The clinical application of PET/CT: a contemporary review

The combination of positron emission tomography (PET) scanners and x-ray computed tomography (CT) scanners into a single PET/CT scanner has resulted in vast improvements in the diagnosis of disease, particularly in the field of oncology. A decade on from the publication of the details of the first PET/CT scanner, we review the technology and applications of the modality. We examine the design aspects of combining two different imaging types into a single scanner, and the artefacts produced such as attenuation correction, motion and CT truncation artefacts. The article also provides a discussion and literature review of the applications of PET/CT to date, covering detection of tumours, radiotherapy treatment planning, patient management, and applications external to the field of oncology

New Mechatronic Systems for the Diagnosis and Treatment of Cancer

Both two dimensional (2D) and three dimensional (3D) imaging modalities are useful tools for viewing the internal anatomy. Three dimensional imaging techniques are required for accurate targeting of needles. This improves the efficiency and control over the intervention as the high temporal resolution of medical images can be used to validate the location of needle and target in real time. Relying on imaging alone, however, means the intervention is still operator dependent because of the difficulty of controlling the location of the needle within the image. The objective of this thesis is to improve the accuracy and repeatability of needle-based interventions over conventional techniques: both manual and automated techniques. This includes increasing the accuracy and repeatability of these procedures in order to minimize the invasiveness of the procedure. In this thesis, I propose that by combining the remote center of motion concept using spherical linkage components into a passive or semi-automated device, the physician will have a useful tracking and guidance system at their disposal in a package, which is less threatening than a robot to both the patient and physician. This design concept offers both the manipulative transparency of a freehand system, and tremor reduction through scaling currently offered in automated systems. In addressing each objective of this thesis, a number of novel mechanical designs incorporating an remote center of motion architecture with varying degrees of freedom have been presented. Each of these designs can be deployed in a variety of imaging modalities and clinical applications, ranging from preclinical to human interventions, with an accuracy of control in the millimeter to sub-millimeter range

Schedule for CT image guidance in treating prostate cancer with helical tomotherapy.

The aim of this study was to determine the effect of reducing the number of image guidance sessions and patient-specific target margins on the dose distribution in the treatment of prostate cancer with helical tomotherapy. 20 patients with prostate cancer who were treated with helical tomotherapy using daily megavoltage CT (MVCT) imaging before treatment served as the study population. The average geometric shifts applied for set-up corrections, as a result of co-registration of MVCT and planning kilovoltage CT studies over an increasing number of image guidance sessions, were determined. Simulation of the consequences of various imaging scenarios on the dose distribution was performed for two patients with different patterns of interfraction changes in anatomy. Our analysis of the daily set-up correction shifts for 20 prostate cancer patients suggests that the use of four fractions would result in a population average shift that was within 1 mm of the average obtained from the data accumulated over all daily MVCT sessions. Simulation of a scenario in which imaging sessions are performed at a reduced frequency and the planning target volume margin is adapted provided significantly better sparing of organs at risk, with acceptable reproducibility of dose delivery to the clinical target volume. Our results indicate that four MVCT sessions on helical tomotherapy are sufficient to provide information for the creation of personalised target margins and the establishment of the new reference position that accounts for the systematic error. This simplified approach reduces overall treatment session time and decreases the imaging dose to the patient

3D fusion of histology to multi-parametric MRI for prostate cancer imaging evaluation and lesion-targeted treatment planning

Multi-parametric magnetic resonance imaging (mpMRI) of localized prostate cancer has the potential to support detection, staging and localization of tumors, as well as selection, delivery and monitoring of treatments. Delineating prostate cancer tumors on imaging could potentially further support the clinical workflow by enabling precise monitoring of tumor burden in active-surveillance patients, optimized targeting of image-guided biopsies, and targeted delivery of treatments to decrease morbidity and improve outcomes. Evaluating the performance of mpMRI for prostate cancer imaging and delineation ideally includes comparison to an accurately registered reference standard, such as prostatectomy histology, for the locations of tumor boundaries on mpMRI. There are key gaps in knowledge regarding how to accurately register histological reference standards to imaging, and consequently further gaps in knowledge regarding the suitability of mpMRI for tasks, such as tumor delineation, that require such reference standards for evaluation. To obtain an understanding of the magnitude of the mpMRI-histology registration problem, we quantified the position, orientation and deformation of whole-mount histology sections relative to the formalin-fixed tissue slices from which they were cut. We found that (1) modeling isotropic scaling accounted for the majority of the deformation with a further small but statistically significant improvement from modeling affine transformation, and (2) due to the depth (mean±standard deviation (SD) 1.1±0.4 mm) and orientation (mean±SD 1.5±0.9°) of the sectioning, the assumption that histology sections are cut from the front faces of tissue slices, common in previous approaches, introduced a mean error of 0.7 mm. To determine the potential consequences of seemingly small registration errors such as described above, we investigated the impact of registration accuracy on the statistical power of imaging validation studies using a co-registered spatial reference standard (e.g. histology images) by deriving novel statistical power formulae that incorporate registration error. We illustrated, through a case study modeled on a prostate cancer imaging trial at our centre, that submillimeter differences in registration error can have a substantial impact on the required sample sizes (and therefore also the study cost) for studies aiming to detect mpMRI signal differences due to 0.5 – 2.0 cm3 prostate tumors. With the aim of achieving highly accurate mpMRI-histology registrations without disrupting the clinical pathology workflow, we developed a three-stage method for accurately registering 2D whole-mount histology images to pre-prostatectomy mpMRI that allowed flexible placement of cuts during slicing for pathology and avoided the assumption that histology sections are cut from the front faces of tissue slices. The method comprised a 3D reconstruction of histology images, followed by 3D–3D ex vivo–in vivo and in vivo–in vivo image transformations. The 3D reconstruction method minimized fiducial registration error between cross-sections of non-disruptive histology- and ex-vivo-MRI-visible strand-shaped fiducials to reconstruct histology images into the coordinate system of an ex vivo MR image. We quantified the mean±standard deviation target registration error of the reconstruction to be 0.7±0.4 mm, based on the post-reconstruction misalignment of intrinsic landmark pairs. We also compared our fiducial-based reconstruction to an alternative reconstruction based on mutual-information-based registration, an established method for multi-modality registration. We found that the mean target registration error for the fiducial-based method (0.7 mm) was lower than that for the mutual-information-based method (1.2 mm), and that the mutual-information-based method was less robust to initialization error due to multiple sources of error, including the optimizer and the mutual information similarity metric. The second stage of the histology–mpMRI registration used interactively defined 3D–3D deformable thin-plate-spline transformations to align ex vivo to in vivo MR images to compensate for deformation due to endorectal MR coil positioning, surgical resection and formalin fixation. The third stage used interactively defined 3D–3D rigid or thin-plate-spline transformations to co-register in vivo mpMRI images to compensate for patient motion and image distortion. The combined mean registration error of the histology–mpMRI registration was quantified to be 2 mm using manually identified intrinsic landmark pairs. Our data set, comprising mpMRI, target volumes contoured by four observers and co-registered contoured and graded histology images, was used to quantify the positive predictive values and variability of observer scoring of lesions following the Prostate Imaging Reporting and Data System (PI-RADS) guidelines, the variability of target volume contouring, and appropriate expansion margins from target volumes to achieve coverage of histologically defined cancer. The analysis of lesion scoring showed that a PI-RADS overall cancer likelihood of 5, denoting “highly likely cancer”, had a positive predictive value of 85% for Gleason 7 cancer (and 93% for lesions with volumes \u3e0.5 cm3 measured on mpMRI) and that PI-RADS scores were positively correlated with histological grade (ρ=0.6). However, the analysis also showed interobserver differences in PI-RADS score of 0.6 to 1.2 (on a 5-point scale) and an agreement kappa value of only 0.30. The analysis of target volume contouring showed that target volume contours with suitable margins can achieve near-complete histological coverage for detected lesions, despite the presence of high interobserver spatial variability in target volumes. Prostate cancer imaging and delineation have the potential to support multiple stages in the management of localized prostate cancer. Targeted biopsy procedures with optimized targeting based on tumor delineation may help distinguish patients who need treatment from those who need active surveillance. Ongoing monitoring of tumor burden based on delineation in patients undergoing active surveillance may help identify those who need to progress to therapy early while the cancer is still curable. Preferentially targeting therapies at delineated target volumes may lower the morbidity associated with aggressive cancer treatment and improve outcomes in low-intermediate-risk patients. Measurements of the accuracy and variability of lesion scoring and target volume contouring on mpMRI will clarify its value in supporting these roles

Importance of heterogeneity correction for prostate therapy planning as it relates to prostate motion

2012 Fall.Includes bibliographical references.Prostate adenocarcinoma is the most common cancer among men and second leading cause of mortality of men in the United States. External beam radiotherapy (RT) is often used for local prostate tumor control as part of multimodality therapy. Dosimetric treatment planning for RT is based on complex calculations made by computerized planning software, which are designed to achieve a target prescribed dose to the prostate while not exceeding normal tissue constraints. Those RT planning calculations are made from an initial pre-treatment computed tomographic (CT) scan, which provides the location, volume and density of the prostate and critical normal tissues. The calculation step applies Heterogeneity Correction (HC) during RT planning, which adjusts the delivered radiation fields according to regional tissue densities such as the presence of bone in the anatomic region of interest. Inter-fraction and intra-fraction prostate movement are both known to occur during the course of radiotherapy. Current standards of practice utilize ways to track and account for prostatic movement in order to maintain accurate delivery to that organ. However, those methods do not adjust for the HC that was already applied during the original treatment plan calculations. The use of HC for prostate cancer RT is therefore of particular importance because prostate movement relative to the pelvic skeleton might result in dosimetric inaccuracies, since the HC used in initial RT planning is based on the original prostate position. This project was part of a larger research study in which intact normal male dogs received hypofractionated stereotactic radiation to the prostate, as a translational animal model for human prostate cancer. In this study, inter-fraction prostate motion was evaluated and then those data were used to examine the impact of this movement on the use of heterogeneity correction (HC) on stereotactic body radiation therapy (SBRT) of the prostate, by evaluating the dose received by the planned target volume (PTV) and surrounding tissue during prostate RT planning. In Aim 1, cone beam CT (CBCT) images from ten dogs were evaluated retrospectively to estimate typical inter-fraction prostate movement. Organs of interest were contoured on each daily treatment CBCT data set, and those images were registered (fused) to the original planning CT. Prostate motion was quantified by determining the displacement of each isocenter relative to the original radiotherapy planning CT. For Aim 2, CT scans acquired during the course of SBRT were used to prospectively calculate new treatment plans that incorporated prostate displacement from four dogs, with and without HC. Organs of interest were contoured on each CT data set, and images were registered (fused) to the original planning CT. As above, prostate motion was quantified by measuring the isocenter movement in three axes relative to original RT planning CT. An optimal original planning CT was run twice for each CT, with and without HC, while adjusting the prostatic isocenter. Dosimetric data for organs of interest were evaluated using dose volume histograms (DVH) and comparing doses to previously defined constraint values. Results indicated a wide range of inter-fraction prostate displacement in both Aims 1 and 2, slightly greater in magnitude than similar human prostate movement data. The greatest prostate displacement was in the y axis (anteroposterior). No statistically significant differences were seen in target or normal tissue doses, with or without HC, suggesting that even in the presence of marked prostate motion, potential inaccuracies caused by HC may not have a great impact on the prostate RT planning. As expected, without HC there was a trend for the dose to the most organs of interest to increase slightly. In terms of how displacement affected tissue doses, maximum displacement of prostate was associated with adjacent tissues exceeding the known normal tissue tolerance. In particular, caudal and left displacement led to large doses exceeding the constraint limits for the posterior rectal wall. Those data indicate the importance of continued tracking or other methods to counteract prostate motion. The results provide a more informed approach for using HC relative to prostate motion during treatment of prostate cancer, as well as providing data relevant to tumor control, acute and late toxicities associated with inter-fraction movement of prostate RT