74 MeV  Lung Bone <ul><li>These experiments were intended to independently reproduce earlier findings [2,3] that correlated prompt gamma measurements with the distal edge of the Bragg peak in water for proton beams of incident energies 38 and 150 MeV. </li></ul><ul><li>We measured inelastic gamma ray emission profiles that exhibited a steady increase with depth along the entrance plateau region, followed by a sharp decline at or near the Bragg peak. A spatial resolution on the mm scale is realized. Our results are consistent with previously published reports and have encouraged a series of calculations that simulate prompt gamma emissions under pseudo therapeutic conditions. </li></ul><ul><li>Reducing ambient background appears to significantly improve the sensitivity of detection and future efforts will focus on shielding, collimation and detector geometry to optimize signal detection for which funding has been sought. </li></ul><ul><li>Methods </li></ul><ul><li>Experiments were performed in one of the three available therapy rooms at the Francis H. Burr Proton Therapy Center. To minimize background radiation ordinarily produced in the treatment room by scattering devices currently used during therapy, measurements were performed with a pencil beam (approximate diameter 5-6 mm) of 150 MeV protons. The beam was incident upon a 10.2 cm diameter, 30 cm long cylindrical phantom made from PMMA that is routinely used for quality assurance measurements. The protons have a range of 151 mm in the phantom. Gamma rays were measured at 90 degrees to the central axis of the incident beam with the shielded detector positioned 52 cm from the central axis of the beam. The shielding has a slit opening 5 mm wide for the detector to view the emitted radiation as protons traverse the phantom. The assembly was scanned through the depth of the Bragg peak by moving the treatment couch parallel to the beam direction. </li></ul><ul><li>Equipment </li></ul><ul><li>NaI(Tl) scintillator 2.5x5 cm (diameter x length) </li></ul><ul><li>Photonis photomultiplier tube </li></ul><ul><li>Canberra DSA 1000k/Genie 2000 pulse processing spectroscopy system </li></ul><ul><li>Energy calibration with photopeaks at 1173 and 1332 keV from 60 Co </li></ul>Results Spectra were acquired at different positions along the beam path (proton intensity approximately 5 nA) for a dose of 100 MU. The acquired pulse height spectra were continuous and predominately featureless extending up to approximately 10 MeV with little discernible detail and no identifiable peaks as illustrated. Pulse height spectra were integrated above a threshold equivalent to 4 MeV for direct comparison with Min et al. , 2006 as a measure of the intensity of the prompt gamma ray production from oxygen and carbon in the phantom. This yielded approximately 15 counts per MU with a statistical uncertainty of 2-3%. The results of these integrations are plotted in Figure 3 normalized to 100% at the location of the Bragg peak together with calculations of the corresponding gamma ray emissions (see calculations section) as well as the depth dose curve both similarly normalized for comparison. The ratio of the peak to entrance plateau measured with our rudimentary, non-optimized experimental set up is approximately 100:60, which appears better than the 100:75 achieved previously [2,3]. A distal fall off is also observed and a spatial resolution of several mm is apparent. The relatively high counts beyond the distal edge are attributed to scattered radiation in the therapy vault from which the detector must be shielded in future. A reduction of the background component will only enhance the measurement technique. Measurements supported by the US Department of Energy under grant number DE-FG02-87-ER-6060 Radiation Monitoring Devices, Inc. Radiation Monitoring Devices, Inc. Figure 3: Measured and calculated prompt gamma emission profiles for incident 150 MeV proton beam. Figure 1: Photograph of the detector positioned perpendicular to the beam direction on the treatment couch behind a shielding wall 10 cm thick and 80 cm long made of steel and lead bricks. Figure 2: Representative pulse height spectra collected with the detector positioned at and beyond the Bragg peak. All spectra possessed the same featureless character independent of measurement position.