Whole-tumor Histogram Analysis Research Articles

Whole-tumor histogram analysis of multiple non-Gaussian diffusion models at high b values for assessing cervical cancer.

To assess the diagnostic potential of whole-tumor histogram analysis of multiple non-Gaussian diffusion models for differentiating cervical cancer (CC) aggressive status regarding of pathological types, differentiation degree, stage, and p16 expression. Patients were enrolled in this prospective single-center study from March 2022 to July 2023. Diffusion-weighted images (DWI) were obtained including 15 b-values (0 ~ 4000s/mm2). Diffusion parameters derived from four non-Gaussian diffusion models including continuous-time random-walk (CTRW), diffusion-kurtosis imaging (DKI), fractional order calculus (FROC), and intravoxel incoherent motion (IVIM) were calculated, and their histogram features were analyzed. To select the most significant features and establish predictive models, univariate analysis and multivariate logistic regression were performed. Finally, we evaluated the diagnostic performance of our models by using receiver operating characteristic (ROC) analyses. 89 women (mean age, 55 ± 11 years) with CC were enrolled in our study. The combined model, which incorporated the CTRW, DKI, FROC, and IVIM diffusion models, offered a significantly higher AUC than that from any individual models (0.836 vs. 0.664, 0.642, 0.651, 0.649, respectively; p < 0.05) in distinguishing cervical squamous cell cancer from cervical adenocarcinoma. To distinguish tumor differentiation degree, except the combined model showed a better predictive performance compared to the DKI model (AUC, 0.839 vs. 0.697, respectively; p < 0.05), no significant differences in AUCs were found among other individual models and combined model. To predict the International Federation of Gynecology and Obstetrics (FIGO) stage, only DKI and FROC model were established and there was no significant difference in predictive performance among different models. In terms of predicting p16 expression, the predictive ability of DKI model is significantly lower than that of FROC and combined model (AUC, 0.693 vs. 0.850, 0.859, respectively; p < 0.05). Multiple non-Gaussian diffusion models with whole-tumor histogram analysis show great promise to assess the aggressive status of CC.

Non-Gaussian diffusion metrics with whole-tumor histogram analysis for bladder cancer diagnosis: muscle invasion and histological grade

PurposeTo investigate the performance of histogram features of non-Gaussian diffusion metrics for diagnosing muscle invasion and histological grade in bladder cancer (BCa).MethodsPatients were prospectively allocated to MR scanner1 (training cohort) or MR2 (testing cohort) for conventional diffusion-weighted imaging (DWIconv) and multi-b-value DWI. Metrics of continuous time random walk (CTRW), diffusion kurtosis imaging (DKI), fractional-order calculus (FROC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) were simultaneously calculated using multi-b-value DWI. Whole-tumor histogram features were extracted from DWIconv and non-Gaussian diffusion metrics for logistic regression analysis to develop diffusion models diagnosing muscle invasion and histological grade. The models’ performances were quantified by area under the receiver operating characteristic curve (AUC).ResultsMR1 included 267 pathologically-confirmed BCa patients (median age, 67 years [IQR, 46–82], 222 men) and MR2 included 83 (median age, 65 years [IQR, 31–82], 73 men). For discriminating muscle invasion, CTRW achieved the highest testing AUC of 0.915, higher than DWIconv’s 0.805 (p = 0.014), and similar to the combined diffusion model’s AUC of 0.885 (p = 0.076). For differentiating histological grade of non-muscle-invasion bladder cancer, IVIM outperformed a testing AUC of 0.897, higher than DWIconv’s 0.694 (p = 0.020), and similar to the combined diffusion model’s AUC of 0.917 (p = 0.650). In both tasks, DKI, FROC, and SEM failed to show diagnostic superiority over DWIconv (p > 0.05).ConclusionCTRW and IVIM are two potential non-Gaussian diffusion models to improve the MRI application in assessing muscle invasion and histological grade of BCa, respectively.Critical relevance statementOur study validates non-Gaussian diffusion imaging as a reliable, non-invasive technique for early assessment of muscle invasion and histological grade in BCa, enhancing accuracy in diagnosis and improving MRI application in BCa diagnostic procedures.Key PointsMuscular invasion largely determines bladder salvageability in bladder cancer patients.Evaluated non-Gaussian diffusion metrics surpassed DWIconv in BCa muscle invasion and histological grade diagnosis.Non-Gaussian diffusion imaging improved MRI application in preoperative diagnosis of BCa.Graphical

Whole-tumor histogram analysis of synthetic magnetic resonance imaging predicts isocitrate dehydrogenase mutation status in gliomas.

An accurate assessment of isocitrate dehydrogenase (IDH) status in patients with glioma is crucial for treatment planning and is a key factor in predicting patient outcomes. In this study, we investigated the potential value of whole-tumor histogram metrics derived from synthetic magnetic resonance imaging (MRI) in distinguishing IDH mutation status between astrocytoma and glioblastoma. In this prospective study, 80 glioma patients were enrolled from September 2019 to June 2022. All patients underwent pre- and post-contrast synthetic MRI scan protocol. Immunohistochemistry (IHC) staining or gene sequencing were used to assess IDH mutation status in tumor tissue samples. Whole-tumor histogram metrics, including T1, T2, proton density (PD), etc., were extracted from the quantitative maps, while radiological features were assessed by synthetic contrast-weighted maps. Basic clinical features of the patients were also evaluated. Differences in clinical, radiological, and histogram metrics between IDH-mutant astrocytoma and IDH-wildtype glioblastoma were analyzed using univariate analyses. Variables with statistical significance in univariate analysis were included in multivariate logistic regression analysis to develop the combined model. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic performance of metrics and models. The histopathologic analysis revealed that of the 80 cases, 41 were classified as IDH-mutant astrocytoma and 39 as IDH-wildtype glioblastoma. Compared to IDH-wildtype glioblastoma, IDH-mutant astrocytoma showed significantly lower T1 [10th percentile (10th), mean, and median] and post-contrast PD (10th, 90th percentile, mean, median, and maximum) values as well as higher post-contrast T1 (cT1) (10th, mean, median, and minimum) values (all P<0.05). The combined model (T1-10th + cT1-10th + age) was developed by integrating the independent influencing factors of IDH-mutant astrocytoma using the multivariate logistic regression. The diagnostic performance of this model [AUC =0.872 (0.778-0.936), sensitivity =75.61%, and specificity =89.74%] was superior to the clinicoradiological model, which was constructed using age and enhancement degree (AUC =0.822 (0.870-0.898), P=0.035). The combined model constructed using histogram metrics derived from synthetic MRI could be a valuable preoperative tool to distinguish IDH mutation status between astrocytoma and glioblastoma, and subsequently, could assist in the decision-making process of pretreatment.

Whole-tumor histogram analysis of postcontrast T1-weighted and apparent diffusion coefficient in predicting the grade and proliferative activity of adult intracranial ependymomas.

To investigate the value of histogram analysis of postcontrast T1-weighted (T1C) and apparent diffusion coefficient (ADC) images in predicting the grade and proliferative activity of adult intracranial ependymomas. Forty-seven adult intracranial ependymomas were enrolled and underwent histogram parameters extraction (including minimum, maximum, mean, 1st percentile (Perc.01), Perc.05, Perc.10, Perc.25, Perc.50, Perc.75, Perc.90, Perc.95, Perc.99, standard deviation (SD), variance, coefficient of variation (CV), skewness, kurtosis, and entropy of T1C and ADC) using FireVoxel software. Differences in histogram parameters between grade 2 and grade 3 adult intracranial ependymomas were compared. Receiver operating characteristic curves and logistic regression analyses were conducted to evaluate the diagnostic performance. Spearman's correlation analysis was used to evaluate the relationship between histogram parameters and Ki-67 proliferation index. Grade 3 intracranial ependymomas group showed significantly higher Perc.95, Perc.99, SD, variance, CV, and entropy of T1C; lower minimum, mean, Perc.01, Perc.05, Perc.10, Perc.25, Perc.50 of ADC; and higher CV and entropy of ADC than grade 2 intracranial ependymomas group (all p < 0.05). Entropy (T1C) and Perc.10 (ADC) had a higher diagnostic performance with AUCs of 0.805 and 0.827 among the histogram parameters of T1C and ADC, respectively. The diagnostic performance was improved by combining entropy (T1C) and Perc.10 (ADC), with an AUC of 0.857. Significant correlations were observed between significant histogram parameters of T1C (r = 0.296-0.417, p = 0.001-0.044) and ADC (r = -0.428-0.395, p = 0.003-0.038). Whole-tumor histogram analysis of T1C and ADC may be a promising approach for predicting the grade and proliferative activity of adult intracranial ependymomas.

Whole-tumor histogram analysis of multiparametric breast magnetic resonance imaging to differentiate pure mucinous breast carcinomas from fibroadenomas with high-signal intensity on T2WI

PurposeTo investigate the utility of whole-tumor histogram analysis based on multiparametric MRI in distinguishing pure mucinous breast carcinomas (PMBCs) from fibroadenomas (FAs) with strong high-signal intensity on T2-weighted imaging (T2-SHi). Material and methodsThe study included 20 patients (mean age, 55.80 ± 15.54 years) with single PBMCs and 29 patients (mean age, 42.31 ± 13.91 years) with single FAs exhibiting T2-SHi. A radiologist performed whole-tumor histogram analysis between PBMC and FA groups with T2-SHi using multiparametric MRI, including T2-weighted imaging (T2WI), diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps, and the first (DCE_T1) and last (DCE_T4) phases of T1-weighted dynamic contrast-enhanced imaging (DCE) images, to extract 11 whole-tumor histogram parameters. Histogram parameters were compared between the two groups to identify significant variables using univariate analyses, and their diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis and logistic regression analyses. In addition, 15 breast lesions were randomly selected and histogram analysis was repeated by another radiologist to assess the intraclass correlation coefficient for each histogram feature. Pearson's correlation coefficients were used to analyze the correlations between histogram parameters and Ki-67 expression of PMBCs. ResultsFor T2WI images, mean, median, maximum, 90th percentile, variance, uniformity, and entropy significantly differed in PBMCs and FAs with T2-SHi (all P < 0.05), yielding a combined area under the curve (AUC) of 0.927. For ADC maps, entropy was significantly lower in FAs with T2-SHi than in PMBCs (P = 0.03). In both DCE_T1 and DCE_T4 sequences, FAs with T2-SHi showed significantly higher minimum values than PBMCs (P = 0.007 and 0.02, respectively). The highest AUC value of 0.956 (sensitivity, 0.862; specificity, 0.944; positive predictive value, 0.962; negative predictive value, 0.810) was obtained when all significant histogram parameters were combined. ConclusionsWhole-tumor histogram analysis using multiparametric MRI is valuable for differentiating PBMCs from FAs with T2-SHi.

Characterization of parotid gland tumors: Whole-tumor histogram analysis of diffusion weighted imaging, diffusion kurtosis imaging, and intravoxel incoherent motion – A pilot study

PurposeTo investigate the diagnostic performance of histogram features of diffusion parameters in characterizating parotid gland tumors. MethodFrom December 2018 to January 2023, patients who underwent diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) were consecutively enrolled in this retrospective study. The histogram features of diffusion parameters, including apparent diffusion coefficient (ADC), diffusion coefficient (Dk), diffusion kurtosis (K), pure diffusion coefficient (D), pseudo-diffusion coefficient (DP), and perfusion fraction (FP) were analyzed. The Mann-Whitney U test was used for comparison between benign parotid gland tumors (BPGTs) and malignant parotid gland tumors (MPGTs). Receiver operating characteristic curve and logistic regression analysis were used to identify the differential diagnostic performance. The Spearman’s correlation coefficient was used to analyze the correlation between diffusion parameters and Ki-67 labeling index. ResultsFor diffusion MRI, twenty-three histogram features of diffusion parameters showed significant differences between BPGTs and MPGTs (all P < 0.05). Compared with the DWI model, the IVIM model and combined model had better diagnostic specificity (58 %, 94 %, and 88 %, respectively; both corrected P < 0.001) and accuracy (64 %, 89 %, and 86 %, respectively; both corrected P = 0.006). The combined model was superior to the single DWI model with improved IDI (IDI improvement 0.25). Significant correlations were found between Ki-67 and ADCmean, Dkmean, Kmean, and Dmean (r = -0.57 to 0.53; all P < 0.05). ConclusionsWhole-tumor histogram analysis of IVIM and combined diffusion model could further improve the diagnostic performance for differentiating BPGTs from MPGTs.

Whole-tumor histogram analysis of multi-parametric MRI for differentiating brain metastases histological subtypes in lung cancers: relationship with the Ki-67 proliferation index.

This study aims to investigate the predictive value of preoperative whole-tumor histogram analysis of multi-parametric MRI for histological subtypes in patients with lung cancer brain metastases (BMs) and explore the correlation between histogram parameters and Ki-67 proliferation index. The preoperative MRI data of 95 lung cancer BM lesions obtained from 73 patients (42 men and 31 women) were retrospectively analyzed. Multi-parametric MRI histogram was used to distinguish small-cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC), and adenocarcinoma (AC) from squamous cell carcinoma (SCC), respectively. The T1-weighted contrast-enhanced (T1C) and apparent diffusion coefficient (ADC) histogram parameters of the volumes of interest (VOIs) in all BMs lesions were extracted using FireVoxel software. The following histogram parameters were obtained: maximum, minimum, mean, standard deviation (SD), variance, coefficient of variation (CV), skewness, kurtosis, entropy, and 1st-99th percentiles. Then investigated their relationship with the Ki-67 proliferation index. The skewness-T1C, kurtosis-T1C, minimum-ADC, mean-ADC, CV-ADC and 1st - 90th ADC percentiles were significantly different between the SCLC and NSCLC groups (all p < 0.05). When the 10th-ADC percentile was 668, the sensitivity, specificity, and accuracy (90.80%, 76.70% and 86.32%, respectively) for distinguishing SCLC from NSCLC reached their maximum values, with an AUC of 0.895 (0.824 - 0.966). Mean-T1C, CV-T1C, skewness-T1C, 1st - 50th T1C percentiles, maximum-ADC, SD-ADC, variance-ADC and 75th - 99th ADC percentiles were significantly different between the AC and SCC groups (all p < 0.05). When the CV-T1C percentiles was 3.13, the sensitivity, specificity and accuracy (75.00%, 75.60% and 75.38%, respectively) for distinguishing AC and SCC reached their maximum values, with an AUC of 0.829 (0.728-0.929). The 5th-ADC and 10th-ADC percentiles were strongly correlated with the Ki-67 proliferation index in BMs. Multi-parametric MRI histogram parameters can be used to identify the histological subtypes of lung cancer BMs and predict the Ki-67 proliferation index.

Whole-tumor histogram analysis of apparent diffusion coefficients for predicting lymphovascular space invasion in stage IB-IIA cervical cancer.

To investigate the value of apparent diffusion coefficient (ADC) histogram analysis based on whole tumor volume for the preoperative prediction of lymphovascular space invasion (LVSI) in patients with stage IB-IIA cervical cancer. Fifty consecutive patients with stage IB-IIA cervical cancer were stratified into LVSI-positive (n = 24) and LVSI-negative (n = 26) groups according to the postoperative pathology. All patients underwent pelvic 3.0T diffusion-weighted imaging with b-values of 50 and 800 s/mm2 preoperatively. Whole-tumor ADC histogram analysis was performed. Differences in the clinical characteristics, conventional magnetic resonance imaging (MRI) features, and ADC histogram parameters between the two groups were analyzed. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of ADC histogram parameters in predicting LVSI. ADCmax, ADCrange, ADC90, ADC95, and ADC99 were significantly lower in the LVSI-positive group than in the LVSI-negative group (all P-values < 0.05), whereas no significant differences were reported for the remaining ADC parameters, clinical characteristics, and conventional MRI features between the groups (all P-values > 0.05). For predicting LVSI in stage IB-IIA cervical cancer, a cutoff ADCmax of 1.75×10-3 mm2/s achieved the largest area under ROC curve (Az) of 0.750, followed by a cutoff ADCrange of 1.36×10-3 mm2/s and ADC99 of 1.75×10-3 mm2/s (Az = 0.748 and 0.729, respectively), and the cutoff ADC90 and ADC95 achieved an Az of <0.70. Whole-tumor ADC histogram analysis has potential value for preoperative prediction of LVSI in patients with stage IB-IIA cervical cancer. ADCmax, ADCrange, and ADC99 are promising prediction parameters.

Whole-tumor histogram analysis of apparent diffusion coefficient maps with machine learning algorithms for predicting histologic grade of sinonasal squamous cell carcinoma: a preliminary study.

Accurate histologic grade assessment is helpful for clinical decision making and prognostic assessment of sinonasal squamous cell carcinoma (SNSCC). This research aimed to explore whether whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps with machine learning algorithms can predict histologic grade of SNSCC. One hundred and forty-seven patients with pathologically diagnosed SNSCC formed this retrospective study. Sixty-six patients were low-grade (grade I/II) and eighty-one patients were high-grade (grade III). Eighteen histogram features were obtained from quantitative ADC maps. Additionally, the mean ADC value and clinical features were analyzed for comparison with histogram features. Machine learning algorithms were applied to build the best diagnostic model for predicting histological grade. The receiver operating characteristic (ROC) curve was used to evaluate the performance of each model prediction, and the area under the ROC curve (AUC) were analyzed. The histogram model based on three features (10th Percentile, Mean, and 90th Percentile) with support vector machine (SVM) classifier demonstrated excellent diagnostic performance, with an AUC of 0.947 on the testing dataset. The AUC of the histogram model was similar to that of the mean ADC value model (0.947 vs 0.957; P = 0.7029). The poor diagnostic performance of the clinical model (AUC = 0.692) was improved by the combined model incorporating histogram features or mean ADC value (P < 0.05). ADC histogram analysis improved the projection of SNSCC histologic grade, compared with clinical model. The complex histogram model had comparable but not better performance than mean ADC value model.

Whole-tumor histogram analysis of diffusion and perfusion metrics for noninvasive pediatric glioma grading

An accurate assessment of the World Health Organization grade is vital for patients with pediatric gliomas to direct treatment planning. We aim to evaluate the diagnostic performance of whole-tumor histogram analysis of diffusion-weighted imaging (DWI) and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) for differentiating pediatric high-grade gliomas from pediatric low-grade gliomas. Sixty-eight pediatric patients (mean age, 10.47 ± 4.37years; 42 boys) with histologically confirmed gliomas underwent preoperative MR examination. The conventional MRI features and whole-tumor histogram features extracted from apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps were analyzed, respectively. Receiver operating characteristic curves and the binary logistic regression analysis were performed to determine the diagnostic performance of parameters. For conventional MRI features, location, hemorrhage and tumor margin showed significant difference between pediatric high- and low-grade gliomas (all, P < .05). For advanced MRI parameters, ten histogram features of ADC and CBV showed significant differences between pediatric high- and low-grade gliomas (all, P < .05). The diagnostic performance of the combination of DSC-PWI and DWI (AUC = 0.976, sensitivity = 100%, NPV = 100%) is superior to conventional MRI or DWI model, respectively (AUCcMRI = 0.700, AUCDWI = 0.830; both, P < .05). The whole-tumor histogram analysis of DWI and DSC-PWI is a promising method for grading pediatric gliomas.

Whole-tumor amide proton transfer-weighted imaging histogram analysis to predict pathological extramural venous invasion in rectal adenocarcinoma: a preliminary study.

To evaluate amide proton transfer-weighted (APTw)-derived whole-tumor histogram analysis parameters in predicting pathological extramural venous invasion (pEMVI) positive status of rectal adenocarcinoma (RA). Preoperative MR including APTw imaging of 125 patients with RA (mean 61.4 ± 11.6years) were retrospectively analyzed. Two radiologists reviewed each case's EMVI status based on the MR-based modified 5-point scale system with conventional MR images. The APTw histogram parameters of primary tumors were obtained automatically using whole-tumor volume histogram analysis. The independent risk factors markedly correlated with pEMVI-positive status were assessed using univariate and multivariate logistic regression analyses. Diagnosis performance was assessed by receiver operating characteristic curve (ROC) analysis. The AUCs were compared using the Delong method. Univariate analysis demonstrated that MR-tumor (T) stage, MR-lymph node (N) stage, APTw-10%, APTw-90%, interquartile range, APTw-minimum, APTw-maximum, APTw-mean, APTw-median, entropy, kurtosis, mean absolute deviation (MAD), and robust MAD were significantly related to pEMVI-positive status (all p < 0.05). Multivariate analysis demonstrated that MR-T stage (OR = 4.864, p = 0.018), MR-N stage (OR = 4.967, p = 0.029), interquartile range (OR = 0.892, p = 0.037), APT-minimum (OR = 1.046, p = 0.031), entropy (OR = 11.604, p = 0.006), and kurtosis (OR = 1.505, p = 0.007) were the independent risk factors enabling prediction of pEMVI-positive status. The AUCs for diagnostic ability of conventional MRI assessment, the APTw histogram model, and the combined model (including APTw histogram and clinical variables) were 0.785, 0.853, and 0.918, respectively. The combined model outperformed the APTw histogram model (p = 0.013) and the conventional MRI assessment (p = 0.006). Whole-tumor histogram analysis of APTw images combined with clinical factors showed better diagnosis efficiency in predicting EMVI involvement in RA. • Rectal adenocarcinomas with pEMVI-positive status are typically associated with higher APTw-SI values. • APTw-minimum, interquartile range, entropy, kurtosis, MR-T stage, and MR-N stage are the independent risk factors for EMVI involvement. • The best prediction for EMVI involvement was obtained with a combined model of APTw histogram and clinical variables (area under the curve, 0.918).

Differentiating renal cell carcinoma and oncocytoma with volumetric MRI histogram analysis.

In this study, the utility of histogram parameters derived from diffusion-weighted imaging for differentiate renal cell carcinoma (RCC) from oncocytoma was investigated. This research tracked 126 individuals who were diagnosed with RCC and oncocytoma through histopathological analysis, using magnetic resonance imaging (MRI) assessments from 2015 to 2023. We observed various attributes of these patients, including demographic details, surgical records, pre-surgery MRI results, MRI apparent diffusion coefficient (ADC) histogram analysis, and post-surgery histopathological outcomes. Calculations of ADC measurements such as mean, minimum, and maximum in conjunction with the 5th, 10th, 25th, 50th, 75th, 90th, and 95th quantile points were made. In addition, we also noted the skewness, kurtosis, and variance of these data points. The focus group for this investigation consisted of 75 male and 51 female patients. Out of these, 82 were diagnosed with RCC and 44 with oncocytoma. All ADC parameters including ADCmin, ADCmedian, ADCmean, and ADCmax, including the 5th, 10th, 25th, 50th, 75th, 90th, and 95th quantile divisions among the oncocytoma cohort were observed to be higher than the corresponding ones in the RCC group. A statistically meaningful difference was discovered between the minimum ADC value along with the 5th ranking of ADC measurements (p<0.001), in addition to mean of ADC (p=0.050), and the 10th (p=0.002) and 25th (p=0.015) quantiles of ADC data. When considering the region below the curve (AUC) in ROC analysis, the value of ADCmin was recorded as 0.739, with a sensitivity of 75.0%, and specificity of 68.2%. To distinguish oncocytoma from RCC, it may be useful to conduct a whole-tumor histogram and textural analysis of ADC values.

Whole-tumor histogram analysis of diffusion-weighted imaging and dynamic contrast-enhanced MRI for soft tissue sarcoma: correlation with HIF-1alpha expression.

To investigate the correlation of histogram metrics from diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with HIF-1alpha expression in soft tissue sarcoma (STS). We enrolled 71 patients with STS who underwent 3.0-T MRI, including conventional MRI, DWI, and DCE-MRI sequences. Location, maximum tumor diameter, envelope, T2-weighted tumor heterogeneity, peritumoral edema, peritumoral enhancement, necrosis, tail-like pattern, bone invasion, and vessel/nerve invasion and/or encasement were determined using conventional MRI images. The whole-tumor histogram metrics were calculated on the apparent diffusion coefficient (ADC), Ktrans, Kep, and Ve maps. Independent-samples t test and one-way ANOVA were used for testing the differences between normally distributed categorical data with HIF-1alpha expression. Pearson and Spearman correlations and multiple linear regression analyses were performed to determine the correlations between histogram metrics and HIF-1alpha expression. Survival curves were plotted using the Kaplan-Meier method. Regarding conventional MRI features, only highly heterogeneous on T2-weighted images (55.6 ± 19.9% vs. 45.4 ± 20.5%, p = 0.041) and more than 50% necrotic area (57.3 ± 20.4% vs. 43.9 ± 19.7%, p = 0.002) were prone to indicate STS with higher HIF-1alpha expression. Histogram metrics obtained from ADC (mean, median, 10th, and 25th percentile values), Ktrans (mean, median, 75th, and 90th percentile values), and Kep (90th percentile values) were significantly correlated with HIF-1alpha expression. Multiple linear regression analysis demonstrated that more than 50% necrosis, ADCskewness, Ktrans90th, and grade III were independently associated with HIF-1alpha expression. DWI and DCE-MRI histogram parameters were significantly correlated with HIF-1alpha expression in STS. • DWI and DCE-MRI histogram parameters are correlated with HIF-1alpha expression in STS. • More than 50% necrosis, ADCskewness, Ktrans90th, and grade III were independently associated with HIF-1alpha expression in STS.

Interval changes of histogram-derived diffusion indices predict treatment response to induction chemotherapy in head and neck cancer: a feasibility study.

This retrospective study investigated whether the interval change of apparent diffusion coefficient (∆ADC) [baseline and after the first cycle of induction chemotherapy (ICT)] can be used as a valid predictive imaging biomarker of the treatment response to ICT in head and neck cancer (HNC). A total of 19 consecutive patients with HNC who underwent diffusion-weighted magnetic resonance imaging (DWI) at baseline and after the first cycle of ICT were included. Whole-tumor ADC histogram parameters (mean, median, kurtosis, skewness, entropy, minimal, maximum, 25th percentile, and 75th percentile) were obtained. The correlations of ∆ADC histogram parameters, volume, T-stage, N-stage, and age with the treatment response were examined using the Mann-Whitney U test. The predictive value of histogram parameters was examined using receiver operating characteristic (ROC) curves. Responders showed significantly higher values of ∆ADC25 (0.19±0.23) and ∆ADCmin (1.78±2.98) than non-responders (-0.09±0.15 and -0.73±0.36; P=0.035 and 0.009, respectively). When ∆ADC25 and ∆ADCmin were used for predicting the treatment response, the area under the ROC curve was 0.850/0.933 with a sensitivity of 73.3%/80.0% and specificity of 100%/100% (P=0.036 and 0.009, respectively). ∆ADC25 and ∆ADCmin derived from whole-tumor histogram analysis are valuable imaging biomarkers for the early prediction of the ICT response in HNC.

Assessment of Prognostic Factors and Molecular Subtypes of Breast Cancer With a Continuous-Time Random-Walk MR Diffusion Model: Using Whole Tumor Histogram Analysis.

The continuous-time random-walk (CTRW) diffusion model to evaluate breast cancer prognosis is rarely reported. To investigate the correlations between apparent diffusion coefficient (ADC) and CTRW-specific parameters with prognostic factors and molecular subtypes of breast cancer. Retrospective. One hundred fifty-seven women (median age, 50 years; range, 26-81 years) with histopathology-confirmed breast cancer. Simultaneous multi-slice readout-segmented echo-planar imaging at 3.0T. The histogram metrics of ADC, anomalous diffusion coefficient (D), temporal diffusion heterogeneity (α), and spatial diffusion heterogeneity (β) were calculated for whole-tumor volume. Associations between histogram metrics and prognostic factors (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and Ki-67 proliferation index), axillary lymph node metastasis (ALNM), and tumor grade were assessed. The performance of histogram metrics, both alone and in combination, for differentiating molecular subtypes (HER2-positive, Luminal or triple negative) was also assessed. Comparisons were made using Mann-Whitney test between different prognostic factor statuses and molecular subtypes. Receiver operating characteristic curve analysis was used to assess the performance of mean and median histogram metrics in differentiating the molecular subtypes. A P value <0.05 was considered statistically significant. The histogram metrics of ADC, D, and α differed significantly between ER-positive and ER-negative status, and between PR-positive and PR-negative status. The histogram metrics of ADC, D, α, and β were also significantly different between the HER2-positive and HER2-negative subgroups,and between ALNM-positive and ALNM-negative subgroups. The histogram metrics of α and β significantly differed between high and low Ki-67 proliferation subgroups, and between histological grade subgroups. The combination of αmean and βmean achieved the highest performance (AUC=0.702) to discriminate the Luminal and HER2-positive subtypes. Whole-tumor histogram analysis of the CTRW model has potential to provide additional information on the prognosis and intrinsic subtyping classification of breast cancer. 4 TECHNICAL EFFICACY: Stage 2.

Role of diffusion-weighted MRI in differentiation between benign and malignant anterior mediastinal masses.

Diffusion-weighted imaging (DWI) is considered to be a useful biomarker to characterize the cellularity of lesions, yet its application in the thorax to evaluate anterior mediastinal lesions has not been well investigated. The aims of our study were to describe the magnetic resonance (MR) characteristics of anterior mediastinal masses and to assess the role of apparent diffusion coefficient (ADC) value in distinguishing benign from malignant lesions of the anterior mediastinum. We conducted a retrospective cross-sectional study including 55 patients with anterior mediastinal masses who underwent preinterventional MR scanning with the following sequences: T1 VIBE DIXON pre and post-contrast, T2 HASTE, T2 TIRM, DWI-ADC map (b values of 0 and 2000 sec/mm2). The ADC measurements were obtained by two approaches: hot-spot ROI and whole-tumor histogram analysis. The lesions were grouped by three distinct ways: benign versus malignant, group A (benign lesions and type A, AB, B1 thymoma) versus group B (type B2, B3 thymoma and other malignant lesions), lymphoma versus other malignancies. The study was composed of 55 patients, with 5 benign lesions and 50 malignant lesions. The ADCmean, ADCmedian, ADC10, ADC90 in the histogram-based approach and the hot-spot-ROI-based mean ADC of the malignant lesions were significantly lower than those of benign lesions (P values< 0.05). The hot-spot-ROI-based mean ADC had the highest value in differentiation between benign and malignant mediastinal lesions, as well as between group A and group B; the ADC cutoffs (with sensitivity, specificity) to differentiate malignant from benign lesions and group A from group B were 1.17 x 10-3 mm2/sec (80%, 80%) and 0.99 x 10-3 mm2/sec (78.4%, 88.9%), respectively. The ADC values obtained by using the hot-spot-ROI-based and the histogram-based approaches are helpful in differentiating benign and malignant anterior mediastinal masses.

The value of whole-tumor histogram and texture analysis based on apparent diffusion coefficient (ADC) maps for the discrimination of breast fibroepithelial lesions: corresponds to clinical management decisions.

This study aims to comprehensively evaluate the diagnostic value of quantitative parameters extracted from apparent diffusion coefficient (ADC) maps in distinguishing fibroepithelial tumors using whole-tumor histogram and texture analysis. This retrospective study included 66 female patients with single phyllodes tumor (PT) and 29 female patients with single fibroadenoma (FA) who underwent preoperative magnetic resonance imaging. By independently performing whole-tumor histogram and texture analysis based on ADC maps, two radiologists extracted seven histogram parameters and four texture parameters. The extracted parameters were compared using univariate analysis to determine their ability to distinguish FAs from PTs, benign PTs from FAs, as well as benign PTs from borderline and malignant PTs. When FAs and PTs were compared, ADC_skewness values of PTs were significantly lower than those of FAs (p < 0.05), whereas other significant extracted parameter values of PTs were significantly higher than those of FAs (p ≤ 0.001); the area under the curve of significant parameters combined was 0.936. Regarding the differences between FAs and benign PTs, ADC_SD, ADC_95th percentile and ADC_kurtosis of FAs were significantly lower than those of benign PT group, and ADC_skewness was higher than that of benign PT group (all p < 0.05). Furthermore, ADC_SD, ADC_95th percentile and all texture parameters are significantly higher in the borderline and malignant PT group than in FA and benign PT group (p < 0.05). In addition, ADC_kurtosis of malignant PT group was significantly lower than that of borderline PT group (p = 0.045). The extracted whole-tumor histogram and texture features of ADC maps can improve differential diagnosis of breast fibroepithelial tumors and contribute to optimal selection for clinical management of patients with fibroepithelial tumors.

Tumor grading of soft tissue sarcomas: Assessment with whole-tumor histogram analysis of apparent diffusion coefficient

PurposeTo evaluate the usefulness of whole-tumor ADC histogram analysis based on entire tumor volume in determining the histologic grade of STS (soft tissue sarcoma)s. MethodsFrom January 2015 to December 2020, 53 patients with STS who underwent preoperative magnetic resonance imaging, including diffusion weighted imaging and ADC maps (b = 0 and 1400 s/mm2), within 1 month before surgical resection were included in the study. Regions of interest were drawn on every section of the ADC map containing tumor and were summated to derive volume-based histogram data of the entire tumor. Histogram parameters were correlated with histologic tumor grade using Kruskal-Wallis test and compared between high-(grade II and III) and low-grade STSs (grade I) using Mann-Whitney U test. Multivariable logistic regression analysis was applied to identify significant histogram parameters for high-grade STS prediction, and receiver operating characteristic curves (AUC) were constructed to determine optimum threshold. ResultsEight patients with low-grade STS (15.1%) and 45 with high-grade STS (26.4% [14/53] for grade II; 58.5% [31/53] for grade III) were included. High-grade STS showed positive skewness and low-grade STS showed negative skewness (0.503 vs −0.726, p=.001). High-grade STS showed lower mean ADC (p =.03) and 5th to 50th percentile values (p ≤. 03) than those of low-grade STS. Positive skewness was an independent predictor of high-grade STS (odds ratio: 6.704, p=.002) with 84.4% sensitivity and 87.5% specificity (cut-off values > -0.1757, AUC = 0.842). ConclusionSkewness is the most promising histogram parameter for discriminating high-grade from low-grade STS. The mean ADC values and lower half of percentile values are helpful for differentiating high from low-grade STSs.

The Value of Whole-Tumor Histogram and Texture Analysis Using Intravoxel Incoherent Motion in Differentiating Pathologic Subtypes of Locally Advanced Gastric Cancer.

PurposeTo determine if whole-tumor histogram and texture analyses using intravoxel incoherent motion (IVIM) parameters values could differentiate the pathologic characteristics of locally advanced gastric cancer.MethodsEighty patients with histologically confirmed locally advanced gastric cancer who received surgery in our institution were retrospectively enrolled into our study between April 2017 and December 2018. Patients were excluded if they had lesions with the smallest diameter < 5 mm and severe image artifacts. MR scanning included IVIM sequences (9 b values, 0, 20, 40, 60, 100, 150,200, 500, and 800 s/mm2) used in all patients before treatment. Whole tumors were segmented by manually drawing the lesion contours on each slice of the diffusion-weighted imaging (DWI) images (with b=800). Histogram and texture metrics for IVIM parameters values and apparent diffusion coefficient (ADC) values were measured based on whole-tumor volume analyses. Then, all 24 extracted metrics were compared between well, moderately, and poorly differentiated tumors, and between different Lauren classifications, signet-ring cell carcinomas, and other poorly cohesive carcinomas using univariate analyses. Multivariate logistic analyses and multicollinear tests were used to identify independent influencing factors from the significant variables of the univariate analyses to distinguish tumor differentiation and Lauren classifications. ROC curve analyses were performed to evaluate the diagnostic performance of these independent influencing factors for determining tumor differentiation and Lauren classifications and identifying signet-ring cell carcinomas. The interobserver agreement was also conducted between the two observers for image quality evaluations and parameter metric measurements.ResultsFor diagnosing tumor differentiation, the ADCmedian, pure diffusion coefficient median (Dslowmedian), and pure diffusion coefficient entropy (Dslowentropy) showed the greatest AUCs: 0.937, 0.948, and 0.850, respectively, and no differences were found between the three metrics, P>0.05). The 95th percentile perfusion factor (FP P95th) was the best metric to distinguish diffuse-type GCs vs. intestinal/mixed (AUC=0.896). The ROC curve to distinguish signet-ring cell carcinomas from other poorly cohesive carcinomas showed that the Dslowmedian had AUC of 0.738. For interobserver reliability, image quality evaluations showed excellent agreement (interclass correlation coefficient [ICC]=0.85); metrics measurements of all parameters indicated good to excellent agreement (ICC=0.65-0.89), except for the Dfast metric, which showed moderate agreement (ICC=0.41-0.60).ConclusionsThe whole-tumor histogram and texture analyses of the IVIM parameters based on the biexponential model provided a non-invasive method to discriminate pathologic tumor subtypes preoperatively in patients with locally advanced gastric cancer. The metric FP P95th derived from IVIM performed better in determining Lauren classifications than the mono-exponential model.

Whole-Tumor Histogram Analysis of Multiple Diffusion Metrics for Glioma Genotyping.

Background The isocitrate dehydrogenase (IDH) genotype and 1p/19q codeletion status are key molecular markers included in glioma pathologic diagnosis. Advanced diffusion models provide additional microstructural information. Purpose To compare the diagnostic performance of histogram features of multiple diffusion metrics in predicting glioma IDH and 1p/19q genotyping. Materials and Methods In this prospective study, participants were enrolled from December 2018 to December 2020. Diffusion-weighted imaging was performed by using a spin-echo echo-planar imaging sequence with five b values (500, 1000, 1500, 2000, and 2500 sec/mm2) in 30 directions for every b value and one b value of 0. Diffusion metrics of diffusion-tensor imaging (DTI), diffusion-kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator (MAP) were calculated, and their histogram features were analyzed in regions that included the entire tumor and peritumoral edema. Comparisons between groups were performed according to IDH genotype and 1p/19q codeletion status. Logistic regression analysis was used to predict the IDH and 1p/19q genotypes. Results A total of 215 participants (115 men, 100 women; mean age, 48 years ± 13 [standard deviation]) with grade II (n = 68), grade III (n = 35), and grade IV (n = 112) glioma were included. Among the DTI, DKI, NODDI, MAP, and total diffusion models, there were no significant differences in the areas under the receiver operating characteristic curve (AUCs) for predicting IDH mutations (AUC, 0.76, 0.82, 0.78, 0.81, and 0.82, respectively; P > .05) and 1p/19q codeletion in gliomas with IDH mutations (AUC, 0.83, 0.81, 0.82, 0.83, and 0.88, respectively; P > .05). A regression model with an R2 value of 0.84 was used for the Ki-67 labeling index and histogram features of the diffusion metrics. Conclusion Whole-tumor histogram analysis of multiple diffusion metrics is a promising approach for glioma isocitrate dehydrogenase and 1p/19q genotyping, and the performance of diffusion-tensor imaging is similar to that of advanced diffusion models. Clinical trial registration no. ChiCTR2100048119 © RSNA, 2021 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on December 14, 2021.