Radiomics using non-contrast CT to predict hemorrhagic transformation risk in stroke patients undergoing revascularization.

OBJECTIVES: This study explores whether textural features from initial non-contrast CT scans of infarcted brain tissue are linked to hemorrhagic transformation susceptibility. MATERIALS AND METHODS: Stroke patients undergoing thrombolysis or thrombectomy from Jan 2012 to Jan 2022 were analyzed retrospectively. Hemorrhagic transformation was defined using follow-up magnetic resonance imaging. A total of 94 radiomic features were extracted from the infarcted tissue on initial NCCT scans. Patients were divided into training and test sets (7:3 ratio). Two models were developed with fivefold cross-validation: one incorporating first-order and textural radiomic features, and another using only textural radiomic features. A clinical model was also constructed using logistic regression with clinical variables, and test set validation was performed. RESULTS: Among 362 patients, 218 had hemorrhagic transformations. The LightGBM model with all radiomics features had the best performance, with an area under the receiver operating characteristic curve (AUROC) of 0.986 (95% confidence interval [CI], 0.971-1.000) on the test dataset. The ExtraTrees model performed best when textural features were employed, with an AUROC of 0.845 (95% CI, 0.774-0.916). Minimum, maximum, and ten percentile values were significant predictors of hemorrhagic transformation. The clinical model showed an AUROC of 0.544 (95% CI, 0.431-0.658). The performance of the radiomics models was significantly better than that of the clinical model on the test dataset (p < 0.001). CONCLUSIONS: The radiomics model can predict hemorrhagic transformation using NCCT in stroke patients. Low Hounsfield unit was a strong predictor of hemorrhagic transformation, while textural features alone can predict hemorrhagic transformation. CLINICAL RELEVANCE STATEMENT: Using radiomic features extracted from initial non-contrast computed tomography, early prediction of hemorrhagic transformation has the potential to improve patient care and outcomes by aiding in personalized treatment decision-making and early identification of at-risk patients. KEY POINTS: • Predicting hemorrhagic transformation following thrombolysis in stroke is challenging since multiple factors are associated. • Radiomics features of infarcted tissue on initial non-contrast CT are associated with hemorrhagic transformation. • Textural features on non-contrast CT are associated with the frailty of the infarcted tissue.

Current research trends on the effect of diabetes mellitus on rotator cuff tendon healing/tendinopathy.

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.

Natural language processing to predict isocitrate dehydrogenase genotype in diffuse glioma using MR radiology reports.

OBJECTIVES: To evaluate the performance of natural language processing (NLP) models to predict isocitrate dehydrogenase (IDH) mutation status in diffuse glioma using routine MR radiology reports. MATERIALS AND METHODS: This retrospective, multi-center study included consecutive patients with diffuse glioma with known IDH mutation status from May 2009 to November 2021 whose initial MR radiology report was available prior to pathologic diagnosis. Five NLP models (long short-term memory [LSTM], bidirectional LSTM, bidirectional encoder representations from transformers [BERT], BERT graph convolutional network [GCN], BioBERT) were trained, and area under the receiver operating characteristic curve (AUC) was assessed to validate prediction of IDH mutation status in the internal and external validation sets. The performance of the best performing NLP model was compared with that of the human readers. RESULTS: A total of 1427 patients (mean age ± standard deviation, 54 ± 15; 779 men, 54.6%) with 720 patients in the training set, 180 patients in the internal validation set, and 527 patients in the external validation set were included. In the external validation set, BERT GCN showed the highest performance (AUC 0.85, 95% CI 0.81-0.89) in predicting IDH mutation status, which was higher than LSTM (AUC 0.77, 95% CI 0.72-0.81; p = .003) and BioBERT (AUC 0.81, 95% CI 0.76-0.85; p = .03). This was higher than that of a neuroradiologist (AUC 0.80, 95% CI 0.76-0.84; p = .005) and a neurosurgeon (AUC 0.79, 95% CI 0.76-0.84; p = .04). CONCLUSION: BERT GCN was externally validated to predict IDH mutation status in patients with diffuse glioma using routine MR radiology reports with superior or at least comparable performance to human reader. CLINICAL RELEVANCE STATEMENT: Natural language processing may be used to extract relevant information from routine radiology reports to predict cancer genotype and provide prognostic information that may aid in guiding treatment strategy and enabling personalized medicine. KEY POINTS: • A transformer-based natural language processing (NLP) model predicted isocitrate dehydrogenase mutation status in diffuse glioma with an AUC of 0.85 in the external validation set. • The best NLP models were superior or at least comparable to human readers in both internal and external validation sets. • Transformer-based models showed higher performance than conventional NLP model such as long short-term memory.

Association of partial T2-FLAIR mismatch sign and isocitrate dehydrogenase mutation in WHO grade 4 gliomas: results from the ReSPOND consortium.

PURPOSE: While the T2-FLAIR mismatch sign is highly specific for isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted astrocytomas among lower-grade gliomas, its utility in WHO grade 4 gliomas is not well-studied. We derived the partial T2-FLAIR mismatch sign as an imaging biomarker for IDH mutation in WHO grade 4 gliomas. METHODS: Preoperative MRI scans of adult WHO grade 4 glioma patients (n = 2165) from the multi-institutional ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium were analyzed. Diagnostic performance of the partial T2-FLAIR mismatch sign was evaluated. Subset analyses were performed to assess associations of imaging markers with overall survival (OS). RESULTS: One hundred twenty-one (5.6%) of 2165 grade 4 gliomas were IDH-mutant. Partial T2-FLAIR mismatch was present in 40 (1.8%) cases, 32 of which were IDH-mutant, yielding 26.4% sensitivity, 99.6% specificity, 80.0% positive predictive value, and 95.8% negative predictive value. Multivariate logistic regression demonstrated IDH mutation was significantly associated with partial T2-FLAIR mismatch (odds ratio [OR] 5.715, 95% CI [1.896, 17.221], p = 0.002), younger age (OR 0.911 [0.895, 0.927], p < 0.001), tumor centered in frontal lobe (OR 3.842, [2.361, 6.251], p < 0.001), absence of multicentricity (OR 0.173, [0.049, 0.612], p = 0.007), and presence of cystic (OR 6.596, [3.023, 14.391], p < 0.001) or non-enhancing solid components (OR 6.069, [3.371, 10.928], p < 0.001). Multivariate Cox analysis demonstrated cystic components (p = 0.024) and non-enhancing solid components (p = 0.003) were associated with longer OS, while older age (p < 0.001), frontal lobe center (p = 0.008), multifocality (p < 0.001), and multicentricity (p < 0.001) were associated with shorter OS. CONCLUSION: Partial T2-FLAIR mismatch sign is highly specific for IDH mutation in WHO grade 4 gliomas.

A Pipeline for the Implementation and Visualization of Explainable Machine Learning for Medical Imaging Using Radiomics Features.

Machine learning (ML) models have been shown to predict the presence of clinical factors from medical imaging with remarkable accuracy. However, these complex models can be difficult to interpret and are often criticized as "black boxes". Prediction models that provide no insight into how their predictions are obtained are difficult to trust for making important clinical decisions, such as medical diagnoses or treatment. Explainable machine learning (XML) methods, such as Shapley values, have made it possible to explain the behavior of ML algorithms and to identify which predictors contribute most to a prediction. Incorporating XML methods into medical software tools has the potential to increase trust in ML-powered predictions and aid physicians in making medical decisions. Specifically, in the field of medical imaging analysis the most used methods for explaining deep learning-based model predictions are saliency maps that highlight important areas of an image. However, they do not provide a straightforward interpretation of which qualities of an image area are important. Here, we describe a novel pipeline for XML imaging that uses radiomics data and Shapley values as tools to explain outcome predictions from complex prediction models built with medical imaging with well-defined predictors. We present a visualization of XML imaging results in a clinician-focused dashboard that can be generalized to various settings. We demonstrate the use of this workflow for developing and explaining a prediction model using MRI data from glioma patients to predict a genetic mutation.

Radiomics risk score may be a potential imaging biomarker for predicting survival in isocitrate dehydrogenase wild-type lower-grade gliomas.

OBJECTIVES: Isocitrate dehydrogenase wild-type (IDHwt) lower-grade gliomas of histologic grades II and III follow heterogeneous clinical outcomes, which necessitates risk stratification. We aimed to evaluate whether radiomics from MRI would allow prediction of overall survival in patients with IDHwt lower-grade gliomas and to investigate the added prognostic value of radiomics over clinical features. METHODS: Preoperative MRIs of 117 patients with IDHwt lower-grade gliomas from January 2007 to February 2018 were retrospectively analyzed. The external validation cohort consisted of 33 patients from The Cancer Genome Atlas. A total of 182 radiomic features were extracted. Radiomics risk scores (RRSs) for overall survival were derived from the least absolute shrinkage and selection operator (LASSO) and elastic net. Multivariable Cox regression analyses, including clinical features and RRSs, were performed. The integrated areas under the receiver operating characteristic curves (iAUCs) from models with and without RRSs were calculated for comparisons. The prognostic value of RRS was assessed in the validation cohort. RESULTS: The RRS derived from LASSO and elastic net independently predicted survival with hazard ratios of 9.479 (95% confidence interval [CI], 3.220-27.847) and 6.148 (95% CI, 3.009-12.563), respectively. Those RRSs enhanced model performance for predicting overall survival (iAUC increased to 0.780-0.797 from 0.726), which was externally validated. The RRSs stratified IDHwt lower-grade gliomas in the validation cohort with significantly different survival. CONCLUSION: Radiomics has the potential for noninvasive risk stratification and can improve prediction of overall survival in patients with IDHwt lower-grade gliomas when integrated with clinical features. KEY POINTS: • Isocitrate dehydrogenase wild-type lower-grade gliomas with histologic grades II and III follow heterogeneous clinical outcomes, which necessitates further risk stratification. • Radiomics risk scores derived from MRI independently predict survival even after incorporating strong clinical prognostic features (hazard ratios 6.148-9.479). • Radiomics risk scores derived from MRI have the potential to improve survival prediction when added to clinical features (integrated areas under the receiver operating characteristic curves increased from 0.726 to 0.780-0.797).

Machine learning and radiomic phenotyping of lower grade gliomas: improving survival prediction.

BACKGROUND AND PURPOSE: Recent studies have highlighted the importance of isocitrate dehydrogenase (IDH) mutational status in stratifying biologically distinct subgroups of gliomas. This study aimed to evaluate whether MRI-based radiomic features could improve the accuracy of survival predictions for lower grade gliomas over clinical and IDH status. MATERIALS AND METHODS: Radiomic features (n = 250) were extracted from preoperative MRI data of 296 lower grade glioma patients from databases at our institutional (n = 205) and The Cancer Genome Atlas (TCGA)/The Cancer Imaging Archive (TCIA) (n = 91) datasets. For predicting overall survival, random survival forest models were trained with radiomic features; non-imaging prognostic factors including age, resection extent, WHO grade, and IDH status on the institutional dataset, and validated on the TCGA/TCIA dataset. The performance of the random survival forest (RSF) model and incremental value of radiomic features were assessed by time-dependent receiver operating characteristics. RESULTS: The radiomics RSF model identified 71 radiomic features to predict overall survival, which were successfully validated on TCGA/TCIA dataset (iAUC, 0.620; 95% CI, 0.501-0.756). Relative to the RSF model from the non-imaging prognostic parameters, the addition of radiomic features significantly improved the overall survival prediction accuracy of the random survival forest model (iAUC, 0.627 vs. 0.709; difference, 0.097; 95% CI, 0.003-0.209). CONCLUSION: Radiomic phenotyping with machine learning can improve survival prediction over clinical profile and genomic data for lower grade gliomas. KEY POINTS: • Radiomics analysis with machine learning can improve survival prediction over the non-imaging factors (clinical and molecular profiles) for lower grade gliomas, across different institutions.

MR image phenotypes may add prognostic value to clinical features in IDH wild-type lower-grade gliomas.

PURPOSE: To identify significant prognostic magnetic resonance imaging (MRI) features and their prognostic value when added to clinical features in patients with isocitrate dehydrogenase wild-type (IDHwt) lower-grade gliomas. MATERIALS AND METHODS: Preoperative MR images of 158 patients (discovery set = 112, external validation set = 46) with IDHwt lower-grade gliomas (WHO grade II or III) were retrospectively analyzed using the Visually Accessible Rembrandt Images feature set. Radiologic risk scores (RRSs) for overall survival were derived from the least absolute shrinkage and selection operator and elastic net. Multivariable Cox regression analysis, including age, Karnofsky Performance score, extent of resection, WHO grade, and RRS, was performed. The added prognostic value of RRS was calculated by comparing the integrated area under the receiver operating characteristic curve (iAUC) between models with and without RRS. RESULTS: The presence of cysts, pial invasion, and cortical involvement were favorable prognostic factors, while ependymal extension, multifocal or multicentric distribution, nonlobar location, proportion of necrosis > 33%, satellites, and eloquent cortex involvement were significantly associated with worse prognosis. RRS independently predicted survival and significantly enhanced model performance for survival prediction when integrated to clinical features (iAUC increased to 0.773-0.777 from 0.737), which was successfully validated on the validation set (iAUC increased to 0.805-0.830 from 0.735). CONCLUSION: MRI features associated with prognosis in patients with IDHwt lower-grade gliomas were identified. RRSs derived from MRI features independently predicted survival and significantly improved performance of survival prediction models when integrated into clinical features. KEY POINTS: • Comprehensive analysis of MRI features conveys prognostic information in patients with isocitrate dehydrogenase wild-type lower-grade gliomas. • Presence of cysts, pial invasion, and cortical involvement of the tumor were favorable prognostic factors. • Radiological phenotypes derived from MRI independently predict survival and have the potential to improve survival prediction when added to clinical features.

Diffusion tensor imaging radiomics in lower-grade glioma: improving subtyping of isocitrate dehydrogenase mutation status.

PURPOSE: To evaluate whether diffusion tensor imaging (DTI) radiomics with machine learning improves the prediction of isocitrate dehydrogenase (IDH) mutation status of lower-grade gliomas beyond radiomic features from conventional MRI and DTI histogram parameters. METHODS: A total of 168 patients with pathologically confirmed lower-grade gliomas were retrospectively enrolled. A total of 158 and 253 radiomic features were extracted from DTI (DTI radiomics) and conventional MRI (T1-weighted image with contrast enhancement, T2-weighted image, and FLAIR [conventional radiomics]), respectively. The random forest models for predicting IDH status were trained with variable combinations as follows: (1) DTI radiomics, (2) conventional radiomics, (3) conventional radiomics + DTI radiomics, and (4) conventional radiomics + DTI histogram. The models were validated with nested cross-validation. The predictive performances of those models were compared by using area under the curve (AUC) from receiver operating characteristic analysis, and 95% confidence interval (CI) was calculated. RESULTS: Adding DTI radiomics to conventional radiomics significantly improved the accuracy of IDH status subtyping (AUC, 0.900 [95% CI, 0.855-0.945], p = 0.006), whereas adding DTI histogram parameters yielded nonsignificant trend toward improvement (0.869 [95% CI, 0.816-0.922], p = 0.150) compared with the model with conventional radiomics alone (0.835 [95% CI, 0.773-0.896]). The performance of the model consisting of both DTI and conventional radiomics was significantly superior than that of model consisting of both DTI histogram parameters and conventional radiomics (0.900 vs 0.869, p = 0.040). CONCLUSION: DTI radiomics with machine learning can help improve the subtyping of IDH status beyond conventional radiomics and DTI histogram parameters in patients with lower-grade gliomas.

The added prognostic value of radiological phenotype combined with clinical features and molecular subtype in anaplastic gliomas.

PURPOSE: To determine whether radiological phenotype can improve the predictive performance of the risk model based on molecular subtype and clinical risk factors in anaplastic glioma patients. METHODS: This retrospective study was approved by our institutional review board with waiver of informed consent. MR images of 86 patients with pathologically diagnosed anaplastic glioma (WHO grade III) between January 2007 and February 2016 were analyzed according to the Visually Accessible Rembrandt Images (VASARI) features set. Significant imaging findings were selected to generate a radiological risk score (RRS) for overall survival (OS) and progression-free survival (PFS) using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The prognostic value of RRS was evaluated with multivariate Cox regression including molecular subtype and clinical risk factors. The C-indices of multivariate models with and without RRS were compared by bootstrapping. RESULTS: Eight VASARI features contributed to RRS for OS and six contributed to PFS. Multifocality or multicentricity was the most influential feature, followed by restricted diffusion. RRS was significantly associated with OS and PFS (P < .001), as well as age and molecular subtype. The multivariate model with RRS demonstrated a significantly higher predictive performance than the model without (C-index difference: 0.074, 95% confidence interval [CI]: 0.031, 0.148 for OS; C-index difference: 0.054, 95% CI: 0.014, 0.123 for PFS). CONCLUSION: RRS derived from VASARI features was an independent predictor of survival in patients with anaplastic gliomas. The addition of RRS significantly improved the predictive performance of the molecular feature based model.

Radiomics and machine learning may accurately predict the grade and histological subtype in meningiomas using conventional and diffusion tensor imaging.

OBJECTIVES: Preoperative, noninvasive prediction of the meningioma grade is important because it influences the treatment strategy. The purpose of this study was to evaluate the role of radiomics features of postcontrast T1-weighted images (T1C), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps, based on the entire tumor volume, in the differentiation of grades and histological subtypes of meningiomas. METHODS: One hundred thirty-six patients with pathologically diagnosed meningiomas (108 low-grade [benign], 28 high-grade [atypical and anaplastic]), who underwent T1C and diffusion tensor imaging, were included in the discovery set. The T1C image, ADC, and FA maps were analyzed to derive volume-based data of the entire tumor. Radiomics features were correlated with meningioma grades and histological subtypes. Various machine learning classifiers were trained to build classification models to predict meningioma grades. We tested the model in a validation set (58 patients; 46 low-grade; 12 high-grade). RESULTS: The machine learning classifiers showed variable performances depending on the machine learning algorithms. The best classification system for the prediction of meningioma grades had an area under the curve of 0.86 (95% confidence interval [CI], 0.74-0.98) in the validation set. The accuracy, sensitivity, and specificity of the best classifier were 89.7, 75.0, and 93.5% in the validation set, respectively. Various texture parameters differed significantly between fibroblastic and non-fibroblastic subtypes. CONCLUSIONS: Radiomics feature-based machine learning classifiers of T1C images, ADC, and FA maps are useful for differentiating meningioma grades. KEY POINTS: • Preoperative, noninvasive differentiation of the meningioma grade is important because it influences the treatment strategy. • Radiomics feature-based machine learning classifiers of T1C images, ADC, and FA maps are useful for differentiating meningioma grades. • In benign meningiomas, there were significant differences in the various texture parameters between fibroblastic and non-fibroblastic meningioma subtypes.

Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma.

OBJECTIVES: To assess the utility of amide proton transfer (APT) imaging as an imaging biomarker to predict prognosis and molecular marker status in high-grade glioma (HGG, WHO grade III/IV). METHODS: We included 71 patients with pathologically diagnosed HGG who underwent preoperative MRI with APT imaging. Overall survival (OS) and progression-free survival (PFS) according to APT signal, clinical factors, MGMT methylation status, and IDH mutation status were analyzed. Multivariate Cox regression models with and without APT signal data were constructed. Model performance was compared using the integrated AUC (iAUC). Associations between APT signals and molecular markers were assessed using the Mann-Whitney test. RESULTS: High APT signal was a significant predictor for poor OS (HR = 3.21, 95% CI = 1.62-6.34) and PFS (HR = 2.22, 95% CI = 1.33-3.72) on univariate analysis. On multivariate analysis, high APT signals were an independent predictor of poor OS and PFS when clinical factors alone (OS: HR = 2.89; PFS: HR = 2.13), or in combination with molecular markers (OS: HR = 2.85; PFS: HR = 2.00), were included as covariates. The incremental prognostic value of APT signals was significant for OS and PFS. IDH-wild type was significantly associated with high APT signals (p = 0.001) when compared to IDH-mutant; however, there was no difference based on MGMT methylation status (p = 0.208). CONCLUSION: High APT signal was a significant predictor of poor prognosis in HGG. APT data showed significant incremental prognostic value over clinical prognostic factors and molecular markers and may also predict IDH mutation status. KEY POINTS: • Amide proton transfer (APT) imaging is a promising prognostic marker of high-grade glioma. • APT signals were significantly higher in IDH-wild type compared to IDH-mutant high-grade glioma. • APT imaging may be valuable for preoperative screening and treatment guidance.

Differentiation between spinal cord diffuse midline glioma with histone H3 K27M mutation and wild type: comparative magnetic resonance imaging.

PURPOSE: Diffuse midline glioma with histone H3 K27M mutation is a new entity described in the 2016 update of the World Health Organization Classification of Tumors of the Central Nervous System. The purpose of this study was to evaluate the clinical and imaging characteristics to predict the presence of H3 K27M mutation in spinal cord glioma using a machine learning-based classification model. METHODS: A total of 41 spinal cord glioma patients consisting of 24 H3 K27M mutants and 17 wild types were enrolled in this retrospective study. A total of 17 clinical and radiological features were evaluated. The random forest (RF) model was trained with the clinical and radiological features to predict the presence of H3 K27M mutation. The diagnostic ability of the RF model was evaluated using receiver operating characteristic (ROC) analysis. Area under the ROC curves (AUC) was calculated. RESULTS: MR imaging features of spinal cord diffuse midline gliomas were heterogeneous. Hemorrhage was the only variable that was able to differentiate H3 K27M mutated tumors from wild-type tumors in univariate analysis (p = 0.033). RF classifier yielded 0.632 classification AUC (95% CI, 0.456-0.808), 63.4% accuracy, 45.8% sensitivity, and 88.2% specificity. CONCLUSION: Our findings indicate that clinical and radiological features are associated with H3 K27M mutation status in spinal cord glioma.

Radiomic MRI Phenotyping of Glioblastoma: Improving Survival Prediction.

Purpose To investigate whether radiomic features at MRI improve survival prediction in patients with glioblastoma multiforme (GBM) when they are integrated with clinical and genetic profiles. Materials and Methods Data in patients with a diagnosis of GBM between December 2009 and January 2017 (217 patients) were retrospectively reviewed up to May 2017 and allocated to training and test sets (3:1 ratio). Radiomic features (n = 796) were extracted from multiparametric MRI. A random survival forest (RSF) model was trained with the radiomic features along with clinical and genetic profiles (O-6-methylguanine-DNA-methyltransferase promoter methylation and isocitrate dehydrogenase 1 mutation statuses) to predict overall survival (OS) and progression-free survival (PFS). The RSF models were validated on the test set. The incremental values of radiomic features were evaluated by using the integrated area under the receiver operating characteristic curve (iAUC). Results The 217 patients had a mean age of 57.9 years, and there were 87 female patients (age range, 22-81 years) and 130 male patients (age range, 17-85 years). The median OS and PFS of patients were 352 days (range, 20-1809 days) and 264 days (range, 21-1809 days), respectively. The RSF radiomics models were successfully validated on the test set (iAUC, 0.652 [95% confidence interval {CI}, 0.524, 0.769] and 0.590 [95% CI: 0.502, 0.689] for OS and PFS, respectively). The addition of a radiomics model to clinical and genetic profiles improved survival prediction when compared with models containing clinical and genetic profiles alone (P = .04 and .03 for OS and PFS, respectively). Conclusion Radiomic MRI phenotyping can improve survival prediction when integrated with clinical and genetic profiles and thus has potential as a practical imaging biomarker. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Jain and Lui in this issue.

Primary central nervous system lymphoma and atypical glioblastoma: Differentiation using radiomics approach.

OBJECTIVES: To evaluate the diagnostic performance of magnetic resonance (MR) radiomics-based machine-learning algorithms in differentiating primary central nervous system lymphoma (PCNSL) from non-necrotic atypical glioblastoma (GBM). METHODS: Seventy-seven patients (54 individuals with PCNSL and 23 with non-necrotic atypical GBM), diagnosed from January 2009 to April 2017, were enrolled in this retrospective study. A total of 6,366 radiomics features, including shape, volume, first-order, texture, and wavelet-transformed features, were extracted from multi-parametric (post-contrast T1- and T2-weighted, and fluid attenuation inversion recovery images) and multiregional (enhanced and non-enhanced) tumour volumes. These features were subjected to recursive feature elimination and random forest (RF) analysis with nested cross-validation. The diagnostic abilities of a radiomics machine-learning classifier, apparent diffusion coefficient (ADC), and three readers, who independently classified the tumours based on conventional MR sequences, were evaluated using receiver operating characteristic (ROC) analysis. Areas under the ROC curves (AUC) of the radiomics classifier, ADC value, and the radiologists were compared. RESULTS: The mean AUC of the radiomics classifier was 0.921 (95 % CI 0.825-0.990). The AUCs of the three readers and ADC were 0.707 (95 % CI 0.622-0.793), 0.759 (95 %CI 0.656-0.861), 0.695 (95 % CI 0.590-0.800) and 0.684 (95 % CI0.560-0.809), respectively. The AUC of the radiomics-based classifier was significantly higher than those of the three readers and ADC (p< 0.001 for all). CONCLUSIONS: Large-scale radiomics with a machine-learning algorithm can be useful for differentiating PCNSL from atypical GBM, and yields a better diagnostic performance than human radiologists and ADC values. KEY POINTS: • Machine-learning algorithm radiomics can help to differentiate primary central PCNSL from GBM. • This approach yields a higher diagnostic accuracy than visual analysis by radiologists. • Radiomics can strengthen radiologists' diagnostic decisions whenever conventional MRI sequences are available.

Amide proton transfer imaging for differentiation of benign and atypical meningiomas.

PURPOSE: To investigate the difference in amide proton transfer (APT)-weighted signals between benign and atypical meningiomas and determine the value of APT imaging for differentiating the two. METHODS: Fifty-seven patients with pathologically diagnosed meningiomas (benign, 44; atypical, 13), who underwent preoperative MRI with APT imaging between December 2014 and August 2016 were included. We compared normalised magnetisation transfer ratio asymmetry (nMTR asym ) values between benign and atypical meningiomas on APT-weighted images. Conventional MRI features were qualitatively assessed. Both imaging features were evaluated by multivariable logistic regression analysis. The discriminative value of MRI with and without nMTR asym was evaluated. RESULTS: The nMTR asym of atypical meningiomas was significantly greater than that of benign meningiomas (2.46% vs. 1.67%; P < 0.001). In conventional MR images, benign and atypical meningiomas exhibited significant differences in maximum tumour diameter, non-skull base location, and heterogeneous enhancement. On multivariable logistic regression analysis, high nMTR asym was an independent predictor of atypical meningiomas (adjusted OR, 11.227; P = 0.014). The diagnostic performance of MRI improved with nMTR asym for predicting atypical meningiomas. CONCLUSION: Atypical meningiomas exhibited significantly higher APT-weighted signal intensities than benign meningiomas. The discriminative value of conventional MRI improved significantly when combined with APT imaging for diagnosis of atypical meningioma. KEY POINTS: • APT imaging is useful for differentiating between atypical and benign meningiomas. • Atypical meningiomas exhibited high APT-weighted signal intensity than benign meningiomas. • The diagnostic performance of MRI improved with nMTR asym for predicting atypical meningiomas.

Characterizing amide proton transfer imaging in haemorrhage brain lesions using 3T MRI.

OBJECTIVES: The aim of this study was to characterize amide proton transfer (APT)-weighted signals in acute and subacute haemorrhage brain lesions of various underlying aetiologies. METHODS: Twenty-three patients with symptomatic haemorrhage brain lesions including tumorous (n = 16) and non-tumorous lesions (n = 7) were evaluated. APT imaging was performed and analyzed with magnetization transfer ratio asymmetry (MTR asym ). Regions of interest were defined as the enhancing portion (when present), acute or subacute haemorrhage, and normal-appearing white matter based on anatomical MRI. MTR asym values were compared among groups and components using a linear mixed model. RESULTS: MTR asym values were 3.68 % in acute haemorrhage, 1.6 % in subacute haemorrhage, 2.65 % in the enhancing portion, and 0.38 % in normal white matter. According to the linear mixed model, the distribution of MTR asym values among components was not significantly different between tumour and non-tumour groups. MTR asym in acute haemorrhage was significantly higher than those in the other regions regardless of underlying pathology. CONCLUSIONS: Acute haemorrhages showed high MTR asym regardless of the underlying pathology, whereas subacute haemorrhages showed lower MTR asym than acute haemorrhages. These results can aid in the interpretation of APT imaging in haemorrhage brain lesions. KEY POINTS: • Acute haemorrhages show significantly higher MTR asym values than subacute haemorrhages. • MTR asym is higher in acute haemorrhage than in enhancing tumour tissue. • MTR asym in haemorrhage does not differ between tumorous and non-tumorous lesions.

Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume.

OBJECTIVES: To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas. METHODS: Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement. RESULTS: The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222). CONCLUSIONS: APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas. KEY POINTS: • Higher APT values were correlated with higher glioma grades. • Adding the APT signal to the ADC improved glioma grading. • Adding the APT signal to rCBV did not improve glioma grading. • APT is a useful adjunct to the ADC for glioma grading.

Gadolinium deposition in the brain: association with various GBCAs using a generalized additive model.

OBJECTIVES: To determine the relationship between the number of administrations of various gadolinium-based contrast agents (GBCAs) and increased T1 signal intensity in the globus pallidus (GP) and dentate nucleus (DN). METHODS: This retrospective study included 122 patients who underwent double-dose GBCA-enhanced magnetic resonance imaging. Two radiologists calculated GP-to-thalamus (TH) signal intensity ratio, DN-to-pons signal intensity ratio and relative change (Rchange) between the baseline and final examinations. Interobserver agreement was evaluated. The relationships between Rchange and several factors, including number of each GBCA administrations, were analysed using a generalized additive model. RESULTS: Six patients (4.9%) received linear GBCAs (mean 20.8 number of administration; range 15-30), 44 patients (36.1%) received macrocyclic GBCAs (mean 26.1; range 14-51) and 72 patients (59.0%) received both types of GBCAs (mean 31.5; range 12-65). Interobserver agreement was almost perfect (0.99; 95% CI: 0.99-0.99). Rchange (DN:pons) was associated with gadodiamide (p = 0.006) and gadopentetate dimeglumine (p < 0.001), but not with other GBCAs. Rchange (GP:TH) was not associated with GBCA administration. CONCLUSIONS: Previous administration of linear agents gadoiamide and gadopentetate dimeglumine is associated with increased T1 signal intensity in the DN, whereas macrocyclic GBCAs do not show an association. KEY POINTS: • Certain linear GBCAs are associated with T1 signal change in the dentate nucleus. • The signal change is related to the administration number of certain linear GBCAs. • Difference in signal change may reflect differences in stability of agents.

Primary central nervous system lymphoma and atypical glioblastoma: differentiation using the initial area under the curve derived from dynamic contrast-enhanced MR and the apparent diffusion coefficient.

OBJECTIVES: To evaluate the ability of the initial area under the curve (IAUC) derived from dynamic contrast-enhanced MR imaging (DCE-MRI) and apparent diffusion coefficient (ADC) in differentiating between primary central nervous system lymphoma (PCNSL) and atypical glioblastoma (GBM). METHODS: We retrospectively identified 19 patients with atypical GBM (less than 13 % necrosis of the enhancing tumour), and 23 patients with PCNSL. The histogram parameters of IAUC at 30, 60, 90 s (IAUC30, IAUC60, and IAUC90), and ADC were compared between PCNSL and GBM. The diagnostic performances and added values of the IAUC and ADC for differentiating between PCNSL and GBM were evaluated. Interobserver agreement was assessed via intraclass correlation coefficient (ICC). RESULTS: The IAUC and ADC parameters were higher in GBM than in PCNSL. The 90th percentile (p90) of IAUC30 and 10th percentile (p10) of ADC showed the best diagnostic performance. Adding p90 of IAUC30 to p10 of ADC improved the differentiation between PCNSL and GBM (area under the ROC curve [AUC] = 0.886), compared to IAUC30 or ADC alone (AUC = 0.789 and 0.744; P < 0.05 for all). The ICC was 0.96 for p90 of IAUC30. CONCLUSIONS: The IAUC may be a useful parameter together with ADC for differentiating between PCNSL and atypical GBM. KEY POINTS: • High reproducibility is essential for practical implementation of advanced MRI parameters. • IAUC and ADC are highly reproducible parameters. • IAUC values were higher in atypical GBM than in PCNSL. • Adding IAUC to ADC improved the differentiation between PCNSL and GBM. • IAUC with ADC are useful for differentiating PCNSL from GBM.