Segmentation of pelvic structures from preoperative images for surgical planning and guidance

Prostate cancer is one of the most frequently diagnosed malignancies globally and the second leading cause of cancer-related mortality in males in the developed world. In recent decades, many techniques have been proposed for prostate cancer diagnosis and treatment. With the development of imaging technologies such as CT and MRI, image-guided procedures have become increasingly important as a means to improve clinical outcomes. Analysis of the preoperative images and construction of 3D models prior to treatment would help doctors to better localize and visualize the structures of interest, plan the procedure, diagnose disease and guide the surgery or therapy. This requires efficient and robust medical image analysis and segmentation technologies to be developed. The thesis mainly focuses on the development of segmentation techniques in pelvic MRI for image-guided robotic-assisted laparoscopic radical prostatectomy and external-beam radiation therapy. A fully automated multi-atlas framework is proposed for bony pelvis segmentation in MRI, using the guidance of MRI AE-SDM. With the guidance of the AE-SDM, a multi-atlas segmentation algorithm is used to delineate the bony pelvis in a new \ac{MRI} where there is no CT available. The proposed technique outperforms state-of-the-art algorithms for MRI bony pelvis segmentation. With the SDM of pelvis and its segmented surface, an accurate 3D pelvimetry system is designed and implemented to measure a comprehensive set of pelvic geometric parameters for the examination of the relationship between these parameters and the difficulty of robotic-assisted laparoscopic radical prostatectomy. This system can be used in both manual and automated manner with a user-friendly interface. A fully automated and robust multi-atlas based segmentation has also been developed to delineate the prostate in diagnostic MR scans, which have large variation in both intensity and shape of prostate. Two image analysis techniques are proposed, including patch-based label fusion with local appearance-specific atlases and multi-atlas propagation via a manifold graph on a database of both labeled and unlabeled images when limited labeled atlases are available. The proposed techniques can achieve more robust and accurate segmentation results than other multi-atlas based methods. The seminal vesicles are also an interesting structure for therapy planning, particularly for external-beam radiation therapy. As existing methods fail for the very onerous task of segmenting the seminal vesicles, a multi-atlas learning framework via random decision forests with graph cuts refinement has further been proposed to solve this difficult problem. Motivated by the performance of this technique, I further extend the multi-atlas learning to segment the prostate fully automatically using multispectral (T1 and T2-weighted) MR images via hybrid \ac{RF} classifiers and a multi-image graph cuts technique. The proposed method compares favorably to the previously proposed multi-atlas based prostate segmentation. The work in this thesis covers different techniques for pelvic image segmentation in MRI. These techniques have been continually developed and refined, and their application to different specific problems shows ever more promising results.Open Acces

Dense Vision in Image-guided Surgery

Image-guided surgery needs an efficient and effective camera tracking system in order to perform augmented reality for overlaying preoperative models or label cancerous tissues on the 2D video images of the surgical scene. Tracking in endoscopic/laparoscopic scenes however is an extremely difficult task primarily due to tissue deformation, instrument invasion into the surgical scene and the presence of specular highlights. State of the art feature-based SLAM systems such as PTAM fail in tracking such scenes since the number of good features to track is very limited. When the scene is smoky and when there are instrument motions, it will cause feature-based tracking to fail immediately. The work of this thesis provides a systematic approach to this problem using dense vision. We initially attempted to register a 3D preoperative model with multiple 2D endoscopic/laparoscopic images using a dense method but this approach did not perform well. We subsequently proposed stereo reconstruction to directly obtain the 3D structure of the scene. By using the dense reconstructed model together with robust estimation, we demonstrate that dense stereo tracking can be incredibly robust even within extremely challenging endoscopic/laparoscopic scenes. Several validation experiments have been conducted in this thesis. The proposed stereo reconstruction algorithm has turned out to be the state of the art method for several publicly available ground truth datasets. Furthermore, the proposed robust dense stereo tracking algorithm has been proved highly accurate in synthetic environment (< 0.1 mm RMSE) and qualitatively extremely robust when being applied to real scenes in RALP prostatectomy surgery. This is an important step toward achieving accurate image-guided laparoscopic surgery.Open Acces

Exploiting Temporal Image Information in Minimally Invasive Surgery

Minimally invasive procedures rely on medical imaging instead of the surgeons direct vision. While preoperative images can be used for surgical planning and navigation, once the surgeon arrives at the target site real-time intraoperative imaging is needed. However, acquiring and interpreting these images can be challenging and much of the rich temporal information present in these images is not visible. The goal of this thesis is to improve image guidance for minimally invasive surgery in two main areas. First, by showing how high-quality ultrasound video can be obtained by integrating an ultrasound transducer directly into delivery devices for beating heart valve surgery. Secondly, by extracting hidden temporal information through video processing methods to help the surgeon localize important anatomical structures. Prototypes of delivery tools, with integrated ultrasound imaging, were developed for both transcatheter aortic valve implantation and mitral valve repair. These tools provided an on-site view that shows the tool-tissue interactions during valve repair. Additionally, augmented reality environments were used to add more anatomical context that aids in navigation and in interpreting the on-site video. Other procedures can be improved by extracting hidden temporal information from the intraoperative video. In ultrasound guided epidural injections, dural pulsation provides a cue in finding a clear trajectory to the epidural space. By processing the video using extended Kalman filtering, subtle pulsations were automatically detected and visualized in real-time. A statistical framework for analyzing periodicity was developed based on dynamic linear modelling. In addition to detecting dural pulsation in lumbar spine ultrasound, this approach was used to image tissue perfusion in natural video and generate ventilation maps from free-breathing magnetic resonance imaging. A second statistical method, based on spectral analysis of pixel intensity values, allowed blood flow to be detected directly from high-frequency B-mode ultrasound video. Finally, pulsatile cues in endoscopic video were enhanced through Eulerian video magnification to help localize critical vasculature. This approach shows particular promise in identifying the basilar artery in endoscopic third ventriculostomy and the prostatic artery in nerve-sparing prostatectomy. A real-time implementation was developed which processed full-resolution stereoscopic video on the da Vinci Surgical System

Optimizing Magnetic Resonance Imaging for Image-Guided Radiotherapy

Magnetic resonance imaging (MRI) is playing an increasingly important role in image-guided radiotherapy. MRI provides excellent soft tissue contrast, and is flexible in characterizing various tissue properties including relaxation, diffusion and perfusion. This thesis aims at developing new image analysis and reconstruction algorithms to optimize MRI in support of treatment planning, target delineation and treatment response assessment for radiotherapy. First, unlike Computed Tomography (CT) images, MRI cannot provide electron density information necessary for radiation dose calculation. To address this, we developed a synthetic CT generation algorithm that generates pseudo CT images from MRI, based on tissue classification results on MRI for female pelvic patients. To improve tissue classification accuracy, we learnt a pelvic bone shape model from a training dataset, and integrated the shape model into an intensity-based fuzzy c-menas classification scheme. The shape-regularized tissue classification algorithm is capable of differentiating tissues that have significant overlap in MRI intensity distributions. Treatment planning dose calculations using synthetic CT image volumes generated from the tissue classification results show acceptably small variations as compared to CT volumes. As MRI artifacts, such as B1 filed inhomogeneity (bias field) may negatively impact the tissue classification accuracy, we also developed an algorithm that integrates the correction of bias field into the tissue classification scheme. We modified the fuzzy c-means classification by modeling the image intensity as the true intensity corrupted by the multiplicative bias field. A regularization term further ensures the smoothness of the bias field. We solved the optimization problem using a linearized alternating direction method of multipliers (ADMM) method, which is more computational efficient over existing methods. The second part of this thesis looks at a special MR imaging technique, diffusion-weighted MRI (DWI). By acquiring a series of DWI images with a wide range of b-values, high order diffusion analysis can be performed using the DWI image series and new biomarkers for tumor grading, delineation and treatment response evaluation may be extracted. However, DWI suffers from low signal-to-noise ratio at high b-values, and the multi-b-value acquisition makes the total scan time impractical for clinical use. In this thesis, we proposed an accelerated DWI scheme, that sparsely samples k-space and reconstructs images using a model-based algorithm. Specifically, we built a 3D block-Hankel tensor from k-space samples, and modeled both local and global correlations of the high dimensional k-space data as a low-rank property of the tensor. We also added a phase constraint to account for large phase variations across different b-values, and to allow reconstruction from partial Fourier acquisition, which further accelerates the image acquisition. We proposed an ADMM algorithm to solve the constrained image reconstruction problem. Image reconstructions using both simulated and patient data show improved signal-to-noise ratio. As compared to clinically used parallel imaging scheme which achieves a 4-fold acceleration, our method achieves an 8-fold acceleration. Reconstructed images show reduced reconstruction errors as proved on simulated data and similar diffusion parameter mapping results on patient data.PHDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143919/1/llliu_1.pd

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)