Roles of Nontraditional Lipid Parameters for Predicting Restenosis in Patients with Intracranial Atherosclerotic Stenosis After Endovascular Treatment.

PURPOSE: Nontraditional lipid parameters are associated with intracranial atherosclerotic stenosis (ICAS) progression. This study aimed to investigate the association of nontraditional lipid parameters with the risk of restenosis in patients with ICAS after endovascular treatment (EVT). METHODS: This study retrospectively enrolled consecutive patients with symptomatic ICAS after successful EVT followed by at least 3 months of angiography. Participants were divided into restenosis or non-restenosis groups based on the angiographic follow-up results. The nontraditional lipid parameters were calculated from conventional lipid parameters. The COX regression models and restricted cubic splines (RCS) were used to explore the association between nontraditional lipid parameters and restenosis. RESULTS: This study recruited 222 cases with 224 lesions eligible for our study, of which 56 (25%) had restenosis. Compared with the non-restenosis group, patients in the restenosis group had higher levels of the atherogenic index of plasma (AIP) (0.211, interquartile range, IQR, 0.065-0.404 vs. 0.083, IQR, -0.052-0.265, P = 0.001), remnant cholesterol (RC) (0.55, IQR, 0.33-0.77 vs. 0.30, IQR, 0.18-0.49, P < 0.001) and Castelli's index­I (CRI-I) (4.13, IQR, 3.39-5.34 vs. 3.74, IQR, 2.94-4.81, P = 0.030). In the multivariable COX regression analysis, a 0.1 unit increase of AIP was an independent risk factor for restenosis (hazard ratio, HR = 1.20, 95% confidence interval, CI 1.05-1.35, P = 0.005) whereas such an association was not observed for RC (HR = 1.01, 95% CI 0.90-1.15, P = 0.835). The restricted cubic spline (RCS) plot revealed a linear relationship between AIP and restenosis (P for nonlinear = 0.835) but a nonlinear relationship for RC (P for nonlinear = 0.012). Patients were stratified according to tertiles (T) of AIP and RC and the risk of restenosis increased in T3 compared to T1 (HR = 3.21, 95% CI 1.35-7.62, P = 0.008 and HR = 2.99, 95% CI 1.11-8.03, P = 0.030, respectively). Furthermore, this association remained stable within each LDL­C level subgroup. CONCLUSION: The AIP and RC were positively and independently associated with restenosis in patients with ICAS after EVT.

Wall characteristics of atherosclerotic middle cerebral arteries in patients with single or multiple infarcts: A high-resolution MRI Study.

Background and purpose: Understanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis may inform secondary prevention. The aim of this study was to explore the relationship between vascular wall characteristics and infarction patterns using high-resolution magnetic resonance imaging (HRMRI) and diffusion-weighted imaging (DWI). Methods: From November 2018 to March 2021, patients with acute ischemic stroke due to MCA atherosclerotic disease were retrospectively analyzed. The wall characteristics of atherosclerotic MCA, including conventional characteristics and histogram-defined characteristics, were evaluated using HRMRI. Patients were divided into single-infarction and multiple-infarction groups based on DWI, and wall characteristics were compared between the two groups. Results: Of 92 patients with MCA plaques, 59 patients (64.1%) had multiple infarcts, and 33 (35.9%) had single infarcts. The histogram-defined characteristics showed no differences between the single-infarction and multiple-infarction groups (P>0.05). Plaque burden, degree of stenosis, and prevalence of intraplaque hemorrhage (IPH) were significantly greater in the multiple-infarction group than in the single-infarction group (plaque burden: P = 0.001; degree of stenosis: P = 0.010; IPH: P = 0.019). Multivariate analysis showed that plaque burden (odds ratio: 1.136; 95% confidence interval: 1.054-1.224, P = 0.001) and IPH (odds ratio: 5.248; 95% confidence interval: 1.573-17.512, P = 0.007) were independent predictors for multiple infarction. Conclusion: IPH and plaque burden are independently associated with multiple infarcts. HRMRI may provide new insight into the mechanisms underlying the different MCA infarction patterns.

Multi-assessment of critical steno-occlusive middle cerebral arteries: transcranial Doppler combined with magnetic resonance angiography.

Background: Accurate assessment of a stenotic or occluded middle cerebral artery (MCA) is essential before making optimal therapeutic decisions. However, complete occlusion is not always easy to determine for both magnetic resonance angiography (MRA) and neurologists. We aimed to study noninvasive technology using transcranial Doppler (TCD) combined with MRA to assess severe stenosis and occlusion of the MCA. Methods: We studied consecutive patients with severe steno-occlusive MCA by digital subtraction angiography from Oct. 2011 to Mar. 2020 in our stroke center. Hemodynamic measurements of TCD, including peak velocity (PSV), mean flow velocity (MFV) and pulse index (PI), were recorded specifically at the steno-occlusive site by MRA. Results: A total of 152 MCAs of 148 patients were enrolled (60.0 ± 11.5 y, 107 male), including 82 severe stenotic MCAs and 70 occluded MCAs (Group S & Group O) by DSA. There were 86/152 (57%) MCAs showing discontinuity in MRA, which was significantly distributed more in Group O than in Group S (84% vs. 33%, P < 0.001). The PSV and MFV in Group S were greater (264 ± 78 cm/s vs. 33 ± 34 cm/s and 182 ± 61 cm/s vs. 21 ± 23 cm/s, respectively, P < 0.001), while the PI in Group O was greater (0.98 ± 0.49 vs. 0.72 ± 0.17, P < 0.001). PSV was positively correlated with severe MCA stenosis (ß = 0.036, P < 0.001, OR = 0.965, 95% confidence interval (CI): 0.952-0.978). In severe steno-occlusive MCA, using PSV and MFV to detect MCA severe stenosis yielded areas under the curve of 0.983 (CI: 0.964-1.0) and 0.982 (CI: 0.962-1.0), respectively. The cutoff points of PSV ≥ 77 cm/s and MFV ≥ 51 cm/s both yielded an optimized sensitivity of 96.3% and specificity of 98.6%. Conclusion: The critical velocity at the steno-occlusive site is reliable for distinguishing between severe MCA stenosis and occlusion.

Development and validation of an MRI-based nomogram for the preoperative prediction of tumor mutational burden in lower-grade gliomas.

Background: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors. In this study, we aimed to determine the value of magnetic resonance (MR)-based preoperative nomogram in predicting TMB status in lower-grade glioma (LGG) patients. Methods: Overall survival (OS) data were derived from The Cancer Genome Atlas (TCGA) and then analyzed by using the Kaplan-Meier method and time-dependent receiver operating characteristic (tdROC) analysis. The magnetic resonance imaging (MRI) data of 168 subjects obtained from The Cancer Imaging Archive (TCIA) were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analyses. Finally, we performed tenfold cross validation. TMB values were retrieved from the supplementary information of a previously published article. Results: The high TMB subtype was associated with the shortest median OS (high vs. low: 50.9 vs. 95.6 months, P<0.05). The tdROC for the high-TMB tumors was 74% (95% CI: 61-86%) for survival at 12 months, and 71% (95% CI: 60-82%) for survival at 24 months. Multivariate logistic regression analysis confirmed that three risk factors [extranodular growth: odds ratio (OR): 8.367, 95% CI: 3.153-22.199, P<0.01; length-width ratio ≥ median: OR: 1.947, 95% CI: 1.025-3.697, P<0.05; frontal lobe: OR: 0.455, 95% CI: 0.229-0.903, P<0.05] were significant independent predictors of high-TMB tumors. The nomogram showed good calibration and discrimination. This model had an area under the curve (AUC) of 0.736 (95% CI: 0.655-0.817). Decision curve analysis (DCA) demonstrated that the nomogram was clinically useful. The average accuracy of the tenfold cross validation was 71.6% for high-TMB tumors. Conclusions: Our results indicated that a distinct OS disadvantage was associated with the high TMB group. In addition, extranodular growth, nonfrontal lobe tumors and length-width ratio ≥ median can be conveniently used to facilitate the prediction of high-TMB tumors.

Relationship Between Fragmented QRS Complex and Left Ventricular Fibrosis and Function in Patients With Danon Disease.

Background: Fragmented QRS (f-QRS) complex on the surface ECG is a cardiac conduction abnormality that indicates myocardial scarring. The relationship between the f-QRS complex and cardiac status in patients with Danon disease (DD) remains unclear and will be explored in this study. Methods: Patients with genetically confirmed DD and cardiac magnetic resonance imaging (CMR) examinations were recruited from multiple centers. The number of leads, pattern, score, and segmental distribution of the f-QRS complex were assessed by surface 12-lead ECG. Cardiac status, such as left ventricular (LV) volume, function, and extent of late gadolinium enhancement (LGE), was demonstrated by CMR. The segmental distribution of LGE was also assessed. Correlations between the f-QRS and cardiac status were assessed. Results: Fifteen patients (14 men) with DD who underwent 12-lead ECG and CMR imaging were included. The f-QRS complex was documented in all patients (n = 15, 100%). Three patterns of f-QRS were found, with the notched R/S pattern (74%) being the most common, followed by fragmented QRS (16%) and various RSR' (11%). The fragmented QRS pattern showed an association with a higher level of myocardial fibrosis (LGE > 35%). The burden of f-QRS in each patient was assessed by the number of leads with f-QRS (median 7, range 2-12) and the f-QRS score (median 9, range 2-33). In the correlation analysis, the f-QRS score was positively correlated with LGE% (r = 0.726, p = 0.002), negatively correlated with LV ejection function (LVEF; r = -0.617, p = 0.014) as evaluated by CMR. In the local distribution, f-QRS score and LGE% were both predominant in the LV free wall but did not correlate well among the anterior, lateral, and inferior segments. Conclusion: In this DD cohort, the quantitative f-QRS was correlated well with myocardial fibrosis burden and LV dysfunction in general. This finding suggests that f-QRS can be used as a simple screening tool to assess cardiac status in patients with DD.

Development of MR-based preoperative nomograms predicting DNA copy number subtype in lower grade gliomas with prognostic implication.

OBJECTIVES: We aimed to determine the value of MR-based preoperative nomograms in predicting DNA copy number (CN) subtype in lower grade glioma (LGG) patients. METHODS: The overall survival (OS) data were analyzed. MRI data of 170 subjects were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analysis. RESULTS: CN2 subtype was associated with shortest median OS (CN2 subtype vs. others: 46.8 vs. 221.7 months, p < 0.05). The time-dependent receiver operating characteristic for the CN2 subtype was 0.80 (95% CI: 0.74-0.85) for survival at 1 year, 0.80 (95% CI: 0.75-0.85) for survival at 2 years, and 0.77 (95% CI: 0.73-0.83) for survival at 3 years. On multivariate analysis, hemorrhage (OR: 0.118; p < 0.001; 95% CI: 0.037-0.376), poorly defined margin (OR: 4.592; p < 0.001; 95% CI: 1.965-10.730), extranodular growth (OR: 0.247; p = 0.006; 95% CI: 0.091-0.671), and volume ≥ 60 cm3 (OR: 4.734.256; p < 0.001; 95% CI: 2.051-10.924) were associated with CN1 subtype (AUC: 0.781). Proportion CE tumor (OR: 5.905; p = 0.007; 95% CI: 1.622-21.493), extranodular growth (OR: 9.047; p = 0.001; 95% CI: 2.349-34.846), width ≥ median (OR: 0.231; p = 0.049; 95% CI: 0.054-0.998), and depth ≥ median (OR: 0.192; p = 0.023; 95% CI: 0.046-0.799) were associated with CN2 subtype (AUC: 0.854). Necrosis/cystic (OR: 6.128; p = 0.007; 95% CI: 1.635-22.968), hemorrhage (OR: 5.752; p = 0.002; 95% CI: 1.953-16.942), poorly defined margin (OR: 0.164; p < 0.001; 95% CI: 0.063-0.427), and volume ≥ median (OR: 4.422; p < 0.001; 95% CI: 1.925-10.160) were associated with CN3 subtype (AUC: 0.808). All three nomograms showed good discrimination and calibration. Decision curve analysis supported that all nomograms were clinically useful. The average accuracy of the tenfold cross-validation was 0.680 (CN1), 0.794 (CN2), and 0.894 (CN3), respectively. CONCLUSIONS: The shortest OS was observed in patients with CN2 subtype. This preliminary radiogenomics analysis revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients. KEY POINTS: • This preliminary radiogenomics analysis of LGG revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients. • The AUC for the ROC curve was 0.781 for CN1 subtype, 0.854 for CN2 subtype, and 0.808 for CN3 subtype. Decision curve analysis supported that all nomograms were clinically useful. • The sensitivity was 0.779 (CN1), 0.731 (CN2), and 0.851 (CN3), respectively. The specificity was 0.664 (CN1), 0.872 (CN2), and 0.625 (CN3), respectively. And the accuracy was 0.717 (CN1), 0.849 (CN2), and 0.692 (CN3), respectively.

Radiomics nomogram outperforms size criteria in discriminating lymph node metastasis in resectable esophageal squamous cell carcinoma.

OBJECTIVES: To determine the value of radiomics in predicting lymph node (LN) metastasis in resectable esophageal squamous cell carcinoma (ESCC) patients. METHODS: Data of 230 consecutive patients were retrospectively analyzed (154 in the training set and 76 in the test set). A total of 1576 radiomics features were extracted from arterial-phase CT images of the whole primary tumor. LASSO logistic regression was performed to choose the key features and construct a radiomics signature. A radiomics nomogram incorporating this signature was developed on the basis of multivariable analysis in the training set. Nomogram performance was determined and validated with respect to its discrimination, calibration and reclassification. Clinical usefulness was estimated by decision curve analysis. RESULTS: The radiomics signature including five features was significantly associated with LN metastasis. The radiomics nomogram, which incorporated the signature and CT-reported LN status (i.e. size criteria), distinguished LN metastasis with an area under curve (AUC) of 0.758 in the training set, and performance was similar in the test set (AUC 0.773). Discrimination of the radiomics nomogram exceeded that of size criteria alone in both the training set (p <0.001) and the test set (p=0.005). Integrated discrimination improvement (IDI) and categorical net reclassification improvement (NRI) showed significant improvement in prognostic value when the radiomics signature was added to size criteria in the test set (IDI 17.3%; p<0.001; categorical NRI 52.3%; p<0.001). Decision curve analysis supported that the radiomics nomogram is superior to size criteria. CONCLUSIONS: The radiomics nomogram provides individualized risk estimation of LN metastasis in ESCC patients and outperforms size criteria. KEY POINTS: • A radiomics nomogram was built and validated to predict LN metastasis in resectable ESCC. • The radiomics nomogram outperformed size criteria. • Radiomics helps to unravel intratumor heterogeneity and can serve as a novel biomarker for determination of LN status in resectable ESCC.

Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model.

OBJECTIVE: To develop and validate a radiomics prediction model for individualized prediction of perineural invasion (PNI) in colorectal cancer (CRC). METHODS: After computed tomography (CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort (346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen (CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation (separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram. RESULTS: The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index (c-index): 0.817; 95% confidence interval (95% CI): 0.811-0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination (c-index: 0.803; 95% CI: 0.794-0.812). CONCLUSIONS: Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.

CT-based Radiomics Signature to Discriminate High-grade From Low-grade Colorectal Adenocarcinoma.

RATIONALE AND OBJECTIVES: To develop and validate a computed tomography-based radiomics signature for preoperatively discriminating high-grade from low-grade colorectal adenocarcinoma (CRAC). MATERIALS AND METHODS: This retrospective study was approved by our institutional review board, and the informed consent requirement was waived. This study enrolled 366 patients with CRAC (training dataset: n = 222, validation dataset: n = 144) from January 2008 to August 2015. A radiomics signature was developed with the least absolute shrinkage and selection operator method in training dataset. Mann-Whitney U test was applied to explore the correlation between radiomics signature and histologic grade. The discriminative power of radiomics signature was investigated with the receiver operating characteristics curve. An independent validation dataset was used to confirm the predictive performance. We further performed a stratified analysis to validate the predictive performance of radiomics signature in colon adenocarcinoma and rectal adenocarcinoma. RESULTS: The radiomics signature demonstrated discriminative performance for high-grade and low-grade CRAC, with an area under the curve of 0.812 (95% confidence interval [CI]: 0.749-0.874) in training dataset and 0.735 (95%CI: 0.644-0.826) in validation dataset. Stratified analysis demonstrated that radiomics signature also showed distinguishing ability for histologic grade in both colon adenocarcinoma and rectal adenocarcinoma, with area under the curve of 0.725 (95%CI: 0.653-0.797) and 0.895 (95%CI: 0.838-0.952), respectively. CONCLUSIONS: We developed and validated a radiomics signature as a complementary tool to differentiate high-grade from low-grade CRAC preoperatively, which may make contribution to personalized treatment.

An MRI-based Radiomics Classifier for Preoperative Prediction of Ki-67 Status in Breast Cancer.

RATIONALE AND OBJECTIVES: This study aims to investigate the value of a magnetic resonance imaging-based radiomics classifier for preoperatively predicting the Ki-67 status in patients with breast cancer. MATERIALS AND METHODS: We chronologically divided 318 patients with clinicopathologically confirmed breast cancer into a training dataset (n = 200) and a validation dataset (n = 118). Radiomics features were extracted from T2-weighted (T2W) and contrast-enhanced T1-weighted (T1+C) images of breast cancer. Radiomics feature selection and radiomics classifiers were generated using the least absolute shrinkage and selection operator regression analysis method. The correlation between the radiomics classifiers and the Ki-67 status in patients with breast cancer was explored. The predictive performances of the radiomics classifiers for the Ki-67 status were evaluated with receiver operating characteristic curves in the training dataset and validated in the validation dataset. RESULTS: Through the radiomics feature selection, 16 and 14 features based on T2W and T1+C images, respectively, were selected to constitute the radiomics classifiers. The radiomics classifier based on T2W images was significantly correlated with the Ki-67 status in both the training and the validation datasets (both P < .0001). The radiomics classifier based on T1+C images was significantly correlated with the Ki-67 status in the training dataset (P < .0001) but not in the validation dataset (P = .083). The T2W image-based radiomics classifier exhibited good discrimination for Ki-67 status, with areas under the receiver operating characteristic curves of 0.762 (95% confidence interval: 0.685, 0.838) and 0.740 (95% confidence interval: 0.645, 0.836) in the training and validation datasets, respectively. CONCLUSIONS: The T2W image-based radiomics classifier was a significant predictor of Ki-67 status in patients with breast cancer. Thus, it may serve as a noninvasive approach to facilitate the preoperative prediction of Ki-67 status in clinical practice.

CT-based radiomics signature for differentiating Borrmann type IV gastric cancer from primary gastric lymphoma.

PURPOSE: To evaluate the value of CT-based radiomics signature for differentiating Borrmann type IV gastric cancer (GC) from primary gastric lymphoma (PGL). MATERIALS AND METHODS: 40 patients with Borrmann type IV GC and 30 patients with PGL were retrospectively recruited. 485 radiomics features were extracted and selected from the portal venous CT images to build a radiomics signature. Subjective CT findings, including gastric wall peristalsis, perigastric fat infiltration, lymphadenopathy below the renal hila and enhancement pattern, were assessed to construct a subjective findings model. The radiomics signature, subjective CT findings, age and gender were integrated into a combined model by multivariate analysis. The diagnostic performance of these three models was assessed with receiver operating characteristics curves (ROC) and were compared using DeLong test. RESULTS: The subjective findings model, the radiomics signature and the combined model showed a diagnostic accuracy of 81.43% (AUC [area under the curve], 0.806; 95% CI [confidence interval]: 0.696-0.917; sensitivity, 63.33%; specificity, 95.00%), 84.29% (AUC, 0.886 [95% CI: 0.809-0.963]; sensitivity, 86.67%; specificity, 82.50%), 87.14% (AUC, 0.903 [95%CI: 0.831-0.975]; sensitivity, 70.00%; specificity, 100%), respectively. There were no significant differences in AUC among these three models (P=0.051-0.422). CONCLUSION: Radiomics analysis has the potential to accurately differentiate Borrmann type IV GC from PGL.

Can lymphovascular invasion be predicted by preoperative multiphasic dynamic CT in patients with advanced gastric cancer?

OBJECTIVES: To determine whether multiphasic dynamic CT can preoperatively predict lymphovascular invasion (LVI) in advanced gastric cancer (AGC). METHODS: 278 patients with AGC who underwent preoperative multiphasic dynamic CT were retrospectively recruited. Tumour CT attenuation difference between non-contrast and arterial (ΔAP), portal (ΔPP) and delayed phase (ΔDP), tumour-spleen attenuation difference in the portal phase (ΔT-S), tumour contrast enhancement ratios (CERs), tumour-to-spleen ratio (TSR) and tumour volumes were obtained. All CT-derived parameters and clinicopathological variables associated with LVI were analysed by univariate analysis, followed by multivariate and receiver operator characteristics (ROC) analysis. Associations between CT predictors for LVI and histopathological characteristics were evaluated by the chi-square test. RESULTS: ΔPP (OR, 1.056; 95% CI: 1.032-1.080) and ΔT-S (OR, 1.043; 95% CI: 1.020-1.066) are independent predictors for LVI in AGC. ΔPP, ΔT-S and their combination correctly predicted LVI in 74.8% (AUC, 0.775; sensitivity, 88.6%; specificity, 54.1%), 68.7% (AUC, 0.747; sensitivity, 68.3%; specificity, 69.4%) and 71.7% (AUC, 0.800; sensitivity, 67.6%; specificity, 77.8%), respectively. There were significant associations between CT predictors for LVI with tumour histological differentiation and Lauren classification. CONCLUSION: Multiphasic dynamic CT provides a non-invasive method to predict LVI in AGC through quantitative enhancement measurement. KEY POINTS: • Lymphovascular invasion rarely can be evaluated preoperatively in advanced gastric cancer (AGC). • Δ PP and Δ T-S were independent predictors for LVI in patients with AGC. • Δ PP and Δ T-S showed acceptable predictive performance for LVI. • Combination of Δ PP and Δ T-S improved predictive performance for LVI. • Multiphasic dynamic CT may be a useful adjunct for detecting LVI preoperatively.

Multiparametric MR diffusion-weighted imaging for monitoring the ultra-early treatment effect of sorafenib in human hepatocellular carcinoma xenografts.

PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) for monitoring the ultra-early (within 24 hours) treatment effect of sorafenib in human hepatocellular carcinoma (HCC) xenografts. MATERIALS AND METHODS: With institutional Animal Care and Use Committee approval, 16 BALB/c nude mice bearing subcutaneous HCC xenografts underwent serial Gaussian and non-Gaussian DWI at baseline and 1, 3, 6, 12, and 24 hours posttreatment using a 1.5T whole-body MRI system. Gaussian-DWI-derived apparent diffusion coefficient (ADC), D, D*, and f, and non-Gaussian-DWI-derived MD, MK, DDC, and α were calculated and compared between the control (n = 6) and sorafenib-treated groups (n = 10) with respect to each timepoint using Mann-Whitney or Wilcoxon signed-rank test. Results were validated by pathology. RESULTS: Compared to baseline, ADC and D at 1 hour posttreatment (P = 0.005 and P = 0.013, respectively) and MD and DDC at 3 hours posttreatment (P = 0.009 and P = 0.005, respectively) significantly decreased and remained lower through 12 hours of follow-up (P = 0.005-0.022), followed by recovery to baseline levels at 24 hours posttreatment (P = 0.139-0.646). MK significantly increased at 1 hour posttreatment (P = 0.013) and remained higher through 24 hours of follow-up (P = 0.009-0.028). No significant differences were found in D*, f, and α at different timepoints (P = 0.188-0.714). Light microscopy did not reveal abnormal findings until 3 hours posttreatment, when central patchy necrosis was observed; more prominent diffuse necrosis was observed at 24 hours. Electron microscopy revealed swollen mitochondria at 1 hour posttreatment and accumulation of intracellular autophagosomes from 3 to 24 hours posttreatment. CONCLUSION: Multiparametric DWI might evaluate therapeutic effects of sorafenib in HCC, where metrics of ADC, D, and MK could potentially serve as imaging biomarkers for monitoring therapeutic effects as early as 1 hour after treatment. Level of Evidence 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;46:248-256.

Non-small cell lung cancer: quantitative phenotypic analysis of CT images as a potential marker of prognosis.

This was a retrospective study to investigate the predictive and prognostic ability of quantitative computed tomography phenotypic features in patients with non-small cell lung cancer (NSCLC). 661 patients with pathological confirmed as NSCLC were enrolled between 2007 and 2014. 592 phenotypic descriptors was automatically extracted on the pre-therapy CT images. Firstly, support vector machine (SVM) was used to evaluate the predictive value of each feature for pathology and TNM clinical stage. Secondly, Cox proportional hazards model was used to evaluate the prognostic value of these imaging signatures selected by SVM which subjected to a primary cohort of 138 patients, and an external independent validation of 61 patients. The results indicated that predictive accuracy for histopathology, N staging, and overall clinical stage was 75.16%, 79.40% and 80.33%, respectively. Besides, Cox models indicated the signatures selected by SVM: "correlation of co-occurrence after wavelet transform" was significantly associated with overall survival in the two datasets (hazard ratio [HR]: 1.65, 95% confidence interval [CI]: 1.41-2.75, p = 0.010; and HR: 2.74, 95%CI: 1.10-6.85, p = 0.027, respectively). Our study indicates that the phenotypic features might provide some insight in metastatic potential or aggressiveness for NSCLC, which potentially offer clinical value in directing personalized therapeutic regimen selection for NSCLC.

Effects of contrast-enhancement, reconstruction slice thickness and convolution kernel on the diagnostic performance of radiomics signature in solitary pulmonary nodule.

The Effects of contrast-enhancement, reconstruction slice thickness and convolution kernel on the diagnostic performance of radiomics signature in solitary pulmonary nodule (SPN) remains unclear. 240 patients with SPNs (malignant, n = 180; benign, n = 60) underwent non-contrast CT (NECT) and contrast-enhanced CT (CECT) which were reconstructed with different slice thickness and convolution kernel. 150 radiomics features were extracted separately from each set of CT and diagnostic performance of each feature were assessed. After feature selection and radiomics signature construction, diagnostic performance of radiomics signature for discriminating benign and malignant SPN was also assessed with respect to the discrimination and classification and compared with net reclassification improvement (NRI). Our results showed NECT-based radiomics signature demonstrated better discrimination and classification capability than CECT in both primary (AUC: 0.862 vs. 0.829, p = 0.032; NRI = 0.578) and validation cohort (AUC: 0.750 vs. 0.735, p = 0.014; NRI = 0.023). Thin-slice (1.25 mm) CT-based radiomics signature had better diagnostic performance than thick-slice CT (5 mm) in both primary (AUC: 0.862 vs. 0.785, p = 0.015; NRI = 0.867) and validation cohort (AUC: 0.750 vs. 0.725, p = 0.025; NRI = 0.467). Standard convolution kernel-based radiomics signature had better diagnostic performance than lung convolution kernel-based CT in both primary (AUC: 0.785 vs. 0.770, p = 0.015; NRI = 0.156) and validation cohort (AUC: 0.725 vs.0.686, p = 0.039; NRI = 0.467). Therefore, this study indicates that the contrast-enhancement, reconstruction slice thickness and convolution kernel can affect the diagnostic performance of radiomics signature in SPN, of which non-contrast, thin-slice and standard convolution kernel-based CT is more informative.

Radiomics Signature: A Potential Biomarker for the Prediction of Disease-Free Survival in Early-Stage (I or II) Non-Small Cell Lung Cancer.

Purpose To develop a radiomics signature to estimate disease-free survival (DFS) in patients with early-stage (stage I-II) non-small cell lung cancer (NSCLC) and assess its incremental value to the traditional staging system and clinical-pathologic risk factors for individual DFS estimation. Materials and Methods Ethical approval by the institutional review board was obtained for this retrospective analysis, and the need to obtain informed consent was waived. This study consisted of 282 consecutive patients with stage IA-IIB NSCLC. A radiomics signature was generated by using the least absolute shrinkage and selection operator, or LASSO, Cox regression model. Association between the radiomics signature and DFS was explored. Further validation of the radiomics signature as an independent biomarker was performed by using multivariate Cox regression. A radiomics nomogram with the radiomics signature incorporated was constructed to demonstrate the incremental value of the radiomics signature to the traditional staging system and other clinical-pathologic risk factors for individualized DFS estimation, which was then assessed with respect to calibration, discrimination, reclassification, and clinical usefulness. Results The radiomics signature was significantly associated with DFS, independent of clinical-pathologic risk factors. Incorporating the radiomics signature into the radiomics-based nomogram resulted in better performance (P < .0001) for the estimation of DFS (C-index: 0.72; 95% confidence interval [CI]: 0.71, 0.73) than with the clinical-pathologic nomogram (C-index: 0.691; 95% CI: 0.68, 0.70), as well as a better calibration and improved accuracy of the classification of survival outcomes (net reclassification improvement: 0.182; 95% CI: 0.02, 0.31; P = .02). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinical-pathologic nomogram. Conclusion The radiomics signature is an independent biomarker for the estimation of DFS in patients with early-stage NSCLC. Combination of the radiomics signature, traditional staging system, and other clinical-pathologic risk factors performed better for individualized DFS estimation in patients with early-stage NSCLC, which might enable a step forward precise medicine. © RSNA, 2016 Online supplemental material is available for this article.

Development and Validation of a Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer.

PURPOSE: To develop and validate a radiomics nomogram for preoperative prediction of lymph node (LN) metastasis in patients with colorectal cancer (CRC). PATIENTS AND METHODS: The prediction model was developed in a primary cohort that consisted of 326 patients with clinicopathologically confirmed CRC, and data was gathered from January 2007 to April 2010. Radiomic features were extracted from portal venous-phase computed tomography (CT) of CRC. Lasso regression model was used for data dimension reduction, feature selection, and radiomics signature building. Multivariable logistic regression analysis was used to develop the predicting model, we incorporated the radiomics signature, CT-reported LN status, and independent clinicopathologic risk factors, and this was presented with a radiomics nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed. An independent validation cohort contained 200 consecutive patients from May 2010 to December 2011. RESULTS: The radiomics signature, which consisted of 24 selected features, was significantly associated with LN status (P < .001 for both primary and validation cohorts). Predictors contained in the individualized prediction nomogram included the radiomics signature, CT-reported LN status, and carcinoembryonic antigen level. Addition of histologic grade to the nomogram failed to show incremental prognostic value. The model showed good discrimination, with a C-index of 0.736 (C-index, 0.759 and 0.766 through internal validation), and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (C-index, 0.778 [95% CI, 0.769 to 0.787]) and good calibration. Decision curve analysis demonstrated that the radiomics nomogram was clinically useful. CONCLUSION: This study presents a radiomics nomogram that incorporates the radiomics signature, CT-reported LN status, and clinical risk factors, which can be conveniently used to facilitate the preoperative individualized prediction of LN metastasis in patients with CRC.

The development and validation of a CT-based radiomics signature for the preoperative discrimination of stage I-II and stage III-IV colorectal cancer.

OBJECTIVES: To investigative the predictive ability of radiomics signature for preoperative staging (I-IIvs.III-IV) of primary colorectal cancer (CRC). METHODS: This study consisted of 494 consecutive patients (training dataset: n=286; validation cohort, n=208) with stage I-IV CRC. A radiomics signature was generated using LASSO logistic regression model. Association between radiomics signature and CRC staging was explored. The classification performance of the radiomics signature was explored with respect to the receiver operating characteristics(ROC) curve. RESULTS: The 16-feature-based radiomics signature was an independent predictor for staging of CRC, which could successfully categorize CRC into stage I-II and III-IV (p <0.0001) in training and validation dataset. The median of radiomics signature of stage III-IV was higher than stage I-II in the training and validation dataset. As for the classification performance of the radiomics signature in CRC staging, the AUC was 0.792(95%CI:0.741-0.853) with sensitivity of 0.629 and specificity of 0.874. The signature in the validation dataset obtained an AUC of 0.708(95%CI:0.698-0.718) with sensitivity of 0.611 and specificity of 0.680. CONCLUSIONS: A radiomics signature was developed and validated to be a significant predictor for discrimination of stage I-II from III-IV CRC, which may serve as a complementary tool for the preoperative tumor staging in CRC.

MR diffusion-weighted imaging-based subcutaneous tumour volumetry in a xenografted nude mouse model using 3D Slicer: an accurate and repeatable method.

Accurate and repeatable measurement of the gross tumour volume(GTV) of subcutaneous xenografts is crucial in the evaluation of anti-tumour therapy. Formula and image-based manual segmentation methods are commonly used for GTV measurement but are hindered by low accuracy and reproducibility. 3D Slicer is open-source software that provides semiautomatic segmentation for GTV measurements. In our study, subcutaneous GTVs from nude mouse xenografts were measured by semiautomatic segmentation with 3D Slicer based on morphological magnetic resonance imaging(mMRI) or diffusion-weighted imaging(DWI)(b = 0,20,800 s/mm(2)) . These GTVs were then compared with those obtained via the formula and image-based manual segmentation methods with ITK software using the true tumour volume as the standard reference. The effects of tumour size and shape on GTVs measurements were also investigated. Our results showed that, when compared with the true tumour volume, segmentation for DWI(P = 0.060-0.671) resulted in better accuracy than that mMRI(P < 0.001) and the formula method(P < 0.001). Furthermore, semiautomatic segmentation for DWI(intraclass correlation coefficient, ICC = 0.9999) resulted in higher reliability than manual segmentation(ICC = 0.9996-0.9998). Tumour size and shape had no effects on GTV measurement across all methods. Therefore, DWI-based semiautomatic segmentation, which is accurate and reproducible and also provides biological information, is the optimal GTV measurement method in the assessment of anti-tumour treatments.