Sarcoidosis is a multisystem granulomatous disease commonly involving the lungs and mediastinal lymph nodes with the exact etiology being unclear. The simultaneous presence of malignant disease such as breast cancer and sarcoidosis has been reported. Sarcoidosis preceding a diagnosis of malignancy and that occurring years after treatment of malignant disease has been noted in the past. The presence of sarcoidosis in the setting of malignant disease carries a high risk of misdiagnosis. In this article, we report the case of a 45-year-old female with stage IA invasive ductal carcinoma of left breast that was in remission for 2 years; however, radiological imaging including magnetic resonance imaging of thoracic spine and positron emission tomography–computed tomography scanning were highly suspicious for malignant disease metastasis versus lymphoma with the widespread lymphadenopathy. Multiple tissue biopsies with histopathological evaluation allowed us to definitively exclude malignant disease metastasis and to correctly diagnose her atypical presentation of sarcoidosis.

京都大学 / 0048 / 新制・課程博士 / 博士(薬学) / 甲第18550号 / 薬博第812号 / 新制||薬||238(附属図書館) / 31450 / 京都大学大学院薬学研究科医療薬科学専攻 / (主査)教授 佐治 英郎, 教授 橋田 充, 教授 髙倉 喜信 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第18907号 / 社医博第65号 / 新制||社医||9(附属図書館) / 31858 / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 川上 浩司, 教授 富樫 かおり, 教授 武藤 学 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20610号 / 医博第4259号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 村井 俊哉, 教授 渡邉 大, 教授 林 康紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20612号 / 医博第4261号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 溝脇 尚志, 教授 小泉 昭夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Single-photon avalanche diodes’ (SPADs) capabilities of detecting even a single photon with excellent timing resolution and compatibility with strong magnetic fields make them the most promising sensor for positron emission tomography imaging systems. With the advancements of silicon fabrication techniques, SPADs designed in standard planar complementary metal-oxide-semiconductor (CMOS) processes show competitive performance and a lower manufacturing cost. Additionally, CMOS SPADs have the potential for monolithic integration with other CMOS signal conditioning and processing circuits to achieve simple, low-cost, and high-performance imaging solutions. This work targets the design and optimization of SPAD sensors to improve their performance using low-cost standard CMOS technologies. Firstly, a detailed review on the SPADs in recent literature is presented. Then, the random telegraph signal (RTS) noise is investigated based on n+/p-well SPADs fabricated in a standard 130 nm CMOS process. Through the measurements and analysis, the RTS noise of a SPAD is found to correlate with its dark count rate and afterpulsing. Next, we design n+/p-well SPADs with field poly gates to improve the noise performance. Furthermore, a SPAD pixel, consisting of a p+/n-well SPAD and a compact and high-speed active quench and reset circuit is designed and fabricated in a standard TSMC 65 nm CMOS process. The post-layout simulations show that this pixel achieves a short 0.1 ns quenching time and a 3.35 ns minimum dead time. The measurement results show that the SPAD pixel has a dark count rate of 21 kHz, a peak photon detection probability of 23.8% at a 420 nm wavelength and a timing jitter of 139 ps using a 405 nm pulsed laser when the excess voltage is set to 0.5 V. Due to the short quenching time, almost no afterpulsing is observed even at a low operating temperature of -35 °C. Finally, a new differential quench and reset (QR) circuit consisting of two QR circuits on both the cathode and anode to quench and reset the SPAD through both terminals is proposed to reduce the reset time, to increase the count rate, to reduce the afterpulsing and to reject the common-mode noise. / Thesis / Doctor of Philosophy (PhD) / Positron emission tomography (PET) imaging is a powerful tool for diagnosis and assessment of cancers and tumors in the clinical field. Due to their capabilities of detecting even a single photon, excellent timing resolution, and their compatibility with magnetic fields to build PET/MRI (magnetic resonance imaging) multimodal imaging systems; single-photon avalanche diodes (SPADs) become the most promising sensor technology for PET imaging applications. SPADs fabricated in standard complementary metal-oxide-semiconductor (CMOS) technologies allow for a lower manufacturing cost and present the potential to integrate with other CMOS circuits to form a complete imaging system. In this thesis, random telegraph signal noise in SPADs is investigated first. Then, the poly gate is used in the design of an n+/p-well SPAD to improve the noise performance. In addition, a compact and high-speed SPAD pixel is designed and fabricated using an advanced standard CMOS process. Thanks to the fast quench and reset circuit, the SPAD pixel achieves a very short quenching time and a high-count rate. Finally, a differential quench and reset (QR) circuit consisting of two QR circuits on both the cathode and anode to quench and reset the SPAD through both terminals is proposed and studied.

Despite the development of therapeutic interventions to prevent mortality following myocardial infarction (MI), there is a significant long-term risk of developing heart failure (HF). Injectable collagen hydrogels have demonstrated considerable promise as a therapeutic solution to reduce adverse ventricle remodeling associated with the development of HF post-MI. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in the degradation of the structural components of the extracellular matrix (ECM). The activation of MMPs following MI is an essential step in the cardiac repair process. However, uncontrolled enzymatic activity during this time has been associated with the formation of adverse fibrosis. Given the role of the proteases in tissue remodeling, MMPs may be a potential biomarker to predict the development of HF. This thesis work seeks to examine the effect of a novel hydrogel matrix therapy on cardiac tissue post-MI using broad-spectrum MMP-targeted radiotracer, [18F]BR3531. In Study 1, serial positron emission tomography (PET) imaging was performed to elucidate the spatial and temporal binding of [18F]BR351 post-MI using a murine model. Imaging was performed by administering [18F]BR351 at time points corresponding with periods of peak MMP activation post-MI. In vivo PET imaging and in vitro autoradiography demonstrated decreased [18F]BR351 binding in the infarct region. In Study 2, the model was used to evaluate the efficacy of a therapeutic collagen hydrogel to attenuate tissue remodeling. The groups that received the matrix treatment exhibited improved [18F]BR351 uptake in the infarct region. However, conflicting results between in vivo imaging and in vitro autoradiography, and immunohistochemistry using MMP2 and MMP9 indicate that [18F]BR351 may not be suited for MMP imaging in mouse models of MI.

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