Investigating the value of radiomics stemming from DSC quantitative biomarkers in IDH mutation prediction in gliomas.

Objective: This study aims to assess the value of biomarker based radiomics to predict IDH mutation in gliomas. The patient cohort consists of 160 patients histopathologicaly proven of primary glioma (WHO grades 2-4) from 3 different centers. Methods: To quantify the DSC perfusion signal two different mathematical modeling methods were used (Gamma fitting, leakage correction algorithms) considering the assumptions about the compartments contributing in the blood flow between the extra- and intra vascular space. Results: The Mean slope of increase (MSI) and the K1 parameter of the bidirectional exchange model exhibited the highest performance with (ACC 74.3% AUROC 74.2%) and (ACC 75% AUROC 70.5%) respectively. Conclusion: The proposed framework on DSC-MRI radiogenomics in gliomas has the potential of becoming a reliable diagnostic support tool exploiting the mathematical modeling of the DSC signal to characterize IDH mutation status through a more reproducible and standardized signal analysis scheme for facilitating clinical translation.

ADC values as a biomarker of fetal brain maturation.

BACKGROUND: During the period of fetal development, myelination plays a key role and follows specific time and spatial sequences. The water content in the brain is inversely proportional to myelination - the more myelinated the brain, the lower the water content in it. The diffusion of water molecules can be quantitatively assessed using the apparent diffusion coefficient (ADC). We were interested in whether, by determining the ADC values, we could quantitatively evaluate the development of the fetal brain. PATIENTS AND METHODS: The study included 42 fetuses with gestational age 25 to 35 weeks. We manually selected 13 regions on diffusion-weighted images. Statistically significant differences between ADC values were checked using one-way analysis of variance and Tukey's post hoc test. The relationship between the ADC values and the gestational age of the fetuses was then assessed using linear regression. RESULTS: The average gestational age of the fetuses was 29.8 ± 2.4 weeks. ADC values in the thalami, pons and cerebellum differed significantly among each other and from the ADC values in other brain regions. In the thalami, pons and cerebellum, linear regression showed a significant decrease in ADC values with increasing gestational age. CONCLUSIONS: ADC values change with the increasing gestational age of the fetus and differ among different brain regions. In the pons, cerebellum and thalami, the ADC coefficient could be used as a biomarker of fetal brain maturation since ADC values decrease linearly with increasing gestational age.

Clinical indications and acquisition protocol for the use of dynamic contrast-enhanced MRI in head and neck cancer squamous cell carcinoma: recommendations from an expert panel.

BACKGROUND: The clinical role of perfusion-weighted MRI (PWI) in head and neck squamous cell carcinoma (HNSCC) remains to be defined. The aim of this study was to provide evidence-based recommendations for the use of PWI sequence in HNSCC with regard to clinical indications and acquisition parameters. METHODS: Public databases were searched, and selected papers evaluated applying the Oxford criteria 2011. A questionnaire was prepared including statements on clinical indications of PWI as well as its acquisition technique and submitted to selected panelists who worked in anonymity using a modified Delphi approach. Each panelist was asked to rate each statement using a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). Statements with scores equal or inferior to 5 assigned by at least two panelists were revised and re-submitted for the subsequent Delphi round to reach a final consensus. RESULTS: Two Delphi rounds were conducted. The final questionnaire consisted of 6 statements on clinical indications of PWI and 9 statements on the acquisition technique of PWI. Four of 19 (21%) statements obtained scores equal or inferior to 5 by two panelists, all dealing with clinical indications. The Delphi process was considered concluded as reasons entered by panelists for lower scores were mainly related to the lack of robust evidence, so that no further modifications were suggested. CONCLUSIONS: Evidence-based recommendations on the use of PWI have been provided by an independent panel of experts worldwide, encouraging a standardized use of PWI across university and research centers to produce more robust evidence.

Dynamic contrast-enhanced MRI in malignant pleural mesothelioma: prediction of outcome based on DCE-MRI measurements in patients undergoing cytotoxic chemotherapy.

BACKGROUND: The malignant pleural mesothelioma (MPM) response rate to chemotherapy is low. The identification of imaging biomarkers that could help guide the most effective therapy approach for individual patients is highly desirable. Our aim was to investigate the dynamic contrast-enhanced (DCE) MR parameters as predictors for progression-free (PFS) and overall survival (OS) in patients with MPM treated with cisplatin-based chemotherapy. METHODS: Thirty-two consecutive patients with MPM were enrolled in this prospective study. Pretreatment and intratreatment DCE-MRI were scheduled in each patient. The DCE parameters were analyzed using the extended Tofts (ET) and the adiabatic approximation tissue homogeneity (AATH) model. Comparison analysis, logistic regression and ROC analysis were used to identify the predictors for the patient's outcome. RESULTS: Patients with higher pretreatment ET and AATH-calculated Ktrans and ve values had longer OS (P≤.006). Patients with a more prominent reduction in ET-calculated Ktrans and kep values during the early phase of chemotherapy had longer PFS (P =.008). No parameter was identified to predict PFS. Pre-treatment ET-calculated Ktrans was found to be an independent predictive marker for longer OS (P=.02) demonstrating the most favourable discrimination performance compared to other DCE parameters with an estimated sensitivity of 89% and specificity of 78% (AUC 0.9, 95% CI 0.74-0.98, cut off > 0.08 min-1). CONCLUSIONS: In the present study, higher pre-treatment ET-calculated Ktrans values were associated with longer OS. The results suggest that DCE-MRI might provide additional information for identifying MPM patients that may respond to chemotherapy.

Multicenter DSC-MRI-Based Radiomics Predict IDH Mutation in Gliomas.

To address the current lack of dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI)-based radiomics to predict isocitrate dehydrogenase (IDH) mutations in gliomas, we present a multicenter study that featured an independent exploratory set for radiomics model development and external validation using two independent cohorts. The maximum performance of the IDH mutation status prediction on the validation set had an accuracy of 0.544 (Cohen's kappa: 0.145, F1-score: 0.415, area under the curve-AUC: 0.639, sensitivity: 0.733, specificity: 0.491), which significantly improved to an accuracy of 0.706 (Cohen's kappa: 0.282, F1-score: 0.474, AUC: 0.667, sensitivity: 0.6, specificity: 0.736) when dynamic-based standardization of the images was performed prior to the radiomics. Model explainability using local interpretable model-agnostic explanations (LIME) and Shapley additive explanations (SHAP) revealed potential intuitive correlations between the IDH-wildtype increased heterogeneity and the texture complexity. These results strengthened our hypothesis that DSC-MRI radiogenomics in gliomas hold the potential to provide increased predictive performance from models that generalize well and provide understandable patterns between IDH mutation status and the extracted features toward enabling the clinical translation of radiogenomics in neuro-oncology.

Prognostic value of CT perfusion and permeability imaging in traumatic brain injury.

BACKGROUND: Currently established prognostic models in traumatic brain injury (TBI) include noncontrast computed tomography (CT) which is insensitive to early perfusion alterations associated with secondary brain injury. Perfusion CT (PCT) on the other hand offers insight into early perfusion abnormalities. We hypothesized that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model. METHODS: A prospective cohort study of consecutive 50 adult patients with head injury and Glasgow Coma Scale score of 12 or less was performed at a single Level 1 Trauma Centre. Perfusion CT was added to routine control CT 12 hours to 24 hours after admission. Region of interest analysis was performed in six major vascular territories on perfusion and permeability parametric maps. Glasgow Outcome Scale (GOS) was used 6 months later to categorize patients' functional outcomes to favorable (GOS score > 3) or unfavorable (GOS score ≤ 3). We defined core prognostic model, consisting of age, motor Glasgow Coma Scale score, pupillary reactivity, and CT Rotterdam Score. Next, we added perfusion and permeability data as predictors and compared updated models to the core model using cross-validated areas under the receiver operator curves (cv-AUC). RESULTS: Significant advantage over core model was shown by the model, containing both mean cerebral extravascular-extracellular volume per unit of tissue volume and cerebral blood volume of the least perfused arterial territory in addition to core predictors (cv-AUC, 0.75; 95% confidence interval, 0.51-0.84 vs. 0.6; 95% confidence interval, 0.37-0.74). CONCLUSION: The development of cerebral ischemia and traumatic cerebral edema constitutes the secondary brain injury and represents the target for therapeutic interventions. Our results suggest that adding CT perfusion and permeability data to the established outcome predictors improves the performance of the prognostic model in the setting of moderate and severe TBI. LEVEL OF EVIDENCE: Prognostic study, level III.

Machine learning assisted DSC-MRI radiomics as a tool for glioma classification by grade and mutation status.

BACKGROUND: Combining MRI techniques with machine learning methodology is rapidly gaining attention as a promising method for staging of brain gliomas. This study assesses the diagnostic value of such a framework applied to dynamic susceptibility contrast (DSC)-MRI in classifying treatment-naïve gliomas from a multi-center patients into WHO grades II-IV and across their isocitrate dehydrogenase (IDH) mutation status. METHODS: Three hundred thirty-three patients from 6 tertiary centres, diagnosed histologically and molecularly with primary gliomas (IDH-mutant = 151 or IDH-wildtype = 182) were retrospectively identified. Raw DSC-MRI data was post-processed for normalised leakage-corrected relative cerebral blood volume (rCBV) maps. Shape, intensity distribution (histogram) and rotational invariant Haralick texture features over the tumour mask were extracted. Differences in extracted features across glioma grades and mutation status were tested using the Wilcoxon two-sample test. A random-forest algorithm was employed (2-fold cross-validation, 250 repeats) to predict grades or mutation status using the extracted features. RESULTS: Shape, distribution and texture features showed significant differences across mutation status. WHO grade II-III differentiation was mostly driven by shape features while texture and intensity feature were more relevant for the III-IV separation. Increased number of features became significant when differentiating grades further apart from one another. Gliomas were correctly stratified by mutation status in 71% and by grade in 53% of the cases (87% of the gliomas grades predicted with distance less than 1). CONCLUSIONS: Despite large heterogeneity in the multi-center dataset, machine learning assisted DSC-MRI radiomics hold potential to address the inherent variability and presents a promising approach for non-invasive glioma molecular subtyping and grading.

Transarterial embolization of the external carotid artery in the treatment of life-threatening haemorrhage following blunt maxillofacial trauma.

Background Severe bleeding after blunt maxillofacial trauma is a rare but life-threatening event. Non-responders to conventional treatment options with surgically inaccessible bleeding points can be treated by transarterial embolization (TAE) of the external carotid artery (ECA) or its branches. Case series on such embolizations are small; considering the relatively high incidence of maxillofacial trauma, the ECA TAE procedure has been hypothesized either underused or underreported. In addition, the literature on the ECA TAE using novel non-adhesive liquid embolization agents is remarkably scarce. Patients and methods PubMed review was performed to identify the ECA TAE literature in the context of blunt maxillofacial trauma. If available, the location of the ECA injury, the location of embolization, the chosen embolization agent, and efficacy and safety of the TAE were noted for each case. Survival prognostic factors were also reviewed. Additionally, we present an illustrative TAE case using a precipitating hydrophobic injectable liquid (PHIL) to safely and effectively control a massive bleeding originating bilaterally in the ECA territories. Results and conclusions Based on a review of 205 cases, the efficacy of TAE was 79.4-100%, while the rate of major complications was about 2-4%. Successful TAE haemostasis, Glasgow Coma Scale score ≥ 8 at presentation, injury severity score ≤ 32, shock index ≤ 1.1 before TAE and ≤ 0.8 after TAE were significantly correlated with higher survival rate. PHIL allowed for fast yet punctilious application, thus saving invaluable time in life-threatening situations while simultaneously diminishing the possibility of inadvertent injection into the ECA-internal carotid artery (ICA) anastomoses.

Prognostic role of diffusion weighted and dynamic contrast-enhanced MRI in loco-regionally advanced head and neck cancer treated with concomitant chemoradiotherapy.

Background In the study, the value of pre-treatment dynamic contrast-enhanced (DCE) and diffusion weighted (DW) MRI-derived parameters as well as their changes early during treatment was evaluated for predicting disease-free survival (DFS) and overall survival (OS) in patients with locoregionally advanced head and neck squamous carcinoma (HNSCC) treated with concomitant chemoradiotherapy (cCRT) with cisplatin. Patients and methods MRI scans were performed in 20 patients with locoregionally advanced HNSCC at baseline and after 10 Grays (Gy) of cCRT. Tumour apparent diffusion coefficient (ADC) and DCE parameters (volume transfer constant [Ktrans], extracellular extravascular volume fraction [ve], and plasma volume fraction [Vp]) were measured. Relative changes in parameters from baseline to 10 Gy were calculated. Univariate and multivariate Cox regression analysis were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify parameters with the best diagnostic performance. Results None of the parameters was identified to predict for DFS. On univariate analysis of OS, lower pre-treatment ADC (p = 0.012), higher pre-treatment Ktrans (p = 0.026), and higher reduction in Ktrans (p = 0.014) from baseline to 10 Gy were identified as significant predictors. Multivariate analysis identified only higher pre-treatment Ktrans (p = 0.026; 95% CI: 0.000-0.132) as an independent predictor of OS. At ROC curve analysis, pre-treatment Ktrans yielded an excellent diagnostic accuracy (area under curve [AUC] = 0.95, sensitivity 93.3%; specificity 80 %). Conclusions In our group of HNSCC patients treated with cisplatin-based cCRT, pre-treatment Ktrans was found to be a good predictor of OS.

Dynamic contrast-enhanced MRI of malignant pleural mesothelioma: a comparative study of pharmacokinetic models and correlation with mRECIST criteria.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive thoracic malignancy that is difficult to cure. Dynamic contrast-enhanced (DCE) MRI is a functional imaging technique used to analyze tumor microvascular properties and to monitor therapy response. Purpose of this study was to compare two tracer kinetic models, the extended Tofts (ET) and the adiabatic approximation tissue homogeneity model (AATH) for analysis of DCE-MRI and examine the value of the DCE parameters to predict response to chemotherapy in patients with MPM. METHOD: This prospective, longitudinal, single tertiary radiology center study was conducted between October 2013 and July 2015. Patient underwent DCE-MRI studies at three time points: prior to therapy, during and after cisplatin-based chemotherapy. The images were analyzed using ET and AATH models. In short-term follow-up, the patients were classified as having disease control or progressive disease according to modified response evaluation criteria in solid tumors (mRECIST) criteria. Receiver operating characteristic curve analysis was used to examine specificity and sensitivity of DCE parameters for predicting response to therapy. Comparison tests were used to analyze whether derived parameters are interchangeable between the two models. RESULTS: Nineteen patients form the study population. The results indicate that the derived parameters are not interchangeable between the models. Significant correlation with response to therapy was found for AATH-calculated median pre-treatment efflux rate (kep) showing sensitivity of 83% and specificity of 100% (AUC 0.9). ET-calculated maximal pre-treatment kep showed 100% sensitivity and specificity for predicting treatment response during the early phase of the therapy and reached a favorable trend to significant prognostic value post-therapy. CONCLUSION: Both models show potential in predicting response to therapy in MPM. High pre-treatment kep values suggest MPM disease control post-chemotherapy.

The use of quetiapine in treatment of acute psychotic symptoms in an adolescent patient with primary brain calcification: a case report.

BACKGROUND: Primary brain calcification (PBC), a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas, typically presents with various neurological and psychiatric symptoms in the fourth or fifth decade of life or later. We present the case of a patient with psychiatric manifestations much earlier than usual, in the second decade of life. CASE PRESENTATION: The case of an adolescent female with acute psychotic symptoms, emotional instability, disorganized and suicidal behavior, stereotypical movements, below average intelligence and a three-year history of headaches is reported. Among others, the presentation included tactile hallucinations with secondary hypochondriacal delusions, which are rarely described in this diagnosis. Massive calcinations in the area of the basal ganglia and thalamus were determined by computerized tomography. Other causes of brain calcification were excluded. No causative mutations were found in selected genes. All the symptoms apart from lower intellectual abilities improved with quetiapine and sertraline. The patient showed no side effects. CONCLUSIONS: This case report highlights the successful use of quetiapine for symptomatic treatment of acute psychosis due to PBC in an adolescent without exacerbating extrapyramidal symptoms.

Magnetic resonance imaging of temporomandibular joint dysfunction-correlation with clinical symptoms, age, and gender.

OBJECTIVE: To determine whether the morphological (magnetic resonance imaging) MRI manifestations correlate with the signs and symptoms of temporomandibular joint (TMJ) dysfunction according to gender and age of the patients. STUDY DESIGN: One hundred and forty-four subjects with TMJ dysfunction underwent a MRI of both TMJ to establish the presence of disk displacement, osteoarthritis, and effusion. Chi-square test and logistic regression analysis were preformed. For the comparison of mean values between samples, we used T-test. RESULTS: A significant relationship between symptoms and morphological manifestations was found. In the group without reduction there were significant increases in the risk of experiencing symptoms (P = .002). Significant correlation between age and osteoarthritis (P = .001) and age and effusion (P = .022) was found. There was no correlation between gender and morphological manifestations. CONCLUSION: MRI morphological manifestations of the TMJ correlate with the presence of symptoms, therefore MRI has a crucial role in the diagnosis of TMJ dysfunction.

Dynamic contrast-enhanced CT of head and neck tumors: comparison of first-pass and permeability perfusion measurements using two different commercially available tracer kinetics models.

RATIONALE AND OBJECTIVES: To evaluate the interchangeability of perfusion parameters between two software packages for the postprocessing of dynamic contrast-enhanced (DCE) computed tomographic images of head and neck tumors. MATERIALS AND METHODS: DCE computed tomographic images of 75 patients with head and neck tumors were postprocessed using a software package based on the maximum-slope approach and Patlak analysis, as well as a software package with deconvolution-based analysis incorporating an adiabatic approximation of tissue homogeneity (ATH) model. The evaluated perfusion parameters included blood flow (F), blood volume (v), and permeability-surface area product (PS). Region-of-interest (ROI) analysis of the tumors and the metastatic lymph nodes was performed. The perfusion parameters were compared using the Wilcoxon matched-pairs test and Bland-Altman plots. RESULTS: One hundred fifty-two ROIs of tumors and nodes were outlined and analyzed. Moderate to good correlations were demonstrated between the various perfusion values (r = 0.56-0.72, P < .0001). The Wilcoxon test revealed a significant difference between the two methods (P < .001), with the F, v, and PS values obtained using the maximum-slope approach and Patlak analysis higher than those obtained using deconvolution-based analysis with the assumptions of the ATH model. The Bland-Altman plots for F and v values revealed a proportionality trend with outliers, which were strongly associated with the magnitudes of the parameters. Analysis of the PS values did not show any systematic bias. CONCLUSION: There were significant differences in the perfusion parameters obtained using the two software packages, and thus, these parameters are not directly interchangeable.

Functional CT of squamous cell carcinoma in the head and neck: repeatability of tumor and muscle quantitative measurements, inter- and intra-observer agreement.

Our purpose was to determine the repeatability of squamous cell cancer in head and neck (SCCHN) and muscle tissue vascularity measurements as well as the inter- and intra-observer agreement using dynamic contrast-enhanced (DCE) multi-detector CT (MDCT). Twelve patients with histologically proven SCCHN were twice examined within 46 h. Measurement error and repeatability were assessed for each of the four functional parameters using the Bland-Altman plots. Two independent observers recorded the vascularity values of the tumor tissue; inter- and intra-observer agreement was assessed using the Bland-Altman plot analysis and intraclass correlation coefficients. For the tumor, the mean difference (95% limits of agreement) was 0.40 ml/min/100 g tissue (-6.80, 9.60); 0.01 (-0.96, 0.97) ml/100 g tissue; 0.20 (-1.80, 2.30) s; and 0.40 (-2.00, 2.80) ml/min/100 g tissue for BF, BV, MTT, and PS, respectively. For the muscle, the mean difference (95% limits of agreement) was -0.18 (-1.70, 1.35), 0.04 (-1.17, 1.35), -0.10 (-5.80, 5.60), and -0.10 (-2.20, 2.00), respectively. Measurement changes of at least +/-8%, 30%, 36%, and 13% were found to be significant for BF, BV, MTT, and PS, respectively. There was better intra- than inter-observer agreement.