Radiomics-based detection of acute myocardial infarction on noncontrast enhanced midventricular short-axis cine CMR images.

Cardiac magnetic resonance cine images are primarily used to evaluate functional consequences, whereas limited information is extracted from the noncontrast pixel-wise myocardial signal intensity pattern. In this study we want to assess whether characterizing this inherent contrast pattern of noncontrast-enhanced short axis (SAX) cine images via radiomics is sufficient to distinguish subjects with acute myocardial infarction (AMI) from controls. Cine balanced steady-state free-precession images acquired at 1.5 T from 99 AMI and 49 control patients were included. First, radiomic feature extraction of the left ventricular myocardium of end-diastolic (ED) and end-systolic (ES) frames was performed based on automated (AUTO) or manually corrected (MAN) segmentations. Next, top features were selected based on optimal classification results using a support vector machine (SVM) approach. The classification performances of the four radiomics models (using AUTO or MAN segmented ED or ES images), were measured by AUC, classification accuracy (CA), F1-score, sensitivity and specificity. The most accurate model was found when combining the features RunLengthNonUniformity, ClusterShade and Median obtained from the manually segmented ES images (CA = 0.846, F1 score = 0.847). ED analysis performed worse than ES, with lower CA and F1 scores (0.769 and 0.770, respectively). Manual correction of automated contours resulted in similar model features as the automated segmentations and did not improve classification results. A radiomics analysis can capture the inherent contrast in noncontrast mid-ventricular SAX cine images to distinguishing AMI from healthy subjects. The ES radiomics model was more accurate than the ED model. Manual correction of the autosegmentation did not provide significant classification improvements.

Risk Severity Model for Pediatric Autosomal Dominant Polycystic Kidney Disease Using 3D Ultrasound Volumetry.

BACKGROUND: Height-adjusted total kidney volume (htTKV) measured by imaging defined as Mayo Imaging Class (MIC) is a validated prognostic measure for autosomal dominant polycystic kidney disease (ADPKD) in adults to predict and stratify disease progression. However, no stratification tool is currently available in pediatric ADPKD. Because magnetic resonance imaging and computed tomography in children are difficult, we propose a novel 3D ultrasound-based pediatric Leuven Imaging Classification to complement the MIC. METHODS: A prospective study cohort of 74 patients with genotyped ADPKD (37 female) was followed longitudinally with ultrasound, including 3D ultrasound, and they underwent in total 247 3D ultrasound assessments, with patients' median age (interquartile range [IQR]) at diagnosis of 3 (IQR, 0-9) years and at first 3D ultrasound evaluation of 10 (5-14) years. First, data matching was done to the published MIC classification, followed by subsequent optimization of parameters and model type. RESULTS: PKD1 was confirmed in 70 patients (95%), PKD2 in three (4%), and glucosidase IIα unit only once (1%). Over these 247 evaluations, the median height was 143 (IQR, 122-166) cm and total kidney volume was 236 (IQR, 144-344) ml, leading to an htTKV of 161 (IQR, 117-208) ml/m. Applying the adult Mayo classification in children younger than 15 years strongly underestimated ADPKD severity, even with correction for height. We therefore optimized the model with our pediatric data and eventually validated it with data of young patients from Mayo Clinic and the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease used to establish the MIC. CONCLUSIONS: We proposed a five-level Leuven Imaging Classification ADPKD pediatric model as a novel classification tool on the basis of patients' age and 3D ultrasound-htTKV for reliable discrimination of childhood ADPKD severity.

AI-based MRI auto-segmentation of brain tumor in rodents, a multicenter study.

Automatic segmentation of rodent brain tumor on magnetic resonance imaging (MRI) may facilitate biomedical research. The current study aims to prove the feasibility for automatic segmentation by artificial intelligence (AI), and practicability of AI-assisted segmentation. MRI images, including T2WI, T1WI and CE-T1WI, of brain tumor from 57 WAG/Rij rats in KU Leuven and 46 mice from the cancer imaging archive (TCIA) were collected. A 3D U-Net architecture was adopted for segmentation of tumor bearing brain and brain tumor. After training, these models were tested with both datasets after Gaussian noise addition. Reduction of inter-observer disparity by AI-assisted segmentation was also evaluated. The AI model segmented tumor-bearing brain well for both Leuven and TCIA datasets, with Dice similarity coefficients (DSCs) of 0.87 and 0.85 respectively. After noise addition, the performance remained unchanged when the signal-noise ratio (SNR) was higher than two or eight, respectively. For the segmentation of tumor lesions, AI-based model yielded DSCs of 0.70 and 0.61 for Leuven and TCIA datasets respectively. Similarly, the performance is uncompromised when the SNR was over two and eight respectively. AI-assisted segmentation could significantly reduce the inter-observer disparities and segmentation time in both rats and mice. Both AI models for segmenting brain or tumor lesions could improve inter-observer agreement and therefore contributed to the standardization of the following biomedical studies.

Early Whole-Body Diffusion-weighted MRI Helps Predict Long-term Outcome Following Peptide Receptor Radionuclide Therapy for Metastatic Neuroendocrine Tumors.

Purpose To evaluate the predictive value of 7-week apparent diffusion coefficient change from baseline (ADCratio7w) at whole-body diffusion-weighted MRI (WB-DWI MRI) after one peptide receptor radionuclide therapy (PRRT) cycle to predict outcome in patients with metastatic neuroendocrine tumor (mNET). Materials and Methods From April 2009 to May 2012, participants in a prospective clinical trial investigating yttrium 90-DOTA Phe1-Tyr3-octreotide (DOTATOC) treatment for mNET (EudraCT no. 2008-007965-22) underwent WB-DWI MRI and gallium 68 (68Ga)-DOTATOC PET/CT before and 7 weeks after one PRRT cycle. ADCratio7w response was compared with the 7-week Response Evaluation Criteria in Solid Tumors version 1.1 and 68Ga-DOTATOC PET/CT quantitative responses to predict overall survival (OS) and progression-free survival (PFS) with Cox regression analysis. Results Forty participants were analyzed (mean age, 60 years ± 11 [SD]; 21 men). Median PFS and OS were 10.5 months (range, 2-36 months) and 18 months (range, 3-81 months), respectively. Survival analysis showed significantly positive effects on PFS by age (hazard ratio [HR] = 0.96, P = .007), tumor grade (HR = 2.84, P = .006), Ki-67 index (HR = 1.05, P = .01), ADCratio7w of the least-responding lesion (ADCratio7w-least) (HR = 0.94, P < .001), and baseline mean standardized uptake values (SUVmean) (HR = 0.89, P = .02), with ADCratio7w-least and SUVmean remaining significant in multivariable analysis (P < .001, P = .02, respectively). There were significantly positive effects on OS by pretreatment lesion volume (HR = 1.004, P = .004), tumor grade (HR = 2.14, P = .04), Ki-67 index (HR = 1.05, P = .01), and ADCratio7w-least (HR = 0.97, P < .001), with pretreatment volume and ADCratio7w-least remaining significant at multivariable analysis (P = .005, P = .002, respectively). Conclusion The ADCratio7w after start of PRRT for mNET was an independent predictor of patient outcome. Keywords: MR-Diffusion-Weighted Imaging, Radionuclide Therapy, Whole-Body Imaging, Metastases, Tumor Response, Treatment Effects EudraCT no. 2008-007965-22 © RSNA, 2022.

Development and characterization of a rat brain metastatic tumor model by multiparametric magnetic resonance imaging and histomorphology.

To facilitate the development of new brain metastasis (BM) treatment, an easy-to-use and clinically relevant animal model with imaging platform is needed. Rhabdomyosarcoma BM was induced in WAG/Rij rats. Post-implantation surveillance and characterizations were systematically performed with multiparametric MRI including 3D T1 and T2 weighted imaging, diffusion-weighted imaging (DWI), T1 and T2 mapping, and perfusion-weighted imaging (PWI), which were validated by postmortem digital radiography (DR), µCT angiography and histopathology. The translational potential was exemplified by the application of a vascular disrupting agent (VDA). BM was successfully induced in most rats of both genders (18/20). Multiparametric MRI revealed significantly higher T2 value, pre-contrast-enhanced (preCE) T1 value, DWI-derived apparent diffusion coefficient (ADC) and CE ratio, but a lower post-contrast-enhanced (postCE) T1 value in BM lesions than in adjacent brain (p < 0.01). PWI showed the dynamic and higher contrast agent uptake in the BM compared with the adjacent brain. DR, µCT and histopathology characterized the BM as hypervascular tumors. After VDA treatment, the BM showed drug-related perfusion changes and partial necrosis as evidenced by anatomical, functional MRI parameters and postmortem findings. The present BM model and imaging modalities represent a feasible and translational platform for developing BM-targeting therapeutics.

Comparing breast cancer imaging characteristics of CHEK2 with BRCA1 and BRCA2 gene mutation carriers.

PURPOSE: Breast cancer gene (BRCA) 1 and 2 mutations are frequently studied gene mutations (GM); the incidence of checkpoint kinase 2 (CHEK2) is increasing. We describe the imaging features of breast cancer (BC) in CHEK2 mutations, compared to BRCA 1 and 2 using mammography, ultrasound (US) and magnetic resonance imaging (MRI). METHOD: Inclusion criteria were primary BC in GM carriers, treated in the same hospital. Age at diagnosis, histology, hormone receptor and human epidermal growth factor receptor 2 (HER2) status were retrieved. Mammography descriptors were mass, asymmetry and suspicious microcalcifications. The enhancement pattern (MRI), shape and border, architectural distortion, the presence of a hyperechoic rim and cystic complex structure (US) were documented. Analyses were performed using SAS software (version 9.4). Fishers' exact test was used to test associations between two categorical variables. RESULTS: In 191 women, 233 malignant lesions were diagnosed (78 in BRCA1, 109 in BRCA2, 46 in CHEK2). In CHEK2 carriers, mammographically, suspicious microcalcifications (54%) were more prevalent (BRCA2 (48%) and BRCA1 carriers (33%)) (p-value = 0.057) compared to mass lesions (35%). On US, lesions were most frequently ill-defined (86%) (p = 0.579) and irregular (94.5%) (p = 0.098) compared to BRCA2 (77% and 80% resp.) and BRCA1 carriers (71% and 72% resp.). On MRI, mass lesions showed a type 3 curve in CHEK2 (67%) compared to BRCA1 (36%) and BRCA2 (50%) (p = 0.056). CONCLUSIONS: Malignant radiological characteristics of breast cancer, more specifically suspicious microcalcifications, were more frequently seen in CHEK2 and BRCA2 compared to BRCA1 mutation carriers (without a significant difference) indicating the importance of mammography in follow-up of CHEK2 carriers.

Quantitative Whole-Body Diffusion-weighted MRI after One Treatment Cycle for Aggressive Non-Hodgkin Lymphoma Is an Independent Prognostic Factor of Outcome.

Purpose: To evaluate the prognostic utility of apparent diffusion coefficient (ADC) changes at whole-body diffusion-weighted (WB-DW) MRI after one treatment cycle for aggressive non-Hodgkin lymphoma (NHL) compared with response assessment at interim and end-of-treatment fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. Materials and Methods: This was a secondary analysis of a prospective study (ClinicalTrials.gov identifier: NCT01231269) in which participants with aggressive NHL were recruited between March 2011 and April 2015 and underwent WB-DW MRI before and after one cycle of immunochemotherapy. Volunteers were recruited for test-retest WB-DW MRI (ClinicalTrials.gov identifier: NCT01231282) to assess ADC measurement repeatability. Response assessment was based on ADC change after one treatment cycle at WB-DW MRI and Deauville criteria at 18F-FDG PET/CT. To evaluate prognostic factors of disease-free survival (DFS), Kaplan-Meier survival analysis and univariable and multivariable Cox regression were performed; intraclass correlation coefficient (ICC) and mean difference with limits of agreement were calculated to determine inter- and intraobserver repeatability of ADC measurements. Results: Forty-five patients (mean age, 58 years ± 17 [standard deviation]; 31 men) and nine volunteers (mean age, 22 years ± 3; seven men) were enrolled. Median DFS was 48 months (range, 2-48 months). Outcome prediction accuracy was 86.7% (39 of 45), 71.4% (30 of 42), and 73.8% (31 of 42) for WB-DW MRI and interim and end-of-treatment 18F-FDG PET/CT, respectively. WB-DW MRI (hazard ratio [HR], 17.8; P < .001) and interim (HR, 5; P = .008) and end-of-treatment (HR, 4.3; P = .017) 18F-FDG PET/CT were prognostic of DFS. After multivariable analysis, WB-DW MRI remained an independent predictor of outcome (HR, 26.8; P = .002). Intra- and interobserver agreement for ADC measurements were excellent (ICC = 0.85-0.99). Conclusion: Quantitative WB-DW MRI after only one cycle of immunochemotherapy predicts DFS in aggressive NHL and is noninferior to routinely performed interim and end-of-treatment 18F-FDG PET/CT.Keywords: MR-Diffusion Weighted Imaging, Lymphoma, Oncology, Tumor Response, Whole-Body ImagingSupplemental material is available for this article.© RSNA, 2021.

Accuracy of whole-body diffusion-weighted MRI (WB-DWI/MRI) in diagnosis, staging and follow-up of gastric cancer, in comparison to CT: a pilot study.

BACKGROUND: Accurate staging of patients with gastric cancer is necessary for selection of the most appropriate and personalized therapy. Computed tomography (CT) is currently used as primary staging tool, being widely available with a relatively high accuracy for the detection of parenchymal metastases, but with low sensitivity for the detection of peritoneal metastases. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has a very high contrast resolution, suggesting a higher diagnostic performance in the detection of small peritoneal lesions. The aim of this study was to retrospectively evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for detection of peritoneal carcinomatosis (PC) and distant metastases in the preoperative staging of gastric cancer. METHODS: This retrospective study included thirty-two patients with a suspicion of gastric cancer/recurrence, who underwent WB-DWI/MRI at 1.5 T, in addition to CT of thorax and abdomen. Images were evaluated by two experienced abdominal radiologists in consensus. Histopathology, laparoscopy and/or 1-year follow-up were used as reference standard. RESULTS: For overall tumour detection (n = 32), CT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 83.3%, 100%, 100% and 82.4% respectively. For WB-DWI/MRI these values were 100%, 92.9%, 94.7% and 100%, respectively. For staging (n = 18) malignant lymph nodes and metastases, CT had a sensitivity, specificity/PPV/NPV of 50%/100%/100%/71.4%, and 15.4%/100%/100%/31.3% respectively. For WB-DWI/MRI, all values were 100%, for both malignant lymph nodes and metastases. WB-DWI/MRI was significantly better than CT in detecting tumour infiltration of the mesenteric root, serosal involvement of the small bowel and peritoneal metastases for which WB-DWI/MRI was correct in 100% of these cases, CT 0%. CONCLUSIONS: WB-DWI/MRI is highly accurate for diagnosis, staging and follow-up of patients with suspected gastric cancer.

Qualitative and quantitative analysis of diffusion-weighted brain MR imaging in comatose survivors after cardiac arrest.

PURPOSE: The aim of this study is to compare a qualitative and a quantitative assessment of brain diffusion-weighted imaging (DWI) in predicting outcome of comatose patients after cardiac arrest (CA). METHODS: Two observers used a scoring template to analyze the DWI of 75 patients. A total of 13 regions were scored from 0 to 3 (0 = normal, 1 = probably normal, 2 = probably abnormal, 3 = definitely abnormal). The total cerebral cortex (TCC), the total deep grey nuclei (TDGN), the total brain stem, the total cerebellum, and the total brain score were calculated. Intra- and inter-observer variability were tested. The mean whole brain apparent diffusion coefficient (ADC) values and percentage of voxels below a specific ADC value cut-off were calculated. The data were correlated with clinical outcome (cerebral performance category score after 180 days, dichotomized in a score 1-2 with favorable outcome and score 3-5 with unfavorable outcome) using ROC analysis. RESULTS: Intra-observer variability was excellent for the TCC score (ICC 0.95 and 0.86) and the TDGN score (ICC 0.89 and 0.75). Inter-observer variability was good to excellent for total cerebral cortex score and total deep grey nuclei score in both the first (ICC 0.78 and 0.69) and third (ICC 0.86 and 0.83) image assessment. TCC and TDGN score show the best correlation with clinical outcome (highest AUC values 0.87 and 0.87). Quantitative parameters did not show good correlation with clinical outcome (AUC values 0.57 and 0.60). CONCLUSION: A qualitative assessment of brain DWI using a scoring template provides useful data regarding patient outcome while quantitative data appeared less reliable.

Whole-body diffusion-weighted magnetic resonance imaging for the detection of bone metastases and their prognostic impact in metastatic renal cell carcinoma patients treated with angiogenesis inhibitors.

Background: Metastatic renal cell carcinoma (mRCC) patients with bone metastases (BM) are at high risk for skeletal related events and have a poorer outcome when treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs). Computed tomography (CT) lacks sensitivity to detect BM in mRCC. We aimed to determine the added value of whole body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) to CT for the detection of BM in mRCC and to estimate the prognostic impact of the number of BM in mRCC patients treated with VEGFR-TKIs.Material and methods: We conducted a prospective study including consecutive mRCC patients treated with a first-line VEGFR-TKI in the metastatic setting. All patients underwent a pretreatment thoracic-abdominal-pelvic CT and WB-DWI/MRI. CT and WB-DWI/MRI were compared for the detection of BM. The number of detected BM was correlated with response rate (RR), progression-free survival (PFS) and overall survival (OS) after start of the VEGFR-TKI.Results: Ninety-two patients were included. BM were found in 55% of the patients by WB-DWI/MRI and in 43% of the patients by CT (p = .003). Mean number of BM discovered per patient was 6.8 by WB-DWI/MRI versus 1.9 by CT (p = .006). The cutoff of ≤5 versus >5 BM on WB-DWI/MRI had the highest discriminative power for all outcome measures. Patients with >5 BM had a lower RR (10% versus 42%), more frequently early progressive disease (43% versus 13%, p = .003), shorter PFS (4 versus 10 months, p = .006) and shorter OS (10 versus 35 months, p < .0001) compared to patients with ≤5 BM.Conclusion: WB-DWI/MRI detects significantly more BM in mRCC patients than CT, allowing better estimation of the prognostic impact of BM in mRCC patients treated with VEGFR-TKIs. The prognostic impact should now be validated in patients treated with immune checkpoint inhibitors.

Predicting Therapeutic Efficacy of Vascular Disrupting Agent CA4P in Rats with Liver Tumors by Hepatobiliary Contrast Agent Mn-DPDP-Enhanced MRI.

To evaluate hepatobiliary-specific contrast agent (CA) mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance imaging (MRI) for predicting the therapeutic efficacy of the vascular disrupting agent combretastatin A4 phosphate (CA4P) in rats with primary and secondary liver tumors, 36 primary hepatocellular carcinomas (HCCs) were raised by diethylnitrosamine gavage in 16 male rats, in 6 of which one rhabdomyosarcomas (R1) was intrahepatically implanted as secondary liver tumors. On a 3.0T MR scanner with a wrist coil, tumors were monitored weekly by T2-/T1-weighted images (T2WI/T1WI) and characterized by Mn-DPDP-enhanced MRI. CA4P-induced intratumoral necrosis was depicted by nonspecific gadoterate meglumine (Gd-DOTA)-enhanced MRI before and 12 h after therapy. Changes of tumor-to-liver contrast (ΔT/L) on Mn-DPDP-enhanced images were analyzed. In vivo MRI findings were verified by postmortem microangiography and histopathology. Rat models of primary HCCs in a full spectrum of differentiation and secondary R1 liver tumors were successfully generated. Mn-DPDP-enhanced ΔT/L was negatively correlated with HCC differentiation grade (P < 0.01). After treatment with CA4P, more extensive tumoral necrosis was found in highly differentiated HCCs than that in moderately and poorly differentiated ones (P < 0.01); nearly complete necrosis was induced in secondary liver tumors. Mn-DPDP-enhanced MRI may help in imaging diagnosis of primary and secondary liver malignancies of different cellular differentiations and further in predicting CA4P therapeutic efficacy in primary HCCs and intrahepatic metastases.

Whole-body diffusion-weighted MRI for operability assessment in patients with colorectal cancer and peritoneal metastases.

BACKGROUND: Correct staging of patients with colorectal cancer is of utmost importance for the prediction of operability. Although computed tomography (CT) has a good overall performance, estimation of peritoneal cancer spread is a known weakness, a problem that cannot always be overcome by Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT); especially in infiltrative and miliary disease spread. Due to its high spatial and contrast resolution magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) might have a better performance. Our aim was to evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for prediction of peritoneal cancer spread and operability assessment in colorectal cancer patients with clinically suspected peritoneal carcinomatosis (PC). METHODS: This institutional review board approved retrospective study included sixty colorectal cancer patients who underwent WB-DWI/MRI in addition to CT for clinically suspected peritoneal metastases. WB-DWI/MRI and CT were assessed for detecting PC following the peritoneal cancer index (PCI), determination of PCI-score categorized as PC < 12, PCI = 12-15 and PCI > 15, detection of nodal and distant metastases and estimation of overall operability. Histopathology after surgery and biopsy and/or 6 months follow-up were used as reference standard. RESULTS: For detection of PC, CT had 43.2% sensitivity, 95.6% specificity, 84.5% positive predictive value (PPV) and 75.2% negative predictive value (NPV). WB-DWI/MRI had 97.8% sensitivity, 93.2% specificity, 88.9% PPV and 98.7% NPV. WB-DWI/MRI enabled better detection of inoperable distant metastases (all 12 patients) than CT (2/12 patients) and significantly improved prediction of PCI category [WB-DWI/MRI PCI < 12: 37/39 patients (94.9%); PCI = 12-15: 4/4 patients (100%); PCI > 15: 16/17 patients (94.1%) versus CT PCI < 12: 38/39 patients (97.4%); PCI = 12-15: 0/4 patients (0%); PCI > 15: 2/17 patients (11.8%); p < 0.0001)]. WB-DWI/MRI improved prediction of inoperability over CT with 90.6% sensitivity compared to 25% (p < 0.0001). CONCLUSIONS: WB-DWI/MRI significantly outperformed CT for estimation of spread of PC, overall staging and prediction of operability. Pending validation in larger prospective trials, WB-DWI/MRI could be used to guide surgical planning and minimize unnecessary exploratory laparotomies.

Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers.

AIM: To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate (CA4P), among hepatocellular carcinomas (HCCs) and implanted rhabdomyosarcoma (R1) in the same rats by magnetic-resonance-imaging (MRI), microangiography and histopathology. METHODS: Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images (T2WI/T1WI) on a 3.0T clinical MRI-scanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced (DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg (treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg (control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve (AUC30). In vivo MRI findings were verified by postmortem techniques. RESULTS: On CE-T1WIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure (66%) in R1-tumors at 1 h (P < 0.05), followed by further perfusion decrease at 12 h (P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors (92.6%) than in HCCs (50.2%) (P < 0.01); tumor vascularity heterogeneously scored +~+++ in HCCs but homogeneously scored ++ in R1-tumors. CONCLUSION: This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disrupting-agents.​.

The first study on therapeutic efficacies of a vascular disrupting agent CA4P among primary hepatocellular carcinomas with a full spectrum of differentiation and vascularity: Correlation of MRI-microangiography-histopathology in rats.

To better inform the next clinical trials of vascular disrupting agent combretastatin-A4-phosphate (CA4P) in patients with hepatic malignancies, this preclinical study aimed at evaluating CA4P therapeutic efficacy in rats with primary hepatocellular carcinomas (HCCs) of a full spectrum of differentiation and vascularity by magnetic resonance imaging (MRI), microangiography and histopathology. Ninety-six HCCs were raised in 25 rats by diethylnitrosamine gavage. Tumor growth was monitored by T2-/T1-weighted-MRI (T2WI, T1WI) using a 3.0 T scanner. Early vascular response and later intratumoral necrosis were detected by dynamic-contrast-enhanced (DCE) MRI and diffusion-weighted-imaging (DWI) before, 1 and 12 hr after CA4P iv-administration. In vivo MRI-findings were validated by postmortem-techniques. Multi-parametric MRI revealed rapid CA4P-induced tumor vascular shutdown within 1 hr, followed by variable intratumoral necrosis at 12 hr. Tumor volumes decreased by 10% at 1 hr (p < 0.05), but resumed at 12 hr. Correlations of semi-quantitative DCE parameter initial-area-under-the-gadolinium-curve (IAUGC30) with histopathology proved partial vascular closure and compensational reopening (p < 0.05). The higher grades of vascularity prevented those residual tumor tissues from CA4P-caused ischemic necrosis. By histopathology using a 4-scale cellular-differentiation criteria and a 4-grade tumor-vascularity classification, percentage of CA4P-induced necrosis negatively correlated with HCC differentiation (r = -0.404, p < 0.001) and tumor vascularity (r = -0.370, p < 0.001). Ordinal-logistic-regression helped to predict early tumor responses to CA4P in terms of tumoral differentiation and vascularity. Our study demonstrated that CA4P could induce vascular shutdown in primary HCCs within 1 hr, resulting in various degrees of tumor necrosis at 12 hr. MRI as a real-time imaging biomarker may help to define tumor vascularity and differentiation and further to predict CA4P therapeutic outcomes.

Improving lymph node characterization in staging malignant lymphoma using first-order ADC texture analysis from whole-body diffusion-weighted MRI.

BACKGROUND: Correct staging and treatment initiation in malignant lymphoma depends on accurate lymph node characterization. However, nodal assessment based on conventional and diffusion-weighted (DWI) MRI remains challenging, particularly in smaller nodes. PURPOSE: To evaluate first-order apparent diffusion coefficient (ADC) texture parameters compared to mean ADC for lymph node characterization in non-Hodgkin lymphoma (NHL) using whole-body DWI (WB-DWI). STUDY TYPE: Retrospective. POPULATION: Twenty-eight patients with NHL. FIELD STRENGTH/SEQUENCE: 3T whole-body DWI using two b-values (0-1000 s/mm2 ). ASSESSMENT: Regions of interest were drawn on the three most hyperintense lymph nodes on b1000-images, irrespective of size, in all nodal body regions. Diagnostic performance of mean ADC (ADCmean ) was compared with first-order ADC texture parameters: standard deviation (ADCstdev ), kurtosis (ADCkurt ), and skewness (ADCskew ). Additional subanalyses focused on the accuracy of ADCmean and ADC texture parameters in different lymph node volumes and nodal regions. STATISTICAL TESTS: Benign and malignant nodes were compared using Mann-Whitney U-tests with 18-Fluoro-deoxyglucose positron emission tomography computed tomography and bone marrow biopsy as reference standard. Receiver operating characteristic analyses were performed to determine cutoff values and calculate sensitivity, specificity, accuracy, and positive and negative predictive value (PPV, NPV). RESULTS: ADCmean (P = 0.008), ADCskew and ADCkurt differed significantly between benign and malignant nodes (P < 0.001), while ADCstdev didn't (P = 0.21). ADCskew was the best discriminating parameter, with 79% sensitivity, 86% specificity, 83% accuracy, 85% PPV, and 81% NPV. In every volume category, ADCskew yielded the highest accuracy (88% in 0-25th percentile volume, 75% in 25th -75th percentile, 93% in 75-100th percentile). On a per-region basis, ADCskew accuracy varied 13.6% between nodal regions, while ADCmean , ADCkurt , and ADCstdev showed interregional variation of 17.4%, 20.3%, and 14.9%, respectively. DATA CONCLUSION: First-order ADC texture analysis with WB-DWI improved lymph node characterization compared to ADCmean . ADCskew was the most accurate and robust discriminatory parameter over all lymph node volumes and nodal body regions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:897-906.

3DUS as an alternative to MRI for measuring renal volume in children with autosomal dominant polycystic kidney disease.

BACKGROUND: Total kidney volume, measured by magnetic resonance imaging (MRI), is a validated disease progression marker in adults with autosomal dominant polycystic kidney disease (ADPKD). However, in childhood, MRI is burdensome, explaining the need for alternatives. METHODS: Kidney volume (KV) was evaluated in 30 children with ADPKD, using three-dimensional ultrasound (3DUS), applying the ellipsoid method and manual contouring (KV3DUS-ellipsoid, KV3DUS-contour respectively); manual contouring on MRI (KVMRI), and the ellipsoid method on two-dimensional ultrasound (2DUS, KV2DUS). Correlations and differences were evaluated using Pearson's r and Wilcoxon signed-rank tests, and variability using Bland-Altman plots. RESULTS: All ultrasound volumetry methods showed significantly lower mean (± SD) KV (mL), compared with MRI-KV2DUS: 159 (±101); K3DUS-ellipsoid: 169 (±105); KV3DUS-contour: 185 (±110); KVMRI: 206 (±130); all p < 0.001. All had a strong correlation with KVMRI: 2DUS: r = 0.96; 3DUS-ellipsoid: r = 0.89 and 3DUS-contour: r = 0.94. Both before and after correction factor application, Bland-Altman plots showed lower variability and absolute error for KV3DUS-contour vs KV2DUS and KV3DUS-ellipsoid. CONCLUSIONS: Compared with MRI, ultrasound volumetry was prone to underestimation. However, KV3DUS-contour represents a valuable alternative for MRI in early ADPKD. Although more time-consuming, KV3DUS-contour is recommended over KV2DUS for estimation and follow-up of KV in ADPKD children, given its smaller error.

Feasibility of whole-body diffusion-weighted MRI for detection of primary tumour, nodal and distant metastases in women with cancer during pregnancy: a pilot study.

OBJECTIVES: To evaluate the feasibility of whole-body diffusion-weighted MRI (WB-DWI/MRI) for detecting primary tumour, nodal and distant metastases in pregnant women with cancer. METHODS: Twenty pregnant patients underwent WB-DWI/MRI in additional to conventional imaging. Reproducibility of WB-DWI/MRI between two readers was evaluated using Cohen's κ statistics and accuracy was compared to conventional imaging for assessing primary tumour site, nodal and visceral metastases. RESULTS: Both WB-DWI/MRI readers showed good-very good agreement for lesion detection (primary lesions: κ=1; lymph nodes: κ=0.89; distant metastases: κ=0.61). Eight (40 %) patients were upstaged after WB-DWI/MRI. For nodal metastases, WB-DWI/MRI showed 100 % (95 % CI: 83.2-100) sensitivity for both readers with specificity of 99.4 % (96.9-100) and 100 % (80.5-100) for readers 1 and 2, respectively. For distant metastases, WB-DWI/MRI showed 66.7 % (9.4-99.2) and 100 % (29.2-100) sensitivity and specificity of 94.1 % (71.3-99.9) and 100 % (80.5-100) for readers 1 and 2, respectively. Conventional imaging showed sensitivity of 50 % (27.2-72.8) and 33.3 % (0.8-90.6); specificity of 100 % (98-100) and 100 % (80.5-100), for nodal and distant metastases respectively. CONCLUSIONS: WB-DWI/MRI is feasible for single-step non-invasive staging of cancer during pregnancy with additional value for conventional imaging procedures. KEY POINTS: • In our study, WB-DWI/MRI was more accurate than conventional imaging during pregnancy. • WB-DWI/MRI improves diagnostic assessment of patients with cancer during pregnancy. • Accurate imaging and oncologic staging improves treatment and outcome.

Diagnostic value of whole body diffusion-weighted MRI compared to computed tomography for pre-operative assessment of patients suspected for ovarian cancer.

BACKGROUND: Despite excellent per-lesion performance for peritoneal staging, the additional clinical value of diffusion-weighted magnetic resonance imaging (DWI/MRI) compared to computed tomography (CT) remains to be established in ovarian cancer. Our purpose was to evaluate whole body (WB)-DWI/MRI for diagnosis, staging and operability assessment of patients suspected for ovarian cancer compared to CT. METHODS: One hundred and sixty-one patients suspected for ovarian carcinoma underwent 3 T WB-DWI/MRI and contrast-enhanced CT. WB-DWI/MRI and CT were compared for confirmation of the malignant nature and primary origin of the ovarian mass, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging and prediction of incomplete resection using institutional operability criteria. Interobserver agreement between two readers was determined for WB-DWI/MRI and CT. RESULTS: WB-DWI/MRI showed a significantly higher accuracy than CT (93 versus 82%, p = 0.001) to confirm the malignant nature of the ovarian mass and correctly identified 26 of 32 (81%) cancers of non-ovarian origin compared to 10/32 (31%) for CT (p < 0.001). WB-DWI/MRI assigned more ovarian carcinoma patients to the correct FIGO stage (82/94, 87%) compared with CT (33/94, 35%). For prediction of incomplete resection, WB-DWI/MRI showed significantly higher sensitivity (94 versus 66%), specificity (97.7 versus 77.3%) and accuracy (95.7 versus 71.3%) compared to CT (p < 0.001). Interobserver agreement was almost perfect (κ = 0.90) for WB-DWI/MRI and moderate (κ = 0.52) for CT for prediction of incomplete resection. CONCLUSIONS: WB-DWI/MRI was superior to CT for primary tumour characterisation, staging and prediction of incomplete resection in patients suspected for ovarian cancer.

Rationale for Modernising Imaging in Advanced Prostate Cancer.

CONTEXT: To effectively manage patients with advanced prostate cancer (APC), it is essential to have accurate, reproducible, and validated methods for detecting and quantifying the burden of bone and soft tissue metastases and for assessing their response to therapy. Current standard of care imaging with bone and computed tomography (CT) scans have significant limitations for the assessment of bone metastases in particular. OBJECTIVE: We aimed to undertake a critical comparative review of imaging methods used for diagnosis and disease monitoring of metastatic APC from the perspective of their availability and ability to assess disease presence, extent, and response of bone and soft tissue disease. EVIDENCE ACQUISITION: An expert panel of radiologists, nuclear medicine physicians, and medical physicists with the greatest experience of imaging in advanced prostate cancer prepared a review of the practicalities, performance, merits, and limitations of currently available imaging methods. EVIDENCE SYNTHESIS: Meta-analyses showed that positron emission tomography (PET)/CT with different radiotracers and whole-body magnetic resonance imaging (WB-MRI) are more accurate for bone lesion detection than CT and bone scans (BSs). At a patient level, the pooled sensitivities for bone disease by using choline (CH)-PET/CT, WB-MRI, and BS were 91% (95% confidence interval [CI], 83-96%), 97% (95% CI, 91-99%), and 79% (95% CI, 73-83%), respectively. The pooled specificities for bone metastases detection using CH-PET/CT, WB-MRI, and BS were 99% (95% CI, 93-100%), 95% (95% CI, 90-97%), and 82% (95% CI, 78-85%), respectively. The ability of PET/CT and WB-MRI to assess therapeutic benefits is promising but has not been comprehensively evaluated. There is variability in the cost, availability, and quality of PET/CT and WB-MRI. CONCLUSIONS: Standardisation of acquisition, interpretation, and reporting of WB-MRI and PET/CT scans is required to assess the performance of these techniques in clinical trials of treatment approaches in APC. PATIENT SUMMARY: PET/CT and whole-body MRI scans have the potential to improve detection and to assess response to treatment of all states of advanced prostate cancer. Consensus recommendations on quality standards, interpretation, and reporting are needed but will require validation in clinical trials of established and new treatment approaches.

Novel imaging techniques in gynaecological cancer.

PURPOSE OF REVIEW: To describe the added value of novel functional MRI techniques towards detection, staging, characterization, response monitoring and prognostication in gynaecological cancer. RECENT FINDINGS: Functional MRI including diffusion-weighted imaging (DWI)-MRI and dynamic contrast-enhanced (DCE)-MRI adds structural, hemodynamic and physiological information to anatomical MRI. In endometrial and cervical cancer, the addition of DWI-MRI and DCE-MRI improves tumour detection as well as staging of uterine and extra-uterine pelvic spread. Quantitative assessment of DWI and DCE-MRI reflecting tissue properties of biological aggressiveness or treatment resistance may enable the prediction of risk of extra-uterine or extra-ovarian disease spread, predict risk of recurrence and assess treatment response. DWI shows high accuracy for detecting peritoneal metastases and allows for comprehensive staging of (recurrent) ovarian cancer following the clinical development of whole body DWI-MRI. SUMMARY: The added value of DWI/DCE-MRI for characterization and staging of gynaecological malignancy is becoming increasingly established and may improve treatment stratification. Ongoing multicentre studies are expected to further consolidate its use in clinical routine. Quantitative evaluation of functional MRI may help in prognostication and risk stratification.