Targeted intraoperative fluorescence imaging for the visualization of ground-glass nodules in the lung.
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ABSTRACT:
SUBMITTER: Choi HS
PROVIDER: S-EPMC9742616 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Targeted intraoperative fluorescence imaging for the visualization of ground-glass nodules in the lung.
Choi Hak Soo HS Lee Jun Hee JH Kim Hyun Koo HK
Translational lung cancer research 20221101 11
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Project description:BackgroundIdentifying ground glass opacities (GGOs) is challenging during robot-assisted thoracic surgery (RATS). Intraoperative molecular imaging (IMI) using tumor-targeted fluorescent tracers may address this clinical problem, but has never been evaluated in RATS. In a pilot study, we sought to determine whether IMI during RATS (RIMI) can localize GGOs.MethodsTen patients with a cT1 GGO were enrolled. Prior to resection, participants received a folate-receptor targeted fluorescent tracer (OTL38). During RATS, a white-light robotic scope was utilized to identify tumors. RIMI was then conducted using a RATS thoracoscope with a wavelength-specific camera. Finally, a video-assisted thoracic surgery (VATS) thoracoscope designed to detect OTL38 was used as a control to compare to RIMI. The lesions were then resected under RIMI guidance.ResultsBy white-light robotic scope, 7/10 (70%) GGOs were visually identifiable by pleuroparenchymal distortions. RIMI identified tumor-specific fluorescence in all (100%) subjects. RIMI clearly located the three nodules that could not be seen by robotic white-light imaging. The mean fluorescence intensity (MFI) of tumors was 99.48 arbitrary units (A.U.) (IQR, 75.72-130.49 A.U.), which was significantly higher than background tissue with mean MFI 20.61 A.U. (IQR, 13.49-29.93 A.U., P<0.0001). Mean signal-to-background ratio was 5.71 (range, 2.28-10.13). When compared to VATS-IMI as a control, there were no significant differences in MFI of tumors, background tissue, or signal-to-background ratios. In summary, RIMI compared favorably to VATS-IMI by all measured imaging characteristics.ConclusionsRIMI is feasible for identification of GGOs during robotic resection as compared to white light thoracoscopy and compares favorably to VATS-IMI.
| S-EPMC9459620 | biostudies-literature
Project description:PURPOSE:Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins. METHODS:In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging. RESULTS:We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited. CONCLUSIONS:This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.
| S-EPMC6015787 | biostudies-literature
Project description:Background:The method of locating pulmonary nodules before operation plays a crucial role in the surgery of pulmonary ground-glass nodules (GGNs). However, the methodologies surrounding intraoperative localization remains limited, with the majority procedures requiring specific additional equipment. We report a new approach in locating pulmonary GGNs by image-localized body surface marking intraoperative (IBMI) localization. Methods:A retrospective review of the medical records of 76 patients with pulmonary GGNs was performed. All patients underwent IBMI localization between January 2018 and March 2019. Twenty-six patients underwent CT-guided hook wire localization before IBMI localization during surgery. IBMI localization was undertaken directly without pre-treatment in the remaining patients. The efficacy and complications of this approach were analyzed and compared with other pre- or intraoperative localization methods in the current literature. Results:The intraoperative localizations were performed successfully in 72 of all 76 patients pulmonary GGNs within a mean duration of 5.3±1.8 (range, 2.0 to 9.6) minutes. The GGNs in four cases were found to have a significant deviation (>1.5 cm) from the positioning points. All GGNs were successfully resected. Except for five cases of active chest wall bleeding (6.5%), no other intra- or postoperative complications occurred. Conclusions:The IBMI localization approach is a safe and short-duration procedure with high success rates and fewer complications. We used it for the first time for intraoperative localization of peripheral GGNs with excellent results.
| S-EPMC7417760 | biostudies-literature
Project description:As an early type of lung adenocarcinoma, ground glass nodule (GGN) has been detected increasingly and now accounts for most lung cancer outpatients. GGN has a satisfactory prognosis and its characteristics are quite different from solid adenocarcinoma (SADC). We compared the GGN adenocarcinoma (GGN-ADC) with SADC using the single-cell RNA sequencing (scRNA-seq) to fully understand GGNs. The tumor samples of five patients with lung GGN-ADCs and five with SADCs underwent surgery were digested to a single-cell suspension and analyzed using 10× Genomic scRNA-seq techniques. We obtained 60,459 cells and then classified them as eight cell types, including cancer cells, endothelial cells, fibroblasts, T cells, B cells, Nature killer cells, mast cells, and myeloid cells. We provided a comprehensive description of the cancer cells and stromal cells. We found that the signaling pathways related to cell proliferation were downregulated in GGN-ADC cancer cells, and stromal cells had different effects in GGN-ADC and SADC based on the analyses of scRNA-seq results. In GGN-ADC, the signaling pathways of angiogenesis were downregulated, fibroblasts expressed low levels of some collagens, and immune cells were more activated. Furthermore, we used flow cytometry to isolate the cancer cells and T cells in 12 GGN-ADC samples and in an equal number of SADC samples, including CD4+ T and CD8+ T cells, and validated the expression of key molecules by quantitative real-time polymerase chain reaction analyses. Through comprehensive analyses of cell phenotypes in GGNs, we provide deep insights into lung carcinogenesis that will be beneficial in lung cancer prevention and therapy.
| S-EPMC7536439 | biostudies-literature
Project description:ObjectivesTo investigate the value of radiomics based on CT imaging in predicting invasive adenocarcinoma manifesting as pure ground-glass nodules (pGGNs).MethodsThis study enrolled 395 pGGNs with histopathology-confirmed benign nodules or adenocarcinoma. A total of 396 radiomic features were extracted from each labeled nodule. A Rad-score was constructed with the least absolute shrinkage and selection operator (LASSO) in the training set. Multivariate logistic regression analysis was conducted to establish the radiographic model and the combined radiographic-radiomics model. The predictive performance was validated by receiver operating characteristic (ROC) curve. Based on the multivariate logistic regression analysis, an individual prediction nomogram was developed and the clinical utility was assessed.ResultsFive radiomic features and four radiographic features were selected for predicting the invasive lesions. The combined radiographic-radiomics model (AUC 0.77; 95% CI, 0.69-0.86) performed better than the radiographic model (AUC 0.71; 95% CI, 0.62-0.81) and Rad-score (AUC 0.72; 95% CI, 0.63-0.81) in the validation set. The clinical utility of the individualized prediction nomogram developed using the Rad-score, margin, spiculation, and size was confirmed in the validation set. The decision curve analysis (DCA) indicated that using a model with Rad-score to predict the invasive lesion would be more beneficial than that without Rad-score and the clinical model.ConclusionsThe proposed radiomics-based nomogram that incorporated the Rad-score, margin, spiculation, and size may be utilized as a noninvasive biomarker for the assessment of invasive prediction in patients with pGGNs.Key points• CT-based radiomics analysis helps invasive prediction manifested as pGGNs. • The combined radiographic-radiomics model may be utilized as a noninvasive biomarker for predicting invasive lesion for pGGNs. • Radiomics-based individual nomogram may serve as a vital decision support tool to identify invasive pGGNs, obviating further workup and blind follow-up.
| S-EPMC7305264 | biostudies-literature
Project description:A fundamental goal of many surgeries is nerve preservation, as inadvertent injury can lead to patient morbidity including numbness, pain, localized paralysis and incontinence. Nerve identification during surgery relies on multiple parameters including anatomy, texture, color and relationship to surrounding structures using white light illumination. We propose that fluorescent labeling of nerves can enhance the contrast between nerves and adjacent tissue during surgery which may lead to improved outcomes. Methods: Nerve binding peptide sequences including HNP401 were identified by phage display using selective binding to dissected nerve tissue. Peptide dye conjugates including FAM-HNP401 and structural variants were synthesized and screened for nerve binding after topical application on fresh rodent and human tissue and in-vivo after systemic IV administration into both mice and rats. Nerve to muscle contrast was quantified by measuring fluorescent intensity after topical or systemic administration of peptide dye conjugate. Results: Peptide dye conjugate FAM-HNP401 showed selective binding to human sural nerve with 10.9x fluorescence signal intensity (1374.44 ± 425.96) compared to a previously identified peptide FAM-NP41 (126.17 ± 61.03). FAM-HNP401 showed nerve-to-muscle contrast of 3.03 ± 0.57. FAM-HNP401 binds and highlight multiple human peripheral nerves including lower leg sural, upper arm medial antebrachial as well as autonomic nerves isolated from human prostate. Conclusion: Phage display has identified a novel peptide that selectively binds to ex-vivo human nerves and in-vivo using rodent models. FAM-HNP401 or an optimized variant could be translated for use in a clinical setting for intraoperative identification of human nerves to improve visualization and potentially decrease the incidence of intra-surgical nerve injury.
| S-EPMC6096382 | biostudies-literature
Project description:Recent widespread use of high resolution computed tomography (HRCT) for the screening of lung cancer have led to an increase in the detection rate of very faint and smaller lesions known as ground-glass nodule (GGN). However, it had been proved that GGN was well associated with lung cancer in previous studies. Therefore, the classification, imaging characteristics, pathological type, follow-up, suggested managements and other clinical concerns of GGN were reviewed in this paper.?.
| S-EPMC6712268 | biostudies-literature
Project description:Introduction: Lung adenocarcinoma (LUAD) is the most prevalent lung cancer. LUAD presents as ground glass nodules (GGN) and solid nodules (SN) in imaging studies. GGN is an early type of LUAD with good prognosis. However, SN exhibits a more malignant behavior than GGN, including worse pathological staging and tumor prognosis. The mechanism leading to the different malignancy levels of GGN and SN remains elusive. Methods: Three patients with GGN and three patients with SN diagnosed with early LUAD were enrolled. The tumor samples were digested to a single-cell suspension and analyzed using 10× Genomic Single-cell ribonucleic acid sequences (scRNA-seq) techniques. Results: A total of 15,902 cells were obtained and classified into nine major types. The tumor microenvironment (TME) was subsequently described in detail. ScRNA-seq revealed that ribosome-related pathways and cell adhesion played similar but distinct roles in the two groups. SN also had more active cell proliferation, enriched cell cycle regulatory pathways, and severe inflammatory responses. Conclusion: We observed changes in the cellular composition and transcriptomic profile of GGN and SN. The study improved the understanding of the underlying mechanisms of lung carcinogenesis and contributed to lung cancer prevention and treatment.
| S-EPMC10513029 | biostudies-literature
Project description:Objective: To evaluate whether radiomic features extracted from intra and peri-nodular lesions can enhance the ability to differentiate between invasive adenocarcinoma (IA), minimally invasive adenocarcinoma (MIA), and adenocarcinoma in situ (AIS) manifesting as ground-glass nodule (GGN). Materials and Methods: This retrospective study enrolled 120 patients with a total of 121 pathologically confirmed lung adenocarcinomas (85 IA and 36 AIS/MIA) from January 2015 to May 2019. The recruited patients were randomly divided into training (84 nodules) and validation sets (37 nodules), with a ratio of 7:3. The minority group in the training set was balanced by the synthetic minority over-sampling (SMOTE) method. The intra-, peri-nodular, and gross region of interests (ROI) were delineated with manual annotation. Image features were quantitatively extracted from each ROI on CT images. The minimum redundancy maximum relevance (mRMR) feature ranking method and the least absolute shrinkage and selection operator (LASSO) classifier were used to eliminate unnecessary features. The intra- and peri-nodular radiomic features were combined to produce the gross radiomic signature. A combined clinical-radiomic model was constructed by multivariable logistic regression analysis. The predicted performances of different models were evaluated using receiver operating curve (ROC) and calibration curve. Results: The gross radiomic signature (AUC: training set = 0.896; validation set = 0.876) showed a good ability to discriminate the invasiveness of adenocarcinoma, comparing to intra-nodular (AUC: training set = 0.862; validation set = 0.852) or peri-nodular radiomic signature (AUC: training set = 0.825; validation set = 0.820). The AUC of the combined clinical-radiomic model was 0.917 for the training and 0.876 for the validation cohort, respectively. Conclusions: The gross radiomic signature of intra- and peri-nodular regions improved the prediction ability and aided predicting the invasiveness of lung adenocarcinoma appearing as GGN.
| S-EPMC7267037 | biostudies-literature
Project description:BackgroundRecent advances in imaging modalities and recommended low-dose computed tomography screening programs have made it easier to diagnose early lung cancer. However, the diagnosis of small ground-glass nodules (GGNs) has been problematic due to inappropriate specimen procurement and failure of conventional percutaneous core needle biopsy. Thus, we aimed to evaluate the usefulness of electromagnetic navigation bronchoscopy (ENB)-guided video-assisted lung resection for not only the diagnosis but also treatment of GGNs.MethodsFrom 2017 to 2019, 110 patients with suspicious lung cancer lesions that were not diagnosed by conventional procedure underwent ENB-guided lung resection. Among 35 cases of GGNs, 33 cases of localization were included in this study (two cup biopsy cases were excluded). We used SuperDimension™ for the ENB procedure. After general anesthesia, indigo carmine (0.3-0.5 mL) was injected, and GGNs were resected through video-assisted thoracoscopic surgery.ResultsOf the 33 GGNs, 16 were pure (2 adenocarcinomas in situ, 5 minimally invasive adenocarcinomas (MIAs), 3 adenocarcinomas, and 6 benign lesions) and 17 were mixed (1 MIA, 11 adenocarcinomas, and 5 benign lesions). The mean size of all lesions was 11.2±7.78 mm, mean distance to the pleura was 11.2±14.2 mm, and mean ENB procedure time was 18.8±8.88 minutes. Dye localization and surgical resection of GGN were successful in all cases. There was no procedure-related complication.ConclusionsENB is a feasible and highly accurate localization method for minimally invasive lung resection of small GGNs.
| S-EPMC7330407 | biostudies-literature