Neurofibrillary tangles and plaques are not accompanied by white matter pathology in aged triple transgenic-Alzheimer disease mice

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aging populations. Although senile plaques and neurofibrillary tangles are well-established hallmarks of AD, changes in cerebral white matter correlate with cognitive decline and may increase the risk of the development of dementia. We used the triple transgenic (3xTg)-AD mouse model of AD, previously used to show that white matter changes precede plaque formation, to test the hypothesis that MRI detectable changes occur in the corpus callosum, external capsule and the fornix. T₂-weighted and diffusion tensor magnetic resonance imaging and histological stains were employed to assess white matter in older (11–17 months) 3xTg-AD mice and controls. We found no statistically significant changes in white matter between 3xTg-AD mice and controls, despite well-developed neurofibrillary tangles and beta amyloid immunoreactive plaques. Myelin staining was normal in affected mice. These data suggest that the 3xTg-AD mouse model does not develop MRI detectable white matter changes at the ages we examined.     

Polarimetric imaging of amyloid

New developments in optical microscopy are discussed with relevance to the imaging of amyloid plaques that are pathognomonic of a variety of degenerative disorders. We present the results of linear birefringence, linear dichroism, and circular dichroism imaging of Congo red stained plaques ex vivo and in vitro. A new technique for measuring rapid changes in linear anisotropies is introduced. The application of polarimetric imaging as demonstrated here can be extended to broader pathological practice since polarimetric measurements are sensitive to transformations in tissues that are specific disease signatures.     

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

Background  

The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss.     

Intravascular photoacoustic imaging of lipid in atherosclerotic plaques in the presence of luminal blood

Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.     

Simultaneous optical coherence tomography imaging and beta particle detection

A prototype hybrid catheter device designed for imaging and detection of vascular diseases is introduced. The prototype device integrates a high-resolution optical coherent tomography probe and a high-sensitivity beta detector into a single unit. With this prototype device we demonstrate the feasibility of simultaneous optical coherence tomography imaging and detection of beta particles.     

基于光声效应的深层组织选键成像 (cited: 1)

基于分子振动吸收的光声成像技术为生物组织的化学成像提供了一个新的平台．该技术在脊髓损伤、肿瘤、及心血管疾病的检测方面有广泛的应用前景．本文综述该技术的发展历史及其在生物医学中的应用．     

Time evolution of enhanced ultrasonic reflection using a fibrin-targeted nanoparticulate contrast agent

Complex molecular signaling heralds the early stages of pathologies such as angiogenesis, inflammation, unstable atherosclerotic plaques, and areas of remote thrombi. In previous studies, acoustic enhancement of blood clot morphology was demonstrated with the use of a nongaseous, fibrin-targeted acoustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this study, a system was designed and constructed that allows visualization of the evolution of acoustic contrast enhancement. To evaluate the system, two targets were examined: avidin-complexed nitrocellulose membrane and human plasma clots. The time evolution of enhancement was visualized in 10-min increments for 1 h. A monotonic increase was observed in ultrasonic reflection enhancement from specially treated nitrocellulose membranes for targeted emulsions containing perfluorooctylbromide (1.30+/-0.3 dB) and for perfluorooctane (2.64+/-0.5 dB) within the first 60 min of imaging. In comparison, the inherently nonechogenic plasma clots showed a substantial increase of 12.0+/-0.9 dB when targeted with a perfluoro-octane emulsion. This study demonstrates the concept of molecular imaging and provides the first quantifiable time-evolution report of the binding of a site-targeted ultrasonic contrast agent. Moreover, with the incorporation of specific drug treatments into the nanoparticulate contrast agent, ultrasonic molecular imaging may yield reliable detection and quantification of nascent pathologies and facilitate targeted drug therapy.     

早期乳腺肿瘤的超宽带微波稳健波束形成成像检测系统

提出了一种基于自主设计小型超宽带天线的微波稳健波束形成(RCB)成像肿瘤检测系统.仿真结果表明,该检测系统对肿瘤反射信号有很高的敏感度.在简单平面模型和核磁共振成像图(MRI)导出模型中进行仿真检测实验,并将天线阵列接收信号用RCB算法进行成像处理.从乳房重构图像中能够得到正确的肿瘤位置及大小信息,实现了平面模型中最小直径3 mm和MRI导出模型中最小直径4 mm的肿瘤检测,证实了该检测系统用于早期乳腺肿瘤检测的可行性.     

Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function

Background  

Neurodegeneration in Alzheimer's disease is associated with increased apoptosis and parallels increased levels of amyloid beta, which can induce neuronal apoptosis. Estrogen exposure prior to neurotoxic insult of hippocampal neurons promotes neuronal defence and survival against neurodegenerative insults including amyloid beta. Although all underlying molecular mechanisms of amyloid beta neurotoxicity remain undetermined, mitochondrial dysfunction, including altered calcium homeostasis and Bcl-2 expression, are involved in neurodegenerative vulnerability.     

Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing and periplaque white matter

Introduction

Diffusion tensor imaging (DTI) reveals white matter pathology in patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging technique, q-space imaging (QSI), may provide several advantages over conventional MRI techniques in regard to in vivo evaluation of the disease process in patients with MS. The purpose of this study is to investigate the use of root mean square displacement (RMSD) derived from QSI data to characterize plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM) in patients with MS.

Methods

We generated apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS patients; we generated RMSD maps by using QSI data from these patients. We used the Steel–Dwass test to compare the diffusion metrics of regions of interest in plaques, PWM, and NAWM.

Results

ADC differed (P < 0.05) between plaques and PWM and between plaques and NAWM. FA differed (P < 0.05) between plaques and NAWM. RMSD differed (P < 0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM.

Conclusion

RMSD values from QSI may reflect microstructural changes and white-matter damage in patients with MS with higher sensitivity than do conventional ADC and FA values.     

MRI-based biomechanical imaging: initial study on early plaque progression and vessel remodeling

The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomechanical imaging technique to address biomechanical pathways of atherosclerotic progression and regression in vivo using a 3D fluid-structure interaction (FSI) model. Initial in vivo study was carried out in an early plaque model in pigs that underwent balloon-overstretch injury to the left carotid arteries. Consecutive MRI scans were performed while the pigs were maintained on high cholesterol (progression) or normal chow (regression), with an injection of a plaque-targeted contrast agent, Gadofluorine M. At the end of study, the specimens of carotid arterial segments were dissected and underwent dedicated mechanical testing to determine their material properties. 3D FSI computational model was applied to calculate structure stress and strain distribution. The plaque structure resembles early plaque with thickened intima. Lower maximal flow shear stress correlates with the growth of plaque volume during progression, but not during regression. In contrast, maximal principle structure stress/stain (stress-P1 and strain-P1) were shown to correlate strongly with the change in the plaque dimension during regression, but moderately during progression. This MRI-based biomechanical imaging method may allow for noninvasive dynamic assessment of local hemodynamic forces on the development of atherosclerotic plaques in vivo.     

Visualization and Characterization of Atherosclerotic Plaques by Micro-MRI at 4.7 T In Vivo and 11.7 T Ex Vivo

The aim of this study was to evaluate the capability of using micro-magnetic resonance imaging (MRI) to visualize and characterize atherosclerotic plaques of mouse models. Twenty five apolipoprotein E-knockout mice were fed atherogenic diet, which enabled creation of aortic atherosclerotic plaques. Aortic plaques were examined in vivo by 4.7 T MRI and then characterized ex vivo by 11.7 T three-dimensional MRI. MR images were correlated with subsequent histological confirmation. In vivo 4.7-T MRI demonstrated unevenly thickened aortic walls due to formation of atherosclerotic plaques. Ex vivo 11.7-T MRI enabled not only to acquire full volume-rendered images of the entire vessels but also to characterize plaque components (such as lipid cores and fibrous caps) at any level and any projection, which were confirmed by histological correlation. Micro-MRI provides an excellent imaging tool for basic science to investigate atherosclerosis in small animal models, which may become a supplement to histopathology of atherosclerotic cardiovascular disease.     

超宽带微波检测早期乳腺肿瘤三维仿真

超宽带微波成像技术可作为有效的方法用于乳房早期乳腺肿瘤的检测. 该方法基于乳房组织和肿瘤之间较大的电学特性差异的特点进行成像, 能提供足够的分辨率以及足够的穿透深度. 本文采用时域有限差分方法建立超宽带微波信号在三维乳房组织中传播的模型, 并采用单极德拜模型完成了生物组织色散特性的模拟. 利用8发9收的天线阵列实现微波肿瘤探测, 利用共焦成像算法对乳房组织进行图像重构并进行肿瘤定位. 仿真结果显示共焦成像算法能够实现最小直径3 mm的肿瘤的检测, 同时证实了超宽带微波成像技术应用于早期乳腺肿瘤检测的有效性. 关键词： 微波成像 肿瘤检测 时域有限差分 共焦成像算法     

Diagnosis of colon cancer using frequency domain fluorescence imaging technique

Early detection and treatment of colon cancer has been associated with better disease prognosis. Conventional and reported optical techniques have limitations in detecting early stages of colon cancer growth. In this paper, a homodyne signal processing assisted frequency domain (FD) fluorescence imaging methodology is proposed for the early diagnosis of colon cancer. Simulated phantom tissues representing the biopsy samples at different stages of colon cancer growth are prepared and used for the imaging study. Selective imaging of healthy and diseased sites simulated in the samples was achieved even for fluorescence emissions having close lifetimes and wavelength values. Possible extension of the methodology for in vivo investigations is also discussed.     

A Case of Effusive-Constrictive Pericarditis: An Efficacy of Gd-DTPA Enhanced Magnetic Resonance Imaging to Detect a Pericardial Thickening

A 38-year-old man underwent pericardiectomy because of effusive-constrictive pericarditis. The gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging showed pericardial thickening separate from the effusion, which could not be shown by unenhanced computed tomography. Gd-DTPA enhanced magnetic resonance imaging could be useful for the early detection of effusive-constrictive pericarditis.     

Structure‐Making Effects of Metal Nanoparticles in Amyloid Peptide Fibrillation

There is growing concern that nanoparticles (NPs) may accelerate amyloid protein aggregation and thus cause amyloid‐related diseases. Here, the potential of silver and gold NPs is explored (diameter 20 nm) on the aggregation of the amyloid peptide sequences NNFGAIL from human islet amyloid polypeptide and the yeast prion protein sequence GNNQQNY, which are both the sequences of the full systems, which are able to aggregate into characteristic amyloid cross‐beta sheet fibrillar structures. Here, it is shown that silver and gold NPs in physiological aqueous solution at ambient temperatures accelerate the aggregation kinetics of both peptides significantly (in vitro). Scanning electron microscopy and X‐ray diffraction provide solid evidence for a “structure‐making” effect of the NPs. In particular, we are able to image the initial peptide corona and measure its structural reorganization in time‐resolved kinetic experiments. After a conversion time Δt, the coated NPs appear to act as templates or seeds for rapid fibrillation. Interestingly, cross‐fibrillation experiments with different peptide‐coated NPs (pcNPs) reveal that they can efficiently induce aggregation of similar peptides once the pcNPs are structurally converted. It is discussed that these structurally converted pcNPs may display similar kinetic features as toxic and aggregation inducing oligomers/protofibrils in normal amyloid aggregation, without being transient and very low‐concentration species. Finally, we suggest and discuss a simple mechanistic picture with the biomolecule corona of NPs being central to the function of the coated NPs in amyloid fibrillation.     

Using a portable total reflection X-ray fluorescence system for a multielement analysis of Swiss mice brains with experimental Alzheimer's disease induced by β-amyloid oligomers

Alzheimer's disease (AD) is a progressive and irreversible disorder whose pathological features include β-amyloid (Aβ) plaques and neuronal and synaptic loss. Metals such as iron, copper, and zinc are increased in the brains of patients with AD. Those metals can interact with Aβ, resulting in the promotion of Aβ deposition and formation of plaque. However, no study analyzing the effects of single injection of Aβ soluble oligomers (AβOs) in the elements' homeostasis in mice was developed. Total reflection X-ray fluorescence (TXRF) is a multielement analytical technique that can be utilized to identify and quantify trace elements present in a sample at very low concentrations. In this study, in order to evaluate the concentration of metals in brain regions of Swiss mice, three groups of female mice and three of male mice were studied: control, AD10, and AD100. The AD groups received an AβOs intracerebroventricular injection so as to induce experimental AD. Afterwards, a craniotomy was performed, and six brain compartments were dissected and evaluated. TXRF measurements were performed using a portable TXRF system that uses an X-ray tube with a molybdenum anode and a detector Si-PIN. It is proved to determine the following elements' concentrations: phosphorus, sulfur, potassium, iron, copper, zinc, and rubidium. Results showed differences in the elemental concentration in some brain regions between AD groups. These alterations suggest that AβOs act quickly, even before the amyloid plaques' formation, explaining cognitive deficits independently of amyloid plaques. This study helped to understand that this modification on elemental concentration can be influenced by AβOs.     

基于生物阻抗谱成像的生物组织检测方法

基于电阻抗成像技术和生物阻抗谱技术,提出一种面向生物组织检测的生物阻抗谱成像方法.该方法将目标区域可视化并精准识别目标种类,可用于肺癌早期检测,协助临床医生对早期肺癌进行精准检测,提高早期肺癌的治愈率.本文通过数值仿真的方法验证生物阻抗谱成像方法在肺癌早期检测中的可行性和有效性,仿真结果表明:1)生物阻抗谱成像方法可以实现早期肺癌区域的可视化,并精确判别出早期肺癌种类; 2)生物阻抗谱成像方法中阻抗谱的最佳采集模式是4次循环采集,最佳分类器是Linear-SVM, 5折交叉验证的平均分类准确率可以达到99.9%.为了验证仿真结果,本文选取3种具有不同电学特性的生物组织模拟癌变区域进行了检测.实验结果表明该方法可以对生物组织区域可视化,并判别出生物组织的种类.该方法可以兼顾电阻抗成像和生物阻抗谱方法的优点,有望用于肺癌早期检测.     

高光谱荧光成像技术在识别早期腐烂脐橙中的应用研究

腐烂是发生在柑橘类水果中最普遍、最严重的病害,早期腐烂果的自动化检测有助于提高水果加工业的市场竞争力.然而,目前没有有效的自动化检测技术.以脐橙为研究对象,利用荧光高光谱成像检测早期腐烂果.最佳指数OIF理论用于识别腐烂果的最优波段组合(498.6和591.4 nm).基于最优波长的比图像及双阈值分割算法,识别率达到1...     

Heterogeneity of Accelerated Photooxidation in Stabilized Bulk Commodity Polymers Studied by X-Band ESRI

Heterogeneity of photooxidation processes in plaques made of commodity polymers, high-density polyethylene, and cyclic olefin copolymer poly(ethylene-co-norbornene) (Topas^® 8007) stabilized with various hindered amine stabilizers; some of them in combination with UV stabilizers exposed to accelerated weathering were studied using electron spin resonance imaging (ESRI) and three independent microscopic-scale methods: scanning electron microscopy, infrared microscopy, and microhardness testing. Concentration profiles of nitroxides mapping photooxidation process inside polymer plaques along the direction of incident radiation (perpendicular to the irradiated surface of the plaques) were determined by ESRI technique in dependence on the duration of the accelerated photooxidation. ESRI data were complemented with profiles of oxidation products, crystallinity, and microhardness measured inside the plaques along the same direction. Selection of stabilizers in the study was completed with α-tocopherol that is considered as the most active component of excellent processing stabilizer vitamin E.