Reticulation Sign on Thin-Section CT: Utility for Predicting Invasiveness of Pure Ground-Glass Nodules.

BACKGROUND. Pure ground-glass nodules (pGGNs) may represent a diverse range of histologic entities of varying aggressiveness. OBJECTIVE. The purpose of this study was to evaluate the use of the reticulation sign on thin-section CT images for predicting the invasiveness of pGGNs. METHODS. This retrospective study included 795 patients (mean age, 53.4 ± 11.1 [SD] years; 254 men, 541 women) with a total of 876 pGGNs on thin-section CT that underwent resection between January 2015 and April 2022. Two fellowship-trained thoracic radiologists independently reviewed unenhanced CT images to assess the pGGNs for a range of features, including diameter, attenuation, location, shape, air bronchogram, bubble lucency, vascular change, lobulation, spiculation, margins, pleural indentation, and the reticulation sign (defined as multiple small linear opacities resembling a mesh or a net); differences were resolved by consensus. The relationship between the reticulation sign and lesion invasiveness on pathologic assessment was evaluated. RESULTS. On pathologic assessment, the 876 pGGNs included 163 nonneoplastic and 713 neoplastic pGGNs (323 atypical adenomatous hyperplasias [AAHs] or adenocarcinomas in situ [AISs], 250 minimally invasive adenocarcinomas [MIAs], and 140 invasive adenocarcinomas [IACs]). Interobserver agreement for the reticulation sign, expressed as kappa, was 0.870. The reticulation sign was detected in 0.0% of nonneoplastic lesions, 0.0% of AAHs/AISs, 6.8% of MIAs, and 54.3% of IACs. The reticulation sign had sensitivity of 24.0% and specificity of 100.0% for a diagnosis of MIA or IAC and sensitivity of 54.3% and specificity of 97.7% for a diagnosis of IAC. In multivariable regression analyses including all of the assessed CT features, the reticulation sign was a significant independent predictor of IAC (OR, 3.64; p = .001) but was not a significant independent predictor of MIA or IAC. CONCLUSION. The reticulation sign, when observed in a pGGN on thin-section CT, has high specificity (albeit low sensitivity) for invasiveness and is an independent predictor of IAC. CLINICAL IMPACT. Those pGGNs that show the reticulation sign should be strongly suspected to represent IAC; this suspicion may guide risk assessments and follow-up recommendations.

Significance of marginal vessels in differentiating peripheral small-cell lung cancer and benign lung tumor.

BACKGROUND: Some peripheral small cell lung cancers (pSCLCs) and benign lung tumors (pBLTs) have similar morphological features but different treatment and prognosis. PURPOSE: To determine the significance of marginal vessels in differentiating pSCLCs and pBLTs. MATERIAL AND METHODS: A total of 57 and 95 patients with pathological confirmed nodular (≤3 cm) pSCLC and pBLT with similar morphological features were enrolled in this study retrospectively. The patients' clinical characteristics and computed tomography (CT) features of tumors and marginal vessels (vessels connecting with tumors) were analyzed and compared. RESULTS: Compared with pBLTs, pSCLCs had a larger diameter (P = 0.001) but lower enhancement (P = 0.015) and fewer had calcification (P = 0.013). Compared with pBLTs, more lesions had proximal (70.2% vs. 22.1%) and distal (59.6% vs. 4.2%) marginal vessels in pSCLCs (each P < 0.0001). In addition, in pSCLCs, the numbers of proximal (1.3 ± 1.4 vs. 0.3 ± 0.6), distal (2.4 ± 3.1 vs. 0.1 ± 0.5), and total (3.6 ± 3.5 vs. 0.4 ± 1.0) marginal vessels were all more than those in pBLTs (each P < 0.001). Receiver operating characteristic curve analysis revealed the positive distal marginal vessel sign had the highest specificity (95.8%), and the number of total marginal vessels had the best performance in discriminating pSCLC from pBLT (cutoff value = 1.5, AUC = 0.80, 95% CI = 0.72-0.89, sensitivity = 70.2%, and specificity = 91.6%). CONCLUSION: For peripheral solid nodules similar to pBLTs but without any calcification, the possibility of pSCLC should be considered if they have multiple marginal vessels (≥2), especially the distal ones.

Differential diagnosis of benign and malignant patchy ground-glass opacity by thin-section computed tomography.

BACKGROUND: Previous studies confirmed that ground-glass nodules (GGNs) with certain CT manifestations had a higher probability of malignancy. However, differentiating patchy ground-glass opacities (GGOs) and GGNs has not been discussed solely. This study aimed to investigate the differences between the CT features of benign and malignant patchy GGOs to improve the differential diagnosis. METHODS: From January 2016 to September 2021, 226 patients with 247 patchy GGOs (103 benign and 144 malignant) confirmed by postoperative pathological examination or follow-up were retrospectively enrolled. Their clinical and CT data were reviewed, and their CT features were compared. A binary logistic regression analysis was performed to reveal the predictors of malignancy. RESULTS: Compared to patients with benign patchy GGOs, malignant cases were older (P <  0.001), had a lower incidence of malignant tumor history (P = 0.003), and more commonly occurred in females (P = 0.012). Based on CT images, there were significant differences in the location, distribution, density pattern, internal bronchial changes, and boundary between malignant and benign GGOs (P <  0.05). The binary logistic regression analysis revealed that the independent predictors of malignant GGOs were the following: patient age ≥ 58 years [odds ratio (OR), 2.175; 95% confidence interval (CI), 1.135-6.496; P = 0.025], locating in the upper lobe (OR, 5.481; 95%CI, 2.027-14.818; P = 0.001), distributing along the bronchovascular bundles (OR, 12.770; 95%CI, 4.062-40.145; P < 0.001), centrally distributed solid component (OR, 3.024; 95%CI, 1.124-8.133; P = 0.028), and well-defined boundary (OR, 5.094; 95%CI, 2.079-12.482; P < 0.001). CONCLUSIONS: In older patients (≥58 years), well-defined patchy GGOs with centric solid component, locating in the upper lobe, and distributing along the bronchovascular bundles should be highly suspected as malignancy.

Clinical validation of a nanodiamond-embedded thermoplastic biomaterial.

Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications.

CT Characteristics and Clinical Findings of Bronchopneumonia Caused by Pepper Aspiration.

Purpose: To explore the computed tomography (CT) features of bronchopneumonia caused by pepper aspiration to improve the diagnosis. Materials and Methods: 28 adult patients diagnosed with obstructive pneumonia caused by pepper aspiration from January 2016 to September 2022 were enrolled. The CT characteristics of bronchial changes and pulmonary lesions caused by pepper were analyzed and summarized. Results: Among 28 patients, the most common symptom was cough (26, 92.9%), followed by expectoration (23, 82.1%). Bronchoscopy revealed that peppers were mainly found in the bronchus of the right lower lobe (n = 18, 64.3%), followed by the bronchus of the left lower lobe (n = 5, 17.9%). In combination with bronchoscopy results, the pepper in the bronchus manifested as circular or V/U-shaped high-density, localized soft tissue, and flocculent opacification in 8 (28.6%), 16 (57.1%), and 3 (10.7%) cases on CT images, respectively. The bronchial wall around the pepper was thickened with localized occlusion (n = 19, 67.9%) and stenosis (n = 9, 32.1%). Regarding adjacent bronchi without peppers, extensive wall thickening with stenosis and/or occlusion was found in 23 (82.1%) cases. Distal pulmonary lesions frequently involved two or three segments (21, 75.0%) and mainly presented as patchy consolidation or atelectasis (24, 85.7%). Conclusion: In combination to a history of eating peppers and clinical symptoms, bronchopneumonia caused by pepper should be highly suspected if U/V-shaped and annular high-density or localized soft tissue density is detected in the bronchi of the lower lobes, accompanied by extensive bronchial wall thickening, stenosis, or occlusion, and consolidation or atelectasis in multiple distal lung segments.

A combined non-enhanced CT radiomics and clinical variable machine learning model for differentiating benign and malignant sub-centimeter pulmonary solid nodules.

BACKGROUND: Radiomics has been used to predict pulmonary nodule (PN) malignancy. However, most of the studies focused on pulmonary ground-glass nodules. The use of computed tomography (CT) radiomics in pulmonary solid nodules, particularly sub-centimeter solid nodules, is rare. PURPOSE: This study aims to develop a radiomics model based on non-enhanced CT images that can distinguish between benign and malignant sub-centimeter pulmonary solid nodules (SPSNs, <1 cm). METHODS: The clinical and CT data of 180 SPSNs confirmed by pathology were analyzed retrospectively. All SPSNs were divided into two groups: training set (n = 144) and testing set (n = 36). From non-enhanced chest CT images, over 1000 radiomics features were extracted. Radiomics feature selection was performed using the analysis of variance and principal component analysis. The selected radiomics features were fed into a support vector machine (SVM) to develop a radiomics model. The clinical and CT characteristics were used to develop a clinical model. Associating non-enhanced CT radiomics features with clinical factors were used to develop a combined model using SVM. The performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS: The radiomics model performed well in distinguishing between benign and malignant SPSNs, with an AUC of 0.913 (95% confidence interval [CI], 0.862-0.954) in the training set and an AUC of 0.877 (95% CI, 0.817-0.924) in the testing set. The combined model outperformed the clinical and radiomics models with an AUC of 0.940 (95% CI, 0.906-0.969) in the training set and an AUC of 0.903 (95% CI, 0.857-0.944) in the testing set. CONCLUSIONS: Radiomics features based on non-enhanced CT images can be used to differentiate SPSNs. The combined model, which included radiomics and clinical factors, had the best discrimination power between benign and malignant SPSNs.

Quantitative evaluation of density variability in the lesion-lung boundary zone to differentiate pulmonary subsolid nodules.

Background: Transition of the CT values from nodule to peripheral normal lung is related to pathological changes and may be a potential indicator for differential diagnosis. This study investigated the significance of the standard deviation (SD) values in the lesion-lung boundary zone when differentiating between benign and neoplastic subsolid nodules (SSNs). Methods: From January 2012 to July 2021, a total of 229 neoplastic and 84 benign SSNs confirmed by pathological examination were retrospectively and nonconsecutively enrolled in this study. The diagnostic study was not registered with a clinical trial platform, and the study protocol was not published. Computed tomography (CT) values of the ground-glass component (CT1), adjacent normal lung tissue (CT2), and lesion-lung boundary zone (CT3) were measured consecutively. The SD of CT3 was recorded to assess density variability. The CT1, CT2, CT3, and SD values were compared between benign and neoplastic SSNs. Results: No significant differences in CT1 and CT2 were observed between benign and neoplastic SSNs (each P value >0.05). CT3 (-736.1±51.0 vs. -792.6±73.9; P<0.001) and its SD (135.6±29.6 vs. 83.6±20.6; P<0.001) in neoplastic SSNs were significantly higher than those in benign SSNs. Moreover, the SD increased with the invasiveness degree of neoplastic SSNs (r=0.657; P<0.001). The receiver operating characteristic (ROC) curve revealed that the area under the curve was 0.927 (95% CI: 0.896-0.959) when using the SD (cutoff value =106.98) as a factor to distinguish SSNs, which increased to 0.966 (95% CI: 0.934-0.985) when including nodules with a CT1 of ≥-715 Hounsfield units (HU) only (cutoff of SD 109.9, sensitivity 0.930, and specificity 0.914). Conclusions: The SD as an objective index is valuable for differentiating SSNs, especially for those with a CT1 of ≥-715 HU, which have a higher possibility of neoplasm if the SD is >109.9.

Clinical and Computed Tomography Characteristics of Solitary Pulmonary Nodules Caused by Fungi: A Comparative Study.

Purpose: To clarify the clinical and computed tomography (CT) indicators in distinguishing pulmonary nodules caused by fungal infection from lung cancers. Methods: From January 2013 to April 2022, 68 patients with solitary fungal nodules (64 were solid and 4 were mixed ground-glass nodules) and 140 cases with solid cancerous nodules with similar size were enrolled. Their clinical characteristics and CT manifestations of the solid nodules were summarized and compared, respectively. Results: Compared with patients with lung cancers, cases were younger (51.2 ± 11.5 vs 61.3 ± 10.2 years) and non-smokers (72.1% vs 57.9%) and immunocompromised (44.1% vs 17.9%) individuals were more common in patients with fungal nodules (each P < 0.05). The air crescent sign (ACS) (34.4% vs 0%), halo sign (HS) (23.4% vs 4.3%), and satellite lesions (45.3% vs 2.9%) were more frequently detected in fungal nodules than in cancerous ones (each P < 0.05). Air bronchogram similarly occurred in fungal and cancerous nodules, whereas the natural ones were more common in the former (100% vs 16.7%, P = 0.000). However, the fungal nodules had a lower enhancement degree (29.0 ± 19.2 HU vs 40.3 ± 28.3 HU, P = 0.038) and frequency of hilar and/or mediastinal lymph node enlargement (2.9% vs 14.3%, P = 0.013) compared with the cancerous nodules. Conclusion: In the younger, non-smoking and immunocompromised patients, a solitary pulmonary solid nodule with ACS, HS, satellite lesions and/or natural air bronchogram but without significant enhancement, fungal infection is a probable diagnosis.

Features for Predicting Absorbable Pulmonary Solid Nodules as Depicted on Thin-Section Computed Tomography.

PURPOSE: To investigate the clinical and computed tomography (CT) characteristics of absorbable pulmonary solid nodules (PSNs) and to clarify CT features for distinguishing absorbable PSNs from malignant ones. MATERIALS AND METHODS: From January 2015 to February 2021, a total of 316 patients with 348 PSNs (171 absorbable and 177 size-matched malignant) were retrospectively enrolled. Their clinical and CT data were analyzed and compared to determine CT features for predicting absorbable PSNs. RESULTS: Between absorbable and malignant PSNs, there were significant differences in patients' age, lesions' locations, shapes, homogeneity, borders, distance from the pleura, vacuoles, air bronchograms, lobulation, spiculation, halo sign, multiple concomitant nodules and pleural indentation (each P < 0.05). Multivariate analysis revealed that the independent predictors of absorbable PSNs were the following: patient age ≤55 years (OR, 2.660; 95% CI, 1.432-4.942; P = 0.002), homogeneous density (OR, 2.487; 95% CI, 1.107-5.590; P = 0.027), ill-defined border (OR, 5.445; 95% CI, 1.661-17.846; P = 0.005), halo sign (OR, 3.135; 95% CI, 1.154-8.513; P = 0.025), multiple concomitant nodules (OR, 8.700; 95% CI, 4.401-17.197; P<0.001), and abutting pleura (OR, 3.759; 95% CI, 1.407-10.044; P = 0.008). The indicators for malignant PSNs were the following: lobulation (OR, 3.904; 95% CI, 1.956-7.791; P<0.001), spiculation (OR, 4.980; 95% CI, 2.202-11.266, P<0.001), and pleural indentation (OR, 4.514; 95% CI, 1.223-16.666; P = 0.024). CONCLUSION: In patients younger than 55 years, PSNs with homogeneous density, ill-defined border, halo sign, multiple concomitant nodules, and abutting pleura should be highly suspected as absorbable ones.

Minced Pulp as Source of Pulpal Mesenchymal Stem Cells with Odontogenic Differentiation Capacity.

INTRODUCTION: Pulp tissue regeneration is becoming a reality after discovery of mesenchymal stem cells (MSCs) residing in the pulp tissues through various clinical innovations, although MSC transplantation into the pulp space has met with challenges of in vitro cell expansion and cultures. As a way to circumvent the regulatory and technical complexities of in vitro MSC culture, we investigated the use of minced pulp tissues as a source of pulpal MSCs for tissue regeneration. METHODS: We characterized the phenotype of cells explanted from minced pulp (MP), namely MP-derived MSCs (MP-MSCs), compared with dental pulp stem cells (DPSCs) established from pulp tissues by enzyme digestion. Phenotypic characterization included replication kinetics, immunophenotyping, and multilineage differentiation. Using the tooth slice model, we assessed odonto/osteogenic differentiation of DPSCs, MP-MSCs, and minced pulp tissues in situ. RESULTS: In vitro replication of MP-MSCs occurred more rapidly during the initial phase of subcultures compared with DPSCs; however, MP-MSCs arrived at senescence at population doubling 47, whereas DPSCs replicated until population doubling 64, indicating shorter replicative lifespan. MP-MSCs also demonstrated stronger odonto/osteogenic differentiation than DPSCs by alkaline phosphatase activity and the protein expression. Both MP-MSCs and DPSCs demonstrated odonto/osteogenic and adipogenic differentiation capacities. Both cell types also showed mineralized tissue formation in the tooth slice model. Seeding minced pulp tissue on poly-L-lactic acid scaffold allowed for migration of MP-MSCs from the tissues and odontogenic differentiation with dentin sialophosphoprotein expression in the tooth slice model. CONCLUSIONS: These data indicated that MP may be an alternative source of pulpal MSCs that may allow de novo pulp-dentin regeneration without the need for in vitro culture and expansion.