光学分子影像技术及其在药物研发领域的应用

光学分子影像技术是一种发展迅速的生物医学影像技术,能够利用生物发光技术或荧光蛋白等,对生物体内特定的生物过程进行无创的定性或定量研究。应用该技术可以对药物进行筛选,选取具有潜在治疗效果的药物进行后续研究,而终止对可能无效药物的研究,同时可以评价药物对肿瘤的代谢、增殖、血管形成、凋亡和组织乏氧等方面的影响。本文主要介绍光学分子影像技术及其在药物研发,尤其是抗肿瘤药物研发领域的应用。     

Cell block as an adjunct to conventional Papanicolaou smear for diagnosis of cervical cancer in resource-limited settings

OBJECTIVE: To assess the utility of indigenously prepared cell blocks (CBs) as an adjunct to a conventional smear test in providing a reliable diagnosis of clinically suspicious cervical cancer in resource-limited settings. METHODS: Eighty-six clinically suspicious cervical cancer cases underwent a conventional smear test, CB preparation from residual cellular samples and biopsies at the same sitting. Correlations were performed between these modalities in order to derive the sensitivity and specificity of the CB technique to diagnose cervical cancer. OBSERVATION & RESULTS: Out of 86 clinically suspicious cervical cancers, 72 (83.7%), 70 (81.4%) and 67 (77.9%) cases were diagnosed as malignant on tissue biopsies, CBs and smears respectively. CB-biopsy agreement in the diagnosis of malignancy was feasible in 87.5% of the cases while CB-Pap smear agreement was feasible in 92.5% of the cases. Sensitivity and specificity of CB preparation to diagnose malignancy was 92.5% and 100%, respectively, when the smear was taken as the reference test (excluding the unsatisfactory smears). When biopsy was taken as the gold standard, the sensitivity and specificity of CBs were 87.5% and 100% respectively (excluding the unsatisfactory biopsies). In 8/19 cases where the smear diagnoses were either unsatisfactory or atypical squamous cells/atypical glandular cells, CBs picked up malignant lesions. CONCLUSION: CBs prepared from the residual cellular sample of conventional cervical scrapes augment the sensitivity of the smear test. When used as an adjunct to the smear, CBs aid in providing a reliable diagnosis of cervical cancer in the majority of the clinically suspected cases and thus the biopsy load can be reduced significantly in resource-poor settings.     

Receptor-specific targeting with complementary peptide nucleic acids conjugated to peptide analogs and radionuclides

Summary Genomic sequencing makes it possible to identify all the genes of an organism, now includingHomo sapiens. Yet measurement of the expression of each gene of interest still presents a daunting prospect. Northern blots, RNase protection assays, as well as microarrays and related technologies permit measurement of gene expression in total RNA extracted from cultured cells or tissue samples. It would be most valuable, however, to quantitate gene expression noninvasively in living cells and tissues. Unfortunately, no reliable method has been available to measure levels of specific mRNAsin vivo. Peptide nucleic acids (PNAs) display superior ruggedness and hybridization properties as a diagnostic tool for gene expression, and could be used for this purpose. On the down side, they are negligibly internalized by normal or malignant cells in the absence of conjugated ligands. Nevertheless, we have observed that Tc-99m-peptides can delineate tumors, and PNA-peptides designed to bind to IGF-1 receptors on malignant cells are taken up specifically and concentrated in nuclei. We have postulated that antisense Tc-99m-PNA-peptides will be taken up by human cancer cells, will hybridize to complementary mRNA targets, and will permit scintigraphic imaging of oncogene mRNAs in human cancer xenografts in a mouse model. The oncogenes cyclin D1,ERBB2, c-MYC, K-RAS, and tumor suppressor p53 are being probed initially. These experiments provide a proof-of-principle for noninvasive detection of oncogene expression in living cells and tissues. This scintigraphic imaging technique should be applicable to any particular gene of interest in a cell or tissue type with characteristic receptors.     

Computational fluid dynamics endpoints for assessment of adenotonsillectomy outcome in obese children with obstructive sleep apnea syndrome

Background

Improvements in obstructive sleep apnea syndrome (OSAS) severity may be associated with improved pharyngeal fluid mechanics following adenotonsillectomy (AT). The study objective is to use image-based computational fluid dynamics (CFD) to model changes in pharyngeal pressures after AT, in obese children with OSAS and adenotonsillar hypertrophy.

Methods

Three-dimensional models of the upper airway from nares to trachea, before and after AT, were derived from magnetic resonance images obtained during wakefulness, in a cohort of 10 obese children with OSAS. Velocity, pressure, and turbulence fields during peak tidal inspiratory flow were computed using commercial software. CFD endpoints were correlated with polysomnography endpoints before and after AT using Spearman?s rank correlation (r_s).

Results

Apnea hypopnea index (AHI) decreases after AT was strongly correlated with reduction in maximum pressure drop (dP_TAmax) in the region where tonsils and adenoid constrict the pharynx (r_s=0.78, P=0.011), and with decrease of the ratio of dP_TAmax to flow rate (r_s=0.82, P=0.006). Correlations of AHI decrease to anatomy, negative pressure in the overlap region (including nasal flow resistance), or pressure drop through the entire pharynx, were not significant. In a subgroup of subjects with more than 10% improvement in AHI, correlations between flow variables and AHI decrease were stronger than in all subjects.

Conclusions

The correlation between change in dP_TAmax and improved AHI suggests that dP_TAmax may be a useful index for internal airway loading due to anatomical narrowing, and may be better correlated with AHI than direct airway anatomic measurements.     

X-ray absorption and phase contrast imaging to study the interplay between plant roots and soil structure

Plant performance is, at least partly, linked to the location of roots with respect to soil structure features and the micro-environment surrounding roots. Measurements of root distributions from intact samples, using optical microscopy and field tracings have been partially successful but are imprecise and labour-intensive. Theoretically, X-ray computed micro-tomography represents an ideal solution for non-invasive imaging of plant roots and soil structure. However, before it becomes fast enough and affordable or easily accessible, there is still a need for a diagnostic tool to investigate root/soil interplay. Here, a method for detection of undisturbed plant roots and their immediate physical environment is presented. X-ray absorption and phase contrast imaging are combined to produce projection images of soil sections from which root distributions and soil structure can be analyzed. The clarity of roots on the X-ray film is sufficient to allow manual tracing on an acetate sheet fixed over the film. In its current version, the method suffers limitations mainly related to (i) the degree of subjectivity associated with manual tracing and (ii) the difficulty of separating live and dead roots. The method represents a simple and relatively inexpensive way to detect and quantify roots from intact samples and has scope for further improvements. In this paper, the main steps of the method, sampling, image acquisition and image processing are documented. The potential use of the method in an agronomic perspective is illustrated using surface and sub-surface soil samples from a controlled wheat trial. Quantitative characterization of root attributes, e.g. radius, length density, branching intensity and the complex interplay between roots and soil structure, is presented and discussed. This revised version was published online in June 2006 with corrections to the Cover Date.     

活细胞内5-羟色胺可见荧光的多光子激发成像

应用多光子激发激光扫描显微镜对5-羟色胺（5-hydroxytryptamine, 5-HT）孵育的大鼠粘膜型肥大细胞进行自发荧光成像,首次观察到了活细胞内5-HT相关的可见荧光,并对其产生机理进行了初步探讨.实现了对活细胞内5-HT空间分布的高分辨成像,为研究活组织或细胞内5-HT的空间分布和含量与细胞功能状态的关系提供了新的实验方法.     

Machine Learning Approach to Detect Cardiac Arrhythmias in ECG Signals: A Survey

Cardiac arrhythmia is a condition when the heart rate is irregular either the beat is too slow or too fast. It occurs due to improper electrical impulses that coordinates the heart beats. Sudden cardiac death may occurs due to some dangerous arrhythmias conditions. Hence the main objective of the electrocardiogram (ECG) analysis is to detect the life-threatening arrhythmias accurately for appropriate treatment in order to save life. Since the last decades, several methods were reported for automatic ECG beat classifications. In this work, we present a systematic review of the current state-of-the-art methods used to detect cardiac arrhythmia using on ECG signals. It includes the signal decomposition, feature extraction and machine learning approaches used for automatic detection and decision making process. The articles covers the pre-processing, detection of QRS complex, feature extraction and classification of ECG beats. Based on the past studies, it is understood that the automated approach using computer-aided decision making process is highly required for real-time detection of cardiac arrhythmias. The advantages and limitations of different methods are discussed and also the future scopes is highlighted in the process of effective detection of cardiac arrhythmias. This study could be beneficial for researchers to analyze the existing state-of-art techniques used in detection of arrhythmia conditions.