体素内不相干运动成像对于周围型肺癌血供情况及细胞密集程度的价值研究

摘要 目的：探究周围型肺癌3.0 T磁共振成像（MRI）的体素内不相干运动成像（IVIM-DWI）各参数值对其血供情况以及细胞密集程度的价值。方法：选取2019年1月-2021年10月于本院行手术切除后并经病理检查证实为周围型肺癌的患者50例,术前均行常规MRI平扫、增强以及IVIM-DWI成像,分别测量所有病灶以及对侧相对称正常肺组织的标准表观扩散系数（sADC）、真实扩散系数（D）、灌注相关扩散系数（Ｄ*）以及灌注分数（?）。比较两者IVIM-DWI参数;比较不同强化程度下周围型肺癌病灶IVIM-DWI参数;Spearman 秩相关分析周围型肺癌病灶IVIM-DWI参数与强化程度的相关性;通过绘制受试者工作特征（ROC）曲线,分析与强化程度存在相关性的IVIM-DWI参数对周围型肺癌血供情况及细胞密集程度的评估价值。结果：周围型肺癌病灶的sADC、D均低于正常肺组织,D*、?均高于正常肺组织,差异均具有统计学意义（P<0.05）。高度强化下周围型肺癌病灶D*高于中度强化、轻度强化,?低于中度强化、轻度强化,而D仅高于轻度强化,差异均具有统计学意义（P<0.05）,不同强化程度间sADC均无统计学差异（P>0.05）。Spearman秩相关分析显示周围型肺癌病灶的D*与强化程度呈正相关（P<0.05）,?与强化程度呈负相关（P<0.05）。通过绘制ROC曲线分析显示D*、?对周围型肺癌血供情况以及细胞密集程度评估的AUC大于0.700,提示其具有较高的评估价值。结论：IVIM-DWI模型既可以反映周围型肺癌的血供情况,也可以反映病变细胞密集程度,有助于提高对周围性肺癌血管情况及细胞密集程度的评估价值。     

Differential magnetic resonance diagnosis of central lung cancer and acute pneumonia

The paper analyzes the authors' own data of chest magnetic resonance imaging (MRI) in 86 patients with verified central lung cancer and acute pneumonia. The MRI signs of lung cancer are systematized in exo-, endo-, and peribronchial forms of growth. The additional capacities of contrast enhancement are analyzed. The MRI semiotics of acute pneumonia has been developed. The differential diagnostic criteria for recognizing central lung cancer and acute pneumonia have been also elaborated.     

直径大于3厘米的周围型肺癌血流动力学的多排螺旋CT动态增强扫描研究

目的:研究直径3厘米以上周围型肺癌血流动力学的螺旋CT(电子计算机断层扫描,Computed Tomography)动态增强扫描的特点。方法:选取我院收治的肿瘤直径3 cm的周围型肺癌患者55例,肺部腺瘤(良性)患者10例,肺部炎性结节患者26例。分别进行螺旋CT动态增强扫描,记录其CT值、强化峰值(Peak enhancement,PH),绘制动态增强时间-密度曲线,计算并比较曲线最大增强线性斜率(steepes slope,SS)以及血流灌注量(blood perfusion,BP)。结果:肺部炎性结节患者的密度曲线在120 s达到最大值;肺癌患者的密度曲线至65 s达到高峰;胸腺瘤患者的密度曲线变化不明显。肺癌组PH平均值大于胸腺瘤组,差异有统计学意义(P0.05);胸腺瘤组PH平均值小于肺部炎性结节组,差异有统计学意义(P0.05);肺癌组SS和BP大于胸腺瘤组,差异有统计学意义(P0.05);胸腺瘤组SS和BP小于肺部炎性结节组,差异有统计学意义(P0.05)。结论:螺旋CT动态增强扫描能够反映直径3厘米以上周围型肺癌的血流动力学特点从而有助于在肺癌的诊断和鉴别诊断。     

Central cancer of the lung in MR image

The paper analyzes the authors' own material based on the data of chest magnetic resonance imaging (MRI) in 48 patients with verified central cancer of the lung. The algorithm of chest MRI optimized by the authors is presented. The MRI signs of lung cancer in exo- and peribronchial forms of cancer are systematized. The MRI semiotics of chest structural damages are given in the extent of a tumor when progressing, and a metastatic lesion. The MRI signs of complications of this disease are specified.     

Identification with MRI of the pleura as a major site of the acute inflammatory effects induced by ovalbumin and endotoxin challenge in the airways of the rat

Inflammatory effects in the rat lung have been investigated, non-invasively by MRI, at early time points (3 and 6 h) after ovalbumin (OA) or endotoxin (LPS) challenges. Six hours after challenge with OA, a strong, even inflammatory signal was present around the periphery of the lung in a region corresponding to the pleura. Histological analysis confirmed the presence of marked edema associated with the pleural cavity of OA-treated animals. Lower levels of pleural edema were observed in MRI and histological evaluation of LPS-treated animals and no abnormality was observed in actively sensitized and na?ve, saline-treated groups. Diffuse edematous signals were detected in the lung 3 and 6 h after challenge with OA or LPS; the signal volumes were larger at both time points following OA instillation. Bronchoalveolar lavage (BAL) fluid analysis performed 6 h after challenge revealed increased levels of protein and greater cellular activation in OA- than in LPS-treated animals. Furthermore, increased levels of peribronchial edema were found by histology 6 h after OA. BAL fluid and histological assessments demonstrated that the inflammatory signals were due to edema and not mucus as no significant changes in BAL mucin concentrations or differences in goblet cells were identified between OA or LPS challenge and their respective vehicle groups. Our data show that MRI is able to detect, non-invasively, inflammatory signals in both the lung and the pleura in spontaneously breathing animals, highlighting its potential to study the consequences of pulmonary insults on both sites.     

Differential proteome profiling of pleural effusions from lung cancer and benign inflammatory disease patients

The pleural effusion proteome has been found containing information that directly reflects pathophysiological status and represents a potential diagnostic value for pulmonary diseases. However, the variability in protein composition between malignant and benign effusions is not well understood. Herein, we investigated the changes of proteins in pleural effusions from lung adenocarcinoma and benign inflammatory disease (pneumonia and tuberculosis) patients by two-dimensional difference gel electrophoresis (2D-DIGE). Twenty-eight protein spots displayed significantly different expression levels were positively identified by MALDI-TOF-MS representing 16 unique proteins. Five identified protein candidates were further validated and analyzed in effusions, sera or tissues. Among them, hemopexin, fibrinogen gamma and transthyretin (TTR) were up-regulated in cancer samples. The effusion concentration of serum amyloid P component (SAP) was significantly lower in lung cancer patients than in benign inflammatory patients, but no differences were found in sera samples. Moreover, a Jumonji C (JmjC)-domain-containing protein, JMJD5, was observed to be down-regulated in malignant effusions, lung cancer tissues and cancer cells. These results shed light on the altered pleural effusion proteins as a useful and important complement to plasma or other routine clinical tests for pulmonary disease diagnosis.     

Genetics of preneoplasia: lessons from lung cancer

From biological, histopathologic, and clinical perspectives, lung cancer is a highly complex neoplasm probably having multiple preneoplastic pathways. The sequence of histopathologic changes in the bronchial mucosa that precedes the development of squamous carcinomas of the lung has been identified. For the other major forms of lung cancer, however, such sequences have been poorly documented. This review summarizes the current knowledge regarding the molecular and histopathologic pathogenesis of lung cancer and discusses the complexity of identifying novel molecular mechanisms involved in the development of the lung premalignant disease, and their relevance to the development of new strategies for early detection and chemoprevention. Although our current knowledge of the molecular pathogenesis of lung cancer is still meager, work over the last decade has taught several important lessons about the molecular pathogenesis of this tumor, including the following: a) Better characterization of the high-risk population is needed. b) There are several histopathologic and molecular pathways associated with the development of the major types of non-small cell lung cancer. c) Although there is a field effect phenomenon for lung preneoplastic lesions, recent data suggest that there are at least two distinct lung airway compartments (central and peripheral) for lung cancer pathogenesis. d) Inflammation may play an important role in lung cancer development and could be an important component of the field effect phenomenon. e) For lung adenocarcinoma, at least two pathways (smoking-related and nonsmoking-related) have been identified. f) Finally, the identification of deregulated molecular signaling pathways in lung cancer preneoplasias may provide a rationale for designing novel strategies for early detection and targeted chemoprevention of lung cancer.     

磁共振成像对非小细胞肺癌的诊断价值分析

目的:探讨磁共振成像(Magnetic resonance imaging,MRI)对非小细胞肺癌的诊断价值。方法:选择2016年9月-2019年4月南京医科大学附属脑科医院(胸科院区)放射科收治的肺部结节患者74例,包括病理证实为肺部良性病变54例(良性组)和非小细胞肺癌20例(肺癌组)。所有患者都给予常规MRI、增强MRI与磁共振扩散加权成像(Diffusion weighted imaging,DWI),记录影像学特征并评估其诊断价值。结果:肺癌组的病灶形态、边缘等MRI特征与良性组对比差异无统计学意义(P0.05)。在b值=0、600、800、1000 s/mm~2条件下,肺癌组的病灶表观扩散系数(Apparent diffusion coefficient,ADC)值都显著低于良性组(P0.05)。肺癌组的病灶MRI增强Ⅰ型+Ⅱ型比例显著高于良性组(P0.05)。MRI鉴别诊断非小细胞肺癌的敏感性与特异性为98.1%和94.4%。结论:MRI用于非小细胞肺癌的诊断能反映病灶组织的血流动力学与水分子活动状况,具有较高的诊断敏感性与特异性。     

肺部微生物组通过炎症反应介导慢性阻塞性肺疾病转化为肺癌的研究进展

肺部微生物组存在于呼吸道和实质组织中,通过菌群紊乱、代谢产物、炎症反应、免疫反应、基因毒性等方面介导肺部损伤。随着肺部微生物组的深入研究,发现肺部微生物组的相关活动与慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)和肺癌息息相关,能够促使COPD向肺癌的转变。本文主要介绍了肺部微生物组稳态及其通过炎症反应导致COPD和肺癌,重点探讨了肺部微生物组如何通过炎症反应介导COPD转化为肺癌,以期为COPD和肺癌的临床预防、优化治疗以及新型药物设计提供新的理论依据。     

Neurotrophins and lung disease

Neurotrophins are growth factors that exert multiple actions on neuronal and nonneuronal cells. Neurotrophin receptors are expressed on central and peripheral neurons, lymphocytes, monocytes, mast cells, and fibroblasts. In accordance with the distribution of their receptors, neurotrophins control the development and function of neurons and regulate inflammatory processes. Production of neurotrophins is altered in asthma, lung cancer, and pulmonary fibrosis. Evidence from animal models has implicated nerve growth factor (NGF) as a mediator of pulmonary inflammation, bronchoconstriction, and airway hyperreactivity, all of which are hallmarks of asthma. NGF regulates the growth of lung tumor cells and cultured lung fibroblasts. Thus neurotrophins, particularly NGF, are candidate molecules for regulating disease processes in asthma, lung cancer, and pulmonary fibrosis.     

Peripheral carcinoma of the lung in magnetic resonance imaging

This study shows magnetic resonance imaging (MRI) to be a technique in the comprehensive diagnosis of peripheral carcinoma of the lung and in the determination of the extent of a tumor process in the chest. The paper specifies and systematizes the MRI signs of peripheral carcinoma of the lung, the signs of tumor invasion into the pleura, chest, and mediastinal structures. It also analyzes additional capacities of contrast enhancement.     

血清CEA、NSE、CYFRA21-1 联合支气管活检在周围型肺癌诊断鉴别中的应用

目的:探讨血清肿瘤标志物癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFRA21-1)联合经纤维支气管镜肺活检(TBLB)在周围型肺癌诊断鉴别中的应用价值。方法:选择2012年9月到2014年9月在我院临床确诊的402例周围型肺癌患者。检测所有患者的血清CEA、NSE和CYFRA21-1的浓度及分析TBLB检测结果,分析不同病理类型和不同病灶直径大小时各项检测指标及联合检测的阳性检出率。结果:所有肺癌患者中,血清CEA、NSE、CYFRA21-1和TBLB的阳性检出率分别为51.74%,35.07%,41.79%和60.70%。四项指标联合检测的阳性检出率为89.05%,明显分别高于四项指标的阳性检出率(均P0.05)。腺癌、鳞癌、小细胞肺癌及其他类型肺癌组四项联合检测的阳性检出率明显高于四项单独检测(均P0.05)。病灶直径为2 cm、2-6 cm和6 cm时,四项联合检测的阳性检出率明显高于四项单独检测(均P0.05)。结论:血清CEA、NSE、CYFRA21-1联合TBLB检测周围型肺癌较单项检测,阳性检出率高,值得在临床上推广应用。     

Functional expression of transient receptor potential melastatin- and vanilloid-related channels in pulmonary arterial and aortic smooth muscle

Although the accumulation of neutrophils in the lungs and airways is common to many inflammatory lung diseases, including acute lung injury, the alterations that neutrophils undergo as they leave the peripheral circulation and migrate into the lungs have not been well characterized. Human volunteers were exposed to endotoxin by bronchoscopic instillation. The resulting air space neutrophil accumulation and peripheral blood neutrophils were isolated 16 h later, compared with circulating neutrophils isolated before or after to the pulmonary endotoxin exposure, and compared with circulating neutrophils exposed to endotoxin in vitro. Microarray analysis was performed on air space, circulatory, and in vitro endotoxin-stimulated neutrophils. Functional analysis included the determination of neutrophil apoptosis, chemotaxis, release of cytokines and growth factors, and superoxide anion release. Dramatic gene expression differences were apparent between air space and circulating neutrophils: approximately 15% of expressed genes have altered expression levels, including broad increases in inflammatory- and chemotaxis-related genes, as well as antiapoptotic and IKK-activating pathways. Functional analysis of air space compared with circulating neutrophils showed increased superoxide release, diminished apoptosis, decreased IL-8-induced chemotaxis, and a pattern of IL-8, macrophage inflammatory protein-1beta, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha release different from either unstimulated or LPS-stimulated circulating neutrophils. Many of these changes are not elicited by in vitro treatment with endotoxin. Limited differences were detected between circulating neutrophils isolated before and 16 h after pulmonary endotoxin instillation. These results suggest that neutrophils sequestered in the lung become fundamentally different from those resident in the circulation, and this difference is distinct from in vitro activation with endotoxin.     

X线片和多层螺旋CT诊断及鉴别周围型肺癌的对比研究

目的:对比X线平片和多层螺旋CT诊断及鉴别周围型肺癌的效果。方法:选取了100例周围型肺癌患者,所有患者入院后先行X线片检查,后进行多层螺旋CT检查。通过观察并记录X线片与多层螺旋CT对周围型肺癌的影像学特征、临床TNM分期的诊断效果,评价X线平片和多层螺旋CT对周围型肺癌的诊断效果。结果:多层螺旋CT对周围型肺癌的肿块、分叶征、支气管气象征、空洞、胸膜凹陷、血管集束征,胸腔积液的检出率均高于X线片(P0.05)。根据外科病理TNM分期结果,多层螺旋CT对周围型肺癌的临床TNM分期诊断符合率为92.0%,X线对周围型肺癌的临床TNM分期诊断符合率为61.0%,多层螺旋CT对周围型肺癌的临床TNM分期诊断符合率明显高于X线(P0.05)。结论:多层螺旋CT对于周围型肺癌各类型影像学征象具有较好的检出率,对周围型肺癌临床TNM分期诊断准确性接近病理诊断结果。     

Magnetic resonance imaging of Klebsiella pneumoniae-induced pneumonia in mice

In vivo imaging of small animals is a rapidly developing field. However, the potential of global imaging of infectious processes in animal models remains poorly explored. We used magnetic resonance imaging (MRI) to follow the development and regression of inflammatory lesions caused by infection by Klebsiella pneumoniae in mouse lungs. A virulent strain caused an intense inflammation within 2 days in the whole lungs, while an avirulent strain did not show significant changes. Mice infected with the virulent strain and subsequently treated with antibiotics presented a severe inflammation localized mainly in the left lung that disappeared after a week. The lesions observed by MRI correlated with the damage seen by histological analysis and a 3D representation of the tissue allowed better visualization of the development and healing of inflammatory lesions. MRI thus represents a powerful technique to study in vivo the interactions between a pathogen and its host in real time.     

Multipotent capacity of immortalized human bronchial epithelial cells

While the adult murine lung utilizes multiple compartmentally restricted progenitor cells during homeostasis and repair, much less is known about the progenitor cells from the human lung. Translating the murine stem cell model to humans is hindered by anatomical differences between species. Here we show that human bronchial epithelial cells (HBECs) display characteristics of multipotent stem cells of the lung. These HBECs express markers indicative of several epithelial types of the adult lung when experimentally tested in cell culture. When cultured in three different three-dimensional (3D) systems, subtle changes in the microenvironment result in unique responses including the ability of HBECs to differentiate into multiple central and peripheral lung cell types. These new findings indicate that the adult human lung contains a multipotent progenitor cell whose differentiation potential is primarily dictated by the microenvironment. The HBEC system is not only important in understanding mechanisms for specific cell lineage differentiation, but also for examining changes that correlate with human lung diseases including lung cancer.     

Selection of 3LL tumor subline resistant to natural effector cells concomitantly selected for increased metastatic potency

Summary The numbers of strongly adherent monocytes in the peripheral blood of normal subjects and cancer patients were determined. The method used was to place peripheral blood mononuclear cells in microwells and culture them for 1 week. At the end of that period, adherent macrophages were counted in the Coulter counter after release. Adherent cells per milliliter of blood, per total cells, and per mononuclear cells or monocytes plated were markedly diminished in the peripheral blood mononuclear cells of 44 melanoma, 23 breast cancer, 18 lung cancer, nine colon cancer, and 27 leukemia patients. Median values were 14.8×10⁴ adherent cells per ml peripheral blood for 86 normal subjects, as against 2.5×10⁴ per ml in the peripheral blood of the 125 patients (P<0.001). There was a poor correlation between the adherent cell numbers and the peripheral blood leukocyte counts, but an excellent correlation of the different adherent cell counts with each other. The number of adherent cells in the peripheral blood varied inversely with age in the cancer patients, but not in the normal subjects (r=0.29, P<0.005). When patients under age 50 were compared to the controls, the deficiency of adherent cells was slightly more severe in patients with stage IV lung cancer than in those with stage III lung cancer. In contrast, there was no difference in the degree of deficiency between patients with stage III melanoma and no evident disease and patients with stage IV disseminated metastatic disease. The implications of these results are discussed.     

Augmentation of impaired tumoricidal function in alveolar macrophages from lung cancer patients by cocultivation with allogeneic, but not autologous lymphocytes

 It has been reported that the in vitro development of tumoricidal function in alveolar macrophages from lung cancer patients is reduced significantly when compared to that in peripheral blood monocytes from the same patients or alveolar macrophages from control patients. In the present investigation, a method for potentiating the development of tumoricidal function in alveolar macrophages from lung cancer patients is described. This method, which relies on priming the macrophages with purified, allogeneic peripheral blood lymphocytes from normal donors, could not be demonstrated when autologous lymphocytes from lung cancer patients were used in the priming coculture. The augmentation of tumoricidal function appears to be mediated by one or more soluble factors, since supernatants from cocultures of alveolar macrophages and allogeneic peripheral blood lymphocytes could enhance the cytotoxic function of freshly obtained alveolar macrophages. Furthermore, it appears that NK cells are necessary for this effect, since depletion of CD56⁺/CD57⁺ cells from allogeneic lymphocytes eliminated their capacity to enhance alveolar macrophage cytotoxic function. The augmentation of cytotoxic function elicited in alveolar macrophages by this method was not associated with changes in the secretion of tumor necrosis factor α, or interleukin 1β. Received: 15 March 1997 / Accepted: 11 June 1997     

MRI-guided lung SBRT: Present and future developments

Stereotactic body radiotherapy (SBRT) is rapidly becoming an alternative to surgery for the treatment of early-stage non-small cell lung cancer patients. Lung SBRT is administered in a hypo-fractionated, conformal manner, delivering high doses to the target. To avoid normal-tissue toxicity, it is crucial to limit the exposure of nearby healthy organs-at-risk (OAR).Current image-guided radiotherapy strategies for lung SBRT are mostly based on X-ray imaging modalities. Although still in its infancy, magnetic resonance imaging (MRI) guidance for lung SBRT is not exposure-limited and MRI promises to improve crucial soft-tissue contrast. Looking beyond anatomical imaging, functional MRI is expected to inform treatment decisions and adaptations in the future.This review summarises and discusses how MRI could be advantageous to the different links of the radiotherapy treatment chain for lung SBRT: diagnosis and staging, tumour and OAR delineation, treatment planning, and inter- or intrafractional motion management. Special emphasis is placed on a new generation of hybrid MRI treatment devices and their potential for real-time adaptive radiotherapy.     

Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI

Magnetic resonance imaging (MRI) has been used previously to follow noninvasively inflammatory processes in rat acute models of lung inflammation. Here the technique was applied to a model involving repeated intratracheal administration of ovalbumin (OA). Anatomical MRI was performed at different time points with respect to a single or multiple OA challenges in Brown Norway rats actively sensitized to the allergen. Vascular permeability was assessed using dynamic contrast-enhanced MRI (DCE-MRI). Bronchoalveolar lavage (BAL) fluid analysis and histology were performed to validate the MRI data. The time course of MRI signals after a single OA challenge reached a maximum at 48 h and decreased significantly at 96 h. After the second and subsequent challenges, the maximum signal occurred at 6 h with a time-dependent decline over the remainder of the time course. A reduction of the inflammatory response following repeated administration of OA was also detected by BAL fluid analysis. The decrease in vascular permeability assessed by DCE-MRI in repeatedly OA-challenged rats was consistent with the thickening of the vascular wall for vessels of diameter up to 300 microm revealed by histology. Angiogenesis of vessels smaller than 30 microm was also detected histologically. These results suggest that MRI can be used to detect the inflammatory response and vascular remodeling associated with chronic airway inflammation in rat models involving repeated administration of allergen. As the contrast agent used in the DCE-MRI experiments is approved for clinical use, there is potential to translate the approach to patients.