皱纹盘鲍血细胞内活性氧抗病机制及几种环境污染物及其影响的研究

本研究首次揭示了皱纹盘鲍(Haliotis discus hannai) 血细胞内存在着利用活性氧（Reactive oxygen species, ROS）的抗病机制。为今后我国研究贝类的活性氧抗病机制和筛选免疫药物提供了理论基础。本研究主要结果如下：1. 利用鲁米诺（Luminol, 3-氨基邻苯二甲酰肼）为依赖的化学发光法在体外条件下用不同刺激物（酵母细胞和酵母聚糖）对皱纹盘鲍血细胞进行刺激，测定血细胞吞噬活动中历经呼吸爆发产生活性氧的化学发光反应。结果表明皱纹盘鲍血细胞在体外条件下，经刺激物诱导吞噬活动中有明显的呼吸爆现象和很强的活性氧产生。不同有刺激物诱导血细胞产生的化学发光强度不同；同一刺激物的不同处理和不同浓度对血细胞产生活性氧的化学发光强度的影响不同。刺激物经皱纹盘鲍自体血清调理和未经调理对血细胞刺激所产生的化学发光强度不同。SOD和NaN_3对皱纹盘鲍血细胞吞噬过程中活性氧产生的化学发光有抑制作用。上述结果证明了皱纹盘鲍血细胞内存在有象高等动物血细胞内一样的MPO-H_2O-卤素系统的氧化性抗病机制，即在血细胞吞噬异物过程中能够释放活性氧（ROS）对异物进行杀灭的功能。2. 利用活性氧清除剂（过氧化氢酶、SOD、苯甲酸钠、2，5-二甲基呋喃、NBT和EDTA等）对皱纹盘鲍血细胞释放的活性氧进行分类测试，结果表明活性氧清除剂对皱纹盘鲍血细胞吞噬的化学发光都有明显的抑制作用，从而证明皱纹盘鲍血细胞能够释放的活性氧的种类有：超氧阴离子（O_2~-），过氧化氢（H_2O_2），羟自由基（OH~·）和单线态氧（~1O_2）。3. 在体外条件下利用化学发光法定量地研究了不同种类和不同浓度的农药：对硫磷（Parathion）、敌敌畏（Dichlorovos)、乐果（Dimethoate)、2，4-D 丁酯(2,4-D butylester)和甲胺磷（Methamidophos）对皱纹盘鲍血细胞氧化性抗病机制的影响。结果显示不同农药对皱纹鲍血细胞产生ROS的影响程度不同，及同一种农药的不同浓度的浸泡1h或浸泡12h处理皱纹盘鲍血细胞都能够抑制血细胞吞噬时的化学发光，表明农药能够抑制皱纹敌国鲍血细胞吞噬活动中的活性氧（ROS）的产生，而且这种抑制作用随着农药浓度的增加而加强。几种农药抑制皱纹盘鲍血细胞产生活性氧（ROS）的强度不同：2，4D-丁酯，敌敌畏和乐果的抑制作用强于对硫磷和甲胺磷。同时测定了不同浓度的农药浸泡12h后的皱纹盘鲍因细胞吞噬酵母细胞的吞噬百分率和吞噬指数，结果显示多数农药在低浓度时能够提高皱纹盘鲍血细胞的吞噬百分率和吞噬指数，而在高浓度时则能抑制血细胞吞噬酵母细胞的活力而降低血细胞的吞噬百分率的吞噬指数。4. 在体外条件下利用化学发光法定量地研究了不同种类和不同浓度的重金属：铭（Cr）、镉（Cd）、汞（Hg）、铅（Pb）、铜（Cu）和锌（Zn）对皱纹盘鲍血细胞氧化性抗病机制的影响。结果显示不同种类和不同浓度的重金属浸泡1hr.处理皱纹盘鲍血细胞都不同程度地抑制了血细胞吞噬时的化学发光，表明重金属能够抑制皱纹盘鲍血细胞吞噬活动中的活性氧（ROS）的产生，而且这种抑制作用随着重金属浓度的增加而加强。不同的重金属抑制强度不同，从强到弱依次为Hg > Cd > Cu > Pb > Cr > Zn. 研究表明六种重金属中，Hg对皱纹盘鲍血细胞的免疫毒性最大。

肉食性鱼类补偿生长特性的研究

本文主要以花鲈[Lateolabrax．japonicus (C．& V．)]和褐牙鲆[Paralichthys olivaceus(T. & S.)]作为海洋肉食性鱼类的代表种类，根据鱼类生态生理学理论，通过设定不同饥饿时问下因子水平，研究两种鱼类摄食率、排粪率、转化效率和SGR等生态生理效率的状态变化。其目的在于研究高营养级鱼类在海洋生态系统中的下行控制作用(Top-down Effect)，以及肉食性鱼类的生态对策与鱼类资源补充机制的相互关系，为深入解析鱼类资源生产力及其持续利用海洋生物资源，提供科学依据。其主要研究结果概述如下：1．花鲈： 饥饿0(对照组)、4、8、12、16d后恢复投喂，过量投喂淡水桡足类，温度为19.5±2.0℃，初始体重为0.61-0.93g，平均体重为0．79g实验周期为28d。1.1饥饿时间对花鲈的体重损失率产生显著影响，受过饥饿的个体的湿重失率 (LR_W)与饥饿时间(t)的关系为：LR_W=2.2164t-3.6634(r~2=0.9767，p13d)的个体的排粪率显著大于其它各组，其它各组间排粪率差异不显著；2.2在整个实验周期36d内，对照组与经受3—8d饥饿的实验组的SGR显著大于经受饥饿时间大于lOd的实验组，饥饿3-8d的完全补偿生长，饥饿10-15d 的个体发生部分补偿生长，饥饿18d的个体不能补偿生长；经受饥饿个体的摄食率低于对照组；除了饥饿18d的个体的饵料转化率显著小于对照组外，其它各组的转化率没有显著差异；经受长时间饥饿(>13d)的个体的排粪率显著大于其它各组，其它各组问没有显著的差异。2．3平均体重为2．59g的褐牙鲆，饥饿至不可恢复点(PNR)的时间大于18d。3．花鲈和褐牙鲆在经受饥饿后的体重损失率与饥饿的时间正相关。在实验期间，花鲈体重损失率与饥饿时间成一次线性关系，褐牙鲆体重损失率与饥饿时间成对数函数关系。在饥饿后均会发生补偿生长。3.1比较研究结果，表明在适当时间饥饿后的个体均会发生补偿生长，其超生长速度与饥饿时间密切相关。花鲈在饥饿至不可恢复点的临界状态时发生最强烈的超生长现象，而褐牙鲆则是在饥饿3—5d后恢复投喂时可以观测到最高速度的超生长。3.2经受适当时间饥饿后的个体在短期内，其摄食率大于对照组的摄食强度。曾经饥饿的时间越长，花鲈在饥饿结束后的摄食率越高，褐牙鲆在饥饿结束后的高摄食率持续的时间越长。3.3经受适当时间饥饿后的个体，在短期内的转化率均会大于对照组的转化 效率，且随饥饿时间而加强；高转化效率持续的时间与饥饿时间无关。褐牙鲆的高转化率持续的时间很短，且很快下降至低于对照组的水平，其下降程度与饥饿时问成正相关，经受过度饥饿的花鲈和褐牙鲆转化率显著低于对照组。3．4花鲈的补偿生长是饵料转化率提高的结果；而褐牙鲆的补偿生长的原因则因其经受的饥饿程度而异。从饥饿后恢复投喂较短的时间周期(4d和6d)看，花鲈和褐牙鲆的补偿生长是转化率和摄食率共同提高的结果；但从饥饿后恢复投喂较长的时问周期(12d和1 8d)看，经受短期(4-8d)饥饿的花鲈的补偿生长是转化率显著提高的结果，而经受长期(12d)饥饿的花鲈的补偿生长是转化率显著提高的结果，褐牙鲆则是摄食率显著提高的结果。3．5从整个实验周期来看，对花鲈的饥饿降低了其生长速度和饵料转化率，但对褐牙鲆的短期饥饿(<8d)不会降低其生长速度，也不会影响一定时间(3-13d)饥饿的个体的饵料转化率。

高山植物扁蕾的延迟自交机制

扁蕾（Gentianopsis barbata）具有鲜艳的花和显著的腺体，并且花开放的前5d柱头和花药始终处于不同的位置（雌雄异位），这些花综合征表明该植物应为异花传粉。为检验这一假设，我们对青藏高原植物扁蕾的海北站种群进行了3年的传粉生物学研究实验。与花综合征所表明的繁育系统相反，两年的野外观察发现昆虫的访花频率十分低，不去雄并隔离昆虫处理也能产生大量种子，说明这一种群的繁殖主要是依赖于白花传粉。尽管利用种子结实评价的柱头可授性从花开放4d后开始下降，但随着花的发育进程，雄蕊的伸长能使得花药与柱头完全接触。实验也证明，柱头可授性和花粉活力都超过5d，说明花药和柱头的接触能够发生白花授粉。扁蕾的这种白花传粉机制应属于典型的延迟自交类型。白花授粉发生在单花花期快要结束前，自交之前仍然保持异交传粉机制，这种延迟自交避免了自交与异交竞争造成的花粉或者种子折损，并为扁蕾在青藏高原极端环境下由于访花昆虫缺乏造成的异交失败提供了繁殖保障。

青海小叶杨物候变化及其对气候变化的响应

以青海省4个农气观测站的小叶杨物候期及气候资料，分析了小叶杨物候期变化及其对气候变化的响应。结果表明：小叶杨呈现出近10多年来树木绿叶期延长的趋势，但物候的早晚存在着明显的地域性差异；小叶杨物候对气温变化的反应比较敏感，上年9月至当年4月的平均气温升高1℃，小叶杨平均叶芽开放期提早5d，展叶普期提早4d，开花始期提早4d；上年9月至当年6月的平均气温升高1℃，平均种子成熟提早3d左右；上年9月至当年8月的平均气温升高1℃，平均叶全变色期约推迟4—5d，树木绿叶期延长12d；但小叶杨物候对降水的响应不明显，对日照时数变化的响应各地不一。

胜坨油田注聚后油藏动态模型及剩余油分布

The topic of Dynamic reservoir model and the distribution of remaining oil after polymer injection of Shengtuo oilfield is a front problem of "the 11th Five-Year Plan" scientific and technological disciplines of Sinopec Corporation. Reservoirs in study area is distributary channel sandstone. After 34 years of water-injection exploitation and 7 years of polymer injection pilot experiments, a highly complex heterogeneous dynamic evolution has been occurred in macro and micro parameters of reservoir model, together with its flow field. Therefore, it’s essential to construct completed reservoir dynamic model for a successfully prediction of the distribution of remaining oil. With a comprehensive application of multidisciplinary theory and technique, using a variety of data and information to maximize the use of computer technology, combining a static and dynamic, macro and micro and 1~4D integration, the research reveals main features, evolution and mechanism, types of geological disasters and their destructivity of reservoir flow field, the macro field, the micro field, the flow field and reservoir development hydrodynamic geological function in different development periods after a long term of polymer injection in Es2 in Shengtuo oilfield. The principle innovation achievements obtained are: 1. Established A, B, C, D four flow units in target formations, revealed the various features and distribution of flow units. 2. Stated environmental pollution and geological disasters induced during oilfield exploitation in study area, and also explained their formation mechanism, controlling factors, destructivity and approaches to disaster reduction. 3. Established dynamic evolution of the macro parameter model, micro-matrix field, pore network field, clay minerals field, seepage dynamic evolution model of six different exploitation stages in study area, also revealed reservoir flow evolution, the law of evolution mechanism after polymer injection. 4. Established macro and micro distribution model of remaining oil after three mining polymer injection during different water cut periods in study area, revealed the formation mechanism and distribution of remaining oil. 5. Established remaining oilforecasting model in study area, and forecasted the formation and distribution of remaining oil in the following six years. 6. It is proposed that reservoir fluid dynamic geological processes are major driving forces for the evolution of different water cut periods, reservoir macro field after the polymer injection and micro seepage field. 7. Established a dynamic reservoir model, proposed matching theory, methods and technology for the description of the remaining oil characterization and prediction, which can deepen the theory and techniques of continental rift basin development geology. Key words: Polymer reservoir; Geological disasters; Dynamic model; Residual oil forecast

高含水油藏复合驱剩油分布研究-以羊三木油田馆陶组油藏复合驱为例

Based on the study of the combined flooding test block of Guantao formation in Third faulted block of Yangsanmu oil field, this paper carries out the integration of reservoir precise characterization for very high water cut reservoir, establishes precise 3D geologic model for high water cut development period and states the changing law of the reservoir architecture dtiring development by combined flooding. Then, by subdivided the thick oil reservoir, the study of remaining oil saturation monitoring in fiber glass cased well and tracer monitoring is developed. According the study of multiple constrained combined flooding reservoir numerical simulation, remaining oil distribution are predicted, the methods architecture of predicting remaining oil distribution are established for fluvial facies reservoir at late development stage, develops plan is designed and adjustment associating technologies for enhancing oil recovery. On these base, related measures for tapping the potential are given, it is verified and optimized through the field former test and the good economic effect is achieved . The major achievements of this paper are as follows. The changing law of the reservoir architecture and it's property parameters is revealed, The result indicates that the temperature-pressure of the injecting material and the interaction effect of the injecting material and reservoir petrography are the main factors of the dynamic changes of the reservoir architecture. The quantitative reservoir geologic model, which is tallied with dynamic reservoir parameters of the study area, is established. Subdivided the thick oil reservoir is very important for the study of the remaining oil distribution within the thick oil reservoir. Subdivided the thick oil reservoir technology, which consists of six technologies as follow: micro-cyclic divided, flow unit method, architectural element method, high resolution log technology, high resolution-process technology for normal logging data and using the production data is presented. 3. It is established dynamic monitoring system of remaining oil saturation quantitative research which are inner and interlayer remaining oil saturation from time-lapse logging in fiber glass cased well, inter-well remaining oil saturation from the technology of isotopic tracer monitoring technology, and 4d remaining oil saturation distribution from combined flooding numerical modeling integrated by production datao The forming mechanism of remaining oil for polymer flooding and alkali/polymer combined flooding is clarified, and the plane and vertical distribution law of remaining oil after combined flooding is revealed. Predicting methods and technologies for the combined flooding reservoir of fluvial facies is developed. Combined flooding has been achieved good displacement result in the pilot of Third fault block in Yangsanmu oil field, and accumulated types of important parameters and optimum plans, this technology of combined flooding is expected to increase recovery ratio by 4.77%.

胜坨油田沙二段油藏流场剩余油形成机理和分布模式

By applying multi-discipline theory and methods comprehensively and with full use of computer, the paper deeps into studying changing rule and control factor of fluid field of ES2 Shengtuo oil field during waterflood development, physical and chemical function, and stress. Matrix field, network field, fluid field, stress field and physical chemistry field and fluid model for dynamic function were established. Macroscopic and microscopic genesis mechanics, distribution rule and control factor of remaining oil were revealed. Remaining oil and emulate model were established. Macroscopic and microscopic distribution rule of mover remaining oil were predicted, several results were achieved as following: The distribution of remaining oil was controlled by micro-structure. At the same development stage, remaining oil saturation of the wells located in higher position of micro-structure is higher than the average saturation in the same layer. The water content ratio has same law. It is the enrichment district that the high position of micro-structure controlled by seal faults. The remaining oil distribution was affected by sedimentary micro-facies, micro-structure, fault sealing, reservoir heterogeneity and affusion-oil extraction. On the plane, the zone owning higher saturation of remaining oil is the area that at the edge miacro-facies and sand-body distribution discontinuously; on the section, the content of waterflood of the upper or middle-upper oil layer of positive rhythm and positive comprehensive rhythm is lower, middle and weak waterflood is main, remaining oil is in enrichment relatively. The remaining oil is relative enrichment at the zones of well network of affusion and oil extraction not affected. 4D dynamic model of reservoir of Es2in Shengtuo oil field was established. Macroscopic and microscopic forming mechanics, distribution rule and control factor were revealed. The emulate model of dynamic function of Shengtuo oil field was established, the space distribution of remaining oil were predicted. Reservoir flow field, matrix field, network field, seep field, physical and chemical field, stress field and fluid field models were established. Reservoir flow field character and distribution were revealed. An improvement of the development geology theory in continental fault depression continental basin was brought on.

文33块沙二下段油藏动态模型及剩余油预测

By applying synthetically multi-subject theories, methods and technology, such as petroleum geology, sedimentology, seep mechanics, geochemistry, geophysics and so on; and by making full use of computer; combining quantity and quality, macroscopic and microscopic, intensive static and active description, comprehensive studying and physical modeling, 3 dimension and 4 dimension description; the paper took Wen-33 block of Zhongyuan oil field as an example; and studied reservoir macroscopic and microscopic parameter changing rule and evolve mechanics in different water-blood stage. The reservoir dynamic model and remaining-oil distribution mode was established, and several results were achieved as follows: (1) Three types of parameter gaining, optimizing and whole data body of Wen33th reservoir were established. Strata framework, structure framework, reservoir types and distribution of Wen33th reservoir were discussed. Reservoir genesis types, space distribution law and evolve rule of Wen33th reservoir were explained. 4D dynamic model of macroscopic parameter of reservoir flow dynamic geologic function of Wen33th reservoir was established. The macroscopic remaining-oil distribution and control factor was revealed. The models of the microscopic matrix field, pore-throat network field, fluid field, clay mineral field of Wen-33 block were established. The characters, changing rules and controlled factors in different water stage were revealed. The evolve rule and mechanics of petroleum fluid field in Wen-33 block reservoir were revealed. Macroscopic and microscopic remaining oil distribution mode of Wen-33 block were established. Seven types, namely 12 shapes of dynamic model of microscopic remaining oil were discussed, and the distribution of mover remaining oil was predicted. Emulation model: mathematical model and prediction model of Wen-33 block were established. The changing mechanics of reservoir parameter and distribution of remaining-oil were predicted. Firstly, the paper putting forward that the dynamic geologic function of petroleum development is the factor of controlling remaining-oil, which is the main factor leading to matrix field, network field, clay mineral field, fluid field, physic and chemical field, stress field and fluid field forming and evolving. (10) A set of theories, methods and technologies of investigating, describing, characterizing and predicting complex fault-block petroleum were developed.

可见光响应光催化剂K4Ce2M10O30（M=Ta, Nb）及其光解水特性的研究

氢能已被广泛认为是最具有潜力解决能源危机和环境问题的理想替代能源之一，其开发备受各个领域科学家的重视，更是从根本上解决环境地球化学工作者的主要目标：对已被破坏的环境和生态进行修复以及对可能破坏环境与生态的人类活动进行干预和指导。在众多的氢能开发手段中，利用太阳能光催化分解水制取氢气是一种兼顾能耗、资源和环境的最为理想和最有前途的氢能开发手段之一。在光催化分解水过程中，最为首要的研究内容就是开发具有适宜能带结构能响应可见光，稳定地、高量子效率地光解水的固相半导体光催化剂。 本论文中，通过高温固相反应合成了呈四方晶系钨青铜结构的半导体光催化剂K4Ce2M10O30(M=Ta, Nb)，吸收边分别达到580 nm (M＝Ta) 和690 nm (M＝Nb)，对应带隙为2.2 eV和1.8 eV。可见光下（λ> 420 nm）光催化分解H2O产生H2和O2的活性表明它们不仅有适宜的带隙响应可见光，并且其价带和导带位置能满足完全分解水的电化学电位需要。在担载Pt、RuO2以及NiO（NiOx）等助催化剂对产氢性能有显著的提高。同时以乙醇钽和草酸铌可溶性前驱体，分别通过溶胶凝胶法（Sol-gel）和聚合物络合法(Polymerizable Complex)制备了K4Ce2Ta10O30和K4Ce2Nb10O30。通过湿法化学合成的光催化剂显示了更高的光催化活性，并且通过PC法制备的K4Ce2Nb10O30更是实现了在大于300 nm 的光辐射下完全分解纯水产生摩尔比为约2:1 的H2和O2。 通过高温固相反应得到Nb取代K4Ce2Ta10O30中部分晶格Ta形成的单相无限固溶体系列K4Ce2Ta10-xNbxO30（x=0~10）是结构一致的同系物，吸收边介于540 nm～710 nm 之间，并且随着x的增加，吸收边依次红移，光催化产氢活性依次降低，但是x=2，5，8时的产氧活性比x=0和10的高，光催化活性的差异主要源于它们光吸收特性和能带结构的差异。基于密度范函理论DFT的第一性原理计算结果表明，光催化剂K4Ce2M10O30(M=Ta, Nb)的能带结构为：导带主要由Ta 5d (Nb 4d)组成，处于高能级的电子未占据态的Ce 4f 与其有很明显的重迭，但由于其高度局域特性，不能很好地参与光生电子在导带的传导，从而其对光催化活性的贡献很小，而价带则由O 2p与Ta 5d (Nb 4d)以及电子占据态的Ce 4f杂化轨道组成。同时通过高温固相反应合成了系列含稀土元素的光催化剂K4Re2M10O30(Re=La, Ce, Nd, Sm, Y; M=Ta, Nb)，通过对它们及其前驱体氧化物的光吸收特性以及电子结构的第一性原理计算研究，合理的解释了只有当Ln＝Ce时才具有可见光响应特性的微观机理。

8～12岁男孩的性激素与智力、人格的关系

Recently there emerged more and more researhes concerning about sex hormone-related cognitive ability and behaviours. Few were carried out in pre- to early adolescent children., and the objective of the current study is to investigate whether there are covariance between sex hormones, intelligence and personality in 232 pre- to early adolescent boys, including 62 gifted boys. Indexes of sex hormone levels were salivary testosterone and estradiol concentrations, the 2D:4D digit ratio ( a reliable pointer of prenatal sex hormone concentraions). The Cattell Culture Fair Intelligence Test and a Chinese version of Children’s Personality Questionaire was applied in the current study. The main findings are: 1) salivary sex hormone concentrations significantly positively correlated with intelligence performance in 10-year-old boys; 2) salivary testosterone negatively related to intelligence performance in 12-year-old boys; 3) gifted boys bears lower testosterone concentrations in both prenatal period and pre- to early adolescence; 4) for personality, higher salivary estradiol was related to extraversion and digit ratios correlated with several personality factors in 8-year-old boys. In conclusion, results in the current study suggested that for male early maturers, intelligence may be negatively influenced by early coming androgen surge. In contrast, male late matures may benefit from their lately and moderately increasing hormone. Besides, the results suggested that the relationship between 2D:4D digit ratio and personality may also be paid attention to.

Synthesis and structural characterization of (pyrazolyl)alkenyl Fischer carbene complexes of chromium and tungsten

Michael addition of substituted pyrazoles 2 to 1-alkynyl Fischer carbene complexes (CO)(5)M=C(OEt)(CdropCPh) (1) (a, M = Cr and b M = W) afforded (pyrazolyl)alkenyl Fischer carbene complexes (CO)(5)M=C(OEt)(CH=C(R(1)R(2)R(3)pz)Ph) (R(1)R(2)R(3)pz = pyrazolyl) 3 (M = Cr) and 4 (M = W), respectively, with an exclusive (E)-configuration in mild to excellent yields. The reaction of la and 3,5-dimethylpyrazole (2b) was monitored to demonstrate the formation and decomposition of complex 3b by H-1 NMR measurements in CDCl3 at 23degreesC. Complexes 3 and 4 were characterized with H-1, C-13{H-1} NMR, IR spectroscopies and elemental analysis. When the substituted pyrazoles were 3-methylpyrazole (2a) and 3,5-di-tert-butylpyrazole (2d), molecular structures of the corresponding (pyrazolyl)alkenyl Fischer carbene complexes 3a and 4d were characterized by X-ray crystallographic study. (C) 2004 Elsevier Ltd. All rights reserved.

Imaging through turbulence using compressive coherence sensing.

Previous studies have shown that the isoplanatic distortion due to turbulence and the image of a remote object may be jointly estimated from the 4D mutual intensity across an aperture. This Letter shows that decompressive inference on a 2D slice of the 4D mutual intensity, as measured by a rotational shear interferometer, is sufficient for estimation of sparse objects imaged through turbulence. The 2D slice is processed using an iterative algorithm that alternates between estimating the sparse objects and estimating the turbulence-induced phase screen. This approach may enable new systems that infer object properties through turbulence without exhaustive sampling of coherence functions.

Magnetic Resonance Imaging Biomarkers of Renal Structure and Function

The kidney's major role in filtration depends on its high blood flow, concentrating mechanisms, and biochemical activation. The kidney's greatest strengths also lead to vulnerability for drug-induced nephrotoxicity and other renal injuries. The current standard to diagnose renal injuries is with a percutaneous renal biopsy, which can be biased and insufficient. In one particular case, biopsy of a kidney with renal cell carcinoma can actually initiate metastasis. Tools that are sensitive and specific to detect renal disease early are essential, especially noninvasive diagnostic imaging. While other imaging modalities (ultrasound and x-ray/CT) have their unique advantages and disadvantages, MRI has superb soft tissue contrast without ionizing radiation. More importantly, there is a richness of contrast mechanisms in MRI that has yet to be explored and applied to study renal disease.

The focus of this work is to advance preclinical imaging tools to study the structure and function of the renal system. Studies were conducted in normal and disease models to understand general renal physiology as well as pathophysiology. This dissertation is separated into two parts--the first is the identification of renal architecture with ex vivo MRI; the second is the characterization of renal dynamics and function with in vivo MRI. High resolution ex vivo imaging provided several opportunities including: 1) identification of fine renal structures, 2) implementation of different contrast mechanisms with several pulse sequences and reconstruction methods, 3) development of image-processing tools to extract regions and structures, and 4) understanding of the nephron structures that create MR contrast and that are important for renal physiology. The ex vivo studies allowed for understanding and translation to in vivo studies. While the structure of this dissertation is organized by individual projects, the goal is singular: to develop magnetic resonance imaging biomarkers for renal system.

The work presented here includes three ex vivo studies and two in vivo studies:

1) Magnetic resonance histology of age-related nephropathy in sprague dawley.

2) Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice.

3) Susceptibility tensor imaging of the kidney and its microstructural underpinnings.

4) 4D MRI of renal function in the developing mouse.

5) 4D MRI of polycystic kidneys in rapamycin treated Glis3-deficient mice.

On-board Robotic Multi-pinhole SPECT System for Region-of-interest (ROI) Imaging

On-board image guidance, such as cone-beam CT (CBCT) and kV/MV 2D imaging, is essential in many radiation therapy procedures, such as intensity modulated radiotherapy (IMRT) and stereotactic body radiation therapy (SBRT). These imaging techniques provide predominantly anatomical information for treatment planning and target localization. Recently, studies have shown that treatment planning based on functional and molecular information about the tumor and surrounding tissue could potentially improve the effectiveness of radiation therapy. However, current on-board imaging systems are limited in their functional and molecular imaging capability. Single Photon Emission Computed Tomography (SPECT) is a candidate to achieve on-board functional and molecular imaging. Traditional SPECT systems typically take 20 minutes or more for a scan, which is too long for on-board imaging. A robotic multi-pinhole SPECT system was proposed in this dissertation to provide shorter imaging time by using a robotic arm to maneuver the multi-pinhole SPECT system around the patient in position for radiation therapy.

A 49-pinhole collimated SPECT detector and its shielding were designed and simulated in this work using the computer-aided design (CAD) software. The trajectories of robotic arm about the patient, treatment table and gantry in the radiation therapy room and several detector assemblies such as parallel holes, single pinhole and 49 pinholes collimated detector were investigated. The rail mounted system was designed to enable a full range of detector positions and orientations to various crucial treatment sites including head and torso, while avoiding collision with linear accelerator (LINAC), patient table and patient.

An alignment method was developed in this work to calibrate the on-board robotic SPECT to the LINAC coordinate frame and to the coordinate frames of other on-board imaging systems such as CBCT. This alignment method utilizes line sources and one pinhole projection of these line sources. The model consists of multiple alignment parameters which maps line sources in 3-dimensional (3D) space to their 2-dimensional (2D) projections on the SPECT detector. Computer-simulation studies and experimental evaluations were performed as a function of number of line sources, Radon transform accuracy, finite line-source width, intrinsic camera resolution, Poisson noise and acquisition geometry. In computer-simulation studies, when there was no error in determining angles (α) and offsets (ρ) of the measured projections, the six alignment parameters (3 translational and 3 rotational) were estimated perfectly using three line sources. When angles (α) and offsets (ρ) were provided by Radon transform, the estimation accuracy was reduced. The estimation error was associated with rounding errors of Radon transform, finite line-source width, Poisson noise, number of line sources, intrinsic camera resolution and detector acquisition geometry. The estimation accuracy was significantly improved by using 4 line sources rather than 3 and also by using thinner line-source projections (obtained by better intrinsic detector resolution). With 5 line sources, median errors were 0.2 mm for the detector translations, 0.7 mm for the detector radius of rotation, and less than 0.5° for detector rotation, tilt and twist. In experimental evaluations, average errors relative to a different, independent registration technique were about 1.8 mm for detector translations, 1.1 mm for the detector radius of rotation (ROR), 0.5° and 0.4° for detector rotation and tilt, respectively, and 1.2° for detector twist.

Simulation studies were performed to investigate the improvement of imaging sensitivity and accuracy of hot sphere localization for breast imaging of patients in prone position. A 3D XCAT phantom was simulated in the prone position with nine hot spheres of 10 mm diameter added in the left breast. A no-treatment-table case and two commercial prone breast boards, 7 and 24 cm thick, were simulated. Different pinhole focal lengths were assessed for root-mean-square-error (RMSE). The pinhole focal lengths resulting in the lowest RMSE values were 12 cm, 18 cm and 21 cm for no table, thin board, and thick board, respectively. In both no table and thin board cases, all 9 hot spheres were easily visualized above background with 4-minute scans utilizing the 49-pinhole SPECT system while seven of nine hot spheres were visible with the thick board. In comparison with parallel-hole system, our 49-pinhole system shows reduction in noise and bias under these simulation cases. These results correspond to smaller radii of rotation for no-table case and thinner prone board. Similarly, localization accuracy with the 49-pinhole system was significantly better than with the parallel-hole system for both the thin and thick prone boards. Median localization errors for the 49-pinhole system with the thin board were less than 3 mm for 5 of 9 hot spheres, and less than 6 mm for the other 4 hot spheres. Median localization errors of 49-pinhole system with the thick board were less than 4 mm for 5 of 9 hot spheres, and less than 8 mm for the other 4 hot spheres.

Besides prone breast imaging, respiratory-gated region-of-interest (ROI) imaging of lung tumor was also investigated. A simulation study was conducted on the potential of multi-pinhole, region-of-interest (ROI) SPECT to alleviate noise effects associated with respiratory-gated SPECT imaging of the thorax. Two 4D XCAT digital phantoms were constructed, with either a 10 mm or 20 mm diameter tumor added in the right lung. The maximum diaphragm motion was 2 cm (for 10 mm tumor) or 4 cm (for 20 mm tumor) in superior-inferior direction and 1.2 cm in anterior-posterior direction. Projections were simulated with a 4-minute acquisition time (40 seconds per each of 6 gates) using either the ROI SPECT system (49-pinhole) or reference single and dual conventional broad cross-section, parallel-hole collimated SPECT. The SPECT images were reconstructed using OSEM with up to 6 iterations. Images were evaluated as a function of gate by profiles, noise versus bias curves, and a numerical observer performing a forced-choice localization task. Even for the 20 mm tumor, the 49-pinhole imaging ROI was found sufficient to encompass fully usual clinical ranges of diaphragm motion. Averaged over the 6 gates, noise at iteration 6 of 49-pinhole ROI imaging (10.9 µCi/ml) was approximately comparable to noise at iteration 2 of the two dual and single parallel-hole, broad cross-section systems (12.4 µCi/ml and 13.8 µCi/ml, respectively). Corresponding biases were much lower for the 49-pinhole ROI system (3.8 µCi/ml), versus 6.2 µCi/ml and 6.5 µCi/ml for the dual and single parallel-hole systems, respectively. Median localization errors averaged over 6 gates, for the 10 mm and 20 mm tumors respectively, were 1.6 mm and 0.5 mm using the ROI imaging system and 6.6 mm and 2.3 mm using the dual parallel-hole, broad cross-section system. The results demonstrate substantially improved imaging via ROI methods. One important application may be gated imaging of patients in position for radiation therapy.

A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150-L110 robot). An imaging study was performed with a phantom (PET CT PhantomTM), which includes 5 spheres of 10, 13, 17, 22 and 28 mm in diameter. The phantom was placed on a flat-top couch. SPECT projections were acquired with a parallel-hole collimator and a single-pinhole collimator both without background in the phantom, and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180 degrees and 228 degrees respectively. The pinhole detector viewed a 14.7 cm-diameter common volume which encompassed the 28 mm and 22 mm spheres. The common volume for parallel-hole was a 20.8-cm-diameter cylinder which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the flat-top table while avoiding collision with the table and maintaining the closest possible proximity to the common volume. For image reconstruction, detector trajectories were described by radius-of-rotation and detector rotation angle θ. These reconstruction parameters were obtained from the robot base and tool coordinates. The robotic SPECT system was able to maneuver the parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector to center-of-rotation (COR) distance. In no background case, all five spheres were visible in the reconstructed parallel-hole and pinhole images. In with background case, three spheres of 17, 22 and 28 mm diameter were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameter) were readily observed in the pinhole ROI imaging.

In conclusion, the proposed on-board robotic SPECT can be aligned to LINAC/CBCT with a single pinhole projection of the line-source phantom. Alignment parameters can be estimated using one pinhole projection of line sources. This alignment method may be important for multi-pinhole SPECT, where relative pinhole alignment may vary during rotation. For single pinhole and multi-pinhole SPECT imaging onboard radiation therapy machines, the method could provide alignment of SPECT coordinates with those of CBCT and the LINAC. In simulation studies of prone breast imaging and respiratory-gated lung imaging, the 49-pinhole detector showed better tumor contrast recovery and localization in a 4-minute scan compared to parallel-hole detector. On-board SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frames could be an effective means to estimate detector pose for use in SPECT image reconstruction.

A LabVIEW Platform for Preclinical Imaging Using Digital Subtraction Angiography and Micro-CT.

CT and digital subtraction angiography (DSA) are ubiquitous in the clinic. Their preclinical equivalents are valuable imaging methods for studying disease models and treatment. We have developed a dual source/detector X-ray imaging system that we have used for both micro-CT and DSA studies in rodents. The control of such a complex imaging system requires substantial software development for which we use the graphical language LabVIEW (National Instruments, Austin, TX, USA). This paper focuses on a LabVIEW platform that we have developed to enable anatomical and functional imaging with micro-CT and DSA. Our LabVIEW applications integrate and control all the elements of our system including a dual source/detector X-ray system, a mechanical ventilator, a physiological monitor, and a power microinjector for the vascular delivery of X-ray contrast agents. Various applications allow cardiac- and respiratory-gated acquisitions for both DSA and micro-CT studies. Our results illustrate the application of DSA for cardiopulmonary studies and vascular imaging of the liver and coronary arteries. We also show how DSA can be used for functional imaging of the kidney. Finally, the power of 4D micro-CT imaging using both prospective and retrospective gating is shown for cardiac imaging.