Table of contents

Hyperpolarized gases have found a steadily increasing range of applications in nuclear magnetic resonance (NMR) and NMR imaging (MRI). They can be regarded as a new class of MR contrast agent or as a way of greatly enhancing the temporal resolution of the measurement of processes relevant to areas as diverse as materials science and biomedicine. We concentrate on the properties and applications of hyperpolarized xenon. This review discusses the physics of producing hyperpolarization, the NMR-relevant properties of ¹²⁹Xe, specific MRI methods for hyperpolarized gases, applications of xenon to biology and medicine, polarization transfer to other nuclear species and low-field imaging.

The basic concept, design and performance of a novel needle-based x-ray system for medical applications are reported. The main principle of the system is based on a two-stage production of x-rays. The system comprises a conventional x-ray tube with an Ag anode, any known type of conditioning optics and a 2.2 mm diameter hollow needle with an interchangeable Mo target. The target can be moved along the needle axis and rotated around the needle axis. The needle x-ray device allows for adjustment in energy and flux intensity of the x-rays emitted by the target. The depth dependence of the intensity, dose rate as well as spatial and energy distribution of the radiation emitted by the target have been experimentally measured. The depth dose rate results have been compared with theoretical calculations using a Monte Carlo simulation of the x-ray production process. These studies have experimentally confirmed that the concept of this x-ray system is correct. Further improvement of the device can increase the dose rate up to the levels required for clinical applications.

Factor based methods for absorbed dose or monitor unit calculations are often based on separate data sets for open and wedged beams. The determination of basic beam parameters can be rather time consuming, unless equivalent square methods are applied. When considering irregular wedged beams shaped with a multileaf collimator, parametrization methods for dosimetric quantities, e.g. output ratios or wedge factors as a function of field size and shape, become even more important. A practical method is presented to derive wedged output ratios in air (S_c,w) for any rectangular field and for any irregular MLC shaped beam. This method was based on open field output ratios in air (S_c) for a field with the same collimator setting, and a relation f_w between S_c,w and S_c. The relation f_w can be determined from measured output ratios in air for a few open and wedged fields including the maximum wedged field size. The function f_w and its parametrization were dependent on wedge angle and treatment head design, i.e. they were different for internal and external wedges. The proposed method was tested for rectangular wedged fields on three accelerators with internal wedges (GE, Elekta, BBC) and two accelerators with external wedges (Varian). For symmetric regular beams the average deviation between calculated and measured S_c,w/S_c ratios was 0.3% for external wedges and about 0.6% for internal wedges. Maximum deviations of 1.8% were obtained for elongated rectangular fields on the GE and ELEKTA linacs with an internal wedge. The same accuracy was achieved for irregular MLC shaped wedged beams on the accelerators with MLC and internal wedges (GE and Elekta), with an average deviation <1% for the fields tested. The proposed method to determine output ratios in air for wedged beams from output ratios of open beams, combined with equivalent square approaches, can be easily integrated in empirical or semi-empirical methods for monitor unit calculations.

Solid-state radiation dosimetry by electron paramagnetic resonance (EPR) spectroscopy and thermoluminescence (TL) was utilized for the determination of absorbed doses in the range of 0.5–2.5 Gy. The dosimeter materials used were lithium formate and lithium fluoride (TLD-100 rods) for EPR dosimetry and TL dosimetry, respectively. ⁶⁰Co γ-rays and 4, 6, 10 and 15 MV x-rays were employed. The main objectives were to compare the variation in dosimeter reading of the respective dosimetry systems and to determine the photon energy dependence of the two dosimeter materials. The EPR dosimeter sensitivity was constant over the dose range in question, while the TL sensitivity increased by more than 5% from 0.5 to 2.5 Gy, thus displaying a supralinear dose response. The average relative standard deviation in the dosimeter reading per dose was 3.0% and 1.2% for the EPR and TL procedures, respectively. For EPR dosimeters, the relative standard deviation declined significantly from 4.3% to 1.1% over the dose range in question. The dose-to-water energy response for the megavoltage x-ray beams relative to ⁶⁰Co γ-rays was in the range of 0.990–0.979 and 0.984–0.962 for lithium formate and lithium fluoride, respectively. The results show that EPR dosimetry with lithium formate provides dose estimates with a precision comparable to that of TL dosimetry (using lithium fluoride) for doses above 2 Gy, and that lithium formate is slightly less dependent on megavoltage photon beam energy than lithium fluoride.

Iterative image reconstruction algorithms have the potential to produce low noise images. Early stopping of the iteration process is problematic because some features of the image may converge slowly. On the other hand, there may be noise build-up with increased number of iterations. Therefore, we examined the stabilizing effect of using two different prior functions as well as image representation by blobs so that the number of iterations could be increased without noise build-up. Reconstruction was performed of simulated phantoms and of real data acquired by positron emission tomography. Image quality measures were calculated for images reconstructed with or without priors. Both priors stabilized the iteration process. The first prior based on the Huber function reduced the noise without significant loss of contrast recovery of small spots, but the drawback of the method was the difficulty in finding optimal values of two free parameters. The second method based on a median root prior has only one Bayesian parameter which was easy to set, but it should be taken into account that the image resolution while using that prior has to be chosen sufficiently high not to cause the complete removal of small spots. In conclusion, the Huber penalty function gives accurate and low noise images, but it may be difficult to determine the parameters. The median root prior method is not quite as accurate but may be used if image resolution is increased.

Iterative statistical reconstruction methods are becoming the standard in positron emission tomography (PET). Conventional maximum-likelihood expectation-maximization (MLEM) and ordered-subsets (OSEM) algorithms act on data which have been pre-processed into corrected, evenly-spaced histograms; however, such pre-processing corrupts the Poisson statistics. Recent advances have incorporated attenuation, scatter and randoms compensation into the iterative reconstruction. The objective of this work was to incorporate the remaining pre-processing steps, including arc correction, to reconstruct directly from raw unevenly-spaced line-of-response (LOR) histograms. This exactly preserves Poisson statistics and full spatial information in a manner closely related to listmode ML, making full use of the ML statistical model. The LOR-OSEM algorithm was implemented using a rotation-based projector which maps directly to the unevenly-spaced LOR grid. Simulation and phantom experiments were performed to characterize resolution, contrast and noise properties for 2D PET. LOR-OSEM provided a beneficial noise-resolution tradeoff, outperforming AW-OSEM by about the same margin that AW-OSEM outperformed pre-corrected OSEM. The relationship between LOR-ML and listmode ML algorithms was explored, and implementation differences are discussed. LOR-OSEM is a viable alternative to AW-OSEM for histogram-based reconstruction with improved spatial resolution and noise properties.

A double-ring sensor was applied in photoacoustic tomographic imaging of artificial blood vessels as well as blood vessels in a rabbit ear. The peak-to-peak time (τ_pp) of the laser (1064 nm) induced pressure transient was used to estimate the axial vessel diameter. Comparison with the actual vessel diameter showed that the diameter could be approximated by 2cτ_pp, with c the speed of sound in blood. Using this relation, the lateral diameter could also precisely be determined. In vivo imaging and monitoring of changes in vessel diameters was feasible. Finally, acoustic time traces were recorded while flushing a vessel in the rabbit ear with saline, which proved that the main contribution to the laser-induced pressure transient is caused by blood inside the vessel and that the vessel wall gives only a minor contribution.

We report on a novel and compact reliable laser source capable of short-wavelength two-photon laser scanning fluorescence microscopy based on soliton self-frequency shift effects in photonic crystal fibre. We demonstrate the function of the system by performing two-photon microscopy of smooth muscle cells and cardiac myocytes from the rat pulmonary vein and Chinese hamster ovary cells loaded with the fluorescent calcium indicator fura-2/AM.

In this study, a direct, fast image reconstruction algorithm, based on the fact that equipotential lines are perpendicular to current lines in a volume conductor, is proposed for magnetic resonance electrical impedance tomography (MR-EIT). The proposed technique is evaluated both on simulated and measured data for conductor and insulator objects.

Optical tomography is an emerging method for non-invasive imaging of human tissues using near-infrared light. Generally, the tissue is assumed isotropic, but this may not always be true. In this paper, we present a method for the estimation of optical absorption coefficient allowing the background to be anisotropic. To solve the forward problem, we model the light propagation in tissue using an anisotropic diffusion equation. The inverse problem consists of the estimation of the absorption coefficient based on boundary measurements. Generally, the background anisotropy cannot be assumed to be known. We treat the uncertainties in the background anisotropy parameter values as modelling error, and include this in our model and reconstruction. We present numerical examples based on simulated data. For reference, examples using an isotropic inversion scheme are also included. The estimates are qualitatively different for the two methods.

Ultraviolet light can affect the appearance and medical condition of the human skin by triggering biophysical processes such as erythema, melanogenesis, photoaging and carcinogenesis. The evolution of these processes is related to the amount of ultraviolet light absorbed by skin pigments. This amount may vary with the wavelength and path length of the radiation that is propagated within the skin tissues. For many years, biomedical researchers have been investigating the propagation of ultraviolet light in skin tissues through Monte Carlo simulations. The scattering of the incident radiation by tissue internal structures, a key component in this process, is usually approximated by functions without a plausible connection with the underlying physical phenomena. In this paper, we examine the origins of such an approach, and question its generalized use with respect to wavelengths and biological materials for which there is no supporting data available. Furthermore, we perform comparisons to demonstrate that the accuracy and predictability of Monte Carlo simulations of ultraviolet propagation in skin tissues can be improved by using a data-driven approach to represent the scattering profile of these tissues.

Based on experimental estimates for acute and chronic tumour hypoxia, a speculative analysis of the therapeutic ratio dependence on the number of once-daily five-days-per-week fractions (n) for non-small cell lung cancer (NSCLC) radiotherapy is proposed. For this purpose an adapted formulation of the linear-quadratic model has been derived, including the effects of tumour repopulation, inter-tumour α-heterogeneity and oxygen enhancement ratio dependence on the dose per fraction. The relation between the curative dose D₅₀, assuring 50% tumour control probability, and n has been computed: for (n, D₅₀) fractionation schemes, the therapeutic ratios have been compared in terms of effective normalized total doses to the lungs (NTD^eff_L), estimated by a few supposed fractions of the normalized total dose to the tumour. Results suggest that D₅₀ is dominated by chronic hypoxia for shortly hypofractionated treatments and by acute hypoxia for multifractionated treatments. Furthermore, the optimum number of fractions depends on the rapidity of the reoxygenation from chronically hypoxic cells, almost independently of the extent of both chronic and acute hypoxia. For NSCLC, both the reduction of n until about 20 fractions in hypofractionated dose-escalation trials, and the extension of extra-cranial stereotactic radiotherapy schedules to include at least 5–10 fractions, seem to be supported by this model.

Ongoing clinical trials designed to explore the use of extracranial stereotactic radiosurgery (ESR) for different tumour sites use large doses per fraction (15, 20, 30 Gy or even larger). The question of whether the linear–quadratic (LQ) model is appropriate to describe radiation response for such large fraction doses has been raised and has not been answered definitively. It has been proposed that mechanism-based models, such as the lethal–potentially lethal (LPL) model, could be more appropriate for such large fraction/acute doses. However, such models are not well characterized with clinical data and they are generally not easy to use. The purpose of this work is to modify the LQ model to more accurately describe radiation response for high fraction/acute doses. A new parameter is introduced in the modified LQ (MLQ) model. The new parameter introduced is characterized based both on in vitro cell survival data of several human tumour cell lines and in vivo animal iso-effect curves. The MLQ model produces a better fit to the iso-effect data than the LQ model. For a high single dose irradiation, the prediction of the MLQ is consistent with that from the LPL model. Unlike the LPL model, the MLQ model retains the simplicity of the LQ model and uses the well-characterized α and β parameters. This work indicates that the standard LQ model can lead to erroneous results when used to calculate iso-effects with large fraction doses, such as those used for ESR. We present a solution to this problem.

The change in linear attenuation coefficient with absorbed dose has been investigated for aqueous polyacrylamide, gelatine and tetrakis (PAGAT) and aqueous methacrylic acid, gelatine and tetrakis (MAGAT) normoxic polymer gel dosimeters using tetrakis (hydroxy methyl) phosphonium chloride as the antioxidant. The measured linear attenuation coefficient increased linearly with absorbed dose up to 15 Gy for PAGAT gels and 10 Gy for MAGAT gels. Computerized tomography (CT) numbers or Hounsfield units (H) were calculated from the linear attenuation coefficients and compared with values obtained using a CT scanner. Both calculated and measured CT numbers followed a similar pattern when fitted with a biexponential curve. The CT numbers obtained from linear attenuation measurements were found to be greater than that obtained with the CT scanner for both PAGAT and MAGAT polymer gels. The H-dose sensitivities of the MAGAT and PAGAT polymer gel dosimeters measured on a CT scanner were calculated to be (0.85 ± 0.08) H Gy⁻¹ and (0.31 ± 0.03) H Gy⁻¹, respectively. The H-dose sensitivities of the MAGAT and PAGAT polymer gel dosimeters from attenuation measurements were found to be (1.10 ± 0.66) H Gy⁻¹ and (0.34 ± 0.01) H Gy⁻¹, respectively.