Table of contents

The aim of this paper is to assess the overall geometric accuracy of the Novalis system using the Robotic Tilt Module in terms of the uncertainty in frameless stereotactic radiotherapy. We analyzed the following three metrics: (1) the correction accuracy of the robotic couch, (2) the uncertainty of the isocenter position with gantry and couch rotation, and (3) the shift in position between the isocenter and central point detected with the ExacTrac x-ray system. Based on the concept of uncertainty, the overall accuracy was calculated from these values. The accuracy in positional correction with the robotic couch was 0.07 ± 0.22 mm, the positional shift of the isocenter associated with gantry rotation was 0.35 mm, the positional shift of the isocenter associated with couch rotation was 0.38 mm and the difference in position between the isocenter and the ExacTrac x-ray system was 0.30 mm. The accuracy of intracranial stereotactic radiosurgery with the Novalis system in our clinic was 0.31 ± 0.77 mm. The overall geometric accuracy based on the concept of uncertainty was 0.31 ± 0.77 mm, which is within the tolerance given in the American Association of Physicists in Medicine report no. 54.

In this work, we report a unified methodology to express the molecular wavefunctions of water in both vapor and liquid phases by means of a single-center approach. These latter are then used as input data in a theoretical treatment—previously published and successfully tested—for describing the water ionization process in the first Born approximation (Champion et al 2006 Phys. Rev. A 73 012717). The multi-differential and total cross sections also obtained are reported for the two thermodynamical phases investigated and compared to the rare existing experimental and theoretical data.

The aim of this study was to explore similarities between intensity-modulated radiotherapy (IMRT) and intensity-modulated arc therapy (IMAT) techniques in the context of the number of multi-leaf collimator (MLC) segments required to achieve plan objectives, the major factor influencing plan quality. Three clinical cases with increasing complexity were studied: (a) prostate only, (b) prostate and seminal vesicles and (c) prostate and pelvic lymph nodes. Initial 'gold-standard' plans with the maximum possible organ-at-risk sparing were generated for all three cases. For each case, multiple IMRT and IMAT plans were generated with varying intensity levels (IMRT) and arc control points (IMAT), which translate into varying MLC segments in both modalities. The IMAT/IMRT plans were forced to mimic the organ-at-risk sparing and target coverage in the gold-standard plans, thereby only allowing the target dose inhomogeneity to be variable. A higher target dose inhomogeneity (quantified as D5—dose to the highest 5% of target volume) implies that the plan is less capable of modulation. For each case, given a similar number of MLC segments, both IMRT and IMAT plans exhibit similar target dose inhomogeneity, indicating that there is no difference in their ability to provide dose painting. Target dose inhomogeneity remained approximately constant with decreasing segments, but sharply increased below a specific critical number of segments (70, 100, 110 for cases a, b, c, respectively). For the cases studied, IMAT and IMRT plans are similar in their dependence on the number of MLC segments. A minimum critical number of segments are required to ensure adequate plan quality. Future studies are needed to establish the range of minimum critical number of segments for different treatment sites and target-organ geometries.

A prototype time-of-flight (TOF) PET scanner based on cerium-doped lanthanum bromide [LaBr₃ (5% Ce)] has been developed. LaBr₃ has a high light output, excellent energy resolution and fast timing properties that have been predicted to lead to good image quality. Intrinsic performance measurements of spatial resolution, sensitivity and scatter fraction demonstrate good conventional PET performance; the results agree with previous simulation studies. Phantom measurements show the excellent image quality achievable with the prototype system. Phantom measurements and corresponding simulations show a faster and more uniform convergence rate, as well as more uniform quantification, for TOF reconstruction of the data, which have 375 ps intrinsic timing resolution, compared to non-TOF images. Measurements and simulations of a hot and cold sphere phantom show that the 7% energy resolution helps to mitigate residual errors in the scatter estimate because a high energy threshold (>480 keV) can be used to restrict the amount of scatter accepted without a loss of true events. Preliminary results with incorporation of a model of detector blurring in the iterative reconstruction algorithm not only show improved contrast recovery but also point out the importance of an accurate resolution model of the tails of LaBr₃'s point spread function. The LaBr₃ TOF-PET scanner demonstrated the impact of superior timing and energy resolutions on image quality.

Electromagnetic tracking technology is primarily used for continuous prostate localization during radiotherapy, but offers potential value for evaluation of dosimetric coverage and adequacy of treatment for dynamic targets. We developed a highly automated method for daily computation of cumulative dosimetric effects of intra- and inter-fraction target motion for prostate cancer patients using fiducial-based electromagnetic tracking. A computer program utilizing real-time tracking data was written to (1) prospectively determine appropriate rotational/translational motion limits for patients treated with continuous isocenter localization; (2) retrospectively analyze dosimetric target coverage after daily treatment, and (3) visualize three-dimensional rotations and translations of the prostate with respect to the planned target volume and dose matrix. We present phantom testing and a patient case to validate and demonstrate the utility of this application. Gamma analysis of planar dose computed by our application demonstrated accuracy within 1%/1 mm. Dose computation of a patient treatment revealed high variation in minimum dose to the prostate (D_min) over 40 fractions and a drop in the D_min of ≈8% between a 5 mm and a 3 mm PTV margin plan. The infrastructure has been created for patient-specific treatment evaluation using continuous tracking data. This application can be used to increase confidence in treatment delivery to targets influenced by motion.

The first purpose of this paper is to shed some new light on the old question of selecting the number of beams in intensity-modulated radiation therapy (IMRT). The second purpose is to illuminate the related issue of discrete static beam angles versus rotational techniques, which has recently re-surfaced due to the advancement of volumetric modulated arc therapy (VMAT). A specific objective is to find analytical expressions that allow one to address the points raised above. To make the problem mathematically tractable, it is assumed that the depth dose is flat and that the lateral dose profile can be approximated by polynomials, specifically Chebyshev polynomials of the first kind, of finite degree. The application of methods known from image reconstruction then allows one to answer the first question above as follows: the required number of beams is determined by the maximum degree of the polynomials used in the approximation of the beam profiles, which is a measure of the dose variability. There is nothing to be gained by using more beams. In realistic cases, in which the variability of the lateral dose profile is restricted in several ways, the required number of beams is of the order of 10–20. The consequence of delivering the beams with a 'leaf sweep' technique during continuous rotation of the gantry, as in VMAT, is also derived in an analytical form. The main effect is that the beams fan out, but the effect near the axis of rotation is small. This result can serve as a theoretical justification of VMAT. Overall the analytical derivations in this paper, albeit based on strong simplifications, provide new insights into, and a deeper understanding of, the beam angle problem in IMRT. The decomposition of the beam profiles into well-behaved and easily deliverable smooth functions, such as Chebyshev polynomials, could be of general interest in IMRT treatment planning.

Scattered radiation is a major source of artifacts in flat detector computed tomography (FDCT) due to the increased irradiated volumes. We propose a fast projection-based algorithm for correction of scatter artifacts. The presented algorithm combines a convolution method to determine the spatial distribution of the scatter intensity distribution with an object-size-dependent scaling of the scatter intensity distributions using a priori information generated by Monte Carlo simulations. A projection-based (PBSE) and an image-based (IBSE) strategy for size estimation of the scanned object are presented. Both strategies provide good correction and comparable results; the faster PBSE strategy is recommended. Even with such a fast and simple algorithm that in the PBSE variant does not rely on reconstructed volumes or scatter measurements, it is possible to provide a reasonable scatter correction even for truncated scans. For both simulations and measurements, scatter artifacts were significantly reduced and the algorithm showed stable behavior in the z-direction. For simulated voxelized head, hip and thorax phantoms, a figure of merit Q of 0.82, 0.76 and 0.77 was reached, respectively (Q = 0 for uncorrected, Q = 1 for ideal). For a water phantom with 15 cm diameter, for example, a cupping reduction from 10.8% down to 2.1% was achieved. The performance of the correction method has limitations in the case of measurements using non-ideal detectors, intensity calibration, etc. An iterative approach to overcome most of these limitations was proposed. This approach is based on root finding of a cupping metric and may be useful for other scatter correction methods as well. By this optimization, cupping of the measured water phantom was further reduced down to 0.9%. The algorithm was evaluated on a commercial system including truncated and non-homogeneous clinically relevant objects.

The purpose of this work is to quantify the accuracy of pharmacokinetic parameter measurement in DCE-MRI of breast cancer at 3 T in relation to three sources of error. Individually, T1 measurement error, temporal resolution and transmitted RF field inhomogeneity are considered. Dynamic contrast enhancement curves were simulated using standard acquisition parameters of a DCE-MRI protocol. Errors on pre-contrast T1 due to incorrect RF spoiling were considered. Flip angle errors were measured and introduced into the fitting routine, and temporal resolution was also varied. The error in fitted pharmacokinetic parameters, K^trans and v_e, was calculated. Flip angles were found to be reduced by up to 55% of the expected value. The resultant errors in our range of K^trans and v_e were found to be up to 66% and 74%, respectively. Incorrect T1 estimation results in K^trans and v_e errors up to 531% and 233%, respectively. When the temporal resolution is reduced from 10 to 70 s K^trans drops by up to 48%, while v_e shows negligible variation. In combination, uncertainties in tissue T1 map and applied flip angle were shown to contribute to errors of up to 88% in K^trans and 73% in v_e. These results demonstrate the importance of high temporal resolution, accurate T1 measurement and good B1 homogeneity.

Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI_AM and female RPI_AF phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon exposure showed good agreement between FASH/MASH and REGINA/REX, but large differences between FASH/MASH and the mesh-based RPI_AM and the RPI_AF phantoms, developed at the Rensselaer Polytechnic Institute (RPI).

Optical coherence tomography (OCT) provides high-resolution, cross-sectional imaging of tissue microstructure in situ and in real time, while fluorescence molecular imaging (FMI) enables the visualization of basic molecular processes. There is a great deal of interest in combining these two modalities so that the tissue's structural and molecular information can be obtained simultaneously. This could greatly benefit biomedical applications such as detecting early diseases and monitoring therapeutic interventions. In this research, an optical system that combines OCT and FMI was developed. The system demonstrated that it could co-register en face OCT and FMI images with a 2.4 × 2.4 mm² field-of-view. The transverse resolutions of OCT and FMI of the system are both ∼10 µm. Capillary tubes filled with fluorescent dye Cy 5.5 in different concentrations under a scattering medium are used as the phantom. En face OCT images of the phantoms were obtained and successfully co-registered with FMI images that were acquired simultaneously. A linear relationship between FMI intensity and dye concentration was observed. The relationship between FMI intensity and target fluorescence tube depth measured by OCT images was also observed and compared with theoretical modeling. This relationship could help in correcting reconstructed dye concentration. Imaging of colon polyps of the APC^min mouse model is presented as an example of biological applications of this co-registered OCT/FMI system.

Online adaptive radiation therapy (ART) promises the ability to deliver an optimal treatment in response to daily patient anatomic variation. A major technical barrier for the clinical implementation of online ART is the requirement of rapid image segmentation. Deformable image registration (DIR) has been used as an automated segmentation method to transfer tumor/organ contours from the planning image to daily images. However, the current computational time of DIR is insufficient for online ART. In this work, this issue is addressed by using computer graphics processing units (GPUs). A gray-scale-based DIR algorithm called demons and five of its variants were implemented on GPUs using the compute unified device architecture (CUDA) programming environment. The spatial accuracy of these algorithms was evaluated over five sets of pulmonary 4D CT images with an average size of 256 × 256 × 100 and more than 1100 expert-determined landmark point pairs each. For all the testing scenarios presented in this paper, the GPU-based DIR computation required around 7 to 11 s to yield an average 3D error ranging from 1.5 to 1.8 mm. It is interesting to find out that the original passive force demons algorithms outperform subsequently proposed variants based on the combination of accuracy, efficiency and ease of implementation.

Tumor heterogeneities observed in positron emission tomography (PET) imaging are frequently compromised by partial volume effects which may affect treatment prognosis, assessment or future implementations such as biologically optimized treatment planning (dose painting). This paper presents a method for partial volume correction of PET-imaged heterogeneous tumors. A point source was scanned on a GE Discovery LS at positions of increasing radii from the scanner's center to obtain the spatially varying point spread function (PSF). PSF images were fit in three dimensions to Gaussian distributions using least squares optimization. Continuous expressions were devised for each Gaussian width as a function of radial distance, allowing for generation of the system PSF at any position in space. A spatially varying partial volume correction (SV-PVC) technique was developed using expectation maximization (EM) and a stopping criterion based on the method's correction matrix generated for each iteration. The SV-PVC was validated using a standard tumor phantom and a tumor heterogeneity phantom and was applied to a heterogeneous patient tumor. SV-PVC results were compared to results obtained from spatially invariant partial volume correction (SINV-PVC), which used directionally uniform three-dimensional kernels. SV-PVC of the standard tumor phantom increased the maximum observed sphere activity by 55 and 40% for 10 and 13 mm diameter spheres, respectively. Tumor heterogeneity phantom results demonstrated that as net changes in the EM correction matrix decreased below 35%, further iterations improved overall quantitative accuracy by less than 1%. SV-PVC of clinically observed tumors frequently exhibited changes of ±30% in regions of heterogeneity. The SV-PVC method implemented spatially varying kernel widths and automatically determined the number of iterations for optimal restoration, parameters which are arbitrarily chosen in SINV-PVC. Comparing SV-PVC to SINV-PVC demonstrated that similar results could be reached using both methods, but large differences result for the arbitrary selection of SINV-PVC parameters. The presented SV-PVC method was performed without user intervention, requiring only a tumor mask as input. Research involving PET-imaged tumor heterogeneity should include correcting for partial volume effects to improve the quantitative accuracy of results.

The use of functional imaging in radiotherapy treatment (RT) planning requires accurate co-registration of functional imaging scans to CT scans. We evaluated six methods of image registration for use in SPECT-guided radiotherapy treatment planning. Methods varied in complexity from 3D affine transform based on control points to diffeomorphic demons and level set non-rigid registration. Ten lung cancer patients underwent perfusion SPECT-scans prior to their radiotherapy. CT images from a hybrid SPECT/CT scanner were registered to a planning CT, and then the same transformation was applied to the SPECT images. According to registration evaluation measures computed based on the intensity difference between the registered CT images or based on target registration error, non-rigid registrations provided a higher degree of accuracy than rigid methods. However, due to the irregularities in some of the obtained deformation fields, warping the SPECT using these fields may result in unacceptable changes to the SPECT intensity distribution that would preclude use in RT planning. Moreover, the differences between intensity histograms in the original and registered SPECT image sets were the largest for diffeomorphic demons and level set methods. In conclusion, the use of intensity-based validation measures alone is not sufficient for SPECT/CT registration for RTTP. It was also found that the proper evaluation of image registration requires the use of several accuracy metrics.

We propose a completely automated algorithm for the detection of the spinal centreline and the centres of vertebral bodies and intervertebral discs in images acquired by computed tomography (CT) and magnetic resonance (MR) imaging. The developed methods are based on the analysis of the geometry of spinal structures and the characteristics of CT and MR images and were evaluated on 29 CT and 13 MR images of lumbar spine. The overall mean distance between the obtained and the ground truth spinal centrelines and centres of vertebral bodies and intervertebral discs were 1.8 ± 1.1 mm and 2.8 ± 1.9 mm, respectively, and no considerable differences were detected among the results for CT, T₁-weighted MR and T₂-weighted MR images. The knowledge of the location of the spinal centreline and the centres of vertebral bodies and intervertebral discs is valuable for the analysis of the spine. The proposed method may therefore be used to initialize the techniques for labelling and segmentation of vertebrae.

A positron emission tomography (PET) system or 'insert' has been constructed for placement and operation in the bore of a small animal magnetic resonance imaging (MRI) scanner to allow simultaneous MR and PET imaging. The insert contains electronics, components with a variety of magnetic properties and large continuous sheets of metal—all characteristics of an object that should, by conventional wisdom, never be placed in the bore of an MR scanner, especially near the imaging volume. There are a variety of ways the two systems might be expected to interact that could negatively impact the performance of either or both. In this article, the interaction mechanisms, particularly the impact of the PET insert and shielding on MR imaging, are defined and explored. Additionally, some of the difficulties in quantifying errors introduced into the MR images as a result of the presence of the PET components are demonstrated. Several different approaches are used to characterize image artifacts and determine optimal placement of the shielding. Data are also presented that suggest ways the shielding could be modified to reduce errors and enable placement closer to the isocenter of the magnet.

Directly injecting therapeutics into brain tissue has been investigated both experimentally and theoretically. Paul Morrison and others from the National Institutes of Health pointed out the importance of backflow along and outside a catheter inserted into the tissue, once steady state conditions have been reached. Here we investigate and extend their model. We begin with a reformulation of their results and demonstrate an exact solution that exhibits the scaling behavior of the model where the surrounding tissue medium is homogeneous and isotropic. We report on experimental tests of our predictions in agarose gels. We describe the limitations of the assumptions used and the utility of our reformulation. Extensions of the model, including improvements on some of its crude assumptions and generalizations to inhomogeneous media, will be submitted separately.

A four-dimensional deformable image registration (4D DIR) algorithm, referred to as 4D local trajectory modeling (4DLTM), is presented and applied to thoracic 4D computed tomography (4DCT) image sets. The theoretical framework on which this algorithm is built exploits the incremental continuity present in 4DCT component images to calculate a dense set of parameterized voxel trajectories through space as functions of time. The spatial accuracy of the 4DLTM algorithm is compared with an alternative registration approach in which component phase to phase (CPP) DIR is utilized to determine the full displacement between maximum inhale and exhale images. A publically available DIR reference database (http://www.dir-lab.com) is utilized for the spatial accuracy assessment. The database consists of ten 4DCT image sets and corresponding manually identified landmark points between the maximum phases. A subset of points are propagated through the expiratory 4DCT component images. Cubic polynomials were found to provide sufficient flexibility and spatial accuracy for describing the point trajectories through the expiratory phases. The resulting average spatial error between the maximum phases was 1.25 mm for the 4DLTM and 1.44 mm for the CPP. The 4DLTM method captures the long-range motion between 4DCT extremes with high spatial accuracy.

This paper presents calculated specific absorption rate (SAR) dosimetry in 4 and 8 week Japanese pregnant-woman models exposed to plane waves over the frequency range of 10 MHz–1.5 GHz. Two types of 2 mm spatial-resolution pregnant-woman models comprised a woman model, which is similar to the average-sized Japanese adult female in height and weight, with a cubic (4 week) embryo or spheroidal (8 week) one. The averaged SAR in the embryos exposed to vertically and horizontally polarized plane waves at four kinds of propagation directions are calculated from 10 MHz to 1.5 GHz. The results indicate that the maximum average SAR in the embryos exposed to plane waves is lower than 0.08 W kg⁻¹ when the incident power density is at the reference level of ICNIRP guideline for general public environment.

Various aspects of RF-induced heating of guide wires during their MRI guidance have been investigated in the past. However, the previous works focused on inducing tip heating in either fully immersed or tip-immersed (and otherwise free) wires of impractical lengths in small phantoms. This study simulates real clinical conditions using a product guide wire and a same-length conductive wire partially inserted into a torso-size phantom filled with saline solution. The purpose was to identify potential safety concerns relevant to real clinical applications, as opposed to identifying the worst-case heating scenario. Significant heating occurred at the insertion point, independent of tip heating, with a strong correlation with excitation frequency-dependent imaging parameters. Heat transfer through the wire was also demonstrated to be a safety concern. From these experiments, we have been able to demonstrate additional impacting factors that increase the complexity of safety considerations for the use of conductive guide wires during MR imaging. Safety under a particular set of conditions does not imply safety in all possible conditions that can be encountered during real MRI-guided interventions.