Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Highly accelerated subtractive femoral non-contrast-enhanced MRA using compressed sensing with k-space subtraction, phase and intensity correction.

PURPOSE: To develop an improved reconstruction method, k-space subtraction with phase and intensity correction (KSPIC), for highly accelerated, subtractive, non-contrast-enhanced MRA. METHODS: The KSPIC method is based on k-space subtraction of complex raw data. It applies a phase-correction procedure to restore the polarity of negative signals caused by subtraction and an intensity-correction procedure to improve background suppression and thereby sparsity. Ten retrospectively undersampled data sets and 10 groups of prospectively undersampled data sets were acquired in 12 healthy volunteers. The performance of KSPIC was compared with another improved reconstruction based on combined magnitude subtraction, as well as with conventional k-space subtraction reconstruction and magnitude subtraction reconstruction, both using quantitative metrics and using subjective quality scoring. RESULTS: In the quantitative evaluation, KSPIC had the best performance in terms of peak SNR, structural similarity index measure, contrast-to-noise ratio of artery-to-background and sharpness, especially at high acceleration factors. The KSPIC method also had the highest subjective scores for all acceleration factors in terms of vessel delineation, image noise and artifact, and background contamination. The acquisition can be accelerated by a factor of 20 without significant decreases of subjective scores. The optimal size of the phase-correction region was found to be 12-20 pixels in this study. CONCLUSION: Compared with combined magnitude subtraction and conventional reconstructions, KSPIC has the best performance in all of the quantitative and qualitative measurements, permitting good image quality to be maintained up to higher accelerations. The KSPIC method has the potential to further reduce the acquisition time of subtractive MRA for clinical examinations.

Subtractive NCE-MRA: Improved background suppression using robust regression-based weighted subtraction.

PURPOSE: To correct the intensity difference of static background signal between bright blood images and dark blood images in subtractive non-contrast-enhanced MR angiography using robust regression, thereby improving static background signal suppression on subtracted angiograms. METHODS: Robust regression (RR), using iteratively reweighted least squares, is used to calculate the regression coefficient of background tissues from a scatter plot showing the voxel intensity of bright blood images versus dark blood images. The weighting function is based on either the Euclidean distance from the estimated regression line or the deviation angle. Results from RR using the deviation angle (RRDA), conventional RR using the Euclidean distance, and ordinary leastsquares regression were compared with reference values determined manually by two observers. Performance was evaluated over studies using different sequences, including 36 thoracic flow-sensitive dephasing data sets, 13 iliac flow-sensitive dephasing data sets, and 26 femoral fresh blood imaging data sets. RESULTS: RR deviation angle achieved robust and accurate performance in all types of images, with small bias, small mean absolute error, and high-correlation coefficients with reference values. Background tissues, such as muscle, veins, and bladder, were suppressed while the vascular signal was preserved. Euclidean distance gave good performance for thoracic and iliac flow-sensitive dephasing, but could not suppress background tissues in femoral fresh blood imaging. Ordinary least squares regression was sensitive to outliers and overestimated regression coefficients in thoracic flow-sensitive dephasing. CONCLUSION: Weighted subtraction using RR was able to acquire the regression coefficients of background signal and improve background suppression of subtractive non-contrast-enhanced MR angiography techniques. RR deviation angle has the most robust and accurate overall performance among three regression methods.

Quantifying normal human brain metabolism using hyperpolarized [1-13C]pyruvate and magnetic resonance imaging.

Hyperpolarized 13C Magnetic Resonance Imaging (13C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1-13C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13C images demonstrated 13C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (kPL) for exchange of the hyperpolarized 13C label between [1-13C]pyruvate and the endogenous lactate pool was 0.012 ±â€¯0.006 s-1 and the apparent rate constant (kPB) for the irreversible flux of [1-13C]pyruvate to [13C]bicarbonate was 0.002 ±â€¯0.002 s-1. Imaging also revealed that [1-13C]pyruvate, [1-13C]lactate and [13C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1-13C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.

Subtractive non-contrast-enhanced MRI of lower limb veins using multiple flow-dependent preparation strategies.

PURPOSE: To evaluate the performance of acceleration-dependent vascular anatomy for non-contrast-enhanced MR venography (ADVANCE-MRV) in femoral veins and to investigate whether venous signal uniformity can be improved by applying multiple acquisitions with different flow suppressions or multiple flow suppressions in 1 acquisition. METHODS: The ADVANCE-MRV method uses flow-sensitized modules to acquire a dark-artery image set and a dark-artery vein set, which are subsequently subtracted. Ten healthy volunteers were imaged using the ADVANCE-MRV sequence with improved venous suppression uniformity in the dark-artery vein images achieved by applying multiple flow suppressions in the same acquisition or by combining multiple images acquired with different flow suppressions. The performance of the improved technique was also evaluated in 13 patients with lower-limb deep venous thrombosis. RESULTS: Multiple-preparation and multiple-acquisition approaches all improved venous signal uniformity and reduced the signal void artifacts observed in the original ADVANCE-MRV images. The multiple-acquisition approaches achieved excellent blood signal uniformity and intensity, albeit at the cost of an increase in the total acquisition time. The double-preparation approach demonstrated good performance in all measurements, providing a good compromise between signal uniformity and acquisition time. The blood signal spatial variation and its variation using different gradient amplitudes were reduced by 20% and 29%. All patient images showed uniform and bright venous signal in nonoccluded sections of vein. CONCLUSION: The enhanced ADVANCE-MRV methods substantially improved signal uniformity in healthy volunteers and patients with known deep venous thrombosis. The double-preparation approach gave good-quality femoral vein images, providing improved venous signal uniformity without increasing acquisition time in comparison to the original sequence.

Gadofosveset-enhanced thoracic MR venography: a comparative study evaluating steady state imaging versus conventional first-pass time-resolved dynamic imaging.

Background Dedicated blood-pool contrast agents combined with optimal angiographic protocols could improve the diagnostic accuracy of thoracic magnetic resonance angiography (MRA). Purpose To assess the clinical utility of Gadofesveset-enhanced imaging and compare an optimized steady-state (SS) sequence against conventional first-pass dynamic multi-phase (DMP) imaging. Material and Methods Twenty-nine patients (17 men, 12 women; mean age = 42.7, age range = 18-72 years) referred for MR thoracic venography were recruited. Imaging was performed on a 1.5T MRI system. A blood-pool contrast agent (Gadofesveset) was administered intravenously. Thirty temporal phases were acquired using DMP. This was immediately followed by a high-resolution SS sequence. Three radiologists in consensus reviewed seven thoracic vascular segments after randomizing the acquisition order. Image quality, stenoses, thromboses, and artifacts were graded using a categorical scoring system. The image quality for both approaches was compared using Wilcoxon's signed-rank test. McNemar's test was used to compare the proportions of stenosis grades, thrombus and artifacts. Results SS had significantly better image quality than DMP (3.14 ± 0.73 and 2.92 ± 0.60, respectively; P < 0.001). SS identified fewer stenoses (>50%) than DMP; the differences in stenosis categorizations was statistically significant ( P = 0.013). There was no significant difference in the proportions of vessels with thromboses ( P = 0.617). DMP produced more artifacts than SS (101 versus 85); however, the difference was not statistically significant ( P = 0.073). Conclusion Gadofesveset-enhanced thoracic angiography is clinically feasible. SS imaging produces better image quality and fewer artifacts than conventional DMP imaging.

Evaluation of velocity-sensitized and acceleration-sensitized NCE-MRA for below-knee peripheral arterial disease.

PURPOSE: To evaluate the diagnostic performance of velocity- and acceleration-sensitized noncontrast-enhanced magnetic resonance angiography (NCE-MRA) of the infrageniculate arteries using contrast-enhanced MRA (CE-MRA) as a reference standard. MATERIALS AND METHODS: Twenty-four patients with symptoms of peripheral arterial disease were recruited. Each patient's infrageniculate arterial tree was examined using a velocity-dependent flow-sensitized dephasing (VEL-FSD) technique, an acceleration-dependent (ACC-FSD) technique, and our conventional CE-MRA technique performed at 1.5T. The images were independently reviewed by two experienced vascular radiologists, who evaluated each vessel segment to assess visibility, diagnostic confidence, venous contamination, and detection of pathology. RESULTS: In all, 432 segments were evaluated by each of the three techniques by each reader in total. Overall diagnostic confidence was rated as moderate or high in 98.5% of segments with CE-MRA, 92.1% with VEL-FSD, and 79.9% with ACC-FSD. No venous contamination was seen in 96% of segments with CE-MRA, 72.2% with VEL-FSD, and 85.8% with ACC-FSD. Per-segment, per-limb, and per-patient sensitivities for detecting significant stenotic disease were 63.4%, 73%, and 92%, respectively, for ACC-FSD, and 65.3%, 87.2%, and 96% for VEL-FSD, and as such no significant statistical change was detected using McNemar's chi-squared test with P-values of 1.00, 0.13, and 0.77 obtained, respectively. CONCLUSION: Flow-dependent NCE-MRA techniques may have a role to play in evaluation of patients with peripheral vascular disease. Increased sensitivity of a velocity-based technique compared to an acceleration-based technique comes at the expense of greater venous contamination. LEVEL OF EVIDENCE: 2J. Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1846-1853.

A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data.

Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge.

PURPOSE: To evaluate the utility of oxygen challenge and report on temporal changes in blood oxygenation level-dependent (BOLD) contrast in normal liver, hepatocellular carcinoma (HCC) and background fibrosis. MATERIALS AND METHODS: Eleven volunteers (nine male and two female, mean age 33.5, range 27-41 years) and 10 patients (nine male and one female, mean age 68.9, range 56-87 years) with hepatocellular carcinoma on a background of diffuse liver disease were recruited. Imaging was performed on a 3T system using a multiphase, multiecho, fast gradient echo sequence. Oxygen was administered via a Hudson mask after 2 minutes of free-breathing. Paired t-tests were performed to determine if the mean pre- and post-O2 differences were statistically significant. RESULTS: In patients with liver fibrosis (n = 8) the change in T2* following O2 administration was elevated (0.88 ± 0.582 msec, range 0.03-1.69 msec) and the difference was significant (P = 0.004). The magnitude of the BOLD response in patients with HCC (n = 10) was larger, however the response was more variable (1.07 ± 1.458 msec, range -0.93-3.26 msec), and the difference was borderline significant (P = 0.046). The BOLD response in the volunteer cohort was not significant (P = 0.121, 0.59 ± 1.162 msec, range -0.81-2.44 msec). CONCLUSION: This work demonstrates that the BOLD response following oxygen challenge within cirrhotic liver is consistent with a breakdown in vascular autoregulatory mechanisms. Similarly, the elevated BOLD response within HCC is consistent with the abnormal capillary vasculature within tumors and the arterialization of the blood supply. Our results suggest that oxygen challenge may prove a viable BOLD contrast mechanism in the liver. J. Magn. Reson. Imaging 2016;44:739-744.

Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled analysis.

OBJECTIVES: We conducted an individual participant data (IPD) pooled analysis on diagnostic accuracy of MRE to detect fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Through a systematic literature search, we identified studies of MRE (at 60-62.5 Hz) for staging fibrosis in patients with NAFLD, using liver biopsy as gold standard, and contacted study authors for IPD. Through pooled analysis, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (≥stage 1), significant (≥stage 2) and advanced (≥stage 3) fibrosis and cirrhosis (stage 4). RESULTS: We included nine studies with 232 patients with NAFLD (mean age, 51 ± 13 years; 37.5% males; mean BMI, 33.5 ± 6.7 kg/m(2); interval between MRE and biopsy <1 year, 98.3%). Fibrosis stage distribution (stage 0/1/2/3/4) was 33.6, 32.3, 10.8, 12.9 and 10.4%, respectively. Mean AUROC (and 95% CIs) for diagnosis of any, significant or advanced fibrosis and cirrhosis was 0.86 (0.82-0.90), 0.87 (0.82-0.93), 0.90 (0.84-0.94) and 0.91 (0.76-0.95), respectively. Similar diagnostic performance was observed in stratified analysis based on sex, obesity and degree of inflammation. CONCLUSIONS: MRE has high diagnostic accuracy for detection of fibrosis in NAFLD, independent of BMI and degree of inflammation. KEY POINTS: • MRE has high diagnostic accuracy for detection of fibrosis in NAFLD. • BMI does not significantly affect accuracy of MRE in NAFLD. • Inflammation had no significant influence on MRE performance in NAFLD for fibrosis.

Diagnostic accuracy of magnetic resonance elastography in liver transplant recipients: A pooled analysis.

BACKGROUND AND AIMS: We conducted an individual participant data (IPD) pooled analysis on the diagnostic accuracy of magnetic resonance elastography (MRE) to detect fibrosis stage in liver transplant recipients. MATERIAL AND METHODS: Through a systematic literature search, we identified studies on diagnostic performance of MRE for staging liver fibrosis, using liver biopsy as gold standard. We contacted study authors for published and unpublished IPD on age, sex, body mass index, liver stiffness, fibrosis stage, degree of inflammation and interval between MRE and biopsy; from these we limited analysis to patients who had undergone liver transplantation. Through pooled analysis using nonparametric two-stage receiver-operating curve (ROC) regression models, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (≥ stage 1), significant (≥ stage 2) and advanced fibrosis (≥ stage 3) and cirrhosis (stage 4). RESULTS: We included 6 cohorts (4 published and 2 unpublished series) reporting on 141 liver transplant recipients (mean age, 57 years; 75.2% male; mean BMI, 27.1 kg/m2). Fibrosis stage distribution stage 0, 1, 2, 3, or 4, was 37.6%, 23.4%, 24.8%, 12% and 2.2%, respectively. Mean AUROC values (and 95% confidence intervals) for diagnosis of any (≥ stage 1), significant (≥ stage 2), or advanced fibrosis (≥ stage 3) and cirrhosis were 0.73 (0.66-0.81), 0.69 (0.62-0.74), 0.83 (0.61-0.88) and 0.96 (0.93-0.98), respectively. Similar diagnostic performance was observed in stratified analysis based on sex, obesity and inflammation grade. CONCLUSIONS: In conclusion, MRE has high diagnostic accuracy for detection of advanced fibrosis and cirrhosis in liver transplant recipients, independent of BMI and degree of inflammation.

Impact of D181V and A69T on the function of ferroportin as an iron export pump and hepcidin receptor.

Mutations in the only known mammalian iron exporter ferroportin cause a rare iron overload disorder termed ferroportin disease. Two distinct clinical phenotypes are caused by different disease mechanisms: mutations in ferroportin either cause loss of iron export function or gain of function due to resistance to hepcidin, the peptide hormone that normally downregulates ferroportin. The aim of the present study was to examine the disease mechanisms of the thus far unclassified A69T and D181V ferroportin mutations. We overexpressed wild-type and mutant ferroportin fused to green fluorescent protein in human embryonic kidney cells and used a (59)Fe-assay, intracellular ferritin concentrations, confocal microscopy and flow cytometry to study iron export function, subcellular localization and the responsiveness to hepcidin. While the A69T ferroportin mutation seems not to affect the iron export function it causes dose-dependent hepcidin resistance. We further found that D181V mutated ferroportin is iron export defective and hepcidin resistant, similar to the loss of function mutations A77D and C367X. This indicates that intact iron export might be necessary for hepcidin-induced downregulation of ferroportin. This hypothesis was investigated by studying the hepcidin response under modulation of iron availability. Incubation of wild-type ferroportin overexpressing cells with holo-transferrin increases the hepcidin effect whereas chelating extracellular ferrous iron causes hepcidin resistance. In this study we present data that postulates to classify the D181V ferroportin mutation as loss of function and the A69T mutation as dose-dependent hepcidin resistant and outline a possible causal link between iron export function and the hepcidin effect.

Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: a systematic review and meta-analysis of individual participant data.

BACKGROUND & AIMS: Magnetic resonance elastography (MRE) is a noninvasive tool for staging liver fibrosis. We conducted a meta-analysis of individual participant data collected from published studies to assess the diagnostic accuracy of MRE for staging liver fibrosis in patients with chronic liver diseases (CLD). METHODS: Through a systematic literature search of multiple databases (2003-2013), we identified studies on diagnostic performance of MRE for staging liver fibrosis in patients with CLD with native anatomy, using liver biopsy as the standard. We contacted study authors to collect data on each participant's age, sex, body mass index (BMI), liver stiffness (measured by MRE), fibrosis stage, staging system used, degree of inflammation, etiology of CLD, and interval between MRE and biopsy. Through a pooled analysis, we calculated cluster-adjusted area under the receiver-operating curve, sensitivity, and specificity of MRE for any fibrosis (≥stage 1), significant fibrosis (≥stage 2), advanced fibrosis (≥stage 3), and cirrhosis (stage 4). RESULTS: We analyzed data from 12 retrospective studies, comprising 697 patients (mean age, 55 ± 13 y; 59.4% male; mean BMI, 26.9 ± 6.7 kg/m(2); 92.1% with <1 year interval between MRE and biopsy; and 47.1% with hepatitis C). Overall, 19.5%, 19.4%, 15.5%, 15.9%, and 29.7% patients had stage 0, 1, 2, 3, and 4 fibrosis, respectively. The mean area under the receiver-operating curve values (and 95% confidence intervals) for the diagnosis of any (≥stage 1), significant (≥stage 2), advanced fibrosis (≥stage 3), and cirrhosis, were as follows: 0.84 (0.76-0.92), 0.88 (0.84-0.91), 0.93 (0.90-0.95), and 0.92 (0.90-0.94), respectively. A similar diagnostic performance was observed in stratified analysis based on sex, obesity, and etiology of CLD. The overall rate of failure of MRE was 4.3%. CONCLUSIONS: Based on a pooled analysis of data from individual participants, MRE has a high accuracy for the diagnosis of significant or advanced fibrosis and cirrhosis, independent of BMI and etiology of CLD. Prospective studies are warranted to better understand the diagnostic performance of MRE.

Reliability of magnetic resonance elastography using multislice two-dimensional spin-echo echo-planar imaging (SE-EPI) and three-dimensional inversion reconstruction for assessing renal stiffness.

BACKGROUND: To evaluate the reliability of MRE using a spin-echo echo-planar imaging (SE-EPI) renal MRE technique in healthy volunteers. METHODS: Institutional review board approved prospective study in which all participants provided written informed consent. Sixteen healthy volunteers comprising seven males and nine females with a median age of 35 years (age range: 23 to 59 years) were included. Coronal 90 Hz and 60 Hz MRE acquisitions were performed twice within a 30-min interval between examinations. Renal MRE reliability was assessed by (i) test-retest repeatability, and (ii) inter-rater agreement between two independent readers. The MRE-measured averaged renal stiffness values were evaluated using: intraclass correlation coefficient (ICC), Bland-Altman and the within-subject coefficient of variation (COV). RESULTS: For test-retest repeatability, Bland-Altman showed a mean stiffness difference between examinations of 0.07 kPa (95% limits of agreement: -1.41, 1.54) at 90 Hz and 0.01 kPa (95% limits of agreement: -0.51, 0.53) at 60 Hz. Coefficient of repeatability was 1.47 kPa and 0.52 kPa at 90 Hz and 60 Hz, respectively. The within-subject COV was 13.6% and 7.7% at 90 Hz and 60 Hz, respectively. ICC values were 0.922 and 0.907 for test-retest repeatability and 0.998 and 0.989 for inter-rater agreement, respectively (P < 0.001). CONCLUSION: SE-EPI renal MRE is a reliable technique.

Magnetic resonance elastography in the detection of hepatorenal syndrome in patients with cirrhosis and ascites.

OBJECTIVE: Hepatorenal syndrome (HRS) is the most lethal cause of renal impairment in cirrhosis. Magnetic resonance elastography (MRE) is a diagnostic test that characterises tissues based on their biomechanical properties. The aim of this study was to assess the feasibility of MRE for detecting HRS in cirrhotic patients. METHODS: A prospective diagnostic investigation was performed. Renal MRE was performed on 21 hospitalised patients with cirrhosis and ascites. Six patients had HRS, one patient had non-HRS renal impairment, and 14 patients had normal renal function. The MRE-measured renal stiffness was compared against the clinical diagnosis as determined by clinical review alongside laboratory and radiologic results. RESULTS: The MRE-measured renal stiffness was significantly lower in patients with HRS (median stiffness of 3.30 kPa at 90 Hz and 2.62 kPa at 60 Hz) compared with patients with normal renal function (median stiffness of 5.08 kPa at 90 Hz and 3.41 kPa at 60 Hz) (P ≤ 0.014). For the detection of HRS, MRE had an area under the receiver operating characteristic curve of 0.94 at 90 Hz and 0.89 at 60 Hz. MRE had excellent inter-rater agreement, as assessed by Bland-Altman and intraclass correlation coefficient (> 0.9). CONCLUSION: MRE shows potential in the detection of HRS. KEY POINTS: • Magnetic resonance elastography (MRE) shows promise in the detection of hepatorenal syndrome. • MRE has the potential to track renal disease in a clinical population. • MRE is a reliable diagnostic test with excellent inter-rater agreement.

Interactive neonatal gastrointestinal magnetic resonance imaging using fruit juice as an oral contrast media.

BACKGROUND: The objective was to evaluate the use of fruit juice with an interactive inversion recovery (IR) MR pulse sequence to visualise the gastrointestinal tract. METHODS: We investigated the relaxation properties of 12 different natural fruit juices in vitro, to identify which could be used as oral contrast. We then describe our initial experience using an interactive MR pulse sequence to allow optimal visualisation after administering pineapple juice orally, and suppressing pre-existing bowel fluid contents, with variable TI in three adult and one child volunteer. RESULTS: Pineapple juice (PJ) had both the shortest T1 (243 ms) and shortest T2 (48 ms) of the fruit juices tested. Optimal signal differentiation between pre-existing bowel contents and oral PJ administration was obtained with TIs of between 900 and 1100 ms. CONCLUSION: The use of an inversion recovery preparation allowed long T1 pre-existing bowel contents to be suppressed whilst the short T1 of fruit juice acts as a positive contrast medium. Pineapple juice could be used as oral contrast agent for neonatal gastrointestinal magnetic resonance imaging.

Latest developments in the imaging of fibrotic liver disease.

According to the World Health Organization, liver cirrhosis accounted for 1.8% of all deaths in Europe, causing about 170,000 deaths per year. Approximately 29 million persons in the EU suffer from chronic liver disease and this trend is on the rise. Liver disease is the EU's fifth most common cause of death accounting for at least one in six deaths. Early detection and monitoring of fibrosis has the potential to direct management of these chronic liver diseases and avert morbidity and mortality. Although the available techniques are in their infancy and the very early stages of fibrosis are difficult to detect, there have been significant advances in imaging over the last decade that has resulted in the use of these new imaging techniques being introduced into the patient pathway. This review explores the accuracies of these imaging techniques, their role in the management of patients, and the potential for the future.

Imaging of vascular complications and their consequences following transplantation in the abdomen.

Transplantation is the surgical treatment of choice for end-stage organ failure. Transplantation procedures performed in the abdomen include liver, renal, pancreas, islet, intestinal, and multivisceral transplantations. Imaging plays a pivotal role in the posttransplantation setting for monitoring the transplant allograft and screening for complications. Knowledge of the surgical techniques employed in abdominal transplantation is essential because it facilitates radiologic understanding and interpretation of the posttransplantation anatomy. This article includes a basic description of the standard surgical techniques performed in the abdomen, with emphasis on the relevant vascular anastomotic reconstructions used. Posttransplantation complications can be broadly classified as vascular or nonvascular in origin. Many of these complications can be accurately depicted and characterized at imaging and dealt with definitively by using interventional radiology techniques, which can be graft- and life-saving and can obviate further complex surgical intervention. The article discusses imaging appearances of vascular complications and their consequences after transplantation in the abdomen. These vascular complications include arterial thrombosis, arterial stenosis, venous thrombosis and stenosis, arteriovenous fistula formation, and pseudoaneurysm formation. The relevant predisposing factors, clinical features, imaging appearances, and potential treatment options for vascular complications of various types of transplantation are presented in a logical and integrated fashion. Knowledge and imaging recognition of the posttransplantation vascular complications discussed in this article will aid radiologists in accurate imaging characterization and thereby facilitate appropriate clinical management and therapy.

Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis.

Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.

Modulation of blood pressure by central melanocortinergic pathways.

BACKGROUND: Weight gain and weight loss are associated with changes in blood pressure through unknown mechanisms. Central melanocortinergic signaling is implicated in the control of energy balance and blood pressure in rodents, but there is no information regarding such an association with blood pressure in humans. METHODS: We assessed blood pressure, heart rate, and urinary catecholamines in overweight or obese subjects with a loss-of-function mutation in MC4R, the gene encoding the melanocortin 4 receptor, and in equally overweight control subjects. We also examined the effects of an MC4R agonist administered for 7 days in 28 overweight or obese volunteers. RESULTS: The prevalence of hypertension was markedly lower in the MC4R-deficient subjects than in the control subjects (24% vs. 53%, P=0.009). After the exclusion of subjects taking antihypertensive medications, blood-pressure levels were significantly lower in MC4R-deficient subjects than in control subjects, with mean (+/-SE) systolic blood pressures of 123+/-14 mm Hg and 131+/-12 mm Hg, respectively (P=0.02), and mean diastolic blood pressures of 73+/-10 mm Hg and 79+/-7 mm Hg, respectively (P=0.03). As compared with control subjects, MC4R-deficient subjects had a lower increase in heart rate on waking (P=0.007), a lower heart rate during euglycemic hyperinsulinemia (P<0.001), and lower 24-hour urinary norepinephrine excretion (P=0.04). The maximum tolerated daily dose of 1.0 mg of the MC4R agonist led to significant increases of 9.3+/-1.9 mm Hg in systolic blood pressure and of 6.6+/-1.1 mm Hg in diastolic blood pressure (P<0.001 for both comparisons) at 24 hours, as compared with placebo. Differences in blood pressure were not explained by changes in insulin levels; there were no significant adverse events. CONCLUSIONS: Results of our genetic and pharmacologic studies implicate melanocortinergic signaling in the control of human blood pressure through an insulin-independent mechanism.