Tony DiMauro
Coronary artery disease is one of the leading causes of death in the western world. Percutaneous transluminal coronary angioplasty is a procedure toopenobstructed coronary arteries. However, restenosis is a significant problem associated with these balloon angioplasty procedures. Beginning in 1995, clinical trials were begun in the United States to investigate the safety and viability ofusing radiation to reduce this restenosis process. A number of trials have begun not only to study the issues of safety and efficacy but also toinvestigate avariety of methods for intravascular brachytherapy radiation dose delivery.
In balloon angioplasty, an inflated catheter is used to open arteries that are clogged because of plaque formation. The balloon procedure is designed to crush the plaque, but it often tears the arterial wall as well. Some of the cells in the blood vessel respond to this injury by initiating repair, which leads to restenosis (reclosing) of the artery. But if the lesion is treated with radiation (on the order of 8–30 Gy), this restenotic effect is suppressed.
Radionuclide therapy remains an important treatment option today because ionizing radiation from radionuclides can kill cells, and thus inhibit growth in the benign and cancerous lesions that result from proliferative diseases. The irradiation of coronary arteries performed immediately after balloon angioplasty has shown promise for reducing the incidence of re-blockage of the arteries by plaque buildup (coronary artery restenosis). Approximately 50 percent of subjects ( around half a million each year in the United States alone and nearly a million worldwide) experience restenosis after balloon angioplasty.
Radiochromic Film Specifics
Intravascular Brachytherapy research requires meticulous knowledge of isodose curves that must be accurate down to a tenth of a millimeter. Conventional measuring systems such as ionization chambers, thermoluminescent detectors and semiconductors are not capable of such spatial resolution. Radiochromic film dosimetry offers the researcher phenomenal spatial resolution of dose distribution.
Radiochromic dye-cyanide films have disposed of some of the problems experienced with conventional radiation dosimetry. The high spatial resolution and low spectral sensitivity of radiochromic films make this dosimeter ideal for the measurement of dose distributions in regions of high dose gradient in radiation fields (1).
Radiochromic effects involve the direct coloration of a material by the absorption of energetic radiation, without requiring latent chemical, optical, or thermal development or amplification (2). Radiochromic film based on polydiacetylene has been introduced for medical applications, known as GafChromic MD-55(I and II). The film consists of a thin microcrystalline monomeric dispersion coated on a flexible polyester film base. The film is clear (translucent) before it is irradiated. It turns progressively blue upon exposure to radiation. The radiochromic radiation chemical mechanism is a relatively slow first order solid state topochemical polymerization reaction initiated by irradiation, resulting in homogenous, planar polyconjugation along the carbon-chain backbone (2).
The increase in absorbance is roughly proportional to the absorbed dose of ionizing radiation. The bluing becomes relatively stable after 24 hours. The response of the film is spatially nonuniform. Researchers have found that the uniformity is better in the direction in which the base is coated with the sensitive emulsion than it is in the transverse direction (3).
Radiochromic Film has many important limitations that must be considered when using it to determine the dose distribution of any experiment. All researchers must note and calibrate each lot of the film before any determination of dose to optical density. The temperature during calibration and experimentation should be the same. Many researchers report that the Optical density decreased with increasing temperature and the percent change per degree increased at higher temperatures (4). Most radiochromic films are sensitive to ultraviolet radiation, which spontaneously colors the film. Sensible care must be taken to protected the film from sunlight or white fluorescent lights (2). There is negligible dependence on changes in humidity. Films should always be kept in a dry dark environment at the temperature and humidity at which they will be utilized. The film orientation and alignment should be consistent during actual use and scanning to determine dose distribution.
The sensitive layers have a preferred direction when irradiated and many researchers have found that scanning in different directions produced anomalous readings. The film also has local and regional fluctuations. Both fluctuations can be handled with relative ease during the image processing. Radiochromic films will turn bluer after they have been irradiated. This post-irradiation instability is one of the most important to consider. A two day wait before image processing is necessary. It is also necessary for the calibration and the experiment to scan the film at the same time delay. The Optical Density changes by nearly 16% in a 24-hour period and as much as 4% after a two week period (5). Radiochromic film has relatively little energy dependence of response in the therapuetic x-ray range, radiochromic film is suitable for determination of dose distribution (5).
To use radiochromic film as a research tool, it must be calibrated. Radiochromic film response is somewhat dependent upon the researcher and the experiment. With great care an accurate and direct relationship between absorbed dose and film response can be obtained. Each batch of film obtained from the distributor must be calibrated.
A well characterized radiation field means that the average energy of the photons or electrons be known. A standard ortho voltage X-Ray machine, a Cobalt-60 source, or any known uniform radiation field is required.
2. Aluminum or Copper Filters (beam hardening).
3. A calibrated ion chamber to measure the Exposure.
4. A thermometer, pressure gauge and timer.
After the exposures are made, they must be stored for at least two days because of the post-irradiation instability associated with the film. The amount of time necessary depends upon the amount of time that the experimental exposures were stored before scanning.
The last step in the process is to scan the irradiated pieces of radiochromic film using a scanning densitometer. What is needed is a calibration curve. This curve is obtained by knowing the amount of light transmitted through the unirradiated film to that of the irradiated film (Pixel Intensity). Using this number one can relate this to the absorbed dose. Each film piece has been irradiated for a certain amount of time and each film piece has a Pixel Intensity associated with it’s exposure. So, that now the researcher has a relationship of bluing to absorbed dose. The darker the bluing the higher the dose. This will be used to obtained absorbed doses in the experiment.
Researchers want to demonstrate the effects of radiation to the epithelial cells of an artery after angioplasty surgery. The effects of this process will inhibit restenosis. Medical researchers want to provide an accurate dose distribution that can be shown to the FDA for approval of this process. Dosimetry at distances of a millimeter from radioactive sources is poorly known. In traditional brachytherapy the dose is typically specified at 1 cm from the source and effects of low energy photons and electrons are essentially ignored. In intravascular brachytherapy, however, the entire lesion may ne 1-3 mm in thickness. It is essential to determine the dosimetry in the millimeter range (7). Below is a dose distribution taken from Duggan.
The high resolution of the MD-55 allows researchers to acquire doses within tenths of millimeters from the source. Placement of the source in the artery is critical. The irradiation of the surrounding area must be known to within a few millimeters. From research done as SDSU (opposite page) one can see with great accuracy using radiochromic film the dose distribution around an Ir-192 source. There are as many as 55 data points per millimeter. Resolution is mostly dependent on the scanner. The film itself can be resolved to 1200 lines/mm. As shown in the figure, the film study is compared to the Monte Carlo Simulation. The actual data points are not shown because there are too many. The other two figures show the dependence of post-irradiation stability and the actual dose to pixel intensity.
Radiochromic
Film Applications
Radiochromic films are relatively insensitive to radiation
compared to other detectors. this lack of sensitivity makes them ideal
where high doses are used. Radiochromic film also has the elemental composition
that is close to water, which reduces their sensitivity to photon energy
for applications dealing with the determination of dose delivered to water.
Here are a few applications.
Ophthalmic applicator dosimetry
Theses Sr-90 applicators have been used for decades,
but problems with their dosimetry have just been recently resolved. Until
a few years ago there was no standardized method for calibration of the
dose rate, discrepancies of up to 50% were reported. A technique using
radiochromic film was used to determine the surface dose rate and dose
distribution of these sources to agreement within 6%.
Hot Particle Dosimetry
In 1990, Soares, presented preliminary results
of measurements of the distribution of skin doses from hot particles which
are micron size particles containing radioactive materials. Hot particles
are a concern in the environment of a nuclear reactor because they represent
a potential source of harmful radiation exposure to workers. This work
was also a first demonstration of the high resolution dosimtery that is
possible with radiochromic film.
Radiation Inactivation and Target size analysis
Large doses in the range of thousands of Grays are necessary
for the inactivation of some proteins active in cellular metabolism. From
a knowledge of accurate dosimetry in this high dose region and the shape
of the inactivation dose response curve, it is possible to ascertain the
molecular size of putative proteins.
Proton Dosimetry
Radiochromic film has been useful for dosimtery measurements
in clinical proton beams. The studies of the MD-55 film in different beams
have shown a similar linear response within the dose region 10-100 Gy
for high energy proton, electron, and photon beams. The MD-55 was also
used to measure complex dose distributions in an irradiated phantom, enabling
verification of dose delivery of proton Bragg peak sterotactic radiosurgery
with multiple noncoplanar beams. The spatial resolution of the phantom
verification technique was such that possible misalignments greater than
2 mm, could be detected.
References
1 A.
S. Meigooni, et al., “Dosimetric characteristics of an improved radiochromic
film,” Med. Phys. 23(11), 1883-1888 (1996).
2 A. Niroomand, et al., “Radiochromic film dosimetry:Recommendations
of AAPM Radiation Therapy Committee Task Group 55,” Med. Phys. 25(11),
2093-2115 (1998).
3 D.M. Duggan et al, “Radiochromic film dosimetry of a high
dose rate beta source for intravascular brachytherapy,” Med. Phys.
26(11), 2461-2464 (1999).
4 N.V. Klassen et al, “GafChromic MD-55: Investigated as a precision
dosimeter,” Med. Phys. 24(12), 1924-1934 (1997).
5 P.J. Muench et al, “Photon Energy dependence of the sensitivity
of radiochromic film and comparison with silver halide and LIF TLDs used
for brachytherapy dosimetry,” Med. Phys. 18(4), 769-775 (1991).
6 L.E. Reinstein et al, “Predicting optical densitimeter response
as a function of light source characteristics for radiochromic film dosimetry,”
Med. Phys. 24(12), 1935-1942 (1997).
7 R.Nath et al, “Intravascular Brachytherapy physics: report of the
AAPM radiation Therapy Committee task Group No. 60,” Med. Phys. 26(2),
119-152 (1999).
