MRI proton density fat fraction for estimation of tumor grade in steatotic hepatocellular carcinoma.

OBJECTIVES: Image-based detection of intralesional fat in focal liver lesions has been established in diagnostic guidelines as a feature indicative of hepatocellular carcinoma (HCC) and associated with a favorable prognosis. Given recent advances in MRI-based fat quantification techniques, we investigated a possible relationship between intralesional fat content and histologic tumor grade in steatotic HCCs. METHODS: Patients with histopathologically confirmed HCC and prior MRI with proton density fat fraction (PDFF) mapping were retrospectively identified. Intralesional fat of HCCs was assessed using an ROI-based analysis and the median fat fraction of steatotic HCCs was compared between tumor grades G1-3 with non-parametric testing. ROC analysis was performed in case of statistically significant differences (p < 0.05). Subgroup analyses were conducted for patients with/without liver steatosis and with/without liver cirrhosis. RESULTS: A total of 57 patients with steatotic HCCs (62 lesions) were eligible for analysis. The median fat fraction was significantly higher for G1 lesions (median [interquartile range], 7.9% [6.0─10.7%]) than for G2 (4.4% [3.2─6.6%]; p = .001) and G3 lesions (4.7% [2.8─7.8%]; p = .036). PDFF was a good discriminator between G1 and G2/3 lesions (AUC .81; cut-off 5.8%, sensitivity 83%, specificity 68%) with comparable results in patients with liver cirrhosis. In patients with liver steatosis, intralesional fat content was higher than in the overall sample, with PDFF performing better in distinguishing between G1 and G2/3 lesions (AUC .92; cut-off 8.8%, sensitivity 83%, specificity 91%). CONCLUSIONS: Quantification of intralesional fat using MRI PDFF mapping allows distinction between well- and less-differentiated steatotic HCCs. CLINICAL RELEVANCE: PDFF mapping may help optimize precision medicine as a tool for tumor grade assessment in steatotic HCCs. Further investigation of intratumoral fat content as a potential prognostic indicator of treatment response is encouraged. KEY POINTS: • MRI proton density fat fraction mapping enables distinction between well- (G1) and less- (G2 and G3) differentiated steatotic hepatocellular carcinomas. • In a retrospective single-center study with 62 histologically proven steatotic hepatocellular carcinomas, G1 tumors showed a higher intralesional fat content than G2 and G3 tumors (7.9% vs. 4.4% and 4.7%; p = .004). • In liver steatosis, MRI proton density fat fraction mapping was an even better discriminator between G1 and G2/G3 steatotic hepatocellular carcinomas.

Three Tesla magnetic resonance imaging detects oxalate osteopathy in patients with primary hyperoxaluria type I.

BACKGROUND: With declining kidney function and therefore increasing plasma oxalate, patients with primary hyperoxaluria type I (PHI) are at risk to systemically deposit calcium-oxalate crystals. This systemic oxalosis may occur even at early stages of chronic kidney failure (CKD) but is difficult to detect with non-invasive imaging procedures. METHODS: We tested if magnetic resonance imaging (MRI) is sensitive to detect oxalate deposition in bone. A 3 Tesla MRI of the left knee/tibial metaphysis was performed in 46 patients with PHI and in 12 healthy controls. In addition to the investigator's interpretation, signal intensities (SI) within a region of interest (ROI, transverse images below the level of the physis in the proximal tibial metaphysis) were measured pixelwise, and statistical parameters of their distribution were calculated. In addition, 52 parameters of texture analysis were evaluated. Plasma oxalate and CKD status were correlated to MRI findings. MRI was then implemented in routine practice. RESULTS: Independent interpretation by investigators was consistent in most cases and clearly differentiated patients from controls. Statistically significant differences were seen between patients and controls (p < 0.05). No correlation/relation between the MRI parameters and CKD stages or Pox levels was found. However, MR imaging of oxalate osteopathy revealed changes attributed to clinical status which differed clearly to that in secondary hyperparathyroidism. CONCLUSIONS: MRI is able to visually detect (early) oxalate osteopathy in PHI. It can be used for its monitoring and is distinguished from renal osteodystrophy. In the future, machine learning algorithms may aid in the objective assessment of oxalate deposition in bone. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Diagnostic value of magnetic resonance parametric mapping for non-invasive assessment of liver fibrosis in patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by bile duct inflammation and destruction, leading to biliary fibrosis and cirrhosis. The purpose of this study was to investigate the utility of T1 and T2 mapping parameters, including extracellular volume fraction (ECV) for non-invasive assessment of fibrosis severity in patients with PSC. METHODS: In this prospective study, patients with PSC diagnosis were consecutively enrolled from January 2019 to July 2020 and underwent liver MRI. Besides morphological sequences, MR elastography (MRE), and T1 and T2 mapping were performed. ECV was calculated from T1 relaxation times. The presence of significant fibrosis (≥ F2) was defined as MRE-derived liver stiffness ≥ 3.66 kPa and used as the reference standard, against which the diagnostic performance of MRI mapping parameters was tested. Student t test, ROC analysis and Pearson correlation were used for statistical analysis. RESULTS: 32 patients with PSC (age range 19-77 years) were analyzed. Both, hepatic native T1 (r = 0.66; P < 0.001) and ECV (r = 0.69; P < 0.001) correlated with MRE-derived liver stiffness. To diagnose significant fibrosis (≥ F2), ECV revealed a sensitivity of 84.2% (95% confidence interval (CI) 62.4-94.5%) and a specificity of 84.6% (CI 57.8-95.7%); hepatic native T1 revealed a sensitivity of 52.6% (CI 31.7-72.7%) and a specificity of 100.0% (CI 77.2-100.0%). Hepatic ECV (area under the curve (AUC) 0.858) and native T1 (AUC 0.711) had an equal or higher diagnostic performance for the assessment of significant fibrosis compared to serologic fibrosis scores (APRI (AUC 0.787), FIB-4 (AUC 0.588), AAR (0.570)). CONCLUSIONS: Hepatic T1 and ECV can diagnose significant fibrosis in patients with PSC. Quantitative mapping has the potential to be a new non-invasive biomarker for liver fibrosis assessment and quantification in PSC patients.

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis.

BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis. METHODS: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint. RESULTS: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA. CONCLUSION: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. LAY SUMMARY: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.

Association Between Portosystemic Shunts and Increased Complications and Mortality in Patients With Cirrhosis.

BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) have been associated with hepatic encephalopathy (HE). Little is known about their prevalence among patients with cirrhosis or clinical effects. We investigated the prevalence and characteristics of SPSS in patients with cirrhosis and their outcomes. METHODS: We performed a retrospective study of 1729 patients with cirrhosis who underwent abdominal computed tomography or magnetic resonance imaging analysis from 2010 through 2015 at 14 centers in Canada and Europe. We collected data on demographic features, etiology of liver disease, comorbidities, complications, treatments, laboratory and clinical parameters, Model for End-Stage Liver Disease (MELD) score, and endoscopy findings. Abdominal images were reviewed by a radiologist (or a hepatologist trained by a radiologist) and searched for the presence of SPSS, defined as spontaneous communications between the portal venous system or splanchnic veins and the systemic venous system, excluding gastroesophageal varices. Patients were assigned to groups with large SPSS (L-SPSS, ≥8 mm), small SPSS (S-SPSS, <8 mm), or without SPSS (W-SPSS). The main outcomes were the incidence of complications of cirrhosis and mortality according to the presence of SPSS. Secondary measurements were the prevalence of SPSS in patients with cirrhosis and their radiologic features. RESULTS: L-SPSS were identified in 488 (28%) patients, S-SPSS in 548 (32%) patients, and no shunt (W-SPSS) in 693 (40%) patients. The most common L-SPSS was splenorenal (46% of L-SPSS). The presence and size of SPSS increased with liver dysfunction: among patients with MELD scores of 6-9, 14% had L-SPSS and 28% had S-SPSS; among patients with MELD scores of 10-13, 30% had L-SPSS and 34% had S-SPSS; among patients with MELD scores of 14 or higher, 40% had L-SPSS and 32% had S-SPSS (P < .001 for multiple comparison among MELD groups). HE was reported in 48% of patients with L-SPSS, 34% of patients with S-SPSS, and 20% of patients W-SPSS (P < .001 for multiple comparison among SPSS groups). Recurrent or persistent HE was reported in 52% of patients with L-SPSS, 44% of patients with S-SPSS, and 37% of patients W-SPSS (P = .007 for multiple comparison among SPSS groups). Patients with SPSS also had a larger number of portal hypertension-related complications (bleeding or ascites) than those W-SPSS. Quality of life and transplantation-free survival were lower in patients with SPSS vs without. SPSS were an independent factor associated with death or liver transplantation (hazard ratio, 1.26; 95% confidence interval, 1.06-1.49) (P = .008) in multivariate analysis. When patients were stratified by MELD score, SPSS were associated with HE independently of liver function: among patients with MELD scores of 6-9, HE was reported in 23% with L-SPSS, 12% with S-SPSS, and 5% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among those with MELD scores of 10-13, HE was reported in 48% with L-SPSS, 33% with S-SPSS, and 23% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among patients with MELD scores of 14 or more, HE was reported in 59% with L-SPSS, 57% with S-SPSS, and 48% with W-SPSS (P = .043 for multiple comparison among SPSS groups). Patients with SPSS and MELD scores of 6-9 were at higher risk for ascites (40.5% vs 23%; P < .001) and bleeding (15% vs 9%; P = .038) than patients W-SPSS and had lower odds of transplant-free survival (hazard ratio 1.71; 95% confidence interval, 1.16-2.51) (P = .006). CONCLUSIONS: In a retrospective analysis of almost 2000 patients, we found 60% to have SPSS; prevalence increases with deterioration of liver function. SPSS increase risk for HE and with a chronic course. In patients with preserved liver function, SPSS increase risk for complications and death. ClinicalTrials.gov ID NCT02692430.

Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis.

Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cutoff values are missing, and most studies have used computed tomography. This study evaluated fat-free muscle area (FFMA) as a marker of sarcopenia using magnetic resonance imaging (MRI) in patients with decompensated cirrhosis with transjugular intrahepatic portosystemic shunt (TIPS). The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the FFMA in 116 patients with cirrhosis by TIPS and MRI. The training cohort of 71 patients compared computed tomography-measured transversal psoas muscle thickness with FFMA. In 15 patients MRI was performed before and after TIPS, and in 12 patients follistatin serum measurements were carried out. The results on FFMA were confirmed in a validation cohort of 45 patients. FFMA correlated with follistatin and transversal psoas muscle thickness and showed slightly better association with survival than transversal psoas muscle thickness. Gender-specific cutoff values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS in the sarcopenia group but resolved in the nonsarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure. FFMA was an independent predictor of survival in these patients. CONCLUSION: This study offers an easy-to-apply MRI-based measurement of fat-free muscle mass as a marker of sarcopenia in decompensated patients; while TIPS might improve sarcopenia and thereby survival, persistence of sarcopenia after TIPS is associated with a reduced response to TIPS and a higher risk of acute-on-chronic liver failure development and mortality. (Hepatology 2018;67:1014-1026).

Proton density fat fraction MRI of vertebral bone marrow: Accuracy, repeatability, and reproducibility among readers, field strengths, and imaging platforms.

BACKGROUND: Chemical shift-encoding based water-fat MRI is an emerging method to noninvasively assess proton density fat fraction (PDFF), a promising quantitative imaging biomarker for estimating tissue fat concentration. However, in vivo validation of PDFF is still lacking for bone marrow applications. PURPOSE: To determine the accuracy and precision of MRI-determined vertebral bone marrow PDFF among different readers and across different field strengths and imager manufacturers. STUDY TYPE: Repeatability/reproducibility. SUBJECTS: Twenty-four adult volunteers underwent lumbar spine MRI with one 1.5T and two different 3.0T MR scanners from two vendors on the same day. FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T/3D spoiled-gradient echo multipoint Dixon sequences. ASSESSMENT: Two independent readers measured intravertebral PDFF for the three most central slices of the L1-5 vertebral bodies. Single-voxel MR spectroscopy (MRS)-determined PDFF served as the reference standard for PDFF estimation. STATISTICAL TESTS: Accuracy and bias were assessed by Pearson correlation, linear regression analysis, and Bland-Altman plots. Repeatability and reproducibility were evaluated by Wilcoxon signed rank test, Friedman test, and coefficients of variation. Intraclass correlation coefficients were used to validate intra- and interreader as well as intraimager agreements. RESULTS: MRI-based PDFF estimates of lumbar bone marrow were highly correlated (r2 = 0.899) and accurate (mean bias, -0.6%) against the MRS-determined PDFF reference standard. PDFF showed high linearity (r2 = 0.972-0.978) and small mean bias (0.6-1.5%) with 95% limits of agreement within ±3.4% across field strengths, imaging platforms, and readers. Repeatability and reproducibility of PDFF were high, with the mean overall coefficient of variation being 0.86% and 2.77%, respectively. The overall intraclass correlation coefficient was 0.986 as a measure for an excellent interreader agreement. DATA CONCLUSION: MRI-based quantification of vertebral bone marrow PDFF is highly accurate, repeatable, and reproducible among readers, field strengths, and MRI platforms, indicating its robustness as a quantitative imaging biomarker for multicentric studies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1762-1772.

Quantification of Liver Fibrosis at T1 and T2 Mapping with Extracellular Volume Fraction MRI: Preclinical Results.

Purpose To evaluate MRI T1 and T2 mapping with calculation of extracellular volume (ECV) for diagnosis and grading of liver fibrosis. Materials and Methods Different grades of fibrosis were induced in 60 male Sprague-Dawley rats by bile duct ligation (BDL) and carbon-tetrachloride (CCl4) intoxication. Portal pressure was measured invasively, whereas hepatic fibrosis was quantified by hydroxyproline content, Sirius red staining, and α smooth muscle actin staining. T1 values, T2 values, and ECV were assessed by using quantitative MRI mapping techniques. Results T1 values in animals 4 weeks after BDL were greater than in control animals (718 msec ± 74 vs 578 msec ± 33, respectively; P < .001). T2 values at 4 weeks were also greater in animals that underwent BDL than in control animals (46 msec ± 6 vs 29 msec ± 2, respectively; P < .001). Similar T1 and T2 findings were observed after CCl4 intoxication. ECV was greater in animals 4 weeks after BDL compared with control animals (31.3% ± 1.3 vs 18.2% ± 3.5, respectively; P < .001), with similar results after CCl4 intoxication. High correlations were found between ECV and hepatic hydroxyproline content (BDL: r = 0.68, P < .001; CCl4: r = 0.65, P < .001), Sirius red staining (BDL: r = 0.88, P < .001; CCl4: r = 0.82, P < .001), α smooth muscle actin staining (BDL: r = 0.70, P < .001; CCl4: r = 0.73, P < .001), and portal pressure (BDL: r = 0.54, P = .003; CCl4: r = 0.39, P = .043). Conclusion Elevation of T1 and T2 values and ECV was associated with severity of liver fibrosis and portal hypertension in an experimental animal model.

Linearity, Bias, and Precision of Hepatic Proton Density Fat Fraction Measurements by Using MR Imaging: A Meta-Analysis.

Purpose To determine the linearity, bias, and precision of hepatic proton density fat fraction (PDFF) measurements by using magnetic resonance (MR) imaging across different field strengths, imager manufacturers, and reconstruction methods. Materials and Methods This meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search identified studies that evaluated the linearity and/or bias of hepatic PDFF measurements by using MR imaging (hereafter, MR imaging-PDFF) against PDFF measurements by using colocalized MR spectroscopy (hereafter, MR spectroscopy-PDFF) or the precision of MR imaging-PDFF. The quality of each study was evaluated by using the Quality Assessment of Studies of Diagnostic Accuracy 2 tool. De-identified original data sets from the selected studies were pooled. Linearity was evaluated by using linear regression between MR imaging-PDFF and MR spectroscopy-PDFF measurements. Bias, defined as the mean difference between MR imaging-PDFF and MR spectroscopy-PDFF measurements, was evaluated by using Bland-Altman analysis. Precision, defined as the agreement between repeated MR imaging-PDFF measurements, was evaluated by using a linear mixed-effects model, with field strength, imager manufacturer, reconstruction method, and region of interest as random effects. Results Twenty-three studies (1679 participants) were selected for linearity and bias analyses and 11 studies (425 participants) were selected for precision analyses. MR imaging-PDFF was linear with MR spectroscopy-PDFF (R2 = 0.96). Regression slope (0.97; P < .001) and mean Bland-Altman bias (-0.13%; 95% limits of agreement: -3.95%, 3.40%) indicated minimal underestimation by using MR imaging-PDFF. MR imaging-PDFF was precise at the region-of-interest level, with repeatability and reproducibility coefficients of 2.99% and 4.12%, respectively. Field strength, imager manufacturer, and reconstruction method each had minimal effects on reproducibility. Conclusion MR imaging-PDFF has excellent linearity, bias, and precision across different field strengths, imager manufacturers, and reconstruction methods. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on October 2, 2017.

Proton density fat fraction (PDFF) MR imaging for differentiation of acute benign and neoplastic compression fractures of the spine.

OBJECTIVES: To evaluate the diagnostic performance of proton density fat fraction (PDFF) magnetic resonance imaging (MRI) to differentiate between acute benign and neoplastic vertebral compression fractures (VCFs). METHODS: Fifty-seven consecutive patients with 46 acute benign and 41 malignant VCFs were prospectively enrolled in this institutional review board approved study and underwent routine clinical MRI with an additional six-echo modified Dixon sequence of the spine at a clinical 3.0-T scanner. All fractures were categorised as benign or malignant according to either direct bone biopsy or 6-month follow-up MRI. Intravertebral PDFF and PDFFratio (fracture PDFF/normal vertebrae PDFF) for benign and malignant VCFs were calculated using region-of-interest analysis and compared between both groups. Additional receiver operating characteristic and binary logistic regression analyses were performed. RESULTS: Both PDFF and PDFFratio of malignant VCFs were significantly lower compared to acute benign VCFs [PDFF, 3.48 ± 3.30% vs 23.99 ± 11.86% (p < 0.001); PDFFratio, 0.09 ± 0.09 vs 0.49 ± 0.24 (p < 0.001)]. The areas under the curve were 0.98 for PDFF and 0.97 for PDFFratio, yielding an accuracy of 96% and 95% for differentiating between acute benign and malignant VCFs. PDFF remained as the only imaging-based variable to independently differentiate between acute benign and malignant VCFs on multivariate analysis (odds ratio, 0.454; p = 0.005). CONCLUSIONS: Quantitative assessment of PDFF derived from modified Dixon water-fat MRI has high diagnostic accuracy for the differentiation of acute benign and malignant vertebral compression fractures. KEY POINTS: • Chemical-shift-encoding based water-fat MRI can reliably assess vertebral bone marrow PDFF • PDFF is significantly higher in acute benign than in malignant VCFs • PDFF provides high accuracy for differentiating acute benign from malignant VCFs.

Revised PROPELLER for T2-weighted imaging of the prostate at 3 Tesla: impact on lesion detection and PI-RADS classification.

PURPOSE: To evaluate revised PROPELLER (RevPROP) for T2-weighted imaging (T2WI) of the prostate as a substitute for turbo spin echo (TSE). MATERIALS AND METHODS: Three-Tesla MR images of 50 patients with 55 cancer-suspicious lesions were prospectively evaluated. Findings were correlated with histopathology after MRI-guided biopsy. T2 RevPROP, T2 TSE, diffusion-weighted imaging, dynamic contrast enhancement, and MR-spectroscopy were acquired. RevPROP was compared to TSE concerning PI-RADS scores, lesion size, lesion signal-intensity, lesion contrast, artefacts, and image quality. RESULTS: There were 41 carcinomas in 55 cancer-suspicious lesions. RevPROP detected 41 of 41 carcinomas (100%) and 54 of 55 lesions (98.2%). TSE detected 39 of 41 carcinomas (95.1%) and 51 of 55 lesions (92.7%). RevPROP showed fewer artefacts and higher image quality (each p < 0.001). No differences were observed between single and overall PI-RADS scores based on RevPROP or TSE (p = 0.106 and p = 0.107). Lesion size was not different (p = 0.105). T2-signal intensity of lesions was higher and T2-contrast of lesions was lower on RevPROP (each p < 0.001). CONCLUSION: For prostate cancer detection RevPROP is superior to TSE with respect to motion robustness, image quality and detection rates of lesions. Therefore, RevPROP might be used as a substitute for T2WI. KEY POINTS: • Revised PROPELLER can be used as a substitute for T2-weighted prostate imaging. • Revised PROPELLER detected more carcinomas and more suspicious lesions than TSE. • Revised PROPELLER showed fewer artefacts and better image quality compared to TSE. • There were no significant differences in PI-RADS scores between revised PROPELLER and TSE. • The lower T2-contrast of revised PROPELLER did not impair its diagnostic quality.

Proton density fat fraction (PDFF) MRI for differentiation of benign and malignant vertebral lesions.

OBJECTIVES: To investigate whether proton density fat fraction (PDFF) measurements using a six-echo modified Dixon sequence can help to differentiate between benign and malignant vertebral bone marrow lesions. METHODS: Sixty-six patients were prospectively enrolled in our study. In addition to conventional MRI at 3.0-Tesla including at least sagittal T2-weighted/spectral attenuated inversion recovery and T1-weighted sequences, all patients underwent a sagittal six-echo modified Dixon sequence of the spine. The mean PDFF was calculated using regions of interest and compared between vertebral lesions. A cut-off value of 6.40% in PDFF was determined by receiver operating characteristic curves and used to differentiate between malignant (< 6.40%) and benign (≥ 6.40%) vertebral lesions. RESULTS: There were 77 benign and 44 malignant lesions. The PDFF of malignant lesions was statistically significant lower in comparison with benign lesions (p < 0.001) and normal vertebral bone marrow (p < 0.001). The areas under the curves (AUC) were 0.97 for differentiating benign from malignant lesions (p < 0.001) and 0.95 for differentiating acute vertebral fractures from malignant lesions (p < 0.001). This yielded a diagnostic accuracy of 96% in the differentiation of both benign lesions and acute vertebral fractures from malignancy. CONCLUSION: PDFF derived from six-echo modified Dixon allows for differentiation between benign and malignant vertebral lesions with a high diagnostic accuracy. KEY POINTS: • Establishing a diagnosis of indeterminate vertebral lesions is a common clinical problem • Benign bone marrow processes may mimic the signal alterations observed in malignancy • PDFF differentiates between benign and malignant lesions with a high diagnostic accuracy • PDFF of non-neoplastic vertebral lesions is significantly higher than that of malignancy • PDFF from six-echo modified Dixon may help avoid potentially harmful bone biopsy.

De novo microdeletions and point mutations affecting SOX2 in three individuals with intellectual disability but without major eye malformations.

Loss-of-function mutations and deletions of the SOX2 gene are known to cause uni- and bilateral anophthalmia and microphthalmia as well as related disorders such as anophthalmia-esophageal-genital syndrome. Thus, anophthalmia/microphthalmia is the primary indication for targeted, "phenotype first" analyses of SOX2. However, SOX2 mutations are also associated with a wide range of non-ocular abnormalities, such as postnatal growth retardation, structural brain anomalies, hypogenitalism, and developmental delay. The present report describes three patients without anophthalmia/microphthalmia and loss-of-function mutations or microdeletions of SOX2 who had been investigated in a "genotype first" manner due to intellectual disability/developmental delay using whole exome sequencing or chromosomal microarray analyses. This result prompted us to perform SOX2 Sanger sequencing in 192 developmental delay/intellectual disability patients without anophthalmia or microphthalmia. No additional SOX2 loss-of-function mutations were detected in this cohort, showing that SOX2 is clearly not a major cause of intellectual disability without anophthalmia/microphthalmia. In our three patients and four further, reported "genotype first" SOX2 microdeletion patients, anophthalmia/microphthalmia was present in less than half of the patients. Thus, SOX2 is another example of a gene whose clinical spectrum is broadened by the generation of "genotype first" findings using hypothesis-free, genome-wide methods. © 2016 Wiley Periodicals, Inc.

The Achilles tendon is mechanosensitive in older adults: adaptations following 14†weeks versus 1.5†years of cyclic strain exercise.

The aging musculoskeletal system experiences a general decline in structure and function, characterized by a reduced adaptability to environmental stress. We investigated whether the older human Achilles tendon (AT) demonstrates mechanosensitivity (via biomechanical and morphological adaptations) in response to long-term mechanical loading. Thirty-four female adults (60-75 years) were allocated to either a medium-term (14 weeks; N=21) high AT strain cyclic loading exercise intervention or a control group (N=13), with 12 participants continuing with the intervention for 1.5 years. AT biomechanical properties were assessed using ultrasonography and dynamometry. Tendon cross-sectional area (CSA) was investigated by means of magnetic resonance imaging. A 22% exercise-related increment in ankle plantarflexion joint moment, along with increased AT stiffness (598.2±141.2 versus 488.4±136.9 N mm-1 at baseline), Young's modulus (1.63±0.46 versus 1.37±0.39 GPa at baseline) and about 6% hypertrophy along the entire free AT were identified after 14 weeks of strength training, with no further improvement after 1.5 years of intervention. The aging AT appears to be capable of increasing its stiffness in response to 14 weeks of mechanical loading exercise by changing both its material and dimensional properties. Continuing exercise seems to maintain, but not cause further adaptive changes in tendons, suggesting that the adaptive time-response relationship of aging tendons subjected to mechanical loading is nonlinear.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Prediction of Early Arterial Blood Flow Stasis in Radioembolization of Breast Cancer Liver Metastases.

PURPOSE: To retrospectively evaluate predictive value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for early arterial blood flow stasis during transarterial radioembolization (TARE) of liver dominant breast metastases (LdBM). MATERIALS AND METHODS: Preinterventional 1.5T DWI (b0, b1, b2 = 0, 50, 800 s/mm(2)) data for 28 liver lobes of 18 female patients treated by resin-based radioembolization (10 bilobar and 8 unilobar treatments) were analyzed. Apparent diffusion coefficient (ADC) (0, 800) and an estimation of the true diffusion coefficient D' and of the perfusion fraction f' were calculated for the 2 largest metastases. Response rate at 3 months and survival were analyzed. Procedures without full dose application because of early stasis were assigned to group A (n = 15), and procedures with full dose application were assigned to group B (n = 13). RESULTS: Metastases in group A showed significantly lower f' (0.035 ± 0.018 vs 0.076 ± 0.015, P < .0001) and a trend toward lower ADC(0, 800) with values given in 10(-6) mm(2)/s (1,066 ± 141 vs 1,189 ± 176, P = .051); no group difference was shown for D'. Groups were best discriminated by weighted mean f' values of the 2 largest metastases with accuracy of 100%. Mean tumor diameter before and after TARE was 51 mm ± 18 and 50 mm ± 24 in group A and 47 mm ± 27 and 48 mm ± 32 for group B. Imaging response did not differ between groups (P = .545). Overall survival did not differ significantly between group A (230 d) and B (155 d) (P = .124). CONCLUSIONS: Perfusion-sensitive IVIM parameter f' may predict early blood flow stasis in patients undergoing TARE for LdBM. Determination of this parameter before intervention may increase awareness of the interventionalist and increase safety of microsphere administration.

Respiratory motion artefacts in dynamic liver MRI: a comparison using gadoxetate disodium and gadobutrol.

OBJECTIVES: Our aim was to retrospectively evaluate the occurrence of respiratory motion artefacts in patients undergoing dynamic liver magnetic resonance (MR) either with gadoxetate disodium or gadobutrol. METHODS: Two hundred and thirty liver MR studies (115 with gadobutrol, 115 with gadoxetate disodium) were analysed. Respiratory motion artefacts on dynamic 3D T1-weighted MR images (pre-contrast, arterial, venous, and late-dynamic phase) were assessed using a five-point rating scale. Severe motion was defined as a score ≥ 4. Mean motion scores were compared with the Mann-Whitney-U-test. The chi-squared-test was used for dichotomous comparisons. RESULTS: Mean motion scores for gadoxetate disodium and gadobutrol showed no relevant differences for each phase of the dynamic contrast series (pre-contrast: 1.85 ± 0.70 vs. 1.88 ± 0.57, arterial: 1.85 ± 0.81 vs. 1.87 ± 0.74, venous: 1.82 ± 0.67 vs. 1.74 ± 0.64, late-dynamic: 1.75 ± 0.62 vs. 1.79 ± 0.63; p = 0.469, 0.557, 0.382 and 0.843, respectively). Severe motion artefacts had a similar incidence using gadoxetate disodium and gadobutrol (11/460 [2.4%] vs. 7/460 [1.5%]; p = 0.341). CONCLUSIONS: Gadoxetate disodium is associated with equivalent motion scores compared to gadobutrol in dynamic liver MRI. In addition, both contrast agents demonstrated a comparable and acceptable rate of severe respiratory motion artefacts. KEY POINTS: • Gadobutrol and gadoxetate disodium showed comparable motion scores in dynamic phase imaging. • The incidence of severe motion artefacts was pronounced in arterial phase imaging. • Adverse respiratory side effects were not recorded in 115 examinations with gadoxetate disodium.

Comparison between modified Dixon MRI techniques, MR spectroscopic relaxometry, and different histologic quantification methods in the assessment of hepatic steatosis.

OBJECTIVES: To compare systematically quantitative MRI, MR spectroscopy (MRS), and different histological methods for liver fat quantification in order to identify possible incongruities. METHODS: Fifty-nine consecutive patients with liver disorders were examined on a 3 T MRI system. Quantitative MRI was performed using a dual- and a six-echo variant of the modified Dixon (mDixon) sequence, calculating proton density fat fraction (PDFF) maps, in addition to single-voxel MRS. Histological fat quantification included estimation of the percentage of hepatocytes containing fat vesicles as well as semi-automatic quantification (qHisto) using tissue quantification software. RESULTS: In 33 of 59 patients, the hepatic fat fraction was >5% as determined by MRS (maximum 45%, mean 17%). Dual-echo mDixon yielded systematically lower PDFF values than six-echo mDixon (mean difference 1.0%; P < 0.001). Six-echo mDixon correlated excellently with MRS, qHisto, and the estimated percentage of hepatocytes containing fat vesicles (R = 0.984, 0.967, 0.941, respectively, all P < 0.001). Mean values obtained by the estimated percentage of hepatocytes containing fat were higher by a factor of 2.5 in comparison to qHisto. Six-echo mDixon and MRS showed the best agreement with values obtained by qHisto. CONCLUSIONS: Six-echo mDixon, MRS, and qHisto provide the most robust and congruent results and are therefore most appropriate for reliable quantification of liver fat. KEY POINTS: • Six-echo mDixon correlates excellently with MRS, qHisto, and the estimated percentage of fat-containing hepatocytes. • Six-echo mDixon, MRS, and qHisto provide the most robust and congruent results. • Dual-echo mDixon yields systematically lower PDFF values than six-echo mDixon. • The percentage of fat-containing hepatocytes is 2.5-fold higher than fat fraction determined by qHisto. • Performance characteristics and systematic differences of the various methods should be considered.

0.125 mm(3) spatial resolution steady-state MR angiography of the thighs with a blood pool contrast agent using the quadrature body coil only at 1.5 Tesla.

PURPOSE: To implement and evaluate high spatial resolution three-dimensional MR contrast-enhanced angiography (3D-CEMRA) of the thighs using a blood pool contrast agent (BPCA) using the quadrature body coil only in patients with peripheral arterial occlusive disease (PAOD) in cases receiver coils cannot be used at 1.5 Tesla (T). MATERIALS AND METHODS: Nineteen patients (mean age: 68.7 ± 11.2 years; range, 38-83 years) with known PAOD (Fontaine stages; III: 16, IV: 3) prospectively underwent 3D-CEMRA at 1.5T with a noninterpolated voxel size of 0.49 × 0.49 × 0.48 mm(3) . Digital subtraction angiography (DSA) was available for comparison in all patients. Two readers independently evaluated movement artifacts, overall image quality of 3D-CEMRA, and grade of stenosis as compared to DSA. SNR and CNR levels were quantified. RESULTS: The 3D-CEMRA was successfully completed in all patients. Patient movement artifacts that affected stenosis grading occurred in 3/38 thighs. Overall image quality was rated excellent in 15/38, good in 12/38, and diagnostic in 8/38 thighs. Stenosis grading matched with that in DSA in 35/38 thighs. High SNR and CNR were measured in all vessels. CONCLUSION: The 0.125 mm(3) spatial resolution 3D-CEMRA of the thighs with a BPCA is feasible using a quadrature body coil exclusively with excellent image quality despite long acquisition times. J. Magn. Reson. Imaging 2014;40:996-1001. © 2014 Wiley Periodicals, Inc.

Diffusion-weighted imaging with acquisition of three b-values for response evaluation of neuroendocrine liver metastases undergoing selective internal radiotherapy.

OBJECTIVES: To evaluate diffusion-weighted MRI with acquisition of three b-values and calculation of fractioned ADCs for response evaluation of neuroendocrine liver metastases undergoing selective internal radiotherapy (SIRT). METHODS: Ten consecutive patients with neuroendocrine liver metastases underwent MRI before and following SIRT. Diffusion-weighted imaging included acquisition of the b-values 0, 50 and 800 s/mm(2) and calculation of ADC(50,800), ADC(0,50) and ADC(0,800) maps. According to therapy response, lesions were categorised into group A [≥20% reduction of the longest diameter (LD) in comparison to baseline MRI] and group B (<20% reduction of the LD). RESULTS: Twelve out of 31 metastases were categorised as group A and 19 out of 31 metastases were categorised as group B. Pretherapeutic values of ADC(0,800) and ADC(50,800) did not differ significantly between the two groups; however, ADC(0,50) was 32% lower in group A (P = 0.049). ADC(0,800) and ADC(50,800) increased significantly after therapy in both groups, however, group differences were not statistically significant. Conversely, the increase in ADC(0,50) was about a factor of 7 larger in group A than in group B (P = 0.023). CONCLUSIONS: Our study showed that the ADC(0,50) is a promising biomarker for response assessment of neuroendocrine liver metastases following SIRT. KEY POINTS: • Diffusion-weighted MRI offers new information about neuroendocrine hepatic metastases. • Evaluation of perfusion and diffusion components requires fractioned apparent diffusion coefficients (ADCs). • Perfusion effects represented by ADC (0.50) can be observed in neuroendocrine metastases. • Pretherapeutic ADC (0.50) was significantly lower in metastases with a response ≥20%. • Such biomarkers may help evaluate liver metastases in patients undergoing therapy.