A non-invasive image based system for early diagnosis of prostate cancer.

Prostate cancer is the second most fatal cancer experienced by American males. The average American male has a 16.15% chance of developing prostate cancer, which is 8.38% higher than lung cancer, the second most likely cancer. The current in-vitro techniques that are based on analyzing a patients blood and urine have several limitations concerning their accuracy. In addition, the prostate Specific Antigen (PSA) blood-based test, has a high chance of false positive diagnosis, ranging from 28%-58%. Yet, biopsy remains the gold standard for the assessment of prostate cancer, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The major limitation of the relatively small needle biopsy samples is the higher possibility of producing false positive diagnosis. Moreover, the visual inspection system (e.g., Gleason grading system) is not quantitative technique and different observers may classify a sample differently, leading to discrepancies in the diagnosis. As reported in the literature that the early detection of prostate cancer is a crucial step for decreasing prostate cancer related deaths. Thus, there is an urgent need for developing objective, non-invasive image based technology for early detection of prostate cancer. The objective of this dissertation is to develop a computer vision methodology, later translated into a clinically usable software tool, which can improve sensitivity and specificity of early prostate cancer diagnosis based on the well-known hypothesis that malignant tumors are will connected with the blood vessels than the benign tumors. Therefore, using either Diffusion Weighted Magnetic Resonance imaging (DW-MRI) or Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), we will be able to interrelate the amount of blood in the detected prostate tumors by estimating either the Apparent Diffusion Coefficient (ADC) in the prostate with the malignancy of the prostate tumor or perfusion parameters. We intend to validate this hypothesis by demonstrating that automatic segmentation of the prostate from either DW-MRI or DCE-MRI after handling its local motion, provides discriminatory features for early prostate cancer diagnosis. The proposed CAD system consists of three majors components, the first two of which constitute new research contributions to a challenging computer vision problem. The three main components are: (1) A novel Shape-based segmentation approach to segment the prostate from either low contrast DW-MRI or DCE-MRI data; (2) A novel iso-contours-based non-rigid registration approach to ensure that we have voxel-on-voxel matches of all data which may be more difficult due to gross patient motion, transmitted respiratory effects, and intrinsic and transmitted pulsatile effects; and (3) Probabilistic models for the estimated diffusion and perfusion features for both malignant and benign tumors. Our results showed a 98% classification accuracy using Leave-One-Subject-Out (LOSO) approach based on the estimated ADC for 30 patients (12 patients diagnosed as malignant; 18 diagnosed as benign). These results show the promise of the proposed image-based diagnostic technique as a supplement to current technologies for diagnosing prostate cancer

Biomechanical Modeling and Inverse Problem Based Elasticity Imaging for Prostate Cancer Diagnosis

Early detection of prostate cancer plays an important role in successful prostate cancer treatment. This requires screening the prostate periodically after the age of 50. If screening tests lead to prostate cancer suspicion, prostate needle biopsy is administered which is still considered as the clinical gold standard for prostate cancer diagnosis. Given that needle biopsy is invasive and is associated with issues including discomfort and infection, it is desirable to develop a prostate cancer diagnosis system that has high sensitivity and specificity for early detection with a potential to improve needle biopsy outcome. Given the complexity and variability of prostate cancer pathologies, many research groups have been pursuing multi-parametric imaging approach as no single modality imaging technique has proven to be adequate. While imaging additional tissue properties increases the chance of reliable prostate cancer detection and diagnosis, selecting an additional property needs to be done carefully by considering clinical acceptability and cost. Clinical acceptability entails ease with respect to both operating by the radiologist and patient comfort. In this work, effective tissue biomechanics based diagnostic techniques are proposed for prostate cancer assessment with the aim of early detection and minimizing the numbers of prostate biopsies. The techniques take advantage of the low cost, widely available and well established TRUS imaging method. The proposed techniques include novel elastography methods which were formulated based on an inverse finite element frame work. Conventional finite element analysis is known to have high computational complexity, hence computation time demanding. This renders the proposed elastography methods not suitable for real-time applications. To address this issue, an accelerated finite element method was proposed which proved to be suitable for prostate elasticity reconstruction. In this method, accurate finite element analysis of a large number of prostates undergoing TRUS probe loadings was performed. Geometry input and displacement and stress fields output obtained from the analysis were used to train a neural network mapping function to be used for elastopgraphy imaging of prostate cancer patients. The last part of the research presented in this thesis tackles an issue with the current 3D TRUS prostate needle biopsy. Current 3D TRUS prostate needle biopsy systems require registering preoperative 3D TRUS to intra-operative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, concept of a robotic system was proposed which can reliably determine the preoperative TRUS probe position relative to the prostate to place at the same position relative to the prostate intra-operatively. For this purpose, a contact pressure feedback system is proposed to ensure similar prostate deformation during 3D and 2D image acquisition in order to bypass the registration step

Development of Surgery Guided NIR Fluorescent Probe Nanoparticles for Cancer Imaging

Background: Early-stage detection is crucial for successful breast cancer treatment and can significantly reduce breast cancer associated death rates. There are several diagnostic approaches available for early breast cancer diagnosis but lack tumor specificity and expose patients with radiation. Therefore, there is a crucial need to develop newer and safer imaging modalities. Indocyanine green (ICG), an FDA approved Near InfraRed (NIR) fluorescent probe-based imaging for early cancer detection and image guided surgery, has gained noticeable attention for the clinical applications as it has high sensitivity, low cost, and real-time visualization/imaging capabilities without ionizing radiation. However, ICG has several limitations associated with its photostability, high concentration toxicity, and short circulation time. To overcome this hurdle, we have recently engineered a novel poly (vinyl pyrrolidone) and tannic acid (PVP-TA) based nanosystem to carry ICG to the cancer cells/tissues. Methods: Pursuing the novel nanotherapy approach, our lab has developed PVP-TA based ICG (PVT-ICG) fluorescent nanoparticles via self-assembly process. Our optimized PVT-ICG nanoformulation was further characterized for its physicochemical properties. An IVIS imaging system was further used to measure NIR fluorescence of novel PVT-ICG. Moreover, Human cancer (Breast, Pancreatic, Liver and Prostate) tissue microarrays (TMAs) were histochemically stained to assess cancer cell targeting/specificity of PVT-ICG. Results: PVT-ICG indicated particle size and surface charge ideal for cancer cell/tissue delivery. PVT-ICG, further, demonstrated improved photostability and fluorescent intensity. Additionally, TMA studies exhibited enhanced internalization and cancer targeting/specificity of PVT-ICG nanoparticles compared to free ICG dye in all cancers. Conclusions: Collectively, our findings suggest that this NIR fluorescent probe PVT-ICG has great potential for becoming a novel and safe imaging modality for breast cancer cells/tumors which can result in early diagnosis leading to improved cancer management

Monte Carlo-based Noise Compensation in Coil Intensity Corrected Endorectal MRI

Background: Prostate cancer is one of the most common forms of cancer found in males making early diagnosis important. Magnetic resonance imaging (MRI) has been useful in visualizing and localizing tumor candidates and with the use of endorectal coils (ERC), the signal-to-noise ratio (SNR) can be improved. The coils introduce intensity inhomogeneities and the surface coil intensity correction built into MRI scanners is used to reduce these inhomogeneities. However, the correction typically performed at the MRI scanner level leads to noise amplification and noise level variations. Methods: In this study, we introduce a new Monte Carlo-based noise compensation approach for coil intensity corrected endorectal MRI which allows for effective noise compensation and preservation of details within the prostate. The approach accounts for the ERC SNR profile via a spatially-adaptive noise model for correcting non-stationary noise variations. Such a method is useful particularly for improving the image quality of coil intensity corrected endorectal MRI data performed at the MRI scanner level and when the original raw data is not available. Results: SNR and contrast-to-noise ratio (CNR) analysis in patient experiments demonstrate an average improvement of 11.7 dB and 11.2 dB respectively over uncorrected endorectal MRI, and provides strong performance when compared to existing approaches. Conclusions: A new noise compensation method was developed for the purpose of improving the quality of coil intensity corrected endorectal MRI data performed at the MRI scanner level. We illustrate that promising noise compensation performance can be achieved for the proposed approach, which is particularly important for processing coil intensity corrected endorectal MRI data performed at the MRI scanner level and when the original raw data is not available.Comment: 23 page

Discovery Radiomics via Deep Multi-Column Radiomic Sequencers for Skin Cancer Detection

While skin cancer is the most diagnosed form of cancer in men and women, with more cases diagnosed each year than all other cancers combined, sufficiently early diagnosis results in very good prognosis and as such makes early detection crucial. While radiomics have shown considerable promise as a powerful diagnostic tool for significantly improving oncological diagnostic accuracy and efficiency, current radiomics-driven methods have largely rely on pre-defined, hand-crafted quantitative features, which can greatly limit the ability to fully characterize unique cancer phenotype that distinguish it from healthy tissue. Recently, the notion of discovery radiomics was introduced, where a large amount of custom, quantitative radiomic features are directly discovered from the wealth of readily available medical imaging data. In this study, we present a novel discovery radiomics framework for skin cancer detection, where we leverage novel deep multi-column radiomic sequencers for high-throughput discovery and extraction of a large amount of custom radiomic features tailored for characterizing unique skin cancer tissue phenotype. The discovered radiomic sequencer was tested against 9,152 biopsy-proven clinical images comprising of different skin cancers such as melanoma and basal cell carcinoma, and demonstrated sensitivity and specificity of 91% and 75%, respectively, thus achieving dermatologist-level performance and \break hence can be a powerful tool for assisting general practitioners and dermatologists alike in improving the efficiency, consistency, and accuracy of skin cancer diagnosis