3D interfractional patient position verification using 2D-3D registration of orthogonal images.

Reproducible positioning of the patient during fractionated external beam radiation therapy is imperative to ensure that the delivered dose distribution matches the planned one. In this paper, we expand on a 2D-3D image registration method to verify a patient's setup in three dimensions (rotations and translations) using orthogonal portal images and megavoltage digitally reconstructed radiographs (MDRRs) derived from CT data. The accuracy of 2D-3D registration was improved by employing additional image preprocessing steps and a parabolic fit to interpolate the parameter space of the cost function utilized for registration. Using a humanoid phantom, precision for registration of three-dimensional translations was found to be better than 0.5 mm (1 s.d.) for any axis when no rotations were present. Three-dimensional rotations about any axis were registered with a precision of better than 0.2 degrees (1 s.d.) when no translations were present. Combined rotations and translations of up to 4 degrees and 15 mm were registered with 0.4 degrees and 0.7 mm accuracy for each axis. The influence of setup translations on registration of rotations and vice versa was also investigated and mostly agrees with a simple geometric model. Additionally, the dependence of registration accuracy on three cost functions, angular spacing between MDRRs, pixel size, and field-of-view, was examined. Best results were achieved by mutual information using 0.5 degrees angular spacing and a 10 x 10 cm2 field-of-view with 140 x 140 pixels. Approximating patient motion as rigid transformation, the registration method is applied to two treatment plans and the patients' setup errors are determined. Their magnitude was found to be < or = 6.1 mm and < or = 2.7 degrees for any axis in all of the six fractions measured for each treatment plan.

Patient specific treatment verifications for helical tomotherapy treatment plans.

We performed two-dimensional treatment verifications for ten patients planned and treated with helical tomotherapy. The treatment verification consisted of a film measurement as well as point dose measurements made with an ion chamber. The agreement between the calculated and the measured film dose distributions was evaluated with the gamma index calculated for three sets of criteria (2 mm and 2%, 4 mm and 3%, and 3 mm and 5%) as recommended in the literature. Good agreement was found between measured and calculated distributions without any need of normalization of the dose data but with dose map registration using reference marks. In this case, 69.8 +/- 17.2%, 92.6 +/- 9.0%, and 93.4 +/- 8.5% passed the 2 mm and 2%, 4 mm and 3%, and 3 mm and 5% criteria, respectively. Agreement was excellent when both normalization and manual registration of the dose maps was employed. In this case 91.2 +/- 5.6%, 99.0 +/- 1.4%, and 99.5 +/- 0.8% passed the 2 mm and 2%, 4 mm and 3%, and 3 mm and 5% criteria, respectively. The mean percent discrepancy for the point dose measurements was -0.5 +/- 1.1%, -2.4 +/- 3.7%, -1.1 +/- 7.3% for the high dose, low dose, and critical structure point, respectively. Three criteria for a satisfactory treatment verification in the high dose regions of a plan were established. For the un-normalized reference mark registered data 80% of pixels must pass the 3 mm and 5% criteria. For the normalized and manually registered data, 80% must pass the 2 mm and 2% criteria, and the point dose measurement must be within 2% of the calculated dose. All low dose region/critical structure point dose measurements were evaluated on a patient by patient basis. The criteria we recommend can be useful for the routine evaluation of treatment plans for tomotherapy systems.

Monte Carlo investigation of single cell beta dosimetry for intraperitoneal radionuclide therapy.

Single event spectra for five beta-emitting radionuclides (Lu-177, Cu-67, Re-186, Re-188, Y-90) were calculated for single cells from two source geometries. The first was a surface-bound isotropically emitting point source and the second was a bath of free radioactivity in which the cell was submerged. Together these represent a targeted intraperitoneal radionuclide therapy. Monoenergetic single event spectra were calculated over an energy range of 11 keV to 2500 keV using the EGSnrc Monte Carlo system. Radionuclide single event spectra were constructed by weighting monoenergetic single event spectra according to radionuclide spectra appropriate for each source geometry. In the case of surface-bound radioactivity, these were radionuclide beta decay spectra. For the free radioactivity, a continuous slowing down approximation spectrum was used that was calculated based on the radionuclide decay spectra. The frequency mean specific energy per event increased as the energy of the beta emitter decreased. This is because, at these energies, the stopping power of the electrons decreases with increasing energy. The free radioactivity produced a higher frequency mean specific energy per event than the corresponding surface-bound value. This was primarily due to the longer mean path length through the target for this geometry. This information differentiates the radionuclides in terms of the physical process of energy deposition and could be of use in the radionuclide selection procedure for this type of therapy.

Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases.

A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate significantly on the tumour surface.