Kira Grogg

Mapping 15O Production Rate for Proton Therapy Verification

PURPOSE This work was a proof-of-principle study for the evaluation of oxygen-15 ((15)O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion. METHODS AND MATERIALS Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions. A differential equation was fitted to phantom and in vivo data, yielding estimates of (15)O production and clearance rates, which were compared to live versus dead rates for the rabbit and to Monte Carlo predictions. RESULTS PET clearance rates agreed with decay constants of the dominant radionuclide species in 3 different phantom materials. In 2 oxygen-rich materials, the ratio of (15)O production rates agreed with the expected ratio. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using (15)O decay constant, whereas the live thigh activity decayed faster. Most importantly, the (15)O production rates agreed within 2% (P>.5) between conditions. CONCLUSIONS We developed a new method for quantitative measurement of (15)O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of (15)O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, (15)O clearance rates may be useful in monitoring permeability changes due to therapy.

Feasibility of using distal endpoints for In-room PET Range Verification of Proton Therapy

In an effort to verify the dose delivery in proton therapy, Positron Emission Tomography (PET) scans have been employed to measure the distribution of β+ radioactivity produced from nuclear reactions of the protons with native nuclei. Because the dose and PET distributions are not directly comparable, the range verification is currently carried out by comparing measured and Monte Carlo (MC) simulation predicted PET distributions. In order to reduce the reliance on MC, MC-PET and dose distal endpoints were compared to explore the feasibility of using distal endpoints for in-room PET range verification. MC simulations were generated for six head and neck patients with corrections for radiological decay, biological washout, and PET resolution. One-dimensional profiles of the dose and MC-PET were examined along the direction of the beam and covering the cross section of the beam. The chosen endpoints of the MC-PET (y-intercept of the linear fit to the distal falloff) and MC dose (20-50% of maximum dose) correspond to where most of the protons are below the threshold energy for the nuclear reactions. The difference in endpoint range between the distal surfaces of the dose and MC-PET are compared and the spread of range differences are assessed. Among the six patients, the mean difference between MC-PET and dose depth was found to be -1.5 mm to +3.7 mm between patients, with a standard deviation of 1.3 to 6 mm across the individual beams.

National Electrical Manufacturers Association and Clinical Evaluation of a Novel Brain PET/CT Scanner

The aim of this study was to determine the performance of a novel mobile human brain/small-animal PET/CT system. The scanner has a 35.7-cm-diameter bore and a 22-cm axial extent. The detector ring has 7 modules each with 3 × 4 cerium-doped lutetium yttrium orthosilicate crystal blocks, each consisting of 22 × 22 outer-layer and 21 × 21 inner-layer crystals, each layer 1-cm thick. Light is collected by 12 × 12 silicon photomultipliers. The integrated CT can be used for attenuation correction and anatomic localization. The scanner was designed as a low-cost device that nevertheless produces high-quality PET images with the unique capability of battery-powered propulsion, enabling use in many settings. Methods: Spatial resolution, sensitivity, and noise-equivalent counting rate were measured based on the National Electrical Manufacturers Association NU2-2012 procedures. Reconstruction was done with tight energy and timing cuts—400–650 keV and 7 ns—and loose cuts—350–700 keV and 10 ns. Additional image quality measurements were made from phantom, human, and animal studies. Performance was compared with a reference scanner with comparable imaging properties. Results: The full width at half maximum transverse resolution at a 1-cm (10-cm) radius was 3.2 mm (5.2-mm radial, 3.1-mm tangential), and the axial resolution was 3.5 mm (4.0 mm). A sensitivity of 7.5 and 11.7 kcps/MBq at the center for tight and loose cuts, respectively, increased to 8.8 and 13.9 kcps/MBq, respectively, at a 10-cm radial offset. The maximum noise-equivalent counting rate of 19.5 and 22.7 kcps for tight and loose cuts, respectively, was achieved for an activity concentration of 2.9 kBq/mL. Contrast recovery for 4:1 hot cylinder to warm background was 76% for the 25-mm-diameter cylinder but decreased with decreasing cylinder size. The quantitation agreed within 2% of the known activity distribution and concentration. Brain phantom and human scans have shown agreement in SUVs and image quality with the reference scanner. Conclusion: We characterized the performance of the NeuroPET/CT and showed images from the first human studies. The study shows that this scanner achieves good performance when spatial resolution, sensitivity, counting rate, and image quality along with a low cost and unique mobile capabilities are considered.

A Recommendation on How to Analyze In-Room PET for In Vivo Proton Range Verification Using a Distal PET Surface Method

We describe the rationale and implementation of a method for analyzing in-room positron emission tomography (PET) data to verify the proton beam range. The method is based on analyzing distal PET surfaces after passive scattering proton beam delivery. Typically in vivo range verification is done by comparing measured and predicted PET distribution for a single activity level at a selected activity line along the beam passage. In the method presented here, we suggest using a middle point method based on dual PET activity levels to minimize the uncertainty due to local variations in the PET activity. Furthermore, we introduce 2-dimensional (2D) PET activity level surfaces based on 3-dimensional maps of the PET activities along the beam passage. This allows determining not only average range differences but also range difference distributions as well as root mean square deviations (RMSDs) for a more comprehensive range analysis. The method is demonstrated using data from 8 patients who were scanned with an in-room PET scanner. For each of the 8 patients, the average range difference was less than 5 mm and the RMSD was 4 to 11 mm between the measured and simulated PET activity level surfaces for single-field treatments. An ongoing protocol at our institution allows the use of a single field for patients being imaged for the PET range verification study at 1 fraction during their treatment course. Visualizing the range difference distributions using the PET surfaces offers a convenient visual verification of range uncertainties in 2D. Using the distal activity level surfaces of simulated and measured PET distributions at the middle of 25% and 50% activity level is a robust method for in vivo range verification.

Feasibility study of using fall-off gradients of early and late PET scans for proton range verification

Purpose While positron emission tomography (PET) allows for the imaging of tissues activated by proton beams in terms of monitoring the therapy administered, most endogenous tissue elements are activated by relatively high‐energy protons. Therefore, a relatively large distance off‐set exists between the dose fall‐off and activity fall‐off. However, 16O(p,2p,2n)13N has a relatively low energy threshold which peaks around 12 MeV and also a residual proton range that is approximately 1 to 2 mm. In this phantom study, we tested the feasibility of utilizing the 13N production peak as well as the differences in activity fall‐off between early and late PET scans for proton range verification. One of the main purposes for this research was developing a proton range verification methodology that would not require Monte Carlo simulations. Methods and materials Both monoenergetic and spread‐out Bragg peak beams were delivered to two phantoms — a water‐like gel and a tissue‐like gel where the proton ranges came to be approximately 9.9 and 9.1 cm, respectively. After 1 min of postirradiation delay, the phantoms were scanned for a period of 30 min using an in‐room PET. Two separate (Early and Late) PET images were reconstructed using two different postirradiation delays and acquisition times; Early PET: 1 min delay and 3 min acquisition, Late PET: 21 min delay and 10 min acquisition. The depth gradients of the PET signals were then normalized and plotted as functions of depth. The normalized gradient of the early PET images was subtracted from that of the late PET images, to observe the 13N activity distribution in relation to depth. Monte Carlo simulations were also conducted with the same set‐up as the measurements stated previously. Results The subtracted gradients show peaks at 9.4 and 8.6 cm in water‐gel and tissue‐gel respectively for both pristine and SOBP beams. These peaks are created in connection with the sudden change of 13N signals with depth and consistently occur 2 mm upstream to where 13N signals were most abundantly created (9.6 and 8.8 cm in water‐gel and tissue‐gel, respectively). Monte Carlo simulations provided similar results as the measurements. Conclusions The subtracted PET signal gradient peaks and the proton ranges for water‐gel and tissue‐gel show distance off‐sets of 4 to 5 mm. This off‐set may potentially be used for proton range verification using only the PET measured data without Monte Carlo simulations. More studies are necessary to overcome various limitations, such as perfusion‐driven washout, for the feasibility of this technique in living patients.

MO-A-213AB-07: Evaluation of Distal Dose Surface with In-Room PET for Proton Therapy Monitoring

PURPOSE The objective of this study is to evaluate the feasibility of proton beam treatment verification using in-room PET. As of February 2012, four patients have been studied in a clinical trial. In addition, we suggest a new method comparing the distal surface of the measured and simulated PET activities to verify the location of the distal dose surface. METHODS Patients were scanned for 20 minutes with an in-room PET positioned next to the proton treatment head in a gantry room for beam delivery using passive scattering. The time between end of treatment and the start of the scan was within about 2 minutes. The predicted distribution of the PET activities and the proton dose distributions in the patients were also calculated using Monte Carlo (MC). Along the beam direction, the 50% fall-off positions of the maximum PET activity at each line profile were compared with the MC simulated and the measured PET images, and then the differences were assessed with root-mean-square deviation (RMSD) and mapped in the beams eye view. RESULTS The measured PET images showed a good spatial correlation with the simulated PET images and the proton dose distributions even though the treated volumes and locations varied between patients. The RMSD values, representing the surface differences between the measured and simulated PET, were assessed to be 4.3-5.1 mm for four patients. Some region including the penumbra showed larger differences but was excluded. CONCLUSIONS We have explored the potential of the in-room PET for proton therapy monitoring through a clinical trial. The PET image analysis method based on MC simulations showed that the distal dose surface could be determined within a few millimeters but not within the aimed accuracy of 2-3 mm. Improvements in PET-CT image registration and biological washout modeling will most likely increase the accuracy further. NIH/NCI P01 CA021239.