Beam Composition for Biology

1. Beam Composition for Biology The beam delivered to radiobiology samples at NSRL can have many components in addition to the nominal beam particles. These beam components may be important to account for when understanding the biological endpoints obtained in NSRL experiments. These additional beam components can come from processes such as scattering and fragmentation of the beam or target nuclei, production of secondary particles such as pions through nuclear interactions, and electrons and gamma rays from collisions or the de-excitation of nuclear states produced in the target or air in the target room. The importance of these beam components to the results of the experiment depends on what kind of experiment is being conducted. If the beam is Fe-56 at 1000 MeV/n, then the LET delivered by the Fe-56 dominates all other sources. Treating the beam as if it were pure Fe-56 at 1000 MeV/n will be close to accurate when total LET is the only measure of dose being considered. In practice, the EGG counter used to calibrate the dose delivered sees virtually all the same beam components that the samples see, so it gives the correct measure of dose. But in some experiments, the mode of dose delivery is also important. In that case additional information will be needed to fully characterize the NSRL beam.

2. NSRL Beam Composition Beam Components 1) Primary Beam Particles 2) Fragments from the Primary Beam Ion 3) Fragments from the Target a) Nuclear Fragments b) Electrons 4) Secondary Particle Production 5) Photons (gamma rays) accompanying the beam 6) Neutrons accompanying the beam 7) De-excitation gamma rays from nuclear excited states 8) Thermal neutrons Each of these components will be discussed in terms of their contribution to the total dose, and methods of measuring them.

3. Primary Beam Particles The dose delivered by the primary beam particles is typically measured using a small ionization chamber (EGG counter) with a tissue-equivalent casing. This dose measurement is used to calibrate a series of ionization chambers that are used to cut off the beam during an exposure. Both the EGG counter and the ionization chambers are sensitive only to charged particles, and measure the total amount of ionization in a gas sample. This ionization is proportional to the square of the beam particle charge, and approximately inversely proportional to the square of the particle velocity. This means that the response of the EGG counter is proportional to the LET in biological samples. That is why the ionization chambers are used to determine the delivered dose due to the primary beam particles and any other source of ionization they are exposed to. Of course not all biological endpoints are proportional to ionization or dose…

4. Fragments from the Primary Beam Ion As the beam is delivered to the samples in the target room, it must pass through a thin aluminum vacuum window, three ionization chambers and several meters of air. All this material can interact with heavy ions in the beam causing them to fragment, scatter, or produce secondary particles. In general, these secondary particles travel at small angles relative to the beam, and at nearly the same velocity as the beam. The example below shows the effect of this fragmentation on a Fe-56 beam of 1000 MeV/n. Many peaks can be identified as the Z=26 ion is fragmented into lighter lower-Z fragments. Each of these fragments will be incident upon the biological samples with an LET that scales with Z2, in general, making the lower Z fragments less of a contribution to the total dose. Fragments from the beam generally travel at velocities close to the velocity of beam ions, with LET that scales like 1/v2 where v is the velocity. Fragments that pass through the ion chambers contribute to the total accumulated dose.

5. Fragments from the Target In contrast to the fragments of the beam ion, interactions between a heavy ion projectile and a target nucleus typically result in target fragments that are scattered less energetically at large angles from the beam. Because the target fragments are slow moving, they can be high LET and contribute significantly to the total dose. They will have a very short range, typically. The wide scattering angle of target fragments means that they disperse with increasing distance from their source. Some of the scattered particles will be electrons from the target atoms. Like fragments from the target nuclei, these electrons will be low energy, short range, and large angle tracks. Since electrons are Z=1 tracks, their contribution to the total dose is less important than the high-Z target fragments. From the standpoint of biology, this has implications for stacking multiple samples along the beam. (See also the information regarding stacked samples). All samples that are sensitive to target fragmentation need to be kept as thin as possible to maintain a uniform exposure throughout the sample. Similar considerations apply to the placement of samples on massive high-Z sample holders that can produce undesirable contributions to the total delivered dose.

6. Secondary Particle Production If the energy of the particles in the beam is high enough, it is possible to produce secondary particles as the beam interacts with material along the way such as air. At the energies NSRL runs at, typically less than 1000 MeV/n, the only secondaries that can be produced are neutral pions. These pions decay into two photons which ultimately turn into electromagnetic showers with total energy of ~100 MeV. An estimate of the pion production rate is ~0.5 pion per incident Fe ion at 1000 MeV/n. This rate drops rapidly to near zero at beam energies of ~300 MeV/n. This can be an important point to consider in the planning of an exposure: if all other things are equal, make use of a lower energy beam to reduce production of secondary particles. For proton beam, the pion production rate is only about 1% of the incident proton rate at 1000 MeV. This rate also falls rapidly with beam energy.

7. Photons accompanying the beam Photons in the target room can come from many sources: - bremsstrahlung from interactions between the ions and nuclei in the vacuum window and air, ~ 1-100 keV. - neutral pion decay, ~100 MeV (see previous). - de-excitation of nuclear excited states created in target room, ~1-5 MeV (see later). Production of bremsstrahlung photons is a coherent process, scaling like Z2, making photons more prevalent in high-Z beams. Since the LET from the beam also scales like Z2, the bremsstrahlung contribution to the total dose is independent of beam ion. Although the bremsstralung photons cover much of the energy spectrum, they fall sharply with increasing energy[1], like 1/E. Bremsstrahlung below 1 keV deposit very little energy and have very short range. Above 100 keV the spectrum falls so fast they contribute little to the total deposited energy. So the energy range between 1 and 100 keV is the part of the bremsstrahlung spectrum that requires consideration. We have not yet made measurements of the beam-related photon spectrum or flux in the NSRL target room. This measurement will be of crucial importance in the understanding of the complete dose profile for samples at NSRL. General comments about the photon flux is that photons have an RBE of 1, like x-rays, and the contribution to the total dose is well measured by the ion chambers. In any HZE exposure, the photon contribution is likely to be small compared to the primary beam particles. In the case of low-Z beam such as protons, the total photon flux is a factor of Z2 less than a beam of nuclear charge Z. [1] Hoefman, M. et al., Coherent Bremsstrahlung in the  + p System at 50 MeV/nucleon, Phys. Rev. Lett. 85, (1404) 14 Aug. 2000.

8. Neutrons accompanying the beam Interactions between the beam particles and material in the beam can result in neutrons that accompany the beam. Because the neutrons are not charged, they do not produce ionization or contribute to dose directly. But through other interactions, they are capable of delivering dose via secondary interactions. The table[2] below gives the RBE appropriate for neutrons of different energies. This RBE applies to the energy deposited by the neutron as it passes through matter, and the changing value is indicative of the changing types of interactions that the neutron can take part in. [2] Particle Data Group, Phys. Rev. D66, 2006.

9. Neutrons interactions Knock-on protons and recoil nuclei produced by elastic nuclear collision can produce ionizing tracks. The track range is typically short, but the local energy density can be very high. This is the primary mechanism for energy deposition by high energy neutrons, En > 10 MeV As a neutron slows down through collisions, it can be captured by a nucleus. Resonances in the neutron fission and capture cross sections can be very large for some nuclei (e.g. B11) but in general the cross section scales with 1/v where v is the neutron velocity. Because of the variability in cross section, the neutron RBE and dose are very sensitive to the details of the sample environment. “Fast neutrons” (En ~ 1-10 MeV) can produce very high LET fission fragments, if high-Z fissionable material is at hand. Eventually all beam particles end up degrading in the beam dump, resulting in a shower of neutrons that do not range out. These neutrons scatter until their kinetic energy is comparable to thermal energies, i.e. En ~ 0.02 eV. At this point they behave more like a diffuse gas of neutrons, expanding from the beam dump in a random walk with a velocity of ~1000 m/s scattering from the hydrogen in the concrete walls until they undergo a capture.

10. Thermal neutrons Interactions between the beam and material in the target room (primarily the beam dump) produces cascades of low energy particles called an hadronic shower. All of the low energy protons range out in the beam dump (as designed) but low energy neutrons, called thermal, are extremely hard to stop. They behave more like a neutron gas rather than a particle beam, diffusing around and through shielding. A thermal neutron detector was installed in NSRL to measure the flux at a variety of locations. The total detection rate of thermal neutrons was proportional to the number of incident nucleons. We studied the rate as function of ion species for protons (H), Silicon (Si) and Iron (Fe). The detection rates (in units of “thermal neutrons per spill per 109 incident nucleons”) was 38 for H, 32 for Si and 33 for Fe for the detector at location 5 in the NSRL labyrinth. The following target room schematic shows how the rate varies throughout the area. Since the thermal neutrons behave like a gas, they fill the target room more or less uniformly and isotropically. They diffuse around corners quite well, giving a measurable rate all the way out of the labyrinth.

11. 8 Schematic of the NSRL Target Area Beam Conditions: 1000 MeV protons Big Beam Spot (20x20) 4 x 1010 protons/spill Relative Rates (thermal neutrons/spill) >>50,000 26,000 12,000 2,000 1,000 200 1 <1 7 Thermal Neutron Detector Locations Detector: Reuter-Stokes BF3 Proportional Tube 3” long, 1” diameter 6 5 4 2 3 1 Target Location Beam Dump 1,2 1,2,3,4 Scintillator Detectors Charged Particle Detectors

12. Thermal Neutrons Although thermal neutrons can have RBEs varying from less than 1 to more than 10, the dose is very sensitive to the environment. This is due to the process by which thermal neutrons deposit energy. The neutrons themselves have kinetic energies that are a fraction of an eV, they can be captured by a nucleus causing that nucleus to break up giving off gamma rays of ~1 MeV, -particles, and/or fission fragments. The -particles and fission fragments deposit all their energy locally (typically a few MeV), whereas the gamma rays have a range in water of ~10 cm at the energy of 1 MeV. In the absence of exotic isotopes (like B-10, etc) the largest cross section for thermal neutron absorption is Hydrogen which converts to D*, decaying via a 2.2 MeV gamma ray. It is this gamma ray that is responsible for most of the thermal neutron dose under normal circumstances. Additional studies of the energy dependence of thermal neutron production are planned.

13. Gamma rays from nuclear excited states Once the thermal or fast neutrons are captured by a nucleus, that nucleus will be in an excited state, and will de-excite by the emission of a photon of energy typically in the range 0.1 MeV < E < 10 MeV. This photon will merely add to the sea of photons coming from charged particle interactions in the beam except: • They will not be generated in the immediate vicinity of the beam, but will be spread throughout the target room • They will not have any directional correlation with the beam, but will have an isotropic angular distribution • They will not be prompt with the beam, but can be delayed by neutron transit times and nuclear lifetimes that may be long compared to an exposure of a biological sample. A scintillator placed in the target cave measured photon hits after the beam was turned off. The hit rate was consistent with the lifetime of an excited state of Nitrogen produced in beam interactions with the air in the target room. In general, contributions to the total dose from these photons is negligible, and will be included in the dose measured by the ion chambers.

14. Beam Composition for Biology One way to characterize the beam is by giving both the “Dose Averaged LET” and the “Event Averaged LET”. The Dose Averaged LET is exactly what the EGG counter measures, giving a total delivered dose per unit time, integrating to a total delivered dose. The result will be the same whether the dose is delivered by a single Fe-56 ion or 676 protons. The Track Averaged LET is the dose per incident beam particle. This integrates to the same total dose as the Dose Averaged LET, but it describes the dose as it is delivered for each incoming track. Some users make use of scintillator-based dosimetry. This relies on counting the tracks in the beam and cutting off the beam when a certain preset number of tracks has been reached. This will be an accurate dosimeter if we know the precise composition of the beam. If the beam is a heavy ion like Fe-56, then it is possible to set the scintillator to count only those tracks with high LET characteristic of Fe-56. This means that the contribution to the dose from low LET components will not be counted at all. Alternatively the scintillator can count all tracks, but then no distinction is made between high-LET and low-LET tracks giving an incorrectly weighted total dose. Careful calibration of the scintillator counter for each species and energy of heavy ion can give good dosimetry, as illustrated in the following graph that compares the dose measured using a scintillator with dose measured using the standard ion chambers. This calibration must include rate-dependent corrections that are also species dependent. And since the fragmentation spectrum changes as a function of energy, the calibration must also be energy dependent.

15. Calibration of Scintillator-Based Dosimetry Smooth transition between PMT/Scintillator-based dosimetry for low dose rate work, and Ion Chamber-based dosimetry for high dose rate work. The horizontal axis is the dose as measured with a thin scintillator in the beam for doses less than about 600 cGy/hour, and with an Ion Chamber for dose rates above 600 cGy/hour. The vertical axis shows the counting rate in a scintillator. There is continuity in the transition from one dosimetry technique to another. Dose rates where Counter-based dosimetry is typically used. Dose rates where Ion Chamber-based dosimetry is typically used

16. Beam Composition Study NSRL Beam: 1000 MeV/n Fe-56 Large Beam - 20 cm x 20 cm uniform field Self Triggered - good efficiency for Z=1 tracks LET measured with a small (14 x 15 mm2 scintillator)

17. LET Spectrum for 1000 MeV/n Fe-56 The peak near 150 keV/ is the Fe-56 beam particles. Beam fragments appear at LET between 10 - 140 keV/. Below 1 keV/ is a large peak due to protons and other low-Z fragments. The Dose-averaged LET is 140 keV/m, close to the pure Fe-56 LET of ~150 keV/m. The Event-averaged LET is 5 keV/m due to the large number of low-LET tracks in the beam. Event Averaged LET Dose Averaged LET LET distribution for all beam particles (keV/) From fe1000_04_10_2006_air_bigbeam

18. LET Spectrum for 1000 MeV/n Fe-56 This plot shows the low LET peak expanded. The peak near 0.2 keV/ is from protons. Alphas may be visible near 0.8. The large peak near 0 may be due to gamma rays from activation in the target cave. Electrons may also contribute to the peak near 0. “other” protons alphas LET distribution for beam particles < 1.3 keV/ From fe1000_04_10_2006_air_bigbeam