3D BrachyView System

Prostate cancer is quickly becoming the most common form of cancer across the globe, and is commonly treated with low dose rate brachytherapy due to its curative measures and highly conformal dose delivery. It is important to ensure there is a means of real time monitoring of the dose and seed placements when radioactive seeds are implanted in the prostate gland during a low dose rate brachytherapy treatment. The BrachyView system presents as a unique system that provides the capability of 3D seed reconstruction within an intraoperative setting. In this thesis the BrachyView system is tested for its suitability, accuracy and the system is further developed so that its application in real-time intraoperative dosime-try can become a reality. The system was tested with a clinically relevant number of seeds, 98, where previously the system had only been tested with a maximum number of 30 seeds. The BrachyView system was able to reconstruct 91.8% of implanted seeds from the 98 seed dataset with an average overall discrepancy of 3.65 mm without the application of the baseline subtraction algorithm, however with its application to the data the detection efficiency was improved to 100% and an overall positional accuracy of 11.5%, correlating to a reduced overall discrepancy of 3.23 mm, was noted. It was found that with seed numbers of 30 or lower that the addition of a background subtrac-tion algorithm was not necessary, whereas for datasets containing a clinically relevant number of seeds the application of a background subtraction algorithm was paramount to reducing the noise, scatter and means for identification of newly implanted seeds that may be masked by those seed previously implanted

Tools for improving high-dose-rate prostate cancer brachytherapy using three-dimensional ultrasound and magnetic resonance imaging

High-dose-rate brachytherapy (HDR-BT) is an interstitial technique for the treatment of intermediate and high-risk localized prostate cancer that involves placement of a radiation source directly inside the prostate using needles. Dose-escalated whole-gland treatments have led to improvements in survival, and tumour-targeted treatments may offer future improvements in therapeutic ratio. The efficacy of tumour-targeted HDR-BT depends on imaging tools to enable accurate dose delivery to prostate sub-volumes. This thesis is focused on implementing ultrasound tools to improve HDR-BT needle localization accuracy and efficiency, and evaluating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for tumour localization. First, we implemented a device enabling sagittally-reconstructed 3D (SR3D) ultrasound, which provides sub-millimeter resolution in the needle insertion direction. We acquired SR3D and routine clinical images in a cohort of 12 consecutive eligible HDR-BT patients, with a total of 194 needles. The SR3D technique provided needle insertion depth errors within 5 mm for 93\% of needles versus 76\% for the clinical imaging technique, leading to increased precision in dose delivered to the prostate. Second, we implemented an algorithm to automatically segment multiple HDR-BT needles in a SR3D image. The algorithm was applied to the SR3D images from the first patient cohort, demonstrating mean execution times of 11.0 s per patient and successfully segmenting 82\% of needles within 3 mm. Third, we augmented SR3D imaging with live-2D sagittal ultrasound for needle tip localization. This combined technique was applied to another cohort of 10 HDR-BT patients, reducing insertion depth errors compared to routine imaging from a range of [-8.1 mm, 7.7 mm] to [-6.2 mm, 5.9 mm]. Finally, we acquired DCE-MRI in 16 patients scheduled to undergo prostatectomy, using either high spatial resolution or high temporal resolution imaging, and compared the images to whole-mount histology. The high spatial resolution images demonstrated improved high-grade cancer classification compared to the high temporal resolution images, with areas under the receiver operating characteristic curve of 0.79 and 0.70, respectively. In conclusion, we have translated and evaluated specialized imaging tools for HDR-BT which are ready to be tested in a clinical trial investigating tumour-targeted treatment

Ultrasound and photoacoustic methods for anatomic and functional imaging in image guided radiation therapy

(MATERIAL and METHODS) First, we define the physical principals and optimal protocols that provide contrast when imaging with US and the transducer properties contributing to resolution limits. The US field of view (FOV) was characterized to determine the optimal settings with regard to imaging depth, focal region, with and without harmonic imaging, and artifact identification. This will allow us to determine the minimum errors expected when registering multimodal volumes (CT, US, CBCT). Next, we designed an in-house integrated US manipulator and platform to relate CT, 3D-US and linear accelerator coordinate systems. To validate our platform, an agar-based phantom with measured densities and speed-of-sound consistent with tissues surrounding the bladder was fabricated. This phantom was rotated relative to the CT and US coordinate systems and imaged with both modalities. These CT and 3D-US images were imported into the treatment planning system, where US-to-US and US-to-CT images were co-registered and the registration matrix used to re-align the phantom relative to the linear accelerator. The measured precision in the phantom setup, which is defined by the standard deviation of the transformation matrix components, was consistent with and exceeding acceptable clinical patient re-alignments (2 mm). Statistical errors from US-US registrations for different patient orientations ranged from 0.06-1.66 mm for x, y, and z translational components, and 0.00-1.05 degrees for rotational components. Statistical errors from US-CT registrations were 0.23-1.18 mm for the x, y and z translational components, and 0.08-2.52 degrees for the rotational components. The high precision in the multimodal registrations suggest the ability to use US for patient positioning when targeting abdominal structures. We are now testing this on a dog patient to obtain both inter and intra-fractional positional errors. The objective of this experiment is to confirm Hill’s equation describing the relationship between hemoglobin saturation (SaO2) and the partial pressure of dissolved oxygen (pO2). The relationship is modeled as a sigmoidal curve that is a function of two parameters – the Hill coefficient, n, and the net association constant of HbO2, K (or pO2 at 50% SaO2). The goal is to noninvasively measure SaO2 in breast tumors in mice using photoacoustic computed tomographic (PCT) imaging and compare those measurements to a gold standard for pO2 using the OxyLite probe. First, a calibration study was performed to measure the SaO2 (co-oximeter) and pO2 (Oxylite probe) in blood using Hill’s equation (P50=23.2 mmHg and n=2.26). Next, non-invasive localized measurements of SaO2 in MDA-MD-231 and MCF7 breast tumors using PCT spectroscopic methods were compared to pO 2 levels using Oxylite probe. The fitted results for MCF7 and MDA-MD-231 data resulted in a P50 of 17.2 mmHg and 20.7 mmHg and a n of 1.76 and 1.63, respectively. The lower value of the P50 is consistent with tumors being more acidic than healthy tissue. Current work applying photon fluence corrections and image artifact reduction is expected to improve the quality of the results. In summary, this study demonstrates that photoacoustic imaging can be used to monitor tumor oxygenation, and its potential use to investigate the effectiveness of radiation therapy and the ability to adapt therapeutic protocols

Is a 3-mm intrafractional margin sufficient for daily image-guided intensity-modulated radiation therapy of prostate cancer?

PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction. MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage was assessed on the post-treatment CT image set. RESULTS: During one treatment fraction (21.4+/-5.5 min), there were reductions in the volumes of the prostate and SVs receiving the prescribed dose (median reduction 0.1% and 1.0%, respectively, p\u3c0.001) and in the minimum dose to 0.1 cm(3) of their volumes (median reduction 0.5 and 1.5 Gy, p\u3c0.001). Of the 46 patients, three patients\u27 prostates and eight patients\u27 SVs did not maintain dose coverage above 70 Gy. Rectal filling correlated with decreased percentage-volume of SV receiving 75.6, 70, and 60 Gy (p\u3c0.02). CONCLUSIONS: The 3-mm intrafractional margin was adequate for prostate dose coverage. However, a significant subset of patients lost SV dose coverage. The rectal volume change significantly affected SV dose coverage. For advanced-stage prostate cancers, we recommend to use larger margins or improve organ immobilization (such as with a rectal balloon) to ensure SV coverage

Analysis of inter-fraction setup errors and organ motion by daily kilovoltage cone beam computed tomography in intensity modulated radiotherapy of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Intensity-modulated radiotherapy (IMRT) enables a better conformality to the target while sparing the surrounding normal tissues and potentially allows to increase the dose to the target, if this is precisely and accurately determined. The goal of this work is to determine inter-fraction setup errors and prostate motion in IMRT for localized prostate cancer, guided by daily kilovoltage cone beam computed tomography (kVCBCT).</p> <p>Methods</p> <p>Systematic and random components of the shifts were retrospectively evaluated by comparing two matching modalities (automatic bone and manual soft-tissue) between each of the 641 daily kVCBCTs (18 patients) and the planning kVCT. A simulated Adaptive Radiation Therapy (ART) protocol using the average of the first 5 kVCBCTs was tested by non-parametric bootstrapping procedure.</p> <p>Results</p> <p>Shifts were < 1 mm in left-right (LR) and in supero-inferior (SI) direction. In antero-posterior (AP) direction systematic prostate motion (2.7 ± 0.7 mm) gave the major contribution to the variability of results; the averages of the absolute total shifts were significantly larger in anterior (6.3 ± 0.2 mm) than in posterior (3.9 mm ± 0.2 mm) direction. The ART protocol would reduce margins in LR, SI and anterior but not in posterior direction.</p> <p>Conclusions</p> <p>The online soft-tissue correction based on daily kVCBCT during IMRT of prostate cancer is fast and efficient. The large random movements of prostate respect to bony anatomy, especially in the AP direction, where anisotropic margins are needed, suggest that daily kVCBCT is at the present time preferable for high dose and high gradients IMRT prostate treatments.</p

A non-invasive diagnostic system for early assessment of acute renal transplant rejection.

Early diagnosis of acute renal transplant rejection (ARTR) is of immense importance for appropriate therapeutic treatment administration. Although the current diagnostic technique is based on renal biopsy, it is not preferred due to its invasiveness, recovery time (1-2 weeks), and potential for complications, e.g., bleeding and/or infection. In this thesis, a computer-aided diagnostic (CAD) system for early detection of ARTR from 4D (3D + b-value) diffusion-weighted (DW) MRI data is developed. The CAD process starts from a 3D B-spline-based data alignment (to handle local deviations due to breathing and heart beat) and kidney tissue segmentation with an evolving geometric (level-set-based) deformable model. The latter is guided by a voxel-wise stochastic speed function, which follows from a joint kidney-background Markov-Gibbs random field model accounting for an adaptive kidney shape prior and for on-going visual kidney-background appearances. A cumulative empirical distribution of apparent diffusion coefficient (ADC) at different b-values of the segmented DW-MRI is considered a discriminatory transplant status feature. Finally, a classifier based on deep learning of a non-negative constrained stacked auto-encoder is employed to distinguish between rejected and non-rejected renal transplants. In the “leave-one-subject-out” experiments on 53 subjects, 98% of the subjects were correctly classified (namely, 36 out of 37 rejected transplants and 16 out of 16 nonrejected ones). Additionally, a four-fold cross-validation experiment was performed, and an average accuracy of 96% was obtained. These experimental results hold promise of the proposed CAD system as a reliable non-invasive diagnostic tool

Diffusion-weighted magnetic resonance imaging in diagnosing graft dysfunction : a non-invasive alternative to renal biopsy.

The thesis is divided into three parts. The first part focuses on background information including how the kidney functions, diseases, and available kidney disease treatment strategies. In addition, the thesis provides information on imaging instruments and how they can be used to diagnose renal graft dysfunction. The second part focuses on elucidating the parameters linked with highly accurate diagnosis of rejection. Four parameters categories were tested: clinical biomarkers alone, individual mean apparent diffusion coefficient (ADC) at 11-different b- values, mean ADCs of certain groups of b-value, and fusion of clinical biomarkers and all b-values. The most accurate model was found to be when the b-value of b=100 s/mm2 and b=700 s/mm2 were fused. The third part of this thesis focuses on a study that uses Diffusion-Weighted MRI to diagnose and differentiate two types of renal rejection. The system was found to correctly differentiate the two types of rejection with a 98% accuracy. The last part of this thesis concludes the work that has been done and states the possible trends and future avenues