No description available.

No

<p> Autosomal Dominant Polycystic Kidney Disease (ADPKD) is among the most prevalent life-threatening genetic conditions. Despite this, no approved medical therapies exist to treat the disease. Until the recent past, no methods could reliably measure the course of the disease far in advance of end stage renal disease (ESRD). As normal tissue is progressively destroyed or blocked by enlarging cysts, remaining nephrons compensate in a process called hyperfiltration. This beneficial physiological response confounds tests of renal function. Thus, potential interventions could not be tested against a reliable measurement of disease progression. </p><p> However, progressive changes are visually apparent on medical imaging examinations throughout the course of ADPKD. The search for ADPKD proxy biomarkers is now focused on quantitative imaging, or the extraction of information from medical images for purposes of diagnosis or disease tracking. Recent studies from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)- sponsored Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) showed Total Kidney Volume (TKV) is a usable quantitative imaging biomarker which can track disease in the early, asymptomatic phase and register measurable changes in as little as 12 months. These findings launched several new trials into potential ADPKD therapies. </p><p> Advanced analysis of polycystic kidney images, however, has never been done. The method CRISP used to extract TKV was stereology, an efficient means to estimate volume. However, stereology was tradi- tionally a dead end for further advanced analysis. TKV is useful for clinical trials and large population-based studies, but cannot accurately predict disease progression or stratify risk due to known out- lier cases. Thus, the utility of TKV for individual patient prognosis is limited. This work builds upon stereology data, describing a reliable and accurate new semi-automatic method to fully segment images us- ing only labeled stereology grids. Then, two new second generation quantitative imaging biomarkers are introduced and analyzed: Cyst- Parenchyma Surface Area (CPSA) and cyst concentration. These new physiologically motivated biomarkers will complement or potentially replace TKV in efforts to bring quantitative imaging to individual patients. </p><p> The goal of this body of work is to enable a pathway for efficient advanced image analysis in ADPKD, never before attempted in this dis- order, and to define new quantitative imaging biomarkers which will complement or replace existing ones in hopes of making individualized disease tracking for ADPKD patients a reality.</p>

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

<p> Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in the world and the liver is a common site of metastases from other primary neoplasms. Many patients are not surgical candidates. Radioembolization is an intra-arterial therapy delivering high doses of radiation emitted from microspheres infused selectively into the tumor feeding arteries. These microspheres land in the tumor microcirculation and deposit radiation to the tumor tissues. Over the past ten years, radioembolization has become part of the treatment guidelines for unresectable HCC, liver-dominant metastatic colorectal cancer, and neuroendocrine liver metastases, and it is often used in the salvage setting for patients with hepatic malignancy progressing on other therapies. The overarching goal of the thesis work was to advance the basic science of ⁹⁰Y radioembolization based on existing clinical needs to ultimately improve patient outcomes. This included 1) setup of pre-clinical laboratory to study radioembolization, 2) optimization of radioembolization protocols in research animals, 3) validation of ⁹⁰Y PET/CT imaging techniques to monitor microsphere delivery and dosing, 4) blood oxygen-level dependent (BOLD) imaging and evaluation of tumor biology and physiology after radioembolization in the VX2 rabbit model at a fixed dose of 50 Gy, 5) evaluation of normal tissue pathology (fibrosis, atrophy) and biology (hepatocyte proliferation, microvessel density, stellate cell activation) in rats after ⁹⁰Y radiation lobectomy at clinically relevant dosing from 150 to >4,000 Gy, and 6) development of new yttrium microsphere compositions for combination therapy with electromagnetic hyperthermia.</p>