Incremental value of volumetric multiparametric MRI over Fudan score for prognosis of unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy.

BACKGROUND: Individualized patient care requires prognostic models customized to a tumor and an individual's disease profile for reliable survival prediction. MRI has prognostic value for intrahepatic cholangiocarcinoma (ICCA). Existing prognostic models for ICCA exclude imaging-based information about an individual's tumor that may reflect important aspects of tumor's biology. Fudan score, a prognostic model applicable to unresectable ICCA, is limited by subjective morphologic imaging parameters. OBJECTIVES: To assess the prognostic value of baseline volumetric multiparametric MRI in unresectable intrahepatic cholangiocarcinoma (ICCA) treated with systemic chemotherapy and the incremental value of MRI over the Fudan score. METHODS: This retrospective study included 114 ICCA patients treated with systemic chemotherapy between 2007 and 2021 after a baseline MRI. The single largest tumor was volumetrically assessed for anatomic (total tumor volume and diameter) and functional parameters (viable tumor volume, percentage-viable tumor volume, viable tumor burden, and ADC). A derivation cohort of 30 patients was utilized to identify MRI parameters associated with overall survival (OS) using Cox regression analysis. The incremental value of MRI over Fudan score was assessed on an independent sub-cohort of 84 patients using Kaplan-Meier analysis and C-index. RESULTS: 114 patients (64 years +/- 11; 61 women) were evaluated. Pre-treatment high (>1350x10-6 mm2/sec) ADC was the only independent predictor of OS (HR, 8.07; P < 0.001). Replacing subjective tumor boundary with objective ADC value, and using modified biochemical thresholds increased the prognostic stratification for the risk groups in the modified ADC-Fudan model compared to the original Fudan model (median survival 12 and 4.5 months; P = 0.055; vs. 11 and 3 months; P < 0.001). The modified ADC-Fudan model demonstrated an 11 % improvement over the original Fudan model (c-index: 0.80 vs. 0.69; P = 0.044) for survival prediction. CONCLUSIONS: High pre-treatment volumetric ADC was associated with unfavorable prognosis in patients with unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy. Supplementing the original Fudan model with ADC and modified serum marker thresholds improved the survival prediction performance by 11% in the resulting modified ADC-Fudan model. CLINICAL IMPACT: Volumetric MRI could improve the survival prediction among ICCA patients prior to receiving potentially toxic and expensive palliative chemotherapies. This could potentially guide individualized therapy for this patient cohort.

Transcranial Magnetic Stimulation and its Imaging Features in Patients With Depression, Post-traumatic Stress Disorder, and Traumatic Brain Injury.

Transcranial magnetic stimulation (TMS) is a type of noninvasive neurostimulation used increasingly often in clinical medicine. While most studies to date have focused on TMS's ability to treat major depressive disorder, it has shown promise in several other conditions including post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). As different treatment protocols are often used across studies, the ability to predict patient outcomes and evaluate immediate and long-term changes using imaging becomes increasingly important. Several imaging features, such as thickness, connectedness, and baseline activity of a variety of cortical and subcortical areas, have been found to be correlated with a greater response to TMS therapy. Intrastimulation imaging can reveal in real time how TMS applied to superficial areas activates or inhibits activity in deeper brain regions. Functional imaging performed weeks to months after treatment can offer an understanding of how long-term effects on brain activity relate to clinical improvement. Further work should be done to expand our knowledge of imaging features relevant to TMS therapy and how they vary across patients with different neurological and psychiatric conditions.

Role of MRI-Derived Radiomics Features in Determining Degree of Tumor Differentiation of Hepatocellular Carcinoma.

Background: To investigate radiomics ability in predicting hepatocellular carcinoma histological degree of differentiation by using volumetric MR imaging parameters. Methods: Volumetric venous enhancement and apparent diffusion coefficient were calculated on baseline MRI of 171 lesions. Ninety-five radiomics features were extracted, then random forest classification identified the performance of the texture features in classifying tumor degree of differentiation based on their histopathological features. The Gini index was used for split criterion, and the random forest was optimized to have a minimum of nine participants per leaf node. Predictor importance was estimated based on the minimal depth of the maximal subtree. Results: Out of 95 radiomics features, four top performers were apparent diffusion coefficient (ADC) features. The mean ADC and venous enhancement map alone had an overall error rate of 39.8%. The error decreased to 32.8% with the addition of the radiomics features in the multi-class model. The area under the receiver-operator curve (AUC) improved from 75.2% to 83.2% with the addition of the radiomics features for distinguishing well- from moderately/poorly differentiated HCCs in the multi-class model. Conclusions: The addition of radiomics-based texture analysis improved classification over that of ADC or venous enhancement values alone. Radiomics help us move closer to non-invasive histologic tumor grading of HCC.

Brain MRI in Autism Spectrum Disorder: Narrative Review and Recent Advances.

Autism spectrum disorder (ASD) is neuropsychiatric continuum of disorders characterized by persistent deficits in social communication and restricted repetitive patterns of behavior which impede optimal functioning. Early detection and intervention in ASD children can mitigate the deficits in social interaction and result in a better outcome. Various non-invasive imaging methods and molecular techniques have been developed for the early identification of ASD characteristics. There is no general consensus on specific neuroimaging features of autism; however, quantitative magnetic resonance techniques have provided valuable structural and functional information in understanding the neuropathophysiology of ASD and how the autistic brain changes during childhood, adolescence, and adulthood. In this review of decades of ASD neuroimaging research, we identify the structural, functional, and molecular imaging clues that most accurately point to the diagnosis of ASD vs. typically developing children. These studies highlight the 1) exaggerated synaptic pruning, 2) anomalous gyrification, 3) interhemispheric under- and overconnectivity, and 4) excitatory glutamate and inhibitory GABA imbalance theories of ASD. The application of these various theories to the analysis of a patient with ASD is mitigated often by superimposed comorbid neuropsychological disorders, evolving brain maturation processes, and pharmacologic and behavioral interventions that may affect the structure and function of the brain. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Integrating baseline MR imaging biomarkers into BCLC and CLIP improves overall survival prediction of patients with hepatocellular carcinoma (HCC).

OBJECTIVES: We aimed to evaluate the independent predictive role of baseline imaging biomarkers for overall survival (OS) and transplant-free survival (TFS) in patients with HCC and assess the incremental value of these biomarkers to current staging systems. METHODS: In this retrospective IRB approved study, the clinical, laboratory, and imaging parameters of 304 HCC patients were collected. Cox regression model was utilized to identify the potential predictors of survival. Recursive partitioning test was utilized to identify the optimal ADC cutoff for stratifying patients' OS. Patients were stratified based on Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Binary ADC value (above vs. below the cutoff) and tumor margin (well- vs. ill-defined) were integrated into BCLC and CLIP. OS and TFS was compared for patients based on standard criteria with and without imaging biomarkers. RESULTS: At baseline, patients with low tumor ADC and well-defined tumor margin (favorable imaging biomarkers) had longer survival, as compared to those with high ADC and ill-defined tumor margin (unfavorable imaging biomarkers) (median OS of 43 months vs. 7 months, respectively) (p < 0.001). Tumor ADC and tumor margin remained strong independent predictors of survival after adjustment for demographics, BCLC and CLIP staging, and tumor burden. Incorporating ADC and tumor margin improved performance of OS prediction by 9% in BCLC group and 6% in CLIP group. CONCLUSION: Incorporating ADC and tumor margin to current staging systems for HCC significantly improve prediction of OS and TFS of these criteria. KEY POINTS: • ADC and tumor margin are predictors of overall survival in HCC patients, independent of clinical, laboratory, and other imaging variables. • Adding ADC and tumor margin improved the prognostic value of BCLC and CLIP criteria by 9% and 6%, respectively. • High ADC and ill-defined tumor margin at baseline predicted poor survival, regardless of patient's liver function and general health status.

Post-TACE changes in ADC histogram predict overall and transplant-free survival in patients with well-defined HCC: a retrospective cohort with up to 10 years follow-up.

OBJECTIVES: To evaluate the role of change in apparent diffusion coefficient (ADC) histogram after the first transarterial chemoembolization (TACE) in predicting overall and transplant-free survival in well-circumscribed hepatocellular carcinoma (HCC). METHODS: Institution database was searched for HCC patients who got conventional TACE during 2005-2016. One hundred four patients with well-circumscribed HCC and complete pre- and post-TACE liver MRI were included. Volumetric MRI metrics including tumor volume, mean ADC, skewness, and kurtosis of ADC histograms were measured. Univariate and multivariable Cox models were used to test the independent role of change in imaging parameters to predict survival. P values < 0.05 were considered significant. RESULTS: In total, 367 person-years follow-up data were analyzed. After adjusting for baseline liver function, tumor volume, and treatment modality, incremental percent change in ADC (ΔADC) was an independent predictor of longer overall and transplant-free survival (p = 0.009). Overall, a decrease in ADC-kurtosis (ΔkADC) showed a strong role in predicting longer survival (p = 0.021). Patients in the responder group (ΔADC ≥ 35%) had the best survival profile, compared with non-responders (ΔADC < 35%) (p < 0.001). ΔkADC, as an indicator of change in tissue homogeneity, could distinguish between poor and fair survival in non-responders (p < 0.001). It was not a measure of difference among responders (p = 0.244). Non-responders with ΔkADC ≥ 1 (homogeneous post-TACE tumor) had the worst survival outcome (HR = 5.70, p < 0.001), and non-responders with ΔkADC < 1 had a fair survival outcome (HR = 2.51, p = 0.029), compared with responders. CONCLUSIONS: Changes in mean ADC and ADC kurtosis, as a measure of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in well-circumscribed HCC, in order to monitor early response to TACE and identify patients with treatment failure and poor survival outcome. KEY POINTS: • Changes in the mean and kurtosis of ADC histograms, as the measures of change in tissue heterogeneity, can be used to predict overall and transplant-free survival in patients with well-defined HCC. • A ≥ 35% increase in volumetric ADC after TACE is an independent predictor of good survival, regardless of the change in ADC histogram kurtosis. • In patients with < 35% ADC change, a decrease in ADC histogram kurtosis indicates partial response and fair survival, while ∆kurtosis ≥ 1 correlates with the worst survival outcome.

Role of volumetric multiparametric MRI in distinguishing between intraductal papillary mucinous neoplasms and serous cystadenoma.

PURPOSE: To evaluate the use of volumetric multiparametric MRI in differentiating pancreatic intraductal papillary mucinous neoplasms (IPMNs) from serous cystadenomas (SCAs) METHODS: Included patients (123 patients with pancreatic cystic neoplasms (PCNs) measuring ≥ 10 mm) were stratified into two groups based on cyst type. Axial cyst size, region of interest (ROI)-based apparent diffusion coefficient (ADC) and volumetric data, including cyst volume, volumetric apparent diffusion coefficient (vADC), and volumetric venous enhancement (vVE) were extracted and compared between the two groups. Univariate and multiple logistic regression was used to develop models for distinguishing between IPMNs and SCAs. RESULTS: Volume and size of the cysts, vVE and vADC and ROI-ADC were significantly different between the two groups. Cyst volume was significantly larger in SCAs (median = 14.1cm3, IQR 3.5-42.5) than in IPMNs (median = 2.5 cm3, IQR 1.1-6) (p < 0.001). IPMNs had a higher volumetric ADC value in comparison to SCAs (2925 ± 294 × 10-6 mm2/s vs 2521 ± 202 × 10-6 mm2/s, p < 0.001). However, IPMNs had lower vVE values compared to SCAs (37 signal intensity (SI) vs 86 SI, p < 0.001). Area under the ROC Curve (AUC) of the model that included vADC and cyst volume had 95% accuracy in distinguishing between the two groups. In comparison, the AUC of the model that included ROI-ADC and axial cyst size had 84% accuracy in distinguishing between the two groups. A threshold of 2615 × 10-6 mm2/s for volumetric ADC resulted in the identification of IPMNs from SCAs with sensitivity and specificity of 90.8% and 73.5%, respectively. CONCLUSION: IPMNs had smaller cyst volume, higher volumetric ADC and lower volumetric VE values compared to SCAs. Volumetric multiparametric MRI could be useful in differentiating between the IPMN and SCA groups.

Which vendor is most cited in the hepatic imaging literature?

PURPOSE: When deciding among imaging equipment vendors, one may use a vendor's prevalence in peer-reviewed publications as a measure of their research and development. We sought to determine which vendors, countries, and journals were dominant in hepatic imaging literature of 2018 with respect to magnetic resonance (MR), computed tomography (CT), and ultrasound (US). METHODS: We recorded and analyzed the modality (MR, CT, US), journal, vendor, and authors' country for all original hepatic imaging articles published in 2018 in 29 imaging journals. RESULTS: Of 197 MR articles, investigators used Siemens in 98 (50%), General Electric (GE) in 65 (33%), and Philips in 63 (32%). Of 115 CT articles, investigators mentioned Siemens in 55 (48%), GE in 45 (39%), Philips in 25 (22%) and other vendors in 27 (24%). Of 68 ultrasound articles, Siemens dominated with 27 (40%), versus GE with 19 (28%), Philips with 11 (16%), and other vendors with 42 (62%). We found a significant difference in vendor usage for MR, CT, and all modalities (p < .01). The plurality of articles was written in the United States (73 [23%]) with South Korea (56 [17%]) and China (56 [17%]) following. European Radiology published the most hepatic articles. For American journals, we found a significant difference in MR (p = .02) and CT (p < .01) vendor usage, whereas non-American journals nearly reached significance in MR (p = .06) and CT (p = .06) vendor usage. CONCLUSION: Siemens was the most cited vendor in hepatic imaging literature for all modalities. American institutions and non-American journals published the most hepatic imaging articles.

Role of tumor margin and ADC change in defining the need for additional treatments after the first TACE in patients with unresectable HCC.

PURPOSE: To define the number of TACE sessions needed to improve patients' overall survival (OS) in different subgroups of unresectable HCC. METHODS: This retrospective cohort included 180 patients who got TACE between 2005-2016 as the initial treatment for unresectable HCC. Tumor margin (well- vs. ill-defined) was determined by two radiologists at baseline. Well-defined group was divided into two groups (ADC-responders vs. ADC-nonresponders) based on %ADC change (ΔADC-cutoff = 25 %). Accordingly, patients were categorized into three groups, ill-defined, well-defined ADC-responders, or well-defined ADC-nonresponders. Cox-analysis was used to compare the survival benefit of multiple TACE in different groups. RESULTS: Ill-defined HCC (n = 108) was associated with worse survival (HR = 1.95,p < 0.001). Multiple TACE were associated with increased OS (HR = 0.88,p = 0.033) in these patients, with significant survival improvement after ≥4TACE. ΔADC was not related to OS in ill-defined group. In well-defined group (n = 72), multiple TACE were not associated with improved OS (HR = 0.181,p = 0.090). These patients were categorized into two groups based on ΔADC-cutoff. ADC-responders (ΔADC≥25 %) had the longest survival than other groups(p = 0.015). Multiple TACE sessions were not associated with better OS in this group (HR = 1.004,p = 0.982). By contrast, incremental number of TACE were associated with significantly longer OS in ADC-nonresponders (ΔADC<25 %) (HR = 0.79,p = 0.034). These patients' OS significantly improved after ≥3TACE. CONCLUSION: The survival benefit of sequential TACE sessions varies for different HCC subgroups. There was no significant survival benefit associated with multiple TACE in well-defined lesions responding to the first TACE. The most survival benefit was for ADC-nonresponder well-defined group and it was least for ill-defined HCC group, regardless of ADC-response.

Cross-sectional imaging in patients with primary sclerosing cholangitis: Single time-point liver or spleen volume is associated with survival.

AIM: To evaluate the association between single time-point quantitative liver and spleen volumes in patients with PSC and transplant-free survival, independent of Mayo risk score. MATERIALS AND METHODS: This HIPAA-compliant retrospective study included 165 PSC patients in a hospital. Total (T), and lobar (right [R], left [L], and caudate [C]) liver volumes and spleen volume (S) were measured. Adverse outcome was identified as being on liver transplantation list, transplantation or death (outcome 1), and transplantation or death (outcome 2). Cox-regression was performed to assess the predictive value of volumetric parameters to predict transplant-free survival with and without Mayo risk score. Stratified analysis by Mayo risk score categories was performed to assess the discriminative value of volumes in the model. Prediction models were developed dependent of Mayo score, based on patients demographics, lab values and volumetric measures for both defined outcomes. Kaplan-Meier curves were depicted for different liver and spleen volumes. P value <0.05 was considered statistically significant. RESULTS: In this cohort (age 43 ±â€¯17 years; 59 % men) 51 % of patients had adverse outcome. Cox-regression analysis demonstrated statistically significant association between values of T, L, R, C, S, L/T, and C/T and outcome 1; and also statistically significant association between values C, S, and C/T and outcome 2. Prediction models included age, INR, total bilirubin, AST, variceal bleeding, S, and C for outcome 1 and age, INR, total bilirubin, AST, variceal bleeding, and S for outcome 2. CONCLUSIONS: Based on our observational study, quantitative liver and spleen volumes may be associated with transplant-free survival in patients with PSC and may have the potential for predicting the outcome but this should be validated by randomized clinical trial studies.

Role of baseline volumetric functional MRI in predicting histopathologic grade and patients' survival in hepatocellular carcinoma.

OBJECTIVES: We aimed to evaluate the role of volumetric ADC (vADC) and volumetric venous enhancement (vVE) in predicting the grade of tumor differentiation in hepatocellular carcinoma (HCC). METHODS: The study population included 136 HCC patients (188 lesions) who had baseline MR imaging and histopathological report. Measurements of vVE and vADC were performed on baseline MRI. Tumors were histologically classified into low-grade and high-grade groups. The parameters between the two groups were compared using Mann-Whitney U and chi-square tests for continuous and categorical parameters, respectively. Area under receiver operating characteristic (AUROC) was calculated to investigate the accuracy of vADC and vVE. Logistic regression and multivariable Cox regression were used to unveil the potential parameters associated with high-grade HCC and patient's survival, respectively. RESULTS: Lesions with higher vADC values and a higher absolute vADC skewness were more likely to be high grade on histopathology assessment (p = 0.001 and p = 0.0291, respectively). Also, vVE showed a trend to be higher in low-grade lesions (p = 0.079). Adjusted multivariable model including vADC, vVE, and vADC skewness could strongly predict HCC degree of differentiation (AUROC = 83%). Additionally, a higher Child-Pugh score (HR = 2.39 [p = 0.02] for score 2 and HR = 3.47 [p = 0.001] for score 3), vADC skewness (HR = 1.52, p = 0.02; per increments in skewness), and tumor volume (HR = 1.1, p = 0.001; per 100 cm3 increments) showed the highest association with patients' survival. CONCLUSIONS: vADC and vVE have the potential to accurately predict HCC differentiation. Additionally, some imaging features in combination with patients' clinical characteristics can predict patient survival. KEY POINTS: • Volumetric functional MRI metrics can be considered as non-invasive measures for determining tumor histopathology in HCC. • Estimating patient survival based on clinical and imaging parameters can be used for modifying management approach and preventing unnecessary adverse events.

Comparison between ROI-based and volumetric measurements in quantifying heterogeneity of liver stiffness using MR elastography.

OBJECTIVES: This study was conducted to quantify the heterogeneity of liver stiffness (LS) on MR elastography (MRE) by comparing ROI-based and volumetric measurements. METHODS: LS was measured by ROI-based and volumetric segmentation of the liver parenchyma. Mean LS (MLS) was calculated and used to assign stages of fibrosis. Volumetric measurements of stiffness maps were used to determine the percentage of liver volume above/below MLS and presence of LS heterogeneity. Heterogeneous stiffness was defined when the first and second most predominant stages were more than one category apart. MLS values by each method were compared using the Wilcoxon signed-rank test. RESULTS: We included 128 patients with suspected liver fibrosis (mean age 54.4 ± 14.8 years). MLS was 2.7 ± 1.0 kPa for ROI measurements and 2.6 ± 0.9 kPa for the volumetric method (p = 0.001). Of 59 patients with normal stage (F0), 31 patients (52.5%) had > 20% of liver volume with abnormal LS (F1-F4). Heterogeneous LS was reported in 18 patients (14%). CONCLUSIONS: MLS measurement may not represent the entire spectrum of hepatic fibrosis. Volumetric segmentation may potentially improve the detection of heterogeneous fibrosis and the accuracy of LS measurement. KEY POINTS: • Heterogeneity of hepatic fibrosis may occur in patients with chronic liver disease. • MR elastography is used to assess hepatic fibrosis by measuring liver stiffness. • Measuring liver stiffness by the ROI method and reporting a mean value may fail to detect heterogeneity of hepatic fibrosis. Volumetric assessment of liver stiffness by MR elastography may detect heterogeneity of parenchymal involvement.

Comparison of acute ischemic stroke evaluation and the etiologic subtypes between university and nonuniversity hospitals in Isfahan, Iran.

BACKGROUND AND PURPOSE: Performing a proper causative workup for ischemic stroke patients is essential as it guides the direction of primary and secondary preventions. We aim to investigate the etiological evaluation of these patients in university and nonuniversity hospitals. METHOD: We enrolled subjects from the Persian Registry of Cardiovascular Disease-stroke. Stroke patients were categorized base on an etiological-based classification (Trial of Org 10172 in Acute Stroke Treatment or TOAST) into five groups. We also separated patients with ischemic stroke of undetermined etiology due to incomplete standard evaluation from ischemic stroke of undetermined etiology due to negative standard evaluation. The etiological subtypes and diagnostic evaluations were compared between the two hospital groups. RESULT: Ischemic stroke of undetermined etiology was the most common subtype overall (43%). The prevalence of ischemic stroke of undetermined etiology (incomplete standard evaluation) was significantly higher in patients evaluated in nonuniversity hospitals versus university hospital (46.2% vs. 22.3%). Patients with ischemic stroke of undetermined etiology (negative standard evaluation) and large-artery atherosclerosis were significantly more prevalent in university hospitals (10.3% vs. 4.6% and 13.9% vs. 4.4%, respectively). All diagnostic workups were performed more significantly for university hospital patients. Patients with Ischemic stroke of undetermined etiology (negative standard evaluation). Patients were significantly younger (64.91 ± 14.44 vs. 71.42 ± 12.93) and had lower prevalence of risk factors such as hypertension (48.5% vs. 65.4%) and diabetes (19.4% vs. 33.1%) than patients in ischemic stroke of undetermined etiology (incomplete standard evaluation) subgroup. University hospital patients had better clinical outcomes in terms of mortality and degree of disability during one-year follow-up. CONCLUSION: The high clinical burden of ischemic stroke of undetermined etiology especially in nonuniversity hospitals shows the rational for promoting ischemic stroke evaluation and providing specialized stroke centers for these hospitals in a developing country like Iran.