scholarly journals Pulmonary Functional Imaging for Lung Adenocarcinoma: Combined MRI Assessment Based on IVIM-DWI and OE-UTE-MRI

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Liu ◽  
Liyun Zheng ◽  
Gaofeng Shi ◽  
Qian Xu ◽  
Qi Wang ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Lung Adenocarcinoma ◽  
Diagnostic Performance ◽  
Pulmonary Function Tests ◽  
Low Grade ◽  
Operating Characteristics ◽  
Invasive Adenocarcinoma ◽  
Minimally Invasive Adenocarcinoma ◽  
The Difference

PurposeThe goal of current study was to introduce noninvasive and reproducible MRI methods for in vivo functional assessment of lung adenocarcinoma (LUAD).MethodsForty-four patients with pathologically confirmed LUAD were included in this study. All the lesions were classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA). The IA lesions were further divided into five subtype patterns, including acinar, lepidic, papillary, micropapillary and solid. Tumors were grouped depending on predominant subtype: low grade (AIS, MIA or lepidic predominant), intermediate grade (papillary or acinar predominant) and high grade (micropapillary, or solid predominant). Spirometry was performed according to American Thoracic Society guidelines. For each patient, Intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) analysis and oxygen-enhanced MRI (OE-MRI) analysis were performed. Spearman’s test was used to assess the relationship between a) whole lung mean percent signal enhancement (PSE) and pulmonary function tests (PFTs) parameters; b) IVIM-derived parameters and PFTs parameters; c) tumor mean PSE and IVIM-derived parameters. Kruskal -Wallis tests were applied to test the difference of tumor mean PSE and IVIM-derived parameters between different histological tumor grades. Receiver operating characteristics (ROC) analysis was used to evaluate the diagnostic performance.ResultsWhole lung mean PSE was significantly positively correlated with PFTs parameters (r = 0.40 ~ 0.44, P < 0.05). f value derived from IVIM-DWI was significantly negatively correlated with PFTs parameters (r = -0.38 ~ -0.47, P < 0.05). Both tumor mean PSE (P = 0.030 < 0.05) and f (P = 0.022 < 0.05) could differentiate different histological grades. f was negatively correlated with tumor mean PSE (r = -0.61, P < 0.001). For the diagnostic performance, the combination of tumor mean PSE and f outperformed than using tumor mean PSE or f alone in both sensitivity and area under the ROC curve.ConclusionsThe combined measurement of OE-MRI and IVIM-DWI may serve as a promising method for the noninvasive and non-radiation evaluation of pulmonary function. Quantitative analyses achieved by OE-MRI and IVIM-DWI offer an approach of the classification of LUAD subtypes.

A Clinicopathological Study of Small Lung Adenocarcinoma 1 cm or Less in Size: Emphasis on Histological Subtypes Associated With Lymph Node Metastasis and Recurrence

2017 ◽  
Vol 26 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Wei Zhao ◽  
Hui Wang ◽  
Jun Xie ◽  
Bo Tian
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lung Adenocarcinoma ◽  
Who Classification ◽  
Limited Resection ◽  
Adenocarcinoma In Situ ◽  
Invasive Adenocarcinoma ◽  
Node Metastasis ◽  
Minimally Invasive Adenocarcinoma

Background. The aim of this study was to assess the prognostic significance of the newly proposed 2015 World Health Organization (WHO) lung adenocarcinoma classification for patients undergoing resection for small (≤1 cm) lung adenocarcinoma. We also investigated whether lobectomy offers prognostic advantage over limited resection for this category of tumors. Methods. A retrospective study of resected pulmonary adenocarcinomas (n = 83) in sizes 1 cm or less was carried out in which comprehensive histologic subtyping was assessed according to the 2015 WHO classification on all consecutive patients who underwent lobectomy or limited resection between 1998 and 2012. Correlation between clinicopathologic parameters and the difference in recurrence between lobectomy and limited resection group was evaluated. Results. Our data show that the proposed 2015 WHO classification identifies histological subsets of small lung adenocarcinomas with significant differences in prognosis. No recurrence was noted for patients with adenocarcinoma in situ and minimally invasive adenocarcinoma. Invasive adenocarcinomas displayed high heterogeneity and the presence of micropapillary component of 5% or greater in adenocarcinomas was significantly related to lymph node involvement and recurrence ( P < .001). Stage IA patients who underwent limited resection had a higher risk of recurrence than did those treated by lobectomy ( P < .05). Conclusions. Application of the 2015 WHO classification identifies patients with adenocarcinoma in situ and minimally invasive adenocarcinoma had excellent prognosis. Micropapillary pattern was associated with high risk of lymph node metastasis and recurrence.

scholarly journals Genomic and immune profiling of pre-invasive lung adenocarcinoma

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Haiquan Chen ◽  
Jian Carrot-Zhang ◽  
Yue Zhao ◽  
Haichuan Hu ◽  
Samuel S. Freeman ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Adenocarcinoma In Situ ◽  
Copy Number Alterations ◽  
Invasive Adenocarcinoma ◽  
Minimally Invasive Adenocarcinoma ◽  
Invasive Lung Adenocarcinoma ◽  
Hla Loss

AbstractAdenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.

scholarly journals Arterial spin labeling MR imaging for differentiation between high- and low-grade glioma—a meta-analysis

2018 ◽  
Vol 20 (11) ◽  
pp. 1450-1461 ◽  
Author(s):  
Alberto Falk Delgado ◽  
Francesca De Luca ◽  
Danielle van Westen ◽  
Anna Falk Delgado
Keyword(s):  
Mr Imaging ◽  
Arterial Spin Labeling ◽  
Diagnostic Performance ◽  
Meta Analysis ◽  
Spin Labeling ◽  
Low Grade Glioma ◽  
Cochrane Library ◽  
Low Grade ◽  
High Grade ◽  
Operating Characteristics

Abstract Background Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) non-invasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods Cochrane Library, Embase, Medline, and Web of Science Core Collection were searched. Study selection ended November 2017. This study was prospectively registered in PROSPERO (CRD42017080885). Two authors screened all titles and abstracts for possible inclusion. Data were extracted independently by 2 authors. Bivariate random effects meta-analysis was used to describe summary receiver operating characteristics. Trial sequential analysis (TSA) was performed. Results In total, 15 studies with 505 patients were included. The diagnostic performance of ASL CBF for glioma grading was 0.90 with summary sensitivity 0.89 (0.79–0.90) and specificity 0.80 (0.72–0.89). The diagnostic performance was similar between pulsed ASL (AUC 0.90) with a sensitivity 0.85 (0.71–0.91) and specificity 0.83 (0.69–0.92) and pseudocontinuous ASL (AUC 0.88) with a sensitivity 0.86 (0.79–0.91) and specificity 0.80 (0.65–0.87). In astrocytomas, the diagnostic performance was 0.89 with sensitivity 0.86 (0.79 to 0.91) and specificity 0.79 (0.63 to 0.89). Sensitivity analysis confirmed the robustness of the findings. TSA revealed that the meta-analysis was adequately powered. Conclusion Arterial spin labeling MR imaging had an excellent diagnostic accuracy for differentiation between high-grade and low-grade glioma. Given its low cost, non-invasiveness, and efficacy, ASL MR imaging should be considered for implementation in the routine workup of patients with glioma.

scholarly journals Experimental evidence of age-related adaptive changes in human acinar airways

2016 ◽  
Vol 120 (2) ◽  
pp. 159-165 ◽  
Author(s):  
James D. Quirk ◽  
Alexander L. Sukstanskii ◽  
Jason C. Woods ◽  
Barbara A. Lutey ◽  
Mark S. Conradi ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Function ◽  
Pulmonary Function Tests ◽  
Functional Decline ◽  
Forced Expiratory Volume ◽  
Compensatory Mechanism ◽  
Age Related ◽  
Lung Morphometry ◽  
Conducting Airways

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized 3He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized 3He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger.

scholarly journals Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma

2018 ◽  
Vol 10 (467) ◽  
pp. eaat5933 ◽  
Author(s):  
Claudio R. Scafoglio ◽  
Brendon Villegas ◽  
Gihad Abdelhady ◽  
Sean T. Bailey ◽  
Jie Liu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Glucose Transporter ◽  
Early Stage ◽  
Premalignant Lesions ◽  
Low Grade ◽  
Lung Tumorigenesis ◽  
Glucose Transporter 2 ◽  
Potential Marker

The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas. SGLT2 activity could be detected in vivo by positron emission tomography (PET) with the tracer methyl 4-deoxy-4-[18F] fluoro-alpha-d-glucopyranoside (Me4FDG), which specifically detects SGLT activity. Using a combination of immunohistochemistry and Me4FDG PET, we identified high expression and functional activity of SGLT2 in lung premalignancy and early-stage/low-grade LADC. Furthermore, selective targeting of SGLT2 with FDA-approved small-molecule inhibitors, the gliflozins, greatly reduced tumor growth and prolonged survival in autochthonous mouse models and patient-derived xenografts of LADC. Targeting SGLT2 in lung tumors may intercept lung cancer progression at early stages of development by pairing Me4FDG PET imaging with therapy using SGLT2 inhibitors.

scholarly journals Identification of a Clinically Relevant Signature for Early Progression in KRAS-Driven Lung Adenocarcinoma

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 600 ◽  
Author(s):  
Neidler ◽  
Kruspig ◽  
Hewit ◽  
Monteverde ◽  
Gyuraszova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Human Lung ◽  
Tumour Progression ◽  
Human Lung Cancer ◽  
Low Grade ◽  
Invasive Adenocarcinoma

Inducible genetically defined mouse models of cancer uniquely facilitate the investigation of early events in cancer progression, however, there are valid concerns about the ability of such models to faithfully recapitulate human disease. We developed an inducible mouse model of progressive lung adenocarcinoma (LuAd) that combines sporadic activation of oncogenic KRasG12D with modest overexpression of c-MYC (KM model). Histological examination revealed a highly reproducible spontaneous transition from low-grade adenocarcinoma to locally invasive adenocarcinoma within 6 weeks of oncogene activation. Laser-capture microdissection coupled with RNA-SEQ (ribonucleic acid sequencing) was employed to determine transcriptional changes associated with tumour progression. Upregulated genes were triaged for relevance to human LuAd using datasets from Oncomine and cBioportal. Selected genes were validated by RNAi screening in human lung cancer cell lines and examined for association with lung cancer patient overall survival using KMplot.com. Depletion of progression-associated genes resulted in pronounced viability and/or cell migration defects in human lung cancer cells. Progression-associated genes moreover exhibited strong associations with overall survival, specifically in human lung adenocarcinoma, but not in squamous cell carcinoma. The KM mouse model faithfully recapitulates key molecular events in human adenocarcinoma of the lung and is a useful tool for mechanistic interrogation of KRAS-driven LuAd progression.

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