Do fluorescence decays remitted from tissues accurately reflect intrinsic fluorophore lifetimes?

Fluorescence spectroscopy and imaging methods, including fluorescence lifetime sensing, are being developed for noninvasive tissue diagnostics. The purpose of this study was to identify and quantify those factors affecting the accurate recovery of fluorophore lifetimes from inhomogeneous tissues in vivo. A Monte Carlo code was developed to numerically simulate time-resolved fluorescence measurements on layered epithelial tissues. Simulations were run with experimental parameters matching previously reported clinical studies in the gastrointestinal tract. The results demonstrate that variations in fluorescence decay time as large as those detected clinically between normal and premalignant tissues (approximately 2 ns) could be simulated by variations in tissue morphology or biochemistry, even when intrinsic fluorophore lifetimes were held constant.     

Medlar (<Emphasis Type="Italic">Achras Sapota</Emphasis> L.) as Oral Contrast Agent for MRI of the Gastrointestinal Tract

Magnetic resonance imaging (MRI) of the gastrointestinal (GI) tract is still limited due to the lack of widely available oral contrast agents (OCA). The availability of OCA for MRI of the GI tract is a necessity; different fruits might be implemented as OCA in order to solve this need throughout the year. The objective of this study is to present an alternative fruit as a clinical OCA for MRI of the GI tract, Achras sapota L. (common medlar). Both physical and chemical characterization of the medlar was performed. It was also tested in situ and in vivo as an OCA for MRI of the GI tract. Results showed that this fruit had a diamagnetic behavior, although it has enough iron, manganese and copper to contrast the GI tract in T ₁- and T ₂-weighted images. Thus we conclude that the medlar fruit has shown a potential as an OCA in GI evaluation by MRI, so it can be considered as an alternative in complementation of natural OCA.     

Utililization of experimental animal model for correlative multispectral MRI and pathological analysis of brain tumors

Magnetic resonance imaging is the method of choice for non-invasive detection and evaluation of tumors of the central nervous system. However, discrimination of tumor boundaries from normal tissue, and the evaluation of heterogeneous lesions have proven to be limitations in traditional magnetic resonance imaging. The use of post-image acquisition processing techniques, such as multispectral tissue segmentation analysis, may provide more accurate clinical information. In this report, we have employed an experimental animal model for brain tumors induced by glial cells transformed by the human neurotropic JC virus to examine the utility of multispectral tissue segmentation for tumor cell identification. Six individual tissue types were discriminated by segmentation analysis, including heterogeneous tumor tissue, a clear demarcation of the boundary between tumor and non-tumor tissue, deep and cortical gray matter, and cerebrospinal fluid. Furthermore, the segmentation analysis was confirmed by histopathological evaluation. The use of multispectral tissue segmentation analysis may optimize the non-invasive determination and volumetric analysis of CNS neoplasms, thus providing improved clinical evaluation of tumor growth and evaluation of the effectiveness of therapeutic treatments.     

Transcutaneous in vivo Raman spectroscopy of breast tumors and pretumors

Breast cancer is the most common cancer amongst women worldwide. Early detection of this cancer results in better prognosis. Owing to the disadvantages of currently available screening tools for early detection of this cancer, rapid and sensitive alternatives such as optical spectroscopic techniques are being extensively explored. Detection of premalignant lesions using these techniques has been reported. However, premalignant lesions are risk indicators and may not be true predictors of tumor development. Therefore, the current study aims at correlation between spectral changes and tumor appearance. In this context, transcutaneous in vivo spectra were acquired from same carcinogen‐induced rats immediately before carcinogen treatment, 3, 8–10, and 12–14 weeks after carcinogen treatment and from frank tumors. These were analyzed using multivariate statistical tools principal component analysis and principal component linear discriminant analysis. Further, a complex test data set consisting of spectra from rats of varying ages, tumor appearance times, and tumor induction protocols was used to test the feasibility of correctly identifying controls and pretumors using Raman spectroscopy. Results suggest feasibility of distinguishing pretumor spectra from controls. Taking into consideration the heterogeneity of afflicted breast, rat‐wise analysis was performed wherein a rat was declared ‘will develop tumor’, even if one spectrum was found abnormal. Using this criterion, in vivo Raman spectroscopy could predict tumor appearance with 82% sensitivity and 95% specificity. Prospectively, combined with emerging technologies like deep Raman spectroscopy and fiber‐probe‐based whole sample imaging, Raman spectroscopy may prove as an invaluable adjunct to currently available breast cancer screening tools. Copyright © 2015 John Wiley & Sons, Ltd.     

新型多光子成像技术研究进展

相比于传统的光学成像技术,近年来获得快速发展的新型多光子成像技术具有穿透深度大,组织光损伤小,信噪比高,且可方便进行光学层析成像的特点,故而被广泛应用于包括脑、肿瘤、胚胎在内的多种活体组织成像中。本综述回顾了新型多光子成像技术的诞生与发展历程,包括微型化双光子成像技术、双光子内窥技术和三光子成像技术,概括分析了其基本原理与成像特点,讨论了这一领域具有代表性的最新研究成果,重点总结了其在生物学基础研究领域和临床医学诊断中的主要应用,并展望了其未来的应用与发展前景。可以预见,随着激光器和光探测技术的不断进步,多光子成像技术将会得到更大的发展与更加广泛的应用。     

Serial MR imaging of intracranial metastases after radiosurgery

Purpose: To evaluate the spatiotemporal evolution of radiosurgical induced changes both in metastases and in normal brain tissue adjacent to the lesions by serial magnetic resonance (MR) imaging. Methods and Materials: Thirty-five intracranial metastases of different primaries were treated in 25 patients by single high-dose radiosurgery. MR images acquired before radiosurgery were available in all patients. Sixty-three follow-up MR studies were performed in these patients including T₂- and contrast-enhanced T₁-weighted MR images. The average follow-up time was 9 ± 5 months (mean ± standard deviation [SD]). Based on contrast-enhanced T₁-weighted MR images, tumor response was radiologically classified in the following four groups: stable disease was assumed if the average tumor diameter after treatment did not show a tumor shrinkage of more than 50% and an increase of more than 25%, partial remission as a shrinkage of tumor size of more than 50%, a disappearance of contrast-enhancing tumor as a complete remission, and an increase of tumor diameter of more than 25% as tumor progress. Moreover, we analysed signal changes on T₂-weighted images in brain parenchyma adjacent to the enhancing metastases. Results: The overall mean survival time was 10.5 ± 7 months, with a 1-year actuarial survival rate of 40%. Stable disease, partial or complete remission of the metastatic tumor was observed in 22 patients (88%). Central or homogeneous loss of contrast enhancement appeared to be a good prognostic sign for stable disease or partial remission. This association was statistically significant (p < 0.05). Three patients (12%) suffered from tumor progression. In eight patients (32%) with stable disease or partial remission, signal changes on T₂-weighted images were observed in tissue adjacent to the contrast enhancing lesions. A progression of the high signal on T₂-weighted images was seen in seven of the eight patients between 3 and 6 months after therapy, followed by a signal regression 6–18 months after irradiation. Conclusion: MR imaging is a sensitive imaging tool to evaluate tumor response as well as the presence or absence of adjacent parenchymal changes following radiosurgery. Loss of homogeneous or central contrast enhancement on Gd-enhanced MR images appeared to be a good prognostic sign for tumor response. Tumor shrinkage seems not to be dependent on time. In addition, most cases of radiation induced changes in normal brain parenchyma observed on T₂-weighted images seem to be self limited.     

“Molecular” MR imaging at high fields

Magnetic resonance imaging (MRI) and spectroscopy (MRS) have contributed considerably to clinical radiology, and a variety of MR techniques have been developed to evaluate pathological processes as well as normal tissue biology at the cellular and molecular level. However, in comparison to nuclear imaging, MRI has relatively poor sensitivity for detecting true molecular changes or for detecting the presence of targeted contrast agents, though these remain under active development. In recent years very high field (7 T and above) MRI systems have been developed for human studies and these provide new opportunities and technical challenges for molecular imaging. We identify 5 types of intrinsic contrast mechanisms that do not require the use of exogenous agents but which can provide molecular and cellular information. We can derive information on tissue composition by (i) imaging different nuclei, especially sodium (ii) exploiting chemical shift differences as in MRS (iii) exploiting specific relaxation mechanisms (iv) exploiting tissue differences in the exchange rates of molecular species such as amides or hydroxyls and (v) differences in susceptibility. The increased signal strength at higher fields enables higher resolution images to be acquired, along with increased sensitivity to detecting subtle effects caused by molecular changes in tissues.     

Nakagami-m parametric imaging for characterization of thermal coagulation and cavitation erosion induced by HIFU

Nowadays, both thermal and mechanical ablation techniques of HIFU associated with cavitation have been developed for noninvasive treatment. A specific challenge for the successful clinical implementation of HIFU is to achieve real-time imaging for the evaluation and determination of therapy outcomes such as necrosis or homogenization. Ultrasound Nakagami-m parametric imaging highlights the degrading shadowing effects of bubbles and can be used for tissue characterization. The aim of this study is to investigate the performance of Nakagami-m parametric imaging for evaluating and differentiating thermal coagulation and cavitation erosion induced by HIFU. Lesions were induced in basic bovine serum albumin (BSA) phantoms and ex vivo porcine livers using a 1.6 MHz single-element transducer. Thermal and mechanical lesions induced by two types of HIFU sequences respectively were evaluated using Nakagami-m parametric imaging and ultrasound B-mode imaging. The lesion sizes estimated using Nakagami-m parametric imaging technique were all closer to the actual sizes than those of B-mode imaging. The p-value obtained from the t-test between the mean m values of thermal coagulation and cavitation erosion was smaller than 0.05, demonstrating that the m values of thermal lesions were significantly different from that of mechanical lesions, which was confirmed by ex vivo experiments and histologic examination showed that different changes result from HIFU exposure, one of tissue dehydration resulting from the thermal effect, and the other of tissue homogenate resulting from mechanical effect. This study demonstrated that Nakagami-m parametric imaging is a potential real-time imaging technique for evaluating and differentiating thermal coagulation and cavitation erosion.     

Visualization of superior mesenteric lymph nodes by the combined oral and intravenous administration of the ultrasmall superparamagnetic iron oxide, AMI-227

Superior mesenteric lymph nodes which lie as a chain near the small intestine are difficult to visualize in the rat with MRI either with or without the use of contrast agents. We previously demonstrated that the oral administration of an ultrasmall superparamagnetic iron oxide (AMI-227) produces a brightening of the lumen of the GI tract with a T₁-weighted spin-echo pulse sequence. We have also shown that AMI-227 darkens abdominal lymph nodes. In the present study we show that the combined oral and intravenous administration of AMI-227 produces a brightening of the lumen of the GI tract and a darkening of the superior mesenteric lymph node chain. As a result of these combined and opposing effects on image signal intensity, a necessary contrast is established to reliably locate the superior mesenteric lymph nodes in vivo, which, to our knowledge, have been elusive by other techniques.     

Morphological aspects of ionizing radiation response of small intestine

Knowledge of the acute and late ionizing radiation exposure damage to the gastrointestinal tract, particularly injury of the small intestine, is of great significance in radiotherapy, as is management of accidental radiation exposure. Irradiation (X-ray, neutron, cobalt gamma) induces a series of events in this rapidly renewing tissue resulting in the well-known symptoms of the gastrointestinal (GI) radiation syndrome, such as GI haemorrhage, endotoxemia, bacterial infection, anorexia, nausea, vomiting, diarrhoea, and loss of electrolytes and fluid. In spite of the significant advances that have occurred in research on underlying mechanisms over the last two decades, the overall etiology and pathogenesis of the GI-syndrome still remains unclear. Currently, to our knowledge, these symptoms are probably due to a rapid modification of the intestinal motility and to the structural alteration of the intestinal mucosa (cell loss and altered crypt integrity). Several evidences suggest that radiation-induced dysfunctions and structural changes of this organ (either changes in subcellular, cellular, and histological structure) are mediated by concerted and interrelated changes of a plethora of various extracellular mediators and their intracellular messengers. The aim of this review is to summarize our current knowledge about the pathomorphology and cell biology of the ionizing radiation response of the GI tract with a focus on the small intestine.     

基于偏振滤波的皮肤镜光学和机械设计

皮肤镜在临床中已广泛用于诊断皮肤病变,然而,如何更加清晰准确地观察表皮、真皮表皮交界处和真皮乳头层内的色素性结构的大小、形状、颜色的深浅及浅层血管丛血管的大小形态依旧是一个挑战。由于皮肤表皮层类似于镜面反射,不改变反射光的偏振态,而皮肤组织表皮层以下的组织会改变原有光线的偏振态,基于此,本文设计了一个视场为22 mm、倍率为10×的手持偏振皮肤镜,通过采用偏振照明成像技术可以更加清晰有效地观察深层皮肤组织的病变以及病变组织形态,从而提高临床诊断与鉴别效率。     

光声内窥镜系统在人体直肠癌离体组织中的实验研究

研制了基于4阵列传感器的光声内窥镜探头,并基于此搭建了光声内窥镜成像系统,开展了仿体实验成像研究,通过内窥镜探头4个阵元位置激光吸收强度的变化情况来分析仿体中吸收体的位置,论证了其定位能力,利用光声内窥镜系统对人体离体的正常组织、直肠癌早期组织进行成像研究;通过对不同阵元位置的光吸收强度分布进行统计分析,证明了光声内窥镜对早期直肠癌组织和正常组织的辨别能力,此项技术有望提高直肠癌早期诊断的准确率,具有潜在的临床应用前景。     

Sodium and proton diffusion MRI as biomarkers for early therapeutic response in subcutaneous tumors

The ability to quantitate early effects of tumor therapeutic response using noninvasive imaging would have a major impact in clinical oncology. One area of active research interest is the ability to use MR techniques to detect subtle changes in tumor cellular density. In this study, sodium and proton diffusion MRI were compared for their ability to detect early cellular changes in tumors treated with a cytotoxic chemotherapy. Subcutaneous 9L gliosarcomas were treated with a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea. Both sodium and diffusion imaging modalities were able to detect changes in tumor cellularity as early as 2 days after treatment, which continued to evolve as increased signal intensities reached a maximum approximately 8 days posttreatment. Early changes in tumor sodium and apparent diffusion coefficient values were predictive of subsequent tumor shrinkage, which occurred approximately 10 days later. Overall, therapeutical induced changes in sodium and diffusion values were found to have similar dynamic and spatial changes. These findings suggest that these imaging modalities detected similar early cellular changes after treatment. The results of this study support the continued clinical testing of diffusion MRI for evaluation of early tumor treatment response and demonstrate the complementary insights of sodium MRI for oncology applications.     

Photodynamic therapy

Photodynamic therapy (PDT) is a new treatment for solid tumors utilizing the combined action of light and a photosensitizing drug. Laser-fiber optic delivery systems make it practical to treat superficial and interstitial cancers, including malignancies of the skin, head and neck, esophagus, endobronchial tract, stomach, urinary bladder, female genital tract, and other sites. The putative action mechanism in PDT involves photochemical destruction of tumor tissue membranes mediated by singlet molecular oxygen. Light dosimetry modeling based on tissue optics is applicable for treatment planning. Related research areas include non-invasive optical diagnosis and imaging, development of new PDT drugs and light sources, and the extension of PDT methods to treatment of atherosclerotic vascular disease and blood detoxification.     

Investigating brain tumor differentiation with diffusion and perfusion metrics at 3T MRI using pattern recognition techniques

The aim of this study was to evaluate the contribution of diffusion and perfusion MR metrics in the discrimination of intracranial brain lesions at 3T MRI, and to investigate the potential diagnostic and predictive value that pattern recognition techniques may provide in tumor characterization using these metrics as classification features. Conventional MRI, diffusion weighted imaging (DWI), diffusion tensor imaging (DTI) and dynamic-susceptibility contrast imaging (DSCI) were performed on 115 patients with newly diagnosed intracranial tumors (low-and- high grade gliomas, meningiomas, solitary metastases). The Mann–Whitney U test was employed in order to identify statistical differences of the diffusion and perfusion parameters for different tumor comparisons in the intra-and peritumoral region. To assess the diagnostic contribution of these parameters, two different methods were used; the commonly used receiver operating characteristic (ROC) analysis and the more sophisticated SVM classification, and accuracy, sensitivity and specificity levels were obtained for both cases. The combination of all metrics provided the optimum diagnostic outcome. The highest predictive outcome was obtained using the SVM classification, although ROC analysis yielded high accuracies as well. It is evident that DWI/DTI and DSCI are useful techniques for tumor grading. Nevertheless, cellularity and vascularity are factors closely correlated in a non-linear way and thus difficult to evaluate and interpret through conventional methods of analysis. Hence, the combination of diffusion and perfusion metrics into a sophisticated classification scheme may provide the optimum diagnostic outcome. In conclusion, machine learning techniques may be used as an adjunctive diagnostic tool, which can be implemented into the clinical routine to optimize decision making.     

Anatomical and Functional Correlates of Voice Quality in Tracheoesophageal Speech

The purpose of the current study was to assess the anatomic and functional correlates of voice quality in tracheoesophageal speech, with dynamic imaging studies of the neoglottis. Videofluoroscopy (providing a lateral view), digital high-speed endoscopy (providing a "birds-eye" view), and their relationships with perceptual evaluations of voice quality were investigated. Several significant relationships were found. Imaging with videofluoroscopy revealed that the following anatomic and functional parameters (established during phonation) are related to voice quality: presence of a neoglottic bar, regurgitation of barium, tonicity of the neoglottis, and minimal neoglottic distance. Furthermore, the index of the increase of the maximal subneoglottic distance from rest to phonation also showed a significant relationship with voice quality. Imaging with digital high-speed endoscopy revealed features relevant to voice quality, including amount of saliva, visibility of the origin of the neoglottis, shape of the neoglottis, and regularity of the vibration. Knowledge of the anatomic and functional correlates of tracheoesophageal voice quality provides prerequisite information for future (phono-) surgical and/or clinical improvements to the voice quality of postlaryngectomy (prosthetic) voice production.     

Frequency-domain fluorescence lifetime imaging for endoscopic clinical cancer photodetection: Apparatus design and preliminary results

We describe a new fluorescence imaging device for clinical cancer photodetection in hollow organs in which the tumor/normal tissue contrast is derived from the fluorescence lifetime of endogenous or exogenous fluorochromes. This fluorescence lifetime contrast gives information about the physicochemical properties of the environment which are different between normal and certain diseased tissues. The excitation light from a CW laser is modulated in amplitude at a radio frequency by an electrooptical modulator and delivered by an optical fiber through an endoscope to the hollow organ. The image of the tissue collected by the endoscope is separated in two spectral windows, one being the backscattered excitation light and the other the fluorescence of the fluorochrome. Each image is then focused on the photocathode of image intensifiers (II) whose optical gain is modulated at the same frequency as the excitation intensity, resulting in homodyne phase-sensitive images. By acquiring stationary phase-sensitive frames at different phases between the excitation and the detection, it is possible to calculate in quasi-real time the apparent fluorescence lifetime of the corresponding tissue region for each pixel. A result obtained by investigating the endogenous fluorochromes present in the mucous membrane of an excised human bladder is presented to illustrate this method and most of the optical parameters which are of major importance for this photodetection modality have been evaluated.     

基于自适应阈值方法实现迭代降噪鬼成像

为了有效降低传统鬼成像中相关噪声对成像质量的影响,本文提出一种基于最佳阈值的迭代降噪鬼成像.首先在迭代降噪鬼成像的基础上,采用自适应阈值迭代法,在不需要目标先验信息的前提下,找到一个逼近传统鬼成像中相关噪声的阈值,根据得到的阈值构造噪声干扰项.为了每次迭代初值更接近原始目标的透射系数,对其进行二值化,降低重构图像背景噪声对迭代性能的影响.仿真以及实验结果表明,本文提出的方法与传统方法相比,视觉效果以及峰值信噪比值有明显提高.     

Effects of laryngeal endoscopy on the vocal performanceof young adult females with normal voices

This study investigated changes in maximum phonation time andacoustic and perceptual measures of voice following topical anesthesia and laryngeal endoscopy with the flexible endoscope. Forty-four females, aged 18–33 years and with normal voices, performed four vocal tasks: (a) 3-second /i/ prolongation, (b) maximum phonation time on /i/, (c) stepwise scale-singing, and (d) reading a standard passage. Subjects performed these tasks prior to anesthesia, after anesthesia, and again during laryngeal endoscopy. Voice samples were analyzed for jitter, shimmer, harmonic-to-noise ratio, speaking fundamental frequency, maximum phonational frequency range, maximum phonation time, harshness, and breathiness. Results demonstrated significant reductions in maximum phonational frequency range following anesthesia and, during laryngeal endoscopy, reductions in maximum phonation time and increases in speaking fundamental frequency, minimum fundamental frequency on scale-singing, and breathiness. Clinicians using laryngeal endoscopy for evaluation and management of vocal dysfunction should, therefore, consider the possible effects of these procedures on vocal functioning.     

Earlier detection of tumor treatment response using magnetic resonance diffusion imaging with oscillating gradients

An improved method for detecting early changes in tumors in response to treatment, based on a modification of diffusion-weighted magnetic resonance imaging, has been demonstrated in an animal model. Early detection of therapeutic response in tumors is important both clinically and in pre-clinical assessments of novel treatments. Noninvasive imaging methods that can detect and assess tumor response early in the course of treatment, and before frank changes in tumor morphology are evident, are of considerable interest as potential biomarkers of treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to changes in water diffusion rates in tissues that result from structural variations in the local cellular environment, but conventional methods mainly reflect changes in tissue cellularity and do not convey information specific to microstructural variations at sub-cellular scales. We implemented a modified imaging technique using oscillating gradients of the magnetic field for evaluating water diffusion rates over very short spatial scales that are more specific for detecting changes in intracellular structure that may precede changes in cellularity. Results from a study of orthotopic 9L gliomas in rat brains indicate that this method can detect changes as early as 24 h following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea, when conventional approaches do not find significant effects. These studies suggest that diffusion imaging using oscillating gradients may be used to obtain an earlier indication of treatment efficacy than previous magnetic resonance imaging methods.