Ex Vivo Estimation of Photoacoustic Imaging for Detecting Thyroid Microcalcifications

Background

The aim of this study was to evaluate the diagnostic utility of PAI at detecting thyroid microcalcifications at 700 nm laser wavelengths.

Methods

This study included 36 resected samples in 18 patients. To evaluate the PA manifestation of microcalcifications in PAI, gray level histogram and co-occurrence matrix (COM) texture parameters were extracted from the 3 fixed ROI US and PA images, respectively, per sample. We compared the textural parameters obtained from specimen PAIs between samples with punctate microcalcifications on specimen radiography and those without microcalcifications.

Results

On specimen US, the mean value (2748.4±862.5) of samples with microcalcifications on specimen radiography was higher than that (1961.9±780.2) of those without microcalcifications (P = 0.007). However, there were no significant differences in textural parameters obtained from specimen PAIs between samples with punctate microcalcifications on specimen radiography and those without when applying both the mean value of the three slices of thyroid specimens and the value of the thyroid specimen slice which had the highest value of the mean values in specimen US.

Conclusion

PAI did not show significant PA contrast on thyroid microcalcifications indicating that the experimental setup and protocols should be enhanced, e.g., method of complete blood rejection from ex vivo specimens, the multi-wavelength spectroscopic PA imaging method which can solely extract the PA signal from microcalcifications even with high spectral interferences, or PA imaging with narrower slice thickness using 2-dimensional array transducer, etc.     

用侧向光源进行前列腺光声扫描成像的研究

光声成像技术是近年来兴起的前列腺早期检测与成像的新技术.前列腺组织的结构特征需要一种无创的且光穿透深度足够大的光声激发方式.本文设计了一种可用于经由尿道对前列腺光辐照的侧向光源,并结合直肠处长焦区聚焦式超声换能器的光声探测展开了前列腺仿体的光声扫描成像.结果表明,侧向光源有利于单侧吸收体的定位和成像,具有较好的成像范围和深度,结合侧向光源的旋转可实现全方位成像.因此该侧向光源有望成为早期前列腺肿瘤光声成像技术中一种新型的光源结构,具有重要意义.     

MicroPure Imaging for the Evaluation of Microcalcifications in Gouty Arthritis Involving the First Metatarsophalangeal Joint: A Preliminary Study

Objective

To assess the value of MicroPure, a new ultrasound image processing technique, in identifying microcalcifications (formed by monosodium urate crystals) in the first metatarsophalangeal joints attacked by gout compared to gray-scale ultrasound images.

Materials and Methods

Thirty-six patients who fulfilled the study inclusion criteria underwent gray-scale ultrasound and MicroPure examinations of the first metatarsophalangeal joints attacked by gout. Static images of the target areas were acquired using gray-scale ultrasound and MicroPure. Two independent and blinded investigators analyzed the images to determine the number of microcalcifications and to score for image quality and artifacts.

Results

The two investigators observed significantly more microcalcifications with MicroPure compared to gray-scale ultrasound (ρ<0.001). The level of agreement between the investigators consistently increased from gray-scale ultrasound to MicroPure imaging (gray-scale interclass correlation coefficient of 0.69 vs. MicroPure interclass correlation coefficient of 0.81). One investigator preferred the MicroPure image quality over gray-scale ultrasound (ρ<0.001), but the other investigator disagreed (ρ<0.001). Both investigators observed fewer artifacts with MicroPure than with gray-scale ultrasound (ρ<0.009).

Conclusion

MicroPure imaging identified significantly more microcalcifications than gray-scale ultrasound.     

Clinical Report on the First Prototype of a Photoacoustic Tomography System with Dual Illumination for Breast Cancer Imaging

Photoacoustic tomography is a recently developed imaging modality that can provide high spatial-resolution images of hemoglobin distribution in tissues such as the breast. Because breast cancer is an angiogenesis-dependent type of malignancy, we evaluated the clinical acceptability of breast tissue images produced using our first prototype photoacoustic mammography (PAM) system in patients with known cancer. Post-excisionally, histological sections of the tumors were stained immunohistochemically (IHC) for CD31 (an endothelial marker) and carbonic anhydrase IX (CAIX) (a marker of hypoxia). Whole-slide scanning and image analyses were used to evaluate the tumor microvessel distribution pattern and to calculate the total vascular perimeter (TVP)/area for each lesion. In this clinical study, 42 lesions were primarily scanned using PAM preoperatively, three of which were reported to be benign and were excluded from statistical analysis. Images were produced for 29 out of 39 cancers (visibility rate = 74.4%) at the median depth of 26.5 (3.25–51.2) mm. Age, menopausal status, body mass index, history of neoadjuvant treatment, clinical stage and histological tumor angiogenesis markers did not seem to affect the visibility. The oxygen saturation level in all of the measured lesions was lower than in the subcutaneous counterpart vessels (Wilcoxon test, p value<0.001), as well as in the counterpart contralateral normal breast region of interest (ROI) (Wilcoxon test, p value = 0.001). Although the oxygen saturation level was not statistically significant between CAIX-positive vs. -negative cases, lesional TVP/area showed a positive correlation with the oxygen saturation level only in the group that had received therapy before PAM. In conclusion, the vascular and oxygenation data obtained by PAM have great potential for identifying functional features of breast tumors.     

不同方位探测对光声成像的影响

为了研究在不同方位探测光声信号对光声层析成像的影响,采用了数值仿真计算,得出了在有限角度扫描的情况下,吸收体分布与探测方向呈45度夹角时,成像效果较好;在条件允许的情况下,采用全方位探测扫描,其成像效果最好。该研究结果对光声成像扫描轨迹的设计、成像效果评估具有较好的参考价值。     

窄等离子体吸收谱线宽度的纳米金锥用于光声成像

无损光声成像技术结合了纯光学成像高选择特性和纯超声成像中深穿透特性的优点,克服了光散射限制,实现了对活体深层组织的高分辨、高对比度成像。该成像技术对内源物质例如脱氧血红蛋白、含氧血红蛋白、黑色素、脂质等进行成像,提供了活体生物组织结构和功能信息,已经在生物医学领域表现出巨大的应用前景。然而,很多与病理过程相关的特征分子的光吸收能力较弱,在活体环境中难以被光声成像系统所识别,从而限制了光声成像技术的应用范围。基于功能纳米探针的光声成像-光声分子成像极大拓展光声成像的应用范围,可以在活体层面对病理过程进行分子水平的定性和定量研究,将为实现目标疾病的早期诊断提供强大的技术支持。本文发展在近红外具有窄吸收线宽(半高宽仅为60 nm)的纳米金锥作为新型的光声探针。通过选择不同径长比的纳米金锥,可以任意调节纳米金锥的吸收峰。通过调谐激光器的波长,可实现对不同吸收峰纳米金锥的选择性激发。纳米金锥将有可能用于多光谱光声成像,实现对不同靶标的目标分子探测。     

Evaluation of Ki67 Expression across Distinct Categories of Breast Cancer Specimens: A Population-Based Study of Matched Surgical Specimens,Core Needle Biopsies and Tissue Microarrays

Introduction

Tumor cell proliferation in breast cancer is strongly prognostic and may also predict response to chemotherapy. However, there is no consensus on counting areas or cut-off values for patient stratification. Our aim was to assess the matched level of proliferation by Ki67 when using different tissue categories (whole sections, WS; core needle biopsies, CNB; tissue microarrays, TMA), and the corresponding prognostic value.

Methods

We examined a retrospective, population-based series of breast cancer (n = 534) from the Norwegian Breast Cancer Screening Program. The percentage of Ki67 positive nuclei was evaluated by visual counting on WS (n = 534), CNB (n = 154) and TMA (n = 459).

Results

The median percentage of Ki67 expression was 18% on WS (hot-spot areas), 13% on CNB, and 7% on TMA, and this difference was statistically significant in paired cases. Increased Ki67 expression by all evaluation methods was associated with aggressive tumor features (large tumor diameter, high histologic grade, ER negativity) and reduced patient survival.

Conclusion

There is a significant difference in tumor cell proliferation by Ki67 across different sample categories. Ki67 is prognostic over a wide range of cut-off points and for different sample types, although Ki67 results derived from TMA sections are lower compared with those obtained using specimens from a clinical setting. Our findings indicate that specimen specific cut-off values should be applied for practical use.     

Dual Energy Spectral CT Imaging for Colorectal Cancer Grading: A Preliminary Study

Objectives

To assess the diagnostic value of dual energy spectral CT imaging for colorectal cancer grading using the quantitative iodine density measurements in both arterial phase (AP) and venous phase (VP).

Methods

81 colorectal cancer patients were divided into two groups based on their pathological findings: a low grade group including well (n = 13) and moderately differentiated cancer (n = 24), and a high grade group including poorly differentiated (n = 42) and signet ring cell cancer (n = 2). Iodine density (ID) in the lesions was derived from the iodine-based material decomposition (MD) image and normalized to that in the psoas muscle to obtain normalized iodine density (NID). The difference in ID and NID between AP and VP was calculated.

Results

The ID and NID values of the low grade cancer group were, 14.65±3.38mg/mL and 1.70±0.33 in AP, and 21.90±3.11mg/mL and 2.05± 0.32 in VP, respectively. The ID and NID values for the high grade cancer group were 20.63±3.72mg/mL and 2.95±0.72 in AP, and 26.27±3.10mg/mL and 3.51±1.12 in VP, respectively. There was significant difference for ID and NID between the low grade and high grade cancer groups in both AP and VP (all p<0.001). ROC analysis indicated that NID of 1.92 in AP provided 70.3% sensitivity and 97.7% specificity in differentiating low grade cancer from high grade cancer.

Conclusions

The quantitative measurement of iodine density in AP and VP can provide useful information to differentiate low grade colorectal cancer from high grade colorectal cancer with NID in AP providing the greatest diagnostic value.     

Three-Dimensional Photoacoustic Endoscopic Imaging of the Rabbit Esophagus

We report photoacoustic and ultrasonic endoscopic images of two intact rabbit esophagi. To investigate the esophageal lumen structure and microvasculature, we performed in vivo and ex vivo imaging studies using a 3.8-mm diameter photoacoustic endoscope and correlated the images with histology. Several interesting anatomic structures were newly found in both the in vivo and ex vivo images, which demonstrates the potential clinical utility of this endoscopic imaging modality. In the ex vivo imaging experiment, we acquired high-resolution motion-artifact-free three-dimensional photoacoustic images of the vasculatures distributed in the walls of the esophagi and extending to the neighboring mediastinal regions. Blood vessels with apparent diameters as small as 190 μm were resolved. Moreover, by taking advantage of the dual-mode high-resolution photoacoustic and ultrasound endoscopy, we could better identify and characterize the anatomic structures of the esophageal lumen, such as the mucosal and submucosal layers in the esophageal wall, and an esophageal branch of the thoracic aorta. In this paper, we present the first photoacoustic images showing the vasculature of a vertebrate esophagus and discuss the potential clinical applications and future development of photoacoustic endoscopy.     

光声成像造影剂的研究进展

光声成像(PAT)是利用光声效应获得生物组织或材料的断层图像或三维立体图像的一种成像方法,它兼具光学和声学成像的优点,从而成为目前比较有应用前景的一种成像模式。光声成像造影剂是光声成像的对比增强剂,它通过改变局部组织的声学和光学特性,提高成像对比度和分辨率,从而显著增强光声成像的成像效果,成为当前生物医学领域研究的一个热点。目前常见的光声成像造影剂主要有金纳米材料,碳纳米材料,染料相关纳米材料以及其他纳米材料,这些材料有它们独特的优势,它们尺寸小,稳定性好,具有良好的生物相容性,但在临床应用时本身又存在一些问题。本文综述了光声成像造影剂的种类并简要概述了其研究进展,并对其未来在生物医学领域的应用前景做了进一步展望。     

不同探测距离对光声成像的影响

为了研究不同探测距离对光声成像的影响,采用了线性扫描和滤波反投影算法,得出了吸收体间距相对探测距离越大,则成像亮度差异明显,吸收体远离探测器,则重建图像变形很明显.采用了光声信号衰减补偿的方法,对前者重建图像取域值,对后者采用旋转扫描重建,均得到了较好的图像质量.该研究结果对光声成像探测距离的合理选择和成像效果评估具有...     

Location of Triple-Negative Breast Cancers: Comparison with Estrogen Receptor-Positive Breast Cancers on MR Imaging

There has been a major need to better understand the biological characteristics of triple-negative breast cancers. Compared with estrogen receptor (ER)-positive cancers, several magnetic resonance (MR) imaging findings have been reported as characteristic findings. However, information regarding their location has not been described. Our study was to compare the location of triple-negative breast cancers with that of ER-positive breast cancers using magnetic resonance (MR) imaging. The locations of 1102 primary breast cancers (256 triple-negative and 846 ER-positive) in 1090 women (mean, 52.1 years) were reviewed using three-dimensional (3D) coordinates. The x-axis measurement was recorded as the transverse distance from the posterior nipple line; y-axis measurement as the anteroposterior distance from the chest wall; z-axis measurement as the superoinferior distance from the posterior nipple line. The association between breast cancer subtype and tumor location was evaluated using multiple linear regression analysis. Triple-negative breast cancers were significantly closer to the chest wall than ER-positive breast cancers in absolute (1.8 cm vs. 2.3 cm, P < .0001) and normalized (0.21 vs. 0.25, P < .0001) y-axis distances. The x- and z-axes distances were not significantly different between triple-negative and ER-positive breast cancers. Multiple linear regression analysis revealed that age, mammographic density, axillary nodal status, and triple-negative subtype were significantly associated with absolute and normalized distances from the chest wall (all P < .05). Our results show that triple-negative breast cancers have a tendency toward a posterior or prepectoral location compared with ER-positive breast cancers.     

玻璃粘连蛋白血清学检测对乳腺癌早期诊断价值的初步研究

目的:探讨玻璃粘连蛋白血清学表达与乳腺癌早期诊断的相关性。方法:采用酶联免疫吸附试验(ELISA)定量测定62例乳腺癌(0-Ⅰ期癌22例,Ⅱ-Ⅲ期癌40例)和8例乳腺良性病变患者血清玻璃粘连蛋白水平,分析玻璃粘连蛋白表达在良性与各期乳腺癌中的变化规律,同时比较CA153、CA125、CEA的表达情况。结果:0-Ⅰ期乳腺癌组血清玻璃粘连蛋白的表达水平(231.45±30.54μg/m L)显著高于良性对照组(197.84±24.31μg/m L)和Ⅱ-Ⅲ期乳腺癌组(209.34±31.25μg/m L),差异均有统计学意义(P0.01);玻璃粘连蛋白血清表达水平与乳腺癌组织学分级、年龄、肿瘤大小、月经状况、ER、PR、Her-2及Ki-67表达无关(P0.05);而血清CA153、CA125、CEA表达水平随着临床分期升高而升高,其中CA153的表达存在统计学差异(P0.05)。结论:血清玻璃粘连蛋白水平在早期阶段乳腺癌(0-Ⅰ期)显著高于良性和中期(Ⅱ-Ⅲ期)乳腺癌患者,提示玻璃粘连蛋白可能是一项有潜力的乳腺癌早期诊断指标,而血清CA153、CA125、CEA表达则主要与乳腺癌病情发展相关。     

In-Line Phase Contrast Imaging of Hepatic Portal Vein Embolization with Radiolucent Embolic Agents in Mice: A Preliminary Study

It is crucial to understand the distribution of embolic agents inside target liver during and after the hepatic portal vein embolization (PVE) procedure. For a long time, the problem has not been well solved due to the radiolucency of embolic agents and the resolution limitation of conventional radiography. In this study, we first reported use of fluorescent carboxyl microspheres (FCM) as radiolucent embolic agents for embolizing hepatic portal veins. The fluorescent characteristic of FCM could help to determine their approximate location easily. Additionally, the microspheres were found to be fairly good embolizing agents for PVE. After the livers were excised and fixed, they were imaged by in-line phase contrast imaging (PCI), which greatly improved the detection of the radiolucent embolic agents as compared to absorption contrast imaging (ACI). The preliminary study has for the first time shown that PCI has great potential in the pre-clinical investigation of PVE with radiolucent embolic agents.     

Imaging of an Inflammatory Injury in the Newborn Rat Brain with Photoacoustic Tomography

Background

The precise assessment of cerebral saturation changes during an inflammatory injury in the developing brain, such as seen in periventricular leukomalacia, is not well defined. This study investigated the impact of inflammation on locoregional cerebral oxygen saturation in a newborn rodent model using photoacoustic imaging.

Methods

1 mg/kg of lipopolysaccharide(LPS) diluted in saline or saline alone was injected under ultrasound guidance directly in the corpus callosum of P3 rat pups. Coronal photoacoustic images were carried out 24 h after LPS exposure. Locoregional oxygen saturation (SO₂) and resting state connectivity were assessed in the cortex and the corpus callosum. Microvasculature was then evaluated on cryosection slices by lectin histochemistry.

Results

Significant reduction of SO₂ was found in the corpus callosum; reduced SO₂ was also found in the cortex ipsilateral to the injection site. Seed-based functional connectivity analysis showed that bilateral connectivity was not affected by LPS exposure. Changes in locoregional oxygen saturation were accompanied by a significant reduction in the average length of microvessels in the left cortex but no differences were observed in the corpus callosum.

Conclusion

Inflammation in the developing brain induces marked reduction of locoregional oxygen saturation, predominantly in the white matter not explained by microvascular degeneration. The ability to examine regional saturation offers a new way to monitor injury and understand physiological disturbance non-invasively.     

光声成像在光动力疗法研究中的应用

组织氧合作用和光敏剂应用在疾病诊治中都有着重要的作用,因此其实时在体无损检测很有意义。光动力疗法涉及光敏剂、光和氧分子三大要素,其疗效受组织氧合作用影响。本文对光声成像(PAI)、光声寿命成像(PALI)和多光谱光声层析成像(MSOT)等光声成像技术在光动力疗法的研究和应用中的使用现状进行了综述。对相关设备系统在检测光敏剂、组织氧分压和微血管损伤等方面的应用原理和技术分别进行了介绍,并总结了这些技术的应用前景。     

基于压缩感知理论的光声成像方法研究现状

光声成像是一种新兴的无损生物医学成像方法,因其兼具高灵敏的光学对比度和超声能够对深层组织进行高分辨成像的优点,已经成为当前生物医学成像领域发展最快的技术之一。光声成像的光吸收对比度能够反映生物组织微小的组织病变,与血氧饱和度等多种功能和生理信息紧密相关,目前已被证明在肿瘤血管新生研究、早期癌症检测和心血管疾病诊断等方面有很大的应用潜力。基于超声阵列探测的常规光声计算层析成像系统,数据采集量大,由此导致的较低数据采集和成像速度成为制约该技术临床应用和转化的重要因素。压缩感知理论可以在远低于Nyquist采样定理的欠采样方式下,高质量重建信号,已被广泛用于信号处理和传统的医学图像重建领域。自2009年压缩感知理论被应用于光声成像以来,已有的研究结果表明,该方法为解决目前大区域光声成像的数据采集和成像速度问题提供了一条有效的途径。本文将重点介绍压缩感知理论用于光声成像的基本原理、研究现状、面临的问题和应用前景。     

在体光声成像检测损伤组织及体内异物

利用旋转扫描光声成像采集系统对脑损伤动物进行在体成像检测研究.对由金属物刺伤的脑内组织损伤和出血现象进行高分辨成像;光声成像成功定位小鼠颅骨内针刺损伤的位置和清晰展现组织损伤引致的颅内瘀血;成功利用光声成像观测到外损伤金属异物在颅内的形态结构及位置信息,分析了光声成像对金属异物定位检测和组织损伤出血分布的检测可行性,为提出新型的脑外伤检测技术作应用基础的研究.     

Breast Milk Substitute: A Bacteriological Study

The increased susceptibility of infants fed on cows'' milk preparations has been attributed, at least in part, to differences in the nature of the large-bowel content—owing to the acidity of the faeces and their high content of Lactobacillus bifidus. In an attempt to mimic these features of the breastfed infant in one who is fed artificially, a breast milk substitute was devised which resembles breast milk in several important ways. When this material was fed to newborn infants the faeces developed the characteristics of those of the breast-fed child.     

Imaging Breast Density: Established and Emerging Modalities

Mammographic density has been proven as an independent risk factor for breast cancer. Women with dense breast tissue visible on a mammogram have a much higher cancer risk than women with little density. A great research effort has been devoted to incorporate breast density into risk prediction models to better estimate each individual’s cancer risk. In recent years, the passage of breast density notification legislation in many states in USA requires that every mammography report should provide information regarding the patient’s breast density. Accurate definition and measurement of breast density are thus important, which may allow all the potential clinical applications of breast density to be implemented. Because the two-dimensional mammography-based measurement is subject to tissue overlapping and thus not able to provide volumetric information, there is an urgent need to develop reliable quantitative measurements of breast density. Various new imaging technologies are being developed. Among these new modalities, volumetric mammographic density methods and three-dimensional magnetic resonance imaging are the most well studied. Besides, emerging modalities, including different x-ray–based, optical imaging, and ultrasound-based methods, have also been investigated. All these modalities may either overcome some fundamental problems related to mammographic density or provide additional density and/or compositional information. The present review article aimed to summarize the current established and emerging imaging techniques for the measurement of breast density and the evidence of the clinical use of these density methods from the literature.