Medical image computing and computer-aided medical interventions applied to soft tissues. Work in progress in urology

Until recently, Computer-Aided Medical Interventions (CAMI) and Medical Robotics have focused on rigid and non deformable anatomical structures. Nowadays, special attention is paid to soft tissues, raising complex issues due to their mobility and deformation. Mini-invasive digestive surgery was probably one of the first fields where soft tissues were handled through the development of simulators, tracking of anatomical structures and specific assistance robots. However, other clinical domains, for instance urology, are concerned. Indeed, laparoscopic surgery, new tumour destruction techniques (e.g. HIFU, radiofrequency, or cryoablation), increasingly early detection of cancer, and use of interventional and diagnostic imaging modalities, recently opened new challenges to the urologist and scientists involved in CAMI. This resulted in the last five years in a very significant increase of research and developments of computer-aided urology systems. In this paper, we propose a description of the main problems related to computer-aided diagnostic and therapy of soft tissues and give a survey of the different types of assistance offered to the urologist: robotization, image fusion, surgical navigation. Both research projects and operational industrial systems are discussed

Artificial Intelligence-based Motion Tracking in Cancer Radiotherapy: A Review

Radiotherapy aims to deliver a prescribed dose to the tumor while sparing neighboring organs at risk (OARs). Increasingly complex treatment techniques such as volumetric modulated arc therapy (VMAT), stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and proton therapy have been developed to deliver doses more precisely to the target. While such technologies have improved dose delivery, the implementation of intra-fraction motion management to verify tumor position at the time of treatment has become increasingly relevant. Recently, artificial intelligence (AI) has demonstrated great potential for real-time tracking of tumors during treatment. However, AI-based motion management faces several challenges including bias in training data, poor transparency, difficult data collection, complex workflows and quality assurance, and limited sample sizes. This review serves to present the AI algorithms used for chest, abdomen, and pelvic tumor motion management/tracking for radiotherapy and provide a literature summary on the topic. We will also discuss the limitations of these algorithms and propose potential improvements.Comment: 36 pages, 5 Figures, 4 Table

Real-time intrafraction motion monitoring in external beam radiotherapy

© 2019 Institute of Physics and Engineering in Medicine. Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to 'see what we treat, as we treat' and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT

Online 4D ultrasound guidance for real-time motion compensation by MLC tracking

PURPOSE: With the trend in radiotherapy moving toward dose escalation and hypofractionation, the need for highly accurate targeting increases. While MLC tracking is already being successfully used for motion compensation of moving targets in the prostate, current real-time target localization methods rely on repeated x-ray imaging and implanted fiducial markers or electromagnetic transponders rather than direct target visualization. In contrast, ultrasound imaging can yield volumetric data in real-time (3D + time = 4D) without ionizing radiation. The authors report the first results of combining these promising techniques-online 4D ultrasound guidance and MLC tracking-in a phantom. METHODS: A software framework for real-time target localization was installed directly on a 4D ultrasound station and used to detect a 2 mm spherical lead marker inside a water tank. The lead marker was rigidly attached to a motion stage programmed to reproduce nine characteristic tumor trajectories chosen from large databases (five prostate, four lung). The 3D marker position detected by ultrasound was transferred to a computer program for MLC tracking at a rate of 21.3 Hz and used for real-time MLC aperture adaption on a conventional linear accelerator. The tracking system latency was measured using sinusoidal trajectories and compensated for by applying a kernel density prediction algorithm for the lung traces. To measure geometric accuracy, static anterior and lateral conformal fields as well as a 358° arc with a 10 cm circular aperture were delivered for each trajectory. The two-dimensional (2D) geometric tracking error was measured as the difference between marker position and MLC aperture center in continuously acquired portal images. For dosimetric evaluation, VMAT treatment plans with high and low modulation were delivered to a biplanar diode array dosimeter using the same trajectories. Dose measurements with and without MLC tracking were compared to a static reference dose using 3%/3 mm and 2%/2 mm γ-tests. RESULTS: The overall tracking system latency was 172 ms. The mean 2D root-mean-square tracking error was 1.03 mm (0.80 mm prostate, 1.31 mm lung). MLC tracking improved the dose delivery in all cases with an overall reduction in the γ-failure rate of 91.2% (3%/3 mm) and 89.9% (2%/2 mm) compared to no motion compensation. Low modulation VMAT plans had no (3%/3 mm) or minimal (2%/2 mm) residual γ-failures while tracking reduced the γ-failure rate from 17.4% to 2.8% (3%/3 mm) and from 33.9% to 6.5% (2%/2 mm) for plans with high modulation. CONCLUSIONS: Real-time 4D ultrasound tracking was successfully integrated with online MLC tracking for the first time. The developed framework showed an accuracy and latency comparable with other MLC tracking methods while holding the potential to measure and adapt to target motion, including rotation and deformation, noninvasively

One-class Gaussian process regressor for quality assessment of transperineal ultrasound images

The use of ultrasound guidance in prostate cancer radiotherapy workflows is not widespread. This can be partially attributed to the need for image interpretation by a trained operator during ultrasound image acquisition. In this work, a one-class regressor, based on DenseNet and Gaussian processes, was implemented to assess automatically the quality of transperineal ultrasound images of the male pelvic region. The implemented deep learning approach achieved a scoring accuracy of 94%, a specificity of 95% and a sensitivity of 93% with respect to the majority vote of three experts, which was comparable with the results of these experts. This is the first step towards a fully automatic workflow, which could potentially remove the need for image interpretation and thereby make the use of ultrasound imaging, which allows real-time volumetric organ tracking in the RT environment, more appealing for hospitals

Real-Time Ultrasound Image-Guidance and Tracking in External Beam Radiotherapy

Background and Purpose - To evaluate the accuracy of Clarity (clinical version) system by using ultrasound phantom and some probe position. - To evaluate the intrafraction motion of prostate by collecting and analyzing ultrasound monitoring data from some patients. - To evaluate the accuracy of Clarity (Anticosti) system by using 3D phantom programmed with sinusoidal and breathing movement patterns to simulate computer-controlled based breath-hold phases interspersed with spontaneous breathing. - To evaluate the clinical applicability of Clarity (Anticosti) system for liver cases in healthy volunteers. The tracking results of healthy volunteers were compared to surface marker. - To evaluate the intrafraction motion during breath-hold in liver case by collecting and analyzing US monitoring data from some patients. Material and Methods The accuracy of Clarity (clinical version) system was evaluated using ultrasound phantom and some probe position. Two different probes were used: transabdominal ultrasound (TAUS) and transperineal ultrasound (TPUS) probe. Two positions of the phantom were used for TPUS, the vertical and the horizontal position. Intrafraction motion assessment of the prostate was based on continuous position monitoring with a 4D US system along the three directions; left(+)-right (LR), anterior(+)-posterior (AP), and inferior(+)-superior (SI). 770 US monitoring sessions in 38 prostate cancer patients’ normo-fractionated VMAT treatment series were retrospectively evaluated. The overall mean values and standard deviations (SD) along with random and systematic SDs were computed. The tracking accuracy of the research 4D US system was evaluated using two motion phantoms programmed with sinusoidal and breathing patterns to simulate free breathing and DIBH. The clinical performance was evaluated with 5 healthy volunteers. US datasets were acquired in computer-controlled DIBH with varying angular scanning angles. Tracked structures were renal pelvis (spherical structure) and portal/liver vein branches (non-spherical structure). An external marker was attached to the surface of both phantoms and volunteers as a secondary tracked object by an infrared camera for comparison. Residual intrafractional motion of DIBH tracking target relative to beginning position in each breath-hold plateau region was analysed along three directions; superior-inferior (SI), left-right (LR) and anterior-posterior (AP). 12 PTVs of 11 patients with primary/secondary liver tumours or adrenal gland/spleen metastases of diverse primaries were irradiated with SBRT in DIBH. Real time tracking of target or neighbouring surrogate structures was performed additionally using 4D US system during CBCT acquisition after permission of local IRB. Results The geometric positioning tolerance for Clarity-Sim and Clarity-Guide is 1 mm according to the manufacturer’s specifications. The results showed that all phantom and probe combinations met this criterion. The mean duration of each prostate monitoring session was 254s. The mean (μ), the systematic error () and the random error (σ) of intrafraction prostate motion were μ=(0.01, -0.08, 0.15)mm, =(0.30, 0.34, 0.23)mm and σ=(0.59, 0.73, 0.64)mm in LR, AP and SI direction, respectively. The percentage of treatments for which prostate motion was 2mm was present in about 0.67% of the data. The percentage increased to 2.42%, 6.14%, and 9.35% at 120s, 180s and 240s, respectively. The phantom measurements using Clarity (Anticosti) system showed increasing accuracy of US tracking with decreasing scanning range. The probability of lost tracking was higher for small scanning ranges (43.09% (10°) and 13.54% (20°)).The tracking success rates in healthy volunteers during DIBH were 93.24% and 89.86% for renal pelvis and portal vein branches, respectively. There was a strong correlation between the motion of the marker and the US tracking for the majority of analyzed breath-holds. 84.06% and 88.41% of renal pelvis target results and 82.26% and 91.94% of liver vein target results in AP and SI direction, the Pearson correlation coefficient was between 0.71 and 0.99. For evaluation of the intrafraction motion during breath-hold, 680 individual BHs during 93 treatment fractions were analysed. On visual control of tracking movies, target was lost in 27.9% of tracking, leaving a total of 490 BHs with optimal tracking. During these BHs, mean(+SD) target displacement were 1.7(+0.8)mm, 0.9(+0.4)mm, 2.2(+1.0)mm and 3.2(+1.0)mm for SI, LR, AP and 3D vector, respectively. Most of target displacement was below 2mm with percentage of 64.6%, 88.1% and 60.5% for SI, LR and AP, respectively. Data percentage of large target displacement increased with added BH time. At 5s, 3D vector of target displacement >10mm could be observed in 0.1% of data. Percentage values increased to 0.2%, 0.6%, and 1.1% at 10s, 15s and 20s, respectively. Conclusions The 4D US system offers a non-invasive method for online organ motion monitoring without additional ionizing radiation dose to the patient. The magnitudes of intrafraction prostate motion along the SI and AP directions were comparable. On average, the smallest motion was in the LR direction and the largest in AP direction. Most of the prostate displacements were within a few millimeters. However, with increased treatment time, larger 3D vector prostate displacements up to 18.30 mm could be observed. Shortening the treatment time can reduce the intrafractional motion and its effects and US monitoring can help to maximize treatment precision particularly in hypofractionated treatment regimens. For organ monitoring during BH application, the 4D US system showed a good performance and tracking accuracy in a 4D motion phantom when tracking a target that moves in accordance to a simulating breathing pattern. A 30°scanning range turned out to be an optimal parameter to track along with respiratory motion considering the accuracy of tracking and the possible loss of the tracked structure. The ultrasound tracking system is also applicable to a clinical setup with the tested hardware solution. The tracking capability of surrogate structures for upper abdominal lesions in DIBH is promising but needs further investigation in a larger cohort of patients. Ultrasound motion data show a strong correlation with surface motion data for most of individual breath-holds. Further improvement of the tracking algorithm is suggested to improve accuracy along with respiratory motion if using larger scanning angles for detection of high-amplitude motion and non-linear transformations of the tracking target. The exact quantification of residual motion impact requires an in-depth analysis of time spent at every position, nevertheless mean residual motion during DIBH is low and predominant direction is SI and AP. Only infrequently larger displacements of 3D vector >1 cm were observed, for short periods. Beam interruption at predefined thresholds could take DIBH treatments close to perfection. Key words: Medical Physics, 4D ultrasound, IGRT (image-guided radiotherapy), prostate motion, stereotactic body radiotherapy (SBRT), deep inspiratory breath-hold (DIBH)

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

A 3D US Guidance System for Permanent Breast Seed Implantation: Development and Validation

Permanent breast seed implantation (PBSI) is a promising breast radiotherapy technique that suffers from operator dependence. We propose and have developed an intraoperative 3D ultrasound (US) guidance system for PBSI. A tracking arm mounted to a 3D US scanner registers a needle template to the image. Images were validated for linear and volumetric accuracy, and image quality in a volunteer. The tracking arm was calibrated, and the 3D image registered to the scanner. Tracked and imaged needle positions were compared to assess accuracy and a patient-specific phantom procedure guided with the system. Median/mean linear and volumetric error was ±1.1% and ±4.1%, respectively, with clinically suitable volunteer scans. Mean tracking arm error was 0.43mm and 3D US target registration error ≤0.87mm. Mean needle tip/trajectory error was 2.46mm/1.55°. Modelled mean phantom procedure seed displacement was 2.50mm. To our knowledge, this is the first reported PBSI phantom procedure with intraoperative 3D image guidance

On the investigation of a novel x-ray imaging techniques in radiation oncology

Radiation therapy is indicated for nearly 50% of cancer patients in Australia. Radiation therapy requires accurate delivery of ionising radiation to the neoplastic tissue and pre-treatment in situ x-ray imaging plays an important role in meeting treatment accuracy requirements. Four dimensional cone-beam computed tomography (4D CBCT) is one such pre-treatment imaging technique that can help to visualise tumour target motion due to breathing at the time of radiation treatment delivery. Measuring and characterising the target motion can help to ensure highly accurate therapeutic x-ray beam delivery. In this thesis, a novel pre-treatment x-ray imaging technique, called Respiratory Triggered 4D cone-beam Computed Tomography (RT 4D CBCT), is conceived and investigated. Specifically, the aim of this work is to progress the 4D CBCT imaging technology by investigating the use of a patient’s breathing signal to improve and optimise the use of imaging radiation in 4D CBCT to facilitate the accurate delivery of radiation therapy. These investigations are presented in three main studies: 1. Introduction to the concept of respiratory triggered four dimensional conebeam computed tomography. 2. A simulation study exploring the behaviour of RT 4D CBCT using patientmeasured respiratory data. 3. The experimental realisation of RT 4D CBCT working in a real-time acquisitions setting. The major finding from this work is that RT 4D CBCT can provide target motion information with a 50% reduction in the x-ray imaging dose applied to the patient