M Bazalova

Investigation of X-ray Fluorescence Computed Tomography (XFCT) and K-Edge Imaging

This work provides a comprehensive Monte Carlo study of X-ray fluorescence computed tomography (XFCT) and K-edge imaging system, including the system design, the influence of various imaging components, the sensitivity and resolution under various conditions. We modified the widely used EGSnrc/DOSXYZnrc code to simulate XFCT images of two acrylic phantoms loaded with various concentrations of gold nanoparticles and Cisplatin for a number of XFCT geometries. In particular, reconstructed signal as a function of the width of the detector ring, its angular coverage and energy resolution were studied. We found that XFCT imaging sensitivity of the modeled systems consisting of a conventional X-ray tube and a full 2-cm-wide energy-resolving detector ring was 0.061% and 0.042% for gold nanoparticles and Cisplatin, respectively, for a dose of ~10cGy. Contrast-to-noise ratio (CNR) of XFCT images of the simulated acrylic phantoms was higher than that of transmission K-edge images for contrast concentrations below 0.4%.

First Demonstration of Multiplexed X-Ray Fluorescence Computed Tomography (XFCT) Imaging

Simultaneous imaging of multiple probes or biomarkers represents a critical step toward high specificity molecular imaging. In this work, we propose to utilize the element-specific nature of the X-ray fluorescence (XRF) signal for imaging multiple elements simultaneously (multiplexing) using XRF computed tomography (XFCT). A 5-mm-diameter pencil beam produced by a polychromatic X-ray source (150 kV, 20 mA) was used to stimulate emission of XRF photons from 2% (weight/volume) gold (Au), gadolinium (Gd), and barium (Ba) embedded within a water phantom. The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry. The X-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector. The spectra were then used to isolate the K shell XRF peak and to generate sinograms for the three elements of interest. The distribution and concentration of the three elements were reconstructed with the iterative maximum likelihood expectation maximization algorithm. The linearity between the XFCT intensity and the concentrations of elements of interest was investigated. We found that measured XRF spectra showed sharp peaks characteristic of Au, Gd, and Ba. The narrow full-width at half-maximum (FWHM) of the peaks strongly supports the potential of XFCT for multiplexed imaging of Au, Gd, and Ba (FWHMAu,Kα1 = 0.619 keV, FWHMAu,Kα2=1.371 keV , FWHMGd,Kα=1.297 keV, FWHMGd,Kβ=0.974 keV , FWHMBa,Kα=0.852 keV, and FWHMBa,Kβ=0.594 keV ). The distribution of Au, Gd, and Ba in the water phantom was clearly identifiable in the reconstructed XRF images. Our results showed linear relationships between the XRF intensity of each tested element and their concentrations (R2Au=0.944 , RGd2=0.986, and RBa2=0.999), suggesting that XFCT is capable of quantitative imaging. Finally, a transmission CT image was obtained to show the potential of the approach for providing attenuation correction and morphological information. In conclusion, XFCT is a promising modality for multiplexed imaging of high atomic number probes.

The importance of tissue segmentation for dose calculations for kilovoltage radiation therapy

PURPOSE The aim of this work was to evaluate the effect of tissue segmentation on the accuracy of Monte Carlo (MC) dose calculations for kilovoltage radiation therapy, which are commonly used in preclinical radiotherapy studies and are also being revisited as a clinical treatment modality. The feasibility of tissue segmentation routinely done on the basis of differences in tissue mass densities was studied and a new segmentation scheme based on differences in effective atomic numbers was developed. METHODS MC dose calculations in a cylindrical mouse phantom with small cylindrical inhomogeneities consisting of 34 ICRU-44 tissues were performed using the EGSnrc/BEAMnrc and DOSXYZnrc codes. The dose to tissue was calculated for five different kilovoltage beams currently used in small animal radiotherapy: a microCT 120 kV beam, two 225 kV beams filtered with either 4 mm of Al or 0.5 mm of Cu, a heavily filtered 320 kV beam, and a 192Ir beam. The mean doses to the 34 ICRU-44 tissues as a function of tissue mass density and effective atomic number and beam energy were studied. A treatment plan for an orthotopic lung tumor model was created, and the dose distribution was calculated for three tissue segmentation schemes using 4, 8, and 39 tissue bins to assess the significance of the simulation results for kilovoltage radiotherapy. RESULTS In our model, incorrect assignment of adipose tissue to muscle caused dose calculation differences of 27%, 13%, and 7% for the 120 kV beam and the 225 kV beams filtered with 4 mm Al and 0.5 mm Cu, respectively. For the heavily filtered 320 kV beam and a 192Ir source, potential dose calculation differences due to tissue mis-assignment were below 4%. There was no clear relationship between the dose to tissue and its mass density for x-ray beams generated by tube potentials equal or less than 225 kV. A second order polynomial fit approximated well the absorbed dose to tissue as a function of effective atomic number for these beams. In the mouse study, the 120 kV beam dose to bone was overestimated by 100% and underestimated by 10% for the 4 and 8-tissue segmentation schemes compared to the 39-tissue segmentation scheme, respectively. Dose to adipose tissue was overestimated by 30% and underestimated by 10%, respectively. In general, organ at risk (OAR) doses were overestimated in the 4-tissue and the 8-tissue segmentation schemes compared to the 39-tissue segmentation. CONCLUSIONS Tissue segmentation was shown to be a key parameter for dose calculations with kilovoltage beams used in small animal radiotherapy when an x-ray tube with a potential < or = 225 kV is used as a source. A new tissue segmentation scheme with 39 tissues based on effective number differences derived from mass density differences has been implemented.

Kilovoltage beam Monte Carlo dose calculations in submillimeter voxels for small animal radiotherapy

PURPOSE Small animal conformal radiotherapy (RT) is essential for preclinical cancer research studies and therefore various microRT systems have been recently designed. The aim of this paper is to efficiently calculate the dose delivered using our microRT system based on a microCT scanner with the Monte Carlo (MC) method and to compare the MC calculations to film measurements. METHODS Doses from 2-30 mm diameter 120 kVp photon beams deposited in a solid water phantom with 0.2 x 0.2 x 0.2 mm3 voxels are calculated using the latest versions of the EGSnrc codes BEAMNRC and DOSXYZNRC. Two dose calculation approaches are studied: a two-step approach using phase-space files and direct dose calculation with BEAMNRC simulation sources. Due to the small beam size and submillimeter voxel size resulting in long calculation times, variance reduction techniques are studied. The optimum bremsstrahlung splitting number (NBRSPL in BEAMNRC) and the optimum DOSXYZNRC photon splitting (Nsplit) number are examined for both calculation approaches and various beam sizes. The dose calculation efficiencies and the required number of histories to achieve 1% statistical uncertainty--with no particle recycling--are evaluated for 2-30 mm beams. As a final step, film dose measurements are compared to MC calculated dose distributions. RESULTS The optimum NBRSPL is approximately 1 x 10(6) for both dose calculation approaches. For the dose calculations with phase-space files, Nsplit varies only slightly for 2-30 mm beams and is established to be 300. Nsplit for the DOSXYZNRC calculation with the BEAMNRC source ranges from 300 for the 30 mm beam to 4000 for the 2 mm beam. The calculation time significantly increases for small beam sizes when the BEAMNRC simulation source is used compared to the simulations with phase-space files. For the 2 and 30 mm beams, the dose calculations with phase-space files are more efficient than the dose calculations with BEAMNRC sources by factors of 54 and 1.6, respectively. The dose calculation efficiencies converge for beams with diameters larger than 30 mm. CONCLUSIONS A very good agreement of MC calculated dose distributions to film measurements is found. The mean difference of percentage depth dose curves between calculated and measured data for 2, 5, 10, and 20 mm beams is 1.8%.

X-Ray Luminescence and X-Ray Fluorescence Computed Tomography: New Molecular Imaging Modalities

X-ray luminescence and X-ray fluorescence computed tomography (CT) are two emerging technologies in X-ray imaging that provide functional and molecular imaging capability. Both emission-type tomographic imaging modalities use external X-rays to stimulate secondary emissions, either light or secondary X-rays, which are then acquired for tomographic reconstruction. These modalities surpass the limits of sensitivity in current X-ray imaging and have the potential of enabling X-ray imaging to extract molecular imaging information. These new modalities also promise to break through the spatial resolution limits of other in vivo molecular imaging modalities. This paper reviews the development of X-ray luminescence and X-ray fluorescence CT and their relative merits. The discussion includes current problems and future research directions and the role of these modalities in future molecular imaging applications.

Order of Magnitude Sensitivity Increase in X-ray Fluorescence Computed Tomography (XFCT) Imaging With an Optimized Spectro-Spatial Detector Configuration: Theory and Simulation

The purpose of this study was to increase the sensitivity of XFCT imaging by optimizing the data acquisition geometry for reduced scatter X-rays. The placement of detectors and detector energy window were chosen to minimize scatter X-rays. We performed both theoretical calculations and Monte Carlo simulations of this optimized detector configuration on a mouse-sized phantom containing various gold concentrations. The sensitivity limits were determined for three different X-ray spectra: a monoenergetic source, a Gaussian source, and a conventional X-ray tube source. Scatter X-rays were minimized using a backscatter detector orientation (scatter direction > 110° to the primary X-ray beam). The optimized configuration simultaneously reduced the number of detectors and improved the image signal-to-noise ratio. The sensitivity of the optimized configuration was 10 μg/mL (10 pM) at 2 mGy dose with the mono-energetic source, which is an order of magnitude improvement over the unoptimized configuration (102 pM without the optimization). Similar improvements were seen with the Gaussian spectrum source and conventional X-ray tube source. The optimization improvements were predicted in the theoretical model and also demonstrated in simulations. The sensitivity of XFCT imaging can be enhanced by an order of magnitude with the data acquisition optimization, greatly enhancing the potential of this modality for future use in clinical molecular imaging.

Investigation of the effects of treatment planning variables in small animal radiotherapy dose distributions

PURPOSE Methods used for small animal radiation treatment have yet to achieve the same dose targeting as in clinical radiation therapy. Toward understanding how to better plan small animal radiation using a system recently developed for this purpose, the authors characterized dose distributions produced from conformal radiotherapy of small animals in a microCT scanner equipped with a variable-aperture collimator. METHODS Dose distributions delivered to a cylindrical solid water phantom were simulated using a Monte Carlo algorithm. Phase-space files for 120 kVp x-ray beams and collimator widths of 1-10 mm at isocenter were generated using BEAMnrc software, and dose distributions for evenly spaced beams numbered from 5 to 80 were generated in DOSXYZnrc for a variety of targets, including centered spherical targets in a range of sizes, spherical targets offset from centered by various distances, and various ellipsoidal targets. Dose distributions were analyzed using dose volume histograms. The dose delivered to a mouse bearing a spontaneous lung tumor was also simulated, and dose volume histograms were generated for the tumor, heart, left lung, right lung, and spinal cord. RESULTS Results indicated that for centered, symmetric targets, the number of beams required to achieve a smooth dose volume histogram decreased with increased target size. Dose distributions for noncentered, symmetric targets did not exhibit any significant loss of conformality with increasing offset from the phantom center, indicating sufficient beam penetration through the phantom for targeting superficial targets from all angles. Even with variable collimator widths, targeting of asymmetric targets was found to have less conformality than that of spherical targets. Irradiation of a mouse lung tumor with multiple beam widths was found to effectively deliver dose to the tumor volume while minimizing dose to other critical structures. CONCLUSIONS Overall, this method of generating and analyzing dose distributions provides a quantitative method for developing practical guidelines for small animal radiotherapy treatment planning. Future work should address methods to improve conformality in asymmetric targets.

Development of XFCT imaging strategy for monitoring the spatial distribution of platinum-based chemodrugs: Instrumentation and phantom validation

PURPOSE Developing an imaging method to directly monitor the spatial distribution of platinum-based (Pt) drugs at the tumor region is of critical importance for early assessment of treatment efficacy and personalized treatment. In this study, the authors investigated the feasibility of imaging platinum (Pt)-based drug distribution using x-ray fluorescence (XRF, a.k.a. characteristic x ray) CT (XFCT). METHODS A 5-mm-diameter pencil beam produced by a polychromatic x-ray source equipped with a tungsten anode was used to stimulate emission of XRF photons from Pt drug embedded within a water phantom. The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry. The x-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector. The spectra were then used for the K-shell XRF peak isolation and sinogram generation for Pt. The distribution and concentration of Pt were reconstructed with an iterative maximum likelihood expectation maximization algorithm. The capability of XFCT to multiplexed imaging of Pt, gadolinium (Gd), and iodine (I) within a water phantom was also investigated. RESULTS Measured XRF spectrum showed a sharp peak characteristic of Pt with a narrow full-width at half-maximum (FWHM) (FWHMKα1 = 1.138 keV, FWHMKα2 = 1.052 keV). The distribution of Pt drug in the water phantom was clearly identifiable on the reconstructed XRF images. Our results showed a linear relationship between the XRF intensity of Pt and its concentrations (R(2) = 0.995), suggesting that XFCT is capable of quantitative imaging. A transmission CT image was also obtained to show the potential of the approach for providing attenuation correction and morphological information. Finally, the distribution of Pt, Gd, and I in the water phantom was clearly identifiable in the reconstructed images from XFCT multiplexed imaging. CONCLUSIONS XFCT is a promising modality for monitoring the spatial distribution of Pt drugs. The technique may be useful in tailoring tumor treatment regimen in the future.

Modality comparison for small animal radiotherapy: A simulation study

PURPOSE Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. METHODS This paper presents a comparison of dose distributions generated by the three approaches-a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. RESULTS All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. CONCLUSIONS The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.

SU‐FF‐T‐408: Tissue Inhomogeneities in Monte Carlo Treatment Planning for Proton Therapy

Purpose: To investigate the effect of tissue segmentation and metal streaking artifacts for Monte Carlo (MC) dose calculations in proton therapy.Method and Materials: CTimages of a phantom with 9 tissue equivalent inserts were segmented into material and mass density maps using the conventional single‐energy CT and a more accurate dual‐energy (DECT) material extraction. MC dose calculations for a broad 200 MeV proton beam were performed in the exact geometry and in the single‐energy and dual‐energy CT geometries in the MCNPX code. The dose calculation errors for the two tissue segmentation approaches were quantified. MC dose calculations were performed for a 147 MeV proton beam treatment plan of a patient with metal bilateral hip prostheses based on water‐only geometry, on original CTimages with severe streaking artifacts and based on artifact corrected images. The effect of the artifacts and their correction on MC dose distribution was evaluated. Results: The materials of three inserts were incorrectly assigned using the conventional approach. The conventional tissue segmentation yielded dose calculation errors below 2%. In both the single‐energy CT and DECT geometry, there was a 0.7 cm shift in the position of the Bragg peak suggesting that density assignment is more important than correct tissue segmentation in proton beam MC dose calculations. The patient dose calculations using CTimages with streaking artifacts showed large statistical errors in the artifact corrupted voxels and differences up to 1.5 cm in the 20% and 30% isodose lines due to the artifacts. Conclusions: The shift in the Bragg peak demonstrates the need for careful mass density assignment in proton beam MC dose calculations. The use of DECT tissue segmentation might therefore have only a small added benefit. The patient study shows that a metal artifact correction is necessary for patients with bilateral hip prostheses.