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Verification of high energy photon therapy based on PET/CT imaging of photonuclear reactions
Stockholm University, Faculty of Science, Department of Physics. (Medicinsk Strålningsfysik)
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

For classical and intensity modulated radiation therapy of deep-seated tumors, high-energy photons are the optimal radiation modality from an integral dose point of view. By using narrow scanned beams the treatment outcome can be improved substantially by delivering biologically optimized intensity modulated distributions often with sharp dose gradients. This requires using photons with energies well above 15 MV enabling verification of the treatment delivery in vivo by PET/CT imaging in a manner not previously possible. This new technique is based on the production of positron emitting radionuclides when the incoming high-energy photons interact through photonuclear reactions with the body tissues. The produced radionuclides, commonly 11C, 15O and 13N can then be monitored by PET and the distribution of activated nuclei show exactly where the radiation has penetrated the patient. In the subcutaneous fat, present in all humans, a high induced activity produces a perfect visualization of the location and even the intensity modulation of the incident beams. The reason for this is the high carbon content in combination with a low biological perfusion in fat tissues. Errors in the patient positioning such as setup errors or misplacement of the beams will thus show up in the PET images as a deviation from the actual radiation treatment plan. Interestingly, the imaged activity distribution from the subcutaneous fat also visualizes how the dose delivery can be deformed when the patient is erroneously positioned on the treatment couch as seen on the cover figure. Furthermore, the different half-lives of the produced radionuclides (20 min, 2 min, and 10 min, for 11C, 15O and 13N, respectively) allows for analysis of the dynamic behavior of tissue activity with the possibility of retrieving information such as tissue composition, biological and physical half-lives. The present thesis shows that considerable clinical information regarding the treatment delivery with high-energy photon beams can be obtained using PET/CT imaging. Although the study is based on the use of 50 MV photons the method may apply for beams with energies > 20 MV at higher doses.

Place, publisher, year, edition, pages
Stockholm: Department of Physics, Stockholm University , 2012. , 49 p.
Keyword [en]
Photonuclear reactions, PET/CT treatment verification, High-energy photon therapy
National Category
Natural Sciences
Research subject
Medical Radiation Physics
Identifiers
URN: urn:nbn:se:su:diva-72385ISBN: 978-91-7447-461-9 (print)OAI: oai:DiVA.org:su-72385DiVA: diva2:496800
Public defence
2012-03-09, föreläsningssalen, Radiumhemmet, Karolinska universitetssjukhuset, Solna, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 3: Submitted. Paper: Manuscript.

Available from: 2012-02-16 Created: 2012-02-09 Last updated: 2017-10-11Bibliographically approved
List of papers
1. Development of dose delivery verification by PET imaging of photonuclear reactions following high energy photon therapy
Open this publication in new window or tab >>Development of dose delivery verification by PET imaging of photonuclear reactions following high energy photon therapy
2006 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 51, no 22, 5769- p.Article in journal (Refereed) Published
Abstract [en]

A method for dose delivery monitoring after high energy photon therapy has been investigated based on positron emission tomography (PET). The technique is based on the activation of body tissues by high energy bremsstrahlung beams, preferably with energies well above 20 MeV, resulting primarily in 11C and 15O but also 13N, all positron-emitting radionuclides produced by photoneutron reactions in the nuclei of 12C, 16O and 14N. A PMMA phantom and animal tissue, a frozen hind leg of a pig, were irradiated to 10 Gy and the induced positron activity distributions were measured off-line in a PET camera a couple of minutes after irradiation. The accelerator used was a Racetrack Microtron at the Karolinska University Hospital using 50 MV scanned photon beams. From photonuclear cross-section data integrated over the 50 MV photon fluence spectrum the predicted PET signal was calculated and compared with experimental measurements. Since measured PET images change with time post irradiation, as a result of the different decay times of the radionuclides, the signals from activated 12C, 16O and 14N within the irradiated volume could be separated from each other. Most information is obtained from the carbon and oxygen radionuclides which are the most abundant elements in soft tissue. The predicted and measured overall positron activities are almost equal (−3%) while the predicted activity originating from nitrogen is overestimated by almost a factor of two, possibly due to experimental noise. Based on the results obtained in this first feasibility study the great value of a combined radiotherapy–PET–CT unit is indicated in order to fully exploit the high activity signal from oxygen immediately after treatment and to avoid patient repositioning. With an RT–PET–CT unit a high signal could be collected even at a dose level of 2 Gy and the acquisition time for the PET could be reduced considerably. Real patient dose delivery verification by means of PET imaging seems to be applicable provided that biological transport processes such as capillary blood flow containing mobile 15O and 11C in the activated tissue volume can be accounted for.

National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging Other Medical Sciences
Identifiers
urn:nbn:se:su:diva-72543 (URN)10.1088/0031-9155/51/22/004 (DOI)
Available from: 2012-02-14 Created: 2012-02-14 Last updated: 2017-12-07Bibliographically approved
2. Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy
Open this publication in new window or tab >>Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy
Show others...
2013 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 16, 5541-5553 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 +/- (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about 20 times lower than that of a patient undergoing standard F-18-FDG treatment. When using a combination of short lived nuclides such as O-15 (half-life: 2 min) and C-11 (half-life: 20 min) with low activity it is not optimal to use clinical reconstruction protocols. Thus, it might be desirable to further optimize reconstruction parameters as well as to address hardware improvements in realizing in vivo treatment verification with PET/CT in the future. A significant improvement with regard to O-15 imaging could also be expected by having the PET/CT unit located close to the radiation treatment room.

National Category
Radiology, Nuclear Medicine and Medical Imaging Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:su:diva-93559 (URN)10.1088/0031-9155/58/16/5541 (DOI)000322775300015 ()
Note

AuthorCount:9;

Available from: 2013-09-11 Created: 2013-09-10 Last updated: 2017-10-11Bibliographically approved
3. Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50 MV photon radiation therapy
Open this publication in new window or tab >>Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50 MV photon radiation therapy
Show others...
(English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667Article in journal (Other academic) Submitted
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:su:diva-72557 (URN)
Available from: 2012-02-14 Created: 2012-02-14 Last updated: 2017-12-07Bibliographically approved
4. Fast IMRT with narrow high energy scanned photon beams
Open this publication in new window or tab >>Fast IMRT with narrow high energy scanned photon beams
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2011 (English)In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 38, no 8, 4774-4784 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: Since the first publications on intensity modulated radiation therapy (IMRT) in the early 1980s almost all efforts have been focused on fairly time consuming dynamic or segmental multileaf collimation. With narrow fast scanned photon beams, the flexibility and accuracy in beam shaping increases, not least in combination with fast penumbra trimming multileaf collimators. Previously, experiments have been performed with full range targets, generating a broad bremsstrahlung beam, in combination with multileaf collimators or material compensators. In the present publication, the first measurements with fast narrow high energy (50 MV) scanned photon beams are presented indicating an interesting performance increase even though some of the hardware used were suboptimal. Methods: Inverse therapy planning was used to calculate optimal scanning patterns to generate dose distributions with interesting properties for fast IMRT. To fully utilize the dose distributional advantages with scanned beams, it is necessary to use narrow high energy beams from a thin bremsstrahlung target and a powerful purging magnet capable of deflecting the transmitted electron beam away from the generated photons onto a dedicated electron collector. During the present measurements the scanning system, purging magnet, and electron collimator in the treatment head of the MM50 racetrack accelerator was used with 3-6 mm thick bremsstrahlung targets of beryllium. The dose distributions were measured with diodes in water and with EDR2 film in PMMA. Monte Carlo simulations with GEANT4 were used to study the influence of the electrons transmitted through the target on the photon pencil beam kernel. Results: The full width at half-maximum (FWHM) of the scanned photon beam was 34 mm measured at isocenter, below 9.5 cm of water, 1 m from the 3 mm Be bremsstrahlung target. To generate a homogeneous dose distribution in a 10 x 10 cm(2) field, the authors used a spot matrix of 100 equal intensity beam spots resulting in a uniformity of collimated 80%-20% penumbra of 9 mm at a primary electron energy of 50 MeV. For the more complex cardioid shaped dose distribution, they used 270 spots, which at a pulse repetition frequency of 200 Hz is completed every 1.36 s. Conclusions: The present measurements indicate that the use of narrow scanned photon beams is a flexible and fast method to deliver advanced intensity modulated beams. Fast scanned photon IMRT should, therefore, be a very interesting modality in the delivery of biologically optimized radiation therapy with the possibility for in vivo treatment verification with PET-CT imaging.

Keyword
IMRT, scanned photon beams, Monte Carlo
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:su:diva-69259 (URN)10.1118/1.3615059 (DOI)000293417500038 ()
Note
authorCount :5 Affiliation for 4 of the authors of the Stockholm University: Department of Medical Radiation Physics, Karolinska Institutet and Stockholm UniversityAvailable from: 2012-01-12 Created: 2012-01-11 Last updated: 2017-12-08Bibliographically approved
5. PET/CT measurements and GEANT4 simulations of the inducedpositron activity from high energy scanned photon beams
Open this publication in new window or tab >>PET/CT measurements and GEANT4 simulations of the inducedpositron activity from high energy scanned photon beams
(English)Manuscript (preprint) (Other academic)
National Category
Radiology, Nuclear Medicine and Medical Imaging Medical Engineering Cancer and Oncology
Identifiers
urn:nbn:se:su:diva-72559 (URN)
Available from: 2012-02-14 Created: 2012-02-14 Last updated: 2012-02-16Bibliographically approved

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