Table of contents

Preformed gas bubbles can increase energy absorption from an ultrasound beam and therefore they have been proposed for an enhancer of ultrasound treatments. Although tissue temperature measurements performed in vivo using invasive thermocouple probes and MRI thermometry have demonstrated increased tissue temperature, the microscopic temperature distribution has not been investigated so far. In this study the transfer of heat between bubbles and tissue during focused ultrasound was simulated. Microbubble oscillations were simulated within a rat cortical microvascular network reconstructed from in vivo dual-photon microscopy images and the power density of these oscillations was used as an input term in the Pennes bioheat transfer equation. The temperature solution from the bioheat transfer equation was mapped onto vascular data to produce a three-dimensional temperature map. The results showed high temperatures near the bubbles and slow temperature rise in the tissue. Heating was shown to increase with increasing bubble frequency and insonation pressure, and showed a frequency-dependent peak. The goal of this research is to characterize the effect of various parameters on bubble-enhanced therapeutic ultrasound to allow better treatment planning. These results show that the induced temperature elevations have nonuniformities which may have a significant impact on the bio-effects of the exposure.

In medical imaging, single-photon emission computed tomography (SPECT) can provide specific functional information while magnetic resonance imaging (MRI) can provide high spatial resolution anatomical information as well as complementary functional information. In this study, we developed a miniaturized dual-modality SPECT/MRI (MRSPECT) system and demonstrated the feasibility of simultaneous SPECT and MRI data acquisition, with the possibility of whole-body MRSPECT systems through suitable scaling of components. For our MRSPECT system, a cadmium-zinc-telluride (CZT) nuclear radiation detector was interfaced with a specialized radiofrequency (RF) coil and placed within a whole-body 4 T MRI system. Various phantom experiments characterized the interaction between the SPECT and MRI hardware components. The metallic components of the SPECT hardware altered the B₀ field and generated a non-uniform reduction in the signal-to-noise ratio (SNR) of the MR images. The presence of a magnetic field generated a position shift and resolution loss in the nuclear projection data. Various techniques were proposed to compensate for these adverse effects. Overall, our results demonstrate that accurate, simultaneous SPECT and MRI data acquisition is feasible, justifying the further development of MRSPECT for either small-animal imaging or whole-body human systems by using appropriate components.

Magnetic particle imaging (MPI) is a new imaging technique capable of imaging the distribution of superparamagnetic particles at high spatial and temporal resolution. For the reconstruction of the particle distribution, a system of linear equations has to be solved. The mathematical solution to this linear system can be obtained using a least-squares approach. In this paper, it is shown that the quality of the least-squares solution can be improved by incorporating a weighting matrix using the reciprocal of the matrix-row energy as weights. A further benefit of this weighting is that iterative algorithms, such as the conjugate gradient method, converge rapidly yielding the same image quality as obtained by singular value decomposition in only a few iterations. Thus, the weighting strategy in combination with the conjugate gradient method improves the image quality and substantially shortens the reconstruction time. The performance of weighting strategy and reconstruction algorithms is assessed with experimental data of a 2D MPI scanner.

A mathematical approach for geometric co-calibration of a dual-modal small-animal imaging system is presented. The system comprises an optical imaging setup for in vivo bioluminescence and fluorescence detection, as well as an x-ray CT, both mounted on a common rotatable gantry enabling fully simultaneous imaging at axially overlapping fields-of-view. Geometric co-calibration is performed once by imaging a single cylindrical light-emitting source with both modalities over 360° at two axial positions, respectively. Given the three-dimensional coordinates of the source positions in the reconstructed CT volume data along with their two-dimensional locations projected at the optical detector plane, the following intrinsic system parameters are calculated: (i) the intrinsic geometric parameters of the optical detection system—five parameters for each view and (ii) the relative positional relationship between the optical and CT systems—two parameters for each view. After co-calibration is performed, experimental studies using phantoms demonstrate the high degree of intrinsic positional accuracy between the optical and CT measurements. The most important advantage of this approach is that dual-modal data fusion is accomplished without any post-registration strategies.

The delivery of spatially modulated radiation fields has been shown to impact on in vitro cell survival responses. To study the effect of modulated fields on cell survival, dose response curves were determined for human DU-145 prostate, T98G glioma tumour cells and normal primary AGO-1552 fibroblast cells exposed to modulated and non-modulated field configurations delivered using a 6 MV Linac with multi-leaf collimator. When exposed to uniform fields delivered as a non-modulated or modulated configuration, no significant differences in survival were observed with the exception of DU-145 cells at a dose of 8 Gy (p = 0.024). Survival responses were determined for exposure to non-uniform-modulated beams in DU-145 and T98G and showed no deviation from the survival response observed following uniform non-modulated exposures. The results of these experiments indicate no major deviation in response to modulated fields compared to uniform exposures.

This paper presents the whole-body specific absorption rate (WBSAR) assessment of embryos and new-born rats' exposure in a reverberating chamber (RC) operating at 2.4 GHz (WiFi). The finite difference in time domain (FDTD) method often used in bio-electromagnetism is facing very slow convergence. A new simulation-measurement hybrid approach has been proposed to characterize the incident power related to the RC and the WBSAR in rats, which are linked by the mean squared electric field strength in the working volume. Peak localized SAR in the rat under exposure is not included in the content of the study. Detailed parameters of this approach are determined by simulations. Evolutions for the physical and physiological parameters of the small rats at different ages are discussed. Simulations have been made to analyse all the variability factors contributing to the global results. WBSAR information and the variability for rats at different ages are also discussed in the paper.

Due to its simplicity, parallel-beam geometry is usually assumed for the development of image reconstruction algorithms. The established reconstruction methodologies are then extended to fan-beam, cone-beam and other non-parallel geometries for practical application. This situation occurs for quantitative SPECT (single photon emission computed tomography) imaging in inverting the attenuated Radon transform. Novikov reported an explicit parallel-beam formula for the inversion of the attenuated Radon transform in 2000. Thereafter, a formula for fan-beam geometry was reported by Bukhgeim and Kazantsev (2002 Preprint N. 99 Sobolev Institute of Mathematics). At the same time, we presented a formula for varying focal-length fan-beam geometry. Sometimes, the reconstruction formula is so implicit that we cannot obtain the explicit reconstruction formula in the non-parallel geometries. In this work, we propose a unified reconstruction framework for extending parallel-beam geometry to any non-parallel geometry using ray-driven techniques. Studies by computer simulations demonstrated the accuracy of the presented unified reconstruction framework for extending parallel-beam to non-parallel geometries in inverting the attenuated Radon transform.

Conventional contrast agents utilized in diagnostic radiology are based on x-ray absorption properties; alternative physical principles capable of providing a contrast enhancement in radiographs have never been applied. This study exploits the possibility of using a novel type of contrast media based on x-ray scattering. The contrast agents consist of microbubble echo-enhancing agents, usually applied in ultrasound examinations, which are invisible with conventional x-ray absorption techniques. The experiment was carried out at the medical beamline of the synchrotron radiation laboratory ELETTRA in Trieste, Italy. A flat silicon analyzer crystal typically used for diffraction-enhanced imaging was utilized as a tool for detecting the scattering properties of the contrast agents. In analyzer-based imaging, it is possible to detect the scattering properties of the sample by shifting the analyzer crystal to selected positions of its reflectivity curve. In particular, when the sample consists of a large number of micro-particles an overall effect can be observed. Phantoms containing contrast agents based on microbubbles were imaged at different angular positions of the analyzer crystal. High visibility of the details was demonstrated, and a strong contrast enhancement was measured compared to normal x-ray absorption techniques.

Much research is being conducted on position-sensitive scintillation detectors for medical imaging, particularly for emission tomography. Monte Carlo simulations play an essential role in many of these research activities. As the scintillation process, the transport of scintillation photons through the crystal(s), and the conversion of these photons into electronic signals each have a major influence on the detector performance; all of these processes may need to be incorporated in the model to obtain accurate results. In this work the optical and scintillation models of the GEANT4 simulation toolkit are validated by comparing simulations and measurements on monolithic scintillator detectors for high-resolution positron emission tomography (PET). We have furthermore made the GEANT4 optical models available within the user-friendly GATE simulation platform (as of version 3.0). It is shown how the necessary optical input parameters can be determined with sufficient accuracy. The results show that the optical physics models of GATE/GEANT4 enable accurate prediction of the spatial and energy resolution of monolithic scintillator PET detectors.

Thin tissue autoradiography is an imaging modality where ex-vivo tissue sections are placed in direct contact with autoradiographic film. These tissue sections contain a radiolabelled ligand bound to a specific biomolecule under study. This radioligand emits β − or β+ particles ionizing silver halide crystals in the film. High spatial resolution autoradiograms are obtained using low energy radioisotopes, such as ³H where an intrinsic 0.1–1 µm spatial resolution can be achieved. Several digital alternatives have been presented over the past few years to replace conventional film but their spatial resolution has yet to equal film, although silicon-based imaging technologies have demonstrated higher sensitivity compared to conventional film. It will be shown in this work how pixel size is a critical parameter for achieving high spatial resolution for low energy uncollimated beta imaging. In this work we also examine the confounding factors impeding silicon-based technologies with respect to spatial resolution. The study considers charge diffusion in silicon and detector noise, and this is applied to a range of radioisotopes typically used in autoradiography. Finally an optimal detector geometry to obtain the best possible spatial resolution for a specific technology and a specific radioisotope is suggested.

Soft tissue stiffness was shown to significantly change after thermal ablation. To better understand this phenomenon, the study aims (1) to quantify and explain the temperature dependence of soft tissue stiffness for different organs, (2) to investigate the potential relationship between stiffness changes and thermal dose and (3) to study the reversibility or irreversibility of stiffness changes. Ex vivo bovine liver and muscle samples (N = 3 and N = 20, respectively) were slowly heated and cooled down into a thermally controlled saline bath. Temperatures were assessed by thermocouples. Sample stiffness (shear modulus) was provided by the quantitative supersonic shear imaging technique. Changes in liver stiffness are observed only after 45 °C. In contrast, between 25 °C and 65 °C, muscle stiffness varies in four successive steps that are consistent with the thermally induced proteins denaturation reported in the literature. After a 6 h long heating and cooling process, the final muscle stiffness can be either smaller or bigger than the initial one, depending on the stiffness at the end of the heating. Another important result is that stiffness changes are linked to thermal dose. Given the high sensitivity of ultrasound to protein denaturation, this study gives promising prospects for the development of ultrasound-guided HIFU systems.

In this study, computer-assisted analysis of prostate lesions was researched by combining information from two different magnetic resonance (MR) modalities: T2-weighted (T2-w) and dynamic contrast-enhanced (DCE) T1-w images. Two issues arise when incorporating T2-w images in a computer-aided diagnosis (CADx) system: T2-w values are position as well as sequence dependent and images can be misaligned due to patient movement during the acquisition. A method was developed that computes T2 estimates from a T2-w and proton density value and a known sequence model. A mutual information registration strategy was implemented to correct for patient movement. Global motion is modelled by an affine transformation, while local motion is described by a volume preserving non-rigid deformation based on B-splines. The additional value to the discriminating performance of a DCE T1-w-based CADx system was evaluated using bootstrapped ROC analysis. T2 estimates were successfully computed in 29 patients. T2 values were extracted and added to the CADx system from 39 malignant, 19 benign and 29 normal annotated regions. T2 values alone achieved a diagnostic accuracy of 0.85 (0.77–0.92) and showed a significantly improved discriminating performance of 0.89 (0.81–0.95), when combined with DCE T1-w features. In conclusion, the study demonstrated a simple T2 estimation method that has a diagnostic performance such that it complements a DCE T1-w-based CADx system in discriminating malignant lesions from normal and benign regions. Additionally, the T2 estimate is beneficial to visual inspection due to the removed coil profile and fixed window and level settings.

Quantification of nuclear medicine image data is a prerequisite for personalized absorbed dose calculations and quantitative biodistribution studies. The spatial response of a detector is a governing factor affecting the accuracy of image quantification, and the aim of this work was to model this impact. To simulate spatial response, a value for the intrinsic spatial resolution (R_intrinsic) of the gamma camera is needed. R_intrinsic for ^99mTc was measured over the field of view (FOV) and an experimental setup was designed to measure R_intrinsic for radioisotopes with higher photon energies. Monte Carlo (MC) simulations, using the codes SIMIND and GATE, were used to investigate the extrinsic effect of R_intrinsic as a function of energy and its variation across the FOV. A method was developed to calculate energy-dependent blurring values for input to MC simulations, by separate consideration of the Compton scatter and photoelectric effect in the crystal and statistical variation in the signal. Inclusion of energy-specific blurring values in simulations showed excellent agreement with experimental measurements. The maximum pixel count rate can change by up to 18% when imaged at two different points in the FOV, and errors in the maximum pixel count rate of up to 11% were shown if a blurring value for ^99mTc was used for simulations of ¹³¹I. We demonstrate that the accuracy of MC simulations of gamma cameras can be significantly improved by accounting for the effect of energy on intrinsic spatial resolution.

In this paper 1D transient elastography was employed in fresh bovine skeletal muscle samples to assess the shear elastic modulus μ while the tissue was locally heated by means of an electrical resistance. The investigation is based on the study of the time shift of the shear wave propagation produced by the local temperature variation. The experiments show that the thermal expansion contribution to the time shift is negligible when compared with the shear wave speed variation. In such a case, the quantification of μ as a function of temperature becomes possible. Repeated experiments in different samples lead to a reproducible behavior of μ as a function of temperature. Irreversible elasticity changes are produced when the temperature exceeds a certain critical value T_c. The proposed method allows estimating this value as well as the spatial extension of the resulting thermal lesion. This point is important when considering applications in monitoring focused ultrasound surgery (FUS) because the surrounding normal tissue should remain unaffected.

The purpose of this note is to evaluate the relationship between the stochastic errors in CT numbers and the standard deviation of the computed proton beam range in radiotherapy planning. The stochastic voxel-to-voxel variation in CT numbers called 'noise,' may be due to signal registration, processing and numerical image reconstruction technique. Noise in CT images may cause a deviation in the computed proton range from the physical proton range, even assuming that the error due to CT number-stopping power calibration is removed. To obtain the probability density function (PDF) of the computed proton range, we have used the continuing slowing down approximation (CSDA) and the uncorrelated white Gaussian noise along the proton path. The model of white noise was accepted because for the slice-based fan-beam CT scanner; the power-spectrum properties apply only to the axial (x, y) domain and the noise is uncorrelated in the z domain. However, the possible influence of the noise power spectrum on the standard deviation of the range should be investigated in the future. A random number generator was utilized for noise simulation and this procedure was iteratively repeated to obtain convergence of range PDF, which approached a Gaussian distribution. We showed that the standard deviation of the range, σ, increases linearly with the initial proton energy, computational grid size and standard deviation of the voxel values. The 95% confidence interval width of the range PDF, which is defined as 4σ, may reach 0.6 cm for the initial proton energy of 200 MeV, computational grid 0.25 cm and 5% standard deviation of CT voxel values. Our results show that the range uncertainty due to random errors in CT numbers may be significant and comparable to the uncertainties due to calibration of CT numbers.

A novel approach to the measurement of arsenic and selenium in nail phantoms is demonstrated. Two-component nail phantoms of 0.7 mm and 1.5 mm thickness were made from a polyester resin-salt mixture and dosed with equal arsenic and selenium concentrations ranging from 0 to 30 µg g⁻¹. A backing was made to simulate the soft tissue and bone of the great toe. Characteristic x-rays for arsenic and selenium were recorded using a portable x-ray tube and a silicon PiN diode detector. The minimum instrumental detection limits for arsenic and selenium in 0.7 mm solitary nail samples were as follows: 0.510 ± 0.018 µg g⁻¹ and 0.519 ± 0.026 µg g⁻¹ respectively; for 1.5 mm solitary nail: 0.465 ± 0.035 µg g⁻¹ and 0.561 ± 0.062 µg g⁻¹; for 0.7 mm nail with backing: 1.522 ± 0.038 µg g⁻¹ and 1.401 ± 0.049 µg g⁻¹; for 1.5 mm nail with backing: 1.354 ± 0.054 µg g⁻¹ and 1.367 ± 0.068 µg g⁻¹.

The IAEA standard thermoluminescent dosimeter (TLD) holder has been developed for the IAEA/WHO TLD postal dose program for audits of high-energy photon beams, and it is also employed by the ESTRO-QUALity assurance network (EQUAL) and several national TLD audit networks. Factors correcting for the influence of the holder on the TL signal under reference conditions have been calculated in the present work from Monte Carlo simulations with the PENELOPE code for ⁶⁰Co γ-rays and 4, 6, 10, 15, 18 and 25 MV photon beams. The simulation results are around 0.2% smaller than measured factors reported in the literature, but well within the combined standard uncertainties. The present study supports the use of the experimentally obtained holder correction factors in the determination of the absorbed dose to water from the TL readings; the factors calculated by means of Monte Carlo simulations may be adopted for the cases where there are no measured data.