Verification of patient position and delivery of IMRT by electronic Portal Imaging

We have taken a new method of calibrating portal images of IMRT beams and used this to measure patient set-up accuracy and delivery errors, such as leaf errors and segment intensity errors during treatment. A calibration technique was used to remove the intensity modulations from the images leaving equivalent open field images that show patient anatomy that can be used for verification of the patient position. The images of the treatment beam can also be used to verify the delivery of the beam in terms of multileaf collimator leaf position and dosimetric errors. A series of controlled experiments delivering an IMRT anterior beam to the head and neck of a humanoid phantom were undertaken. A 2mm translation in the position of the phantom could be detected. With intentional introduction of delivery errors into the beam this method allowed us to detect leaf positioning errors of 2mm and variation in monitor units of 1%. The method was then applied to the case of a patient who received IMRT treatment to the larynx and cervical nodes. The anterior IMRT beam was imaged during four fractions and the images calibrated and investigated for the characteristic signs of patient position error and delivery error that were shown in the control experiments. No significant errors were seen. The method of imaging the IMRT beam and calibrating the images to remove the intensity modulations can be a useful tool in verifying both the patient position and the delivery of the beam.

Prevalence and predictors of refractive error in a genetically isolated population : the Norfolk Island Eye Study

BACKGROUND: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. DESIGN: Population-based study on Norfolk Island, South Pacific. PARTICIPANTS: All permanent residents on Norfolk Island aged ≥ 15 years were invited to participate. METHODS: Patients underwent non-cycloplegic autorefraction, slit-lamp biomicroscope examination and biometry assessment. Only phakic eyes were analysed. MAIN OUTCOME MEASURES: Prevalence and multivariate associations of refractive error and myopia. RESULTS: There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7; range 15-81). Three hundred and seventy-six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥ -1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). CONCLUSIONS: The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.

The Norfolk Island Eye Study (NIES) : rationale, methodology and distribution of ocular biometry (Biometry of the Bounty)

Aim: To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were individuals descended from the English Bounty mutineers and their Polynesian wives. Methods: All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 individuals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. Results: 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg (P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. Conclusion: Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.

Patellar tendon ultrasonography in asymptomatic active athletes reveals hypoechoic regions : a study of 320 tendons

OBJECTIVE: To compare patellar tendon sonographic findings in active, currently asymptomatic, elite athletes with those in nonathletic controls. DESIGN: Cross-sectional cohort study with convenience control sample. SETTING: The Victorian Institute of Sport Tendon Study Group, an institutional elite athlete study group in Australia. PATIENTS AND PARTICIPANTS: Two hundred elite male and female athletes from the sports of basketball, cricket, netball, and Australian rules football. Forty athletes who had current symptoms of jumper's knee were excluded from analysis, leaving 320 subject tendons in athletes who were currently asymptomatic. Twenty-seven nonathletic individuals served as controls. MAIN OUTCOME MEASURE: Sonographic patellar tendon appearance. We measured the dimensions of subject tendons and noted the presence or absence of hypoechoic regions and tendon calcification. Dimensions of hypoechoic regions were measured, and approximate cross-sectional areas were calculated. Chi-squared analysis was used to test the prevalence of hypoechoic regions in subjects and controls and men and women. RESULTS: In currently asymptomatic subjects, hypoechoic regions were more prevalent in athlete tendons (22%) than in controls (4%), in male subject tendons (30%) than in female subjects (14%), and in basketball players (32%) than in other athletes (9%) (all p < 0.01). Bilateral tendon abnormalities were equally prevalent in men and women but more prevalent in basketball players (15%) than in other athletes (3%) (p < 0.05). Sonographic hypoechoic regions were present in 35 of 250 (14%) patellar tendons in athletes who had never had anterior knee pain. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas were present in asymptomatic patellar tendons of a proportion of elite athletes but rarely present in controls. This has implications for clinicians managing athletes with anterior knee pain.

Patellar tendinopathy in junior basketball players : a controlled clinical and ultrasonographic study of 268 patellar tendons in players aged 14-18 years

Anterior knee pain is a common presenting complaint amongst adolescent athletes. We hypothesised that patellar tendinopathy may occur at a younger age than is generally recognised. Thus, we studied the patellar tendons in 134 elite 14- to 18-year-old female (n=64) and male (n=70) basketball players and 29 control swimmers (17 female, 12 male) clinically and with ultrasonography. We found that of 268 tendons, 19 (7%) had current patellar tendinopathy on clinical grounds (11% in males, 2% in females). Twenty-six percent of the basketball players' patellar tendons contained an ultrasonographic hypoechoic region. Ultrasonographic abnormality was more prevalent in the oldest tertile of players (17-18 years) than the youngest tertile (14-15.9 years). Of tendons categorised clinically as 'Never patellar tendinopathy', 22% had an ultrasonographic hypoechoic region nevertheless. This study indicates that patellar tendinopathy can occur in 14- to 18-year-old basketball players. Ultrasonographic tendon abnormality is 3 times as common as clinical symptoms

A poly(lactic-co-glycolic acid) knitted scaffold for tendon tissue engineering: an in vitro and in vivo study

We have designed a composite scaffold for potential use in tendon or ligament tissue engineering. The composite scaffold was made of a cellularized alginate gel that encapsulated a knitted structure. Our hypothesis was that the alginate would act as a cell carrier and deliver cells to the injury site while the knitted structure would provide mechanical strength to the composite construct. The mechanical behaviour and the degradation profile of the poly(lactic-co-glycolic acid) knitted scaffolds were evaluated. We found that our scaffolds had an elastic modulus of 750 MPa and that they lost their physical integrity within 7 weeks of in vitro incubation. Autologous rabbit mesenchymal stem cell seeded composite scaffolds were implanted in a 1-cm-long defect created in the rabbit tendon, and the biomechanical properties and the morphology of the regenerated tissues were evaluated after 13 weeks. The regenerated tendons presented higher normalized elastic modulus of (60%) when compared with naturally healed tendons (40%). The histological study showed a higher cell density and vascularization in the regenerated tendons.

Optical and biomechanical factors, associated with near work and myopia

Near work may play an important role in the development of myopia in the younger population. The prevalence of myopia has also been found to be higher in occupations that involve substantial near work tasks, for example in microscopists and textile workers. When nearwork is performed, it typically involves accommodation, convergence and downward gaze. A number of previous studies have examined the effects of accommodation and convergence on changes in the optics and biometrics of the eye in primary gaze. However, little is known about the influence of accommodation on the eye in downward gaze. This thesis is primarily concerned with investigating the changes in the eye during near work in downward gaze under natural viewing conditions. To measure wavefront aberrations in downward gaze under natural viewing conditions, we modified a commercial Shack-Hartmann wavefront sensor by adding a relay lens system to allow on-axis ocular aberration measurements in primary gaze and downward gaze, with binocular fixation. Measurements with the modified wavefront sensor in primary and downward gaze were validated against a conventional aberrometer using both a model eye and in 9 human subjects. We then conducted an experiment to investigate changes in ocular aberrations associated with accommodation in downward gaze over 10 mins in groups of both myopes (n = 14) and emmetropes (n =12) using the modified Shack-Hartmann wavefront sensor. During the distance accommodation task, small but significant changes in refractive power (myopic shift) and higher order aberrations were observed in downward gaze compared to primary gaze. Accommodation caused greater changes in higher order aberrations (in particular coma and spherical aberration) in downward gaze than primary gaze, and there was evidence that the changes in certain aberrations with accommodation over time were different in downward gaze compared to primary gaze. There were no obvious systematic differences in higher order aberrations between refractive error groups during accommodation or downward gaze for fixed pupils. However, myopes exhibited a significantly greater change in higher order aberrations (in particular spherical aberration) than emmetropes for natural pupils after 10 mins of a near task (5 D accommodation) in downward gaze. These findings indicated that ocular aberrations change from primary to downward gaze, particularly with accommodation. To understand the mechanism underlying these changes in greater detail, we then extended this work to examine the characteristics of the corneal optics, internal optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 mins. Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure corneal topography and ocular biometrics in downward gaze, a rotating Scheimpflug camera and an optical biometer were inclined on a custom built, height and tilt adjustable table. We found that both corneal optics and internal optics change with downward gaze, resulting in a myopic shift (~0.10 D) in the spherical power of the eye. The changes in corneal optics appear to be due to eyelid pressure on the anterior surface of the cornea, whereas the changes in the internal optics (an increase in axial length and a decrease in anterior chamber depth) may be associated with movement of the crystalline lens, under the action of gravity, and the influence of altered biomechanical forces from the extraocular muscles on the globe with downward gaze. Changes in axial length with accommodation were significantly greater in downward gaze than primary gaze (p < 0.05), indicating an increased effect of the mechanical forces from the ciliary muscle and extraocular muscles. A subsequent study was conducted to investigate the changes in anterior biometrics, axial length and choroidal thickness in nine cardinal gaze directions under the actions of the extraocular muscles. Ocular biometry measurements were obtained from 30 young adults (10 emmetropes, 10 low myopes and 10 moderate myopes) through a rotating prism with 15° deviation, along the foveal axis, using a non-contact optical biometer in each of nine different cardinal directions of gaze, over 5 mins. There was a significant influence of gaze angle and time on axial length (both p < 0.001), with the greatest axial elongation (+18 ± 8 μm) occurring with infero-nasal gaze (p < 0.001) and a slight decrease in axial length in superior gaze (−12 ± 17 μm) compared with primary gaze (p < 0.001). There was a significant correlation between refractive error (spherical equivalent refraction) and the mean change in axial length in the infero-nasal gaze direction (Pearson's R2 = 0.71, p < 0.001). To further investigate the relative effect of gravity and extraocular muscle force on the axial length, we measured axial length in 15° and 25° downward gaze with the biometer inclined on a tilting table that allowed gaze shifts to occur with either full head turn but no eye turn (reflects the effect of gravity), or full eye turn with no head turn (reflects the effect of extraocular muscle forces). We observed a significant axial elongation in 15° and 25° downward gaze in the full eye turn condition. However, axial length did not change significantly in downward gaze over 5 mins (p > 0.05) in the full head turn condition. The elongation of the axial length in downward gaze appears to be due to the influence of the extraocular muscles, since the effect was not present when head turn was used instead of eye turn. The findings of these experiments collectively show the dynamic characteristics of the optics and biometrics of the eye in downward gaze during a near task, over time. These were small but significant differences between myopic and emmetropic eyes in both the optical and biomechanical changes associated with shifts of gaze direction. These differences between myopes and emmetropes could arise as a consequence of excessive eye growth associated with myopia. However the potentially additive effects of repeated or long lasting near work activities employing infero-nasal gaze could also act to promote elongation of the eye due to optical and/or biomechanical stimuli.

The influence of cellular source on periodontal regeneration using calcium phosphate coated polycaprolactone scaffold supported cell sheets

Cell-based therapy is considered a promising approach to achieving predictable periodontal regeneration. In this study, the regenerative potential of cell sheets derived from different parts of the periodontium (gingival connective tissue, alveolar bone and periodontal ligament) were investigated in an athymic rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC) and gingival margin-derived cells (GMC) were obtained from human donors. The osteogenic potential of the primary cultures was demonstrated in vitro. Cell sheets supported by a calcium phosphate coated melt electrospun polycaprolactone (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL scaffold alone was able to promote alveolar bone formation within the defect after 4 weeks. The addition of ABC and PDLC sheets resulted in significant periodontal attachment formation. The GMC sheets did not promote periodontal regeneration on the root surface and inhibited bone formation within the CaP-PCL scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP-PCL scaffold could promote periodontal regeneration, but ABC sheets were not as effective as PDLC sheets in promoting new attachment formation.

Choroidal thickness in childhood

Purpose To examine choroidal thickness (ChT) and its spatial distribution across the posterior pole in pediatric subjects with normal ocular health and minimal refractive error. Methods ChT was assessed using spectral domain optical coherence tomography (OCT) in 194 children aged between 4-12 years, with spherical equivalent refractive errors between +1.25 and -0.50 DS. A series of OCT scans were collected, imaging the choroid along 4 radial scan lines centered on the fovea (each separated by 45°). Frame averaging was used to reduce noise and enhance chorio-scleral junction visibility. The transverse scale of each scan was corrected to account for magnification effects associated with axial length. Two independent masked observers manually segmented the OCT images to determine ChT at foveal centre, and averaged across a series of perifoveal zones over the central 5 mm. Results The average subfoveal ChT was 330 ± 65 µm (range 189-538 µm), and was significantly influenced by age (p=0.04). The ChT of the 4 to 6 year old age group (312 ± 62 µm) was significantly thinner compared to the 7 to 9 year olds (337 ± 65 µm, p<0.05) and bordered on significance compared to the 10 to 12 year olds (341 ± 61 µm, p=0.08). ChT also exhibited significant variation across the posterior pole, being thicker in more central regions. The choroid was thinner nasally and inferiorly compared to temporally and superiorly. Multiple regression analysis revealed age, axial length and anterior chamber depth were significantly associated with subfoveal ChT (p<0.001). Conclusions ChT increases significantly from early childhood to adolescence. This appears to be a normal feature of childhood eye growth.

The effect of organ motion of radiotherapy plans

Organ motion as a result of respiration is an important field of research for medical physics. Knowledge of magnitude and direction of this motion is necessary to allow for more accurate radiotherapy treatment planning. This will result in higher doses to the tumour whilst sparing healthy tissue. This project involved human trials, where the radiation therapy patient's kidneys were CT scanned under three different conditions; whilst free breathing (FB), breath-hold at normal tidal inspiration (BHIN), and breath-hold at normal tidal expiration (BHEX). The magnitude of motion was measured by recording the outline of the kidney from a Beam's Eye View (BEV). The centre of mass of this 2D shape was calculated for each set using "ImageJ" software and the magnitude of movement determined from the change in the centroid's coordinates between the BHIN and BHEX scans. The movement ranged from, for the left and right kidneys, 4-46mm and 2-44mm in the superior/inferior (axial) plane, 1-21mm and 2- 16mm in the anterior/posterior (coronal) plane, and 0-6mm and 0-8mm in the lateral/medial (sagittal) plane. From exhale to inhale, the kidneys tended to move inferiorly, anteriorly and laterally. A standard radiotherapy plan, designed to treat the para-aortics with opposed lateral fields was performed on the free breathing (planning) CT set. The field size and arrangement was set up using the same parameters for each subject. The prescription was to deliver 45 Gray in 25 fractions. This field arrangement and prescription was then copied over to the breath hold CT sets, and the dosimetric differences were compared using Dose Volume Histograms (DVH). The point of comparison for the three sets was recorded as the percentage volume of kidney receiving less than or equal to 10 Gray. The QUASAR respiratory motion phantom was used with the range of motion determined from the human study. The phantom was imaged, planned and treated with a linear accelerator with dose determined by film. The effect of the motion was measured by the change in the penumbra of the film and compared to the penumbra from the treatment planning system.

Successful application of a simple specimen transport method for the conduct of respiratory virus surveillance in remote Indigenous communities in Australia

Objective Surveillance programs and research for acute respiratory infections in remote Aboriginal communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting respiratory samples from a remote setting for viral PCR compared with frozen specimens. Methods We sampled every individual who presented to a remote Aboriginal community clinic in a non-epidemic respiratory season. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for 16 viruses was undertaken using real-time multiplex PCR. Results A total of 140 participants were enrolled who contributed 150 study visits. Respiratory illnesses accounted for 10% of the reasons for presentation. Sixty-one viruses were identified in 50 (33.3%) presentations for 40 (28.6%) individuals; bocavirus and rhinovirus were the most common viruses identified (14.0% and 12.6% of episodes respectively). The sensitivity for any virus detected in mailed specimens was 67.2% (95%CI 55.4, 78.9) compared to 65.6% (95%CI 53.7, 77.5) for frozen specimens. Conclusion The mailing of unfrozen nasal specimens from remote communities does not compromise the viability of the specimen for viral studies.

Effects of textured insoles on balance in people with Parkinson’s Disease

Background Degradation of the somatosensory system has been implicated in postural instability and increased falls risk for older people and Parkinson’s disease (PD) patients. Here we demonstrate that textured insoles provide a passive intervention that is an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet. Methods 20 healthy older adults (controls) and 20 participants with PD were recruited for the study. We evaluated effects of manipulating somatosensory information from the plantar surface of the feet using textured insoles. Participants performed standing tests, on two different surfaces (firm and foam), under three footwear conditions: 1) barefoot; 2) smooth insoles; and 3) textured insoles. Standing balance was evaluated using a force plate yielding data on the range of anterior-posterior and medial-lateral sway, as well as standard deviations for anterior-posterior and medial-lateral sway. Results On the firm surface with eyes open both the smooth and textured insoles reduced medial-lateral sway in the PD group to a similar level as the controls. Only the textured insole decreased medial-lateral sway and medial-lateral sway standard deviation in the PD group on both surfaces, with and without visual input. Greatest benefits were observed in the PD group while wearing the textured insoles, and when standing on the foam surface with eyes closed. Conclusions Data suggested that textured insoles may provide a low-cost means of improving postural stability in high falls-risk groups, such as people with PD.

Introducing standardized protocols for anthropological measurement of virtual subadult crania using computed tomography

Objectives This study introduces and assesses the precision of a standardized protocol for anthropometric measurement of the juvenile cranium using three-dimensional surface rendered models, for implementation in forensic investigation or paleodemographic research. Materials and methods A subset of multi-slice computed tomography (MSCT) DICOM datasets (n=10) of modern Australian subadults (birth—10 years) was accessed from the “Skeletal Biology and Forensic Anthropology Virtual Osteological Database” (n>1200), obtained from retrospective clinical scans taken at Brisbane children hospitals (2009–2013). The capabilities of Geomagic Design X™ form the basis of this study; introducing standardized protocols using triangle surface mesh models to (i) ascertain linear dimensions using reference plane networks and (ii) calculate the area of complex regions of interest on the cranium. Results The protocols described in this paper demonstrate high levels of repeatability between five observers of varying anatomical expertise and software experience. Intra- and inter-observer error was indiscernible with total technical error of measurement (TEM) values ≤0.56 mm, constituting <0.33% relative error (rTEM) for linear measurements; and a TEM value of ≤12.89 mm2, equating to <1.18% (rTEM) of the total area of the anterior fontanelle and contiguous sutures. Conclusions Exploiting the advances of MSCT in routine clinical assessment, this paper assesses the application of this virtual approach to acquire highly reproducible morphometric data in a non-invasive manner for human identification and population studies in growth and development. The protocols and precision testing presented are imperative for the advancement of “virtual anthropology” into routine Australian medico-legal death investigation.

Tissue viability imaging of skin microcirculation following exposure to whole body cryotherapy (-110°C) and cold water immersion (8°C)

Cryotherapy is currently used in various clinical, rehabilitative, and sporting settings. However, very little is known regarding the impact of cooling on the microcirculatory response. Objectives: The present study sought to examine the influence of two commonly employed modalities of cryotherapy, whole body cryotherapy (WBC; -110°C) and cold water immersion(CWI; 8±1°C), on skin microcirculation in the mid- thigh region. Methods: The skin area examined was a 3 × 3 cm located between the most anterior aspect of the inguinal fold and the patella. Following 10 minutes of rest, 5 healthy, active males were exposed to either WBC for 3 minutes or CWI for 5 minutes in a randomised order. Volunteers lay supine for five minutes after treatment, in order to monitor the variation of red blood cell (RBC) concentration in the region of interest for a duration of 40 minutes. Microcirculation response was assessed using a non-invasive, portable instrument known as a Tissue Viability imaging system. After a minimum of seven days, the protocol was repeated. Subjective assessment of the volunteer’s thermal comfort and thermal sensation was also recorded. Results: RBC was altered following exposure to both WBC and CWI but appeared to stabilise approximately 35 minutes after treatments. Both WBC and CWI affected thermal sensation (p < 0.05); however no betweengroup differences in thermal comfort or sensation were recorded (p > 0.05). Conclusions: As both WBC and CWI altered RBC, further study is necessary to examine the mechanism for this alteration during whole body cooling.

Non-contact laser-scanning confocal microscopy of the human cornea in vivo

PURPOSE To investigate the utility of using non-contact laser-scanning confocal microscopy (NC-LSCM), compared with the more conventional contact laser-scanning confocal microscopy (C-LSCM), for examining corneal substructures in vivo. METHODS An attempt was made to capture representative images from the tear film and all layers of the cornea of a healthy, 35 year old female, using both NC-LSCM and C-LSCM, on separate days. RESULTS Using NC-LSCM, good quality images were obtained of the tear film, stroma, and a section of endothelium, but the corneal depth of the images of these various substructures could not be ascertained. Using C-LSCM, good quality, full-field images were obtained of the epithelium, subbasal nerve plexus, stroma, and endothelium, and the corneal depth of each of the captured images could be ascertained. CONCLUSIONS NC-LSCM may find general use for clinical examination of the tear film, stroma and endothelium, with the caveat that the depth of stromal images cannot be determined when using this technique. This technique also facilitates image capture of oblique sections of multiple corneal layers. The inability to clearly and consistently image thin corneal substructures - such as the tear film, subbasal nerve plexus and endothelium - is a key limitation of NC-LSCM.