Prognostic Value and Pathological Correlation of Peritumoral Radiomics in Surgically Resected Non-Small Cell Lung Cancer.

RATIONALE AND OBJECTIVES: To determine the additional value of peritumoral radiomics in predicting overall survival (OS) in surgically resected non-small cell lung cancer (NSCLC) and its correlation with pathological findings. METHODS: A total of 526 patients with surgically resected NSCLC were included (191 training, 160 internal validation, and 175 external validation cohorts). CT images were used to segment the gross tumor volume (GTV) and peritumoral volume (PTV) within distances of 3, 6, 9 mm from the tumor boundary (PTV3, PTV6, and PTV9), and radiomic features were extracted. Four prognostic models for OS (GTV, GTV + PTV3, GTV + PTV6, and GTV + PTV9) were constructed using the training cohort. The prognostic ability and feature importance were evaluated using the validation cohorts. Pathological findings were compared between the two patient groups (n = 30 for each) having the top 30 and bottom 30 values of the most important peritumoral feature. RESULTS: The GTV+ PTV3 models exhibited the highest predictive ability, which was higher than that of the GTV model in the internal validation cohort (C-index: 0.666 vs. 0.616, P = 0.027) and external validation cohort (C-index: 0.705 vs. 0.656, P = 0.048). The most important feature was GLDM_Dependence_Entropy, extracted from PTV3. High peritumoral GLDM_Dependence_Entropy was associated with a high proportion of invasive histological types, tumor spread through air spaces, and tumor-infiltrating lymphocytes (all P < 0.05). CONCLUSION: The GTV and PTV3 combination demonstrated a higher prognostic ability, compared to GTV alone. Peritumoral radiomic features may be associated with various pathological prognostic factors.

Quantitative MR texture analysis for the differentiation of uterine smooth muscle tumors with high signal intensity on T2-weighted imaging.

The purpose of this study was to distinguish leiomyosarcomas/smooth muscle tumors of uncertain malignant potential (STUMP) from leiomyomas with high signal intensity (SI) on T2-weighted imaging (T2WI) using quantitative MR texture analysis combined with patient characteristics and visual assessment. Thirty-one leiomyomas, 2 STUMPs, and 6 leiomyosarcomas showing high SI on T2WI were included. First, we searched for differences in patient characteristics and visual assessment between leiomyomas and leiomyosarcomas/STUMPs. We also compared the MR texture on T2WI and the apparent diffusion coefficient (ADC) to identify differences between leiomyomas and leiomyosarcomas/STUMPs. In the univariate analysis, significant differences between leiomyomas and leiomyosarcomas/STUMPs were observed in age, menopausal status, margin, hemorrhage, long diameter, T2-variance, T2-volume, ADC-variance, ADC-entropy, ADC-uniformity, ADC-90th and 95th percentile values, and ADC-volume (P < .05, respectively). There were significantly more postmenopausal patients with leiomyosarcomas/STUMPs than with leiomyomas, and leiomyosarcomas/STUMPs had more irregular margins, more frequent presence of hemorrhage and exhibited larger tumor diameters, T2-volume, T2-variance, ADC-volume, ADC-variance, ADC-entropy, and higher ADC-90th and 95th percentile values but lower ADC-uniformity. Multivariate analyses revealed that the independent differentiators were menopausal status, hemorrhage and ADC-entropy (P < .05, respectively). The area under the curve obtained by combining the 3 items was 0.980. The best cutoff value for ADC-entropy was 9.625 (sensitivity: 100%, specificity: 58%). The combination of menopausal status, hemorrhage, and ADC-entropy can help accurately distinguish leiomyosarcomas/STUMPs from leiomyomas with high SI on T2WI; however, external validation in a larger population is required because of the small sample size of our study.

Effectiveness of one-shot dual-energy subtraction chest radiography with flat-panel detector in distinguishing between calcified and non-calcified nodules.

The purpose of this study was to evaluate the added value of the soft tissue image obtained by the one-shot dual-energy subtraction (DES) method using a flat-panel detector compared with the standard image alone in distinguishing calcified from non-calcified nodules on chest radiographs. We evaluated 155 nodules (48 calcified and 107 non-calcified) in 139 patients. Five radiologists (readers 1 - 5) with 26, 14, 8, 6 and 3 years of experience, respectively, evaluated whether the nodules were calcified using chest radiography. CT was used as the gold standard of calcification and non-calcification. Accuracy and area under the receiver operating characteristic curve (AUC) were compared between analyses with and without soft tissue images. The misdiagnosis ratio (false positive plus false negative ratios) when nodules and bones overlapped was also examined. The accuracy of all radiologists increased after adding soft tissue images (readers 1 - 5: 89.7% vs. 92.3% [P = 0.206], 83.2% vs. 87.7% [P = 0.178], 79.4% vs. 92.3% [P < 0.001], 77.4% vs. 87.1% [P = 0.007], and 63.2% vs. 83.2% [P < 0.001], respectively). AUCs for all the readers improved, except for reader 2 (readers 1 - 5: 0.927 vs. 0.937 [P = 0.495], 0.853 vs. 0.834 [P = 0.624], 0.825 vs. 0.878 [P = 0.151], 0.808 vs. 0.896 [P < 0.001], and 0.694 vs. 0.846 [P < 0.001], respectively). The misdiagnosis ratio for nodules that overlapped with the bone decreased after adding soft tissue images in all readers (11.5% vs. 7.6% [P = 0.096], 17.6% vs. 12.2% [P = 0.144], 21.4% vs. 7.6% [P < 0.001], 22.1% vs. 14.5% [P = 0.050] and 35.9% vs. 16.0% [P < 0.001], respectively), particularly that of readers 3 - 5. In conclusion, the soft tissue images obtained using one-shot DES with a flat-panel detector have added value in distinguishing calcified from non-calcified nodules on chest radiographs, especially for less experienced radiologists.

Role of intratumoral and peritumoral CT radiomics for the prediction of EGFR gene mutation in primary lung cancer.

OBJECTIVES: To determine the added value of combining intratumoral and peritumoral CT radiomics for the prediction of epidermal growth factor receptor (EGFR) gene mutations in primary lung cancer (PLC). METHODS: This study included 478 patients with PLC (348 adenocarcinomas and 130 other histological types) who underwent surgical resection and EGFR gene testing. Two radiologists performed segmentation of tumors and peritumoral regions using precontrast high-resolution CT images, and 398 radiomic features (212 intra- and 186 peritumoral features) were extracted. The peritumoral region was defined as the lung parenchyma within a distance of 3 mm from the tumor border. Model performance was estimated using Random Forest, a machine-learning algorithm. RESULTS: EGFR mutations were found in 162 tumors; 161 adenocarcinomas, and one pleomorphic carcinoma. After exclusion of poorly reproducible and redundant features, 32 radiomic features remained (14 intra- and 18 peritumoral features) and were included in the model building. For predicting EGFR mutations, combining intra- and peritumoral radiomics significantly improved the performance compared to intratumoral radiomics alone (AUC [area under the receiver operating characteristic curve], 0.774 vs 0.730; p < 0.001). Even in adenocarcinomas only, adding peritumoral radiomics significantly increased performance (AUC, 0.687 vs 0.630; p < 0.001). The predictive performance using radiomics and clinical features was significantly higher than that of clinical features alone (AUC, 0.826 vs 0.777; p = 0.005). CONCLUSIONS: Combining intra- and peritumoral radiomics improves the predictive accuracy of EGFR mutations and could be used to aid in decision-making of whether to perform biopsy for gene tests. ADVANCES IN KNOWLEDGE: Adding peritumoral to intratumoral radiomics yields greater accuracy than intratumoral radiomics alone in predicting EGFR mutations and may serve as a non-invasive method of predicting of the gene status in PLC.

Maximum Standardized Uptake Value on Positron Emission Tomography is Associated With More Advanced Disease and High-risk Features in Lung Adenocarcinoma.

18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been widely used for preoperative staging of lung adenocarcinomas. The aim of this study was to determine whether a high maximum standardized uptake value (SUVmax) could correlate with pathological characteristics in those patients. We retrospectively reviewed patients with clinical stage 0-IA lung adenocarcinoma who underwent preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography followed by curative anatomical resection. To identify more advanced disease and high-risk features, representing visceral pleural involvement, pulmonary metastasis, lymph node involvement, and lymphovascular involvement in resected surgical specimens, univariate and multivariate logistic regression analyses were performed. The optimal cutoff point for the SUVmax was determined by receiver operating characteristic analysis. In 2 groups divided according to the cutoff point, the disease-free survivals were calculated and compared using the Kaplan-Meier method and the log-rank test. More advanced disease and high-risk features were identified in 55 (18.9%) of the 291 patients. SUVmax was significantly correlated with more advanced disease and high-risk features, as did the consolidation/tumor ratio on computed tomography. Only 2 (1.2%) of the 169 patients with a SUVmax <3.20 showed more advanced disease and high-risk features, compared with 43.4% of patients with a SUVmax ≥3.20. The disease-free survival was significantly higher in patients with a SUVmax <3.20 than in those with a SUVmax ≥3.20 (P = 0.002). A high SUVmax correlates with more advanced disease and high-risk features in patients with clinical stage 0-IA lung adenocarcinoma. The SUVmax should be considered when deciding treatment strategy in early-stage lung adenocarcinoma.

Low Tube Voltage Computed Tomography Venography for Patients With Deep Vein Thrombosis of the Lower Extremities　- A Comparison With Venous Ultrasonography.

BACKGROUND: Low tube voltage computed tomography venography (CTV) can be expected to increase imaging contrast and decrease radiation exposure by using iterative reconstruction (IR). This study evaluated the diagnostic ability of low tube voltage CTV with IR for deep vein thrombosis (DVT), compared to ultrasonography (US).Methods and Results:Two experienced radiologists retrospectively reevaluated the CTV data of 55 of 318 consecutive patients suspected of having DVT or pulmonary embolism between December 2015 and April 2017. The 55 patients had undergone both low tube voltage CTV and US (within 1 day before or after CTV). The lower extremity veins were divided into 10 segments. The DVT forms were categorized into 3 types: complete, concentric, and eccentric. We analyzed the 534 overall segments (16 segments excluded in US) measured using both CTV and US. The sensitivity-specificity was overall 73.3-90.0%, for femoropopliteal, it was 90.0-93.2%, and for the calf, it was 71.1-87.2%. The diagnostic accuracy between the 'eccentric only' and 'others' groups focusing on DVT forms was compared, and significant differences were revealed, especially in the muscular vein. CONCLUSIONS: The DVT diagnostic ability above the knee was comparable between low tube voltage CTV with IR and conventional CTV, and the radiation dose was reduced. It was suggested that eccentric DVT measured by CTV tend to be a false-positive, especially in the calf muscular vein.

Quantitative 3D Shape Analysis of CT Images of Thymoma: A Comparison With Histological Types.

OBJECTIVE. The purpose of this study is to differentiate between low- and high-risk types of thymoma using quantitative 3D shape analysis of CT images. MATERIALS AND METHODS. This retrospective study included 44 patients with a pathologic diagnosis of thymoma. Two radiologists semiautomatically contoured CT images of the tumors and evaluated 3D shape parameters-namely, quantitative indicators of surface smoothness, including sphericity, ellipsoidality, and discrete compactness. The visual CT findings that were analyzed included longest diameter, shape (round-oval, lobulated, or irregular), calcification, cystic or necrotic changes, and enhancement pattern (homogeneous or heterogeneous). The difference and discriminating performance between low-risk (types A, AB, and B1) and high-risk (types B2 and B3) thymomas were statistically assessed. Interobserver agreement was determined using the concordance correlation coefficient. RESULTS. Twenty-three low-risk and 21 high-risk thymomas were identified on the basis of pathologic findings. The median values of sphericity and ellipsoidality were significantly higher for low-risk thymomas than for high-risk thymomas (for sphericity, 0.566 vs 0.517; for ellipsoidality, 0.941 vs 0.875; p < 0.05 for both). The AUC values of sphericity and ellipsoidality were 0.704 and 0.712, respectively. The best cutoff values were 0.528 and 0.919 for sphericity and ellipsoidality, respectively. Risk assessment combining these cutoff values and the mode of tumor detection (incidental detection or detection based on the presence of symptoms) improved the AUC value to 0.856 (sensitivity, 81.0% [17 of 21 patients]; specificity, 82.6% [19 of 23 patients]). All 3D shape parameters showed almost perfect interobserver agreement (concordance correlation coefficient, > 0.90). The visual CT findings were not significantly different between low- and high-risk thymomas (p > 0.05 for all). CONCLUSION. Quantitative 3D shape analysis has excellent reproducibility, and combining this technique with information on the detection mode helps differentiate low- from high-risk thymomas.

Assessment of a simple method of heart weight estimation by postmortem computed tomography.

BACKGROUND: Measurement of heart weight is important when investigating cause of death, but there is presently no satisfactory method of heart weight estimation by postmortem computed tomography (PMCT). METHOD: We investigated 33 consecutive cases that underwent both PMCT and autopsy between February 2008 and June 2014. Heart and left ventricular (LV) weights were calculated by PMCT morphometry. We used a simple method to estimate LV weight: We assumed that LV was an ellipsoid and multiplied its volume on PMCT with myocardial specific gravity. We then compared the various heart and LV weights using linear regression. The calculated and estimated LV weights on PMCT were also compared. RESULTS: It was not possible to predict heart weight at autopsy from PMCT (R2 = 0.53). However, heart weight at autopsy could be accurately predicted from LV weight calculated by PMCT (R2 = 0.77). In addition, there was a strong correlation between the estimated and calculated LV weights by PMCT (R2 = 0.92). Heart weight at autopsy could also be accurately predicted using the PMCT-estimated LV weight (R2 = 0.72). CONCLUSION: Heart weight at autopsy could be accurately predicted using a simple method in which LV volume was assumed to be an ellipsoid on PMCT.

HRCT texture analysis for pure or part-solid ground-glass nodules: distinguishability of adenocarcinoma in situ or minimally invasive adenocarcinoma from invasive adenocarcinoma.

PURPOSE: To distinguish between adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) showing pure or part-solid ground-glass nodules (GGNs) by high-resolution computed tomography (HRCT) texture analysis. MATERIALS AND METHODS: This retrospective study included 101 consecutive patients with 115 pure or part-solid GGNs ≤ 3 cm diameter, which were surgically resected and pathologically diagnosed with AIS, MIA, or IAC (48 AIS-MIA and 67 IAC) between April 2011 and March 2015. Each tumor was manually segmented on axial CT images, and the following texture features were calculated: volume, mass, mean CT value, variance, skewness, kurtosis, entropy, uniformity, and percentile CT numbers (10th, 25th, 50th, 75th, 90th, 95th percentiles). The differences between AIS-MIA and IAC were statistically evaluated using univariate, multivariate, and receiver operating characteristic analysis. RESULTS: Compared with IAC, AIS-MIA had significantly greater skewness, kurtosis, and uniformity, whereas in the other parameters, AIS-MIA demonstrated significantly lower values than those of IAC. Multivariate analysis revealed that independent differentiators were the 90th percentile CT numbers (P < 0.001) and entropy (P = 0.005) with an excellent accuracy (area under the curve, 0.90). CONCLUSIONS: The 90th percentile CT numbers and entropy can accurately distinguish AIS-MIA from IAC.

Acute coronary syndrome: evaluation of detection capability using non-electrocardiogram-gated parenchymal phase CT imaging.

PURPOSE: To evaluate the capability to detect acute coronary syndrome (ACS) by using non-electrocardiogram-gated parenchymal phase CT imaging. MATERIALS AND METHODS: Of 962 consecutive patients who underwent emergent coronary angiography for suspected ACS, 32 with ACS who underwent CT ≤24 h before angiography and 15 without ACS who underwent CT ≤24 h before or after angiography were included. Parenchymal phase was acquired at 100-s scan delay. The presence of a myocardial perfusion defect (MPD) on the left ventricle (a decrease of >20 HU) and its capability to detect ACS were evaluated. Results were compared with laboratory findings. RESULTS: MPD was detected in 29 of 32 ACSs. The sensitivity, specificity, and positive and negative predictive values were 91 % (29/32), 93 % (14/15), 97 % (29/30), and 82 % (14/17), respectively. The sensitivities of ST- and non-ST-elevation ACSs were 89 % (16/18) and 93 % (13/14), respectively, without significant difference (P > 0.99). Of the CT-detectable ACS, non-ST-elevation on the electrocardiogram and a normal creatine kinase-myocardial band were observed in 41 % (12/29) and 24 % (7/29), respectively. CONCLUSION: ACS is highly detectable even using conventional parenchymal phase CT imaging. Therefore, even when CT is non-gating, radiologists should carefully evaluate the heart to avoid overlooking ACS.

CT measurement of splenic volume changes as a result of hypovolemic shock.

PURPOSE: To evaluate the changes in splenic volume during hypovolemic shock and after recovery by use of multidetector computed tomography (MDCT). MATERIALS AND METHODS: We investigated 22 cases who underwent MDCT during hypovolemic shock up to 3 h after presentation, compared the splenic volume with that after recovery, and evaluated the volume difference. We compared the volume ratio (recovery/shock) for two age groups: under 60 years (n = 10) and 60 years and over (n = 12). For cases (n = 10) undergoing CT examination twice after treatment, we compared the volume ratios by using the initial recovery CT and the second CT images. RESULTS: The average spleen volume in shock was 63 cm(3); under normal conditions it was 132 cm(3) (P < 0.001). The average volume ratio for groups under 60 years old was 2.34; for groups 60 years and over it was 2.05 (P = 0.051). The average volume ratio obtained by use of the initial post-recovery CT was 2.11; the ratio obtained by use of the second post-recovery CT was 2.16 (P = 0.386). CONCLUSIONS: Our results revealed that splenic volume was reduced during hypovolemic shock and rapidly increased after recovery. Splenic contraction is an important CT finding in shock.

A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma.

OBJECTIVES: To assess the prognostic value of combined evaluation of preoperative CT findings and pre/postoperative serum carcinoembryonic antigen (CEA) levels for pathological stage I lung adenocarcinoma. METHODS: This retrospective study included 250 consecutive patients who underwent complete resection for ≤ 3-cm pathological stage I (T1-2aN0M0) adenocarcinomas (132 men, 118 women; mean age, 67.8 years). Radiologists evaluated following CT findings: maximum tumor diameter, percentage of solid component (%solid), air bronchogram, spiculation, adjacency of bullae or interstitial pneumonia (IP) around the tumor, notch, and pleural indent. These CT findings, pre/postoperative CEA levels, age, gender, and Brinkman index were assessed by Cox proportional hazards model to determine the best prognostic model. Prognostic accuracy was examined using the area under the receiver operating characteristic curve (AUC). RESULTS: Median follow-up period was 73.2 months. In multivariate analysis, high %solid, adjacency of bullae or IP around the tumor, and high postoperative CEA levels comprised the best combination for predicting recurrence (P<0.05). A combination of these three findings had a greater accuracy in predicting 5-year disease-free survival than did %solid alone (AUC=0.853 versus 0.792; P=0.023), with a sensitivity of 85.7% and a specificity of 74.3% at the optimal threshold. The best cut-off values of %solid and postoperative CEA levels for predicting high-risk patients were ≥ 48% and ≥ 3.7 ng/mL, respectively. CONCLUSION: Compared to %solid alone, combined evaluation of %solid, adjacency of bullae or IP change around the tumor, and postoperative CEA levels improves recurrence prediction for stage I lung adenocarcinoma.

Analysis of decrease in lung perfusion blood volume with occlusive and non-occlusive pulmonary embolisms.

PURPOSE: The aim of this study was to determine if lung perfusion blood volume (lung PBV) with non-occlusive pulmonary embolism (PE) differs quantitatively and visually from that with occlusive PE and to investigate if lung PBV with non-occlusive PE remains the same as that without PE. MATERIALS AND METHODS: Totally, 108 patients suspected of having acute PE underwent pulmonary dual-energy computed tomography angiography (DECTA) between April 2011 and January 2012. Presence of PE on DECTA was evaluated by one radiologist. Two radiologists visually evaluated the PE distribution (segmental or subsegmental) and its nature (occlusive or non-occlusive) on DECTA and classified perfusion in lung PBV as "decreased," "slightly decreased," and "preserved". Two radiologists used a lung PBV application to set a region of interest (ROI) in the center of the lesion and measured HU values of an iodine map. In the same slice as the ROI of the lesion and close to the lesion, another ROI was set in the normal perfusion area without PE, and HUs were measured. The proportion of lesions was compared between the occlusive and non-occlusive groups. HUs were compared among the occlusive, non-occlusive, and corresponding normal groups. RESULTS: Twenty-five patients had 80 segmental or subsegmental lesions. There were 37 and 43 lesions in the occlusive and non-occlusive groups, respectively. The proportion of decreased lesions was 73.0% (27/37) in the occlusive group, while that of preserved lesions in the non-occlusive group was 76.7% (33/43). There was a significant difference in the proportion of lesions (P<0.001) between the two groups. HUs of the iodine map were significantly higher in the non-occlusive group than in the occlusive group (33.8 ± 8.2 HU vs. 11.9 ± 6.1 HU, P<0.001). There was no significant difference in HUs for the entire lesion between the non-occlusive (33.8 ± 8.2 HU) and corresponding normal group (34.5 ± 6.8 HU; P=0.294). CONCLUSION: Iodine perfusion tended to be visually and quantitatively preserved in lungs with nonocclusive PE. Lung PBV is required to evaluate pulmonary blood flow.