转基因小鼠前列腺癌模型肿瘤三维超声成像与三维病理重建

目的:应用三维超声微成像检测转基因小鼠前列腺癌(TGMAP)模型并与三维病理图像比较.方法:通过三维微超声成像系统对TGMAP小鼠前列腺癌进行三维超声图像采集,对前列腺癌标本进行连续切片,扫描并存储图像,纵向排列所有的二维图像获得重建的三维数字化病理图像,对三维超声图像和三维病理图像进行比较.结果:通过定性比较前列腺癌的三维超声成像与连续组织学切片,证实了该超声系统可以准确显示活体小鼠肿瘤的大小和形状.结论:小鼠前列腺癌模型的三维超声微成像有望成为小鼠临床前期研究的新的微成像手段.     

流式细胞仪和基因芯片分析比较基因敲入和转基因小鼠前列腺癌模型

目的:利用流式细胞仪和基因芯片技术分析比较基因敲入(KIMAP)和转基因(TGMAP)小鼠前列腺癌模型.方法:对于来自KIMAP和TGMAP的肿瘤标本进行流式细胞仪分析和基因芯片分析.结果:来源于TGMAP(n=8)和KIMAP(n=9)的小鼠前列腺癌标本流式细胞仪分析显示,多数KIMAP肿瘤为双倍体,与临床相近,而所有TGMAP肿瘤均为非整倍体.基因芯片分析证明,在KIMAP中免疫应答基因高表达,而TGMAP晚期肿瘤(26～32周)中与神经内分泌肿瘤分化相关的基因占主体.结论:由于KIMAP模型成功地模仿了人类前列腺癌特征,在前列腺癌临床前期研究中具有潜在的应用价值.     

小鼠前列腺癌血清学肿瘤标志物检测系统的建立和应用

目的:建立小鼠前列腺癌的血清学肿瘤标志物前列腺特异性蛋白94氨基酸(PSP94)检测系统。方法:建立小鼠血清PSP94竞争ELISA方法,并检测基因敲入小鼠前列腺癌模型小鼠的血清PSP94变化。结果:建立竞争ELISA方法,并以1ng/mL的灵敏度定量检测血清PSP94水平。野生型小鼠PSP94血清平均水平为49.8ng/mL,对于20周龄、40周龄和>40周龄的前列腺癌小鼠模型分别为150.9、835.5和774.8ng/mL。结论:首个小鼠类前列腺癌血清学标志物的建立将会极大地方便对人类前列腺癌的基础及临床前期研究。     

多肿瘤标志物蛋白芯片检测系统对前列腺癌的诊断价值

目的探讨多肿瘤标志物蛋白芯片检测系统在前列腺癌诊断中的价值。方法使用HD2001A型生物芯片仪系统分别对前列腺癌、良性前列腺疾病患者、健康人联合检测12种肿瘤标志物。结果前列腺癌和良性前列腺疾病患者的前列腺特异性抗原（PSA）、游离前列腺特异性抗原（f-PsA）、铁蛋白等水平均升高，但前列腺癌组增高的幅度明显高于良性前列腺疾病组，前列腺癌时PSA阳性率为73％，f-PSA为78％，如果应用多肿瘤标志物C12检测系统检测，阳性率可提高到80％。结论多肿瘤标志物蛋白芯片检测系统能提高前列腺癌的检出率。     

经直肠三维高频超声诊断前列腺癌

目的：探讨经直肠三维高频超声城像对前列腺癌的诊断价值。方法：应用Combison^R530三维超声成像仪（7.5MHz经直肠探头）检测46例前列腺癌,对其声像图表现进行回顾性分析。结果：前列腺癌在超声声像图上可表现为单纯结节型,结节浸润型及弥漫浸润型三种改变。三维超声新技术通过多平面观察,可获得比二维超声更多的诊断信息,提高了前列腺癌的超声诊断率（尤其对后二型病变）,本组诊断符合率为82.6％,且更容易观察前列腺病灶与包膜及邻近结构之间的空间位置关系,有助于对肿瘤进行分期。结论：经直肠三维超声为操作者提供了更丰富的诊断信息,明显提高了前列腺癌的超声诊断率。     

MRI+超声融合成像引导下前列腺靶向穿刺对PI-RADS评分≥3分的前列腺癌患者的作用

目的:探讨磁共振成像(magnetic resonance image, MRI)+超声融合成像引导下前列腺靶向穿刺对前列腺成像报告和数据系统(PI-RADS)评分≥3分的前列腺癌患者的作用。方法:2019年1月到2021年3月选择入院进行检查的PI-RADS评分≥3分前列腺肿瘤患者80例作为研究对象,所有患者都给予MRI+超声融合成像引导下前列腺靶向穿刺,记录穿刺效果。以手术病理诊断作为金标准,判断诊断效果。结果:在纳入的80例患者经过手术病理检查确诊48例为前列腺癌,将其作为前列腺癌组,其他的32例诊断为前列腺良性肿瘤,作为前列腺良性肿瘤组。两组的一般资料在血压、前列腺体积大小、体指数以及平均年龄方面比较没有较大的差异,无显著性(P>0.05),前列腺癌组的血清前列腺特异性抗原含量明显高于前列腺良性肿瘤组(P<0.05)。前列腺癌组在穿刺过程中的低热、血尿、尿潴留、血便等并发症发生率为8.33%,前列腺良性肿瘤组为9.38%,两组对比无明显差异(P>0.05)。前列腺癌组在MRI上显示外周带内呈低信号灶,形态不规则,边界不清。前列腺良性肿瘤组在MRI上主要显示中央...     

TPB术前DRE、PSA、TRUS、MRI检查的意义

前列腺癌是男性生殖系最常见的恶性肿瘤,超声引导下进行穿刺活检是常用的微创确诊手段,尽管经直肠指征（DRE）、血清前列腺特异抗原（PSA）、经直肠超声（TRUS）、磁共振成像（MRI）有助于前列腺癌的诊断,但特异性均较低。本文通过回顾分析58例经直肠超声引导下前列腺穿刺活检（TPB）确诊为前列腺癌资料,探讨TPB术前联合检测DRE、PSA、TRUS、MRI联合检测的意义。     

3D-TRUS及弹性成像在前列腺良恶性肿瘤鉴别诊断中的应用研究

目的 探讨经直肠三维超声成像(3D-TRUS)、超声弹性成像在前列腺良恶性肿瘤鉴别诊断中的应用价值。方法 选取2020年2月-2022年5月秦皇岛市中医医院前列腺恶性肿瘤患者63例为研究组，另选取同期收治的前列腺良性肿瘤患者63例为对照组。所有研究对象均分别接受3D-TRUS及超声弹性成像检查，统计分析3D-TRUS及超声弹性成像对前列腺良恶性肿瘤的检出情况、诊断效能(敏感度、特异度、准确度、阴性预测值、阳性预测值)。结果 3D-TRUS检查共检出前列腺癌46例、前列腺良性肿瘤61例，超声弹性成像检查共检出前列腺癌45例、前列腺良性肿瘤61例，联合诊断共检出前列腺癌61例、前列腺良性肿瘤60例；联合诊断敏感度(96.83%)、准确度(96.03%)、阴性预测值(96.77%)高于3D-TRUS(73.02%、84.92%、78.21%)、超声弹性成像(71.43%、84.13%、77.22%),差异有统计学意义(P<0.05);联合诊断特异度(95.24%)、阳性预测值(95.31%)与3D-TRUS(96.83%、95.83%)、超声弹性成像(96.83%、95.74%)比较，...     

前列腺癌淋巴转移的影像学检查

前列腺癌患者有无淋巴结转移对前列腺癌的准确分期至关重要,直接影响到临床治疗方案的选择。本文综述了前列腺癌转移淋巴结的成像方法,描述了前列腺淋巴系统的引流方式,并根据不同个体前列腺癌淋巴引流的多样性,总结了淋巴引流及前哨淋巴结的影像学诊断方法,特别对新近研究的超声造影淋巴成像技术作了介绍及展望。     

多参数引导下经直肠前列腺穿刺活检的应用价值

目的探讨多参数引导下经直肠前列腺穿刺,包括TRUS单参数,TRUS+弹性成像双参数,TRUS+弹性成像+MRI图像三参数超声引导下的穿刺,在前列腺癌诊断中的价值比较。方法回顾性分析我院接受前列腺手术患者186例,其中65例患者行TRUS单参数超声引导下的12点系统穿刺活检,68例行TRUS+经直肠弹性成像双参数超声引导下穿刺活检,53例行TRUS+弹性成像+MRI图像三参数超声引导下穿刺活检。对穿刺结果对比分析。结果经手术病理证实,186个患者中前列腺癌有90例,病理为腺癌,前列腺增生有96例。(1)TRUS单参数引导下的12点系统穿刺65例,其中穿刺病理为前列腺癌有21例,手术病理结果证实为前列腺癌有31例。穿刺阳性率为67.7%,与手术病理符合率为84.6%。(2)TRUS+弹性成像双参数引导下穿刺组共68例,其中穿刺病理为前列腺癌有28例,手术病理结果证实前列腺癌有33例,穿刺阳性率为84.8%,与手术病理符合率为92.6%。(3)TRUS+弹性成像+MRI图像三参数超声引导下穿刺组53例,其中穿刺病理为前列腺癌有25例,手术病理结果证实26例为前列腺癌,穿刺阳性率为96.2%,手术病理符合率为98.1%。结论 TRUS+弹性成像+MRI图像三参数超声引导下的前列腺穿刺活检在前列腺癌的早期筛查中阳性率及手术病理符合率为三种检查方法中最高的,表明多参数引导下的前列腺穿刺具有较高的临床应用价值。     

The use of three-dimensional ultrasound micro-imaging to monitor prostate tumor development in a transgenic prostate cancer mouse model

Longitudinal studies of mouse cancer models required large cohorts since autopsy was the only reliable method to evaluate treatment efficacy. This paper reports the use of high-resolution three-dimensional ultrasound micro-imaging to monitor prostate tumor development in genetically engineered mice. Twenty-nine genetically engineered prostate cancer mice, including castrated and uncastrated mice, were imaged by three-dimensional ultrasound. Qualitative comparisons of three-dimensional ultrasound images with histology sections of prostate tumors demonstrate the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. The correlation coefficient of tumor diameter measurements performed in vivo with three-dimensional ultrasound and at autopsy was 0.997. Prospective tumor detection sensitivity and specificity were 91.7% and 100%. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated diameter doubling times from 10 to 37 days for four prostate tumors during an initial period of rapid progression. Three-dimensional ultrasound will likely become the micro-imaging modality most readily adopted for mouse pre-clinical trial studies.     

A novel knock-in prostate cancer model demonstrates biology similar to that of human prostate cancer and suitable for preclinical studies.

Preclinical studies of prostate cancer (CaP) have employed a genetically engineered mouse model, since there is no naturally occurring CaP in rodents. We have previously reported a new knock-in mouse adenocarcinoma prostate (KIMAP) model. In this study, we demonstrate that the new model possesses a tumor architecture of heterogeneity and multifocality similar to that of human CaP, by utilizing a new compound scoring system to compare with the PSP94 (approved gene symbol Msmb) gene-directed transgenic mouse CaP model (TGMAP). KIMAP mice showed a balanced distribution of tumor extent, which penetrated the prostate gland. Comparative studies on cDNA microarrays demonstrated that KIMAP tumors were upregulated with higher contents of immunoresponse genes, whereas PSP-TGMAP tumors had neuroendocrine (NE) differentiation. The majority of KIMAP mice did not progress to NE CaP, which was observed only at a very late stage and a low frequency. Several tumor marker genes characteristic of human CaP were uniquely identified in KIMAP tumors, including hepsin, maspin, Nkx3.1, CD10 and PSP94 (similar to PSA), etc. The differences between these two CaP models are attributed to the introduction of a single endogenous knock-in mutation. Due to the similarities between human CaP tumors and the PSP-KIMAP tumors, this preclinical model may supplement the current transgenic models to study CaP more accurately.     

Prostate boundary detection and volume estimation using TRUS images for brachytherapy applications

Objective: Authors propose a semi-automatic segmentation algorithm for three-dimensional prostate boundary detection from trans-rectal ultrasound images. As a part of brachytherapy treatment with seeds for early stage prostate cancer, a patient’s prostate is scanned using a trans-rectal ultrasound probe, its boundary is manually outlined, and its volume is estimated for dosimetry purposes. Proposed algorithm requires a reduced amount of radiologist’s input, and thus speeds up the surgical procedure. Methods: The proposed segmentation algorithm utilizes texture differences between ultrasound images of the prostate and the surrounding tissues. It is carried out in the polar coordinate system and uses three-dimensional data correlation to improve the smoothness and reliability of the segmentation. The algorithm is applied to axial trans-rectal ultrasound images and the results are compared to the “ground truth” set by manual prostate boundary outlining (by experienced radiologist). Method is validated on six patients. Results: In our tests, the proposed algorithm estimated prostate volume within 95% of the original radiologist’s estimate. Conclusions: The boundary segmentation obtained from the algorithm can reduce manual input by a factor of 3, without significantly affecting the accuracy of the segmentation. The reduction in the manual input reduces the overall brachytherapy procedure time.     

多平面三维超声诊断膀胱肿瘤及其术前分期

目的 探讨多平面三维超声结合表面三维成像诊断膀胱肿瘤及其术前分期的应用价值.方法 对75例膀胱肿瘤患者进行二维、多平面三维和表面三维超声检查,并与手术病理诊断和分期结果及CT术前分期结果进行对照.结果 二维与三维超声诊断符合率分别为 93.3%与 98.7%;二维与三维超声分期诊断符合率分别为 83.5%与 93.2%,两者差异有统计学意义(P＜0.05);术前CT对膀胱肿瘤的诊断符合率为 90.7%,分期符合率为 79.7%.将三维超声分期符合率与CT分期对照,两者差异有统计学意义(P＜0.05).结论 多平面三维超声结合表面三维诊断膀胱肿瘤及其对肿瘤的术前分期符合率较高,可为临床诊断本病提供更多的信息.

Abstract：

Objective To evaluate the clinical value of multi-tomographic imaging mode of three-dimensional ultrasound combined with surface imaging in diagnosing and staging bladder tumors.Methods Seventy-five patients were examined with three-dimensional ultrasound and two-dimensional ultrasound.In addition,54 cases were undergone preoperative multislice spiral CT.All cases were proved by pathology after operation.Results The qualitation accuracy in the diagnosis of bladder tumor with two-dimensional ultrasound was 93.3%(70/75) and that of three-dimensional ultrasound was 98.7%(74/75).The staging accuracy rates with two-dimensional ultrasound and three-dimensional ultrasound were 83.5%(106/127) and 93.2%(123/132) respectively.The difference of bladder tumor staging between three-dimensional ultrasound and two-dimensional ultrasound was significant (P＜0.05).The qualitation accuracy in the diagnosis of bladder tumor with CT was 90.7%(49/54).The preoperative staging rate of CT was 79.7%(59/74),compared with that of three-dimensional ultrasound,the difference was significant(P＜0.05).Conclusions Multi-tomographic imaging mode of three-dimensional ultrasound combined with surface imaging can provide useful information and makes an improvement in detecting and staging bladder tumors.     

BALB/c裸鼠前列腺癌原位种植模型的超声应用研究

目的 应用高频彩色多普勒超声观察裸鼠前列腺癌原位种植模型肿瘤生长规律,为实验研究提供可靠的观察方法.方法 制作BALB/c裸鼠前列腺癌原位种植模型35只,2～8周每周随机抽取5只裸鼠行超声检查,记录肿瘤大小及声像图特征,每次超声检查结束后立即解剖裸鼠,分离前列腺组织,以HE染色光镜观察原位种植是否成功;根据超声测量肿瘤体积大小描绘肿瘤的生长曲线.结果 超声观察到的裸鼠前列腺癌种植肿瘤全部经HE染色证实.原位种植肿瘤超声表现为低回声,内部见彩色血流信号,7周后肿瘤内部出现无回声液化坏死区,并与周围组织边界不清.肿瘤生长曲线在4～6周上升最快,是肿瘤生长最旺盛期.结论 高频彩色多普勒超声是观察前列腺癌原位种植动物模型肿瘤生长规律的可靠方法.     

Spectrum-analysis and neural networks for imaging to detect and treat prostate cancer

Conventional B-mode ultrasound currently is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy to treat prostate cancer. Yet B-mode images do not adequately display cancerous lesions of the prostate. Ultrasonic tissue-type imaging based on spectrum analysis of radiofrequency (rf) echo signals has shown promise for overcoming the limitations of B-mode imaging for visualizing prostate tumors. This method of tissue-type imaging utilizes nonlinear classifiers, such as neural networks, to classify tissue based on values of spectral parameter and clinical variables. Two- and three-dimensional images based on these methods demonstrate potential for guiding prostate biopsies and targeting radiotherapy of prostate cancer. Two-dimensional images are being generated in real time in ultrasound scanners used for real-time biopsy guidance and have been incorporated into commercial dosimetry software used for brachytherapy planning. Three-dimensional renderings show promise for depicting locations and volumes of cancer foci for disease evaluation to assist staging and treatment planning, and potentially for registration or fusion with CT images for targeting external-beam radiotherapy.     

前列腺癌经直肠超声显像与病理组织学类型的关系

目的:观察前列腺癌的超声声像图特点与病理对照,提高前列腺癌的超声诊断水平。方法:分析21例经术后病理证实为前列腺癌的经直肠超声图像,观察有无异常回声肿块以及肿块的超声回声类型,并分析其与病理组织类型的关系。结果:21例前列腺癌患者经直肠超声诊断正确18例,诊断符合率85.7%,误诊3例,占14.3%。13例表现为低回声结节(占61.9%),8例表现为高回声结节或混合回声结节(占38.1%)。低分化腺癌和中分化腺癌主要表现为低回声(分别占64%和75%)。结论:经直肠超声可以提高前列腺癌的检出率。     

基于不同超声技术评价前列腺癌的诊断价值

目的 探讨不同超声技术联合诊断在前列腺癌诊断中的临床价值。方法 选择2019年1月至2020年8月期间于我院住院欲行前列腺病灶切除术的患者,共175例,术前行经直肠不同超声技术检查,术后根据病理结果分为良性组和恶性组。应用Logistic回归分析进行单因素及多因素分析首先建立不同超声技术诊断前列腺癌的回归模型A评分,在此模型的基础上联合各临床指标及实验室检查结果建立不同超声技术超声联合诊断前列腺癌的回归模型B评分。应用受试者工作特征曲线（ROC）比较模型A评分、模型B评分、年龄、PSA的诊断效能。结果 模型A评分、年龄、PSA为诊断前列腺癌的预测因子,构建模型B评分。模型B评分诊断效能最高,且与模型A、年龄、PSA差异均有统计学意义（P<0.05）。结论 不同超声技术联合实验室检查及结合临床资料对诊断前列腺癌的价值更高。     

Photoacoustic tomography: a potential new tool for prostate cancer

The feasibility of photoacoustic tomography (PAT) for noninvasive imaging of prostate cancer was explored through the study on a canine model in vivo. Imaging of blood-rich lesions mimicking prostate tumors was achieved using a commercial medical ultrasound (US) system without affecting its original imaging functions. Based on the optical contrast between hemoglobin and other tissues, PAT has demonstrated good sensitivity and high contrast-to-noise ratio in visualizing deep lesions; while US has presented the morphological features including the boundary and the urethral of the prostate. PAT of prostate cancer may facilitate improved tumor localization, staging of disease, and detection of recurrences.     

Generating prostate models by means of geometric deformation with application to computerized training of cryosurgery

Purpose

As a part of an ongoing project to develop computerized training tools for cryosurgery, the objective of the current study is twofold: to compile literature data on the likelihood of cancer tumor growth and its effect on the prostate shape and to present a deformation scheme for a 3D organ template in order to generate clinically relevant prostate models. The long-term objective of this study is to develop a database of prostate models for computerized training.

Methods

Cryosurgery is typically performed on patients with localized prostate cancer found in stage T3 or earlier. The distribution of key geometric features likely to be found in the prostate at stage T3 is integrated into a 3D prostate template by employing the extended free-form deformation (EFFD) method. The applied scheme combines two steps: pre-selecting a set of geometric parameter values and manipulating the lattice control points until the prostate model meets the desired criteria.

Results

Examples for model generation are displayed, based on two 3D prostate templates previously obtained from ultrasound imaging. These examples include selected cases with unilateral and bilateral stage T3 tumor growth, suitable for incorporation into a training database.

Conclusions

EFFD is an efficient method for rapid generation of prostate models. The compiled criteria for model generation do not lead to a unique shape since the contours for template deformation are randomly selected. Nevertheless, these criteria do lead to shapes resembling cancer growth, as various growth histories can lead to a tumor characterized by the same key parameter values.