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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 9  |  Page : 416-420

Positron imaging for verification of irradiation field during radiotherapy


1 Department of Oral and Maxillofacial-Head and Neck Oncology, Division of Radiation Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2 Department of Radiation Oncology, Wuxi Yiren Tumor Hospital, Jiangsu, China

Date of Web Publication29-Jun-2018

Correspondence Address:
Zhi-Yuan Zhang
Department of Oral and Maxillofacial-Head and Neck Oncology, Division of Radiation Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.179081

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 > Abstract 

Aim of Study: The present study was designed to investigate the application of positron images from photonuclear reactions to verify the location of targeted radiation in vivo.
Materials and Methods: The phantom study was conducted with distilled water, porcine muscle, porcine adipose tissue, and graphite; these subjects were irradiated separately with 50 MV photons generated by an MM50 Racetrack Microtron. The positron emission activity was measured using a Geiger counter, and the radioactive decay curves for each of the irradiated materials were then established. The positron emission tomography (PET) images of the three tissue models were also achieved using the same radiation conditions. The in vivo PET imaging study was also conducted in tumor-bearing rabbits.
Results: Our results demonstrated that the PET imaging could be used to verify the position of the irradiation field in vivo. The dose distribution images of photonuclear reactions of 11 C and 15 O were uniform, using 2-Gy 50 MV photons.
Conclusions: The factors influencing the half-life of radiation activity in various tissues were different from the first order kinetic reaction in physics.

Keywords: 50 MV, location verification, photonuclear reaction, positron imaging


How to cite this article:
Tu WY, Zhang ZY, Jun Z, Xu XL, Ding JP, Su JH, Chen ZM. Positron imaging for verification of irradiation field during radiotherapy. J Can Res Ther 2018;14, Suppl S2:416-20

How to cite this URL:
Tu WY, Zhang ZY, Jun Z, Xu XL, Ding JP, Su JH, Chen ZM. Positron imaging for verification of irradiation field during radiotherapy. J Can Res Ther [serial online] 2018 [cited 2019 Jul 21];14:416-20. Available from: http://www.cancerjournal.net/text.asp?2018/14/9/416/179081


 > Introduction Top


Radiation therapy represents one of the most efficacious therapies in the treatment of solid tumors. There are many factors affecting the radiation dose delivery and outcome of the therapy, such as beam set-up, patient motion, and changes in anatomical position. These uncertainties are particularly important in the case of intensity modulated radiation therapy [1] and image-guided radiation therapy. For instance, a small misalignment of the radiation treatment may cause serious tissue damage. Therefore, there is an urgent need for developing an precise and sensitive system for monitoring radiation location and dosimetry to ensure high-quality delivery of radiotherapy.[2]

Radiological images from X-rays, computed tomography (CT), and magnetic resonance imaging have been used to evaluate the therapeutic effects of radiotherapy.[3],[4] The electronic portal imaging device is a novel portal imaging device for monitoring anatomical position,[5] but it cannot display the final shape of the delivered radiation beam in vivo. Positron emission tomography (PET)/CT imaging can better evaluate the therapeutic effects of radiotherapy than other imaging modalities because it not only reveals the anatomical structures of organs, but also reveals their biological functions.[6] PET/CT is also useful in determining the efficacy of radiotherapy by monitoring the abnormal features (receptors and sugar metabolism) of tumor cells.[7] PET/CT imaging is being increasingly used in radiotherapy for the guidance of radiation to biological targets.[8],[9] However, PET imaging requires tissue labeling using a positron-emitting radionuclide, and different imaging agents are required for different tissues. Therefore, the marker technology itself should be considered a fatal flaw in molecular imaging. The labeled tracers (or probes) need to be chemically synthesized and the structure of these tracers may be changed in vivo, after administered. In addition, the vast majority of newly synthesized tracers are eliminated as clinical candidates during preclinical evaluation.[10]

Positron emissions are primarily produced by (γ, n) reactions and the threshold energy is in the range of 11–18 MV.[11] High energy 50 MV photons may excite the nuclei because of photonuclear reactions.[11] Depending on the feature of the irradiated tissue and the photon energy spectrum applied, nuclei emit nuclear particles, such as neutrons, protons, alpha particles, and 3 He, and positron-emitting radionuclides, such as 11 C,13 N, and 15 O, which are the primary nuclides produced in biological tissues following irradiation with high energy photon beams.[12],[13] The first attempt to perform positron emission imaging took place at Lawrence Berkeley Laboratory.[14],[15] Müller and Enghardt subsequently confirmed the feasibility of positron emission imaging during photon therapy.[16] The positron image produced by (γ, n) reactions may be affected by many factors, such as the size and depth of the irradiation field, radiation dose, tissue composition, and acquisition time; thus, positron imaging from photonuclear reactions cannot be effectively applied at the clinical level.

To solve this problem, we evaluated some of the influencing factors in vivo, verifying the targeting of radiation, by means of positron imaging of photonuclear reactions generated by 50 MV photons. We determined the half-life (T1/2) for the positron imaging involving a phantom. After photon irradiation, positron images of 11 C,15 O, and 13 N isotopes from the tissues were analyzed. A tumor-bearing rabbit model was used for the in vivo positron imaging study. We believe that the results from the present study will facilitate the development of positron imaging as clinically useful imaging approach to improve the efficacy and safety of radiation therapy.


 > Materials and Methods Top


Equipment

In the present study, 50 MV X-rays were generated using the MM50 Racetrack Microtron accelerator (IBA, Louvain, Belgium). The accelerator has a photon energy range of 10–50 MV. A Discovery LS PET/CT and a Geiger counter (GE, Fairfield, CT, USA) were used to carry out the imaging study. The PET scans were performed in a two-dimensional (2D) fashion. The emission data were reconstructed by means of an iterative reconstruction algorithm using two iterations and eight subsets. The transmission scans for the correction of attenuation were performed with 68-Ge rod sources and reconstructed using filtered back projection. During postprocessing, various corrections were applied, such as for random scatter, attenuation, and dead time.

Phantom

The phantom used in the study was made from polymethyl methacrylate, with a length and width of 10 cm × 10 cm, and divided into three chambers [Figure 1]. The up chamber (A chamber) and the low chamber (C chamber) were filled with distilled water to a depth of 5 cm. The thickness of the middle layer (B chamber) was 10 cm. The experimental subjects/tissues including distilled water (50 g), porcine muscle (50 g), porcine fat (50 g), and graphite (50 g), were placed separately in the B chamber and irradiated. The phantom was irradiated at a field size of 10 cm × 10 cm and a source-to-surface distance of 100 cm. The radiation dose delivered using 50 MV X-rays was 2-Gy for each subject.
Figure 1: The design of phantom used in the present study. The phantom was divided into three chambers (A, B, and C). The experimental tissues were separately placed into the B chamber (A and C chambers were filled with water). The phantom was irradiated at a field size of 10 cm × 10 cm and a source-to-surface distance of 100 cm at the direction as indicated by the arrow

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Detection of the radiation activity

The radiation activity (uSV/h) was monitored using a Geiger counter, beginning at 1 min after the electron cyclotron stopped and continuing once per min over a period of 30 min. Since graphite consists of carbon and only 11 C, with a known half-life, could be produced after irradiation, it was used as the calibration material to study the half-life period in the present study.

Acquiring positron emission tomography imaging for the three tissue models

The experimental tissues were each separately placed in the B chamber and irradiated as detailed above. At approximately 1 min after the 50 MV X-ray beam was shut down, a PET scan was initiated with a field size of 10 cm × 10 cm, and PET imaging was successively achieved for three periods every 10 min.

Rabbit VX2 tumor model

All animal experiments were performed in accordance with a protocol approved by our Institutional Animal Care and Use Committee and were in compliance with institutional guidelines. The forelimbs of New Zealand White rabbits were implanted with 1 mm fragments of VX2 tumors harvested from the hind legs of carrier rabbits. When the tumors reached 1 cm in diameter, the tumor-bearing rabbits were used for experimentation (on average, 14 days after tumor implantation).

The tumor-bearing rabbit was anaesthetized so that the three-dimensional (3D) coordinates could be determined using a laser lamp. Four rows of the GE Discovery LS large aperture CT were used to acquire anatomical images with a scanned thickness of 2.5 mm. The CT reconstruction images were transmitted over the local area network to the CMS-XIO radiation treatment planning system (TPS) (XIO-4.33.02). A treatment plan was made using the CMS system and the planned radiation dose for specific points was marked. Then, the rabbit was secured on the couch of the MM50 Racetrack Microtron and the tumor irradiated using a 50 MV X-ray beam at a dose of 2-Gy. The interval between the end of irradiation and placement of the PET apparatus for imaging was 60 s.

Moreover, the PET imaging signals were time-dependent; the shorter the time from irradiation to scanning using the PET instrument, the higher the signal captured. Therefore, the time taken for image acquisition must be standardized in clinical practice. In the present in vivo study, the time interval from irradiation to PET imaging was 60 s. The parameters involved in PET/CT (CT 140 kV) imaging were as follows: 200 mA, a PET E scan time of 1200 s; a T scan time of 900 s; and a maximum system resolution of 2 mm in 2D or 3D modes. All data were collected and transferred to a PET workstation for reconstruction; the matrix was 256 × 256.


 > Results Top


Radioactivity decay curves

The relationship between the radiation intensity determined from the tissue model experiments and the time after irradiation was found to be an exponential decay [Figure 2]. According to the results obtained from semi-logarithmic plots during the first 10 min [Figure 2], the radioactivity equations were y = 74.888e −0.3434t, R2 = 0.994, for distilled water; y = 54.837e −0.3301t, R2 = 0.9993, for muscle tissue; and y = 24.064e −0.2895t, R2 = 0.9996, for adipose tissue, respectively. The T1/2 values were 2.04, 2.11, 2.39, and 20.09 min for distilled water, porcine muscle, adipose tissue, and graphite, respectively. The result from the graphite calibration material was close to the theoretical value of 20.4 min, and the measurement for distilled water was equivalent to homogeneous oxygen.[17] These results confirmed the reliability of the models and the experimental data in the present study.
Figure 2: Radioactivity decay profiles. The radioactivity decay curves were obtained for the various tissue models after 2-Gy irradiation with a 50 MV photon beam a source-to-surface distance of 100 cm

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Positron emission tomography tissue images

PET images from the three model tissues obtained during the first 30 min after irradiation are shown in [Figure 3]. During the first 10 min, the structures of the tissue models were clearly visible on PET images. During the second 10 min, the muscle and adipose tissues remained visible, but distilled water was almost invisible. It was impossible to detect distilled water on the PET images during the third 10 min, when the muscle and adipose tissues remained clearly visible.
Figure 3: Positron emission tomography images. The positron emission tomography images were obtained from three tissue models over three separate time periods after 2-Gy irradiation with 50 MV X-rays

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Images in tumor-bearing rabbits

The tumor-bearing rabbits were irradiated by 2-Gy 50 MV X-rays. The shape and area from different irradiated regions were compared using pseudo-color technology according to the different weights of planned dose and PET counts. [Figure 4]a shows the treatment area from TPS image, with the red lines indicating the target area. [Figure 4]b displays the PET images, which shows a clear and uniform irradiation range and shape of the positron emission radionuclide. Compared with the positron imaging, the range of 90% isodose lines on the TPS image was highly consistent and the deviation was mainly on the inner side of the target area.
Figure 4: Positron emission tomography images in the rabbit tumor model. Images of the irradiation field were obtained using (a) treatment planning system and (b) positron emission tomography. High conformity in accurate positioning and uniform dose distribution can be seen

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 > Discussion Top


There have been several methods for accurate monitoring of patient positioning during radiotherapy, such as mill volt CT,[18] CT in the treatment room,[19] and kilovolt CT mounted on a linac gantry;[20],[21] gated irradiation with an air bag sensor, CCD camera, laser sensor, and other techniques to monitor the patient's breathing cycle;[22] real-time embedded-marker detection using fluoroscopy;[23] and real-time image correlation of 3D ultrasonographic images.[24] The introduction of PET and hybrid PET/CT imaging has brought a revolutionary change in the field because PET/CT imaging can reveal anatomical structures and biological functions more clearly than other approaches.[25],[26] Recently, the use of a PET camera for monitoring beam delivery has been proposed and developed by several groups.[2],[27] The utility of PET-CT at 50 MV has been proposed,[28] and the Monte Carlo calculation results have also been reported for in-beam PET imaging.[16] Several simulation and experimental studies have investigated the dose verification immediately after treatment, using PET imaging of positron-emitting nuclei generated by a high energy photon beam.[29],[30] Determination of the absorbed doses from the radioactivity induced in silver by radiation, when measured using a PET scanner, has been studied as an aid to quality assurance in radiotherapy.[31] However, to our best knowledge, there is no report on verification of the location of radiation, using positron imaging of photonuclear reactions generated by 50 MV X-rays in vivo.

C, N, and O, the building blocks of all living organisms, may have different contents in different tissues.[13] The carbon contents are 0%, 14.3%, and 59.8% in water, muscle, and adipose tissues, respectively, while the oxygen contents in these models are 88.8%, 71.0%, and 27.8%, respectively. For photon energies above 30 MV, the processes involved are photo neutron and photo proton production.[12] The photo neutron reaction is the main reaction of interest, since photo proton reactions do not generate positron-emitting radionuclides. The positron-emitting radionuclides produced are 12 C(γ, n) 11 C,14 N(γ, n) 13 N,16 O(γ, n) 15 O,31 P(γ, n) 30 P and 40 Ca(γ, n) 39 Ca, with the T1/2 values being 20.4, 9.97, 2.04, 2.50, and 0.86 s, respectively. Thus, the radionuclides have different decay times. In the present study, we found that the T1/2 values of distilled water and graphite were 2.04 and 20.09 min, respectively, which were very close to the theoretical values calculated using the decay law of homogeneous oxygen and graphite,[17] confirming that they could be used as calibration substances for PET imaging. The radioactivity equations were y = 54.837e −0.3301t, R2 = 0.9993, for muscle tissue; and y = 24.064e −0.2895t, R2 = 0.9996, for adipose tissue, respectively. The T1/2 values for muscle and adipose tissues were 2.11 and 2.39 min, respectively. Thus, the radiation activity data indicated an exponential decay that could be calculated using the formula “A = A0e γt.” Therefore, this tissue exponential decay function during the first 10 min resulted in a straight line on a semi-logarithmic plot.

We also found that the radiation activity of the three tissue models used in our study decreased at different rates. Coincidently, at the 10th min, the activity counts were approximately equal and subsequently continued to decrease. Moreover, the counts for distilled water, predominantly from 15 O, decreased the fastest, followed by muscle and adipose tissue (oxygen lowest ratio). Therefore, the degree of attenuation of intensity within the first 10 min mainly depended on the proportion of oxygen present. At approximately 16.32 min (eight T1/2 periods for 15 O), the radiation contribution from 15 O was only 0.39%, and therefore, after this time point, the activity signals from the muscle and adipose tissue were mainly related to the carbon isotopes. Indeed, our measurements indicated that after 16 min, the T1/2 values of fat and muscle tissues were 20.6 and 20.11 min, respectively, and that the T1/2 values of the tissues increased progressively, with the T1/2 being longer than the T1/2 that preceded it. Therefore, the T1/2 of tissue would depend on the contents of different elements present and its initial state.

The above analysis was further confirmed by PET images [Figure 3]. During the first 10 min, distilled water formed a uniform image, but its intensity decreased rapidly because of the predominance of 15 O, which had a short T1/2. The muscle tissue could be observed during the entire 30 min, and image intensity declined slowly. The adipose tissue still had a high-intensity image at 30 min after irradiation, with a much slower decline in density. The reason for this would be that the amount of 11 C present in the adipose tissue was significantly higher than that in the muscle tissue. In summary, the signals from the positron-emitting radionuclides 12 C (γ, n) 11 C and 16 O(γ, n) 15 O within the irradiated fields can be labeled in almost any organic matter.

Our comparison of the images from TPS and PET indicated high conformity in the position and uniformity of dose distribution in the rabbit VX2 tumor model [Figure 4]. PET images obtained after irradiation due to photonuclear reactions had a higher degree of clarity. Therefore, by analyzing the PET images, the beam track and irradiation location could be determined. Findings from our study indicated that PET images produced as a result of positron activity could have an important clinical value in monitoring the accuracy of radiotherapy in patients.


 > Conclusions Top


In the present study, we used in vitro and in vivo models to demonstrate that the positron imaging could detect high-intensity signals from 11 C and 15 O in tissues after irradiation with 50 MV X-rays, at a conventional dose level of 2-Gy. PET image could be used to analyze the isotope content in tissue in terms of different decay times and the intensity distribution of 11 C and 15 O.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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