ORCID Profile
0000-0001-8146-1113
Current Organisation
The University of Auckland
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Publisher: Wiley
Date: 19-11-2015
DOI: 10.1118/1.4935343
Abstract: Focal therapy has been proposed as an alternative method to whole-gland treatment for prostate cancer when aiming to reduce treatment side effects. The authors recently validated a radiobiological model which takes into account tumor location and tumor characteristics including tumor cell density, Gleason score, and hypoxia in order to plan optimal dose distributions for focal therapy. The authors propose that this model can be informed using multiparametric MRI (mpMRI) and in this study present a registration framework developed to map prostate mpMRI and histology data, where histology will provide the "ground truth" data regarding tumor location and biology. The authors aim to apply this framework to a growing database to develop a prostate biological atlas which will enable MRI based planning for prostate focal therapy treatment. Six patients scheduled for routine radical prostatectomy were used in this proof-of-concept study. Each patient underwent mpMRI scanning prior to surgery, after which the excised prostate specimen was formalin fixed and mounted in agarose gel in a custom designed sectioning box. T2-weighted MRI of the specimen in the sectioning box was acquired, after which 5 mm sections of the prostate were cut and histology sections were microtomed. A number of image processing and registration steps were used to register histology images with ex vivo MRI and deformable image registration (DIR) was applied to 3D T2w images to align the in vivo and ex vivo MRI data. Dice coefficient metrics and corresponding feature points from two independent annotators were selected in order to assess the DIR accuracy. Images from all six patients were registered, providing histology and in vivo MRI in the ex vivo MRI frame of reference for each patient. Results demonstrated that their DIR methodology to register in vivo and ex vivo 3D T2w MRI improved accuracy in comparison with an initial manual alignment for prostates containing features which were readily visible on MRI. The average estimated uncertainty between in vivo MRI and histology was 3.3 mm, which included an average error of 3.1 mm between in vivo and ex vivo MRI after applying DIR. The mean dice coefficient for the prostate contour between in vivo and ex vivo MRI increased from 0.83 before DIR to 0.93 after DIR. The authors have developed a registration framework for mapping in vivo MRI data of the prostate with histology by implementing a number of processing steps and ex vivo MRI of the prostate specimen. Validation of DIR was challenging, particularly in prostates with few or mostly linear rather than spherical shaped features. Refinement of their MR imaging protocols to improve the data quality is currently underway which may improve registration accuracy. Additional mpMRI sequences will be registered within this framework to quantify prostate tumor location and biology.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2023
Publisher: Springer Science and Business Media LLC
Date: 23-10-2018
Publisher: IOP Publishing
Date: 27-06-2018
Abstract: To provide recommendations for the selection of radiobiological parameters for prostate cancer treatment planning. Recommendations were based on validation of the previously published values, parameter estimation and a consideration of their sensitivity within a tumour control probability (TCP) model using clinical outcomes data from low-dose-rate (LDR) brachytherapy. The proposed TCP model incorporated radiosensitivity (α) heterogeneity and a non-uniform distribution of clonogens. The clinical outcomes data included 849 prostate cancer patients treated with LDR brachytherapy at four Australian centres between 1995 and 2012. Phoenix definition of biochemical failure was used. Validation of the published values from four selected literature and parameter estimation was performed with a maximum likelihood estimation method. Each parameter was varied to evaluate the change in calculated TCP to quantify the sensitivity of the model to its radiobiological parameters. Using a previously published parameter set and a total clonogen number of 196 000 provided TCP estimates that best described the patient cohort. Fitting of all parameters with a maximum likelihood estimation was not possible. Variations in prostate TCP ranged from 0.004% to 0.67% per 1% change in each parameter. The largest variation was caused by the log-normal distribution parameters for α (mean, [Formula: see text], and standard deviation, σ
Publisher: Informa UK Limited
Date: 17-04-2019
Publisher: Springer Science and Business Media LLC
Date: 24-04-2007
DOI: 10.1007/S10439-007-9315-9
Abstract: This study describes three-dimensional (3D) visualization of two-dimensional (2D) melanoma lymphatic mapping data, to provide a framework for analysis of melanoma spread patterns and a platform for recording new lymphoscintigraphy (LS) data more accurately in 3D. Specifically, the Sydney Melanoma Unit's LS database of over 5000 patients' primary cutaneous melanoma sites and sentinel lymph nodes have been mapped from 2D images onto a 3D anatomically based model. Anatomically accurate model geometries were created using the Visible Human dataset, giving a bicubic finite element skin mesh and discrete sentinel lymph node model. The full dataset of 2D melanoma site coordinates, excluding the head and neck, has been transformed onto this 3D skin mesh via free-form deformation and projection techniques. Sentinel lymph nodes were mapped onto the generic lymph node model for each patient. Preliminary spatial analysis indicates that a patient with a primary melanoma on the torso around the waist (on the standardized 3D model this region is 180 mm above and 130 mm below the umbilicus) with lymphatic drainage to the left axilla or left groin, will have a 17.7% probability of dual drainage to both node fields, with 95% confidence limits between 14.5 and 21.0%.
Publisher: Informa UK Limited
Date: 26-04-2018
Publisher: Springer Science and Business Media LLC
Date: 26-04-2023
Publisher: British Institute of Radiology
Date: 12-2019
DOI: 10.1259/BJR.20190373
Abstract: To investigate the association between multiparametric MRI (mpMRI) imaging features and hypoxia-related genetic profiles in prostate cancer. In vivo mpMRI was acquired from six patients prior to radical prostatectomy. Sequences included T 2 weighted (T 2 W) imaging, diffusion-weighted imaging, dynamic contrast enhanced MRI and blood oxygen-level dependent imaging. Imaging data were co-registered with histology using three-dimensional deformable registration methods. Texture features were extracted from T 2 W images and parametric maps from functional MRI. Full transcriptome genetic profiles were obtained using next generation sequencing from the prostate specimens. Pearson correlation coefficients were calculated between mpMRI data and hypoxia-related gene expression levels. Results were validated using glucose transporter one immunohistochemistry (IHC). Correlation analysis identified 34 candidate imaging features (six from the mpMRI data and 28 from T 2 W texture features). The IHC validation showed that 16 out of the 28 T 2 W texture features achieved weak but significant correlations (p 0.05). Weak associations between mpMRI features and hypoxia gene expressions were found. This indicates the potential use of MRI in assessing hypoxia status in prostate cancer. Further validation is required due to the low correlation levels. This is a pilot study using radiogenomics approaches to address hypoxia within the prostate, which provides an opportunity for hypoxia-guided selective treatment techniques.
Publisher: IEEE
Date: 08-2006
Publisher: Elsevier BV
Date: 09-2007
Publisher: Wiley
Date: 03-2010
Publisher: Elsevier BV
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 14-02-2019
DOI: 10.1007/S13246-019-00730-Z
Abstract: Multiparametric MRI (mpMRI) is an imaging modality that combines anatomical MR imaging with one or more functional MRI sequences. It has become a versatile tool for detecting and characterising prostate cancer (PCa). The traditional role of mpMRI was confined to PCa staging, but due to the advanced imaging techniques, its role has expanded to various stages in clinical practises including tumour detection, disease monitor during active surveillance and sequential imaging for patient follow-up. Meanwhile, with the growing speed of data generation and the increasing volume of imaging data, it is highly demanded to apply computerised methods to process mpMRI data and extract useful information. Hence quantitative analysis for imaging data using radiomics has become an emerging paradigm. The application of radiomics approaches in prostate cancer has not only enabled automatic localisation of the disease but also provided a non-invasive solution to assess tumour biology (e.g. aggressiveness and the presence of hypoxia). This article reviews mpMRI and its expanding role in PCa detection, staging and patient management. Following that, an overview of prostate radiomics will be provided, with a special focus on its current applications as well as its future directions.
Publisher: Public Library of Science (PLoS)
Date: 16-08-2018
Publisher: Wiley
Date: 15-02-2023
DOI: 10.1002/MP.16264
Abstract: In prostate radiation therapy, recent studies have indicated a benefit in increasing the dose to intraprostatic lesions (IPL) compared with standard whole gland radiation therapy. Such approaches typically aim to deliver a target dose to the IPL(s) with no deliberate effort to modulate the dose within the IPL. Prostate cancers demonstrate intra‐tumor heterogeneity and hence it is hypothesized that further gains in the optimal delivery of radiation therapy can be achieved through modulation of the dose distribution within the tumor. To account for tumor heterogeneity, biologically targeted radiation therapy (BiRT) aims to utilize a voxel‐wise approach to IPL dose prescription by incorporating knowledge of the spatial distribution of tumor characteristics. The aim of this study was to develop a workflow for generating voxel‐wise optimal dose prescriptions that maximize patient tumor control probability (TCP), and evaluate the feasibility and benefits of applying this workflow on a cohort of 62 prostate cancer patients. The source data for this proof‐of‐concept study included high resolution histology images annotated with tumor location and grade. Image processing techniques were used to compute voxel‐level cell density distribution maps. An absolute tumor cell distribution was calculated via linearly scaling according to published estimated tumor cell numbers. For the IPLs of each patient, optimal dose prescriptions were obtained via three alternative methods for redistribution of IPL boost doses according to maximization of TCP. The radiosensitivity uncertainties were considered using a truncated log‐normally distributed linear radiosensitivity parameter () and compared with Gleason pattern (GP) dependent radiosensitivity parameters that were derived based on previously published methods. An ensemble machine learning method was implemented to identify patient‐specific features that predict the TCP improvement resulting from dose redistribution relative to a uniform dose distribution. The Gleason pattern‐dependent radiosensitivity parameters were calculated for 20 published prostate cancer ratios. Optimal voxel‐level dose prescriptions were generated for all 62 PCa patients. For all dose redistribution scenarios, the optimal dose distribution always shows a higher (or equivalent) TCP level than the uniform dose distribution. The applied random forest regressor could predict patient‐specific TCP improvement with low root mean square error (≤1.5%) by using total tumor number, volume of IPLs and the standard deviation of tumor cell number among all voxels. Biologically‐optimized redistribution of a boost dose can yield TCP improvement relative to a uniform‐boost dose distribution. Patient‐specific tumor characteristics can be used to predict the likelihood of benefit from a redistribution approach for the in idual patient.
Publisher: Springer Science and Business Media LLC
Date: 19-12-2022
DOI: 10.1186/S40644-022-00508-9
Abstract: Biologically targeted radiation therapy treatment planning requires voxel-wise characterisation of tumours. Dynamic contrast enhanced (DCE) DCE MRI has shown promise in defining voxel-level biological characteristics. In this study we consider the relative value of qualitative, semi-quantitative and quantitative assessment of DCE MRI compared with diffusion weighted imaging (DWI) and T2-weighted (T2w) imaging to detect prostate cancer at the voxel level. Seventy prostate cancer patients had multiparametric MRI prior to radical prostatectomy, including T2w, DWI and DCE MRI. Apparent Diffusion Coefficient (ADC) maps were computed from DWI, and semi-quantitative and quantitative parameters computed from DCE MRI. Tumour location and grade were validated with co-registered whole mount histology. Kolmogorov–Smirnov tests were applied to determine whether MRI parameters in tumour and benign voxels were significantly different. Cohen’s d was computed to quantify the most promising biomarkers. The Parker and Weinmann Arterial Input Functions (AIF) were compared for their ability to best discriminate between tumour and benign tissue. Classifier models were used to determine whether DCE MRI parameters improved tumour detection versus ADC and T2w alone. All MRI parameters had significantly different data distributions in tumour and benign voxels. For low grade tumours, semi-quantitative DCE MRI parameter time-to-peak (TTP) was the most discriminating and outperformed ADC. For high grade tumours, ADC was the most discriminating followed by DCE MRI parameters Ktrans, the initial rate of enhancement (IRE), then TTP. Quantitative parameters utilising the Parker AIF better distinguished tumour and benign voxel values than the Weinmann AIF. Classifier models including DCE parameters versus T2w and ADC alone, gave detection accuracies of 78% versus 58% for low grade tumours and 85% versus 72% for high grade tumours. Incorporating DCE MRI parameters with DWI and T2w gives improved accuracy for tumour detection at a voxel level. DCE MRI parameters should be used to spatially characterise tumour biology for biologically targeted radiation therapy treatment planning.
Publisher: IOP Publishing
Date: 16-12-2015
DOI: 10.1088/0031-9155/61/1/430
Abstract: Treatment plans for ten patients, initially treated with a conventional approach to low dose-rate brachytherapy (LDR, 145 Gy to entire prostate), were compared with plans for the same patients created with an inverse-optimisation planning process utilising a biologically-based objective. The 'biological optimisation' considered a non-uniform distribution of tumour cell density through the prostate based on known and expected locations of the tumour. Using dose planning-objectives derived from our previous biological-model validation study, the volume of the urethra receiving 125% of the conventional prescription (145 Gy) was reduced from a median value of 64% to less than 8% whilst maintaining high values of TCP. On average, the number of planned seeds was reduced from 85 to less than 75. The robustness of plans to random seed displacements needs to be carefully considered when using contemporary seed placement techniques. We conclude that an inverse planning approach to LDR treatments, based on a biological objective, has the potential to maintain high rates of tumour control whilst minimising dose to healthy tissue. In future, the radiobiological model will be informed using multi-parametric MRI to provide a personalised medicine approach.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2020
DOI: 10.1186/S13014-020-01568-6
Abstract: This study aimed to develop a framework for optimising prostate intensity-modulated radiotherapy (IMRT) based on patient-specific tumour biology, derived from multiparametric MRI (mpMRI). The framework included a probabilistic treatment planning technique in the effort to yield dose distributions with an improved expected treatment outcome compared with uniform-dose planning approaches. IMRT plans were generated for five prostate cancer patients using two inverse planning methods: uniform-dose to the planning target volume and probabilistic biological optimisation for clinical target volume tumour control probability (TCP) maximisation. Patient-specific tumour location and clonogen density information were derived from mpMRI and geometric uncertainties were incorporated in the TCP calculation. Potential reduction in dose to sensitive structures was assessed by comparing dose metrics of uniform-dose plans with biologically-optimised plans of an equivalent level of expected tumour control. The planning study demonstrated biological optimisation has the potential to reduce expected normal tissue toxicity without sacrificing local control by shaping the dose distribution to the spatial distribution of tumour characteristics. On average, biologically-optimised plans achieved 38.6% ( p- value: 0.01) and 51.2% ( p- value: 0.01) reduction in expected rectum and bladder equivalent uniform dose, respectively, when compared with uniform-dose planning. It was concluded that varying the dose distribution within the prostate to take account for each patient’s clonogen distribution was feasible. Lower doses to normal structures compared to uniform-dose plans was possible whilst providing robust plans against geometric uncertainties. Further validation in a larger cohort is warranted along with considerations for adaptive therapy and limiting urethral dose.
Publisher: Wiley
Date: 31-03-2011
Publisher: Springer Science and Business Media LLC
Date: 18-08-2011
DOI: 10.1007/S10549-011-1737-2
Abstract: Detailed knowledge of the lymphatic drainage of the breast is limited. Lymphoscintigraphy is a technique used during breast cancer treatment to accurately map patterns of lymphatic drainage from the primary tumour to the draining lymph nodes. This study aimed to create a statistical model to analyse the spread of breast cancer and primary tumour location using a large lymphoscintigraphy database, and visualise the results with a novel computational model. This study was based on lymphoscintigraphy data from 2,304 breast cancer patients treated at the Royal Prince Alfred Hospital Medical Centre in Sydney, Australia. Bayesian inferential techniques were implemented to estimate the probabilities of lymphatic drainage from each region of the breast to each draining node field, to multiple node fields, and to determine probabilities of tumour prevalence in each breast region. A finite element model of the torso and discrete model of the draining node fields were created to visualise these data and a software tool was developed to display the results ( www.abi.auckland.ac.nz/breast-cancer ). Results confirmed that lymphatic drainage is most likely to occur to the axillary node field, and that there is significant likelihood of drainage to the internal mammary node field. The likelihood of lymphatic drainage from the whole breast to the axillary, internal mammary, infraclavicular, supraclavicular and interpectoral node fields were 98.2, 35.3, 1.7, 3.1, and 0.7%, respectively whilst the probability of lymphatic drainage to multiple node fields was estimated to be 36.4%. Additionally, primary tumours are most likely to develop in the upper regions of the breast. The models developed provide quantitative estimates of lymphatic drainage of the breast, giving important insights into understanding breast cancer metastasis and have the potential to benefit both clinicians and patients during breast cancer diagnosis and treatment.
Publisher: IOP Publishing
Date: 04-02-2021
Abstract: Hypofractionation of prostate cancer radiotherapy achieves tumour control at lower total radiation doses, however, increased rectal and bladder toxicities have been observed. To realise the radiobiological advantage of hypofractionation whilst minimising harm, the potential reduction in dose to organs at risk was investigated for biofocused radiotherapy. Patient-specific tumour location and cell density information were derived from multiparametric imaging. Uniform-dose plans and biologically-optimised plans were generated for a standard schedule (78 Gy/39 fractions) and hypofractionated schedules (60 Gy/20 fractions and 36.25 Gy/5 fractions). Results showed that biologically-optimised plans yielded statistically lower doses to the rectum and bladder compared to isoeffective uniform-dose plans for all fractionation schedules. A reduction in the number of fractions increased the target dose modulation required to achieve equal tumour control. On average, biologically-optimised, moderately-hypofractionated plans demonstrated 15.3% (p-value: .01) and 23.8% (p-value: 0.02) reduction in rectal and bladder dose compared with standard fractionation. The tissue-sparing effect was more pronounced in extreme hypofractionation with mean reduction in rectal and bladder dose of 43.3% (p-value: 0.01) and 41.8% (p-value: 0.02), respectively. This study suggests that the ability to utilise patient-specific tumour biology information will provide greater incentive to employ hypofractionation in the treatment of localised prostate cancer with radiotherapy. However, to exploit the radiobiological advantages given by hypofractionation, greater attention to geometric accuracy is required due to increased sensitivity to treatment uncertainties.
Publisher: Wiley
Date: 28-01-2019
DOI: 10.1111/BJU.14648
Abstract: To develop a registration framework for correlating positron emission tomography/computed tomography (PET/CT) images with multiparametric magnetic resonance imaging (mpMRI) and histology of the prostate, thereby enabling voxel-wise analysis of imaging parameters. In this prospective proof-of-concept study, nine patients scheduled for radical prostatectomy underwent mpMRI and PET/CT imaging before surgery. One had PET imaging using PET/CT data from all nine patients were successfully registered with mpMRI and histology data. SUV We have developed a novel framework for registering and correlating PET/CT data at a voxel-level with mpMRI and histology. Despite registration uncertainties, perfusion and oxygenation parameters from DCE MRI and BOLD imaging showed correlations with PET SUV. Further analysis will be performed on a larger patient cohort to quantify these proof-of-concept findings. Improved understanding of the correlation between mpMRI and PET will provide supportive information for focal therapy planning of the prostate.
Publisher: MDPI AG
Date: 29-09-2021
Abstract: Purpose: Hypoxia has been linked to radioresistance. Strategies to safely dose escalate dominant intraprostatic lesions have shown promising results, but further dose escalation to overcome the effects of hypoxia require a novel approach to constrain the dose in normal tissue.to safe levels. In this study, we demonstrate a biologically targeted radiotherapy (BiRT) approach that can utilise multiparametric magnetic resonance imaging (mpMRI) to target hypoxia for favourable treatment outcomes. Methods: mpMRI-derived tumour biology maps, developed via a radiogenomics study, were used to generate in idualised, hypoxia-targeting prostate IMRT plans using an ultra- hypofractionation schedule. The spatial distribution of mpMRI textural features associated with hypoxia-related genetic profiles was used as a surrogate of tumour hypoxia. The effectiveness of the proposed approach was assessed by quantifying the potential benefit of a general focal boost approach on tumour control probability, and also by comparing the dose to organs at risk (OARs) with hypoxia-guided focal dose escalation (DE) plans generated for five patients. Results: Applying an appropriately guided focal boost can greatly mitigate the impact of hypoxia. Statistically significant reductions in rectal and bladder dose were observed for hypoxia-targeting, biologically optimised plans compared to isoeffective focal DE plans. Conclusion: Results of this study suggest the use of mpMRI for voxel-level targeting of hypoxia, along with biological optimisation, can provide a mechanism for guiding focal DE that is considerably more efficient than application of a general, dose-based optimisation, focal boost.
Publisher: Wiley
Date: 29-04-2019
DOI: 10.1002/CASP.2406
Publisher: Wiley
Date: 10-2009
DOI: 10.1002/HED.21089
Abstract: Lymphatic drainage from skin on the head and neck is complex. We sought to provide improved visualization and analysis of the patterns of head and neck skin lymphatic drainage using aggregated lymphoscintigraphy data. Lymphoscintigraphy data from 929 patients with cutaneous melanoma on the head and neck collected at the Sydney Melanoma Unit have been mapped onto a 3-dimensional computer model of the skin and lymph nodes. Novel heat maps and interactive software have been created, which show subtle differences in lymphatic drainage patterns when compared with those that are previously reported. Posterior head and neck node fields largely drained posterior regions of the head and neck, whereas anterolateral skin regions were generally drained by the other head and neck node fields. The heat maps and interactive software tool provide novel visualization of head and neck lymphatic drainage patterns, which has both educational and clinical utility.
Start Date: 2023
End Date: 2026
Funder: Ministry of Business, Innovation and Employment
View Funded ActivityStart Date: 2024
End Date: 2027
Funder: Marsden Fund
View Funded ActivityStart Date: 2020
End Date: 2024
Funder: Health Research Council of New Zealand
View Funded ActivityStart Date: 2017
End Date: 2021
Funder: National Health and Medical Research Council
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