Table of contents

We explore dual-ended read out of LSO arrays with two position sensitive avalanche photodiodes (PSAPDs) as a high resolution, high efficiency depth-encoding detector for PET applications. Flood histograms, energy resolution and depth of interaction (DOI) resolution were measured for unpolished LSO arrays with individual crystal sizes of 1.0, 1.3 and 1.5 mm, and for a polished LSO array with 1.3 mm pixels. The thickness of the crystal arrays was 20 mm. Good flood histograms were obtained for all four arrays, and crystals in all four arrays can be clearly resolved. Although the amplitude of each PSAPD signal decreases as the interaction depth moves further from the PSAPD, the sum of the two PSAPD signals is essentially constant with irradiation depth for all four arrays. The energy resolutions were similar for all four arrays, ranging from 14.7% to 15.4%. A DOI resolution of 3–4 mm (including the width of the irradiation band which is ∼2 mm) was obtained for all the unpolished arrays. The best DOI resolution was achieved with the unpolished 1 mm array (average 3.5 mm). The DOI resolution for the 1.3 mm and 1.5 mm unpolished arrays was 3.7 and 4.0 mm respectively. For the polished array, the DOI resolution was only 16.5 mm. Summing the DOI profiles across all crystals for the 1 mm array only degraded the DOI resolution from 3.5 mm to 3.9 mm, indicating that it may not be necessary to calibrate the DOI response separately for each crystal within an array. The DOI response of individual crystals in the array confirms this finding. These results provide a detailed characterization of the DOI response of these PSAPD-based PET detectors which will be important in the design and calibration of a PET scanner making use of this detector approach.

In-beam positron emission tomography (in-beam PET) is currently the only method for an in situ monitoring of highly tumour-conformed charged hadron therapy. At the experimental carbon ion tumour therapy facility, running at the Gesellschaft für Schwerionenforschung, Darmstadt, Germany, all treatments have been monitored by means of a specially adapted dual-head PET scanner. The positive clinical impact of this project triggered the construction of a hospital-based hadron therapy facility, with in-beam PET expected to monitor more delicate radiotherapeutic situations. Therefore, we have studied possible in-beam PET improvements by optimizing the arrangement of the γ-ray detectors. For this, a fully 3D, rebinning-free, maximum likelihood expectation maximization algorithm applicable to several closed-ring or dual-head tomographs has been developed. The analysis of β⁺-activity distributions simulated from real-treatment situations and detected with several detector arrangements allows us to conclude that a dual-head tomograph with narrow gaps yields in-beam PET images with sufficient quality for monitoring head and neck treatments. For monitoring larger irradiation fields, e.g. treatments in the pelvis region, a closed-ring tomograph was seen to be highly desirable. Finally, a study of the space availability for patient and bed, tomograph and beam portal proves the implementation of a closed-ring detector arrangement for in-beam PET to be feasible.

Near-infrared optical techniques for clinical breast cancer screening in humans are rapidly advancing. Based on the computational inversion of the photon diffusion process through the breast, these techniques rely on optical tissue models for accurate image reconstruction. Recent interest has surfaced regarding the effect of refractive index variations on these reconstructions. Although many data exist regarding the scattering and absorption properties of normal and diseased tissue, no measurements of refractive index appear in the literature. In this paper, we present near-infrared refractive index data acquired from N-methyl-N-nitrosourea-induced rat mammary tumours, which are similar in pathology and disease progression to human ductal carcinoma. Eight animals, including one control, were employed in this study, yielding data from 32 tumours as well as adjacent adipose and connective tissues.

Nanoparticles have drawn great attention as targeted imaging and/or therapeutic agents. The small size of the nanoparticles allows them to target cells that are beyond capillary vasculature, such as cancer cells. We investigated the effect of solid nanoparticles for enhancing ultrasonic grey scale images in tissue phantoms and mouse livers in vivo. Silica nanospheres (100 nm) were dispersed in agarose at 1–2.5% mass concentration and imaged by a high-resolution ultrasound imaging system (transducer centre frequency: 30 MHz). Polystyrene particles of different sizes (500–3000 nm) and concentrations (0.13–0.75% mass) were similarly dispersed in agarose and imaged. Mice were injected intravenously with nanoparticle suspensions in saline. B-mode images of the livers were acquired at different time points after particle injection. An automated computer program was used to quantify the grey scale changes. Ultrasonic reflections were observed from nanoparticle suspensions in agarose gels. The image brightness, i.e., mean grey scale level, increased with particle size and concentration. The mean grey scale of mouse livers also increased following particle administration. These results indicated that it is feasible to use solid nanoparticles as contrast enhancing agents for ultrasonic imaging.

Cone beam CT (CBCT) using a zonal filter is introduced. The aims are reduced concomitant imaging dose to the patient, simultaneous control of body scatter for improved image quality in the tumour target zone and preserved set-up detail for radiotherapy. Aluminium transmission diaphragms added to the CBCT x-ray tube of the Elekta Synergy™ linear accelerator produced an unattenuated beam for a central 'target zone' and a partially attenuated beam for an outer 'set-up zone'. Imaging doses and contrast noise ratios (CNR) were measured in a test phantom for transmission diaphragms 12 and 24 mm thick, for 5 and 10 cm long target zones. The effect on automatic registration of zonal CBCT to conventional CT was assessed relative to full-field and lead-collimated images of an anthropomorphic phantom. Doses along the axis of rotation were reduced by up to 50% in both target and set-up zones, and weighted dose (two thirds surface dose plus one third central dose) was reduced by 10–20% for a 10 cm long target zone. CNR increased by up to 15% in zonally filtered CBCT images compared to full-field images. Automatic image registration remained as robust as that with full-field images and was superior to CBCT coned down using lead-collimation. Zonal CBCT significantly reduces imaging dose and is expected to benefit radiotherapy through improved target contrast, required to assess target coverage, and wide-field edge detail, needed for robust automatic measurement of patient set-up error.

A method is proposed to simplify the IAEA TRS398 dosimetry code of practice in respect to dose determination of high-energy electron beams. The proposed method eliminates the use of the intermediate beam quality Q_int (and beam quality correction factor ) applicable for cross calibration and subsequent use of the user's chamber for dose determination in water for high-energy electron beams. This method allows calculation of the dose to water calibration factor for the user's instrument at the reference beam quality directly from a cross calibration in a high-energy electron beam of quality Q_cross at the user's institute.

Pre-existing methods for photon beam spectral reconstruction are briefly reviewed. An alternative reconstruction method by scatter analysis for linear accelerators is introduced. The method consists in irradiating a small plastic phantom at standard 100 cm SSD and inferring primary beam energy spectral information based on the measurement with a standard Farmer chamber of scatter around the phantom at several specific scatter angles: a scatter curve is measured which is indicative of the primary spectrum at hand. A Monte Carlo code is used to simulate the scatter measurement set-up and predict the relative magnitude of scatter measurements for mono-energetic primary beams. Based on mono-energetic primary scatter data, measured scatter curves are analysed and the spectrum unfolded as the sum of mono-energetic individual energy bins using the Schiff bremsstrahlung model. The method is applied to an Elekta/SL18 6 MV photon beam. The reconstructed spectrum matches the Monte Carlo calculated spectrum for the same beam within 6.2% (average error when spectra are compared bin by bin). Depth dose values calculated for the reconstructed spectrum agree with physically measured depth dose data to within 1%. Scatter analysis is preliminarily shown to have potential as a practical spectral reconstruction method requiring few measurements under standard 100 cm SSD and feasible in any radiotherapy department using a phantom and a Farmer chamber.

The fundamentals of IMRT collimation have been studied using ten conceptual collimators. Spanning a range of complexities from the LINAC jaws alone to a full multi-leaf collimator (MLC), these collimators were designed with two abilities in mind: (1) to be able to define arbitrary field shapes, and (2) to be able to irradiate multiple, disconnected regions in a single segment. The collimators were tested by finding decompositions of random and clinical intensity-modulated beams (IMBs), and collimator performance was measured using both the number of segments required to complete the IMB and the monitor-unit efficiency of the treatment. The decompositions were run on 10 × 10 IMBs with integer bixel values randomly between 1 and 10, and clinical IMBs of varying sizes from lung, head and neck, and pelvic patients taken from a Pinnacle treatment-planning system. Results confirmed that although treatment performance improves with increased collimator complexity, it is not solely dependent on the number of segment shapes deliverable by the collimator but instead on how well these shapes lend themselves to IMRT delivery.

In this paper, we deal with the effects of interfractional organ motion during radiation therapy. We consider two problems: first, treatment plan evaluation in the presence of motion, and second, the incorporation of organ motion into IMRT optimization. Concerning treatment plan evaluation, we face the problem that the delivered dose cannot be predicted with certainty at the time of treatment planning but is associated with uncertainties. We present a method to simulate stochastic properties of the dose distribution. This provides the treatment planner with information about motion-related risks of different plans and may support the decision for or against a treatment plan. This information includes the display of probabilities of individual voxels to receive doses from a therapeutical interval or above critical levels, as well as a diagram that shows the variability of the dose volume histogram. Concerning the incorporation of organ motion into IMRT planning, we further analyse the approach of inverse planning based on probability distributions of possible patient geometries. We consider three different sources of uncertainty, namely uncertainty about the amplitude of motion, a systematic error and a random error. We analyse the impact of these sources of uncertainty on the optimized treatment plans for prostate cancer.

Radiotherapy calculations often involve complex geometries such as interfaces between materials of vastly differing atomic number, such as lung, bone and/or air interfaces. Monte Carlo methods have been used to calculate accurately the perturbation effects of the interfaces. However, these methods can be computationally expensive for routine clinical calculations. An alternative approach is to solve the Boltzmann equation deterministically. We present one such deterministic code, Attila™. Further, we computed a brachytherapy example and an external beam benchmark to compare the results with data previously calculated by MCNPX and EGS4. Our data suggest that the presented deterministic code is as accurate as EGS4 and MCNPX for the transport geometries examined in this study.

In prostate permanent seed implants, it has been shown that edema caused by the surgical procedure decreases dose coverage and hence may reduce treatment efficacy. This reduction in treatment efficacy has been characterized by an increase in tumour cell survival, and biomathematical models have been developed to calculate the tumour cell survival increases in seed implanted prostates of different edema magnitudes and durations. External beam boosts can be utilized to neutralize the negative impact of edema so that originally desired treatment efficacy can be achieved. In this study, a linear quadratic model is used to determine fractionation sizes of the external beam boosts for both ¹²⁵I and ¹⁰³Pd seed implants. Calculations were performed for prostates of different edema magnitudes and durations, and for tumour cells of different repair rates and repopulation rates.

Water-to-air stopping power ratio calculations for the ionization chamber dosimetry of clinical carbon ion beams with initial energies from 50 to 450 MeV/u have been performed using the Monte Carlo technique. To simulate the transport of a particle in water the computer code SHIELD-HIT v2 was used, which is a newly developed version where substantial modifications were implemented on its predecessor SHIELD-HIT v1 (Gudowska et al 2004 Phys. Med. Biol.49 1933–58). The code was completely rewritten replacing formerly used single precision variables with double precision variables. The lowest particle transport specific energy was decreased from 1 MeV/u down to 10 keV/u by modifying the Bethe–Bloch formula, thus widening its range for medical dosimetry applications. In addition, the code includes optionally MSTAR and ICRU-73 stopping power data. The fragmentation model was verified and its parameters were also adjusted. The present code version shows excellent agreement with experimental data. It has been used to compute the physical quantities needed for the calculation of stopping power ratios, s_water,air, of carbon beams. Compared with the recommended constant value given in the IAEA Code of Practice, the differences found in the present investigations varied between 0.5% and 1% at the plateau region, respectively for 400 MeV/u and 50 MeV/u beams, and up to 2.3% in the vicinity of the Bragg peak for 50 MeV/u.

The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6–1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.

Radiological contrast-to-noise ratio (CNR) is evaluated in subtracted images of microcalcifications in breast tissue. CNR is calculated for dual-kVp subtraction combining beams available in a Senographe 2000D, assuming single breast compression. Spectra were obtained from Boone et al (1997 Med. Phys.24 1863–73), and the study was limited to lowest 25 kV Mo/Mo and highest 40 kV Rh/Rh beams, for 2.58 × 10⁻⁴ C kg⁻¹ (1R) total exposure. For a standard case combining 25 kVp Mo/Mo and 40 kVp Rh/Rh beams, predicted maximum CNR for 300 µm calcification in 5 cm thick, 50% glandular, breast is about 1.2, below Rose's criterion for visualization. Total mean glandular doses are about 2.5 cGy for a standard case. The effect that input factors might have on predictions has been evaluated. Choice between alternative spectra can affect CNR by 50%. Assumed calcification composition leads to differences of 67% in calculated CNR, and assumed breast tissue composition can alter CNR by 45%; these results are weakly dependent on calcification or breast thickness, or on the assumed fraction of glandular tissue. CNR values are related to detected spectra effective energy. Calculations predict that above 37 kVp Mo/Mo beams are more energetic than Rh/Rh at the same kVp, due to beam hardening.

Under decompression, bubbles can form in the human body, and these can be found both within the body tissues and the bloodstream. Mathematical models for the growth of both types of bubbles have previously been presented, but they have not been coupled together. This work thus explores the interaction between the growth of tissue and blood-borne bubbles under decompression, specifically looking at the extent to which they compete for the common resource of inert gas held in solution in the tissues. The influence of tissue bubbles is found to be significant for densities as low as 10 ml⁻¹ for tissues which are poorly perfused. However, the effects of formation of bubbles in the blood are not found until the density of bubble production sites reaches 10⁶ ml⁻¹. From comparison of the model predictions with experimental evidence for bubbles produced in animals and man under decompression, it is concluded that the density of tissue bubbles is likely to have a significant effect on the number of bubbles produced in the blood. However, the density of nucleation sites in the blood is unlikely to be sufficiently high in humans for the formation of bubbles in the blood to have a significant impact on the growth of the bubbles in the tissue.

Finite-difference time-domain (FDTD) calculations have been performed to investigate the frequency dependence of the specific energy absorption rate (SAR) in a seated voxel model of the human body. The seated model was derived from NORMAN (NORmalized MAN), an anatomically realistic voxel phantom in the standing posture with arms to the side. Exposure conditions included both vertically and horizontally polarized plane wave electric fields between 10 MHz and 3 GHz. The resolution of the voxel model was 4 mm for frequencies up to 360 MHz and 2 mm for calculations in the higher frequency range. The reduction in voxel size permitted the calculation of SAR at these higher frequencies using the FDTD method. SAR values have been calculated for the seated adult phantom and scaled versions representing 10-, 5- and 1-year-old children under isolated and grounded conditions. These scaled models do not exactly reproduce the dimensions and anatomy of children, but represent good geometric information for a seated child. Results show that, when the field is vertically polarized, the sitting position causes a second, smaller resonance condition not seen in resonance curves for the phantom in the standing posture. This occurs at ∼130 MHz for the adult model when grounded. Partial-body SAR calculations indicate that the upper and lower regions of the body have their own resonant frequency at ∼120 MHz and ∼160 MHz, respectively, when the grounded adult model is orientated in the sitting position. These combine to produce this second resonance peak in the whole-body averaged SAR values calculated. Two resonance peaks also occur for the sitting posture when the incident electric field is horizontally polarized. For the adult model, the peaks in the whole-body averaged SAR occur at ∼180 and ∼600 MHz. These peaks are due to resonance in the arms and feet, respectively. Layer absorption plots and colour images of SAR in individual voxels show the specific regions in which the seated human body absorbs the incident field. External electric field values required to produce the ICNIRP basic restrictions were derived from SAR calculations and compared with ICNIRP reference levels. This comparison shows that the reference levels provide a conservative estimate of the ICNIRP whole-body averaged SAR restriction, with the exception of the region above 1.4 GHz for the scaled 1-year-old model.

In proton and ion radiotherapy, the range of particles is calculated from x-ray computed tomography (CT) numbers. Due to the strong absorption of x-rays in a metal and a cut-off for large Hounsfield units (HU) in the software of most CT-scanners, a range calculation in metals cannot be based on the measured HU. This is of special importance when metal implants such as gold fillings or hip prostheses are close to the treatment volume. In order to overcome this problem in treatment planning for heavy charged particles, the correct ranges of ions in the metal relative to water have to be assigned in the CT data. Measurements and calculations of carbon ion ranges in various metals are presented that can be used in treatment planning to allow for a more accurate range calculation of carbon ion beams in titanium, steel, tungsten and gold. The suggested values for the relative water-equivalent range and their uncertainties are 3.13 (±3%) for titanium, 5.59 (±3%) for stainless steel and 10.25 (±4%) for gold.

Alpha-particle emitters are currently being considered for the treatment of micrometastatic disease. Based on in vitro studies, it has been speculated that only a few alpha-particle hits to the cell nucleus are considered lethal. However, such estimates do not consider the stochastic variations in the number of alpha-particle hits, energy deposited, or in the cell survival process itself. Using a tumour control probability (TCP) model for alpha-particle emitters, we derive an estimate of the average number of hits to the cell nucleus required to provide a high probability of eradicating a tumour cell population. In simulation studies, our results demonstrate that the average number of hits required to achieve a 90% TCP for 10⁴ clonogenic cells ranges from 18 to 108. Those cells that have large cell nuclei, high radiosensitivities and alpha-particle emissions occurring primarily in the nuclei tended to require more hits. As the clinical implementation of alpha-particle emitters is considered, this type of analysis may be useful in interpreting clinical results and in designing treatment strategies to achieve a favourable therapeutic outcome.

Abnormal microcirculation is a feature of many neoplastic and non-neoplastic diseases. Physiological variables that characterize tissue microcirculation (capillary permeability and the volume of the extravascular extracellular fluid) are altered in pathological states. Pharmacokinetic analysis of dynamic contrast enhanced MRI (DCE-MRI) has found a widespread use in the assessment of abnormal microcirculation due to the direct link between the contrast agent kinetics and underlying microcirculatory properties. A representation of temporal variation of contrast agent concentration in blood plasma (C_p(t)) is central to this analysis. In clinical applications of DCE-MRI, signal intensity curves derived from rapidly enhancing lesions often display a sigmoid shape during the initial phase of contrast uptake and rapid arrival at the equilibrium phase. In this work, the features of two principal methods for pharmacokinetic analysis of DCE-MRI which allow for theoretical representation of C_p(t) are examined and combined to improve analysis of this particular class of DCE-MRI curves. The proposed method allows the representation of the initial sigmoid part of the enhancement profiles whilst retaining a realistic representation of C_p(t) based on previously published measurements obtained in healthy volunteers. The results of the computer simulations indicate that in rapidly enhancing lesions, with the transfer constant K^trans greater than 0.1 min⁻¹, the DCE-MRI acquisition can be restricted to 5 min post-injection and a mono-exponential representation of C_p(t) decay is sufficient. Furthermore, non-ideal bolus delivery can be represented as a short constant rate infusion when the tissue under investigation exhibits a sigmoid pattern of contrast uptake.

A method to measure the detector-to-object distance from the images obtained with stationary high-spatial-resolution gamma-ray cameras for in vivo studies has been developed. It exploits the shift of the imaged object in the image plane, obtained at a certain tilt of the parallel-hole collimator. A linear dependence of the image displacement on the distance to the object has been measured using a high-spatial-resolution scintillation camera employing an yttrium–aluminium perovskite (YAP) scintillator. It is shown that the modified YAP camera can be used to obtain three-dimensional information without moving the camera or the object. The method could be applied in scintimammography and radioguided surgery, in lymphoscintigraphy, as well as in the analysis of the biodistribution of radiopharmaceuticals.