Dynamic Liver Magnetic Resonance Imaging During Free Breathing: A Feasibility Study With a Motion Compensated Variable Density Radial Acquisition and a Viewsharing High-Pass Filtering Reconstruction.

OBJECTIVE: Robust dynamic contrast-enhanced T1-weighted images are crucial for accurate detection and categorization of focal liver lesions in liver/abdominal magnetic resonance imaging (MRI). As optimal dynamic imaging usually requires multiple breath-holds, its inherent susceptibility to motion artifacts frequently results in degraded image quality in incompliant patients. Because free-breathing imaging may overcome this drawback, the intention of this study was to evaluate a dynamic MRI sequence acquired during free breathing using the variable density, elliptical centric golden angle radial stack-of-stars radial sampling scheme, which so far has not been implemented in 4-dimensional applications. MATERIALS AND METHODS: In a prospective pilot study, 27 patients received a routine abdominal MRI protocol including the prototype free-breathing sequence (4DFreeBreathing) for dynamic imaging. This enables more convenient and faster reconstruction through variable density, elliptical centric golden angle radial stack-of-stars without the use of additional reconstruction hardware, and even higher motion robustness through soft-gating. A standard breath-hold sequence performed subsequently served as reference standard. Of the continuous dynamic data sets, each dynamic phase was analyzed regarding image quality, motion artifacts and vessel conspicuity using 5-point Likert scales. Furthermore, correct timing of the late arterial phase was compared with the preexaminations. RESULTS: 4DFreeBreathing delivered motion-free dynamic images with high temporal resolution in each subject. Overall image quality scores were rated good or excellent for 4DFreeBreathing and the gold standard without significant differences (P = 0.34). There were significantly less motion artifacts in the 4DFreeBreathing sequence (P < 0.0001), whereas vessel conspicuity in each dynamic phase was comparable for both groups (P = 0.45, P > 0.99, P = 0.22, respectively). Correct timing of the late arterial phase could be achieved in 27 of 27 (100%) examinations using 4DFreeBreathing versus 35 of 53 (66%) preexaminations using gold standard (P < 0.001). CONCLUSION: The benefit of convenient and fast image reconstruction combined with the superiority in motion robustness and timing compared with standard breath hold sequences renders 4DFreeBreathing an attractive alternative to existing free-breathing techniques in dynamic liver MRI.

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.

Talimogene Laherparepvec in Advanced Mucosal Melanoma of the Urethra Upon Primary Resistance on Immune Checkpoint Inhibition: A Case Report.

Background: Mucosal melanomas including melanomas of the urogenital tract represent a rare type of melanoma characterized by low mutational burden and poor prognosis. Immune checkpoint inhibition has so far only been assessed in a limited number of mucosal melanoma patients and, in contrast to response in cutaneous melanoma, was associated with disappointing response rates. The oncolytic viral immunotherapy Talimogene laherparepvec (T-VEC) has recently been approved for treatment of locally advanced or unresectable melanoma. T-VEC combines direct oncolytic effects with local and systemic immune-mediated anti-tumor response. Our rationale to use T-VEC in this case was an expected augmentation of immunogenicity by tumor lysis to overcome primary resistance of a mucosal melanoma to immune checkpoint blockade. Objective: To report the first case of an advanced mucosal melanoma of the urethra treated with intralesional application of Talimogene laherparepvec. Case Report: A 78-years old female patient was diagnosed with an advanced mucosal melanoma of the urethra with inguinal lymph node metastases and intravaginal mucosal metastases. Shortly after surgical resection of the tumor mass, intravaginal mucosal metastases, and new nodal metastases in proximity of the left iliac vessels were diagnosed. The patient was treated with the anti-PD1 antibody pembrolizumab and obtained a stable disease lasting for 30 weeks. However, upon checkpoint inhibition the patient developed a loco-regional progressive disease featuring bleeding intravaginal metastases, while nodal metastases remained stable. We stopped treatment with pembrolizumab and administered T-VEC directly into the intravaginal mucosal metastases. After five injections T-VEC yielded a partial response with clinical regression of the injected mucosal metastases. Disease remained stable for 16 weeks under biweekly T-VEC treatment. Thereafter the patient showed disease progression in nodal metastases. T-VEC was discontinued. Immunotherapy with pembrolizumab was restarted but failed to achieve a response. Finally, targeted therapy with imatinib was induced in presence of a druggable c-KIT mutation, leading to a considerable response of all tumor sites that is still ongoing. Conclusion: T-VEC represents an effective and well-tolerated treatment option for patients with loco-regionally advanced mucosal melanoma. In combination with immunotherapy, T-VEC bears the potential of synergistic effects to overcome the specific primary resistance of mucosal melanoma to immune checkpoint blockade.

Quantification of liver fibrosis: extracellular volume fraction using an MRI bolus-only technique in a rat animal model.

BACKGROUND: To determine the utility of single-contrast-bolus hepatic extracellular volume (ECV) fraction measurement at different time points to detect and quantify hepatic fibrosis. METHODS: Different grades of liver fibrosis were induced in 23 male Sprague-Dawley rats by carbon-tetrachloride (CCl4) intoxication. In ten control rats, no fibrosis was induced. Native T1 values and ECV fraction were assessed by using quantitative magnetic resonance imaging (MRI) mapping; only one contrast bolus was applied (gadobutrol 0.1 mmol/kg). ECV values were determined 5, 15, and 25 min after injection. Hepatic fibrosis was quantified histologically by Sirius red staining. RESULTS: For the 8-week-CCl4 group, the ECV fraction values obtained 5 (23.5 ± 4.8%, mean ± standard deviation), 15 (23.6 ± 4.8%), and 25 min (23.7 ± 4.7%) after injection were constant over time (p = 0.998); constant data 5-25 min after injection were also observed for the 16-week-CCl4 group and controls. Liver ECV after 15 min significantly increased with the severity of fibrosis: 18.0 ± 3.0% (controls) versus 23.6 ± 4.8% (8-week-CCl4) versus 30.5 ± 3.3% (16-week-CCl4) (p <  0.001). ECV values after 5, 15, and 25 min significantly correlated with Sirius red staining (p <  0.001 for all parameters). CONCLUSIONS: Hepatic ECV obtained using a single-contrast-bolus technique can be measured 5, 15, and 25 min after injection, obtaining constant values over time, each of them being suitable to detect diffuse hepatic fibrosis. In clinical practice, post-contrast T1 relaxation times for liver ECV fraction determination might be obtained at only one time point.

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.

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.

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.

Intravoxel incoherent motion model-based analysis of diffusion-weighted magnetic resonance imaging with 3 b-values for response assessment in locoregional therapy of hepatocellular carcinoma.

PURPOSE: The aim of this study was to evaluate an intravoxel incoherent motion (IVIM) model-based analysis of diffusion-weighted imaging (DWI) for assessing the response of hepatocellular carcinoma (HCC) to locoregional therapy. PATIENTS AND METHODS: Respiratory-gated DWI (b=0, 50, and 800 s/mm2) was retrospectively analyzed in 25 patients who underwent magnetic resonance imaging at 1.5 T before and 6 weeks following the first cycle of transarterial chemoembolization therapy, transarterial ethanol-lipiodol embolization therapy, and transarterial radioembolization therapy. In addition to the determination of apparent diffusion coefficient, ADC(0,800), an estimation of the diffusion coefficient, D', and the perfusion fraction, f', was performed by using a simplified IVIM approach. Parameters were analyzed voxel-wise. Tumor response was assessed in a central slice by using a region of interest (ROI) covering the whole tumor. HCCs were categorized into two groups, responders and nonresponders, according to tumor size changes on first and second follow ups (if available) and changes of contrast-enhanced region on the first follow up. RESULTS: In total, 31 HCCs were analyzed: 17 lesions were assigned to responders and 14 were to nonresponders. In responders, ADC(0,800) and D' were increased after therapy by ~30% (P=0.00004) and ~42% (P=0.00001), respectively, whereas f' was decreased by ~37% (P=0.00094). No significant changes were found in nonresponders. Responders and nonresponders were better differentiated by changes in D' than by changes in ADC(0,800) (area under the curve =0.878 vs 0.819 or 0.714, respectively). CONCLUSION: In patients with HCCs undergoing embolization therapy, diffusion changes were better reflected by D' than by conventional ADC(0,800), which is influenced by counteracting perfusion changes as assessed by f'.

Evaluation of a Simplified Intravoxel Incoherent Motion (IVIM) Analysis of Diffusion-Weighted Imaging for Prediction of Tumor Size Changes and Imaging Response in Breast Cancer Liver Metastases Undergoing Radioembolization: A Retrospective Single Center Analysis.

To investigate the value of a simplified intravoxel incoherent motion (IVIM) analysis for evaluation of therapy-induced tumor changes and response of breast cancer liver metastases (mBRC) undergoing radioembolization.In 21 females (mean age 54 years, range 43-72) with mBRC tumor size changes and response evaluation criteria in solid tumors (RECIST) response to 26 primary radioembolization procedures were analyzed. Standard 1.5-T liver magnetic resonance imaging including respiratory-gated diffusion-weighted imaging (DWI) with b0 = 0 s/mm, b1 = 50 s/mm, b2 = 800 s/mm before and 6 weeks after each treatment was performed. In addition to the apparent diffusion coefficient (ADC)(0,800), the estimated diffusion coefficient D' and the perfusion fraction f' were determined using a simplified IVIM approach. For each radioembolization, the 2 largest treated metastases (if available) were analyzed. Lesions were categorized according to size changes into group A (reduction of longest diameter [LD]) and group B (LD increase) after 3 months. Radioembolization procedures were further categorized into "response" (partial response and stable disease) and "nonresponse" (progressive disease) according to RECIST after 3 months. ADC and D' are given in 10 mm/s.Forty-five metastases were analyzed. Thirty-two lesions were categorized as A; 13 as B. Before therapy, group A lesions showed significantly larger f'-values than B (P = 0.001), but ADC(0,800) and D' did not differ. After therapy, in group A lesions the ADC(0,800)- and D'-values increased and f' decreased (P < 0.0001); in contrast in group B lesions f' increased (P = 0.001). Groups could be differentiated by preinterventional f' and by changes of D' and f' between pre and postinterventional imaging (area under the curve [AUC] of 0.903, 0.747 and 1.0, respectively).Preinterventional parameters did not differ between responders and nonresponders according to RECIST. ADC(0,800)- and D'-values showed a larger increase in responders compared with nonresponders (P = 0.013 and P = 0.001, respectively). After therapy f'-values decreased significantly in responders (P = 0.001). Good to excellent prediction of long-term RECIST response was possible by therapy-induced changes in LD, D', and f' (AUC 0.903, 0.879, and 0.867, respectively).A simplified IVIM model-based analysis of early post-treatment DWI can deliver additional information on tumor size changes and long-term RECIST response after radioembolization of mBRC. The estimated perfusion fraction f' is better suited for response assessment than the conventional ADC(0,800) or D'. This can be useful to guide further treatment strategy.

Abdominal vasculature in dynamic contrast-enhanced liver MRI at 3.0T: an intraindividual comparative study using gadoxetate disodium and gadofosveset trisodium.

OBJECTIVES: To intraindividually compare gadoxetate disodium and gadofosveset trisodium regarding vessel contrast, image quality and vessel delineation in dynamic contrast-enhanced liver MRI at 3.0T. METHODS: Twelve patients underwent 3.0T MRI twice (24 examinations) with a single dose of gadoxetate disodium and gadofosveset trisodium, respectively. Signal intensity in abdominal vessels and tissue was determined. Vessel-to-background ratio (VBR) was calculated for each vessel and dynamic phase. All images were evaluated by two radiologists regarding image quality, vessel delineation and anatomic variants or pathologies with digital subtraction angiography as the standard of reference. RESULTS: Gadofosveset trisodium demonstrated a significantly higher VBR compared to gadoxetate disodium (arterial phase: 0.57±0.12 [SD] vs. 0.46±0.19; portal venous phase: 0.51±0.11 vs. 0.37±0.14; equilibrium phase: 0.48±0.10 vs. 0.31±0.13; p≤0.01). Image quality and vessel delineation were rated equal or better for gadofosveset trisodium in all cases. These differences were not significant for most vessel segments. All anatomic variants were correctly identified by both readers for both contrast agents. CONCLUSIONS: Although gadofosveset trisodium provides a significantly higher vessel contrast at 3.0T, gadoxetate disodium is equivalent by qualitative measurements. Thus, gadoxetate-enhanced liver MRI at 3.0T enables reliable assessment of the upper abdominal vasculature with the additional benefit of hepatobiliary imaging.

Dixon-based fat-free MR-angiography compared to first pass and steady-state high-resolution MR-angiography using a blood pool contrast agent.

INTRODUCTION: Compared to standard arterial-only first-pass MR-angiography (FPMRA), imaging during the equilibrium phase of a blood pool contrast agent (steady state) has been shown to provide higher image quality and better stenosis grading. Homogenous Dixon fat-suppression promises to increase contrast by suppression of fat adjacent to vessels. This study was performed to compare diagnostic image quality and vessel-to-background contrasts in equilibrium phase Dixon-based fat-free MRA (DFSMRA) of run-off vessels to FPMRA imaging and equilibrium phase T1-weighted non-fat-suppressed ultra-high resolution MRA (SSMRA). MATERIAL AND METHODS: In a prospective, intra-individual comparative study, 17 patients with known or suspected peripheral arterial occlusive disease (PAOD; 11 men, mean age 65.6±18.1 [23-89] years) received FPMRA, DFSMRA, and SSMRA at 1.5 Tesla using a clinical whole body MRI scanner. All sequences were performed within the same session applying a single dose of a blood pool contrast agent (gadofosveset trisodium) that was injected during acquisition of FPMRA. The diagnostic image quality of the run-off vessels was evaluated on a 3-point scale. Quantitative analysis consisted of contrast-ratio (CR) measurements of vascular lumen signals compared to signals of adjacent muscle and fat. RESULTS: The average image quality of vessel visualization was rated highest in SSMRA (mean 1.34±0.41), followed by standard FPMRA (mean 1.15±0.33) and DFSMRA (mean 0.99±0.61). Image quality was rated similarly high in the thighs and pelvic region, whereas small vessels in the lower legs and in the feet were best visualized by SSMRA. CR of vascular lumen compared to adjacent fatty tissue was 2.7 times higher in DFSMRA compared to SSMRA, whereas CR of vascular lumen to muscle was 1.3 times higher in SSMRA. CONCLUSION: Vessel to fat contrast is strongly increased in DFSMRA compared to T1-weighted ultra-high resolution non-fat suppressed SSMRA, whereas vessel to muscle contrast is decreased in DFSMRA. Given the current technical limitations of DFSMRA, possible benefits are outweighed by advantages of first-pass imaging regarding arterial selectivity as well as advantages of SSMRA with respect to spatial resolution.

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.

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.

Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation.

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of diseases presenting with movement disorders and brain iron deposits. In addition to NBIA subtypes caused by mutations in PANK2 and PLA2G6, mutations in the C19orf12 gene were recently described as the third frequent cause of NBIA (called mitochondrial membrane protein-associated neurodegeneration, MPAN). Additionally, the X-linked gene WDR45 was found causative for a special subtype named static encephalopathy in childhood with neurodegeneration in adulthood (also called BPAN); however, analysis of this gene in a broader spectrum of NBIA has not been reported yet. METHODS: In a heterogeneous cohort of 69 patients with suspected NBIA that did not carry mutations in PANK2 and PLA2G6, the coding region of C19orf12 was evaluated by Sanger sequencing. The WDR45 gene was analyzed via high resolution melting and subsequent sequence analysis. RESULTS: Previously described homozygous C19orf12 mutations were found in 3/69 NBIA patients (4.3%). Analysis of the WDR45 gene revealed a novel heterozygous missense mutation in one female NBIA patient showing psychomotor retardation with secondary decline. CONCLUSIONS: C19orf12 mutations were confirmed in our heterogeneous NBIA cohort, while WDR45 mutations appear to be restricted to the subtype showing encephalopathy in childhood with neurodegeneration in adulthood.

Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests.

OBJECTIVES: To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. METHODS: Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. RESULTS: Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). CONCLUSIONS: Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. KEY POINTS: • Relative enhancement (RLE) of Gd-EOB-DTPA is related to biochemical liver function tests. • Correlation of RLE with bilirubin, ALT, AST, GGT, INR and MELD Score is reverse. • The correlation of relative liver enhancement with prothrombin time is positive. • AST, ALT, GLDH, prothrombin time, INR and MELD Score correlate with pre-contrast liver-spleen contrast ratio. • Such biomarkers may help to evaluate liver function.

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.

Simultaneous MR arteriography and venography with blood pool contrast agent detects deep venous thrombosis in suspected arterial disease.

OBJECTIVE: The purpose of this study was to investigate the prevalence of incidental deep venous thrombosis (DVT) in patients with clinically suspected peripheral arterial occlusive disease (PAOD) using contrast-enhanced MR angiography (MRA) with a blood pool contrast agent. SUBJECTS AND METHODS: Two hundred fifty-nine MRA examinations with blood pool contrast agent in 245 consecutive patients (161 men; age range, 36-92 years), yielding a total of 4102 assessable arterial and venous vessel segments, were assessed with regard to the rate of incidentally observed acute and organized DVT and arterial stenosis grades. Incidental DVT was confirmed using duplex ultrasound. Contralateral nondiseased veins served as internal controls. The relationship between PAOD stages and acute and organized DVT was investigated using chi-square tests and a Mann-Whitney U test. RESULTS: Arterial stenosis grading using MRA with blood pool contrast agent revealed less than 50% luminal stenosis in 78% of segments (3199/4102), 50% or greater stenosis in 8% of segments (317/4102), and occlusion in 14% of segments (586/4102). Incidental DVT was observed in 26 of 245 patients (11%) (acute DVT was seen in 10 patients and 26 segments; organized DVT was seen in 17 patients and 35 segments; and one patient had both acute and organized DVT). All incidentally diagnosed cases of DVT were confirmed by duplex ultrasound. Internal controls revealed no false-positive or -negative findings (26 patients and 172 segments). Incidental acute DVT was significantly more common among patients without arterial stenosis greater than 50% (p < 0.05). Otherwise, there was no significant relationship between Fontaine PAOD stages and the occurrence of acute (p = 0.688) or organized (p = 0.995) DVT. CONCLUSION: Incidental DVT was prevalent in 11% of patients with clinically suspected PAOD. MRA with blood pool contrast agent has a potential role in the simultaneous assessment of arteries and veins and can detect concomitant venous disease affecting therapeutic management.