Table of contents

The ability to select a discrete region within the body for signal acquisition is a fundamental requirement of in vivo NMR spectroscopy. Ideally, it should be possible to tailor the selected volume to coincide exactly with the lesion or tissue of interest, without loss of signal from within this volume or contamination with extraneous signals. Many techniques have been developed over the past 25 years employing a combination of RF coil properties, static magnetic field gradients and pulse sequence design in an attempt to meet these goals. This review presents a comprehensive survey of these techniques, their various advantages and disadvantages, and implications for clinical applications. Particular emphasis is placed on the reliability of the techniques in terms of signal loss, contamination and the effect of nuclear relaxation and J-coupling. The survey includes techniques based on RF coil and pulse design alone, those using static magnetic field gradients, and magnetic resonance spectroscopic imaging. Although there is an emphasis on techniques currently in widespread use (PRESS, STEAM, ISIS and MRSI), the review also includes earlier techniques, in order to provide historical context, and techniques that are promising for future use in clinical and biomedical applications.

Recently, our in vivo studies demonstrated a strong correlation between blood glucose concentration and the slope of the optical coherence tomography (OCT) signal when the probing beam was scanned over a straight line. To improve the sensitivity of OCT for blood glucose monitoring, two-dimensional (2D) lateral scanning of the OCT probing beam was proposed. Depth-dependent changes in pig skin properties with variation of blood glucose concentration were revealed due to significant suppression of speckle noise and motion artefacts in 2D scanning mode. The correlation coefficient of the OCT signal slope with blood glucose concentration varied periodically in the range from −0.9 to +0.9 depending on depth. The period of variation of the correlation coefficient was 100–150 µm that corresponded to the distance between neighbour collagen bundles. We also observed a decrease of skin thickness by 10 ± 7.5 µm with an increase of blood glucose concentration by 277 ± 56 mg dl⁻¹. Mechanisms of glucose-induced changes in skin properties owing to tissue layer shift caused by dehydration associated with the glucose osmotic effect were considered.

The aim of this study was to compare mammography systems based on three different detectors—a conventional screen–film (SF) combination, an a-Si/CsI flat-panel (FP)-based detector, and a charge-coupled device (CCD)-based x-ray phosphor-based detector—for their performance in detecting simulated microcalcifications (MCs). 112–150 µm calcium carbonate grains were used to simulate MCs and were overlapped with a slab phantom of simulated 50% adipose/50% glandular breast tissue-equivalent material referred to as the uniform background. For the tissue structure background, 200–250 µm calcium carbonate grains were used and overlapped with an anthropomorphic breast phantom. All MC phantom images were acquired with and without magnification (1.8X). The hardcopy images were reviewed by five mammographers. A five-point confidence level rating was used to score each detection task. Receiver operating characteristic (ROC) analysis was performed, and the areas under the ROC curves (A_zs) were used to compare the performances of the three mammography systems under various conditions. The results showed that, with a uniform background and contact images, the FP-based system performed significantly better than the SF and the CCD-based systems. For magnified images with a uniform background, the SF and the FP-based systems performed equally well and significantly better than the CCD-based system. With tissue structure background and contact images, the SF system performed significantly better than the FP and the CCD-based systems. With magnified images and a tissue structure background, the SF and the CCD-based systems performed equally well and significantly better than the FP-based system. In the detection of MCs in the fibroglandular and the heterogeneously dense regions, no significant differences were found except that the SF system performed significantly better than the CCD-based system in the fibroglandular regions for the contact images.

Margins about a target volume subject to external beam radiation therapy are designed to assure that the target volume of tissue to be sterilized by treatment is adequately covered by a lethal dose. Thus, margins are meant to guarantee that all potential variation in tumour position relative to beams allows the tumour to stay within the margin. Variation in tumour position can be broken into two types of dislocations, reducible and irreducible. Reducible variations in tumour position are those that can be accommodated with the use of modern image-guided techniques that derive parameters for compensating motions of patient bodies and/or motions of beams relative to patient bodies. Irreducible variations in tumour position are those random dislocations of a target that are related to errors intrinsic in the design and performance limitations of the software and hardware, as well as limitations of human perception and decision making. Thus, margins in the era of image-guided treatments will need to accommodate only random errors residual in patient setup accuracy (after image-guided setup corrections) and in the accuracy of systems designed to track moving and deforming tissues of the targeted regions of the patient's body. Therefore, construction of these margins will have to be based on purely statistical data. The characteristics of these data have to be determined through the central limit theorem and Gaussian properties of limiting error distributions. In this paper, we show how statistically determined margins are to be designed in the general case of correlated distributions of position errors in three-dimensional space. In particular, we show how the minimal margins for a given level of statistical confidence are found. Then, how they are to be used to determine geometrically minimal PTV that provides coverage of GTV at the assumed level of statistical confidence. Our results generalize earlier recommendations for statistical, central limit theorem-based recommendations for margin construction that were derived for uncorrelated distributions of errors (van Herk, Remeijer, Rasch and Lebesque 2000 Int. J. Radiat. Oncol. Biol. Phys.47 1121–35; Stroom, De Boer, Huizenga and Visser 1999 Int. J. Radiat. Oncol. Biol. Phys.43 905–19).

In this work we present an algorithm based on the simulated annealing (SA) method for electron beam spectrum reconstruction from central axis PDD data. We use a simulated beam in order to assess the accuracy of the method, and compare it with others usually employed. We found that our modified SA algorithm produced excellent reconstructed PDDs and beam profiles and improved reconstructed spectra. We also tested our method for the simultaneous determination of an electron energy spectrum and the position of a trimmer from central axis PDD data, and found this to be sufficient for the determination of the physical parameters of this hybrid model.

The combination-weighted Feldkamp algorithm (CW-FDK) was developed and tested in a phantom in order to reduce cone-beam artefacts and enhance cranio-caudal reconstruction coverage in an attempt to improve image quality when utilizing cone-beam computed tomography (CBCT). Using a 256-slice cone-beam CT (256CBCT), image quality (CT-number uniformity and geometrical accuracy) was quantitatively evaluated in phantom and clinical studies, and the results were compared to those obtained with the original Feldkamp algorithm. A clinical study was done in lung cancer patients under breath holding and free breathing. Image quality for the original Feldkamp algorithm is degraded at the edge of the scan region due to the missing volume, commensurate with the cranio-caudal distance between the reconstruction and central planes. The CW-FDK extended the reconstruction coverage to equal the scan coverage and improved reconstruction accuracy, unaffected by the cranio-caudal distance. The extended reconstruction coverage with good image quality provided by the CW-FDK will be clinically investigated for improving diagnostic and radiotherapy applications. In addition, this algorithm can also be adapted for use in relatively wide cone-angle CBCT such as with a flat-panel detector CBCT.

Accurate quantification of organ radionuclide uptake is important for patient-specific dosimetry. The quantitative accuracy from conventional conjugate view methods is limited by overlap of projections from different organs and background activity, and attenuation and scatter. In this work, we propose and validate a quantitative planar (QPlanar) processing method based on maximum likelihood (ML) estimation of organ activities using 3D organ VOIs and a projector that models the image degrading effects. Both a physical phantom experiment and Monte Carlo simulation (MCS) studies were used to evaluate the new method. In these studies, the accuracies and precisions of organ activity estimates for the QPlanar method were compared with those from conventional planar (CPlanar) processing methods with various corrections for scatter, attenuation and organ overlap, and a quantitative SPECT (QSPECT) processing method. Experimental planar and SPECT projections and registered CT data from an RSD Torso phantom were obtained using a GE Millenium VH/Hawkeye system. The MCS data were obtained from the 3D NCAT phantom with organ activity distributions that modelled the uptake of ¹¹¹In ibritumomab tiuxetan. The simulations were performed using parameters appropriate for the same system used in the RSD torso phantom experiment. The organ activity estimates obtained from the CPlanar, QPlanar and QSPECT methods from both experiments were compared. From the results of the MCS experiment, even with ideal organ overlap correction and background subtraction, CPlanar methods provided limited quantitative accuracy. The QPlanar method with accurate modelling of the physical factors increased the quantitative accuracy at the cost of requiring estimates of the organ VOIs in 3D. The accuracy of QPlanar approached that of QSPECT, but required much less acquisition and computation time. Similar results were obtained from the physical phantom experiment. We conclude that the QPlanar method, based on 3D organ VOIs and accurate models of the projection process, provided a substantial increase in accuracy of organ activity estimates from planar images compared to CPlanar processing and had accuracy approaching that of QSPECT.

Fluorescence molecular tomography is an emerging imaging technique that resolves the bio-distribution of engineered fluorescent probes developed for in vivo reporting of specific cellular and sub-cellular targets. The method can detect fluorochromes in picomole amounts or less, imaged through entire animals, but the detection sensitivity and imaging performance drop in the presence of background, non-specific fluorescence. In this study, we carried out a theoretical and an experimental investigation on the effect of background fluorescence on the measured signal and on the tomographic reconstruction. We further examined the performance of three subtraction methods based on physical models of photon propagation, using experimental data on phantoms and small animals. We show that the data pre-processing with subtraction schemes can improve image quality and quantification when non-specific background florescence is present.

An accurate, low noise estimate of photon attenuation in the subject is required for quantitative microPET studies of molecular tracer distributions in vivo. In this work, several transmission-based measurement techniques were compared, including coincidence mode with and without rod windowing, singles mode with two different energy sources (⁶⁸Ge and ⁵⁷Co), and postinjection transmission scanning. In addition, the effectiveness of transmission segmentation and the propagation of transmission bias and noise into the emission images were examined. The ⁵⁷Co singles measurements provided the most accurate attenuation coefficients and superior signal-to-noise ratio, while ⁶⁸Ge singles measurements were degraded due to scattering from the object. Scatter correction of ⁶⁸Ge transmission data improved the accuracy for a 10 cm phantom but over-corrected for a mouse phantom. ⁵⁷Co scanning also resulted in low bias and noise in postinjection transmission scans for emission activities up to 20 MBq. Segmentation worked most reliably for transmission data acquired with ⁵⁷Co but the minor improvement in accuracy of attenuation coefficients and signal-to-noise may not justify its use, particularly for small subjects. We conclude that ⁵⁷Co singles transmission scanning is the most suitable method for measured attenuation correction on the microPET Focus 220 animal scanner.

Detecting cancerous lesions is one major application in emission tomography. In this paper, we study penalized maximum-likelihood image reconstruction for this important clinical task. Compared to analytical reconstruction methods, statistical approaches can improve the image quality by accurately modelling the photon detection process and measurement noise in imaging systems. To explore the full potential of penalized maximum-likelihood image reconstruction for lesion detection, we derived simplified theoretical expressions that allow fast evaluation of the detectability of a random lesion. The theoretical results are used to design the regularization parameters to improve lesion detectability. We conducted computer-based Monte Carlo simulations to compare the proposed penalty function, conventional penalty function, and a penalty function for isotropic point spread function. The lesion detectability is measured by a channelized Hotelling observer. The results show that the proposed penalty function outperforms the other penalty functions for lesion detection. The relative improvement is dependent on the size of the lesion. However, we found that the penalty function optimized for a 5 mm lesion still outperforms the other two penalty functions for detecting a 14 mm lesion. Therefore, it is feasible to use the penalty function designed for small lesions in image reconstruction, because detection of large lesions is relatively easy.

In this study, the destruction of the contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was measured in vitro as a function of centre frequency (2–3 MHz), acoustic amplitude (0.66–1.6 MPa), pulse length (2–16 cycles) and PRF (0.5–8.0 kHz). Up to 82% of microbubbles were destroyed after exposure to a single 1.6 MPa acoustic pulse (16 cycles, 2.5 MHz and PRF of 1.0 kHz), while at a low amplitude of 0.66 MPa, fractional destruction increased gradually from 0 to 40% after exposure to 9 (identical) pulses. Fractional destruction increased from approximately 8 to 66% as pulse length was changed from 2 to 16 cycles following exposure to a single 2.5 MHz, 1.3 MPa pulse. As the PRF was increased from 0.5 to 8.0 kHz, shorter exposure time intervals (from 4.8 to 1.2 ms) were needed to achieve the same fractional destruction of 80%. Conversely, as the transmit frequency was increased from 2 to 3 MHz the fractional destruction decreased (by more than half within the first 3 pulses). The influence of changes in acoustic pressure and duty cycle on the destruction of Sonazoid microbubbles was highly statistically significant (p ⩽ 0.01) with a threshold around 0.67 MPa for a duty cycle of 0.0064. In conclusion, the fractional destruction increases with the duty cycle and the acoustic pressure amplitude and decreases with ultrasonic transmit frequency. Better understanding of the influence of the ultrasound transmit parameters on the destruction of contrast microbubbles should help improve existing contrast-assisted imaging modalities and may help develop new techniques for better use of contrast agents.

The present study aims to accurately localize epileptogenic regions which are responsible for epileptic activities in epilepsy patients by means of a new subspace source localization approach, i.e. first principle vectors (FINE), using scalp EEG recordings. Computer simulations were first performed to assess source localization accuracy of FINE in the clinical electrode set-up. The source localization results from FINE were compared with the results from a classic subspace source localization approach, i.e. MUSIC, and their differences were tested statistically using the paired t-test. Other factors influencing the source localization accuracy were assessed statistically by ANOVA. The interictal epileptiform spike data from three adult epilepsy patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were then studied using both FINE and MUSIC. The comparison between the electrical sources estimated by the subspace source localization approaches and MRI lesions was made through the coregistration between the EEG recordings and MRI scans. The accuracy of estimations made by FINE and MUSIC was also evaluated and compared by R² statistic, which was used to indicate the goodness-of-fit of the estimated sources to the scalp EEG recordings. The three-concentric-spheres head volume conductor model was built for each patient with three spheres of different radii which takes the individual head size and skull thickness into consideration. The results from computer simulations indicate that the improvement of source spatial resolvability and localization accuracy of FINE as compared with MUSIC is significant when simulated sources are closely spaced, deep, or signal-to-noise ratio is low in a clinical electrode set-up. The interictal electrical generators estimated by FINE and MUSIC are in concordance with the patients' structural abnormality, i.e. MRI lesions, in all three patients. The higher R² values achieved by FINE than MUSIC indicate that FINE provides a more satisfactory fitting of the scalp potential measurements than MUSIC in all patients. The present results suggest that FINE provides a useful brain source imaging technique, from clinical EEG recordings, for identifying and localizing epileptogenic regions in epilepsy patients with focal partial seizures. The present study may lead to the establishment of a high-resolution source localization technique from scalp-recorded EEGs for aiding presurgical planning in epilepsy patients.

The halftime for repair of sub-lethal damage is an important radiobiological parameter in analysing radiation responses and in designing new treatments involving different dose rates. This work is to resolve an inconsistency existing in the repair halftime for the bladder and rectum, two of the most dose limiting critical structures for pelvic irradiation. Both long (1.5–2 h) and short (0.3–1 h) repair halftimes have been reported previously. In this work, by reconciling clinical data from cervical brachytherapy of different dose rates and by introducing a sparing factor to consider the dose sparing occurring for critical structures, we have estimated that the most likely value of the repair halftime for bladder and rectum is short, 0.2–0.4 h if assuming α/β = 2–4 Gy. The present analysis does not support the long repair halftimes reported previously for the bladder and rectum and for other normal structures.

In treatment planning for hadron therapy, information about the relative stopping power in a patient's body is used to calculate the range of incident ions. This information is obtained from computed tomography (CT) images using a conversion table from x-ray CT numbers into stopping powers relative to the stopping power of water. In treatment planning at the National Institute of Radiological Sciences (NIRS), the conversion table has been created based on the polybinary tissue model. However, it has not been fully verified that the model is accurate enough for use in real animal tissues. In order to irradiate heavy ions more precisely in radiotherapy, we have to evaluate the accuracy of the polybinary tissue calibration in animal tissues. We have measured animal tissue samples with a heavy-ion CT (HICT) and an x-ray CT. The x-ray CT image was converted to an image of relative stopping power by using the table derived from the polybinary tissue calibration (polybinary-tissue-model CT (PTCT) image). On the other hand, with HICT, the two-dimensional distribution of relative stopping power can be obtained directly. A comparison between PTCT and HICT images enabled us to verify the accuracy of the conversion table derived from the polybinary tissue calibration. Consequently, it was found that the agreement between the relative stopping powers of PTCT and HICT is 1.6% for fat, muscle and bone.

We performed a Monte Carlo study to compare dose distributions for a Fletcher–Suit–Delclos (FSD) ovoid used with ¹³⁷Cs low-dose-rate (LDR) sources with those for a Fletcher–Williamson (FW) ovoid used with an ¹⁹²Ir pulsed-dose-rate (PDR) source for intracavitary brachytherapy of cervical cancer. We recently reported on extensive validation of Monte Carlo MCNPX models of these ovoids using radiochromic film measurements. Here, we compared these models assuming identical loading of 10, 15 and 20 mgRaEq (72, 108 and 145 cGy cm² h⁻¹, respectively) in three dose mesh planes: one perpendicular to the ovoid long axis bisecting the ovoid, one parallel to and displaced 2 cm medially from the long axis of the ovoid, and a 'rectal' plane perpendicular to the long axis located 1 cm distal to the distal face of the ovoid cap. The FW ovoid delivered slightly higher doses (within 10%) over all loadings to regions away from the bladder and rectal shields when compared to the FSD ovoid. However, the FW ovoid delivered much higher doses (>50%) in regions near these shields. In the rectal plane, the FW ovoid delivered a slightly higher dose, but within the region directly behind the rectal shield, the FW ovoid delivered a dose ranging from +35% to –35% of the FSD dose distribution. We attribute these differences to intrinsic differences in source characteristics (radial dose function and anisotropy factors) and extrinsic factors such as the solid-angle effect between sources and shields and applicator design.

An evaluation of mono-energetic proton energies ranging from 1.885 MeV to 1.920 MeV was carried out to determine the viability of these near threshold energies in producing neutrons for BNCT via the ⁷Li(p,n)⁷Be reaction. Neutron fields generated at these proton energies were assessed using the treatable protocol depth (TPD) and the maximum TPD (TPD_max) as evaluation indices. The heavy charged particle (HCP) dose rate to tumour was likewise applied as a figure of merit in order to account for irradiation time and required proton current. Incident proton energies closer to the reaction threshold generated deeper TPDs compared to higher energy protons when no boron dose enhancers (BDE) were placed in the irradiation field. Introducing a BDE resulted in improved TPDs for high proton energies but their achievable TPD_max were comparatively lower than that obtained for lower proton energies. In terms of the HCP dose rate to tumour, higher proton energies generated neutron fields that yielded higher dose rates both at TPD_max and at fixed depths of comparison. This infers that higher currents are required to deliver the prescribed treatment dose to tumours for proton beams with energies closer to the ⁷Li(p,n)⁷Be reaction threshold and more achievable proton currents of around 10 mA or less for proton energies from 1.900 MeV and above. The dependence on incident proton energy of the TPD, TPD_max and the HCP dose rate to tumour with respect to the ¹⁰B concentration in tumour and healthy tissues were also clarified in this study. Increasing the ¹⁰B concentration in tumour while maintaining a constant T/N ratio resulted in deeper TPD_max where a greater change in TPD_max was obtained for proton energies closer to the ⁷Li(p,n)⁷Be reaction threshold. The HCP dose rates to tumour for all proton energies also went up, with the higher proton energies benefiting more from the increased ¹⁰B concentration.

Standard treatment machines for external radiotherapy are designed to yield flat dose distributions at a representative treatment depth. The common method to reach this goal is to use a flattening filter to decrease the fluence in the centre of the beam. A side effect of this filtering is that the average energy of the beam is generally lower at a distance from the central axis, a phenomenon commonly referred to as off-axis softening. The off-axis softening results in a relative change in beam quality that is almost independent of machine brand and model. Central axis dose calculations using pencil beam kernels show no drastic loss in accuracy when the off-axis beam quality variations are neglected. However, for dose calculated at off-axis positions the effect should be considered, otherwise errors of several per cent can be introduced. This work proposes a method to explicitly include the effect of off-axis softening in pencil kernel based photon dose calculations for arbitrary positions in a radiation field. Variations of pencil kernel values are modelled through a generic relation between half value layer (HVL) thickness and off-axis position for standard treatment machines. The pencil kernel integration for dose calculation is performed through sampling of energy fluence and beam quality in sectors of concentric circles around the calculation point. The method is fully based on generic data and therefore does not require any specific measurements for characterization of the off-axis softening effect, provided that the machine performance is in agreement with the assumed HVL variations. The model is verified versus profile measurements at different depths and through a model self-consistency check, using the dose calculation model to estimate HVL values at off-axis positions. A comparison between calculated and measured profiles at different depths showed a maximum relative error of 4% without explicit modelling of off-axis softening. The maximum relative error was reduced to 1% when the off-axis softening was accounted for in the calculations.

Recently, several techniques have been developed to improve the quality of computed tomography (CT) images of the thoracic and abdominal region that are degraded by the interference of the scanning process and respiration. Several devices for respiratory-correlated CT are available for clinical usage. They are based on the synchronization of the acquired CT image data with the respiratory motion using a signal from an external respiratory monitoring system. In this work, some practical aspects of clinical implementation of the multi-slice 4D CT scanner Somatom Sensation Open (Siemens Medical Solutions, Erlangen, Germany) equipped with a respiratory gating system (RGS) AZ-733V (Anzai Medical, Tokyo, Japan) are discussed. A new algorithm developed for automatic respiratory phase determination needed for the reconstruction of the 4D CT images is presented.

The development of new biological imaging technologies offers the opportunity to further individualize radiotherapy. Biologically conformal radiation therapy (BCRT) implies the use of the spatial distribution of one or more radiobiological parameters to guide the IMRT dose prescription. Our aim was to implement BCRT in an algorithmic segmentation-based planning approach. A biology-based segmentation tool was developed to generate initial beam segments that reflect the biological signal intensity pattern. The weights and shapes of the initial segments are optimized by means of an objective function that minimizes the root mean square deviation between the actual and intended dose values within the PTV. As proof of principle, [¹⁸F]FDG-PET-guided BCRT plans for two different levels of dose escalation were created for an oropharyngeal cancer patient. Both plans proved to be dosimetrically feasible without violating the planning constraints for the expanded spinal cord and the contralateral parotid gland as organs at risk. The obtained biological conformity was better for the first (2.5 Gy per fraction) than for the second (3 Gy per fraction) dose escalation level.

Helical cone-beam CT is used widely nowadays because of its rapid scan speed and efficient utilization of x-ray dose. Recently, an exact reconstruction algorithm for helical cone-beam CT was proposed (Zou and Pan 2004a Phys. Med. Biol.49 941–59). The algorithm is referred to as a backprojection-filtering (BPF) algorithm. This BPF algorithm for a helical cone-beam CT with a flat-panel detector (FPD-HCBCT) requires minimum data within the Tam–Danielsson window and can naturally address the problem of ROI reconstruction from data truncated in both longitudinal and transversal directions. In practical CT systems, detectors are expensive and always take a very important position in the total cost. Hence, we work on an exact reconstruction algorithm for a CT system with a detector of the smallest size, i.e., a curved PI detector fitting the Tam–Danielsson window. The reconstruction algorithm is derived following the framework of the BPF algorithm. Numerical simulations are done to validate our algorithm in this study.