3D lung and rib cage reconstruction using low dose CT scans of adolescent idiopathic scoliosis pre and post anterior thoracoscopic correction

Adolescent Idiopathic Scoliosis (AIS) has been associated with reduced pulmonary function believed to be due to a restriction of lung volume by the deformed thoracic cavity. A recent study by our group examined the changes in lung volume pre and post anterior thoracoscopic scoliosis correction using pulmonary function testing (1), however the anatomical changes in ribcage shape and left/right lung volume after thoracoscopic surgery which govern overall respiratory capacity are unknown. The aim of this study was to use 3D rendering from CT scan data to compare lung and ribcage anatomical changes from pre to two years post thoracoscopic anterior scoliosis correction. The study concluded that 3D volumetric reconstruction from CT scans is a powerful means of evaluating changes in pulmonary and thoracic anatomy following surgical AIS correction. Most likely, lung volume changes following thoracoscopic scoliosis correction are multifactorial and affected by changes in height (due to residual growth), ribcage shape, diaphragm positioning, Cobb angle correction in the thoracic spine. Further analysis of the 3D reconstructions will be performed to assess how each of these factors affect lung volume in this patient cohort.

Examination of pencil beam predictions of small-field dose using dosimetry film and Monte Carlo simulations

The iPlan treatment planning sys-tem uses a pencil beam algorithm, with density cor-rections, to predict the doses delivered by very small (stereotactic) radiotherapy fields. This study tests the accuracy of dose predictions made by iPlan, for small-field treatments delivered to a planar solid wa-ter phantom and to heterogeneous human tissue using the BrainLAB m3 micro-multileaf collimator.

An investigation of dose calculation accuracy in intensity-modulated radiotherapy of sites in the head & neck

Knowledge of the accuracy of dose calculations in intensity-modulated radiotherapy of the head and neck is essential for clinical confidence in these highly conformal treatments. High dose gradients are frequently placed very close to critical structures, such as the spinal cord, and good coverage of complex shaped nodal target volumes is important for long term-local control. A phantom study is presented comparing the performance of standard clinical pencil-beam and collapsed-cone dose algorithms to Monte Carlo calculation and three-dimensional gel dosimetry measurement. All calculations and measurements are normalized to the median dose in the primary planning target volume, making this a purely relative study. The phantom simulates tissue, air and bone for a typical neck section and is treated using an inverse-planned 5-field IMRT treatment, similar in character to clinically used class solutions. Results indicate that the pencil-beam algorithm fails to correctly model the relative dose distribution surrounding the air cavity, leading to an overestimate of the target coverage. The collapsed-cone and Monte Carlo results are very similar, indicating that the clinical collapsed-cone algorithm is perfectly sufficient for routine clinical use. The gel measurement shows generally good agreement with the collapsed-cone and Monte Carlo calculated dose, particularly in the spinal cord dose and nodal target coverage, thus giving greater confidence in the use of this class solution.

Investigation of stereotactic radiotherapy dose using dosimetry film and Monte Carlo simulations

This study uses dosimetry film measurements and Monte Carlo simulations to investigate the accuracy of type-a (pencil-beam) dose calculations for predicting the radiation doses delivered during stereotactic radiotherapy treatments of the brain. It is shown that when evaluating doses in a water phantom, the type-a algorithm provides dose predictions which are accurate to within clinically relevant criteria, gamma(3%,3mm), but these predictions are nonetheless subtly different from the results of evaluating doses from the same fields using radiochromic film and Monte Carlo simulations. An analysis of a clinical meningioma treatment suggests that when predicting stereotactic radiotherapy doses to the brain, the inaccuracies of the type-a algorithm can be exacerbated by inadequate evaluation of the effects of nearby bone or air, resulting in dose differences of up to 10% for individual fields. The results of this study indicate the possible advantage of using Monte Carlo calculations, as well as measurements with high-spatial resolution media, to verify type-a predictions of dose delivered in cranial treatments.

Adaptive Bayesian compound designs for dose finding studies

We consider the problem of how to efficiently and safely design dose finding studies. Both current and novel utility functions are explored using Bayesian adaptive design methodology for the estimation of a maximum tolerated dose (MTD). In particular, we explore widely adopted approaches such as the continual reassessment method and minimizing the variance of the estimate of an MTD. New utility functions are constructed in the Bayesian framework and are evaluated against current approaches. To reduce computing time, importance sampling is implemented to re-weight posterior samples thus avoiding the need to draw samples using Markov chain Monte Carlo techniques. Further, as such studies are generally first-in-man, the safety of patients is paramount. We therefore explore methods for the incorporation of safety considerations into utility functions to ensure that only safe and well-predicted doses are administered. The amalgamation of Bayesian methodology, adaptive design and compound utility functions is termed adaptive Bayesian compound design (ABCD). The performance of this amalgamation of methodology is investigated via the simulation of dose finding studies. The paper concludes with a discussion of results and extensions that could be included into our approach.

Postoperative low dose CT assessment of interbody fusion two years after thoracoscopic scoliosis surgery

The relationship between radiologic union and clinical outcomes in thoracoscopic scoliosis surgery is not clear, as apparent non-union of a spinal fusion does not always correspond to a poor clinical result. The aim of this study was to evaluate for the first time the interbody fusion rates using low dose CT scans at minimum 24 months after thoracoscopic scoliosis surgery, and to explore the relationship between fusion scores and; (i) rod diameter, (ii) graft type, (iii) fusion level, (iv) implant failure, and (v) lateral position in the disc space. The study found that moderate fusion scores on the Sucato scale secure successful clinical outcomes in thoracoscopic scoliosis surgery.

Neuroprotective effects of low-dose lithium in individuals at ultra-high risk for psychosis. A longitudinal MRI/MRS study

Objectives: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. Methods: Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy (1H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and 1H-MRS percentage change scores between scans were compared using one-way ANOVA and correlated with behavioural change scores. Results: Low-dose lithium significantly reduced HT2RT compared to TAU (p=0.018). No significant group by time effects were seen for any brain metabolites as measured with 1H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU. Conclusions: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.

Dose response relationships between physical activity, walking and health-related quality of life in mid-age and older women

Background Although physical activity is associated with health-related quality of life (HRQL), the nature of the dose-response relationship remains unclear. This study examined the concurrent and prospective dose-response relationships between total physical activity (TPA) and (only) walking with HRQL in two age cohorts of women. Methods Participants were 10,698 women born in 1946-1951 and 7,646 born in 1921-1926, who completed three mailed surveys for the Australian Longitudinal Study on Women's Health. They reported weekly TPA minutes (sum of walking, moderate, and vigorous minutes). HRQL was measured with the Medical Outcomes Study Short-Form 36 Health Status Survey (SF-36). Linear mixed models, adjusted for socio-demographic and health-related variables, were used to examine associations between TPA level (none, very low, low, intermediate, sufficient, high, and very high) and SF-36 scores. For women who reported walking as their only physical activity, associations between walking and SF-36 scores were also examined. Results Curvilinear trends were observed between TPA and walking with SF-36 scores. Concurrently, HRQL scores increased significantly with increasing TPA and walking, in both cohorts, with increases less marked above sufficient activity levels. Prospectively, associations were attenuated although significant and meaningful improvements in physical functioning and vitality were observed across most TPA and walking categories above the low category. Conclusion For women in their 50s-80s without clinical depression, greater amounts of TPA are associated with better current and future HRQL, particularly physical functioning and vitality. Even if walking is their only activity, women, particularly those in their 70s-80s, have better health-related quality of life.

Tracheobronchial and alveolar dose of submicrometer particles for different population age groups in Italy

Exposure to ultrafine particles (diameter less than 100 nm) is an important topic in epidemiological and toxicological studies. This study used the average particle number size distribution data obtained from our measurement survey in major micro-environments, together with the people activity pattern data obtained from the Italian Human Activity Pattern Survey to estimate the tracheobronchial and alveolar dose of submicrometer particles for different population age groups in Italy. We developed a numerical methodology based on Monte Carlo method, in order to estimate the best combination from a probabilistic point of view. More than 106 different cases were analyzed according to a purpose built sub-routine and our results showed that the daily alveolar particle number and surface area deposited for all of the age groups considered was equal to 1.5 x 1011 particles and 2.5 x 1015 m2, respectively, varying slightly for males and females living in Northern or Southern Italy. In terms of tracheobronchial deposition, the corresponding values for daily particle number and surface area for all age groups was equal to 6.5 x 1010 particles and 9.9 x 1014 m2, respectively. Overall, the highest contributions were found to come from indoor cooking (female), working time (male) and transportation (i.e. traffic derived particles) (children).