Schizophrenia is a severe neuropsychiatric disorder characterized by delusions, hallucinations, behavioral symptoms, and cognitive deficits. Roughly, 70%-80% of schizophrenia patients experience auditory verbal hallucinations (AVHs), with 25%-30% demonstrating resistance to conventional antipsychotic medications. Studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in the treatment of medication-refractory AVHs. The mechanisms through which tDCS could be therapeutic in such cases are unclear, but possibly involve neuroplastic effects. In recent years, functional near-infrared spectroscopy (fNIRS) has been used successfully to study tDCS-induced neuroplastic changes. In a double-blind, sham-controlled design, we applied fNIRS to measure task-dependent cerebral blood flow (CBF) changes as a surrogate outcome of single session tDCS-induced effects on neuroplasticity in a schizophrenia patient with persistent auditory hallucinations. The observations are discussed in this case report.

INTRODUCTION: The "vulnerable plaque" is defined as the "precursor lesion" that ultimately ends in acute coronary thrombi (clots) that create a heart attack. Macrophages and inflammatory cells, found preferentially in vulnerable plaque, sustain their activity in the plaque through anaerobic metabolism and lactate production. The ultimate goal is to assess anaerobic metabolism in-vivo by measuring tissue pH and lactate concentration in atherosclerotic plaques using optical spectroscopy. The proposed in-vitro optical probe design, experimental method, and spectroscopic data analysis methodology are established in this research. METHODS: A fiber optic probe was designed and built based on both Monte Carlo simulations and bench testing with the goal to collect light from a small volume of tissue. A simulation of the depth penetration of the proposed probe was performed on normal and atherosclerotic aortic tissue, and the final probe was bench tested using normal aorta. A method was developed to preserve plaque metabolic status of tissue harvested from patients. Human atherosclerotic tissue obtained immediately after carotid endarterectomy was placed in Minimum Essential Medium (MEM) with non-essential amino acids supplement, bubbled with 75%O2/20%N2/5%CO2 at 37°C. Tissue pH, pCO2, pO2 and temperature with (n=7) and without (n=2) the media preparation over time were reviewed to assess plaque viability and maintenance of physiological conditions. Additional plaques placed in media were used for development of chemometric methods to measure pH and lactate. Areas of each plaque were randomly chosen for analysis. Reflectance spectra were collected with a dispersive spectrometer (400-1100 nm) and a Fourier-transform near-infrared spectrometer (1100-2400 nm) using the fiber optic probe. Reference measurements for tissue pH and lactate were made with glass microelectrodes and micro-enzymatic assay, respectively. Partial least-squares (PLS) data analysis was used to develop multivariate calibration models on an initial set of 5-6 plaques relating the optical spectra to the reference tissue pH (n=20) or the lactate concentration (n=21) to assess data quality. The coefficient of multiple determination (R2), the standard error of cross-validation (SECV), and the number of factors were used to assess the model performance. Additional points were collected from ~14 plaques and added to preliminary data. Pre-processing techniques were then used to see if preliminary data results could be improved by reducing different sources of variability with the introduction of more points. RESULTS: Monte Carlo simulations and depth penetration tests with the final probe design showed light is collected from ~1 mm3 volume of tissue using a 50 micron source-receiver separation. Tissue pH, pCO2, pO2 and temperature values demonstrated that the plaques were viable and stable in the media preparation for a maximum of 4 hours. Data from the first six plaques collected for lactate analysis showed that for seventeen points, a six-factor model produced adequate results (R2=0.83 SECV=1.4 micromoles lactate/gram tissue). Data from the first five plaques collected for tissue pH analysis, showed for seventeen different points, a three-factor model produced adequate results (R2=0.75 SECV=0.09 pH units). When additional points were added to either data set, model results were degraded. CONCLUSIONS: The in-vitro optical probe design and experimental procedures was established and the feasibility of the optical method demonstrated with preliminary data. However, with the addition of more data points, different sources of tissue and spectral variability were observed to affect calibration. The gross pathology type and mismatched optical volume to reference measurement volume limited the tissue pH determination. The reference measurement precision, the spatial resolution of the reference lactate measurement, and unmodeled tissue variability (water and proteins) limited the lactate determination. Large variability in all optical measurements was observed. Additional in-vitro data collection would be required such that the variability due to the tissue is reduced and any spectrometer variability adequately compensated to be able to use the optical calibration in-vivo.

No description available.

Carbon nanotubes (CNTs) have special characteristics that made them good agents especially for biomedical applications. In this study, Fe3O4 nanoparticles were incorporated onto the surface of CNTs followed by polyethylene glycol (PEG) grafting forming CNTs-Fe3O4-PEG hybrids. The PEGylation improves their biocompatibility, water solubility, and increases blood circulation. CNTs-Fe3O4-PEG was used as T2-contrat agent for magnetic resonance imaging (MRI). In addition, doxorubicin (DOX) was loaded onto CNTs-Fe3O4-PEG. The release of DOX from DOX-loaded CNTs-Fe3O4-PEG was tested under different pH conditions (7.4, 6.3 and 5.2). The release increased at acidic pH compared to neutral pH, which shows the sensitivity of the system to pH change. Triggering the release by Near Infra-Red (NIR) irradiation was furthermore investigated. The release increased after irradiation with NIR compared to control sample. These result prove that the designed system can be triggered by an internal stimuli (pH) and external stimuli (NIR irradiation) making it a promising candidate to be used for biomedical applications.

The purpose of this dissertation series was to examine oxygen uptake kinetics in skeletal muscle by evaluating responses of local muscle deoxygenation during incremental exercise in healthy individuals using near-infrared spectroscopy (NIRS). Metabolic activity in skeletal muscle, as part of the integrative responses of the cardiovascular, respiratory and neuromuscular systems, are major determinants of an individual’s physical capacity and function. The workings of these systems, called whole-body metabolism, affect the capability of an individual to engage in activities of daily living, to exercise, and participate in athletic performance. Thus, they have a strong impact on health as engagement in physical activity is well known to be effective in improving cardiorespiratory fitness and reducing the risks of chronic disease. At this time, the in vivo relationships between whole-body metabolism and local muscle metabolic activity are not well understood, but with the availability of NIRS technology this is possible. NIRS is a noninvasive optical technique used to continuously measure changes in muscle tissue oxygen saturation locally, allowing interrogation of the functional integration between muscle metabolism and the cardiovascular system in intact human beings, which is what the series of studies in this dissertation evaluate. Healthy adults and adolescents were enrolled as healthy control participants into an observational study evaluating changes in local muscle oxygen uptake in neuromuscular disease during exercise. Participants performed a maximal cardiopulmonary exercise test (CPET) on a recumbent cycle ergometer. Changes in muscle deoxygenation (HHb), reflecting local oxygen uptake, were measured using NIRS and whole-body metabolism was assessed synchronously via expired gas analysis. After an initial increase in HHb at exercise onset, a consistent pattern of plateau in HHb was observed in the healthy participants near the end of peak exercise. Despite increasing workload and oxygen uptake (VO2) in the final minutes of the test, it was unclear what mechanisms were contributing to this HHb response. It was hypothesized that the HHb-Workload relationship evaluated at the time of VO2peak would be non-linear, such that a greater maximum workload achieved at VO2peak would not be linearly matched by greater ΔHHb (i.e., greater total change from rest to VO2peak). First, a critical evaluation of the literature was conducted to explore this hypothesis. Chapter 2 provides the results of a scoping review that was performed in order to better understand the scientific evidence using NIRS that describes the relationships between indices of muscle oxygen saturation and workload during incremental exercise. This formed the basis to pursue the hypothesis-driven research presented in the subsequent chapters, interrogating the overarching question of this dissertation related to the HHb-Workload relationship. The review revealed there are three methodological approaches to examining changes in muscle oxygen saturation and workload, the least common of which was examination of HHb and workload at the VO2peak time point. Changes in muscle oxygen saturation and work have also been studied as the change in muscle oxygenation over the duration of exercise and at a certain time point or intensity during incremental exercise. Based on the literature, it was clear that there was a dearth of research examining the HHb plateau response in relation to work at VO2peak. Accordingly, chapter 3 provides the results of a pilot study that evaluated the relationship between change in HHb (ΔHHb) and the maximum workload (MW) achieved at VO2peak, where it was hypothesized that the relationship at this time point would be non-linear. A polynomial regression model was used to describe the relationship. The results of this study showed that at lower maximum workloads there were initial increases in ΔHHb with increasing maximum workload but at the highest maximum workloads, ΔHHb attenuated. A polynomial model including ΔHHb and MW, with VO2peak (an indicator of cardiorespiratory fitness) as a covariate, best characterized the relationship. Age was not significantly related to ΔHHb or MW, and VO2peak appeared to play a partial role as its inclusion as a covariate helped explain approximately a quarter of the variance, suggesting other factors may be contributing to the attenuated HHb response. From this pilot work it was hypothesized that the attenuation in ΔHHb at higher maximum workloads, and the HHb plateau observed during CPET, could be explained by muscle efficiency. If so, a longer duration and lesser slope of the HHb plateau in the minutes leading up to VO2peak occurs in muscles with higher metabolic efficiency. As muscle efficiency is defined as a ratio of external work accomplished to internal energy expended, the hypothesis, if true, would support a better matching of the internal work (VO2) to the external work (workload on the ergometer). Chapter 4 provides the results of a secondary analysis that sought to determine whether the observed plateau in HHb reflected muscular efficiency by comparing the slope of the HHb plateau (HHb[s]) to a commonly used method of assessing muscle efficiency, delta efficiency (DE). It was hypothesized that HHb[s] and DE would be inversely and significantly correlated, providing a potential mechanism for the attenuated HHb response and a noninvasive method for assessing muscle efficiency. In contrast to the hypothesis, HHb[s] and DE were not associated, suggesting that a mechanism other than muscle efficiency is contributing to the HHb plateau. Collectively, this series of studies demonstrate that there is a need to better understand the relationship between HHb and workload in healthy individuals, because of a paucity of evidence exploring the HHb-MW relationship at VO2peak, the finding that ΔHHb attenuates at higher maximum workloads, and that results suggest the HHb plateau phenomenon cannot be explained by muscle efficiency. Future work should seek to elucidate the mechanism that allows healthy individuals to achieve higher workloads (i.e., continue exercising at high intensity) without further increasing muscle oxygen uptake, in a larger more heterogeneous sample.

京都大学 / 0048 / 新制・課程博士 / 博士(情報学) / 甲第19126号 / 情博第572号 / 新制||情||100(附属図書館) / 32077 / 京都大学大学院情報学研究科システム科学専攻 / (主査)教授 石井 信, 教授 田中 利幸, 教授 加納 学 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20054号 / 医博第4162号 / 新制||医||1018(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 湊谷 謙司, 教授 富樫 かおり, 教授 木村 剛 / 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(工学) / 甲第20401号 / 工博第4338号 / 新制||工||1672(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 中條 善樹, 教授 赤木 和夫, 教授 秋吉 一成 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21301号 / 医博第4390号 / 新制||医||1030(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 川上 浩司, 教授 小池 薫, 教授 福原 俊一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.