Piotr Zygmanski

The measurement of proton stopping power using proton-cone-beam computed tomography

A cone-beam computed tomography (CT) system utilizing a proton beam has been developed and tested. The cone beam is produced by scattering a 160 MeV proton beam with a modifier that results in a signal in the detector system, which decreases monotonically with depth in the medium. The detector system consists of a Gd2O2S:Tb intensifying screen viewed by a cooled CCD camera. The Feldkamp-Davis-Kress cone-beam reconstruction algorithm is applied to the projection data to obtain the CT voxel data representing proton stopping power. The system described is capable of reconstructing data over a 16 x 16 x 16 cm3 volume into 512 x 512 x 512 voxels. A spatial and contrast resolution phantom was scanned to determine the performance of the system. Spatial resolution is significantly degraded by multiple Coulomb scattering effects. Comparison of the reconstructed proton CT values with x-ray CT derived proton stopping powers shows that there may be some advantage to obtaining stopping powers directly with proton CT. The system described suggests a possible practical method of obtaining this measurement in vivo.

Targeted radiotherapy with gold nanoparticles: current status and future perspectives

Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clinical translation. Future prospects and perspectives are discussed.

Angular dose dependency of MatriXX TM and its calibration

One of the applications of MatriXX (IBA Dosimetry) is experimental verification of dose for IMRT, VMAT, and tomotherapy. For cumulative plan verification, dose is delivered for all the treatment gantry angles to a stationary detector. Experimental calibration of MatriXX detector recommended by the manufacturer involves only AP calibration fields and does not address angular dependency of MatriXX. Angular dependency may introduce dose bias in cumulative plan verification if not corrected. For this reason, we characterized angular dependency of MatriXX and developed a method for its calibration. We found relatively large discrepancies in responses to posterior vs. anterior fields for four MatriXX (Evolution series) detectors (up to 11%), and relatively large variability of responses as a function of gantry angle in the gantry angle ranges of 91°–110° and 269°–260°. With our calibration method, the bias due to angular dependency is effectively removed in experimental verification of IMRT and VMAT plans. PACS number: 87.56Fc

Dependence of fluence errors in dynamic IMRT on leaf-positional errors varying with time and leaf number

In d-MLC based IMRT, leaves move along a trajectory that lies within a user-defined tolerance (TOL) about the ideal trajectory specified in a d-MLC sequence file. The MLC controller measures leaf positions multiple times per second and corrects them if they deviate from ideal positions by a value greater than TOL. The magnitude of leaf-positional errors resulting from finite mechanical precision depends on the performance of the MLC motors executing leaf motions and is generally larger if leaves are forced to move at higher speeds. The maximum value of leaf-positional errors can be limited by decreasing TOL. However, due to the inherent time delay in the MLC controller, this may not happen at all times. Furthermore, decreasing the leaf tolerance results in a larger number of beam hold-offs, which, in turn leads, to a longer delivery time and, paradoxically, to higher chances of leaf-positional errors (< or = TOL). On the other end, the magnitude of leaf-positional errors depends on the complexity of the fluence map to be delivered. Recently, it has been shown that it is possible to determine the actual distribution of leaf-positional errors either by the imaging of moving MLC apertures with a digital imager or by analysis of a MLC log file saved by a MLC controller. This leads next to an important question: What is the relation between the distribution of leaf-positional errors and fluence errors. In this work, we introduce an analytical method to determine this relation in dynamic IMRT delivery. We model MLC errors as Random-Leaf Positional (RLP) errors described by a truncated normal distribution defined by two characteristic parameters: a standard deviation sigma and a cut-off value deltax0 (deltaxo approximately TOL). We quantify fluence errors for two cases: (i) deltax0 >> sigma (unrestricted normal distribution) and (ii) deltax0 << sigma (deltax0--limited normal distribution). We show that an average fluence error of an IMRT field is proportional to (i) sigma/ALPO and (ii) deltax0/ALPO, respectively, where ALPO is an Average Leaf Pair Opening (the concept of ALPO was previously introduced by us in Med. Phys. 28, 2220-2226 (2001). Therefore, dose errors associated with RLP errors are larger for fields requiring small leaf gaps. For an N-field IMRT plan, we demonstrate that the total fluence error (if we neglect inhomogeneities and scatter) is proportional to 1/square root of N, where N is the number of fields, which slightly reduces the impact of RLP errors of individual fields on the total fluence error. We tested and applied the analytical apparatus in the context of commercial inverse treatment planning systems used in our clinics (Helios and BrainScan). We determined the actual distribution of leaf-positional errors by studying MLC controller (Varian Mark II and Brainlab Novalis MLCs) log files created by the controller after each field delivery. The analytically derived relationship between fluence error and RLP errors was confirmed by numerical simulations. The equivalence of relative fluence error to relative dose error was verified by a direct dose calculation. We also experimentally verified the truthfulness of fluences derived from the log file data by comparing them to film data.

A method of calculating a lung clinical target volume DVH for IMRT with intrafractional motion

The motion of lung tumors from respiration has been reported in the literature to be as large as 1-2 cm. This motion requires an additional margin between the Clinical Target Volume (CTV) and the Planning Target Volume (PTV). In Intensity Modulated Radiotherapy (IMRT), while such a margin is necessary, the margin may not be sufficient to avoid unintended high and low dose regions to the interior on moving CTV. Gated treatment has been proposed to improve normal tissues sparing as well as to ensure accurate dose coverage of the tumor volume. The following questions have not been addressed in the literature: (a) what is the dose error to a target volume without a gated IMRT treatment? (b) What is an acceptable gating window for such a treatment. In this study, we address these questions by proposing a novel technique for calculating the three-dimensional (3-D) dose error that would result if a lung IMRT plan were delivered without a gated linac beam. The method is also generalized for gated treatment with an arbitrary triggering window. IMRT plans for three patients with lung tumors were studied. The treatment plans were generated with HELIOS for delivery with 6 MV on a CL2100 Varian linear accelerator with a 26 pair MLC. A CTV to PTV margin of 1 cm was used. An IMRT planning system searches for an optimized fluence map phi(x,y) for each port, which is then converted into a dynamic MLC file (DMLC). The DMLC file contains information about MLC subfield shapes and the fractional Monitor Units (MUs) to be delivered for each subfield. With a lung tumor, a CTV that executes a quasiperiodic motion z(t) does not receive phi(x,y), but rather an Effective Incident Fluence EIF(x,y). We numerically evaluate the EIF(x,y) from a given DMLC file by a coordinate transformation to the Targets Eye View (TEV). In the TEV coordinate system, the CTV itself is stationary, and the MLC is seen to execute a motion -z(t) that is superimposed on the DMLC motion. The resulting EIF(x,y) is input back into the dose calculation engine to estimate the 3-D dose to a moving CTV. In this study, we model respiratory motion as a sinusoidal function with an amplitude of 10 mm in the superior-inferior direction, a period of 5 s, and an initial phase of zero.

Method of identifying dynamic multileaf collimator irradiation that is highly sensitive to a systematic MLC calibration error.

In intensity modulated radiotherapy (IMRT), radiation is delivered in a multiple of multileaf collimator (MLC) subfields. A subfield with a small leaf-to-leaf opening is highly sensitive to a leaf-positional error. We introduce a method of identifying and rejecting IMRT plans that are highly sensitive to a systematic MLC gap error (sensitivity to possible random leaf-positional errors is not addressed here). There are two sources of a systematic MLC gap error: centerline mechanical offset (CMO) and, in the case of a rounded end MLC, radiation field offset (RFO). In IMRT planning system, using an incorrect value of RFO introduces a systematic error ARFO that results in all leaf-to-leaf gaps that are either too large or too small by (2*DeltaRFO), whereas assuming that CMO is zero introduces systematic error DeltaCMO that results in all gaps that are too large by DeltaCMO=CMO. We introduce a concept of the average leaf pair Opening (ALPO) that can be calculated from a dynamic MLC delivery file. We derive an analytic formula for a fractional average fluence error resulting from a systematic gap error of Deltax and show that it is inversely proportional to ALPO; explicitly it is equal to Deltax/(ALPO+ 2 * RFO+ epsilon), in which epsilon is generally of the order of 1 mm and Deltax =2 * Delta RFO + CMO. This analytic relationship is verified with independent numerical calculations.

Evaluation of radiation dose delivered by cone beam CT and tomosynthesis employed for setup of external breast irradiation

A systematic set of measurements is reported for evaluation of doses to critical organs resulting from cone-beam CT (CB-CT) and cone-beam tomosynthesis (CB-TS) as applied to breast setup for external beam irradiation. The specific focus of this study was on evaluation of doses from these modalities in a setting of volumetric breast imaging for target localization in radiotherapy treatments with the goal of minimizing radiation to healthy organs. Ion chamber measurements were performed in an anthropomorphic female thorax phantom at the center of each breast and lung and on the phantom surface at one anterior and two lateral locations (seven points total). The measurements were performed for three different isocenters located at the center of the phantom and at offset locations of the right and left breast. The dependence of the dose on angle selection for the CB-TS arc was also studied. For the most typical situation of centrally located CB-CT isocenter the measured doses ranged between 3 and 7 cGy, in good agreement with previous reports. Dose measurements were performed for a range of start/stop angles commonly used for CB-TS and the impact of direct and scatter dose on organs at risk was analyzed. All measured CB-TS doses were considerably lower than CB-CT doses, with greater decrease in dose for the organs outside of the beam (up to 98% decrease in dose). Remarkably, offsetting the isocenter towards the ipsilateral breast resulted on average to additional 46% dose reduction to organs at risk. The lowest doses to the contralateral breast and lung were less than 0.1 cGy when they were measured for the offset isocenter. The biggest reduction in dose was obtained by using CB-TS beams that completely avoid the critical organ. For points inside the CB-TS beam, the dose was reduced in a linear relation with distance from the center of the imaging arc. The data indicate that it is possible to reduce substantially radiation doses to the contralateral organs by proper selection of CB-TS angles and imaging field sizes. Our results provide the first systematic study on CB-TS doses from setup imaging for external breast irradiation and can be a useful resource for estimating anticipated radiation doses as a function of the conditions chosen for imaging breast setup.

A stochastic model of cell survival for high‐Z nanoparticle radiotherapy

PURPOSE The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy. METHODS The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement. RESULTS The authors show relatively large differences in the estimation of cell survival arising from using approximated formulae. They predict degeneration of the cell killing capacity due to different number of GNP per cell and different distances with respect to the cellular target. CONCLUSIONS The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies.

Nanoscale radiation transport and clinical beam modeling for gold nanoparticle dose enhanced radiotherapy (GNPT) using X-rays

We review radiation transport and clinical beam modelling for gold nanoparticle dose-enhanced radiotherapy using X-rays. We focus on the nanoscale radiation transport and its relation to macroscopic dosimetry for monoenergetic and clinical beams. Among other aspects, we discuss Monte Carlo and deterministic methods and their applications to predicting dose enhancement using various metrics.

The effect of flattening filter free delivery on endothelial dose enhancement with gold nanoparticles.

PURPOSE The aim of this study is to quantify and to compare the dose enhancement factor from gold nanoparticles (AuNP) to tumor endothelial cells for different concentrations of AuNP, and clinical MV beam configurations. METHODS Tumor endothelial cells are modeled as slabs measuring 10 × 10 × 2 μm. A spherical AuNP is simulated on the surface of the endothelial cell, within the blood vessel. 6 MV photon beams with and without the flattening filter are investigated for different field sizes, depths in material and beam modulation. The incident photon energy spectra for each configuration is generated using EGSnrc. The dose enhancement in the tumor endothelial cell is found using an analytical calculation. The endothelial dose enhancement factor is defined to be the ratio of the dose deposited with and without AuNPs. RESULTS It is found that clinical beam parameters may be chosen to maximize the effect of gold nanoparticles during radiotherapy. This effect is further amplified ~20% by the removal of the flattening filter. Modulation of the clinical beam with the multileaf collimator tends to decrease the proportion of low energy photons, therefore providing less enhancement than the corresponding open field. CONCLUSIONS The results of this work predict a dose enhancement to tumor blood vessel endothelial cells using conventional therapeutic (MV) x-rays and quantify the relative change in enhancement with treatment depth and field size.