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Yves De Deene Homepage: Radiation Dosimetry

Radiation Dosimetry

Introduction

High-precision conformal radiation treatments such as intensity-modulated radiotherapy (IMRT) and dynamic treatment deliveries such as as Intensity Modulated Arc Therapy (IMAT), Volumetric Modulated Arc Therapy (VMAT) and Tomotherapy are now standard of care in many Australian radiation oncology departments. With these new treatment technologies we have reached a point where the radiation dose can be shaped to the target volume with steep dose gradients to surrounding normal tissues. New technologies have also been introduced to track and compensate for tumour motion during the treatment. Despite the obvious benefit of targeting cancers with more precise radiation treatments, from a safety point-of-view, there is an increasing concern that errors in planning or treatment delivery may not be detected. To quote Julian Rosenman: “We are at increased risk of missing very precisely”. With the new era of real time image guided high precision radiotherapy there is a need for three dimensional (3D) dosimetric quality assurance (QA) of the whole treatment chain.

IMRT of brain tumour MRI scanned dose maps

Figure 1 - Gel dosimeter phantom irradiated according to a conformal radiotherapy treatment (left). The white region is the result of irradiation induced polymerization in the hydrogel. Maps of absorbed radiation dose are obtained by use of high-accuracy quantitative R2 nuclear magnetic resonance imaging on a clinical MRI scanner (right).

During the last 15 years, our research group has developed and optimized a 3D radiation dosimetry technique for high-precision radiotherapy [1]. To verify the delivered dose distribution in three dimensions, several polymer gel dosimeters have been developed [2]. These polymer gel dosimeters consist of a hydrogel in which vinyl monomers are dissolved. Upon high-energetic irradiation, a radiation-induced polymerization reaction occurs in which the amount of polymerization is proportional to the absorbed dose. As a result of the creation of polymer within the hydrogel matrix, the gel changes colour to white (Figure 1 - left). Besides the optically visible changes, a change in nuclear magnetic resonance (NMR) properties can also be observed. The NMR spin-spin relaxation rate (R2) appears to be a sensitive physical property that correlates with the amount of polymerization [2]. As a result, the spatial dose distribution can also be obtained by quantitative magnetic resonance imaging (MRI) (Figure 1 - right). This technique has been successfully adapted for the verification of intensity modulated radiotherapy treatments (IMRT) in soft-tissue regions [3,4]. In a recent elaborate study, we demonstrated the reliability of gel dosimetry when conducted using a strict procedure [5-7]. However, because of the high associated cost and limited availability of MRI and the expertise required to obtain accurate quantitative MR images, this technology has not found its way to the radiation clinic.

Dosimetry of brain tumour Optical CT laser scanner

Figure 2 - A new kind of radiation sensitive 3D gel dosimeter turns green when exposed to radiation (left) which can then be scanned by use of an in house developed optical laser CT scanner (middle).

As an alternative to MRI, optical scanning of 3D gel dosimeters has been pursued (figure 2 - right). An optical laser beam CT scanner for 3D gel dosimeters has been constructed and validated against MRI and a calculated dose distribution [8] (figure 3). A new radiation sensitive gel dosimeter system has been constructed that is more suitable for optical scanning in which the irradiated zone does not scatter the light but absorbs red light instead hence a colour change to green (figure 2 - left).

Dosimetry of brain tumour

Figure 3 - Measured radiation dose maps (left) are compared against dose maps calculated with a commercial treatment planning system (middle). Small deviations between both dose maps become visible on gamma-maps (right).

Radiation Sensitive Dosimeters

Three Dimensional Polymer Gel Dosimeters

Polymer gel dosimeter phantoms are composed of a gelatine hydrogel that contains vinyl monomers [2], freely floating around in the water pool of the gel. The radiation-induced polymerization reaction results in the formation of highly cross-linked microscopically small polymer aggregates that are entangled with the gelatine hydrogel matrix. The density of polymer is related to the amount of absorbed radiation. Because of the entanglement with the hydrogel matrix, the molecular mobility of the polymer is highly restricted. The nuclear magnetic resonance spin-spin relaxation time (T2) is sensitive to the molecular mobility. Consequently, a reduction in T2 can be observed in MR images.

Polymerization Mechanism

Figure 4 - The principle of polymer gel dosimeters. Upon irradiation with high energetic ionising photon beams, a radiation induced polymerization reaction occurs which turns the hydrogel milky white in the irradiated region.

Various polymer gel dosimeters with different chemical composition have been fabricated and their radiation properties have been tested [9]. Essential characteristics of 3D dosimeters are:

  • Tissue equivalence: The dosimeter should absorb the radiation in a similar manner as human soft tissue. This is related to the electron density of the gel.

  • Spatial integrity: The dose distribution captured by the dosimeter should be preserved for an extended time,

  • Temporal stability: The R2-dose response should not change over time,

  • Independent on the temperature during irradiation: The R2-dose response should not vary too much with temperature during irradiation as temperature differences in the order of 2 oC are likely to occur between operator room and the linear accelerator treatment bunker.

  • Dose rate independence: The R2-dose response should not vary much with the rate at which the radiation dose is delivered in order to preserve a unique relation between radiation dose and the measured R2 values.

  • Independent on the temperature during scanning: During readout temperature differences of 1 to 2 oC are likely to occur as a result of temperature differences between operator room and scanner room and temperature fluctuations in the scanner bore.

  • Energy independence: Ideally, the irradiation dose response of the 3D dosimeter should be the same for different types of irradiation and within the energy spectrum of the irradiation beams.

All polymer gel dosimeters that have been investigated exhibit excellent tissue equivalence and energy independence as a result of the high water content in the hydrogel. However, not all polymer gel dosimeters that have been proposed in the literature demonstrate satisfactory dose rate dependence and temperature dependence during irradiation and scanning. Although its lower sensitivity, acrylamide based gel (so called PAGAT) dosimeters have superior characteristics that favour the reliability of the dose measurements [5-7, 9].

To obtain quantitative maps of absorbed dose, quantitative spin-spin relaxation rate (R2 = 1/T2) MR images are acquired using a clinical MRI scanner. It was found that in order to obtain these quantitative R2 MRI maps, adequate artefact compensation techniques needed to be implemented [10-12] and MR imaging sequence parameters needed to be optimized [13]. By exposing calibration vials to well-defined doses, a calibration curve is obtained to calibrate R2 to radiation dose of the 3D dosimeter phantom. It is crucial that the calibration vials and the dosimeter phantom are fabricated from the same batch of gel and are stored together, so that any uncertainties related to the chemical composition and temperature treatment are minimized.

The advantage of polymer gel dosimeters is that they can be poured in anthropomorphic shaped molds such as a head cast, a head and neck cast, a pelvic cast, etc. Large phantoms can be scanned. In addition, lung equivalent gel dosimeters have been fabricated that are created by beating the hydrogel into a stable hydrogel foam [14].

Clinical 3D Dosimetry

Figure 5 - Different clinical examples of 3D dose verification with polymer gel dosimetry. From left to right; IMRT of Nasopharynx tumour, Tomotherapy of Head and Neck carcinoma and experimental grid therapy.

Three Dimensional Micelle Gel Dosimeters

3D polymer gel dosimetry with MRI readout has been perceived by the radiotherapy community as relatively expensive, labour intensive and demanding a significant amount of expertise on MRI scanning. Moreover, most of the monomers used in polymer gel dosimeters are highly toxic and should be handled with care. For that reason, several research groups have started searching for alternatives to MRI scanning. As the radiation induced polymerization in polymer gel dosimeters also results in a gradual change from transparent to opaque for visual light, optical scanning seemed obvious. Unfortunately, in polymer gel dosimeters Tyndall (Mie) scattering of the light leads to imaging artefacts that cause severe uncertainties in the extracted dose distribution. This has encouraged research for new 3D dosimeters that do not scatter light but where the light is only absorbed at specific wavelengths. A first class of hydrogel systems that was developed were the so called Fricke gel dosimeters (named after Hugo Fricke, the inventor of the Fricke solution that served as a chemical dosimeters already in the first half of the 20th century) and in which the colour change was initiated by a radiation induced oxidation reaction that is visualized by the redox-indicator Xylenol Orange [15]. The problem with these Fricke solutions however appeared to be the diffusion of the active substance, hence a loss of spatial integrity of the dose distribution.

Recently, it was also found that a colour change occurs when certain leucodyes are irradiated in solution. In order to avoid diffusion of the leucodye within the hydrogel matrix, the leucodye was first enclosed in micelles which were then dissolved in a hydrogel [16, 17]. The leucodye containing micelles are big enough to prevent diffusion within the hydrogel matrix, hence increasing the spatial stability significantly (figure 6).

Micelle gel chemistry

Figure 6 - Principle of Leucodye Micelle Gel (LMG) dosimeters; Leucodye and a radical initiator are embedded in micelles that are dissolved in a hydrogel. Upon irradiation, the dye is converted to its leuco-form colouring the gel green.

The LMG dosimeters exhibit good radiation properties and were found to be stable and less temperature sensitive than the polymer gel dosimeters. The clinical use of the LMG dosimeter was validated for an IMRT treatment of a pituitary gland carcinoma (Figure 3) [8]. This was a critical treatment because the tumour was located in the vicinity of the optic chiasm. A good agreement between measured dose distribution and calculated dose distribution was found giving clinical confidence to carry out the treatment on the patient.

Three Dimensional Plastic Dosimeters

Another class of 3D dosimeters that can be read out with optical scanning are plastic dosimeters. These dosimeter systems have a polymer matrix instead of a hydrogel. The first kind of plastic dosimeters consisted of a polyurethane matrix and were commercialized under the name PRESAGE™. It has been demonstrated that although they have slightly different absorption of ionizing radiation than the hydrogel-based systems, they are tissue equivalent at photon and electron energies that are encountered in 95% of the radiotherapy cases. A drawback of these systems is that the dosimeters can only be fabricated in a specialized chemistry laboratory using high-pressure chemical reactors.

In search of a flexible but strong 3D dosimeter that can be used for dose verification of deformable organs, we recently invented “FlexyDos”. These dosimeters consist of a transparent poly-dimethyl siloxane (PDMS) elastomer that can be poured in an anthropomorphic shaped negative mold. As in the LMG dosimeters, the radiation active substance in the FlexyDos is Leuco Malachite Green in combination with chloroform. Excellent spatial stability and tissue equivalence was found for these dosimeters and the fabrication process is easier. Moreover, the FlexyDos dosimeters are not toxic and are therefore easy to handle in the hospital.

In order to read out organ-shaped FlexyDos phantoms the optical scanner system needed to be improved significantly. A dual wavelength technique has been implemented. Some first results with motion and deformable phantoms illustrate the great potential of these systems.

Optical CT Scanners

Different kinds of optical scanners have been constructed to read out the 3D radiation dose distribution that is captured by the dosimeters. A comprehensive overview of different scanners is given by Doran and Kristajic [18].

Optical CT laser scanner Optical CT laser scanner

Figure 7 - Optical laser CT scanner; A laser beam (i.) is directed onto a rotational galvano-mirror (ii.). The galvano-mirror can be rotated very precisely with computer control creating a sweeping laser beam that falls onto a large plano convex lens (iii.). The plano convex lens ensures that the laser beams follow parallel paths through the dosimeter phantom (iv.) which is suspended in a fluid tank through a linear stage and rotation stage. The parallel beams of transmitted laser light leaving the fluid tank are directed onto a photo-diode (v.) that measures the transmitted light. In time a projection of transmitted light through the dosimeter phantom is recorded by the photodiode. This procedure of recording transmission line profiles is repeated for various angular positions of the phantom achieved by use of the rotation stage (vi.). After recording transmission line profiles for different rotational positions of the dosimeter phantom, a sinogram (vii.) is created which can be reconstructed into a light absorption cross-section image through the dosimeter phantom. The fluid in the tank (iv.) has a refractive index similar to the gel dosimeter phantom, which avoids deflections of the laser beam when it falls on the curved surface of the dosimeter phantom.

The optical CT laser scanner constructed in our research group (figure 7) is able to scan a complete 3D volume with high-resolution in about 3 hours. A faster optical CT scanner makes use of a CCD camera that records entire images for each angular increment of the phantom instead of transmission line profiles in the optical laser scanner.

Optical Cone beam scanner

Figure 8 - Optical cone beam CT scanner with a diffuse light source of different colours. The transmitted light through the dosimeter is captured by a CCD camera. The cone beam image reconstruction takes the convergence of the beam into account.

In order to avoid repositioning the phantom before and after exposure to ionising radiation, hence giving rise to imaging artefacts related to positioning errors, we have implemented dual wave-length scanning. In this approach, the dosimeter phantom is scanned once with a green light source and once with a red light source. As the dye only absorbs light in the part of the optical spectrum around 630 nm, the radiation induced colouring can be subtracted from background attenuation by subtracting the optical density for green light from the optical density for red light. This dual wavelength scanning technique has enabled optical scanning of non-cylindrically shaped phantoms. With the cone beam optical CT scanner, an entire 3D volume can be scanned in less than 10 minutes. The cone beam image reconstruction is in the order of a few minutes on a modern PC but is currently been speed up by use of parallel computing (GPU - CUDA).

Accounting for Organ Motion and Tissue Deformation

The breakthrough in optical scanning of non-cylindrically shaped phantoms has opened the door for many new applications were the radiotherapy delivery technique compensates for organ motion and deformation. In Image Guided RadioTherapy (IGRT), the tumour is followed during the treatment by various imaging/tracking techniques. This allows to treat the tumour when it is in the field and stops the radiation beam when it is outside of the beam. More advanced techniques are being developed where the radiation beam is shaped and moves with the target volume. In order to validate these techniques 3D radiation dosimetry has become even more important. It is shown in figure 9 how a prostate dosimeter phantom is suspended in a pelvic phantom on a motion controlled arm. During treatment delivery, the prostate dosimeter phantom follows a motion trajectory that is based on the physiological motion within a patient. After treatment, the prostate dosimeter phantom is removed and readout using the double wavelength scanning method.

Pelvic phantom for IGRT

Figure 9 - A prostate dosimeter phantom is suspended in a water filled pelvic phantom and is connected to a motion controlled arm. Image guided treatment delivery is given during physiological motion of the prostate inside the water-filled pelvic phantom.

Conclusions

Over the years, several kinds of 3D dosimeter phantoms have been developed and characterized to measure the integrated radiation dose delivered to the cancer patient in three dimensions. In addition, several readout systems have been constructed and benchmarked to read out the dosimeters. It has been demonstrated that 3D polymer gel dosimeters, readout with MRI, can validate modern conformal radiotherapy. However, the use of these systems was found to be labour intensive, expensive and the toxicity of the dosimeters themselves has impeded their use in radiotherapy centres. Alternative systems have been developed over the years including Fricke gel dosimeters, micelle gel dosimeters and plastic dosimeters. Recently, our research group has proposed a novel dosimeter in combination with a novel optical CT scanning technique that is user-friendly and that meets the new challenges in radiotherapy delivery techniques which take into account patient and organ motion and organ deformation during treatment.

References

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