4DCT radiotherapy for NSCLC: A review of planning methods

Purpose To establish whether the use of a passive or active technique of planning target volume (PTV) definition and treatment methods for non-small cell lung cancer (NSCLC) deliver the most effective results. This literature review assesses the advantages and disadvantages in recent studies of each, while assessing the validity of the two approaches for planning and treatment. Methods A systematic review of literature focusing on the planning and treatment of radiation therapy to NSCLC tumours. Different approaches which have been published in recent articles are subjected to critical appraisal in order to determine their relative efficacy. Results Free-breathing (FB) is the optimal method to perform planning scans for patients and departments, as it involves no significant increase in cost, workload or education. Maximum intensity projection (MIP) is the fastest form of delineation, however it is noted to be less accurate than the ten-phase overlap approach for computed tomography (CT). Although gating has proven to reduce margins and facilitate sparing of organs at risk, treatment times can be longer and planning time can be as much as 15 times higher for intensity modulated radiation therapy (IMRT). This raises issues with patient comfort and stabilisation, impacting on the chance of geometric miss. Stereotactic treatments can take up to 3 hours to treat, along with increases in planning and treatment, as well as the additional hardware, software and training required. Conclusion Four-dimensional computed tomography (4DCT) is superior to 3DCT, with the passive FB approach for PTV delineation and treatment optimal. Departments should use a combination of MIP with visual confirmation ensuring coverage for stage 1 disease. Stages 2-3 should be delineated using ten-phases overlaid. Stereotactic and gated treatments for early stage disease should be used accordingly; FB-IMRT is optimal for latter stage disease.

The ghrelin axis in the skeletal microenvironment

This project characterised the bone microarchitecture of adult mice lacking the hormone, acyl ghrelin, by high resolution micro-computed tomography; and investigated the expression of the ghrelin axis in cells of human and mouse fetal cartilage. This thesis highlights for the first time the physiological role of the ghrelin axis in the bone microenvironment of aged mice. Furthermore it improves our understanding of the complex expression patterns of the ghrelin axis in cartilage cells of human and mouse fetal skeletons.

Morphometric modelling of ageing in the human pubic symphysis : sexual dimorphism in an Australian population

Despite the prominent use of the pubic symphysis for age estimation in forensic anthropology, little has been documented regarding the quantitative morphological and micro-architectural changes of this surface. Specifically, utilising post-mortem computed tomography data from a large, contemporary Australian adult population, this study aimed to evaluate sexual dimorphism in the morphology and bone composition of the symphyseal surface; and temporal characterisation of the pubic symphysis in individuals of advancing age. The sample consisted of multi-slice computed tomography (MSCT) scans of the pubic symphysis(slice thickness: 0.5 mm, overlap: 0.1 mm) of 200 individuals of Caucasian ancestry aged 15–70 years, obtained in 2011. Surface rendering reconstruction of the symphyseal surface was conducted in OsiriX1 (v.4.1) and quantitative analyses in Rapidform XOSTM and OsteomeasureTM. Morphometric variables including inter-pubic distance, surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone compositions were quantified using novel automated engineering software capabilities. The major results of this study are correlated with the macroscopic ossification and degeneration pattern of the symphyseal surface, demonstrating significant age-related changes in the morphometric and bone tissue variables between 15 and 70 years. Regardless of sex, the overall dimensions of the symphyseal surface increased with age, coupled with a decrease in bone mass in the trabecular and cortical bone compartments. Significant differences between the ventral, dorsal and medial cortical surfaces were observed, which may be correlated to bone formation activity dependent on muscle activity and ligamentous attachments. Our study demonstrates significant sexual dimorphism at this site, with males exhibiting greater surface dimensions than females. These baseline results provide a detailed insight into the changes in the structure of the pubic symphysis with ageing and sexually dimorphic features associated with the cortical and trabecular bone profiles.

Weight-related differences in glucose metabolism and free fatty acid production in two South African population groups

OBJECTIVE The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS Anthropometric and various metabolic indices were measured at fasting and during a 7h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS Visceral fat levels were significantly higher (P < 0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P < 0.05 for both) and was found to correlate negatively with weight (r = -0.69, P < 0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OCTT was 24 +/- 12% in OWW and - 38 +/- 23% (P < 0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120 - 420 min) was significantly higher in OWW than OBW (P < 0.01) and LWW (P < 0.01) and correlated positively with visceral fat mass independent of age (r = 0.78, P < 0.05) in the OWW only. Leptin levels were higher (P < 0.01) both at fasting and during the course of the OCTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

Ethnic differences in lipid metabolism in two groups of obese South African women

There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), ah premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin Lipoprotein Lipase activity were measured during an oral glucose tolerance test (OGTT), Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared, with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW. These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial Lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition. - Punyadeera, C., M-T. van der Merwe, N.J. Crowther, M. Toman, C. P. Schlaphoff, and I. P. Gray. Ethnic differences in lipid metabolism in two groups of obese South African women.

Metabolic response to a mixed meal in obese and lean women from two South African populations

Objective Lower lipid and insulin levels are found during a glucose-tolerance test in obese black than obese white South African women. Therefore, β-cell function and lipid metabolism were compared in these populations during a mixed meal. Research Methods and Procedures Blood concentrations of glucose, free fatty acids (FFAs), insulin, lipograms, and in vivo FFA oxidation were determined at fasting and for 7 hours after oral administration of a mixed emulsion containing glucose-casein-sucrose-lipid and [1-13C] palmitic acid in 8 lean black women (LBW), 10 obese black women (OBW), 9 lean white women (LWW), and 10 obese white women (OWW). Subcutaneous and visceral fat mass was assessed by computerized tomography. Results Visceral fat area was higher in OWW (152.7 ± 17.0 cm2) than OBW (80.0 ± 6.7 cm2; p < 0.01). In OBW, 30-minute insulin levels were higher (604.3 ± 117.6 pM) than OWW (311.0 ± 42.9 pM; p < 0.05). Total triglyceride was higher in OWW (706.7 ± 96.0 mM × 7 hours) than OBW (465.7 ± 48.2 mM × 7 hours; p < 0.05) and correlated with visceral fat area (β = 0.38, p = 0.05). Palmitate oxidation was higher in lean than obese women in both ethnic groups and correlated negatively with fat mass (β = −0.58, p < 0.005). Discussion The higher 30-minute insulin response in OBW may reflect a higher insulinotropic effect of FFAs or glucose. The elevated triglyceride level of OWW may be due to their higher visceral fat mass and possibly reduced clearance by adipose tissue.

Supine to standing Cobb angle change in idiopathic scoliosis : the effect of endplate pre-selection

Background Supine imaging modalities provide valuable 3D information on scoliotic anatomy, but the altered spine geometry between the supine and standing positions affects the Cobb angle measurement. Previous studies report a mean 7°-10° Cobb angle increase from supine to standing, but none have reported the effect of endplate pre-selection or whether other parameters affect this Cobb angle difference. Methods Cobb angles from existing coronal radiographs were compared to those on existing low-dose CT scans taken within three months of the reference radiograph for a group of females with adolescent idiopathic scoliosis. Reformatted coronal CT images were used to measure supine Cobb angles with and without endplate pre-selection (end-plates selected from the radiographs) by two observers on three separate occasions. Inter and intra-observer measurement variability were assessed. Multi-linear regression was used to investigate whether there was a relationship between supine to standing Cobb angle change and eight variables: patient age, mass, standing Cobb angle, Risser sign, ligament laxity, Lenke type, fulcrum flexibility and time delay between radiograph and CT scan. Results Fifty-two patients with right thoracic Lenke Type 1 curves and mean age 14.6 years (SD 1.8) were included. The mean Cobb angle on standing radiographs was 51.9° (SD 6.7). The mean Cobb angle on supine CT images without pre-selection of endplates was 41.1° (SD 6.4). The mean Cobb angle on supine CT images with endplate pre-selection was 40.5° (SD 6.6). Pre-selecting vertebral endplates increased the mean Cobb change by 0.6° (SD 2.3, range −9° to 6°). When free to do so, observers chose different levels for the end vertebrae in 39% of cases. Multi-linear regression revealed a statistically significant relationship between supine to standing Cobb change and fulcrum flexibility (p = 0.001), age (p = 0.027) and standing Cobb angle (p < 0.001). The 95% confidence intervals for intra-observer and inter-observer measurement variability were 3.1° and 3.6°, respectively. Conclusions Pre-selecting vertebral endplates causes minor changes to the mean supine to standing Cobb change. There is a statistically significant relationship between supine to standing Cobb change and fulcrum flexibility such that this difference can be considered a potential alternative measure of spinal flexibility.

The effect of endplate preselection when measuring supine versus standing cobb angle change in idiopathic scoliosis

The primary aim of this study was to determine whether endplate pre-selection makes a difference to the Cobb Angle change between supine and standing which is known to occur in idiopathic scoliosis. A secondary aim of this study was to identify which (if any) patient characteristics were correlated with supine versus standing Cobb change. The study found that pre-selecting vertebral endplates causes only has a minor effect on supine to standing Cobb change in scoliosis. There is a statistically significant relationship between supine to standing Cobb Angle change and fulcrum flexibility. Therefore, supine to standing Cobb Angle change can be considered as a measure of spinal flexibility when both standing and supine images are clinically available.

The radiological diagnosis of pneumonia in children

Despite the importance of paediatric pneumonia as a cause of short and long-term morbidity and mortality worldwide, a reliable gold standard for its diagnosis remains elusive. The utility of clinical, microbiological and radiological diagnostic approaches varies widely within and between populations and is heavily dependent on the expertise and resources available in various settings. Here we review the role of radiology in the diagnosis of paediatric pneumonia. Chest radiographs (CXRs) are the most widely employed test, however, they are not indicated in ambulatory settings, cannot distinguish between viral and bacterial infections and have a limited role in the ongoing management of disease. A standardised definition of alveolar pneumonia on a CXR exists for epidemiological studies targeting bacterial pneumonias but it should not be extrapolated to clinical settings. Radiography, computed tomography and to a lesser extent ultrasonography and magnetic resonance imaging play an important role in complicated pneumonias but there are limitations that preclude their use as routine diagnostic tools. Large population-based studies are needed in different populations to address many of the knowledge gaps in the radiological diagnosis of pneumonia in children, however, the feasibility of such studies is an important barrier.

Capturing natural-colour 3D models of insects for species discovery and diagnostics

Collections of biological specimens are fundamental to scientific understanding and characterization of natural diversity - past, present and future. This paper presents a system for liberating useful information from physical collections by bringing specimens into the digital domain so they can be more readily shared, analyzed, annotated and compared. It focuses on insects and is strongly motivated by the desire to accelerate and augment current practices in insect taxonomy which predominantly use text, 2D diagrams and images to describe and characterize species. While these traditional kinds of descriptions are informative and useful, they cannot cover insect specimens "from all angles" and precious specimens are still exchanged between researchers and collections for this reason. Furthermore, insects can be complex in structure and pose many challenges to computer vision systems. We present a new prototype for a practical, cost-effective system of off-the-shelf components to acquire natural-colour 3D models of insects from around 3 mm to 30 mm in length. ("Natural-colour" is used to contrast with "false-colour", i.e., colour generated from, or applied to, gray-scale data post-acquisition.) Colour images are captured from different angles and focal depths using a digital single lens reflex (DSLR) camera rig and two-axis turntable. These 2D images are processed into 3D reconstructions using software based on a visual hull algorithm. The resulting models are compact (around 10 megabytes), afford excellent optical resolution, and can be readily embedded into documents and web pages, as well as viewed on mobile devices. The system is portable, safe, relatively affordable, and complements the sort of volumetric data that can be acquired by computed tomography. This system provides a new way to augment the description and documentation of insect species holotypes, reducing the need to handle or ship specimens. It opens up new opportunities to collect data for research, education, art, entertainment, biodiversity assessment and biosecurity control. © 2014 Nguyen et al.

Assessment of the effects of CT dose in averaged x-ray CT images of a dose-sensitive polymer gel

The signal-to-noise ratio achievable in x-ray computed tomography (CT) images of polymer gels can be increased by averaging over multiple scans of each sample. However, repeated scanning delivers a small additional dose to the gel which may compromise the accuracy of the dose measurement. In this study, a NIPAM-based polymer gel was irradiated and then CT scanned 25 times, with the resulting data used to derive an averaged image and a "zero-scan" image of the gel. Comparison between these two results and the first scan of the gel showed that the averaged and zero-scan images provided better contrast, higher contrast-to- noise and higher signal-to-noise than the initial scan. The pixel values (Hounsfield units, HU) in the averaged image were not noticeably elevated, compared to the zero-scan result and the gradients used in the linear extrapolation of the zero-scan images were small and symmetrically distributed around zero. These results indicate that the averaged image was not artificially lightened by the small, additional dose delivered during CT scanning. This work demonstrates the broader usefulness of the zero-scan method as a means to verify the dosimetric accuracy of gel images derived from averaged x-ray CT data.

Investigation of fiducial marker and soft-tissue image guidance techniques in prostate radiation therapy

This thesis examines and compares imaging methods used during the radiotherapy treatment of prostate cancer. The studies found that radiation therapists were able to localise and target the prostate consistently with planar imaging techniques and that the use of small gold markers in the prostate reduced the variation in prostate localisation when using volumetric imaging. It was concluded that larger safety margins are required when using volumetric imaging without gold markers.

Medical imaging and Biomechanical analysis of scoliosis progression in the growing adolescent spine

Progression of spinal deformity in children was studied with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to identify how gravity affects the deformity and to determine the full three-dimensional character of the deformity. The CT study showed that gravity is significant in deformity progression in some patients which has implications for clinical patient management. The world first MRI study showed that the standard clinical measure used to define the extent of the deformity is inadequate and further use of three-dimensional MRI should be considered by spinal surgeons.

Bayesian computational methods for spatial analysis of images

This thesis introduces a new way of using prior information in a spatial model and develops scalable algorithms for fitting this model to large imaging datasets. These methods are employed for image-guided radiation therapy and satellite based classification of land use and water quality. This study has utilized a pre-computation step to achieve a hundredfold improvement in the elapsed runtime for model fitting. This makes it much more feasible to apply these models to real-world problems, and enables full Bayesian inference for images with a million or more pixels.

A semiautomatic method to identify vertebral end plate lesions (Schmorl's nodes)

Background Context There are differences in definitions of end plate lesions (EPLs), often referred to as Schmorl’s nodes, that may, to some extent, account for the large range of reported prevalence (3.8 to 76%). Purpose To develop a technique to measure the size, prevalence and location of EPLs in a consistent manner. Study Design/Setting This study proposed a method using a detection algorithm which was applied to five adolescent females (average age 15.1 years, range 13.0 to 19.2 years) with idiopathic scoliosis (average major Cobb angle 60°, range 55 to 67°). Methods Existing low-dose, computed tomography scans were segmented semi-automatically to extract 3D morphology of each vertebral endplate. Any remaining attachments to the posterior elements of adjacent vertebrae or endplates were then manually sectioned. An automatic algorithm was used to determine the presence and position of EPLs. Results EPLs were identified in 15 of the 170 (8.8%) endplates analysed with an average depth of 3.1mm. 11/15 of the EPLs were seen in the lumbar spine. The algorithm was found to be most sensitive to changes in the minimum EPL gradient at the edges of the EPL. Conclusions This study describes an imaging analysis technique for consistent measurement of the prevalence, location and size of EPLs. The technique can be used to analyse large populations without observer errors in EPL definitions.