In vivo evaluation of tumor uptake and bio-distribution of 99mTc-labeled 1-thio-ß-D-glucose and 5-thio-D-glucose in mice model.

BACKGROUND: To investigate the capacity of 99mTc-labeled 1-thio-ß-D-glucose (1-TG) and 5-thio-D-glucose (5-TG) to act as a marker for glucose consumption in tumor cells in vivo as well as to evaluate the biodistribution of 1-TG and 5-TG. We investigated the biodistribution, including tumor uptake, of 1-TG and 5-TG at various time points after injection (0.5, 2 and 4 h) in human colorectal carcinoma (HCT-116) and human lung adenocarcinoma (A549) xenograft bearing nude mice (N = 4 per tracer and time point). RESULTS: Ex vivo biodistribution studies revealed a moderate uptake with a maximum tumor-to-muscle ratio of 4.22 ± 2.7 and 2.2 ± 1.3 (HCT-116) and of 3.2 ± 1.1 and 4.1 ± 1.3 (A549) for 1-TG and 5-TG, respectively, with a peak at 4 h for 1-TG and 5-TG. Biodistribution revealed a significantly higher uptake compared to blood in kidneys (12.18 ± 8.77 and 12.69 ± 8.93%ID/g at 30 min) and liver (2.6 ± 2.8%ID/g) for 1-TG and in the lung (7.24 ± 4.1%ID/g), liver (6.38 ± 2.94%ID/g), and kidneys (4.71 ± 1.97 and 4.81 ± 1.91%ID/g) for 5-TG. CONCLUSIONS: 1-TG and 5-TG showed an insufficient tumor uptake with a moderate tumor-to-muscle ratio, not reaching the levels of commonly used tracer, for diagnostic use in human colorectal carcinoma and human lung adenocarcinoma xenograft model.

MR imaging of hepatocellular carcinoma: prospective intraindividual head-to-head comparison of the contrast agents gadoxetic acid and gadoteric acid.

The routine use of dynamic-contrast-enhanced MRI (DCE-MRI) of the liver using hepatocyte-specific contrast agent (HSCA) as the standard of care for the study of focal liver lesions is not widely accepted and opponents invoke the risk of a loss in near 100% specificity of extracellular contrast agents (ECA) and the need for prospective head-to-head comparative studies evaluating the diagnostic performance of both contrast agents. The Purpose of this prospective intraindividual study was to conduct a quantitative and qualitative head-to-head comparison of DCE-MRI using HSCA and ECA in patients with liver cirrhosis and HCC. Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA (gadoteric acid) and the other with HSCA (gadoxetic acid). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), wash-in, wash-out, image quality, artifacts, lesion conspicuity, and major imaging features of LI-RADS v2018 were evaluated. Wash-in and wash-out were significantly stronger with ECA compared to HSCA (P < 0.001 and 0.006, respectively). During the late arterial phase (LAP), CNR was significantly lower with ECA (P = 0.005), while SNR did not differ significantly (P = 0.39). In qualitative analysis, ECA produced a better overall image quality during the portal venous phase (PVP) and delayed phase (DP) compared to HSCA (P = 0.041 and 0.008), showed less artifacts in the LAP and PVP (P = 0.003 and 0.034) and a higher lesion conspicuity in the LAP and PVP (P = 0.004 and 0.037). There was no significant difference in overall image quality during the LAP (P = 1), in artifacts and lesion conspicuity during the DP (P = 0.078 and 0.073) or in the frequency of the three major LI-RADS v2018 imaging features. In conclusion, ECA provides superior contrast of HCC-especially hypervascular HCC lesions-in DCE-MR in terms of better perceptibility of early enhancement and a stronger washout.

CT radiomics to predict Deauville score 4 positive and negative Hodgkin lymphoma manifestations.

18F-FDG-PET/CT is standard to assess response in Hodgkin lymphoma by quantifying metabolic activity with the Deauville score. PET/CT, however, is time-consuming, cost-extensive, linked to high radiation and has a low availability. As an alternative, we investigated radiomics from non-contrast-enhanced computed tomography (NECT) scans. 75 PET/CT examinations of 43 patients on two different scanners were included. Target lesions were classified as Deauville score 4 positive (DS4+) or negative (DS4-) based on their SUVpeak and then segmented in NECT images. From these segmentations, 107 features were extracted with PyRadiomics. All further statistical analyses were then performed scanner-wise: differences between DS4+ and DS4- manifestations were assessed with the Mann-Whitney-U-test and single feature performances with the ROC-analysis. To further verify the reliability of the results, the number of features was reduced using different techniques. The feature median showed a high sensitivity for DS4+ manifestations on both scanners (scanner A: 0.91, scanner B: 0.85). It furthermore was the only feature that remained in both datasets after applying different feature reduction techniques. The feature median from NECT concordantly has a high sensitivity for DS4+ Hodgkin manifestations on two different scanners and thus could provide a surrogate for increased metabolic activity in PET/CT.

Enhancing the stability of CT radiomics across different volume of interest sizes using parametric feature maps: a phantom study.

BACKGROUND: In radiomics studies, differences in the volume of interest (VOI) are often inevitable and may confound the extracted features. We aimed to correct this confounding effect of VOI variability by applying parametric maps with a fixed voxel size. METHODS: Ten scans of a cup filled with sodium chloride solution were scanned using a multislice computed tomography (CT) unit. Sphere-shaped VOIs with different diameters (4, 8, or 16 mm) were drawn centrally into the phantom. A total of 93 features were extracted conventionally from the original images using PyRadiomics. Using a self-designed and pretested software tool, parametric maps for the same 93 features with a fixed voxel size of 4 mm3 were created. To retrieve the feature values from the maps, VOIs were copied from the original images to preserve the position. Differences in feature quantities between the VOI sizes were tested with the Mann-Whitney U-test and agreement with overall concordance correlation coefficients (OCCC). RESULTS: Fifty-five conventionally extracted features were significantly different between the VOI sizes, and none of the features showed excellent agreement in terms of OCCCs. When read from the parametric maps, only 8 features showed significant differences, and 3 features showed an excellent OCCC (≥ 0.85). The OCCCs for 89 features substantially increased using the parametric maps. CONCLUSIONS: This phantom study shows that converting CT images into parametric maps resolves the confounding effect of VOI variability and increases feature reproducibility across VOI sizes.

Extrahepatic Disease in Hepatocellular Carcinoma: Do We Always Need Whole-Body CT or Is Liver MRI Sufficient? A Subanalysis of the SORAMIC Trial.

Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, multicenter, randomized controlled SORAMIC trial, two blinded readers independently analyzed the whole-body contrast-enhanced CT and gadoxetic acid-enhanced liver MRI data sets of 538 HCC patients. EHD (defined as tumor manifestation outside the liver) detection rates of the two imaging modalities were compared using multiparametric statistical tests. In addition, the most appropriate treatment recommendation was determined by a truth panel. Results: EHD was detected significantly more frequently in patients with portal vein infiltration (21% vs. 10%, p < 0.001), macrovascular infiltration (22% vs. 9%, p < 0.001), and bilobar liver involvement (18% vs. 9%, p = 0.006). Further on, the maximum lesion diameter in patients with EHD was significantly higher (8.2 cm vs. 5.8 cm, p = 0.002). CT detected EHD in significantly more patients compared to MRI in both reader groups (p < 0.001). Higher detection rates of EHD in CT led to a change in management only in one patient since EHD was predominantly present in patients with locally advanced HCC, in whom palliative treatment is the standard of care. Conclusions: Whole-body contrast-enhanced CT shows significantly higher EHD detection rates compared to hepatobiliary contrast liver MRI. However, the higher detection rate did not yield a significant impact on patient management in advanced HCC.

Gadoxetic Acid-Based MRI for Decision-Making in Hepatocellular Carcinoma Employing Perfusion Criteria Only-A Post Hoc Analysis from the SORAMIC Trial Diagnostic Cohort.

The value of gadoxetic acid in the diagnosis of hepatocellular carcinoma (HCC), based on perfusion criteria, is under dispute. This post-hoc analysis of the prospective, phase II, randomized, controlled SORAMIC study compared the accuracy of gadoxetic acid-enhanced dynamic magnetic resonance imaging (MRI) (arterial, portovenous, and venous phase only) versus contrast-enhanced computed tomography (CT) for stratifying patients with HCC to curative ablation or palliative treatment. Two reader groups (radiologists, R1 and R2) performed blind reads of CT and gadoxetic acid-enhanced MRI (contrast dynamics only). A truth panel, with access to clinical and imaging follow-up data, served as reference. Primary endpoint was non-inferiority (margin: 5% points) of MRI vs. CT (lower 95% confidence interval [CI] > 0.75) in a first step and superiority (complete 95% CI > 1) in a second step. The intent-to-treat population comprised 538 patients. Accuracy of treatment decisions was 73.4% and 70.8% for CT (R1 and R2, respectively) and 75.1% and 70.3% for gadoxetic acid-enhanced dynamic MRI. Non-inferiority but not superiority of gadoxetic acid-enhanced dynamic MRI versus CT was demonstrated (odds ratio 1.01; CI 0.97-1.05). Despite a theoretical disadvantage in wash-out depiction, gadoxetic acid-enhanced dynamic MRI is non-inferior to CT in accuracy of treatment decisions for curative ablation versus palliative strategies. This outcome was not subject to the use of additional MR standard sequences.

Brain FDG PET for Short- to Medium-Term Prediction of Further Cognitive Decline and Need for Assisted Living in Acutely Hospitalized Geriatric Patients With Newly Detected Clinically Uncertain Cognitive Impairment.

PURPOSE: The aim of this study was to evaluate brain FDG PET for short- to medium-term prediction of cognitive decline, need for assisted living, and survival in acutely hospitalized geriatric patients with newly detected clinically uncertain cognitive impairment (CUCI). MATERIALS AND METHODS: The study included 96 patients (62 females, 81.4 ± 5.4 years) hospitalized due to (sub)acute admission indications with newly detected CUCI (German Clinical Trials Register DRKS00005041). FDG PET was categorized as "neurodegenerative" (DEG+) or "nonneurodegenerative" (DEG-) based on visual inspection by 2 independent readers. In addition, each individual PET was tested voxel-wise against healthy controls (P < 0.001 uncorrected). The resulting total hypometabolic volume (THV) served as reader-independent measure of the spatial extent of neuronal dysfunction/degeneration. FDG PET findings at baseline were tested for association with the change in living situation and change in vital status 12 to 24 months after PET. The association with the annual change of the CDR-SB (Clinical Dementia Rating Sum of Boxes) after PET was tested in a subsample of 72 patients. RESULTS: The mean time between PET and follow-up did not differ between DEG+ and DEG- patients (1.37 ± 0.27 vs 1.41 ± 0.27 years, P = 0.539). Annual change of CDR-SB was higher in DEG+ compared with DEG- patients (2.78 ± 2.44 vs 0.99 ± 1.81, P = 0.001), and it was positively correlated with THV (age-corrected Spearman ρ = 0.392, P = 0.001). DEG+ patients moved from at home to assisted living significantly earlier than DEG- patients (P = 0.050). Survival was not associated with DEG status or with THV. CONCLUSIONS: In acutely hospitalized geriatric patients with newly detected CUCI, the brain FDG PET can contribute to the prediction of further cognitive/functional decline and the need for assisted living within 1 to 2 years.

Differentiation of Pulmonary Lymphoma Manifestations and Nonlymphoma Infiltrates in Possible Invasive Fungal Disease Using Fast T1-weighted Magnetic Resonance Imaging at 3 T Comparison of Texture Analysis, Mapping, and Signal Intensity Quotients.

PURPOSE: This study aimed to evaluate the diagnostic performance of texture analysis (TA), T1 mapping, and signal intensity quotients derived from fast T1-weighted gradient echo (T1w GRE) sequences for differentiating pulmonary lymphoma manifestations and nonlymphoma infiltrates in possible invasive fungal disease in immunocompromised hematological patients. MATERIALS AND METHODS: Twenty patients with hematologic malignancies and concomitant immunosuppression (including 10 patients with pulmonary lymphoma manifestations and 10 patients with nonlymphoma infiltrates) prospectively underwent 3 T magnetic resonance imaging using a conventional T1w GRE sequence and a T1w GRE mapping sequence with variable flip angle. A region of interest was placed around the most representative lesion in each patient. TA was performed using PyRadiomics. T1 relaxation times were extracted from precompiled maps and calculated manually. Signal intensity quotients (lesion/muscle) were calculated from conventional T1w GRE sequences. RESULTS: Of all TA features, variance, mean absolute deviation, robust mean absolute deviation, interquartile range, and minimum were significantly different between the 2 entities (P<0.05), with excellent diagnostic performance in receiver operating characteristic analysis (area under the curve [AUC] >80%). Neither T1 relaxation times from precompiled maps (AUC=63%; P=0.353) nor manual calculation (AUC=63%; P=0.353) nor signal intensity quotients (AUC=70%; P=0.143) yielded significant differences. CONCLUSIONS: TA from fast T1w GRE images can differentiate pulmonary lymphoma manifestations and nonlymphoma infiltrates in possible invasive fungal disease with excellent diagnostic performance using the TA features variance, mean absolute deviation, robust mean absolute deviation, interquartile range, and minimum. Combining a fast T1w GRE sequence with TA seems to be a promising tool to differentiate these 2 entities noninvasively.

Stability of Liver Radiomics across Different 3D ROI Sizes-An MRI In Vivo Study.

We aimed to evaluate the stability of radiomic features in the liver of healthy individuals across different three-dimensional regions of interest (3D ROI) sizes in T1-weighted (T1w) and T2-weighted (T2w) images from different MR scanners. We retrospectively included 66 examinations of patients without known diseases or pathological imaging findings acquired on three MRI scanners (3 Tesla I: 25 patients, 3 Tesla II: 19 patients, 1.5 Tesla: 22 patients). 3D ROIs of different diameters (10, 20, 30 mm) were drawn on T1w GRE and T2w TSE images into the liver parenchyma (segment V-VIII). We extracted 93 radiomic features from the different ROIs and tested features for significant differences with the Mann-Whitney-U (MWU)-test. The MWU-test revealed significant differences for most second- and higher-order features, indicating a systematic difference dependent on the ROI size. The features mean, median, root mean squared (RMS), 10th percentile, and 90th percentile were not significantly different. We also assessed feature robustness to ROI size variation with overall concordance correlation coefficients (OCCCs). OCCCs across the different ROI-sizes for mean, median, and RMS were excellent (>0.90) in both sequences on all three scanners. These features, therefore, seem robust to ROI-size variation and suitable for radiomic studies of liver MRI.

Other (Non-CNS/Testicular) Extramedullary Localizations of Childhood Relapsed Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma-A Report from the ALL-REZ Study Group.

Children with other extramedullary relapse of acute lymphoblastic leukemia are currently poorly characterized. We aim to assess the prevalence and the clinical, therapeutic and prognostic features of extramedullary localizations other than central nervous system or testis in children with relapse of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) treated on a relapsed ALL protocol. PATIENTS AND METHODS: Patients with relapse of ALL and LBL, treated according to the multicentric ALL-REZ BFM trials between 1983 and 2015, were analyzed for other extramedullary relapse (OEMR) of the disease regarding clinical features, treatment and outcome. Local treatment/irradiation has been recommended on an individual basis and performed only in a minority of patients. RESULTS: A total of 132 out of 2323 (5.6%) patients with ALL relapse presented with an OEMR (combined bone marrow relapse n = 78; isolated extramedullary relapse n = 54). Compared to the non-OEMR group, patients with OEMR had a higher rate of T-immunophenotype (p < 0.001), a higher rate of LBL (p < 0.001) and a significantly different distribution of time to relapse, i.e., more very early and late relapses compared to the non-OEMR group (p = 0.01). Ten-year probabilities of event-free survival (pEFS) and overall survival (pOS) in non-OEMR vs. OEMR were 0.38 ± 0.01 and 0.32 ± 0.04 (p = 0.0204) vs. 0.45 ± 0.01 and 0.37 ± 0.04 (p = 0.0112), respectively. OEMRs have been classified into five subgroups according to the main affected compartment: lymphatic organs (n = 32, 10y-pEFS 0.50 ± 0.09), mediastinum (n = 35, 10y-pEFS 0.11 ± 0.05), bone (n = 12, 0.17 ± 0.11), skin and glands (n = 21, 0.32 ± 0.11) and other localizations (n = 32, 0.41 ± 0.09). Patients with OEMR and T-lineage ALL/LBL showed a significantly worse 10y-pEFS (0.15 ± 0.04) than those with B-Precursor-ALL (0.49 ± 0.06, p < 0.001). Stratified into standard risk (SR) and high risk (HR) groups, pEFS and pOS of OEMR subgroups were in the expected range whereas the mediastinal subgroup had a significantly worse outcome. Subsequent relapses involved more frequently the bone marrow (58.4%) than isolated extramedullary compartments (41.7%). In multivariate Cox regression, OEMR confers an independent prognostic factor for inferior pEFS and pOS. CONCLUSION: OEMR is adversely related to prognosis. However, the established risk classification can be applied for all subgroups except mediastinal relapses requiring treatment intensification. Generally, isolated OEMR of T-cell-origin needs an intensified treatment including allogeneic stem cell transplantation (HSCT) as a curative approach independent from time to relapse. Local therapy such as surgery and irradiation may be of benefit in selected cases. The indication needs to be clarified in further investigations.

Radiomics for Everyone: A New Tool Simplifies Creating Parametric Maps for the Visualization and Quantification of Radiomics Features.

Aim was to develop a user-friendly method for creating parametric maps that would provide a comprehensible visualization and allow immediate quantification of radiomics features. For this, a self-explanatory graphical user interface was designed, and for the proof of concept, maps were created for CT and MR images and features were compared to those from conventional extractions. Especially first-order features were concordant between maps and conventional extractions, some even across all examples. Potential clinical applications were tested on CT and MR images for the differentiation of pulmonary lesions. In these sample applications, maps of Skewness enhanced the differentiation of non-malignant lesions and non-small lung carcinoma manifestations on CT images and maps of Variance enhanced the differentiation of pulmonary lymphoma manifestations and fungal infiltrates on MR images. This new and simple method for creating parametric maps makes radiomics features visually perceivable, allows direct feature quantification by placing a region of interest, can improve the assessment of radiological images and, furthermore, can increase the use of radiomics in clinical routine.

Stability of Radiomic Features across Different Region of Interest Sizes-A CT and MR Phantom Study.

We aimed to evaluate radiomic features' stability across different region of interest (ROI) sizes in CT and MR images. We chose a phantom with a homogenous internal structure so no differences for a feature extracted from ROIs of different sizes would be expected. For this, we scanned a plastic cup filled with sodium chloride solution ten times in CT and per MR sequence (T1-weighted-gradient-echo and T2-weighted-turbo-inversion-recovery-magnitude). We placed sphere-shaped ROIs of different diameters (4, 8, and 16 mm, and 4, 8, and 16 pixels) into the phantom's center. Features were extracted using PyRadiomics. We assessed feature stability across ROI sizes with overall concordance correlation coefficients (OCCCs). Differences were tested for significance with the Mann-Whitney U-test. Of 93 features, 87 T1w-derived, 87 TIRM-derived, and 70 CT-derived features were significantly different between ROI sizes. Among MR-derived features, OCCCs showed excellent (>0.90) agreement for mean, median, and root mean squared for ROI sizes between 4 and 16 mm and pixels. We further observed excellent agreement for 10th and 90th percentile in T1w and 10th percentile in T2w TIRM images. There was no excellent agreement among the OCCCs of CT-derived features. In summary, many features indicated significant differences and only few showed excellent agreement across varying ROI sizes, although we examined a homogenous phantom. Since we considered a small phantom in an experimental setting, further studies to investigate this size effect would be necessary for a generalization. Nevertheless, we believe knowledge about this effect is crucial in interpreting radiomics studies, as features that supposedly discriminate disease entities may only indicate a systematic difference in ROI size.

Enhancing the differentiation of pulmonary lymphoma and fungal pneumonia in hematological patients using texture analysis in 3-T MRI.

OBJECTIVES: To evaluate texture analysis in nonenhanced 3-T MRI for differentiating pulmonary fungal infiltrates and lymphoma manifestations in hematological patients and to compare the diagnostic performance with that of signal intensity quotients ("nonenhanced imaging characterization quotients," NICQs). METHODS: MR scans were performed using a speed-optimized imaging protocol without an intravenous contrast medium including axial T2-weighted (T2w) single-shot fast spin-echo and T1-weighted (T1w) gradient-echo sequences. ROIs were drawn within the lesions to extract first-order statistics from original images using HeterogeneityCAD and PyRadiomics. NICQs were calculated using signal intensities of the lesions, muscle, and fat. The standard of reference was histology or clinical diagnosis in follow-up. Statistical testing included ROC analysis, clustered ROC analysis, and DeLong test. Intra- and interrater reliability was tested using intraclass correlation coefficients (ICC). RESULTS: Thirty-three fungal infiltrates in 16 patients and 38 pulmonary lymphoma manifestations in 19 patients were included. Considering the leading lesion in each patient, diagnostic performance was excellent for T1w entropy (AUC 80.2%; p < 0.005) and slightly inferior for T2w energy (79.9%; p < 0.005), T1w uniformity (79.6%; p < 0.005), and T1w energy (77.0%; p < 0.01); the best AUC for NICQs was 72.0% for T2NICQmean (p < 0.05). Intra- and interrater reliability was good to excellent (ICC > 0.81) for these parameters except for moderate intrarater reliability of T1w energy (ICC = 0.64). CONCLUSIONS: T1w entropy, uniformity, and energy and T2w energy showed the best performances for differentiating pulmonary lymphoma and fungal pneumonia and outperformed NICQs. Results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters. KEY POINTS: • Texture analysis in nonenhanced pulmonary MRI improves the differentiation of pulmonary lymphoma and fungal pneumonia compared with signal intensity quotients. • T1w entropy, uniformity, and energy along with T2w energy show the best performances for differentiating pulmonary lymphoma from fungal pneumonia. • The results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters.

Gadoxetic acid-based hepatobiliary MRI in hepatocellular carcinoma.

BACKGROUND & AIMS: SORAMIC is a prospective phase II randomised controlled trial in hepatocellular carcinoma (HCC). It consists of 3 parts: a diagnostic study and 2 therapeutic studies with either curative ablation or palliative Yttrium-90 radioembolisation combined with sorafenib. We report the diagnostic cohort study aimed to determine the accuracy of gadoxetic acid-enhanced magnetic resonance imaging (MRI), including hepatobiliary phase (HBP) imaging features compared with contrast-enhanced computed tomography (CT). The primary objective was the accuracy of treatment decisions stratifying patients for curative or palliative (non-ablation) treatment. METHODS: Patients with clinically suspected HCC underwent gadoxetic acid-enhanced MRI (HBP MRI, including dynamic MRI) and contrast-enhanced CT. Blinded read of the image data was performed by 2 reader groups (radiologists, R1 and R2). A truth panel with access to all clinical data and follow-up imaging served as reference. Imaging criteria for curative ablation were defined as up to 4 lesions <5 cm and absence of macrovascular invasion. The primary endpoint was non-inferiority of HBP MRI vs. CT in a first step and superiority in a second step. RESULTS: The intent-to-treat population comprised 538 patients. Treatment decisions matched the truth panel assessment in 83.3% and 81.2% for HBP MRI (R1 and R2), and 73.4% and 70.8% for CT. Non-inferiority and superiority (second step) of HBP MRI vs. CT were demonstrated (odds ratio 1.14 [1.09-1.19]). HBP MRI identified patients with >4 lesions significantly more frequently than CT. CONCLUSIONS: In HCC, HBP MRI provided a more accurate decision than CT for a curative vs. palliative treatment strategy. LAY SUMMARY: Patients with hepatocellular carcinoma are allocated to curative or palliative treatment according to the stage of their disease. Hepatobiliary imaging using gadoxetic acid-enhanced MRI is more accurate than CT for treatment decision-making.

18F-sodium fluoride bone deposition quantitation with PET in Mice: Variation with age, sex, and circadian rhythm.

AIM: The aim of this study was to establish a data base for normal 18F-sodium fluoride (18F-NaF) bone uptake as a function of age, sex and circadian rhythm in mice. METHODS: In 12 female (F) and 12 male (M) C57BL/6N mice PET images were acquired 90 min after intravenous injection of 20 MBq 18F-NaF for 30 minutes. Each mouse was imaged in follow-up studies at 1, 3, 6, 13 and 21 months of age. In order to assess for physiologic changes related to circadian rhythm, animals were imaged during light (sleep phase) as well as during night conditions (awake phase). Bone uptake is described as the median percentage of the injected activity (%IA) and in relation to bone volume (%IA/ml). RESULTS: A significant smaller bone volume was found in F (1.79 ml) compared to M (1.99 ml; p < 0.001). In sex-pooled data, highest bone uptake occurred at an age of 1 month (61.1 %IA, 44.5 %IA/ml) with a significant reduction (p < 0.001) at age 3 months (43.6 %IA, 23.6 %IA/ml), followed by an increase between 13 (47.3 %IA, 24.5 %IA/ml) and 21 months (52.2 %IA, 28.1 %IA/ml). F had a significantly higher total uptake (F 48.2 %IA, M 43.8 %IA; p = 0.026) as well as a higher uptake per ml bone tissue (F 27.0 %IA/ml; M 22.4 %IA/ml; p < 0.001). A significant impact of circadian rhythm was only found for F at ages of 3 and 6 months with a higher uptake during the sleep phase. CONCLUSION: Circadian rhythm had a significant impact on uptake only in F of 3 and 6 months. Regarding sex, F showed generally higher uptake rates than M. The highest uptake values were observed during bone growth at age 1 month in both sexes, a second uptake peak occurred in elderly F. Designing future bone uptake studies with M, attention must be paid to age only, while in F circadian rhythm and age must be taken into account.

Steady-State Multifrequency Magnetic Resonance Elastography of the Thoracic and Abdominal Human Aorta-Validation and Reference Values.

OBJECTIVES: The aim of this study was to investigate the potential of stroboscopic-wavefield-sampling-based multifrequency magnetic resonance elastography (sMRE) for quantifying the stiffness of the human thoracic and abdominal aorta in vivo. MATERIALS AND METHODS: The sMRE of the thoracic and abdominal aorta was performed at 1.5 T field strength in 20 healthy volunteers aged 27 to 77 years (3 women; median age, 33 years; interquartile range [IQR], 16 years). Compound maps of shear wave speed (SWS) were reconstructed and evaluated during the diastolic phase in 3 anatomical regions: ascending thoracic aorta (AA), descending thoracic aorta (AD), and abdominal aorta (AAb). The SWS maps were read by 2 readers. Blood pressure and pulse wave velocity were determined noninvasively before sMRE. Data are given as median (IQR) and were compared using the Kruskal-Wallis and Wilcoxon rank sum tests. Intraclass correlation was used to determine interobserver and intraobserver agreement, as well as reproducibility. Multiple linear regression analysis was performed to evaluate effects of age, sex, vessel diameter, blood pressure, pulse wave velocity, and aortic segment on measured SWS. RESULTS: All 20 participants underwent successful sMRE, resulting in a total of 60 aortic segments. The median SWS (IQR) of AA, AD, and AAb was 1.62 (0.16) m/s, 2.40 (0.24) m/s, and 2.48 (0.58) m/s, respectively. The SWS in AA was significantly lower (P < 0.001), and no differences in SWS (P = 0.67) were found between AD and AAb. Interobserver and intraobserver agreement, as well as reproducibility, was excellent, with intraclass correlation coefficients ranging between 0.957 and 0.998. A significant but weak influence of age on measured SWS was found, which increased from AA to AD and AAb (R = 0.229, 0.275, 0.377, respectively; P = 0.001-0.005). CONCLUSIONS: Quantification of aortic stiffness in different segments of the human aorta is possible with sMRE. Our results correlate well with known aortic stiffness differences in different anatomical locations and demonstrate the potential of sMRE for clinical stiffness measurement of the thoracoabdominal aorta, which may allow detection of physiological variation and cardiovascular diseases.

Diagnosis of Left Ventricular Diastolic Dysfunction Using Cardiac Magnetic Resonance Imaging: Comparison of Volume-Time Curves Derived from Long- and Short-Axis Cine Steady-State Free Precession Datasets.

PURPOSE: To evaluate the diagnostic performance of diastolic function parameters derived from long-axis (LAX) planimetry compared with short-axis (SAX) volumetry in cardiac magnetic resonance imaging. MATERIALS AND METHODS: Cine steady-state free precession (SSFP) datasets of 15 healthy participants (8 young and 7 middle aged) and 25 patients with echocardiographically proven diastolic dysfunction (9 mild, 9 moderate, and 7 severe) were retrospectively included. Volume-time curves for assessing left ventricular (LV) function were obtained by manually contouring the LV endocardial borders in SAX and LAX datasets. The time needed for contouring was recorded for each dataset. The following LV parameters were determined: end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), myocardial mass (MM), time to peak filling rate (TPFR), normalized peak filling rate (nPFR), and the ratio of early to late peak filling rate (E/A ratio). A Wilcoxon signed-rank test was used to compare subgroups based on age and severity of diastolic dysfunction for statistical differences. Intraclass correlation coefficients were used to assess intermethod and interobserver reliability. RESULTS: Accuracy for the diagnosis of diastolic dysfunction was highest for E/A (mild diastolic dysfunction) and nPFR (any stage of diastolic dysfunction) derived from LAX datasets (E/A: area under the curve (AUC) = 0.97, sensitivity of 68 % and specificity of 100 %; nPFR: AUC = 0.84, sensitivity of 84 % and specificity of 80 %). Diastolic parameters showed a moderate to good intraclass correlation between both methods. The mean differences in EDV, ESV, EF, and MM were 5.3 ml, 1.9 ml, 3.5 %, and 11 g, respectively (each p < 0.001). Significantly less time was needed to derive volume-time curves from LAX images (median 14:45 min, interquartile range 14:15-15:53 min versus median 29:25 min, interquartile range 28:12-32:22 min; p = 0.001). The interobserver reliability was generally good to excellent. CONCLUSION: Diastolic function parameters derived from left ventricular LAX planimetry have high diagnostic performance and can be obtained in significantly less time compared with SAX volumetry. These findings may pave the way for routine use of LAX planimetry in the clinical diagnosis of diastolic dysfunction. KEY POINTS: · Diastolic function parameters derived from long-axis datasets have high diagnostic performance.. · Generation of volume-time curves using long-axis datasets requires significantly less time.. · This time savings may allow use of cardiac MRI for the diagnosis of diastolic dysfunction in the clinical routine.. CITATION FORMAT: · Schaafs LA, Wyschkon S, Elgeti M et al. Diagnosis of Left Ventricular Diastolic Dysfunction Using Cardiac Magnetic Resonance Imaging: Comparison of Volume-Time Curves Derived from Long- and Short-Axis Cine Steady-State Free Precession Datasets. Fortschr Röntgenstr 2020; 192: 764 - 775.

Quantification of Aortic Stiffness by Ultrasound Time-Harmonic Elastography: The Effect of Intravascular Pressure on Elasticity Measures in a Porcine Model.

OBJECTIVES: The aim of this study was to investigate blood pressure dependency of ultrasound time-harmonic elastography (THE) for quantification of aortic stiffness. MATERIALS AND METHODS: Thoracoabdominal aortas were surgically removed from 9 healthy domestic pigs and prepared for elastographic experiments. All vessels were connected to a saline-filled water column with adjustable height and pressurized over a range of 0 to 110 mm Hg in 10 mm Hg increments to simulate different levels of mean arterial pressure. In addition, 3 of the 9 aortas were soaked in 4% buffered formaldehyde for 60 minutes to simulate pathologic aortic stiffening. Ultrasound THE was performed in each vessel at each pressure level. For each pressure level, shear-wave speed (SWS) as a measure of aortic wall stiffness and luminal diameter were recorded. The pressure range between 30 and 110 mm Hg was used for statistical evaluation as it reflects a physiological mean arterial pressure range. Linear regression analysis and multivariate analysis with a general linear model were performed to evaluate the influence of increasing intravascular pressure and vessel diameter on measured SWS. RESULTS: Median SWS in formalin-soaked aortas was significantly higher with 3.22 m/s (interquartile range [IQR], 0.01 m/s) versus 2.14 m/s (IQR, 0.09) at 30 mm Hg and 3.38 m/s (IQR, 0.01 m/s) versus 2.28 m/s (IQR, 0.07 m/s) at 110 mm Hg (each P = 0.01). Using linear regression analysis, an increase of aortic wall SWS of 0.017 m/s per 10 mm Hg intraluminal pressure was found in untreated aortas, whereas SWS increased by 0.020 m/s per 10 mm Hg in formalin-soaked aortas (both P = 0.001). The percentage of SWS caused by intraluminal pressure was 1.89% in formalin-soaked aortas and 2.50% in untreated aortas at 30 mm Hg and 6.61% for formalin-soaked aortas and 8.60% for untreated aortas at 110 mm Hg. Multivariate analysis showed no significant interaction of luminal diameter and measured SWS (P = 0.893). CONCLUSIONS: In our model, aortic stiffness measurements by ultrasound time-harmonic elastography are influenced to a small extent by mean arterial pressure in a range of 1.89% to 8.60%. These findings emphasize the potential of ultrasound THE for measuring the intrinsic stiffness of the aortic wall in clinical routine.

Does Hepatic Steatosis Influence the Detection Rate of Metastases in the Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI?

The aim of this exploratory study was to evaluate the influence of hepatic steatosis on the detection rate of metastases in gadoxetic acid-enhanced liver magnetic resonance imaging (MRI). A total of 50 patients who underwent gadoxetic acid-enhanced MRI (unenhanced T1w in- and opposed-phase, T2w fat sat, unenhanced 3D-T1w fat sat and 3-phase dynamic contrast-enhanced (uDP), 3D-T1w fat sat hepatobiliary phase (HP)) were retrospectively included. Two blinded observers (O1/O2) independently assessed the images to determine the detection rate in uDP and HP. The hepatic signal fat fraction (HSFF) was determined as the relative signal intensity reduction in liver parenchyma from in- to opposed-phase images. A total of 451 liver metastases were detected (O1/O2, n = 447/411). O1/O2 detected 10.9%/9.3% of lesions exclusively in uDP and 20.2%/15.5% exclusively in HP. Lesions detected exclusively in uDP were significantly associated with a larger HSFF (area under curve (AUC) of receiver operating characteristic (ROC) analysis, 0.93; p < 0.001; cutoff, 41.5%). The exclusively HP-positive lesions were significantly associated with a smaller diameter (ROC-AUC, 0.82; p < 0.001; cutoff, 5 mm) and a smaller HSFF (ROC-AUC, 0.61; p < 0.001; cutoff, 13.3%). Gadoxetic acid imaging has the advantage of detecting small occult metastatic liver lesions in the HP. However, using non-optimized standard fat-saturated 3D-T1w protocols, severe steatosis (HSFF > 30%) is a potential pitfall for the detection of metastases in HP.

Diagnostic Performance and Reliability of Non-Enhanced Imaging Characterization Quotients for the Differentiation of Infectious and Malignant Pulmonary Nodules in Hematological Patients Using 3T MRI.

PURPOSE: To evaluate the diagnostic performance and reliability of non-enhanced imaging characterization quotients (NICQs) derived from magnetic resonance imaging (MRI) in the differential diagnosis of pulmonary nodules in hematological patients. MATERIALS AND METHODS: A total of 83 lesions in 45 consecutive hematological patients were analyzed (10 bacterial pneumonias, 16 fungal pneumonias, 19 pulmonary lymphoma manifestations). The MRI protocol included T2-weighted single-shot fast spin echo (FSE) and T1-weighted gradient echo (GRE) sequences. T2-based T2-NICQmean and T2-NICQ90th were calculated from signal intensities measured in the lesion, muscle, and fat ((SILesion - SIMuscle)/(SIFat - SIMuscle) * 100), and simple T1-based T1-Qmean from signal intensities of the lesion and muscle (SILesion/SIMuscle). Images were read by one radiologist with > 7 years and one with 1 year of experience. For statistical evaluation the Kruskal-Wallis or Mann-Whitney U-test, receiver operating characteristic (ROC) analysis with calculation of areas under the curve (AUC), and intraclass correlation coefficients (ICCs) were used. RESULTS: Medians of T2-NICQs differed significantly when comparing infectious lesions and lymphoma manifestations in general (T2-NICQmean 20.33 vs. 10.14; T2-NICQ90th 34.96 vs. 25.52) or fungal lesions and lymphoma manifestations in particular (T2-NICQmean 19.00 vs. 10.14; T2-NICQ90th 34.49 vs. 25.25). The AUCs for T2-NICQs on the per-patient level ranged from 0.73 to 0.79. ICCs were at least > 0.85, except for intrarater testing of T2-NICQ90th (0.79). CONCLUSION: The overall diagnostic performance of T2-NICQs is adequate for differentiating infectious and fungal lesions from lymphoma manifestations. The results show good to excellent intra- and interrater agreement. We therefore consider NICQs helpful in the diagnostic workup of pulmonary nodules in hematological patients. KEY POINTS: · Non-enhanced Imaging Characterization Quotients provide a fast and pragmatic approach for assessing pulmonary lesions in hematological patients.. · The diagnostic performance of Non-enhanced Imaging Characterization Quotients is adequate for differentiating infectious and fungal infiltrates from lymphoma manifestations.. · Non-enhanced Imaging Characterization Quotients show good to excellent intra- and interrater agreement.. CITATION FORMAT: · Nagel SN, Kim D, Wylutzki T et al. Diagnostic Performance and Reliability of Non-Enhanced Imaging Characterization Quotients for the Differentiation of Infectious and Malignant Pulmonary Nodules in Hematological Patients Using 3T MRI. Fortschr Röntgenstr 2020; 192: 327 - 334.