Table of contents

Four-dimensional volumetric modulated arc therapy (4D VMAT) is a treatment strategy for lung cancers that aims to exploit relative target and tissue motion to improve organ at risk (OAR) sparing. The algorithm incorporates the entire patient respiratory cycle using 4D CT data into the optimization process. Resulting treatment plans synchronize the delivery of each beam aperture to a specific phase of target motion. Stereotactic body radiation therapy treatment plans for 4D VMAT, gated VMAT, and 3D VMAT were generated on three patients with non-small cell lung cancer. Tumour motion ranged from 1.4–3.4 cm. The dose and fractionation scheme was 48 Gy in four fractions. A B-spline transformation model registered the 4D CT images. 4D dose volume histograms (4D DVH) were calculated from total dose accumulated at the maximum exhalation. For the majority of OARs, gated VMAT achieved the most radiation sparing but treatment times were 77–148% longer than 3D VMAT. 4D VMAT plan qualities were comparable to gated VMAT, but treatment times were only 11–25% longer than 3D VMAT. 4D VMAT's improvement of healthy tissue sparing can allow for further dose escalation. Future study could potentially adapt 4D VMAT to irregular patient breathing patterns.

Dosimetric accuracy of radiation treatment planning in brachytherapy depends on knowledge of tissue composition. It has been speculated that soft tissues can be decomposed to water, lipid and protein. The aim of our work is to evaluate the accuracy of such tissue decomposition. Selected abdominal soft tissues, whose average elemental compositions were taken from literature, were decomposed using dual energy computed tomography to water, lipid and protein via the three-material decomposition method. The quality of the decomposition was assessed using relative differences between (i) mass energy absorption and (ii) mass energy attenuation coefficients of the analyzed and approximated tissues. It was found that the relative differences were less than 2% for photon energies larger than 10 keV. The differences were notably smaller than the ones for water as the transport and dose scoring medium. The choice of the water, protein and lipid triplet resulted in negative elemental mass fractions for some analyzed tissues. As negative elemental mass fractions cannot be used in general purpose particle transport computer codes using the Monte Carlo method, other triplets should be used for the decomposition. These triplets may further improve the accuracy of the approximation as the differences were mainly caused by the lack of high-Z materials in the water, protein and lipid triplet.

Radiochromic micelle gel dosimeters are promising for three-dimensional (3D) radiation dosimetry because they can be read out by optical CT techniques and they have superior spatial stability compared to polymer and Fricke gel dosimeters. This study evaluates the use of diacetylenes as reporter molecules in micelle gel dosimeters. Several gels containing pentacosa-10,12-diynoic acid (PCDA) emulsified using sodium dodecyl sulfate (SDS) changed from colourless to blue upon irradiation. Unfortunately, all phantoms that experienced a colour change were turbid and would be unsuitable for 3D dosimetry. Two techniques (use of organic solvent and aqueous-phase additives) were successful in increasing colloidal stability to prevent the turbidity problem, but none of the resulting transparent gels changed colour in response to radiation. Transparent PCDA emulsions were prepared using NaOH solutions with no SDS or other emulsifier, but these transparent emulsions also did not change colour. Only turbid gels and emulsions with precipitated particles responded to radiation. These results indicate that the colour change was due to the oligomerization within precipitated PCDA crystals, and that liquid-phase emulsified PCDA did not undergo oligomerization. As a result, PCDA is not suitable for use in micelle gel dosimeters, and other radiochromic reporter molecules will need to be identified.

Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations, and stray radiation doses for photon therapy were determined from measured data. Dose–risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose–risk models and mean radiation weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

We introduce a novel mechanistic model of the yield of tissue damage at the end of radiation treatment and of the subsequent healing kinetics. We find explicit expressions for the total number of functional proliferating cells as well as doomed (functional but non-proliferating) cells as a function of time post treatment. This leads to the possibility of estimating—for any given cohort of patients undergoing radiation therapy—the probability distribution of those kinetic parameters (e.g. proliferation rates) that determine times to injury onset and ensuing resolution. The model is suitable for tissues with simple duplication organization, meaning that functionally competent cells are also responsible for tissue renewal or regeneration following injury. An extension of the model to arbitrary temporal patterns of dose rate is presented. To illustrate the practical utility of the model, as well as its limitations, we apply it to data on the time course of urethral toxicity following fractionated radiation treatment and brachytherapy for prostate cancer.

Accurate understanding and modeling of respiration-induced uncertainties is essential in image-guided radiotherapy. Explicit modeling of the overall lung motion and interaction among different organs promises to be a useful approach. Recently, preliminary studies on 3D fluoroscopic treatment imaging and tumor localization based on principal component analysis motion models and cost function optimization have shown encouraging results. However, the performance of this technique for varying breathing parameters and under realistic conditions remains unclear and thus warrants further investigation. In this work, we present a systematic evaluation of a 3D fluoroscopic image generation algorithm via two different approaches. In the first approach, the model's accuracy is tested for changing parameters for sinusoidal breathing. These parameters include changing respiratory motion amplitude, period and baseline shift. The effects of setup error, imaging noise and different tumor sizes are also examined. In the second approach, we test the model for anthropomorphic images obtained from a modified XCAT phantom. This set of experiments is important as all the underlying breathing parameters are simultaneously tested, as in realistic clinical conditions. Based on our simulation results for more than 250 s of breathing data for eight different lung patients, the overall tumor localization accuracies of the model in left–right, anterior–posterior and superior–inferior directions are 0.1 ± 0.1, 0.5 ± 0.5 and 0.8 ± 0.8 mm, respectively. 3D tumor centroid localization accuracy is 1.0 ± 0.9 mm.

In single-photon emission computed tomography (SPECT), multi-pinhole collimation is often employed nowadays. Most multi-pinhole collimators avoid overlap (multiplexing) of the projections on the detector. This can be done by using additional shielding or by spacing the pinholes far enough apart. Using additional shielding has the drawback that it increases weight, design complexity and cost. Spacing the pinholes far enough apart results in sub-optimal detector usage, the valuable detector area is not entirely used. This is due to the circular projections of pinholes on the detector; these ellipses can not be tiled with high detector coverage. To overcome this we designed a new pinhole geometry, the lofthole, that has a rectangular projection on the detector. The lofthole has a circular aperture and a rectangular entrance/exit opening. Sensitivity formulae have been derived for pinholes and loftholes. These formulae take the penumbra effect into account; the proposed formulae do not take penetration into account. The derived formulae are valid for geometries where the field-of-view and the sensitivity of the aperture are solely limited by the exit window. A flood map measurement was performed to compare the rectangular projection of a lofthole with the circular projection of a pinhole. Finally, measurements were done to compare the amount of penetration of pinholes with the amount of penetration of a lofthole. A square lofthole collimator has less penetration than a knife-edge pinhole collimator that irradiates the same rectangular detector area with full coverage. A multi-lofthole collimator allows high detector coverage without using additional shielding. An additional advantage is the lower amount of penetration.

Uncertainties in the estimated mean excitation energies (I-values) needed for calculating proton stopping powers can be in the order of 10–15%, which introduces a fundamental limitation in the accuracy of proton range determination. Previous efforts have quantified shifts in proton depth dose distributions due to I-value uncertainties in water and homogenous tissue phantoms. This study is the first to quantify the clinical impact of I-value uncertainties on proton dose distributions within patient geometries. A previously developed Geant4 based Monte Carlo code was used to simulate a proton treatment plan for three patients (prostate, pancreases, and liver) with varying tissue I-values. A uniform variation study was conducted in which the tissue I-values were varied by ±5% and ±10% of the nominal values as well as a probabilistic variation study in which the I-values were randomly sampled according to a normal distribution with the mean equal to the nominal I-value and a standard deviation of 5 and 10% of the nominal values. Modification of tissue I-values impacted both the proton range and SOBP width. R₉₀ range shifts up to 7.7 mm (4.4.%) and R₈₀ range shifts up to 4.8 mm (1.9%) from the nominal range were recorded. Modulating the tissue I-values by 10% the nominal value resulted in up to a 3.5% difference mean dose in the target volumes and organs at risk compared to the nominal case. The range and dose differences were the largest for the deeper-seated prostate and pancreas cases. The treatments that were simulated with randomly sampled I-values resulted in range and dose differences that were generally within the upper and lower bounds set by the 10% uniform variations. This study demonstrated the impact of I-value uncertainties on patient dose distributions. Clearly, sub-millimeter precision in proton therapy would necessitate a reduction in I-value uncertainties to ensure an efficacious clinical outcome.

According to the international safety guidelines/standard, the whole-body-averaged specific absorption rate (Poljak et al 2003 IEEE Trans. Electromagn. Compat.45 141–5) and the peak spatial average SAR are used as metrics for human protection from whole-body and localized exposures, respectively. The IEEE standard (IEEE 2006 IEEE C95.1) indicates that the upper boundary frequency, over which the whole-body-averaged SAR is deemed to be the basic restriction, has been reduced from 6 to 3 GHz, because radio-wave energy is absorbed around the body surface when the frequency is increased. However, no quantitative discussion has been provided to support this description especially from the standpoint of temperature elevation. It is of interest to investigate the maximum temperature elevation in addition to the core temperature even for a whole-body exposure. In the present study, using anatomically based human models, we computed the SAR and the temperature elevation for a plane-wave exposure from 30 MHz to 6 GHz, taking into account the thermoregulatory response. As the primary result, we found that the ratio of the core temperature elevation to the whole-body-averaged SAR is almost frequency independent for frequencies below a few gigahertz; the ratio decreases above this frequency. At frequencies higher than a few gigahertz, core temperature elevation for the same whole-body averaged SAR becomes lower due to heat convection from the skin to air. This lower core temperature elevation is attributable to skin temperature elevation caused by the power absorption around the body surface. Then, core temperature elevation even for whole-body averaged SAR of 4 W kg⁻¹ with the duration of 1 h was at most 0.8 °C, which is smaller than a threshold considered in the safety guidelines/standard. Further, the peak 10 g averaged SAR is correlated with the maximum body temperature elevations without extremities and pinna over the frequencies considered. These findings were confirmed for seven models, including models of a child and a pregnant female. Thus, the current basic restriction for whole-body exposure in the international guidelines is conservative. Peak spatial-averaged SAR can be used as a metric for estimating local temperature elevation even for whole-body exposure. Our computational results also support the description in the IEEE standard about the reduction of the upper applicable frequency of whole-body-averaged SAR from 6 and 3 GHz; the power density reference level is more conservative than the basic restriction limit for the whole-body averaged SAR from the standpoint of temperature elevation.

Evidence suggests that compression and shear wave elastography are sensitive to the mechanical property changes occuring in dying cells following chemotherapy, and can hence be used to monitor cancer treatment response. A qualitative and quantitative understanding of the mechanical changes at the cellular level would allow to better infer how these changes affect macroscopic tissue mechanical properties and therefore allow the optimization of elastographic techniques (such as shear wave elastography) for the monitoring of cancer therapy. We used intracellular particle tracking microrheology (PTM) to investigate the mechanical property changes of cells exposed to paclitaxol, a mitotic inhibitor used in cancer chemotherapy. The average elastic and viscous moduli of the cytoplasm of treated MCF-7 breast cancer cells were calculated for frequency ranges between 0.2 and 100 rad s^–1 (corresponding to 0.03 and 15.92 Hz, respectively). A significant increase in the complex shear modulus of the cell cytoplasm was detected at 12 h post treatment. At 24 h after drug exposure, the elastic and viscous moduli increased by a total of 191.3 Pa (>8000×) and 9 Pa (∼9×), respectively for low frequency shear modulus measurements (at 1 rad s^–1). At higher frequencies (10 rad s^–1), the elastic and viscous moduli increased by 188.5 Pa (∼60×) and 1.7 Pa (∼1.1×), respectively. Our work demonstrates that PTM can be used to measure changes in the mechanical properties of treated cells and that cell elasticity significantly increases by 24 h after chemotherapy exposure.

A new method for the estimation of the light scattering phase function of particles is presented. The method allows us to measure the light scattering phase function of particles of any shape in the full angular range (0°–180°) and is based on the analysis of laser Doppler (LD) power density spectra. The theoretical background of the method and results of its validation using data from Monte Carlo simulations will be presented. For the estimation of the scattering phase function, a phantom measurement setup is proposed containing a LD measurement system and a simple model in which a liquid sample flows through a glass tube fixed in an optically turbid material. The scattering phase function estimation error was thoroughly investigated in relation to the light scattering anisotropy factor g. The error of g estimation is lower than 10% for anisotropy factors larger than 0.5 and decreases with increase of the anisotropy factor (e.g. for g = 0.98, the error of estimation is 0.01%). The analysis of influence of the noise in the measured LD spectrum showed that the g estimation error is lower than 1% for signal to noise ratio higher than 50 dB.

The purpose of this work was to present the fundamental dosimetric characteristics of a hypothetical ¹⁵³Gd brachytherapy source using the AAPM TG-43U1 dose-calculation formalism. Gadolinium-153 is an intermediate-energy isotope that emits 40–100 keV photons with a half-life of 242 days. The rationale for considering ¹⁵³Gd as a brachytherapy source is for its potential of patient specific shielding and to enable reduced personnel shielding requirements relative to ¹⁹²Ir, and as an isotope for interstitial rotating shield brachytherapy (I-RSBT). A hypothetical ¹⁵³Gd brachytherapy source with an active core of 0.84 mm diameter, 10 mm length and specific activity of 5.55 TBq of ¹⁵³Gd per gram of Gd was simulated with Geant4. The encapsulation material was stainless steel with a thickness of 0.08 mm. The radial dose function, anisotropy function and photon spectrum in water were calculated for the ¹⁵³Gd source. The simulated ¹⁵³Gd source had an activity of 242 GBq and a dose rate in water 1 cm off axis of 13.12 Gy h⁻¹, indicating that it would be suitable as a low-dose-rate or pulsed-dose-rate brachytherapy source. The beta particles emitted have low enough energies to be absorbed in the source encapsulation. Gadolinium-153 has an increasing radial dose function due to multiple scatter of low-energy photons. Scattered photon dose takes over with distance from the source and contributes to the majority of the absorbed dose. The anisotropy function of the ¹⁵³Gd source decreases at low polar angles, as a result of the long active core. The source is less anisotropic at polar angles away from the longitudinal axes. The anisotropy function increases with increasing distance. The ¹⁵³Gd source considered would be suitable as an intermediate-energy low-dose-rate or pulsed-dose-rate brachytherapy source. The source could provide a means for I-RSBT delivery and enable brachytherapy treatments with patient specific shielding and reduced personnel shielding requirements relative to ¹⁹²Ir.

To perform in vivo animal single photon emission computed tomography imaging on a stationary detector gantry, we introduced a hybrid rotation-translation (HRT) tomographic scan, a combination of translational and limited angle rotational movements of the image object, to minimize gravity-induced animal motion. To quantitatively assess the performance of ten HRT scan schemes and the conventional rotation-only scan scheme, two simulated phantoms were first scanned with each scheme to derive the corresponding image resolution (IR) in the image field of view. The IR results of all the scan schemes were visually assessed and compared with corresponding outputs of four scan scheme evaluation indices, i.e. sampling completeness (SC), sensitivity (S), conventional system resolution (SR), and a newly devised directional spatial resolution (DR) that measures the resolution in any specified orientation. A representative HRT scheme was tested with an experimental phantom study. Eight of the ten HRT scan schemes evaluated achieved a superior performance compared to two other HRT schemes and the rotation-only scheme in terms of phantom image resolution. The same eight HRT scan schemes also achieved equivalent or better performance in terms of the four quantitative indices than the conventional rotation-only scheme. As compared to the conventional index SR, the new index DR appears to be a more relevant indicator of system resolution performance. The experimental phantom image obtained from the selected HRT scheme was satisfactory. We conclude that it is feasible to perform in vivo animal imaging with a HRT scan scheme and SC and DR are useful predictors for quantitatively assessing the performance of a scan scheme.

It has been accepted that the dynamic responses of ultrasound contrast agent (UCA) microbubbles will be significantly affected by the encapsulating shell properties (e.g., shell elasticity and viscosity). In this work, a new model is proposed to describe the complicated rheological behaviors in an encapsulating shell of UCA microbubbles by applying the nonlinear 'Cross law' to the shell viscous term in the Marmottant model. The proposed new model was verified by fitting the dynamic responses of UCAs measured with either a high-speed optical imaging system or a light scattering system. The comparison results between the measured radius–time curves and the numerical simulations demonstrate that the 'compression-only' behavior of UCAs can be successfully simulated with the new model. Then, the shell elastic and viscous coefficients of SonoVue microbubbles were evaluated based on the new model simulations, and compared to the results obtained from some existing UCA models. The results confirm the capability of the current model for reducing the dependence of bubble shell parameters on the initial bubble radius, which indicates that the current model might be more comprehensive to describe the complex rheological nature (e.g., 'shear-thinning' and 'strain-softening') in encapsulating shells of UCA microbubbles by taking into account the nonlinear changes of both shell elasticity and shell viscosity.

We present a study through extensive simulation that considers the impact of inhomogeneous optical scattering coefficient distribution on recovery of optical absorption coefficient maps using tomographic photoacoustic data collected from media mimicking breast tissue. We found that while the impact of scattering heterogeneities/targets is modest on photoacoustic recovery of optical absorption coefficients, the impact of scattering contrast caused by adipose tissue, a layer of normal tissue along the boundary of the breast, is dramatic on reconstruction of optical absorption coefficients using photoacoustic data—up to 25.8% relative error in recovering the absorption coefficient is estimated in such cases. To overcome this problem, we propose a new method to enhance photoacoustic recovery of the optical absorption coefficient in heterogeneous media by considering inhomogeneous scattering coefficient distribution provided by diffuse optical tomography (DOT). Results from extensive simulations show that photoacoustic recovery of absorption coefficient maps can be improved considerably with a priori scattering information from DOT.

We propose a plan adaptation method for fast treatment plan generation in scanned ion beam therapy. Analysis of optimized treatment plans with carbon ions indicates that the particle number modulation of consecutive rasterspots in depth shows little variation throughout target volumes with convex shape. Thus, we extract a depth-modulation curve (DMC) from existing reference plans and adapt it for creation of new plans in similar treatment situations. The proposed method is tested with seven CT serials of prostate patients and three digital phantom datasets generated with the MATLAB code. Plans are generated with a treatment planning software developed by GSI using single-field uniform dose optimization for all the CT datasets to serve as reference plans and 'gold standard'. The adapted plans are generated based on the DMC derived from the reference plans of the same patient (intra-patient), different patient (inter-patient) and phantoms (phantom-patient). They are compared with the reference plans and a re-positioning strategy. Generally, in 1 min on a standard PC, either a physical plan or a biological plan can be generated with the adaptive method provided that the new target contour is available. In all the cases, the V95 values of the adapted plans can achieve 97% for either physical or biological plans. V107 is always 0 indicating no overdosage, and target dose homogeneity is above 0.98 in all cases. The dose received by the organs at risk is comparable to the optimized plans. The plan adaptation method has the potential for on-line adaptation to deal with inter-fractional motion, as well as fast off-line treatment planning, with either the prescribed physical dose or the RBE-weighted dose.

This work aims to investigate the dosimetric impact of dental implants on volumetric modulated arc therapy (VMAT) for head-and-neck patients and to evaluate the effectiveness of using the material's electron-density ratio for the correction. An in-house Monte Carlo (MC) code was utilized for the dose calculation to account for the scattering and attenuation caused by the high-Z implant material. Three different dental implant materials were studied in this work: titanium, Degubond®4 and gold. The dose perturbations caused by the dental implant materials were first investigated in a water phantom with a 1 cm³ insert. The per cent depth dose distributions of a 3 × 3 cm² photon field were compared with the insert material as water and the three selected dental implant materials. To evaluate the impact of the dental implant on VMAT patient dose calculation, four head-and-neck cases were selected. For each case, the VMAT plan was designed based on the artifact-corrected patient geometry using a treatment planning system (TPS) that was typically utilized for routine patient treatment. The plans were re-calculated using the MC code for five situations: uncorrected geometry, artifact-corrected geometry and artifact-corrected geometry with one of the three different implant materials. The isodose distributions and the dose–volume histograms were cross-compared with each other. To evaluate the effectiveness of using the material's electron-density ratio for dental implant correction, the implant region was set as water with the material's electron-density ratio and the calculated dose was compared with the MC simulation with the real material. The main effect of the dental implant was the severe attenuation in the downstream. The 1 cm³ dental implant can lower the downstream dose by 10% (Ti) to 51% (Au) for a 3 × 3 cm² field. The TPS failed to account for the dose perturbation if the dental implant material was not precisely defined. For the VMAT patient dose calculation, the presence of dental implants degrades the PTV coverage significantly. With the material's electron-density ratio applied, the dose calculation accuracy in the water phantom and the VMAT patient was improved to a clinically acceptable level. The effects of the dental implant material can be clinically significant and its impact varies with the density of the dental implant material. We demonstrated that it was effective to use the material's electron-density ratio to account for the dosimetric impact of the dental implant.

Current inverse treatment planning methods that optimize both catheter positions and dwell times in prostate HDR brachytherapy use surrogate linear or quadratic objective functions that have no direct interpretation in terms of dose–volume histogram (DVH) criteria, do not result in an optimum or have long solution times. We decrease the solution time of the existing linear and quadratic dose-based programming models (LP and QP, respectively) to allow optimizing over potential catheter positions using mixed integer programming. An additional average speed-up of 75% can be obtained by stopping the solver at an early stage, without deterioration of the plan quality. For a fixed catheter configuration, the dwell time optimization model LP solves to optimality in less than 15 s, which confirms earlier results. We propose an iterative procedure for QP that allows us to prescribe the target dose as an interval, while retaining independence between the solution time and the number of dose calculation points. This iterative procedure is comparable in speed to the LP model and produces better plans than the non-iterative QP. We formulate a new dose–volume-based model that maximizes V_100% while satisfying pre-set DVH criteria. This model optimizes both catheter positions and dwell times within a few minutes depending on prostate volume and number of catheters, optimizes dwell times within 35 s and gives better DVH statistics than dose-based models. The solutions suggest that the correlation between the objective value and the clinical plan quality is weak in the existing dose-based models.

The purpose of this study is to investigate whether quality assurance (QA) for cone-beam computed tomography (CBCT) image rotation is necessary in order to ensure the accuracy of CBCT based image-guided radiation therapy (IGRT) and adaptive radiotherapy (ART). Misregistration of angular coordinates during CBCT acquisition may lead to a rotated reconstructed image. If target localization is performed based on this image, an under- or over-dosage of the target volume (TV) and organs at risk (OARs) may occur. Therefore, patient CT image sets were rotated by 1° up to 3° and the treatment plans were recalculated to quantify changes in dose–volume histograms. A computer code in C++ was written to model the TV displacement and overlap area of an ellipse shape at the target and dose prescription levels corresponding to the image rotation. We investigated clinical scenarios in IGRT and ART in order to study the implications of image rotation on dose distributions for: (1) lateral TV and isocenter (SBRT), (2) central TV and isocenter (IMRT), (3) lateral TV and isocenter (IMRT). Mathematical analysis showed the dose coverage of TV depends on its shape, size, location, and orientation relative to the isocenter. Evaluation of three first scenario for θ = 1° showed variations in TV D95 in the context of IGRT and ART when compared to the original plan were within 2.7 ± 2.6% and 7.7 ± 6.9% respectively while variations in the second and third scenarios were less significant (<0.5%) for the angular range evaluated. However a larger degree of variation was found in terms of minimum and maximum doses for target and OARs. The rotation of CBCT image data sets may have significant dosimetric consequences in IGRT and ART. The TV's location relative to isocenter and shape determine the extent of alterations in dose indicators. Our findings suggest that a CBCT QA criterion of 1° would be a reasonable action level to ensure accurate dose delivery.

To validate that altering radiotherapy dose rate through either changing pulse repetition frequency or instantaneous dose rate does not have an effect on cell survival, two human carcinoma and a hamster lung cell line were irradiated with various beam settings. Varian TrueBeam linac with a flattening filter free mode of operation was used for all experiments. The results obtained indicate that either method of changing dose rate has no effect on cell survival in the three cell lines studied. Filtered and filter free modes were also compared in treatments with protracted dose delivery which significantly increases overall treatment time. Cell survival indicated no difference between filter and filter free beam delivery in any of the protraction schemes. An increase in survival was seen in both modes upon protracting dose delivery to 15, 30 or 60 min rather than delivering acutely. Further, analysis of induced DNA double-strand breaks via the γH2AX assay showed no difference between filtered and unfiltered beams. The following study suggests that increasing dose rate is an acceptable manner of decreasing radiotherapy treatment time that does not have any detrimental effects on in vitro cell eradication.

The availability of a non-invasive express method for the in vivo measurement of both sound velocity and thickness of the human skull bone would be of great benefit to various transcranial ultrasonic imaging and treatment applications. This paper investigates two ultrasonic methods that measure both parameters and are based on the variable focus technique. All the experiments described in this paper were conducted on specially prepared custom skull bone phantoms, including flat and deformed samples, designed and developed in our laboratory. The first method uses a single immersion 2.25 MHz ultrasonic transducer consecutively focused on the front and back surfaces of the sample. The accuracy and precision of this method are demonstrated via single point measurements on flat samples with and without porosity. The measurement results from a specimen with the randomly curved back surface show the possibility of obtaining the inner profile of the skull bone. The second presented method is a practical modification of the variable focus technique for the linear phased array case. The method was tested on flat and curved skull bone phantoms with and without inner porosity showing higher measurement accuracy and simpler practical realization than its scanning counterpart.

In this paper, we explore the applicability of template-based compensation for the partial volume effect (PVE) for situations where (i) the image has multiple uptake sites (tumors and organs) but only one of them is treated as a region of interest (ROI) with the boundaries available from a high-resolution modality and (ii) no information regarding activities inside or outside this ROI is a priori available. We modeled this situation by performing SPECT acquisitions of phantoms containing 21 containers, which had different shapes and sizes and were filled with different levels of activity. In our analysis, each of these containers was treated as an individual ROI. We compared the performance of two methods of template construction. In method 1, the ROI template value was obtained from a conventionally reconstructed (without PVEC) image. In method 2, the ROI template value was directly (bypassing the PVE-affected conventional image) calculated from projections using region-based reconstruction. Our processing shows that method 1 resulted in consistent (activities for all 21 ROIs were improved) but relatively weak PVE compensation (errors of recovered total activities were equal to or lower than 10% for 5 ROIs only). Application of method 2 resulted in a selective (activities for 19 ROIs were improved) but considerably better compensation when compared to method 1 (errors of recovered total activities were equal to or lower than 10% for 10 ROIs).

The purpose of this work is to investigate how alternative macroscopic dose descriptors track absorbed dose to biologically relevant subcellular targets via Monte Carlo (MC) analysis of cellular models for a variety of cancerous and normal soft tissues for kilovoltage radiation. The relative mass distributions of water, light inorganic elements, and protein components of nuclear and cytoplasm compartments for various tissues are determined from a literature review. These data are used to develop representative cell models to demonstrate the range of mass elemental compositions of these subcellular structures encountered in the literature from which radiological quantities (energy absorption and attenuation coefficients; stopping powers) are computed. Using representative models of cell clusters, doses to subcellular targets are computed using MC simulation for photon sources of energies between 20 and 370 keV and are compared to bulk medium dose descriptors. It is found that cells contain significant and varying mass fractions of protein and inorganic elements, leading to variations in mass energy absorption coefficients for cytoplasm and nuclear media as large as 10% compared to water for sub-50 keV photons. Doses to subcellular structures vary by as much as 23% compared to doses to the corresponding average bulk medium or to small water cavities embedded in the bulk medium. Relationships between cellular target doses and doses to the bulk medium or to a small water cavity embedded in the bulk medium are sensitive to source energy and cell morphology, particularly for lower energy sources, e.g., low energy brachytherapy (<50 keV). Results suggest that cells in cancerous and normal soft tissues are generally not radiologically equivalent to either water or the corresponding average bulk tissue. For kilovoltage photon sources, neither dose to bulk medium nor dose to water quantitatively tracks energy imparted to biologically relevant subcellular targets for the range of cellular morphologies and tissues considered.

We introduce a method for denoising dynamic PET data, spatio-temporal expectation-maximization (STEM) filtering, that combines four-dimensional Gaussian filtering with EM deconvolution. The initial Gaussian filter suppresses noise at a broad range of spatial and temporal frequencies and EM deconvolution quickly restores the frequencies most important to the signal. We aim to demonstrate that STEM filtering can improve variance in both individual time frames and in parametric images without introducing significant bias. We evaluate STEM filtering with a dynamic phantom study, and with simulated and human dynamic PET studies of a tracer with reversible binding behaviour, [C-11]raclopride, and a tracer with irreversible binding behaviour, [F-18]FDOPA. STEM filtering is compared to a number of established three and four-dimensional denoising methods. STEM filtering provides substantial improvements in variance in both individual time frames and in parametric images generated with a number of kinetic analysis techniques while introducing little bias. STEM filtering does bias early frames, but this does not affect quantitative parameter estimates. STEM filtering is shown to be superior to the other simple denoising methods studied. STEM filtering is a simple and effective denoising method that could be valuable for a wide range of dynamic PET applications.

In proton beam therapy, changes in the proton range due to lateral heterogeneity may cause serious errors in the dose distribution. In the present study, the pencil-beam redefinition algorithm (PBRA) was applied to proton beam therapy to address the problem of lateral density heterogeneity. In the calculation, the phase-space parameters were characterized for multiple range (i.e. proton energy) bins for given pencil beams. The particles that were included in each pencil beam were transported and redefined periodically until they had stopped. The redefined beams formed a detouring path that was different from that of the non-redefined pencil beams, and the path of each redefined beam was straight. The results calculated by the PBRA were compared with measured proton dose distributions in a heterogeneous slab phantom and an anthropomorphic phantom. Through the beam redefinition process, the PBRA was able to predict the measured proton-detouring effects. Therefore, the PBRA may allow improved calculation accuracy when dealing with lateral heterogeneities in proton therapy applications.

A nonlinear model for the x-ray linear attenuation coefficient μ is employed for dual energy x-ray analysis (DEXA). Nonlinear simultaneous equations formed by μ and energy dependent model parameters are solved for the electron density N_e and fourth compositional ratio R₄ which has the same 'units' as the atomic number. Computed tomography data was acquired at 20–35 keV using bending magnet synchrotron radiation, a double crystal monochromator, a rotation stage and an area detector. Test objects contained liquid samples as mixtures of ethanol, water and salt solutions with known density and composition. Various noise sources are identified and give μ uncertainties of 1–2%. A fan beam geometry allowed the detection of forward scattered radiation with measured μ being 6% lower than expectations for a narrow beam. Energy dependent model parameters were obtained by solving linear simultaneous equations formed by μ and material parameters based upon N_e and R₄. DEXA accuracy was studied as a function of photon energy and sample composition. Propagation of errors analysis identifies the importance of the fractional compositional cross-products whose difference at the two beam energies should exceed 0.1, requiring 10 keV or more separation. For a reasonable approximation for the adjustable model parameters, the mean difference between the DEXA solution and true values (ΔN_e, ΔR₄) are (1.0%, 0.5%) for soft tissue and (1.5%, 0.8%) for bone like samples.

Precise timing resolution is crucial for applications requiring photon time-of-flight (ToF) information such as ToF positron emission tomography (PET). Silicon photomultipliers (SiPM) for PET, with their high output capacitance, are known to require custom preamplifiers to optimize timing performance. In this paper, we describe simple alternative front-end electronics based on a commercial low-noise RF preamplifier and methods that have been implemented to achieve excellent timing resolution. Two radiation detectors with L(Y)SO scintillators coupled to Hamamatsu SiPMs (MPPC S10362–33-050C) and front-end electronics based on an RF amplifier (MAR-3SM+), typically used for wireless applications that require minimal additional circuitry, have been fabricated. These detectors were used to detect annihilation photons from a Ge-68 source and the output signals were subsequently digitized by a high speed oscilloscope for offline processing. A coincident resolving time (CRT) of 147 ± 3 ps FWHM and 186 ± 3 ps FWHM with 3 × 3 × 5 mm³ and with 3 × 3 × 20 mm³ LYSO crystal elements were measured, respectively. With smaller 2 × 2 × 3 mm³ LSO crystals, a CRT of 125 ± 2 ps FWHM was achieved with slight improvement to 121 ± 3 ps at a lower temperature (15° C). Finally, with the 20 mm length crystals, a degradation of timing resolution was observed for annihilation photon interactions that occur close to the photosensor compared to shallow depth-of-interaction (DOI). We conclude that commercial RF amplifiers optimized for noise, besides their ease of use, can produce excellent timing resolution comparable to best reported values acquired with custom readout electronics. On the other hand, as timing performance degrades with increasing photon DOI, a head-on detector configuration will produce better CRT than a side-irradiated setup for longer crystals.

Accurate characterization of breast tumors is important for the appropriate selection of therapy and monitoring of the response. For this purpose breast imaging and tissue biopsy are important aspects. In this study, a fully automated method for deformable registration of DCE-MRI and PET/CT of the breast is presented. The registration is performed using the CT component of the PET/CT and the pre-contrast T1-weighted non-fat suppressed MRI. Comparable patient setup protocols were used during the MRI and PET examinations in order to avoid having to make assumptions of biomedical properties of the breast during and after the application of chemotherapy. The registration uses a multi-resolution approach to speed up the process and to minimize the probability of converging to local minima. The validation was performed on 140 breasts (70 patients). From a total number of registration cases, 94.2% of the breasts were aligned within 4.0 mm accuracy (1 PET voxel). Fused information may be beneficial to obtain representative biopsy samples, which in turn will benefit the treatment of the patient.

In clinically established—absorption-based—biomedical x-ray imaging, contrast agents with high atomic numbers (e.g. iodine) are commonly used for contrast enhancement. The development of novel x-ray contrast modalities such as phase contrast and dark-field contrast opens up the possible use of alternative contrast media in x-ray imaging. We investigate using ultrasound contrast agents, which unlike iodine-based contrast agents can also be administered to patients with renal impairment and thyroid dysfunction, for application with a recently developed novel x-ray dark-field imaging modality. To produce contrast from these microbubble-based contrast agents, our method exploits ultra-small-angle coherent x-ray scattering. Such scattering dark-field x-ray images can be obtained with a grating-based x-ray imaging setup, together with refraction-based differential phase-contrast and the conventional attenuation contrast images. In this work we specifically show that ultrasound contrast agents based on microbubbles can be used to produce strongly enhanced dark-field contrast, with superior contrast-to-noise ratio compared to the attenuation signal. We also demonstrate that this method works well with an x-ray tube-based setup and that the relative contrast gain even increases when the pixel size is increased from tenths of microns to clinically compatible detector resolutions about up to a millimetre.

Following the proposal by several groups to integrate magnetic resonance imaging (MRI) with radiation therapy, much attention has been afforded to examining the impact of strong (on the order of a Tesla) transverse magnetic fields on photon dose distributions. The effect of the magnetic field on dose distributions must be considered in order to take full advantage of the benefits of real-time intra-fraction imaging. In this investigation, we compared the handling of particle transport in magnetic fields between two Monte Carlo codes, EGSnrc and Geant4, to analyze various aspects of their electromagnetic transport algorithms; both codes are well-benchmarked for medical physics applications in the absence of magnetic fields. A water–air–water slab phantom and a water–lung–water slab phantom were used to highlight dose perturbations near high- and low-density interfaces. We have implemented a method of calculating the Lorentz force in EGSnrc based on theoretical models in literature, and show very good consistency between the two Monte Carlo codes. This investigation further demonstrates the importance of accurate dosimetry for MRI-guided radiation therapy (MRIgRT), and facilitates the integration of a ViewRay MRIgRT system in the University of Wisconsin-Madison's Radiation Oncology Department.