In-beam Positron Emission Tomography Research Articles

Using the gamma-index analysis for inter-fractional comparison of in-beam PET images for head-and-neck treatment monitoring in proton therapy: A Monte Carlo simulation study

Goal:In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with PET, various analysis methods exist, but their clinical interpretation is problematic. The goal of this work is to investigate whether the gamma-index analysis, widely used for dose comparisons, is an appropriate tool for comparing in-beam PET distributions. Focusing on a head-and-neck patient, we investigate whether the gamma-index map and the passing rate are sensitive to progressive anatomical changes. Methods/materials:We simulated a treatment course of a proton therapy patient using FLUKA Monte Carlo simulations. Gradual emptying of the sinonasal cavity was modeled through a series of artificially modified CT scans. The in-beam PET activity distributions from three fields were evaluated, simulating a planar dual head geometry. We applied the 3D-gamma evaluation method to compare the PET images with a reference image without changes. Various tolerance criteria and parameters were tested, and results were compared to the CT-scans. Results:Based on 210 MC simulations we identified appropriate parameters for the gamma-index analysis. Tolerance values of 3 mm/3% and 2 mm/2% were suited for comparison of simulated in-beam PET distributions. The gamma passing rate decreased with increasing volume change for all fields. Conclusion:The gamma-index analysis was found to be a useful tool for comparing simulated in-beam PET images, sensitive to sinonasal cavity emptying. Monitoring the gamma passing rate behavior over the treatment course is useful to detect anatomical changes occurring during the treatment course.

Synthetic CT imaging for PET monitoring in proton therapy: a simulation study.

Objective.This study addresses a fundamental limitation of in-beam positron emission tomography (IB-PET) in proton therapy: the lack of direct anatomical representation in the images it produces. We aim to overcome this shortcoming by pioneering the application of deep learning techniques to create synthetic control CT images (sCT) from combining IB-PET and planning CT scan data.Approach.We conducted simulations involving six patients who underwent irradiation with proton beams. Leveraging the architecture of a visual transformer (ViT) neural network, we developed a model to generate sCT images of these patients using the planning CT scans and the inter-fractional simulated PET activity maps during irradiation. To evaluate the model's performance, a comparison was conducted between the sCT images produced by the ViT model and the authentic control CT images-serving as the benchmark.Main results.The structural similarity index was computed at a mean value across all patients of 0.91, while the mean absolute error measured 22 Hounsfield Units (HU). Root mean squared error and peak signal-to-noise ratio values were 56 HU and 30 dB, respectively. The Dice similarity coefficient exhibited a value of 0.98. These values are comparable to or exceed those found in the literature. More than 70% of the synthetic morphological changes were found to be geometrically compatible with the ones reported in the real control CT scan.Significance.Our study presents an innovative approach to surface the hidden anatomical information of IB-PET in proton therapy. Our ViT-based model successfully generates sCT images from inter-fractional PET data and planning CT scans. Our model's performance stands on par with existing models relying on input from cone beam CT or magnetic resonance imaging, which contain more anatomical information than activity maps.

Design study of a novel geometrical arrangement for an in-beam small animal positron emission tomography scanner

Objective. We designed a geometrical solution for a small animal in-beam positron emission tomography (PET) scanner to be used in the project SIRMIO (Small animal proton irradiator for research in molecular image-guided radiation-oncology). The system is based on 56 scintillator blocks of pixelated LYSO crystals. The crystals are arranged providing a pyramidal-step shape to optimize the geometrical coverage in a spherical configuration. Approach. Different arrangements have been simulated and compared in terms of spatial resolution and sensitivity. The chosen setup enables us to reach a good trade-off between a solid angle coverage and sufficient available space for the integration of additional components of the first design prototype of the SIRMIO platform. The possibility of moving the mouse holder inside the PET scanner furthermore allows for achieving the optimum placement of the irradiation area for all the possible tumor positions in the body of the mouse. The work also includes a study of the scintillator material where LYSO and GAGG are compared with a focus on the random coincidence noise due to the natural radioactivity of Lutetium in LYSO, justifying the choice of LYSO for the development of the final system. Main results. The best imaging performance can be achieved with a sub-millimeter spatial resolution and sensitivity of 10% in the center of the scanner, as verified in thorough simulations of point sources. The simulation of realistic irradiation scenarios of proton beams in PMMA targets with/without air gaps indicates the ability of the proposed PET system to detect range shifts down to 0.2 mm. Significance. The presented results support the choice of the identified optimal design for a novel spherical in-beam PET scanner which is currently under commissioning for application to small animal proton and light ion irradiation, and which might find also application, e.g. for biological image-guidance in x-ray irradiation.

Quasi-real-time range monitoring by in-beam PET: a case for 15O

A fast and reliable range monitoring method is required to take full advantage of the high linear energy transfer provided by therapeutic ion beams like carbon and oxygen while minimizing damage to healthy tissue due to range uncertainties. Quasi-real-time range monitoring using in-beam positron emission tomography (PET) with therapeutic beams of positron-emitters of carbon and oxygen is a promising approach. The number of implanted ions and the time required for an unambiguous range verification are decisive factors for choosing a candidate isotope. An experimental study was performed at the FRS fragment-separator of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany, to investigate the evolution of positron annihilation activity profiles during the implantation of ^{14}O and ^{15}O ion beams in a PMMA phantom. The positron activity profile was imaged by a dual-panel version of a Siemens Biograph mCT PET scanner. Results from a similar experiment using ion beams of carbon positron-emitters ^{11}C and ^{10}C performed at the same experimental setup were used for comparison. Owing to their shorter half-lives, the number of implanted ions required for a precise positron annihilation activity peak determination is lower for ^{10}C compared to ^{11}C and likewise for ^{14}O compared to ^{15}O, but their lower production cross-sections make it difficult to produce them at therapeutically relevant intensities. With a similar production cross-section and a 10 times shorter half-life than ^{11}C, ^{15}O provides a faster conclusive positron annihilation activity peak position determination for a lower number of implanted ions compared to ^{11}C. A figure of merit formulation was developed for the quantitative comparison of therapy-relevant positron-emitting beams in the context of quasi-real-time beam monitoring. In conclusion, this study demonstrates that among the positron emitters of carbon and oxygen, ^{15}O is the most feasible candidate for quasi-real-time range monitoring by in-beam PET that can be produced at therapeutically relevant intensities. Additionally, this study demonstrated that the in-flight production and separation method can produce beams of therapeutic quality, in terms of purity, energy, and energy spread.

Tumour status prediction by means of carbon-ion beam irradiation: comparison of washout rates between in-beam PET and DCE-MRI in rats

Objective. Tumour response to radiation therapy appears as changes in tumour vascular condition. There are several methods for analysing tumour blood circulatory changes one of which is dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), but there is no method that can observe the tumour vascular condition and physiological changes at the site of radiation therapy. Positron emission tomography (PET) has been applied for treatment verification in charged particle therapy, which is based on the detection of positron emitters produced through nuclear fragmentation reactions in a patient’s body. However, the produced positron emitters are washed out biologically depending on the tumour vascular condition. This means that measuring the biological washout rate may allow evaluation of the tumour radiation response, in a similar manner to DCE-MRI. Therefore, this study compared the washout rates in rats between in-beam PET during 12C ion beam irradiation and DCE-MRI. Approach. Different vascular conditions of the tumour model were prepared for six nude rats. The tumour of each nude rat was irradiated by a 12C ion beam with simultaneous in-beam PET measurement. In 10–12 h, the DCE-MRI experiment was performed for the same six nude rats. The biological washout rate of the produced positron emitters (k 2,1st) and the MRI contrast agent (k 2a) were derived using the single tissue compartment model. Main results. A linear correlation was observed between k 2,1st and k 2a, and they were inversely related to fractional necrotic volume. Significance. This is the first animal study which confirmed the biological washout rate of in-beam PET correlates closely with tumour vascular condition measured with the MRI contrast agent administrated intravenously.

A simulation study of in-beam visualization system for proton therapy by monitoring scattered protons.

Recently, in-beam positron emission tomography (PET) has been actively researched for reducing biological washout effects and dose monitoring during irradiation. However, the positron distribution does not precisely reflect the dose distribution since positron production and ionization are completely different physical processes. Thus, a novel in-beam system was proposed to determine proton dose range by measuring scattered protons with dozens of scintillation detectors surrounding the body surface. While previous studies conducted a preliminary experiment with a simple phantom, we simulated more complex situations in this paper. Especially, we conducted three stepwise simulation studies to demonstrate the feasibility of the proposed method. First, a simple rectangular phantom was reproduced on simulation and irradiated with protons for obtaining current values and Monte Carlo (MC) dose. Next, we trained a deep learning model to estimate 2-dimensional-dose range (2D-DL dose) from measured current values for simulation (A). We simulated plastic scintillators as detectors to measure the scattered protons. Second, a rectangular phantom with an air layer was used, and 3D-DL dose was estimated in simulation (B). Finally, a cylindrical phantom that mimics the human body was used for confirming the estimation quality of the simulation (C). Consequently, the position of the Bragg peak was estimated with an error of 1.0 mm in simulation (A). In addition, the position of the air layer, as well as the verifying peak position with an error of 2.1 mm, was successfully estimated in simulation (B). Although the estimation error of the peak position was 12.6 mm in simulation (C), the quality was successfully further improved to 9.3 mm by incorporating the mass density distribution obtained from the computed tomography (CT). These simulation results demonstrated the potential of the as-proposed verification system. Additionally, the effectiveness of CT utilization for estimating the DL dose was also indicated.

Analysis methods for in-beam PET images in proton therapy treatment verification: a comparison based on Monte Carlo simulations

Background and purpose: in-beam Positron Emission Tomography (PET) is one of the modalities that can be used for in-vivo non-invasive treatment monitoring in proton therapy. PET distributions obtained during various treatment sessions can be compared in order to identify regions that have anatomical changes. The purpose of this work is to test and compare different analysis methods in the context of inter-fractional PET image comparison for proton treatment verification. Methods: for our study we used the FLUKA Monte Carlo code and artificially generated CT scans to simulate in-beam PET distributions at different stages during proton therapy treatment. We compared the Beam-Eye-View method, the Most-Likely-Shift method, the Voxel-Based-Morphology method and the gamma evaluation method to compare PET images at the start of treatment, and after a few weeks of treatment. The results were compared to the CT scan. Results and conclusions: three-dimensional methods like VBM and gamma are preferred above two-dimensional methods like MLS and BEV if much statistics is available, since the these methods allow to identify the regions with anomalous activity. The VBM approach has as disadvantage that a larger number of MC simulations is needed. The gamma analysis has the disadvantage that no clinical indication exist on tolerance criteria. In terms of calculation time, the BEV and MLS method are preferred. We recommend to use the four methods together, in order to best identify the location and cause of the activity changes.

Precision of the PET activity range during irradiation with 10C, 11C, and 12C beams

Objective. Beams of stable ions have been a well-established tool for radiotherapy for many decades. In the case of ion beam therapy with stable 12C ions, the positron emitters 10,11C are produced via projectile and target fragmentation, and their decays enable visualization of the beam via positron emission tomography (PET). However, the PET activity peak matches the Bragg peak only roughly and PET counting statistics is low. These issues can be mitigated by using a short-lived positron emitter as a therapeutic beam. Approach. An experiment studying the precision of the measurement of ranges of positron-emitting carbon isotopes by means of PET has been performed at the FRS fragment-separator facility of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany. The PET scanner used in the experiment is a dual-panel version of a Siemens Biograph mCT PET scanner. Main results. High-quality in-beam PET images and activity distributions have been measured from the in-flight produced positron emitting isotopes 11C and 10C implanted into homogeneous PMMA phantoms. Taking advantage of the high statistics obtained in this experiment, we investigated the time evolution of the uncertainty of the range determined by means of PET during the course of irradiation, and show that the uncertainty improves with the inverse square root of the number of PET counts. The uncertainty is thus fully determined by the PET counting statistics. During the delivery of 1.6 × 107 ions in 4 spills for a total duration of 19.2 s, the PET activity range uncertainty for 10C, 11C and 12C is 0.04 mm, 0.7 mm and 1.3 mm, respectively. The gain in precision related to the PET counting statistics is thus much larger when going from 11C to 10C than when going from 12C to 11C. The much better precision for 10C is due to its much shorter half-life, which, contrary to the case of 11C, also enables to include the in-spill data in the image formation. Significance. Our results can be used to estimate the contribution from PET counting statistics to the precision of range determination in a particular carbon therapy situation, taking into account the irradiation scenario, the required dose and the PET scanner characteristics.

Real-time digital signal processing implementation for in-beam PET of radiotherapy imaging in HIMM

The in-beam positron emission tomography (ibPET) is dedicated to radiotherapy imaging of the heavy-ion medical machine (HIMM), which requires precise online measurement, as well as real-time signal processing capability of the electronics. In this paper, we present the implementation of real-time digital signal processing in the data acquisition unit (DAQU) for an ibPET system based on the photomultiplier tube (PMT) readout of lutetium-yttrium oxyorthosilicate (LYSO) scintillator crystals. We have designed 10-channel customized signal processing circuit on a high-performance FPGA, which supports 3 working modes (single event processing mode, self-calibration mode and raw ADC data mode), position calculation, crystal locating, event sorting, and etc. Moreover, the implementation of real-time corrections is capable of dealing with photon peak correction to 511 keV and crystal ID-based time correction. The implemented real-time ibPET system can achieve 46% data compression and beyond 1,000,000 events/sec/channel signal processing capabilities. A series of initial tests is conducted, and the results indicate that this design meets the application requirement on online processing.

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam’s Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.

Feasibility of triple gamma ray imaging of 10C for range verification in ion therapy

Objective. In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive 15O and 11C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of 10C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient’s body during ion therapy. Approach. In this work, we focus on investigating the performance of WGI for 10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a 10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a 10C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba. Main results. The average spatial resolution and sensitivity for the simulated 10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the 10C ion beam was measured, and the triple gamma image of 10C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas. Significance. The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8 ± 0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of 10C ion beams.

Measurement of biological washout rates depending on tumor vascular status in 15O in-beam rat-PET

Objective. The biological washout of positron emitters should be modeled and corrected in order to achieve quantitative dose range verification in charged particle therapy based on positron emission tomography (PET). This biological washout effect is affected by physiological environmental conditions such as blood perfusion and metabolism, but the correlation to tumour pathology has not been studied yet. Approach. The aim of this study was to investigate the dependence of the biological washout rate on tumour vascular status in rat irradiation. Two types of tumour vascularity conditions, perfused and hypoxic, were modelled with nude rats. The rats were irradiated by a radioactive 15O ion beam and time activity curves were acquired by dynamic in-beam PET measurement. Tumour tissue sections were obtained to observe the histology as well. The biological washout rate was derived using a single-compartment model with two decay components (medium decay, k 2m and slow decay, k 2s ). Main results. All k 2m values in the vascular perfused tumour tissue were higher than the values of the normal tissue. All k 2m values in the hypoxic tumour tissue were much lower than the values of the vascular perfused tumour tissue and slightly lower than the values of the normal tissue. Significance. The dependency of the biological washout on the tumour vasculature conditions was experimentally shown.

A design implementation of the Central Process Module for an In-Beam PET in HICTD

To monitor the irradiation dose and position accurately delivered to patient during particle therapy in Heavy-Ion Cancer Therapy Device (HICTD) in Lanzhou, China, an In-Beam Positron Emission Tomography (PET) has been designed as a detection device to obtain time, energy and position information of gamma ray generated from the annihilation event, which is equipped at the beam line of HICTD. Sixteen detection blocks are adopted to construct a Dual-Head Planar-Type detector array in the In-Beam PET, and each detection block is composed of pixel detection elements. Data Acquisition Unit (DAQU) is employed as the processing module to process and digitize signals from detection blocks. Each DAQU faces a pair of detection blocks, there are eight DAQUs in total in this PET at present. A Central Processor Module (CPM) developed for the detector array is presented in this paper. CPM has two crucial functions: first it is as a hub to connect with all DAQUs through the optical links for data transfer and state control, second it is as a data process engine which collects data from different DAQUs and sorts the events into the chronological order for coincidence event discrimination, and then interfaces both control signals and event data to a host server through PCIe interface for image reconstruction. A novel parallel sorting algorithm has been explored and adopted in CPM, which can effectively sort the valid events detected by detection blocks. The key performance of the CPM has been evaluated in experiments. It can handle the events up to 16 million per second at least, which is capable of sorting and discriminating coincidence events efficiently.

A real-time sorting algorithm for in-beam PET of heavy-ion cancer therapy device

A real-time digital time-stamp sorting algorithm used in the In-Beam positron emission tomography (In-Beam PET) is presented. The algorithm is operated in the field programmable gate array (FPGA) and a small amount of registers, MUX and memory cells are used. It is developed for sorting the data of annihilation event from front-end circuits, so as to identify the coincidence events efficiently in a large amount of data. In the In-Beam PET, each annihilation event is detected by the detector array and digitized by the analog to digital converter (ADC) in Data Acquisition Unit (DAQU), with a resolution of 14 bits and sampling rate of 50 MS/s. Test and preliminary operation have been implemented, it can perform a sorting operation under the event count rate up to 1 MHz per channel, and support four channels in total, count rate up to 4 MHz. The performance of this algorithm has been verified by pulse generator and 22Na radiation source, which can sort the events with chaotic order into chronological order completely. The application of this algorithm provides not only an efficient solution for selection of coincidence events, but also a design of electronic circuit with a small-scale structure.

Detection of Interfractional Morphological Changes in Proton Therapy: A Simulation and In Vivo Study With the INSIDE In-Beam PET

In particle therapy, the uncertainty of the delivered particle range during the patient irradiation limits the optimization of the treatment planning. Therefore, an in vivo treatment verification device is required, not only to improve the plan robustness, but also to detect significant interfractional morphological changes during the treatment itself. In this article, an effective and robust analysis to detect regions with a significant range discrepancy is proposed. This study relies on an in vivo treatment verification by means of in-beam Positron Emission Tomography (PET) and was carried out with the INSIDE system installed at the National Center of Oncological Hadrontherapy (CNAO) in Pavia, which is under clinical testing since July 2019. Patients affected by head-and-neck tumors treated with protons have been considered. First, in order to tune the analysis parameters, a Monte Carlo (MC) simulation was carried out to reproduce a patient who required a replanning because of significant morphological changes found during the treatment. Then, the developed approach was validated on the experimental measurements of three patients recruited for the INSIDE clinical trial (ClinicalTrials.govID: NCT03662373), showing the capability to estimate the treatment compliance with the prescription both when no morphological changes occurred and when a morphological change did occur, thus proving to be a promising tool for clinicians to detect variations in the patients treatments.

Dose quantification in carbon ion therapy using in-beam positron emission tomography

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

Energy spread estimation of radioactive oxygen ion beams using optical imaging

Radioactive ion (RI) beams combined with in-beam positron emission tomography enable accurate in situ beam range verification in heavy ion therapy. However, the energy spread of the radioactive beams generated as secondary beams is wider than that of conventional stable heavy ion beams which causes Bragg peak region and distal falloff region broadening. Therefore, the energy spread of the RI beams should be measured carefully for their quality control. Here, we proposed an optical imaging technique for the energy spread estimation of radioactive oxygen ion beams. A polymethyl methacrylate phantom (10.0 × 10.0 × 9.9 cm3) was irradiated with an 15O beam (mean energy = 247.7 MeV u−1, standard deviation = 6.8 MeV u−1) in the Heavy Ion Medical Accelerator in Chiba. Three different momentum acceptances of 1%, 2% and 4% were used to get energy spreads of 1.9 MeV u−1, 3.4 MeV u−1 and 5.5 MeV u−1, respectively. The in-beam luminescence light and offline beam Cerenkov light images were acquired with an optical system consisting of a lens and a cooled charge-coupled device camera. To estimate the energy spread of the 15O ion beams, we proposed three optical parameters: (1) distal-50% falloff length of the prompt luminescence signals; (2) full-width at half maximum of the Cerenkov light signals in the beam direction; and (3) positional difference between the peaks of the Cerenkov light and the luminescence signals. These parameters estimated the energy spread with the respective mean squared errors of 2.52 × 10−3 MeV u−1, 5.91 × 10−3 MeV u−1, and 0.182 MeV u−1. The distal-50% falloff length of the luminescence signals provided the lowest mean squared error among the optical parameters. From the findings, we concluded optical imaging using luminescence and Cerenkov light signals offers an accurate energy spread estimation of 15O ion beams. In the future, the proposed optical parameters will be used for energy spread estimation of other RI beams as well as stable ion beams.

Can B Washout Rate be a Biomarker of Tumor Viability in Charged Particle Therapy? A Rat In-beam PET Study

Positron emission tomography (PET) is a practical tool for range verification in charged particle therapy. We aimed to apply in-beam PET imaging for tracking the evolution of irradiated particles in living tissue. The quantitative biological washout rate of the positron emitters has a potential usefulness as a diagnostic index that provides a unique opportunity to probe the status of tumor viability, but the modeling for this has not been established. Therefore, we measured biological washout rates of tumor-bearing nude rat and performed kinetic analysis on dynamic PET data to explore the biological washout mechanism. C6 rat glioma cells were implanted into right shoulder subcutaneous regions of six nude rats. Tumors volume reached to about 3 cm3 on day 14 after implantation. Tumor tissue (right shoulder) and normal tissue (left shoulder) were irradiated by 11C radioactive ion beam. Time activity curves (TACs) of the irradiated field were acquired by our original PET prototype. The biological washout rate was quantified based on the two-washout model assuming medium decay rate (k2m) and slow decay rate (k2s). In this model, k2m is speculated as the component which spread out via interstitial fluid, and k2s is speculated as the trapping component by the stable molecules in the tissue. After irradiation and PET dynamic scan, pathological morphology of tumor tissue (Hematoxylin & Eosin staining) was observed under microscope. The two-washout model fitted the experimental TACs well for five of six nude-rats irradiation studies. The observed k2m of tumor irradiation was 0.31+/-0.04 min-1, which was consistent with the normal tissue irradiation. While k2s of tumor irradiation was faster (0.017 +/-0.002 min-1) than that of normal tissue irradiation (0.006 +/-0.002 min-1). These results suggested that the component, which was trapped in normal tissue, diffused out more smoothly from tumor tissue due to vascular hyperpermeability which characterizes pathological tumor-angiogenesis. For one of six nude rats, only slow washout component (k2s = 0.014 +/-0.003 min-1) was observed in tumor irradiation study. Necrosis in tumor was observed in pathological tissue sample of this nude rat. It is also suggested that the decrease of washout rate was caused by the decrease of blood flow in the necrotic region. We measured the biological washout rate of irradiated 11C ion beam in tumor tissue and normal tissue. The physiological difference of tissue condition reflected the biological washout rates. This effect may be used as a clinical diagnostic index to monitor the dose response of the tumors in individual patients as well as the observation of the functional metabolism of tumor.

Real-Time PET Imaging for Range Verification of Helium Radiotherapy

Real-time range verification of particle beams is important for optimal exploitation of the tissue-sparing advantages of particle therapy. Positron Emission Tomography (PET) of the beam-induced positron emitters such as 15O (T1/2 = 122 s) and 11C (T1/2 = 1223 s) has been used for monitoring of therapy in both clinical and preclinical studies. However, the half-lives of these nuclides preclude prompt feedback, i.e., on a sub-second timescale, on dose delivery. The in vivo verification technique relying on the in-beam PET imaging of very short-lived positron emitters such as 12N (T1/2 = 11 ms), recently proposed and investigated in feasibility experiments with a proton beam, provides millimeter precision in range measurement a few tens of milliseconds after the start of an irradiation. With the increasing interest in helium therapy, it becomes relevant to study the feasibility of prompt feedback using PET also for helium beams. A recent study has demonstrated the production of very short-lived nuclides (T1/2 = 10 ms attributed to 12N and/or 13O) during irradiation of water and graphite with helium ions. This work is aimed at investigating the range verification potential of imaging these very short-lived nuclides. PMMA targets were irradiated with a 90 AMeV 4He pencil beam consisting of a series of pulses of 10 ms beam-on and 90 ms beam-off. Two modules of a modified Siemens Biograph mCT PET scanner (21 × 21 cm2), installed 25 cm apart, were used to image the beam-induced PET activity during the beam-off periods. For the irradiation of PMMA, we identify the very short-lived activity earlier observed to be 12N (T1/2 = 11.0 ms). The range precision determined from the 12N activity profile that is measured after just one beam pulse was found to be 9.0 and 4.1 mm (1σ) with 1.3 × 1074He ions per pulse and 6.6 × 1074He ions per pulse, respectively. When considering 4.0 × 1074He ions, which is about the intensity of the most intense distal layer spot in a helium therapy plan, a range verification precision in PMMA of 5.7 mm (1σ) can be realized. The range precision scales approximately with the inverse square root of the number of 4He ions, i.e., the relative statistical accuracy of the number of coincidence events. Thus, when summing data over about 10 distal layer spots, this study shows good prospects for obtaining 1.8 mm (1σ) precision in range verification, within 50 ms after the start of a helium irradiation by in-beam PET imaging (scanner 29% solid angle) of 12N.

Biological washout effect in in-beam PET: animal studies

Positron emission tomography (PET) is a practical tool for range verification of hadron therapy. As well, the quantitative washout of the positron emitters has a potential usefulness as a diagnostic index, but the modelling for this has not been established. In this study, we measured washout rates of rabbit brain and performed kinetic analysis to explore the washout mechanism. Six rabbit brains were irradiated by 11C and 15O ion beams, and dynamic PET scan was performed using our original depth of interest (DOI)-PET prototype. The washout rate was obtained based on the two-compartment model, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2, k3 and k4 of 11C were 0.086, 0.137 and 0.007 min−1, and those of 15O were 0.502, 0.360 and 0.007 min−1, respectively. It was suggested permeability of a molecule containing 11C atoms might be regulated by a transporter. The k2 of 15O was comparable with 15O-water. This study provides basic data for modelling of the washout effect.