Table of contents

We validate the dosimetric performance of COMPASS®, a novel 3D quality assurance system for verification of volumetric-modulated arc therapy (VMAT) treatment plans that can correlate the delivered dose to the patient's anatomy, taking into account the tissue inhomogeneity. The accuracy of treatment delivery was assessed by the COMPASS® for 12 VMAT plans, and the resulting assessments were evaluated using an ionization chamber and film measurements. Dose–volume relationships were evaluated by the COMPASS® for three additional treatment plans and these were used to verify the accuracy of treatment planning dose calculations. The results matched well between COMPASS® and measurements for the ionization chamber (⩽3%) and film (73–99% for gamma_(3%/3 mm) < 1 and 98–100% for gamma_(5%/5 mm) < 1) for the phantom plans. Differences in dose–volume statistics for the average dose to the PTV were within 2.5% for three treatment plans. For the structures located in the low-dose region, a maximum difference of <9% was observed. In its current implementation, the system could measure the delivered dose with sufficient accuracy and could project the 3D dose distribution directly on the patient's anatomy. Slight deviations were found for large open fields. These could be minimized by improving the COMPASS® in-built beam model.

Volumetric-modulated arc therapy (VMAT), a form of intensity-modulated arc therapy (IMAT), has become a topic of research and clinical activity in recent years. As a form of arc therapy, portal images acquired during the treatment fraction form a (partial) Radon transform of the patient. We show that these portal images, when used in a modified global cone-beam filtered backprojection (FBP) algorithm, allow a surprisingly recognizable CT-volume to be reconstructed. The possibility of distinguishing anatomy in such VMAT-CT reconstructions suggests that this could prove to be a valuable treatment position-verification tool. Further, some potential for local-tomography techniques to improve image quality is shown.

In this work we present a new 3D numerical model for heat transfer in the human eye, which takes into account the aqueous humour flow in the anterior chamber. We show that consideration of this phenomenon in the calculations alters the temperature distribution on the corneal and lens surfaces, without, however, noticeably changing their absolute values. The most notable effect is that the coolest area of the cornea moves at a point of 2 mm inferior to its geometric centre. The maximum velocity of the fluid in the anterior chamber was found to be 3.36 × 10⁻⁴ m s⁻¹. The effect of the flow on displacing the cool area of the corneal surface temperature is counterbalanced by assuming anisotropic thermal conductivity. The model was implemented in the case of an artificial intraocular lens to show the resulting temperature variations.

The aim of this study is to investigate the quantitative accuracy of the closed-form least-squares solution (LSS) for single photon emission computed tomography (SPECT). The main limitation for employing this method in actual clinical reconstructions is the computational cost related to operations with a large-sized system matrix. However, in some clinical situations, the size of the system matrix can be decreased using targeted reconstruction. For example, some oncology SPECT studies are characterized by intense tracer uptakes that are localized in relatively small areas, while the remaining parts of the patient body have only a low activity background. Conventional procedures reconstruct the activity distribution in the whole object, which leads to relatively poor image accuracy/resolution for tumors while computer resources are wasted, trying to rebuild diagnostically useless background. In this study, we apply a concept of targeted reconstruction to SPECT phantom experiments imitating such oncology scans. Our approach includes two major components: (i) disconnection of the entire imaging system of equations and extraction of only those parts that correspond to the targets, i.e., regions of interest (ROI) encompassing active containers/tumors and (ii) generation of the closed-form LSS for each target ROI. We compared these ROI-based LSS with those reconstructed by the conventional MLEM approach. The analysis of the five processed cases from two phantom experiments demonstrated that the LSS approach outperformed MLEM in terms of the noise level inside ROI. On the other hand, MLEM better recovered total activity if the number of iterations was large enough. For the experiment without background activity, the ROI-based LSS led to noticeably better spatial activity distribution inside ROI. However, the distributions pertaining to both approaches were practically identical for the experiment with the concentration ratio 7:1 between the containers and the background.

The aim is to demonstrate the potential impact of changes in the value of the β parameter in the linear quadratic (LQ) model on the calculation of clinical relative biological effectiveness (RBE) values used for high linear energy transfer (LET) radiotherapy. The parameter RBE_min is introduced into the LQ formulation to account for possible changes in the β radiosensitivity coefficient with changing LET. The model is used to fit fractionated data under two conditions, where RBE_min = 1 and RBE_min ≠ 1. Nonlinear regression and analysis of variance are used to test the hypothesis that the inclusion of a non-unity value of RBE_min better predicts the total iso-effective dose required at low number of fractions for fast neutrons, carbon ions, π-meson and proton fractionation data obtained for various tissues from previous publications. For neutrons the assumption of RBE_min ≠ 1 provided a better fit in 89% of the cases, whereas for carbon ions RBE_min ≠ 1 provided a better fit only for normal tissue at the spread-out Bragg peak. The results provide evidence of the impact that variations in the β parameter may have when calculating clinically relevant RBE values, especially when using high doses per fraction (i.e. hypofractionation) of high-LET radiations.

Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 ± 3.9% and 81.5 ± 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than ∼300 µm, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 ± 23.7 kPa instead of 145.4 ± 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young`s moduli of 31.4 ± 9.7 kPa instead of 17.6 ± 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

Biologically effective dose (BED) may be more of a relevant quantity than absorbed dose for establishing tumour response relationships. By taking into account the dose rate and tissue-specific parameters such as repair and radiosensitivity, it is possible to compare the relative biological effects of different targeted radionuclide therapy (TRT) agents. The aim of this work was to develop an analytical tumour BED calculation for TRT that could predict a relative biological effect based on normal body and tumour pharmacokinetics. This work represents a step in the direction of establishing relative pharmacokinetic criteria of when the BED formalism is more applicable than absorbed dose for TRT. A previously established pharmacokinetic (PK) model for TRT was used and adapted into the BED formalism. An analytical equation for the protraction factor, which incorporates dose rate and repair rate, was derived. Dose rates within the normal body and tumour were related to the slopes of their time–activity curves which were determined by the ratios of their respective PK parameters. The relationships between the tumour influx-to-efflux ratio (k₃₄:k₄₃), central compartment efflux-to-influx ratio (k₁₂:k₂₁), central elimination (k_el), and tumour repair rate (μ), and tumour BED were investigated. As the k₃₄:k₄₃ ratio increases and the k₁₂:k₂₁ ratio decreases, the difference between tumour BED and D increases. In contrast, as the k₃₄:k₄₃ ratios decrease and the k₁₂:k₂₁ ratios increase, the tumour BED approaches D. At large k₃₄:k₄₃ ratios, the difference between tumour BED and D increases to a maximum as k_el increases. At small k₃₄:k₄₃ ratios, the tumour BED approaches D at very small k_el. At small μ and small k₃₄:k₄₃ ratios, the tumour BED approaches D. For large k₃₄:k₄₃ ratios, large μ values cause tumour BED to approach D. This work represents a step in the direction of establishing relative PK criteria of when the BED formalism is more applicable than absorbed dose for TRT. It also provides a framework by which the biological effects of different TRT agents can be compared in order to predict efficacy.

Intracavitary injections of ³²P chromic phosphate are used in the therapy of pleuropulmonary blastoma and pulmonary sarcomas in children. The lung dose, however, has never been calculated despite the potential risk of lung toxicity from treatment. In this work the dosimetry has been calculated in target tissue and lung for pediatric phantoms. Pleural cavities were modeled in the Monte Carlo code MCNP within the pediatric MIRD phantoms. Both the depth–dose curves in the pleural lining and into the lung as well as 3D dose distributions were calculated for either homogeneous or inhomogeneous ³²P activity distributions. Dose–volume histograms for the lung tissue and isodose graphs were generated. The results for the 2D depth–dose curve to the pleural lining and tumor around the pleural cavity correspond well with the point kernel model-based recommendations. With a 2 mm thick pleural lining, one-third of the lung parenchyma volume gets a dose more than 30 Gy (V₃₀) for 340 MBq ³²P in a 10 year old. This is close to lung tolerance. Younger children will receive a larger dose to the lung when the lung density remains equal to the adult value; the V₃₀ relative lung volume for a 5 year old is 35% at an activity of 256 MBq and for a 1 year old 165 MBq yields a V₃₀ of 43%. At higher densities of the lung tissue V₃₀ stays below 32%. All activities yield a therapeutic dose of at least 225 Gy in the pleural lining. With a more normal pleural lining thickness (0.5 mm instead of 2 mm) the injected activities will have to be reduced by a factor 5 to obtain tolerable lung doses in pediatric patients. Previous dosimetry recommendations for the adult apply well down to lung surface areas of 400 cm². Monte Carlo dosimetry quantitates the three-dimensional dose distribution, providing a better insight into the maximum tolerable activity for this therapy.

The aim of this paper is to develop an automated method which operates on echocardiographic dynamic loops for classifying the left ventricular regional wall motion (RWM) in a four-point scale. A non-selected group of 37 patients (2 and 4 chamber views) was studied. Each view was segmented according to the standardized segmentation using three manually positioned anatomical landmarks (the apex and the angles of the mitral annulus). The segmented data were analyzed by two independent experienced echocardiographists and the consensual RWM scores were used as a reference for comparisons. A fast and automatic parametric imaging method was used to compute and display as static color-coded parametric images both temporal and motion information contained in left ventricular dynamic echocardiograms. The amplitude and time parametric images were provided to a cardiologist for visual analysis of RWM and used for RWM quantification. A cross-validation method was applied to the segmental quantitative indices for classifying RWM in a four-point scale. A total of 518 segments were analyzed. Comparison between visual interpretation of parametric images and the reference reading resulted in an absolute agreement (Aa) of 66% and a relative agreement (Ra) of 96% and kappa (κ) coefficient of 0.61. Comparison of the automated RWM scoring against the same reference provided Aa = 64%, Ra = 96% and κ = 0.64 on the validation subset. Finally, linear regression analysis between the global quantitative index and global reference scores as well as ejection fraction resulted in correlations of 0.85 and 0.79. A new automated four-point scale scoring of RWM was developed and tested in a non-selected database. Its comparison against a consensual visual reading of dynamic echocardiograms showed its ability to classify RWM abnormalities.

Here we propose a new magnetic resonance (MR) strategy based on the evaluation of internal gradient (G_i) to assess the trabecular bone (TB) density in spongy bone. Spongy bone is a porous system characterized by a solid trabecular network immersed in bone marrow and characterized by a different relative percentage of water and fats. Using a 9.4 T MR micro-imaging system, we first evaluated the relative water and fat G_i as extracted from the Spin-Echo decay function in vitro of femoral head samples from calves. Indeed, the differential effects of fat and water diffusion result in different types of G_i behavior. Using a clinical MR 3T scanner, we then investigated in vivo the calcanei of individuals characterized by different known TB densities. We demonstrate, on these samples, that water is more prevalent in the boundary zone, while fats are rearranged primarily in the central zone of each pore. In vitro experiments showed that water G_i magnitude from the samples was directly proportional to their TB density. Similar behavior was also observed in the clinical measures. Conversely, fat G_i did not provide any information on spongy-bone density. Our results suggest that water G_i may be a reliable marker to assess the status of spongy bone.

A phenomenological kV beam model was developed to address attenuation and scatter in radiographic images for the purpose of cone-beam imaging. Characterization of a kV beam in terms of the minimal number of parameters and calculation of attenuation and scatter in radiographs of scanned objects are the main applications of this model. Model parameters are derived from radiographs of homogeneous solid water phantoms for various depths and field sizes. The response of the cone-beam detector to kV beams is factorized into different contributions such as output factor, tissue-air ratio and off-axis ratio, with each contribution having an analytical representation. The formulas which are used to characterize the beam model in uniform phantoms are then extended to arbitrary objects using the concept of the water-equivalent pathlength. A weighted sum of three Gaussians in each direction models the dose deposition kernel. Detector response arising from the first Gaussian term can be interpreted as the primary signal while the second and third Gaussians constitute short- and long-range scatter. The model is then applied to predict the primary and scatter signals for arbitrary objects. A technique of scatter removal from the measured radiographs is investigated. The model accurately predicts detector response of varying-thickness phantoms such as multi-step and cylindrical phantoms. The scatter contributes over 90% to the total signal for 20 cm thick phantoms. The calculated scatter-to-primary ratio as a function of spatial coordinates agrees with Monte Carlo studies reported in the literature. Water-equivalent thickness related to primary and scatter contributions calculated from an analysis of radiographs results in an improved calibration technique suitable for CB-CT reconstruction. The kV beam model and the associated theoretical formulations can be utilized to characterize any kV beam line; however, for the specific study the OBI™ system (Varian) was used to obtain experimental radiographs.

There has recently been a great deal of interest in noninvasive high-frequency ultrasound imaging of small animals such as rats due to their being the preferred animal model for gene therapy and cancer research. Improving the interpretation of the obtained images and furthering the development of the imaging devices require a detailed knowledge of the ultrasound attenuation and backscattering of biological tissue (e.g. blood) at high frequencies. In the present study, the attenuation and backscattering coefficients of the rat red blood cell (RBC) suspensions and whole blood with hematocrits ranging from 6% to 40% were measured between 30 and 60 MHz using a modified substitution approach. The acoustic parameters of porcine blood under the same conditions were also measured in order to compare differences in the blood properties between these two animals. For porcine blood, both whole blood and RBC suspension were stirred at a rotation speed of 200 rpm. Three different rotation speeds of 100, 200 and 300 rpm were carried out for rat blood experiments. The attenuation coefficients of both rat and porcine blood were found to increase linearly with frequency and hematocrit (the values of coefficients of determination (r²) are around 0.82–0.97 for all cases). The average attenuation coefficient of rat whole blood with a hematocrit of 40% increased from 0.26 Nepers mm⁻¹ at 30 MHz to 0.47 Nepers mm⁻¹ at 60 MHz. The maximum backscattering coefficients of both rat and porcine RBC suspensions were between 10% and 15% hematocrits at all frequencies. The fourth-power dependence of backscatter on frequency was approximately valid for rat RBC suspensions with hematocrits between 6% and 40%. However, the frequency dependence of the backscatter estimate deviates from a fourth-power law for porcine RBC suspension with hematocrit higher than 20%. The backscattering coefficient plateaued for hematocrits higher than 15% in porcine blood, but for rat blood it was maximal around a hematocrit of 20% at the same rotation speed, and shifted to a hematocrit of 10% at a higher speed. The backscattering properties of rat RBCs in plasma are similar to those of RBCs in saline at a higher rotation speed. The differences in attenuation and backscattering between rat and porcine blood may be attributed to RBCs' being smaller and the RBC aggregation level being lower for rat blood than for porcine blood.

A Geiger-mode avalanche photodiode (Si-PM) is a promising photodetector for PET, especially for use in a magnetic resonance imaging (MRI) system, because it has high gain and is less sensitive to a static magnetic field. We developed a Si-PM-based depth-of-interaction (DOI) PET system for small animals. Hamamatsu 4 × 4 Si-PM arrays (S11065-025P) were used for its detector blocks. Two types of LGSO scintillator of 0.75 mol% Ce (decay time: ∼45 ns; 1.1 mm × 1.2 mm × 5 mm) and 0.025 mol% Ce (decay time: ∼31 ns; 1.1 mm × 1.2 mm × 6 mm) were optically coupled in the DOI direction to form a DOI detector, arranged in a 11 × 9 matrix, and optically coupled to the Si-PM array. Pulse shape analysis was used for the DOI detection of these two types of LGSOs. Sixteen detector blocks were arranged in a 68 mm diameter ring to form the PET system. Spatial resolution was 1.6 mm FWHM and sensitivity was 0.6% at the center of the field of view. High-resolution mouse and rat images were successfully obtained using the PET system. We confirmed that the developed Si-PM-based PET system is promising for molecular imaging research.

As carbon ions, at therapeutic energies, penetrate tissue, they undergo inelastic nuclear reactions and give rise to significant yields of secondary fragment fluences. Therefore, an accurate prediction of these fluences resulting from the primary carbon interactions is necessary in the patient's body in order to precisely simulate the spatial dose distribution and the resulting biological effect. In this paper, the performance of nuclear fragmentation models of the Monte Carlo transport codes, FLUKA and GEANT4, in tissue-like media and for an energy regime relevant for therapeutic carbon ions is investigated. The ability of these Monte Carlo codes to reproduce experimental data of charge-changing cross sections and integral and differential yields of secondary charged fragments is evaluated. For the fragment yields, the main focus is on the consideration of experimental approximations and uncertainties such as the energy measurement by time-of-flight. For GEANT4, the hadronic models G4BinaryLightIonReaction and G4QMD are benchmarked together with some recently enhanced de-excitation models. For non-differential quantities, discrepancies of some tens of percent are found for both codes. For differential quantities, even larger deviations are found. Implications of these findings for the therapeutic use of carbon ions are discussed.

The two-dimensional (2D) Nakagami image complements the ultrasound B-scan image when attempting to visualize the scatterer properties of tissues. The resolution of the Nakagami image is lower than that of the B-scan image, since the former is produced by processing the raw envelope data using a 2D sliding window with side lengths typically corresponding to three times the pulse length of the incident ultrasound. This paper proposes using three-dimensional (3D) Nakagami imaging for improving the resolution of the obtained Nakagami image and providing more complete information of scatterers for a better tissue characterization. The 3D Nakagami image is based on a voxel array composed of the Nakagami parameters constructed using a 3D sliding cube to process the 3D backscattered raw data. Experiments on phantoms with different scatterer concentrations were carried out to determine the optimal size of the sliding cube for a stable estimation of the Nakagami parameter. Tissue measurements on rat livers without and with fibrosis formation were further used to explore the practical feasibility of 3D Nakagami imaging. The results indicated that the side length of the cube used to construct the 3D Nakagami image must be at least two times the pulse length, which improved the resolution for each Nakagami image frame in the 3D Nakagami image. The results further demonstrated that the 3D Nakagami image is better than the conventional 2D Nakagami image for complementing the B-scan in detecting spatial variations in the scatterer concentration and classifying normal and fibrotic livers. This study suggests that 3D Nakagami imaging has the potential to become a new 3D quantitative imaging approach.

Along with increased use of wireless communication devices operating in the radiofrequency (RF) range, concern has been raised about the related possible health risks. Among other concerns, the interaction of medical implants and RF devices has been studied in order to assure the safety of implant carriers under various exposure conditions. In the RF range, the main established quantitative effect of electromagnetic (EM) fields on biological tissues is heating due to vibrational movements of water molecules. The temperature changes induced in tissues also constitute the basis for the setting of RF exposure limits and recommendations. In this study, temperature changes induced by electromagnetic field enhancements near passive metallic implants have been simulated in the head region. Furthermore, the effect of the implant material on the induced temperature change was evaluated using clinically used metals with the highest and the lowest thermal conductivities. In some cases, remarkable increases in maximum temperatures of tissues (as much as 8 °C) were seen in the near field with 1 W power level whereas at lower power levels significant temperature increases were not observed.

The integration of magnetic resonance imaging (MRI) and positron emission tomography (PET) is an upcoming hybrid imaging technique. Prototype scanners for pre-clinical and clinical research have been built and tested. However, the potential of the PET part can be better exploited if the arterial input function (AIF) of the administered tracer is known. This work presents a dedicated MR-compatible blood sampling system for precise measurement of the AIF in an MR-PET study. The device basically consists of an LSO/APD-detector assembly which performs a coincidence measurement of the annihilation photons resulting from positron decays. During the measurement, arterial blood is drawn continuously from an artery and lead through the detector unit. Besides successful tests of the MR compatibility and the detector performance, measurements of the AIF of rats have been carried out. The results show that the developed blood sampling system is a practical and reliable tool for measuring the AIF in MR-PET studies.

Performance of a new high resolution PET detection concept is presented. In this new concept, annihilation radiation enters the scintillator detectors edge-on. Each detector module comprises two 8 × 8 LYSO scintillator arrays of 0.91 × 0.91 × 1 mm³ crystals coupled to two position-sensitive avalanche photodiodes (PSAPDs) mounted on a flex circuit. Appropriate crystal segmentation allows the recording of all three spatial coordinates of the interaction(s) simultaneously with submillimeter resolution. We report an average energy resolution of 14.6 ± 1.7% for 511 keV photons at FWHM. Coincident time resolution was determined to be 2.98 ± 0.13 ns FWHM on average. The coincidence point spread function (PSF) has an average FWHM of 0.837 ± 0.049 mm (using a spherical source) and is uniform across the arrays. Both PSF and coincident time resolution degrade when Compton interactions are included in the data. Different blurring factors were evaluated theoretically, resulting in a calculated PSF of 0.793 mm, in good agreement with the measured value.

Singlet oxygen direct dosimetry and photosensitizer fluorescence photobleaching are being investigated and applied as dosimetric tools during 5-aminolevulinic acid (ALA)-induced protophorphyrin IX (PpIX) photodynamic therapy (PDT) of normal skin and skin cancers. The correlations of photosensitizer fluorescence and singlet oxygen luminescence (SOL) emission signals to distribution and cumulative dose are difficult to interpret because of the temporal and spatial variations of three essential components (light fluence rate, photosensitizer concentration and oxygen concentration) in PDT. A one-dimensional model is proposed in this paper to simulate the dynamic process of ALA-PDT of normal human skin in order to investigate the time-resolved evolution of PpIX, ground-state oxygen and distributions. The model incorporates a simplified three-layer semi-infinite skin tissue, Monte Carlo simulations of excitation light fluence and both PpIX fluorescence and SOL emission signals reaching the skin surface, -mediated photobleaching mechanism for updating PpIX, and distributions after the delivery of each light dose increment, ground-state oxygen supply by diffusion from the atmosphere and perfusion from blood vessels, a cumulative -dependent threshold vascular response, and the initial non-uniform distribution of PpIX. The PpIX fluorescence simulated using this model is compared with clinical data reported by Cottrell et al (2008 Clin. Cancer Res.14 4475–83) for a range of irradiances (10–150 mW cm⁻²). Except for the vascular response, one set of parameters is used to fit data at all irradiances. The time-resolved depth-dependent distributions of PpIX, and at representative irradiances are presented and discussed in this paper, as well as the PDT-induced vascular response at different depths. Tissue hypoxia and shutdown of oxygen supply occur in the upper dermis, where PpIX is also preserved at the end of treatment.

In this paper, we study the transient thermal response of skin layers to determine to which extent the surface temperature distribution reflects the properties of subsurface structures, such as benign or malignant lesions. Specifically, we conduct a detailed sensitivity analysis to interpret the changes in the surface temperature distribution as a function of variations in thermophysical properties, blood perfusion rate, metabolic heat generation and thicknesses of skin layers, using a multilayer computational model. These properties can vary from individual to individual or depend on location, external and internal influences, and in certain situations accurate property data are not available in the literature. Therefore, the uncertainties in these data could potentially affect the accuracy of the interpretation/diagnosis of a lesion in a clinical setting. In this study, relevant parameters were varied within characteristic physiological ranges, and differences in the surface temperature response were quantified. It was observed that variations in these parameters have a small influence on the surface temperature distribution. Analysis using this multilayer model was further conducted to determine the sensitivity of transient thermal response to different lesion sizes. This work validates the idea of examining the transient thermal response obtained using a thermal imaging system with the objective of lesion identification. The modeling effort and the sensitivity analysis reported in this paper comprise a portion of a comprehensive research effort involving experimentation on a skin phantom model as well as measurements on patients in a clinical setting, that are currently underway. One of the preliminary results from the ongoing clinical trial is also included to demonstrate the feasibility of the proposed approach.

Oxygen and carbon are the first and second abundant elements, respectively, in the human body by mass. Although many physiological and pathological processes are accompanied with alteration of total body oxygen (TBO) and carbon (TBC) masses, in vivo measurements of the two elements are limited. Up to now, almost all available information of TBC and TBO is based on in vivo neutron activation (IVNA) analysis which is very expensive and involves moderate radiation exposure. The aim of the present study was to develop and evaluate an alternative strategy for TBC and TBO estimation. Mechanistic models were derived for predicting TBC and TBO masses from dual-energy x-ray absorptiometry (DXA) and total body water (TBW). Twenty-eight adult subjects were studied. IVNA-measured TBC and TBO masses were used as the criterion. TBC masses predicted by DXA-alone and by DXA–TBW models were 20.8 ± 7.1 kg and 20.6 ± 6.8 kg, respectively, close to the IVNA-measured value (19.5 ± 6.3 kg). There were strong correlations (both with r > 0.95, P < 0.001) between the predicted and measured TBC masses. TBO masses predicted by DXA-alone and by DXA–TBW models were 46.0 ± 9.8 kg and 46.5 ± 9.9 kg, respectively, close to the IVNA-measured value (48.0 ± 10.4 kg). Correlations (both with r > 0.97, P < 0.001) were strong between the predicted and measured TBO masses. Bland–Altman analysis validated the applicability of DXA-based models to predict TBC and TBO masses. As both DXA and TBW dilutions are widely available, low-risk, low-cost techniques, the present study provides a safe and practical method for estimating elemental composition in vivo.

The accuracy of a transient elastography liver-scanning ultrasound system was assessed using a novel application of PVA-cryogel as a tissue-mimicking material with acoustic and shear elasticity properties optimized to best represent those of liver tissue. Although the liver-scanning system has been shown to offer a safer alternative for diagnosing liver cirrhosis through stiffness measurement, as compared to the liver needle biopsy exam, the scanner's accuracy has not been fully established. Young's elastic modulus values of 5–6 wt% PVA-cryogel phantoms, also containing glycerol and 0.3 µm Al₂O₃ and 3 µm Al₂O₃, were measured using a 'gold standard' mechanical testing technique and transient elastography. The mechanically measured values and acoustic velocities of the phantoms ranged between 1.6 and 16.1 kPa and 1540 and 1570 m s⁻¹, respectively, mimicking those observed in liver tissue. The values reported by the transient elastography system overestimated Young's elastic modulus values representative of the progressive stages of liver fibrosis by up to 32%. These results were attributed to the relative rather than absolute nature of the measurement arising from the single-point acoustic velocity calibration of the system, rendering the measurements critically dependent on the speed of sound of the sample under investigation. Given the wide range of acoustic velocities which exist in the liver, spanning healthy tissue to cirrhotic pathology, coupled with the system's assumption that the liver is approximately elastic when it is rather highly viscoelastic, care should be exercised when interpreting the results from this system in patient groups.

Optimizing the sensitivity of SQUID (superconducting quantum interference device) relaxometry for detecting cell-targeted magnetic nanoparticles for in vivo diagnostics requires nanoparticles with a narrow particle size distribution to ensure that the Néel relaxation times fall within the measurement timescale (50 ms–2 s, in this work). To determine the optimum particle size, single-core magnetite nanoparticles (with nominal average diameters 20, 25, 30 and 35 nm) were characterized by SQUID relaxometry, transmission electron microscopy, SQUID susceptometry, dynamic light scattering and zeta potential analysis. The SQUID relaxometry signal (detected magnetic moment/kg) from both the 25 nm and 30 nm particles was an improvement over previously studied multi-core particles. However, the detected moments were an order of magnitude lower than predicted based on a simple model that takes into account the measured size distributions (but neglects dipolar interactions and polydispersity of the anisotropy energy density), indicating that improved control of several different nanoparticle properties (size, shape and coating thickness) will be required to achieve the highest detection sensitivity. Antibody conjugation and cell incubation experiments show that single-core particles enable a higher detected moment per cell, but also demonstrate the need for improved surface treatments to mitigate aggregation and improve specificity.

For decades, the heel effect has been known to cause an angular dependence of the emitted spectrum of an x-ray tube. In radiography, artifacts were observed and attributed to the heel effect. However, no problems due to the heel effect were discerned in multi-slice computed tomography (MSCT) so far. With flat-detector CT (FDCT), involving larger cone angles and different system geometries, the heel effect might cause new artifacts. These artifacts were analyzed in this paper for system geometries different from the ones widely used nowadays. Simulations and measurements were performed. Simulations included symmetric as well as asymmetric detector layouts and different x-ray tube orientations with respect to the detector plane. The measurements were performed on a micro-CT system in an asymmetric detector layout. Furthermore, an analytical correction scheme is proposed to overcome heel effect artifacts. It was shown that the type of artifact greatly depends on the orientation of the x-ray tube and also on the type of detector alignment (i.e. symmetric or different types of asymmetric alignment). Certain combinations exhibited almost no significant artifact while others greatly influenced the quality of the reconstructed images. The proposed correction scheme showed good results that were further improved when also applying a scatter correction. When designing CT systems, care should be taken when placing the tube and the detector. Orientation of the x-ray tube like in most MSCT systems seems advisable in asymmetric detector layouts. However, a different type of tube orientation can be overcome with suitable correction schemes.

An intuitive heuristic to establish beam configurations for intensity-modulated radiation therapy is introduced as an extension of beam ensemble selection strategies applying scalar scoring functions. It is validated by treatment plan comparisons for three intra-cranial, pancreas, and prostate cases each. Based on a patient specific matrix listing the radiological quality of candidate beam directions individually for every target voxel, a set of locally ideal beam angles is generated. The spherical distribution of locally ideal beam angles is characteristic for every treatment site and patient: ideal beam angles typically cluster around distinct orientations. We interpret the cluster centroids, which are identified with a spherical K-means algorithm, as irradiation angles of an intensity-modulated radiation therapy treatment plan. The fluence profiles are subsequently optimized during a conventional inverse planning process. The average computation time for the pre-optimization of a beam ensemble is six minutes on a state-of-the-art work station. The treatment planning study demonstrates the potential benefit of the proposed beam angle optimization strategy. For the three prostate cases under investigation, the standard treatment plans applying nine coplanar equi-spaced beams and treatment plans applying an optimized non-coplanar nine-beam ensemble yield clinically comparable dose distributions. For symmetric patient geometries, the dose distribution formed by nine equi-spaced coplanar beams cannot be improved significantly. For the three pancreas and intra-cranial cases under investigation, the optimized non-coplanar beam ensembles enable better sparing of organs at risk while guaranteeing equivalent target coverage. Beam angle optimization by spherical cluster analysis shows the biggest impact for target volumes located asymmetrically within the patient and close to organs at risk.

A growing number of clinical applications using 2D/3D registration have been presented recently. Usually, a digitally reconstructed radiograph is compared iteratively to an x-ray image of the known projection geometry until a match is achieved, thus providing six degrees of freedom of rigid motion which can be used for patient setup in image-guided radiation therapy or computer-assisted interventions. Recently, stochastic rank correlation, a merit function based on Spearman's rank correlation coefficient, was presented as a merit function especially suitable for 2D/3D registration. The advantage of this measure is its robustness against variations in image histogram content and its wide convergence range. The considerable computational expense of computing an ordered rank list is avoided here by comparing randomly chosen subsets of the DRR and reference x-ray. In this work, we show that it is possible to omit the sorting step and to compute the rank correlation coefficient of the full image content as fast as conventional merit functions. Our evaluation of a well-calibrated cadaver phantom also confirms that rank correlation-type merit functions give the most accurate results if large differences in the histogram content for the DRR and the x-ray image are present.

Improvements in the reliable diagnosis of preinvasive ductal carcinoma in situ (DCIS) by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are needed. In this study, we present a new characterization of early contrast kinetics of DCIS using high temporal resolution (HiT) DCE-MRI and compare it with other breast lesions and normal parenchyma. Forty patients with mammographic calcifications suspicious for DCIS were selected for HiT imaging using T₁-weighted DCE-MRI with ∼7 s temporal resolution for 90 s post-contrast injection. Pixel-based and whole-lesion kinetic curves were fit to an empirical mathematical model (EMM) and several secondary kinetic parameters derived. Using the EMM parameterized and fitted concentration time curve for subsequent analysis allowed for calculation of kinetic parameters that were less susceptible to fluctuations due to noise. The parameters' initial area under the curve (iAUC) and contrast concentration at 1 min (C_{1 min}) provided the highest diagnostic accuracy in the task of distinguishing pathologically proven DCIS from normal tissue. There was a trend for DCIS lesions with solid architectural pattern to exhibit a negative slope at 1 min (i.e. increased washout rate) compared to those with a cribriform pattern (p < 0.04). This pilot study demonstrates the feasibility of quantitative analysis of early contrast kinetics at high temporal resolution and points to the potential for such an analysis to improve the characterization of DCIS.