text:
# Dosimetry characterization of 32P intravascular brachytherapy source wires using Monte Carlo codes PENELOPE and GEANT4

## I Introduction

One of the major limitations of coronary interventions lies in the appearance of restenosis of the treated vessel. Restenosis occurs in 35%-40% of the treated patients in case of angioplasty, whilst the percentage reduces to 22%-32% in case coronary stents are used Poc95 .

Intravascular brachytherapy appears to be a useful tool to solve such problems Fox02 . PREVENT Rai99  and INHIBIT Wak00  studies have pointed out the ability of ionizing radiation to inhibit restenosis. Though either gamma and beta radiation have been used, endovascular beta-radiotherapy has become most popular in Europe due to the obvious radiation safety advantages.

This new, rapidly growing interest has led both the AAPM Nat99  and the ESTRO Pot01  to report recommendations on the medical physic issues. At the minimum standard level, dose at the prescription point in the central plane is encouraged to be recorded and reported. Additional dose calculations in peripheral planes require complete two-dimensional (2D) dosimetry information. However, beta sources present a high dose gradient, the distances in which the dose is deposited being considerably small. This has made it difficult to perform adequate dosimetry on intravascular sources.

Recently, the dosimetric characterization of a 27 mm long, catheter based, 32P beta source wire, manufactured by Guidant Corporation (Houston, Texas, USA), has been done by means of plastic scintillator Mou00  and radiochromic film Mou00 ; Boh01 .

Monte Carlo (MC) simulations have proved to be a valuable complementary means for determining the dose distributions around beta emitters. The 32P source mentioned above has been simulated with different MC codes (MCNPv4B2 Mou00 -Seh01 , CYLTRAN/ITS3 Mou00 ; Sel02 , MCNPv4C Mou00 , EGS4 Tod00 ; Wan01 ; Li01  and EGSnrc Wan01 ) and the calculated doses agree within $`<10`$% with the experimental results.

In this work we address the 2D dosimetric characterization of a new, clinically used, 20 mm long catheter based 32P beta source wire, commercially available in the GalileoTM Intravascular Radiotherapy System, manufactured also by Guidant Corporation. This source has been used Mou03  in a detailed study in which a variety of MC codes are intercompared. Also a comparison with measurements done by using radiochromic-dye film and an extrapolation chamber is carried out. Measured and calculated values were found to agree within 10% in a polystyrene phantom. On the other hand, the calculated depth dose curves, using the MC codes, were within 5% at 4 mm depth, after an adequate selection of the tracking parameters. In this last case water was considered the medium surrounding the source.

Here we have used the MC codes PENELOPE Sal01  and GEANT4 Geant . PENELOPE was designed specifically to account for the transport of low-energy electrons, photons and positrons and has been used to simulate other brachytherapy sources San98 ; Ase02 . GEANT4 includes special packages which permit to describe low energy physics processes and, at present, it is being used to simulate different situations of medical physics interest Geant . In this work we have determined the dose rate at the reference point, the depth dose and the two dimensional dose distribution. We also calculated the radial dose and the anisotropy functions, as proposed in the adapted AAPM TG-60 formalism for cylindrical sources Sch01 , used also in Ref. Wan01 . We compare some of our results with those quoted in Ref. Sel02 .

## II Material and Methods

### II.1 Source models

A schematic view of the geometry of the two sources analyzed is shown in Fig. 1. The 27 mm source has been described in Refs. Mou00 ; Boh01 . The geometry of the 20 mm source has been obtained from Ref. Sel02  and corresponds closely to that quoted in Mou03 . The active cores are cylinders with length of 27 and 20 mm, respectively. These cores are made of C2H6O2. The 20 mm source presents a 0.019 mm thick source carrier wrapping the active core. This is made of polymide. The cores are encapsulated by NiTi tubes with thickness of 0.076 mm in both sources. In the 27 mm source, a tungsten X-ray marker of 1 mm in length follows the core at the distal end. In the case of the 20 mm source, two markers of the same characteristics are located at both the distal and the proximal ends of the active core. Both sources include a NiTi plug of 1 mm in length following the distal tungsten X-ray marker. A NiTi hemispherical seal is welded at the distal end and an unbound NiTi wire is attached to the proximal end in both sources. Empty regions between the different pieces and the capsules are supposed to be filled with air.

Sources are centered inside a catheter of Nylon-12. In some of the calculations done for the 27 mm source, we have considered a helicoidal catheter (labeled catheter 1) reported in Refs. Mou00 -Wan01 . In the case of the 20 mm source, we have calculated using both this helicoidal catheter and a lobed catheter (labeled catheter 2) currently in use. This catheter is a new design to increase the blood flow during the procedure. Both catheters were modeled as tubes with an external radius of 0.4445 mm, while the inner diameter was 0.597 mm for catheter 1 and 0.5716 mm for catheter 2. Gaps between catheters and sources are assumed to be filled with air.

Catheter and source were placed in a water phantom the dimensions of which are large enough to ensure no significant loss of radiation.

The composition and density considered in the simulation for the different materials is given in Table 1.

### II.2 Monte Carlo calculations

In this work the PENELOPE Sal01  and GEANT4 Geant  Monte Carlo codes have been used to perform the simulations. PENELOPE is a general purpose MC code which allows to simulate the coupled electron-photon transport. It can be applied to energies ranging from a few hundred eV up to 1 GeV and with arbitrary materials. Besides, PENELOPE permits a good description of the particle transport at interfaces and presents an accurate description of the electron transport at low energies. These characteristics make PENELOPE a useful tool for medical physics applications as previous works have pointed out (see e.g. Refs. San98 ; Ase02 ). We have used the version 2001 of the code. Details about the physical processes included can be found in Ref. Sal01 .

GEANT4 is a toolkit aiming to simulate the passage of particles through matter for applications in high energy physics, nuclear experiments, medical physics studies, etc. Due to its purpose, the available energy range and the possible particles to be simulated are much larger than for PENELOPE. GEANT4 includes low energy packages which extend the energy range of particle interactions for electrons, positrons and photons down to 250 eV, and can be used up to approximately 100 GeV. In this work we have used the version 4.1 with the patch-01 and the low energy package G4EMLOW1.1. Detailed documentation concerning the physics involved can be found in Ref. Geant .

As the sources considered here present cylindrical symmetry, a cylindrical coordinate system was used with the origin in the center of the active core and with the $`z`$ axis along the source and pointing to its distal end. The dose distributions were supposed to be functions of the axial coordinate $`z`$ and the radial coordinate $`\rho `$. The position of the reference point is ($`\rho _0=2`$ mm, $`z_0=0`$).

The radionuclide was assumed to be uniformly distributed inside the active core. The direction of the emitted electrons was supposed to be isotropic around the initial position. The initial electron energies were sampled from the corresponding Fermi distributions, taken from Ref. Gar85 . A calculated average energy of $`0.6957`$ MeV was obtained, in agreement with values reported in previous works Boh01 ; Vyn82 .

In PENELOPE analog simulation is performed for photons. For electrons, instead, the simulation is done in a mixed scheme in which collisions characterized by a scattering angle larger than a certain value are called hard collisions and are individually simulated, while collisions with a scattering angle smaller that the limit value are called soft collisions and are described by means of a multiple scattering theory. The electron tracking is controlled by means of four parameters. $`C_1`$ and $`C_2`$ refer to elastic collisions. $`C_1`$ gives the average angular deflection due to a elastic hard collision and to the soft collisions previous to it. $`C_2`$ represents the maximum value permitted for the average fractional energy loss in a step. On the other hand, $`W_{\mathrm{cc}}`$ and $`W_{\mathrm{cr}}`$ are energy cutoffs to distinguish hard and soft events. Thus, the inelastic electron collisions with energy loss $`W<W_{\mathrm{cc}}`$ and the emission of Bremsstrahlung photons with energy $`W<W_{\mathrm{cr}}`$ are considered in the simulation as soft interactions. In our calculations the simulation parameters were fixed to the following values: $`W_{\mathrm{cc}}=5`$ keV, $`W_{\mathrm{cr}}=1`$ keV, $`C_1=C_2=0.05`$, $`s_{\mathrm{max}}=10^{35}`$. This last parameter is an upper bound for the length of the steps generated in the simulation.

Photons were simulated down to 1 keV. Primary electrons, $`\delta `$ rays and positrons were absorbed when they slow down to kinetic energies of 1 keV, in air, and 50 keV, in all the remaining materials, except in the active core where the cut off energy was fixed to 200 keV. This value takes care of the fact that electrons with such an energy are not expected to leave the active core. Those betas generated with energies below the simulation threshold were not transported and their energy was deposited at the source position.

In case of GEANT4 simulations, it is necessary to choose a given range threshold for each particle type. This threshold is converted, internally, to an energy threshold below which secondary particles are not emitted. In our calculations the range thresholds have been fixed to 100 nm providing energy thresholds of 1 keV for both photons and electrons in all materials considered.

The statistical uncertainties were calculated by scoring both the energy deposited in each voxel and its square for each history. These voxels were taken to be annular bins with thicknesses $`\mathrm{\Delta }\rho =0.1`$ mm and $`\mathrm{\Delta }z=0.2`$ mm. The average energy deposited in a given voxel (per incident particle) is

$$E_{\mathrm{mean}}=\frac{1}{N}\underset{i=1}{\overset{N}{}}e_i,$$

where $`N`$ is the number of simulated histories and $`e_i`$ is the energy deposited by all the particles of the $`i`$-th history (that is, including the primary particle and all the secondaries it generates). The statistical uncertainty is given by

$$\sigma _{E_{\mathrm{mean}}}=\sqrt{\frac{1}{N}\left[\frac{1}{N}\underset{i=1}{\overset{N}{}}e_i^2E_{\mathrm{mean}}^{}{}_{}{}^{2}\right]}.$$

The uncertainties given throughout the paper correspond to 1$`\sigma `$. In tables, and in order to simplify the writing, they are given between parentheses; for example, a value quoted as 0.956(2) means $`0.956\pm 0.002`$.

In case of the 27 mm source, the simulations have been done by following $`2\times 10^7`$ histories for PENELOPE and $`5\times 10^7`$ for GEANT4. For the 20 mm source a total of $`5\times 10^7`$ histories were simulated with both codes. These numbers permitted to keep the statistical uncertainties under reasonable levels.

Additionally, we performed, for the 20 mm source, simulations with PENELOPE by using scoring voxels given by cylindrical annuli of $`\mathrm{\Delta }z=13`$ mm centered along the source axial direction, and $`\mathrm{\Delta }\rho =0.1`$ mm in the radial direction. A total of $`6\times 10^7`$ histories were followed in this case. These scoring voxels warranty radial distributions which are effectively constant over the axial length and permit the uncertainty to be reduced considerably.

## III Results

### III.1 27 mm source

First we validated the MC codes with the old 27 mm source. Our results were compared with those reported in literature.

In Refs. Mou00  and Boh01  the MCNPv4B2 code was used. Mourtada et al. Mou00  transported $`10^6`$ histories in each run, with scoring voxels given by cylindrical annuli of 20 mm in the source axial direction and 0.1 mm in the radial direction. They showed also the dose rate per unit activity along the transverse axis. The same code and voxels were used by Bohm et al. Boh01  for the dose rate per unit activity along the transverse axis. Besides, these authors calculated the dose to water, away and along the source, using thin cylindrical shells with a thickness of 0.1 mm and a height of 0.1 mm as scoring voxels. Wang and Li Wan01  used scoring voxels equal to those we have considered here. Finally, Seltzer Sel02  quoted the results obtained for a simulation with CYLTRAN/ITS3, but did not give information about the scoring voxels.

The dose rate at the reference point for the unsheathed 27 mm source in water was calculated to be $`0.215\pm 0.001`$ and $`0.2312\pm 0.0008`$ cGy s-1 mCi-1 for PENELOPE and GEANT4, respectively, thus differing by 7%. These values must be compared with the results obtained with the other codes. The calculation with EGSnrc Wan01  provides $`0.2185\pm 0.0002`$ cGy s-1 mCi-1. Mourtada et al. Mou00  obtained 0.229 cGy s-1 mCi-1 by means of MCNPv4B2. Finally, in Ref. Boh01  a value of $`0.232\pm 0.00028`$ cGy s-1 mCi-1 was found also with MCNPv4B2. This is the largest value found, which differs from the one we have obtained with PENELOPE (the smallest one) by $`8`$%.

In Table 2 we compare the dose rate per unit activity along the transverse axis (values for $`z=0`$ in the first set of rows) obtained with PENELOPE and GEANT4 with those of Refs. Boh01 ; Wan01 ; Sel02 . The results correspond to the 32P wire source sheathed by catheter 1. As we can see PENELOPE produces results very similar to those of EGSnrc. In this case the differences for any $`\rho `$ value are below 6% with respect to the dose rate obtained with PENELOPE at the reference point, $`\dot{D}_{\mathrm{PEN}}(\rho _0,z_0)`$. Up to $`\rho =3`$ mm PENELOPE practically coincides with EGS4, the differences relative to $`\dot{D}_{\mathrm{PEN}}(\rho _0,z_0)`$ being smaller than 5%. The difference between GEANT4 (MCNPv4B2) and PENELOPE is below 8% (5%), relative to $`\dot{D}_{\mathrm{PEN}}(\rho _0,z_0)`$. In what respect to the results of CYLTRAN/ITS3, they show negligible differences with PENELOPE results. The fact that these last quoted values have been obtained by scanning Figure 11 of Ref. Sel02  makes these differences to be only indicative.

Two-dimensional dose distributions are shown in Tables 2 and 3 for some values of $`\rho `$ and $`z0`$. Similar results are obtained for the negative values of $`z`$, though the source wire is not symmetric with respect to $`z=0`$. In Table 2 our results are compared with those of Bohm et al. Boh01  calculated with MCNPv4B2 for the source sheathed by catheter 1. In Table 3 the dose distributions for the unsheathed source, normalized to the reference point, are compared with the results obtained by Wang and Li Wan01  using EGSnrc.

The differences between MCNPv4B2 and PENELOPE (see Table 2), remain below 5%, relative to $`\dot{D}_{\mathrm{PEN}}(\rho _0,z_0)`$). Same situation appears for MCNPv4B2 and GEANT4, which give very similar results for $`\rho 2`$ mm.

Table 3 shows that EGSnrc and PENELOPE provide very similar normalized doses. It is important to remember here that the difference in the doses at the reference point between both codes is 1.6% only. The differences maintain at more or less the same level for all $`z`$ and $`\rho `$ values studied.

Finally, and as we can see in both tables, the discrepancies between PENELOPE and GEANT4, observed for the dose rate per unit activity along the transverse axis, show up again. In any case the differences remain below 8% with respect to $`\dot{D}_{\mathrm{PEN}}(\rho _0,z_0)`$.

### III.2 20 mm source

#### III.2.1 Unsheathed source

Once we have analyzed the results obtained for the 27 mm source, we will discuss the dose rates found for the 20 mm source. All the results here correspond to the unsheathed source. For clarity, we leave the analysis of the sheathed source for the next subsection.

In Table 4 (box labeled $`z=0`$) we show the results we have obtained for the dose rate per unit activity along the transverse axis. The first row gives the results obtained using PENELOPE for voxels with $`\mathrm{\Delta }z=13`$ mm. The second (third) rows correspond to the results obtained with PENELOPE (GEANT4) for voxels with $`\mathrm{\Delta }z=0.2`$ mm. The dose rates at the reference point calculated with PENELOPE are $`0.2918\pm 0.0001`$ cGy s-1 mCi-1 when the large scoring voxel (that with $`\mathrm{\Delta }z=13`$ mm) is used and $`0.2908\pm 0.0009`$ cGy s-1 mCi-1 for the small one (that with $`\mathrm{\Delta }z=0.2`$ mm). GEANT4 produces a value of $`0.311\pm 0.001`$ cGy s-1 mCi-1, which differs from the previous ones in $`7`$%. On the other hand, the discrepancy between the results obtained with both codes increases with increasing $`\rho `$, showing a behavior similar to that found for the 27 mm source.

Fig. 2 shows the comparison of the axial dose distributions (normalized to the corresponding reference points) obtained with both codes for $`\rho `$ values ranging from 1 to 6 mm. The disagreement between PENELOPE and GEANT4 shows up also in Fig. 3. Therein the dose distributions along transverse axes (normalized to the reference point) for $`z`$ values ranging from 7 to 14 mm are compared to those corresponding to $`z=0`$ mm. PENELOPE results are plotted with symbols, while GEANT4 calculations are only shown (curves) for $`z=0`$, 11 and 14 mm. For a given $`\rho `$ value the discrepancy grows with $`z`$. In general, GEANT4 predicts larger doses at large $`\rho `$ values. The case of the $`z=11`$ mm curve is a clear example of this behavior: up to $`\rho 3`$ mm both results are in a reasonable agreement but for $`\rho 5`$ mm the GEANT4 result coincides with the PENELOPE one obtained for $`z=10`$ mm.

In the case of the 27 mm source, Wang and Li Wan01  quoted an asymmetry of the dose distribution due to the presence of the distal tungsten X-ray marker. Such asymmetry showed up for $`z>13`$ mm and the dose rates at the proximal and distal ends showed a relative difference below 25%. If this is so, the presence of two such markers, in the 20 mm source, should make this asymmetry to disappear. Fig. 4 shows the ratio of the dose at various $`z`$ values to the dose at $`z`$. The results are similar in both codes. As we can see, the ratio of the dose rates does not show statistically significant differences from unity, even at large $`z`$. This means that the asymmetry of the source structure due to the small differences between the distal and the proximal ends is smaller than statistical uncertainties and would therefore probably be irrelevant in practice.

In Fig. 5 we analyze the axial dose uniformity by plotting the ratio of the dose at $`z=3`$ up to 8 mm to the dose at $`z=0`$ as a function of $`\rho `$. The results show that, for a given $`\rho `$ value, doses stay constant for axial positions up to 6-7 mm. This occurs for both PENELOPE and GEANT4 and means that the scoring voxels with $`\mathrm{\Delta }z=13`$ mm, considered above to reduce the uncertainty in calculating the radial dose, can be used safely for that purpose.

The two-dimensional dose rates we have obtained using voxels with $`\mathrm{\Delta }z=0.2`$ mm are listed in Table 4. For each $`z`$ value, the first row corresponds to PENELOPE and the second one to GEANT4. The values for $`z<0`$ are not included because of the symmetry with respect to the corresponding $`z>0`$ results. On the other hand, the uniformity up to $`z6`$ mm is again evident. The comparison between both codes indicates that GEANT4 predicts larger doses than PENELOPE except for $`\rho `$ below 0.5 mm.

To finish with the analysis of the unsheathed source, we calculated the radial dose functions and the anisotropy functions. Following Ref. Sch01 , these quantities are given in the cylindrical coordinate system instead of the spherical one used in the TG-60 formalism Nat99 . For the radial dose we have

$$g(\rho )=\frac{\dot{D}(\rho ,z_0)}{\dot{D}(\rho _0,z_0)}\frac{G(\rho _0,z_0)}{G(\rho ,z_0)}.$$
(1)
The anisotropy function is given by

$$F(\rho ,z)=\frac{\dot{D}(\rho ,z)}{\dot{D}(\rho ,z_0)}\frac{G(\rho ,z_0)}{G(\rho ,z)},$$
(2)
where $`G(\rho ,z)=\beta /(L\rho )`$, with $`L=27`$ or 20 mm, according to the source considered, and $`\beta `$ is the angle between the lines joining the point ($`\rho `$,$`z`$) and the two extremes of $`L`$.

Calculated radial dose functions for PENELOPE and GEANT4 in water are shown in Table 5. As we can see, the discrepancies observed between both codes in previous results are evident here again. Besides, we have included the results obtained with PENELOPE for the 27 mm source and those quoted by Wang and Li for EGSnrc Wan01 . The radial dose function for the 20 mm source appears to be rather similar to that of the 27 mm source. The results obtained with PENELOPE differs less than 10% up to $`\rho =6`$ mm. Finally, PENELOPE and EGSnrc provide results which coincide within the statistical uncertainties for the 27 mm source.

Table 6 shows the anisotropy function calculated for the unsheathed 20 mm source with PENELOPE. These results are compared in Fig. 6 with those obtained with GEANT4. As in previous comparisons, the discrepancies between both codes appear to be noticeable for large $`\rho `$ and/or $`z`$ values, though the absolute differences remain small in comparison with the values obtained at the reference point.

#### III.2.2 Sheathed source

Here we analyze the effect of the catheter on the dosimetry. First we compare the results we have obtained with both codes with the scarce data available in the literature. Table 7 shows this comparison with the data provided by the manufacturer in the source manual (second column) and with the results of a set of calculations with different codes performed by Seltzer Sel02 . In these calculations the scoring voxels were taken to be annuli of radial thickness 0.1 mm and axial length 15 mm, centered along the active wire length. This produces greatly reduced statistical uncertainties. As can be seen, our results for PENELOPE coincide with those found with CYLTRAN/ITS3 and PENELOPE in Ref. Sel02 , except for small deviations (less than 1%) at $`\rho =2`$ mm in the last case. The values provided by Guidant are between 5 and 10% above those we have found for PENELOPE. MCNP4C results are similar to the Guidant ones and those calculated with EGS4 and EGSnrc fall to $`7`$% below those obtained with PENELOPE at $`\rho =4`$ mm. The values found with GEANT4 follow the same trend seen in the previous sections.

Fig. 7 shows the relative difference

$$\frac{\dot{D}_{\mathrm{cath}}(\rho ,z_0)\dot{D}(\rho ,z_0)}{\dot{D}(\rho ,z_0)}$$
(3)
between the depth doses calculated with and without catheter for PENELOPE (squares) and GEANT4 (disks). The results corresponding to the 20 mm source are shown. As we can see, both codes produce similar results with both catheters. However, GEANT4 shows an increase of the effect of the catheter above $`\rho =3.5`$ mm which is not present in the PENELOPE calculation. Similar results are obtained for the 27 mm source sheathed by catheter 1. On the other hand, catheter 2 produces a modification of the dose in water slightly smaller than catheter 1. This last gives rise to enhancements of the dose rate on the transverse axis reaching $`4`$% above $`\rho =3`$ mm, whilst the first one increases the dose rate by $`2.5`$% at most. This result is reasonable if one considers that catheter 2 has a smaller inner radius than catheter 1, thus reducing the air gap. In any case, uncertainties in source strength measurements might outweigh this correction in clinical practice.

## IV Conclusions

In this work we have performed the dosimetric characterization of two wire sources of 32P (of 27 mm and 20 mm active length) manufactured by Guidant Corporation and clinically used in intravascular brachytherapy. To do so we have used the Monte Carlo codes PENELOPE and GEANT4.

First we have validated the codes by comparing the results obtained with these two codes with those available in the literature for the 27 mm source. The main conclusion is that PENELOPE produces dose rates in reasonable agreement with those quoted in Ref. Wan01  for EGSnrc and EGS4 except in the tails of the axial doses (large $`z`$ values). Calculations performed with MCNPv4B2 Mou00 ; Boh01  differ from those obtained with PENELOPE as the distance to the source increases. The comparison between PENELOPE and GEANT4 shows a clear disagreement.

For the 20 mm source, we have calculated the depth doses on the transverse axis, the two-dimensional dose rate table and the radial dose and anisotropy functions (this two last according to the approach proposed in Ref. Sch01  for cylindrical sources). We have checked that the dose distribution remains uniform along the axial direction for $`|z|`$ smaller than 6-7 mm and $`\rho 7`$ mm. Besides, we have tested the symmetry of the dose distribution. The dose rates calculated with PENELOPE show a good agreement with the scarce data available, while those obtained with GEANT4 follow a trend similar to that observed in the 27 mm source.

The presence of the catheter sheathing the sources produces an increase in the dose rate on the transverse axis. This enhancement is larger for the helicoidal catheter (catheter 1) than for the lobed one (catheter 2). For the first one, the dose on the transverse axis increases up to 4% above $`\rho =3`$ mm, while the second one produces a maximum enhancement of $`2.5`$%. These differences could produce non-negligible modifications in the clinical use of the sources.

The results we have obtained indicate that PENELOPE produces a dose rate map which can be considered to represent the dosimetric characterization of the sources here studied. The appreciable discrepancies shown by GEANT4 results need a deeper investigation in order to clarify the origin of these differences. In particular, to determine if they are due to the physics included in the simulations or to the tracking procedure should be of great interest. We are working in this direction.

The full data set we have obtained here is available at http://fm131.ugr.es/P32-IVB

###### Acknowledgements.

Authors wish to acknowledge Guidant Corporation (European division) for the assistance provided concerning the geometrical details of the sources here investigated. We are also indebted to Dr. Jenkins (Guidant, Texas) for his patient answering to our questions. This work has been supported in part by the Junta de Andalucía (FQM0225).