An Adaptive Algorithm to Identify Ambiguous Prostate Capsule Boundary Lines for Three-Dimensional Reconstruction and Quantitation

Currently there are few parameters that are used to compare the efficiency of different methods of cancerous prostate surgical removal. An accurate assessment of the percentage and depth of extra-capsular soft tissue removed with the prostate by the various surgical techniques can help surgeons determine the appropriateness of surgical approaches. Additionally, an objective assessment can allow a particular surgeon to compare individual performance against a standard. In order to facilitate 3D reconstruction and objective analysis and thus provide more accurate quantitation results when analyzing specimens, it is essential to automatically identify the capsule line that separates the prostate gland tissue from its extra-capsular tissue. However the prostate capsule is sometimes unrecognizable due to the naturally occurring intrusion of muscle and connective tissue into the prostate gland. At these regions where the capsule disappears, its contour can be arbitrarily reconstructed by drawing a continuing contour line based on the natural shape of the prostate gland. Presented here is a mathematical model that can be used in deciding the missing part of the capsule. This model approximates the missing parts of the capsule where it disappears to a standard shape by using a Generalized Hough Transform (GHT) approach to detect the prostate capsule. We also present an algorithm based on a least squares curve fitting technique that uses a prostate shape equation to merge previously detected capsule parts with the curve equation to produce an approximated curve that represents the prostate capsule. We have tested our algorithms using three shapes on 13 prostate slices that are cut at different locations from the apex and the results are promisin

Treatment outcome and radioiodine dose-response in differentiated thyroid carcinoma

Radioiodine (131I) has been used to treat differentiated thyroid carcinoma for the past fifty years. The activity administered remains empirical and most clinicians prescribe a fixed activity for ablation and therapy based upon experience and likely side effects. This lack of tumour dosimetry contrasts sharply with planning for external beam radiotherapy where precise tumour-dose prescription is mandatory. Estimation of absorbed radiation dose delivered to target tissue has been largely ignored in the past partly beacuse of the difficulty in measuring that part of the target volume which is metabolically active. Where absorbed dose has been estimated there is no consensus as to what absorbed dose should be delivered in order to destroy thyroid remnants and metastatic lesions. In order to calculate the absorbed radiation dose to those tissues which concentrate radioiodine, three parameters must be determined: the initial activity in the target tissue; the effective half-life of the radioiodine and the mass of tissue. Tumour and normal thyroid absorbed doses have been determined using a dual-headed whole-body scanner with special high- resolution low-sensitivity collimators. Improved accuracy in the estimation of functioning tumour mass has been achieved using positron emission tomography with a low-cost large area multi-wire proportional chamber camera, developed by the Physics Department of the Royal Marsden Hospital in collaboration with the Rutherford Appleton Laboratories. Dosimetry studies were performed for 54 patients with differentiated thyroid carcinoma (40 papillary, 14 follicular). There were 39 females and 15 males, ages 22 to 79 years. Dose-response graphs have been constructed in order to determine the tumouricidal dose for differentiated thyroid carcinoma metastases and thus enable precise activities of radioiodine to be prescribed in order to maximise tumour kill and minimise morbidity. The clinical data demonstrate that the administration of fixed activities of radioiodine results in a very large range of radiation absorbed dose to residual normal thyroid tissue and metastases of differentiated thyroid carcinoma. Following near-total thyroidectomy and 3.0 GBq 131I, a mean absorbed dose of 349 Gy achieved complete ablation of thyroid remnants in 67[percent] of patients (73[percent] of sites). Patients who had persistent uptake in the thyroid region on subsequent radioiodine scanning had received a mean absorbed dose of only 80 Gy. Failure to ablate may be attributed to two possible factors: large residua following less than radical surgery and the presence of tumour in association with normal tissue. Radioiodine therapy appears to be most effective in destroying small volumes of tissue after optimum surgical cytoreduction. Moreover, when tumour remains in association with normal tissue, the results here indicate that a much lower concentration of radioiodine can be achieved. For these two groups of patients, higher activities of are indicated. Successful destruction of cervical node metastases has been accomplished with absorbed doses of 150 Gy following functional neck dissection. Bone metastases, which are generally associated with a poor prognosis, require doses in excess of 100 Gy for eradication but this can be achieved for solitary deposits following initial surgical debulking. Nevertheless, worthwhile palliation may still be achieved with absorbed doses lower than this. However, the clinical data suggest that absorbed doses less than 20 Gy are sub-therapeutic and that alternative therapy should be considered if less than this can be achieved with radioiodine therapy. The dose-response data explain the spectrum of clinical response to fixed activities of radioiodine. In future they will enable precise prescription of radioiodine to achieve tumouricidal doses whilst avoiding the morbidity, staff hazards and expense of ineffective therapy

Applications of quantitative phase imaging for pathology

Prostate cancers, which account for 14% of all cancers diagnosed in the United States, and colorectal cancers, which account for 8.2% of all cancers, present a unique set of diagnostic problems [1]. In the case of prostate cancer, overdiagnosis of early-stage disease and poor accuracy at characterizing high-risk disease, especially when diagnosed at the intermediate stage, are major problems. A new prognostic method is thus necessary for improving prostate cancer management. In the case of colorectal cancer, early disease diagnosis is of critical importance for the purpose of reduction in disease-specific death rates. An automated screening tool which identifies cases that warrant further examination by the pathologist would assist in the implementation of a wide-spread screening program. Quantitative phase imaging (QPI) of unstained tissue provides information on the refractive index distribution, or tissue morphology, with nanometer level sensitivity. Subtle morphological changes in both the epithelial and stromal regions of tissue, which are not visible in stained tissue sections used in current pathological settings, can be measured using QPI. Thus QPI would be a valuable addition to current diagnostic pathology

A Study of Prostate Cancer by Using Single-Voxel and Hadamard Multi-Voxel 2D Localized COSY and JPRESS MR Spectroscopy Techniques

Prostate cancer is the most common cancer among men in the western countries. It grows indolently and can take more than 10 years to turn deadly. Currently no imaging methods can provide both high sensitivity and specificity for prostate cancer detection and characterization. 1H Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique, which can provide biochemical information of the prostate gland. (Choline + Creatine)/ Citrate ratio is widely used as a criterion for the diagnosis of prostate cancer. The specificity of multi-voxel 1D* 1H MRS is still limited due to the severe overlap of 1D* 1H MRS spectrum and voxel bleeding artifacts. Two-dimensional 1H MRS, which spreads the metabolite resonance peaks on a two-spectral dimensional surface, can help to differentiate most of the overlapping resonance peaks compared to conventional 1D* MRS spectrum. In the present study, a Hadamard multi-voxel 2D* localized COrrelated SpectroscopY (COSY) MRS technique was developed and implemented on a whole-body 4T MR system. The combination of localized 2D* 1H MR correlation spectroscopy and Hadamard encoding enables the simultaneous acquisition of multiple volumes of interest with the benefits of improved spectral resolution, increased SNR without an increase in the experimental duration, and with limited voxel bleeding compared to 1D* CSI acquisition. Most of the metabolites were measured without contamination of other resonances. The developed technique solves the severe resonances overlap problem in 1D* 1H MR spectra and offers multi-regional analysis of MRS due to the multi-focal and heterogeneous nature of prostate adeno-carcinoma, which can be easily overlooked by a single-voxel based MR spectroscopy method. By using this technique, more metabolites can be identified and additional information about the metabolites can be gained from the extended 2D* MRS spectra. This offers an opportunity to accurately follow up the metabolism in vivo. New biomarker of prostate cancer -polyamine spermine resonances are very well-resolved in 2D* L-COSY spectra and can be traced longitudinally by its cross-peaks for chemoprevention research of prostate cancer. 2D* Localized J-resolved Pointed RESolved Spectroscopy (JPRESS) MRS technique was also implemented to compare it with the 2D* L-COSY technique. The advantages and disadvantages of both techniques are thoroughly investigated

Image Processing and Analysis for Preclinical and Clinical Applications

Radiomics is one of the most successful branches of research in the field of image processing and analysis, as it provides valuable quantitative information for the personalized medicine. It has the potential to discover features of the disease that cannot be appreciated with the naked eye in both preclinical and clinical studies. In general, all quantitative approaches based on biomedical images, such as positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI), have a positive clinical impact in the detection of biological processes and diseases as well as in predicting response to treatment. This Special Issue, “Image Processing and Analysis for Preclinical and Clinical Applications”, addresses some gaps in this field to improve the quality of research in the clinical and preclinical environment. It consists of fourteen peer-reviewed papers covering a range of topics and applications related to biomedical image processing and analysis

Magnetic Resonance imaging Assessment of Tumor Microvessels and Response to Antiangiogenesis Therapy

Magnetic resonance Imaging (MRI) is a diagnostic modality with high inherent contrast resolution and multiplanar imaging capability. Advances in MR technology and image processing have increased the utility and availability of this technique in the past two decades. MRI has become one of the leading modalities in current diagnostic imaging, combining soft tissue contrast with high anatomic and temporal resolution. MRI is now a widely employed diagnostic method for the clinical evaluation of tumors. One of the most recent applications of MRI is the investigation of angiogenesis using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI represents the acquisition of serial MR images before, during, and after the administration of an intravenous contrast agent. The use of contrast enhancement in conjunction with magnetic resonance imaging provides a means to evaluate tissue function, as well as morphology. Tissue blood volume, blood flow, perfusion and capillary permeability represent indicators of the status of the vasculature that can be investigated with DCE-MRI. Use of such quantitation potentially allows tumors to be characterized in terms of pathophysiology and to be monitored over time, during the course of therapeutic interventions. The understanding of the angiogenesis process and the evaluation of new drugs that inhibit or stimulate angiogenesis are directly related to the development of an imaging assay of angiogenic activity. This method should provide functionally relevant and quantitative images, should be high in spatial resolution, should sample the entire tumor and could be repeated at frequent intervals. DCE-MRI has grown in importance with the development of antiangiogenic and neoadjuvant strategies for tumor therapy. Dedicated software makes it possible to interpret imaging pharmacokinetics and aid the assessment of physiological parameters such as capillary permeability and tissue perfusion. For instance, the permeability of functional tumor microvessels can be assessed noninvasively by dynamic MRI of contrast agent uptake in the tumor tissue (1-4). The analysis of contrast kinetics can be applied to differentiate between a malignant and a benign lesion and to determine whether a tumor is responding to treatment (5). It has been demonstrated that the permeability of blood vessels correlates with the ability of the tumor to metastasize, and with its response to treatment (6, 7). Thus, information concerning the status of vascular permeability might help assessing the metastatic potential of tumors and predict the sensitivity to chemotherapy or to antiangiogenic treatment

Understanding Key Biomechanical Factors that Influence Rotator Cuff Tear Propagation

The high frequency of rotator cuff tears in an aging population, combined with their capacity to cause pain and limit normal activity, underscores the importance of treating these injuries in a judicious manner. However, high failure rates have been reported for non-operative and surgical treatment. Tear propagation may explain high failure rates of treatment as larger tears are more difficult to treat and are associated with worse clinical outcomes. Abnormal glenohumeral arthrokinematics and localized changes in mechanical properties are factors that explain why some tears propagate more easily than others. Furthermore, clinicians lack a tool to non-invasively quantify tendon mechanical properties. Therefore, the objective of this dissertation is to better understand the role of glenohumeral arthrokinematics and location specific mechanical properties on tear propagation as well as the utility of ultrasound techniques to quantify mechanical properties of tendons through in-vivo, cadaveric, and computational experiments. Following exercise therapy for 5 subjects with a rotator cuff tear, glenohumeral arthrokinematics for internal/external rotation with the arm at the side did not improve. Abnormal glenohumeral arthrokinematics may be a result of unbalanced force couples, exposing the torn supraspinatus tendon to loads that may promote tendon remodeling that increases the likelihood of tear propagation. Using a subject-specific finite element model of a supraspinatus tendon, tendon remodeling in terms of increased stiffness at the tear tips lead to more tear propagation. Cadaveric experiments showed that quantitative ultrasound measures, which analyze the grayscale echotexture of an ultrasound image, correlates to measures of tendon quality as quantified through histology. Acoustic Radiation Force Impulse (ARFI) imaging a technique where localized radiation forces push onto the tissue, the resulting displacement is measured. The mechanical properties of the tissue can then be inferred. However, our findings suggest that ARFI imaging is limited for high stiffness tissues such as tendons. Despite large differences in tissue modulus, differences in ARFI displacement are minimal. Ultimately, understanding how changes in localized tendon mechanical properties influence tear propagation and the capabilities of currently available ultrasound techniques to measure tendon mechanical properties will enable clinicians to make better treatment decisions for patients with a rotator cuff tear