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Selective subvolume boosting can theoretically improve tumour control probability while maintaining normal tissue complication probabilities similar to those of uniform dose distributions. In this work the abilities of intensity-modulated x-ray therapy (IMXT) and intensity-modulated proton therapy (IMPT) to deliver boosts to multiple subvolumes of varying size and proximities are compared in a thorough phantom study. IMXT plans were created using the step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) methods. IMPT plans were created with the spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT) methods. IMPT-DGT is a generalization of the distal edge tracking method designed to reduce the number of proton beam spots required to deliver non-uniform dose distributions relative to IMPT-SS. The IMPT methods were delivered over both 180° and 360° arcs. The IMXT-SAS and IMPT-SS methods optimally satisfied the non-uniform dose prescriptions the least and the most, respectively. The IMPT delivery methods reduced the normal tissue integral dose by a factor of about 2 relative to the IMXT delivery methods, regardless of the delivery arc. The IMPT-DGT method reduced the number of proton beam spots by a factor of about 3 relative to the IMPT-SS method.

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The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole–Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

For more information on this article, see medicalphysicsweb.org

A Monte Carlo simulation has been developed for neutron stimulated emission computed tomography (NSECT) using the GEANT4 toolkit. NSECT is a new approach to biomedical imaging that allows spectral analysis of the elements present within the sample. In NSECT, a beam of high-energy neutrons interrogates a sample and the nuclei in the sample are stimulated to an excited state by inelastic scattering of the neutrons. The characteristic gammas emitted by the excited nuclei are captured in a spectrometer to form multi-energy spectra. Currently, a tomographic image is formed using a collimated neutron beam to define the line integral paths for the tomographic projections. These projection data are reconstructed to form a representation of the distribution of individual elements in the sample. To facilitate the development of this technique, a Monte Carlo simulation model has been constructed from the GEANT4 toolkit. This simulation includes modeling of the neutron beam source and collimation, the samples, the neutron interactions within the samples, the emission of characteristic gammas, and the detection of these gammas in a Germanium crystal. In addition, the model allows the absorbed radiation dose to be calculated for internal components of the sample. NSECT presents challenges not typically addressed in Monte Carlo modeling of high-energy physics applications. In order to address issues critical to the clinical development of NSECT, this paper will describe the GEANT4 simulation environment and three separate simulations performed to accomplish three specific aims. First, comparison of a simulation to a tomographic experiment will verify the accuracy of both the gamma energy spectra produced and the positioning of the beam relative to the sample. Second, parametric analysis of simulations performed with different user-defined variables will determine the best way to effectively model low energy neutrons in tissue, which is a concern with the high hydrogen content in biological tissue. Third, determination of the energy absorbed in tissue during neutron interrogation in order to estimate the dose. Results from these three simulation experiments demonstrate that GEANT4 is an effective simulation platform that can be used to facilitate the future development and optimization of NSECT.

Most statistical reconstruction methods for emission tomography are designed for data modeled as conditionally independent Poisson variates. In reality, due to scanner detectors, electronics and data processing, correlations are introduced into the data resulting in dependent variates. In general, these correlations are ignored because they are difficult to measure and lead to computationally challenging statistical reconstruction algorithms. This work addresses the second concern, seeking to simplify the reconstruction of correlated data and provide a more precise image estimate than the conventional independent methods. In general, correlated variates have a large non-diagonal covariance matrix that is computationally challenging to use as a weighting term in a reconstruction algorithm. This work proposes two methods to simplify the use of a non-diagonal covariance matrix as the weighting term by (a) limiting the number of dimensions in which the correlations are modeled and (b) adopting flexible, yet computationally tractable, models for correlation structure. We apply and test these methods with simple simulated PET data and data processed with the Fourier rebinning algorithm which include the one-dimensional correlations in the axial direction and the two-dimensional correlations in the transaxial directions. The methods are incorporated into a penalized weighted least-squares 2D reconstruction and compared with a conventional maximum a posteriori approach.

Identification of specific tissue types in conventional mammographic examinations is extremely limited. However, the use of x-ray diffraction effects during imaging has the potential to characterize the tissue types present due to the fact that each tissue type produces its own unique diffraction signature. Nevertheless, the analysis and categorization of these diffraction signatures by tissue type can be hampered by the inhomogeneous nature of breast tissue, leading to categorization errors where several types are present. This work aims to reduce sample categorization errors by combining spectral diffraction signature collection with sample imaging, giving more detailed data on the composition of each sample. Diffraction microCT was carried out on 19 unfixed breast tissue samples using an energy resolving translate–rotate CT system. High-resolution transmission microCT images were also recorded for comparison and sample composition analysis. Following imaging, the samples were subjected to histopathological analysis. Reconstructing on various momentum transfer regions allows different tissue types to be identified in the diffraction images. Results show a correlation between measured x-ray diffraction images and stained histopathological tissue sections. X-ray diffraction signatures generated from the measured data were categorized and analysed, with a t-test indicating that they have the potential for use in tissue type identification.

In this paper, we develop an approximate analytical reconstruction algorithm that compensates for uniform attenuation in 2D parallel-beam SPECT with a 180° acquisition. This new algorithm is in the form of a direct Fourier reconstruction. The complex variable central slice theorem is used to derive this algorithm. The image is reconstructed with the following steps: first, the attenuated projection data acquired over 180° are extended to 360° and the value for the uniform attenuator is changed to a negative value. The Fourier transform (FT) of the image in polar coordinates is obtained from the Fourier transform of an analytic function interpolated from an extension of the projection data according to the complex central slice theorem. Finally, the image is obtained by performing a 2D inverse Fourier transform. Computer simulations and comparison studies with a 360° full-scan algorithm are provided.

The objective of this work was to evaluate the feasibility of a two-compartment distributed-parameter (DP) tracer kinetic model to generate functional images of several physiologic parameters from dynamic contrast-enhanced CT data obtained of patients with extracranial head and neck tumors and to compare the DP functional images to those obtained by deconvolution-based DCE-CT data analysis. We performed post-processing of DCE-CT studies, obtained from 15 patients with benign and malignant head and neck cancer. We introduced a DP model of the impulse residue function for a capillary-tissue exchange unit, which accounts for the processes of convective transport and capillary-tissue exchange. The calculated parametric maps represented blood flow (F), intravascular blood volume (v₁), extravascular extracellular blood volume (v₂), vascular transit time (t₁), permeability–surface area product (PS), transfer ratios k₁₂ and k₂₁, and the fraction of extracted tracer (E). Based on the same regions of interest (ROI) analysis, we calculated the tumor blood flow (BF), blood volume (BV) and mean transit time (MTT) by using a modified deconvolution-based analysis taking into account the extravasation of the contrast agent for PS imaging. We compared the corresponding values by using Bland–Altman plot analysis. We outlined 73 ROIs including tumor sites, lymph nodes and normal tissue. The Bland–Altman plot analysis revealed that the two methods showed an accepted degree of agreement for blood flow, and, thus, can be used interchangeably for measuring this parameter. Slightly worse agreement was observed between v₁ in the DP model and BV but even here the two tracer kinetic analyses can be used interchangeably. Under consideration of whether both techniques may be used interchangeably was the case of t₁ and MTT, as well as for measurements of the PS values. The application of the proposed DP model is feasible in the clinical routine and it can be used interchangeably for measuring blood flow and vascular volume with the commercially available reference standard of the deconvolution-based approach. The lack of substantial agreement between the measurements of vascular transit time and permeability–surface area product may be attributed to the different tracer kinetic principles employed by both models and the detailed capillary tissue exchange physiological modeling of the DP technique.

Energy and angular distributions of electron beams with different energies were simulated by Monte Carlo calculations. These beams were generated by the NOVAC7® system (Hitesys, Italy), a mobile electron accelerator specifically dedicated to intra-operative radiation therapy (IORT). The electron beam simulations were verified by comparing the measured dose distributions with the corresponding calculated distributions. As expected, a considerable difference was observed in the energy and angular distributions between the IORT beams studied in the present work and the electron beams produced by conventional accelerators for non-IORT applications. It was also found that significant differences exist between the IORT beams used in this work and other IORT beams with different collimation systems. For example, the contribution from the scattered electrons to the total dose was found to be up to 15% higher in the NOVAC7® beams. The water-to-air stopping power ratios of the IORT beams used in this work were calculated on the basis of the beam energy distributions obtained by the Monte Carlo simulations. These calculated stopping power ratios, s_w,air, were compared with the corresponding s_w,air values recommended by the TRS-381 and TRS-398 IAEA dosimetry protocols in order to estimate the deviations between a dosimetry based on generic parameters and a dosimetry based on parameters specifically obtained for the actual IORT beams. The deviations in the s_w,air values were found to be as large as up to about 1%. Therefore, we recommend that a preliminary analysis should always be made when dealing with IORT beams in order to assess to what extent the possible differences in the s_w,air values have to be accounted for or may be neglected on the basis of the specific accuracy needed in clinical dosimetry.

Numerical modelling is a powerful tool for the investigation of human blood flow and arterial diseases such as atherosclerosis. It is known that near wall shear is important in the pathogenesis and progression of atherosclerosis. When modelling arterial blood flow it is generally assumed that blood is Newtonian. In this paper, blood flow is modelled in a realistic two-dimensional carotid artery geometry in order to investigate this assumption and its effect on the measurement of near wall shear. The assumption is tested in stenosed and unstenosed geometries and the non-Newtonian blood is modelled using the Carreau–Yasuda model. It is found that the velocity and shear fields, particularly near the walls of the geometries, exhibit small differences in general (<5%) between Newtonian and non-Newtonian models, even in the stenosed geometry with peak differences of 13.6%. Thus, when using numerical modelling to study the haemodynamic influences on atherosclerotic progression, we can safely neglect the non-Newtonian nature of blood.

Precise lung tumor localization in real time is particularly important for some motion management techniques, such as respiratory gating or beam tracking with a dynamic multi-leaf collimator, due to the reduced clinical tumor volume (CTV) to planning target volume (PTV) margin and/or the escalated dose. There might be large uncertainties in deriving tumor position from external respiratory surrogates. While tracking implanted fiducial markers has sufficient accuracy, this procedure may not be widely accepted due to the risk of pneumothorax. Previously, we have developed a technique to generate gating signals from fluoroscopic images without implanted fiducial markers using a template matching method (Berbeco et al2005 Phys. Med. Biol.50 4481–90, Cui et al2007 Phys. Med. Biol.52 741–55). In this paper, we present an extension of this method to multiple-template matching for directly tracking the lung tumor mass in fluoroscopy video. The basic idea is as follows: (i) during the patient setup session, a pair of orthogonal fluoroscopic image sequences are taken and processed off-line to generate a set of reference templates that correspond to different breathing phases and tumor positions; (ii) during treatment delivery, fluoroscopic images are continuously acquired and processed; (iii) the similarity between each reference template and the processed incoming image is calculated; (iv) the tumor position in the incoming image is then estimated by combining the tumor centroid coordinates in reference templates with proper weights based on the measured similarities. With different handling of image processing and similarity calculation, two such multiple-template tracking techniques have been developed: one based on motion-enhanced templates and Pearson's correlation score while the other based on eigen templates and mean-squared error. The developed techniques have been tested on six sequences of fluoroscopic images from six lung cancer patients against the reference tumor positions manually determined by a radiation oncologist. The tumor centroid coordinates automatically detected using both methods agree well with the manually marked reference locations. The eigenspace tracking method performs slightly better than the motion-enhanced method, with average localization errors less than 2 pixels (1 mm) and the error at a 95% confidence level of about 2–4 pixels (1–2 mm). This work demonstrates the feasibility of direct tracking of a lung tumor mass in fluoroscopic images without implanted fiducial markers using multiple reference templates.

The relative uncertainty of the ionometric determination of the absorbed dose to water, D_w, in the reference dosimetry of high-energy photon beams is in the order of 1.5% and is dominated by the uncertainty of the calculated chamber- and energy-dependent correction factors k_Q. In the present investigation, k_Q values were determined experimentally in 5 cm × 5 cm and 10 cm × 10 cm radiotherapy beams of 8 MV and 16 MV bremsstrahlung by means of a water calorimeter operated at 4 °C. Ionization chambers of the types NE 2561 and NE 2571 were calibrated directly in the water phantom of the calorimeter. The measurements were carried out at the linear accelerator of the Physikalisch-Technische Bundesanstalt. It is shown that the k_Q factor of a single ionization chamber can be measured with a standard uncertainty of less than 0.3%. No significant variations of k_Q were found for the different lateral sizes of the radiation fields used in this investigation.

Cerebral endothelial cells interconnected by tight and adherens junctions constitute the structural basis of the blood-brain barrier. Extracellular calcium ions have been reported to play an important role in the formation and maintenance of the junctional complex. However, little is known about the action of calcium depletion on the structural characteristics of cerebral endothelial cells. Using atomic force microscopy we analyzed the effect of calcium depletion and readdition on the shape and size of living brain endothelial cells. It was found that the removal of extracellular calcium from confluent cell cultures induced the dissociation of the cells from each other accompanied by an increase in their height. After readdition of calcium a gradual recovery was observed until total confluency was regained. We have also demonstrated that Rho-kinase plays an important role in the calcium-depletion-induced disassembly of endothelial tight and adherens junctions. The Rho-kinase inhibitor Y27632 could prevent the morphological changes induced by a lack of calcium as well. Our results suggest that calcium depletion induces Rho-kinase-dependent cytoskeletal changes that may be partly responsible for the disassembly of the junctional complex.

Flat-panel detector CT (FD-CT) scanners offer large volume coverage, but as a consequence are more susceptible to scatter artifacts than standard clinical CT scanners with smaller cone angles. FD-CT scanners can employ antiscatter grids as a scatter rejection technique. We evaluated three standard fluoroscopic antiscatter grids for two different field sizes with respect to scatter suppression efficiency and image quality improvement. The evaluations included simulations and measurements. Regarding the simulation a hybrid model combining deterministic and Monte Carlo (MC) calculations was used combined with an analytical calculation of grid transmission. The scatter-to-primary ratio (SPR) was measured using an adapted collimator technique in order to validate our simulations. The SPR obtained by simulations and measurements with and without antiscatter grids were in agreement typically within 10%. The employment of a grid does not generally provide a significant improvement of the signal-to-noise ratio (SNR). Antiscatter grids led to a significant reduction of cupping artifacts in all cases. There is a trade-off between the SNR and the reduction of the scatter intensity described by the signal-to-noise improvement factor (SNR_if). For low- or medium-scatter conditions the increase in noise caused by the reduced primary transmission through the grid has to be compensated by a higher exposure. For high scatter conditions SNR_if is significantly greater than 1; i.e. a decrease of dose of up to 50% can be reached.

Near-infrared spectroscopy or imaging has been extensively applied to various biomedical applications since it can detect the concentrations of oxyhaemoglobin (HbO₂), deoxyhaemoglobin (Hb) and total haemoglobin (Hb_total) from deep tissues. To quantify concentrations of these haemoglobin derivatives, the extinction coefficient values of HbO₂ and Hb have to be employed. However, it was not well recognized among researchers that small differences in extinction coefficients could cause significant errors in quantifying the concentrations of haemoglobin derivatives. In this study, we derived equations to estimate errors of haemoglobin derivatives caused by the variation of haemoglobin extinction coefficients. To prove our error analysis, we performed experiments using liquid-tissue phantoms containing 1% Intralipid in a phosphate-buffered saline solution. The gas intervention of pure oxygen was given in the solution to examine the oxygenation changes in the phantom, and 3 mL of human blood was added twice to show the changes in [Hb_total]. The error calculation has shown that even a small variation (0.01 cm⁻¹ mM⁻¹) in extinction coefficients can produce appreciable relative errors in quantification of Δ[HbO₂], Δ[Hb] and Δ[Hb_total]. We have also observed that the error of Δ[Hb_total] is not always larger than those of Δ[HbO₂] and Δ[Hb]. This study concludes that we need to be aware of any variation in haemoglobin extinction coefficients, which could result from changes in temperature, and to utilize corresponding animal's haemoglobin extinction coefficients for the animal experiments, in order to obtain more accurate values of Δ[HbO₂], Δ[Hb] and Δ[Hb_total] from in vivo tissue measurements.

The integration of electroanatomic maps with highly resolved computed tomography cardiac images plays an important role in the successful planning of the ablation procedure of arrhythmias. In this paper, we present and validate a fully-automated strategy for the registration and fusion of sparse, atrial endocardial electroanatomic maps (CARTO maps) with detailed left atrial (LA) anatomical reconstructions segmented from a pre-procedural MDCT scan. Registration is accomplished by a parameterized geometric transformation of the CARTO points and by a stochastic search of the best parameter set which minimizes the misalignment between transformed CARTO points and the LA surface. The subsequent fusion of electrophysiological information on the registered CT atrium is obtained through radial basis function interpolation. The algorithm is validated by simulation and by real data from 14 patients referred to CT imaging prior to the ablation procedure. Results are presented, which show the validity of the algorithmic scheme as well as the accuracy and reproducibility of the integration process. The obtained results encourage the application of the integration method in post-intervention ablation assessment and basic AF research and suggest the development for real-time applications in catheter guiding during ablation intervention.

Treatment plan optimization is a multi-criteria process. Optimizing solely on one objective or on a sum of a priori weighted objectives may result in inferior treatment plans. Manually adjusting weights or constraints in a trial and error procedure is time consuming. In this paper we introduce a novel multi-criteria optimization approach to automatically optimize treatment constraints (dose–volume and maximum-dose). The algorithm tries to meet these constraints as well as possible, but in the case of conflicts it relaxes lower priority constraints so that higher priority constraints can be met. Afterwards, all constraints are tightened, starting with the highest priority constraints. Applied constraint priority lists can be used as class solutions for patients with similar tumour types. The presented algorithm does iteratively apply an underlying algorithm for beam profile optimization, based on a quadratic objective function with voxel-dependent importance factors. These voxel-dependent importance factors are automatically adjusted to reduce dose–volume and maximum-dose constraint violations.

Within the linear-quadratic model the biologically-effective dose (BED)—taken to represent treatments with an equal tumor control probability (TCP)—is commonly (and plausibly) calculated according to BED(D) = −log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T_eff. By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T_eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T_eff) may result in a miscalculation (underestimation) of the initial number of clonogens.

In this note, we present the first experimental results of in-beam PET measurements during high energy photon phantom irradiation. An inhomogeneous phantom was irradiated with pulsed 34 MV bremsstrahlung. The measurements have been conducted with a dedicated double head positron camera. A high material contrast could be achieved and furthermore production rates of ¹¹C and ¹⁵O were derived from the time-dependent activity.

This note summarizes the characterization of the acoustic properties of four materials intended for the development of tissue, and especially breast tissue, phantoms for the use in photoacoustic and ultrasound imaging. The materials are agar, silicone, polyvinyl alcohol gel (PVA) and polyacrylamide gel (PAA). The acoustical properties, i.e., the speed of sound, impedance and acoustic attenuation, are determined by transmission measurements of sound waves at room temperature under controlled conditions. Although the materials are tested for application such as photoacoustic phantoms, we focus here on the acoustic properties, while the optical properties will be discussed elsewhere. To obtain the acoustic attenuation in a frequency range from 4 MHz to 14 MHz, two ultrasound sources of 5 MHz and 10 MHz core frequencies are used. For preparation, each sample is cast into blocks of three different thicknesses. Agar, PVA and PAA show similar acoustic properties as water. Within silicone polymer, a significantly lower speed of sound and higher acoustical attenuation than in water and human tissue were found. All materials can be cast into arbitrary shapes and are suitable for tissue-mimicking phantoms. Due to its lower speed of sound, silicone is generally less suitable than the other presented materials.

It is well known that a skin dose from high-energy x-ray radiation varies with the angle of beam incidence or the presence of a radiotherapy linear accelerator couch top material. This note investigates changes produced to the skin dose from a Varian carbon fibre grid couch top at differing angles of incidence for 6 MV x-rays as is often the case clinically. Results have shown that the skin dose can easily be measured using an EBT Gafchromic film whereby the delivered skin dose can be quantified to a high level of spatial resolution, not easily achieved with other skin dose detectors. Results have shown a significant increase in the skin dose specifically at the point of a cross-sectional carbon fibre grid. Values in % of the skin dose increased from approximately 27% (an open area within a 10 cm × 10 cm field) up to 55% (same field size) at the centre of the carbon fibre mesh strip (0° incidence). This is compared to 19% of the skin dose for an open field of a 10 cm × 10 cm beam without the couch material present. At larger angles similar effects occur with values changing from 52% to 75% (60°, 10 cm × 10 cm) in the open area and under the grid, respectively. This produces a wave effect for the skin dose. The average skin dose magnitude increases with the angle of incidence of the beam, ranging from 37.5% to 66% from 0° to 60° (10 × 10 cm), respectively. The symmetric wave nature of the skin dose profile skews to deliver an increased dose on the posterior side of the carbon fibre grid as the angle of incidence increases. Simulated fractional dose delivery on a phantom has shown that over 30 fractions the wave nature of the delivered skin dose is minimized due to the random nature of most patient positioning on the treatment couch. However, some variations are still present as the ratio of the open to grid area is approximately 4:1 and the dose spread is not necessarily completely averaged during a typical fractionated radiotherapy treatment. As such, if the treatment type results in a more rigorously positioned patient on the treatment couch, the wave nature of skin dose delivery may need to be taken into account.