BACKGROUND:A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington's disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements.RESULTS:Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey.CONCLUSIONS:This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.

Considering the unsatisfying approximation result of dynamic nearest neighbor clustering algorithm when center is selected improper and hidden layer nodes are fewer,an approach that improved dynamic nearest neighbor clustering algorithm is used to construct RBF neural network(IDARBF neural networks) is raised,which calibrates the sensor's output characteristic and effectively overcomes the problems in the original algorithm.An experimental result shows that IDARBF neural network has a better ability of non-linear correction,and the performance of sensor significantly is improved after the improved dynamic nearest neighbor clustering algorithm is used.Invisible injury rate is 100% tested and the detection efficiency of 128 / minute.

Noninvasive monitoring of blood flow in retinal circulation will reveal the progression and treatment of ocular disorders, such as diabetic retinopathy, age-related macular degeneration and glaucoma. A non-invasive and direct BF measurement technique with high spatial-temporal resolution is needed for retinal imaging. Laser speckle imaging (LSI) is such a method. Currently, there are two analysis methods for LSI: spatial statistics LSI (SS-LSI) and temporal statistical LSI (TS-LSI). Comparing these two analysis methods, SS-LSI has higher signal to noise ratio (SNR) and TS-LSI is less susceptible to artifacts from stationary speckle. We proposed a hybrid temporal and spatial analysis method (HTS-LSI) to measure the retinal blood flow. Gas challenge experiment was performed and images were analyzed by HTS-LSI. Results showed that HTS-LSI can not only remove the stationary speckle but also increase the SNR. Under 100% O-2, retinal BF decreased by 20-30%. This was consistent with the results observed with laser Doppler technique. As retinal blood flow is a critical physiological parameter and its perturbation has been implicated in the early stages of many retinal diseases, HTS-LSI will be an efficient method in early detection of retina diseases.

Temporal-statistical analysis of laser-speckle image (TS-LSI) preserves the original spatial resolution, in contrast to conventional spatial-statistical analysis (SS-LSI). Concerns have been raised regarding the temporal independency of TS-LSI signals and its insensitivity toward stationary-speckle contamination. Our results from flow phantoms and in vivo rat retinas demonstrated that the TS-LSI signals are temporally statistically independent and TS-LSI minimizes stationary-speckle contamination. The latter is because the stationary speckle is "non-random" and thus non-ergodic where the temporal average of stationary speckle needs not equal its spatial ensemble average. TS-LSI detects blood flow in smaller blood vessels and is less susceptible to stationary-speckle artifacts.

Most retinal imaging has been performed using optical techniques. This paper reviews alternative retinal imaging methods based on MRI performed with spatial resolution sufficient to resolve multiple well-defined retinal layers. The development of these MRI technologies to study retinal anatomy, physiology (blood flow, blood volume, and oxygenation) and function, and their applications to the study of normal retinas, retinal degeneration and diabetic retinopathy in animal models are discussed. Although the spatiotemporal resolution of MRI is poorer than that of optical imaging techniques, it is unhampered by media opacity and can thus image all retinal and pararetinal structures, and has the potential to provide multiple unique clinically relevant data in a single setting and could thus complement existing retinal imaging techniques. In turn, the highly structured retina with well-defined layers is an excellent model for advancing emerging high-resolution anatomical, physiological and functional MRI technologies. Copyright (C) 2008 John Wiley & Sons. Ltd.

Laser speckle imaging (LSI) is widely used to study blood flow at high spatiotemporal resolution. Several papers recently pointed out that the commonly used LSI equation involves an approximation that could result in incorrect data analysis. We investigated the impact of such an approximation and introduced a simplified analysis method to improve computation time. Flow phantom studies were performed for validation. Moreover, we demonstrated a novel LSI application by imaging blood flow of rat retinas under normal and physiologic-challenge conditions. Because blood-flow abnormality is implicated in many retinal diseases, LSI could provide valuable physiologic, and potentially diagnostic, information.

PURPOSE This study aims to investigate quantitative basal blood flow as well as hypercapnia- and hyperoxia-induced blood flow changes in the retinas of the Royal College of Surgeons (RCS) rats with spontaneous retinal degeneration, and to compare with those of normal rat retinas. METHODS Experiments were performed on male RCS rats at post-natal days P90 (n=4) and P220 (n=5), and on age-matched controls at P90 (n=7) and P220 (n=6). Hyperoxic (100% O(2)) and hypercapnic (5% CO(2), 21% O(2), balance N(2)) challenges were used to modulate blood flow. Quantitative baseline blood flow, and hypercapnia- and hyperoxia-induced blood flow changes in the retinas were imaged using continuous arterial spin labeling MRI at 90 x 90 x 1500 microm. RESULTS In the normal rat retinas, basal blood flow of the whole-retina was 5.5 mL/gram per min, significantly higher than those reported in the brain (approximately 1 mL/gram per min). Hyperoxia decreased blood flow due to vasoconstriction and hypercapnia increased blood flow due to vasodilation in the normal retinas. In the RCS rat retinas, basal blood flow was diminished significantly (P<0.05). Interestingly, absolute hyperoxia- and hypercapnia-induced blood flow changes in the RCS retinas were not statistically different from those in the normal retinas (P>0.05). However, blood flow percent changes in RCS retinas were significantly larger than in normal retinas due to lower basal blood flow in the RCS retinas. CONCLUSIONS Retinal degeneration markedly reduces basal blood flow but does not appear to impair vascular reactivity. These data also suggest caution when interpreting relative stimulus-evoked functional MRI changes in diseased states where basal parameters are significantly perturbed. Quantitative blood flow MRI may serve as a valuable tool to study the retina without depth limitation.

MRI is a noninvasive diagnostic modality that reveals anatomy, physiology, and function in vivo without depth limitation or optical interference. MRI application to the retina, however, remains challenging. We improved spatial resolution to resolve layer-specific structure and functional responses in the retina and confirmed the laminar resolution in an established animal model of retinal degeneration. Structural MRI of normal rat retinas revealed three bands corresponding histologically to (i) the combined ganglion cell layer/inner nuclear layer plus the embedded retinal vessels, (ii) the avascular outer nuclear (photoreceptor) layer and its photoreceptor segments, and (iii) the choroidal vascular layer. Imaging with an intravascular contrast agent (gadolinium-diethylene-tri-amine-pentaacetic acid) enhanced the retinal and choroidal vascular layers bounding the retina, but not the avascular outer nuclear layer and the vitreous. Similarly, blood-oxygen-level-dependent (BOLD) functional MRI revealed layer-specific responses to hyperoxia and hypercapnia. Importantly, layer-specific BOLD responses in the two vascular layers were divergent, suggesting the two vasculatures are differentially regulated. To corroborate sensitivity and specificity, we applied layer-specific MRI to document photoreceptor degeneration in Royal College of Surgeons rats. Consistent with histology, layer-specific MRI detected degeneration of the outer nuclear layer. Surprisingly, MRI revealed increased thickness in the choroidal vascular layer and diminished BOLD responses to hyperoxia and hypercapnia in the Royal College of Surgeons rat retinas, suggesting perturbation of vascular reactivity secondary to photoreceptor loss. We conclude that MRI is a powerful investigative tool capable of resolving lamina-specific structures and functional responses in the retina as well as probing lamina-specific changes in retinal diseases.

建立了一套激光散斑成像系统 ,对该成像系统的性能参数进行了分析 ,并利用该系统对区域性的流速分布进行监测 ,结果表明 ,该系统能在不需扫描的情况下对区域性的流速分布进行有效监测 ,具有较高的时间分辨率 （2 5 m s）和空间分辨率（取决于系统的放大倍数 ,可达几个 μm） ,对较慢的速度变化敏感。该系统为监测区域性流速分布提供了一种高时—空分辨率的实时动态手段

Monitoring the spatio-temporal characteristics of microcirculation is crucial for studying the functional activities of biotissue and the mechanism of disease. However, conventional methods used to measure blood flow suffer from limited spatial resolution or the injection of exogenous substances or the need of scanning to obtain the dynamic of regional blood flow. Laser speckle imaging (LSI) technique makes up these disadvantages by obtaining the regional blood flow distribution with high spatio-temporal resolution without the need to scan. In this paper, LSI was introduced to investigate the dynamic responses of the rat mesenteric microcirculation to an incremental dose of phentolamine. The results showed that when the dose of phentolamine was less than 4 microg ml(-1), local application of phentolamine on the mesentery would increase the blood perfusion as the concentration increased. When the dose increased further, the improvement decreased. At a dose of 200 microg ml(-1), a microcirculation impediment was caused. At the same time, different responses between veinules and arterioles were manifested. These suggested that LSI is promising to be a useful contribution to drug development and testing.

非损伤激光嫩肤技术作为一种很有前途的技术,它的优点是保护表皮不受损伤而刺激真皮胶原蛋白的再生,预防和治疗皮肤衰老,目前这种技术尚处于探索阶段.本文根据光源类型介绍了非损伤光嫩肤技术的最新进展,并探讨目前的研究热点和存在的难题,为进一步的研究提供参考.

We investigated the influence of a hyperosmotic agent (glycerol) on the normal physiological function of tissue by applying the glycerol in vitro and in vivo to rabbit dura mater to assess the changes in the tissue's optical properties. We used a laser speckle imaging technique to study the effect of epidurally applied glycerol on resting cerebral blood flow (CBF). Our results showed that resting CBF decreased as the transparency of the dura mater increased. The challenges for the design of an optical clearing technique were not only the clearing effects and the duration of the action of the chemical agents but also the influence of the glycerol on the tissue's normal physiological function.

采用激光散斑成像方法,监测了对去甲肾上腺素作用前后大鼠肠系膜上区域性的微循环血流变化。结果表明:在去甲肾上腺素作用下,3min后,肠系膜上微循环的血流逐渐减慢,小静脉比小动脉流减慢得更为明显,5min后部分血管中的血流开始恢复,小动脉恢复速度较快。这些提示,激光散斑成像方法在无需扫描的条件下,可同时获得肠系膜上区域性血流的时空间变化特性,为微循环研究提供一种对区域性流速变化进行监测的新方法。

The regional blood flow in the rat mesentery under the effect of noradrenalin is monitored using the laser speckle imaging method. The results show that at the third minute of application of noradrenalin, the blood flow begins to decrease, and the venule blood flow decreases more rapidly than that in the arteriole. Five minutes later blood flow in part of blood vessels begins to resume and the blood flow in the arteriole recovers more quickly than that in the venule. These suggest that laser speckle imaging can obtain the temporal-spatial characteristic of blood flow in mesentery without the need of scanning. It provides a new approach for investigating the change of regional blood flow in the mesentery in microcirculation studies.

We present a noninvasive full-field method--laser speckle imaging (LSI)--for measuring the regional mesenteric blood flow without scanning. A system of LSI was designed and validated in a model experiment. Dynamics of regional blood flow in the rat mesentery under the influence of noradrenaline were monitored by this method. Spatial and temporal characteristics of the mesenteric blood-flow response were achieved with high resolution. These suggested that LSI might provide a new approach to microcirculation studies.

A technique of monitoring the change of blood perfusion utilizing the principle of laser speckle technique combined with CCD imaging method was studied. A laser speckle measurement system of measuring the velocities of blood flow in rat's mesentery was designed in present paper. The parameter and precision of the system was testified by a model experiment. On this basis, the dynamic changes of the velocities of the blood flow in rat's mesentery under different temperatures were measured. Meanwhile, the diameter of blood vessels was measured with CCD camera. With these measurements, changes of blood perfusion by heat were studied. The results indicated that this system and method could be used to monitor the change of blood perfusion effectively. This work provides a new method to measure thermal induced change in blood perfusion of tissue.