Magnetic Resonance Liver Iron Concentration Can Guide Venesection Decision-Making in Hyperferritinemia.

BACKGROUND: The clinical benefit of venesection in suspected iron overload can be unclear and serum ferritin may overestimate the degree of iron overload. AIMS: To help inform practice, we examined magnetic resonance liver iron concentration (MRLIC) in a cohort investigated for haemochromatosis. METHODS: One hundred and six subjects with suspected haemochromatosis underwent HFE genotyping and MRLIC with time-matched serum ferritin and transferrin saturation values. For those treated with venesection, volume of blood removed was calculated as a measure of iron overload. RESULTS: Forty-seven C282Y homozygotes had median ferritin 937 µg/l and MRLIC 4.83 mg/g; MRLIC was significantly higher vs non-homozygotes for any given ferritin concentration. No significant difference in MRLIC was observed between homozygotes with and without additional risk factors for hyperferritinemia. Thirty-three compound heterozygotes (C282Y/H63D) had median ferritin 767 µg/l and MRLIC 2.58 mg/g; ferritin < 750 µg/l showed 100% specificity for lack of significant iron overload (< 3.2 mg/g). 79% of C282Y/H63D had additional risk factors-mean MRLIC was significantly lower in this sub-group (2.4 mg/g vs 3.23 mg/g). 26 C282Y heterozygous or wild-type had median ferritin 1226 µg/l and MRLIC 2.13 mg/g; 69% with additional risk factors had significantly higher ferritin concentrations (with comparable MRLIC) and ferritin < 1000 µg/l showed 100% specificity for lack of significant iron overload. In 31 patients (26 homozygotes, 5 C282Y/H63D) venesected to ferritin < 100 µg/l, MRLIC and total venesection volume correlated strongly (r = 0.749), unlike MRLIC and serum ferritin. CONCLUSION: MRLIC is an accurate marker of iron overload in haemochromatosis. We propose serum ferritin thresholds in non-homozygotes which, if validated, could tailor cost-effective use of MRLIC in venesection decision-making.

Juvenile haemochromatosis.

Juvenile haemochromatosis is a severe inherited iron-loading disorder that can present in children and adolescents. Typical manifestations include heart failure, endocrine failure (including diabetes and hypogonadism), cirrhosis, and arthropathy. Compared with HFE haemochromatosis, juvenile haemochromatosis affects female and male individuals similarly, presents at a younger age, and causes multiple organ dysfunction; the principle of iron loading into tissues from the gut is shared by both forms, but the process is far more rapid in juvenile haemochromatosis. Juvenile haemochromatosis is initially recognised by extreme increases of serum ferritin and transferrin saturation, which is supported by an MRI showing iron deposition in the heart and liver. MRI software techniques allow quantification of iron in these organs, and can therefore be used to monitor progress. Juvenile haemochromatosis is autosomal recessive and is generally associated with mutations in HJV (type 2A) or HAMP (type 2B). Mutations in TFR2 cause an intermediate severity phenotype (type 3), but this phenotype can cross over into the juvenile haemochromatosis spectrum so it might need to be additionally considered during diagnosis. Treatment needs to be administered without delay, in the form of aggressive iron chelation, and a multidisciplinary approach is essential. Because iron is removed, organ function is restored, which could obviate the need for cardiac or liver transplantation. Substantial restoration of health can ensue, but patients require life-long monitoring. Family screening is an important component of the management of juvenile haemochromatosis. Genetic advances which underpin the haemochromatosis types also clarify the role of iron metabolism in health and disease, particularly the role of hepcidin in regulating iron homoeostasis. Therefore, juvenile haemochromatosis is an important condition to understand; it can present insidiously in children and adolescents, and awareness of the diagnosis is needed to inform early recognition and treatment.

Chronic genotype 1 hepatitis E infection from immunosuppression for ileo-colonic Crohn's disease.

We report a case of a 33-year-old man with a background of longstanding ileo-colonic Crohn's disease and primary sclerosing cholangitis. Following a trip to India he developed diarrhoea which was treated as an exacerbation of Crohn's disease. Liver tests became chronically deranged after increasing immunosuppression, which comprised mercaptopurine, adalimumab and prednisolone. Chronic genotype 1 hepatitis E was diagnosed and successfully treated with reduction of immunosuppression followed by a 24-week course of ribavirin. We believe that this is the first reported case of chronic hepatitis E in genotype 1. Deranged liver tests should prompt testing for hepatitis E infection in the context of immunosuppression for inflammatory bowel disease.

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.

An investigation into the effects of temporal resolution on hepatic dynamic contrast-enhanced MRI in volunteers and in patients with hepatocellular carcinoma.

This study investigated the effect of temporal resolution on the dual-input pharmacokinetic (PK) modelling of dynamic contrast-enhanced MRI (DCE-MRI) data from normal volunteer livers and from patients with hepatocellular carcinoma. Eleven volunteers and five patients were examined at 3 T. Two sections, one optimized for the vascular input functions (VIF) and one for the tissue, were imaged within a single heart-beat (HB) using a saturation-recovery fast gradient echo sequence. The data was analysed using a dual-input single-compartment PK model. The VIFs and/or uptake curves were then temporally sub-sampled (at interval ▵t = [2-20] s) before being subject to the same PK analysis. Statistical comparisons of tumour and normal tissue PK parameter values using a 5% significance level gave rise to the same study results when temporally sub-sampling the VIFs to HB < ▵t <4 s. However, sub-sampling to ▵t > 4 s did adversely affect the statistical comparisons. Temporal sub-sampling of just the liver/tumour tissue uptake curves at ▵t ≤ 20 s, whilst using high temporal resolution VIFs, did not substantially affect PK parameter statistical comparisons. In conclusion, there is no practical advantage to be gained from acquiring very high temporal resolution hepatic DCE-MRI data. Instead the high temporal resolution could be usefully traded for increased spatial resolution or SNR.

Radiology of eating disorders: a pictorial review.

Eating disorders are a major challenge for health professionals, with many patients receiving ineffective care due to underdiagnosis or poor compliance with treatment. The incidence of eating disorders is increasing worldwide, producing an increasing burden on healthcare systems, and they most often affect young patients, with significant long-term complications. The effects of long-term malnutrition manifest in almost every organ system, and many can be detected radiologically, even without overt clinical findings. Musculoskeletal complications including osteoporosis result in a high incidence of insufficiency fractures, with long-term implications for bone health and growth, while respiratory complications are often recognized late due to disordered physiologic responses to infection. Gastrointestinal complications are numerous and in extreme cases may result in fatal outcomes after acute gastric dilatation and rupture subsequent to binge eating. In patients with severely disordered eating, in particular anorexia nervosa, marked derangement of electrolyte levels may result in refeeding syndrome, which requires emergent management. Recognition of such complications is critical to effective patient care and requires radiologists to be aware of the spectrum of imaging abnormalities that may be seen. Since many patients are reluctant to disclose their underlying condition, radiologists also play a critical role in identifying previously undiagnosed eating disorders.

Angiogenesis imaging in neoplasia.

Angiogenesis plays a key role in physiological and pathophysiological processes and is recognized as being essential for tumor growth and metastases. The recent oncological development of anti-angiogenic drugs brings with it a need for angiogenesis quantification and monitoring of response. The nature of these agents means that traditional anatomical methods of assessing morphologic change are outmoded and functional imaging techniques and/or agents are necessary. Herein, we describe the various imaging techniques that can be employed to assess angiogenesis, along with their inherent advantages and disadvantages and discuss the current and future developments in the field.

Association between aneurysm shoulder stress and abdominal aortic aneurysm expansion: a longitudinal follow-up study.

BACKGROUND: Aneurysm expansion rate is an important indicator of the potential risk of abdominal aortic aneurysm (AAA) rupture. Stress within the AAA wall is also thought to be a trigger for its rupture. However, the association between aneurysm wall stresses and expansion of AAA is unclear. METHODS AND RESULTS: Forty-four patients with AAAs were included in this longitudinal follow-up study. They were assessed by serial abdominal ultrasonography and computed tomography scans if a critical size was reached or a rapid expansion occurred. Patient-specific 3-dimensional AAA geometries were reconstructed from the follow-up computed tomography images. Structural analysis was performed to calculate the wall stresses of the AAA models at both baseline and final visit. A nonlinear large-strain finite element method was used to compute the wall-stress distribution. The relationship between wall stresses and expansion rate was investigated. Slowly and rapidly expanding aneurysms had comparable baseline maximum diameters (median, 4.35 cm [interquartile range, 4.12 to 5.0 cm] versus 4.6 cm [interquartile range, 4.2 to 5.0 cm]; P=0.32). Rapidly expanding AAAs had significantly higher shoulder stresses than slowly expanding AAAs (median, 300 kPa [interquartile range, 280 to 320 kPa] versus 225 kPa [interquartile range, 211 to 249 kPa]; P=0.0001). A good correlation between shoulder stress at baseline and expansion rate was found (r=0.71; P=0.0001). CONCLUSION: A higher shoulder stress was found to have an association with a rapidly expanding AAA. Therefore, it may be useful for estimating the expansion of AAAs and improve risk stratification of patients with AAAs.

Diffusion-weighted magnetic resonance imaging for the detection of lipid-rich necrotic core in carotid atheroma in vivo.

INTRODUCTION: Research has shown that knowing the morphology of carotid atheroma improves current risk stratification for predicting subsequent thrombo-embolic events. Previous magnetic resonance (MR) ex vivo studies have shown that diffusion-weighted imaging (DWI) can detect lipid-rich necrotic core (LR/NC) and fibrous cap. This study aims to establish if this is achievable in vivo. METHODS: Twenty-six patients (mean age 73 years, range 54-87 years) with moderate to severe carotid stenosis confirmed on ultrasound were imaged. An echo-planar DWI sequence was performed along with standard high-resolution MR imaging. Apparent diffusion coefficient (ADC) maps were evaluated. Two independent readers reported the mean ADC values from regions of interest defining LR/NCs and fibrous caps. For subjects undergoing carotid endarterectomy (n = 19), carotid specimens were obtained and stained using Nile red. RESULTS: The mean ADC values were 1.0 × 10(-3) mm(2)/s (±SD 0.3 × 10(-3) mm(2)/s) and 0.7 × 10(-3) mm(2)/s (±SD 0.2 × 10(-3) mm(2)/s) for fibrous cap and LR/NC, respectively; the difference was significant (p < 0.0001). The intra-class correlation coefficients summarising the agreement between the two independent readers were 0.84 and 0.60 for fibrous cap and LR/NC, respectively. Comparison of quantitative ADC values and histology (by subjective grading of lipid content) showed a significant correlation: heavier lipid staining matched lower ADC values (r = -0.435, p = 0.005). CONCLUSIONS: This study indicates that DWI can be used to distinguish LR/NC and the fibrous cap. The study also suggests that the mean ADC value may be linearly related to subjective graded LR/NC content determined by histology.

Cost-effectiveness analysis of endovascular versus open surgical repair of acute abdominal aortic aneurysms based on worldwide experience.

PURPOSE: To present an economic evaluation of endovascular versus open surgical repair of ruptured abdominal aortic aneurysms (AAA). METHODS: Endovascular aneurysm repair (EVAR) is currently being appraised by the National Institute for Clinical Excellence. To aid in this appraisal, a health economic model developed to demonstrate the cost-effectiveness of EVAR for elective treatment of non-ruptured AAAs versus OSR was used for an analysis in the emergency setting. The base case data on 730 patients undergoing EVAR was extracted from our recently published 22-study meta-analysis of 7040 patients presenting with acute AAA (ruptured or symptomatic) treated with either emergency EVAR or OSR. These data reflected a patient population with an average age of 70 years. The base case model, which assumed a time horizon of 30 years and applied all-cause mortality rates, was subjected to a number of 1-way sensitivity analyses. A multivariate analysis was undertaken using 10,000 Monte-Carlo simulations. RESULTS: EVAR dominated OSR in the base case analysis, with a mean cumulative cost/patient of pound17,422 ($26,133) for EVAR and pound18,930 ($28,395) for OSR [- pound1508 ($2262) difference]. The mean quality-adjusted life years (QALYs)/patient was 3.09 for EVAR versus 2.49 for OSR (0.64 difference). EVAR was cost-effective compared with OSR at a threshold value of pound20,000 to pound30,000 ($30,000-$45,000)/QALY. In no single combination tested did open surgical repair provide the patient with more QALYs than EVAR. Sensitivity analyses demonstrated that the results were most sensitive to length of hospital and intensive care stays, use of blood products, and the cost of the evar device, which were the main cost drivers. CONCLUSION: While the UK's National Institute for Clinical Excellence does not set an absolute limit at which treatments would not be funded, pound30,000 ($45,000) is generally regarded as the upper limit of acceptability. At this level, there is almost a 100% probability that EVAR is a cost-effective treatment for ruptured AAA.

Utility of high resolution MR imaging to assess carotid plaque morphology: a comparison of acute symptomatic, recently symptomatic and asymptomatic patients with carotid artery disease.

OBJECTIVES: Compare carotid plaque morphology of acute symptomatic, recently symptomatic and asymptomatic patients (groups 1, 2 and 3 respectively) with carotid artery disease using high resolution magnetic resonance imaging (MRI), to identify high-risk plaque characteristics best associated with risk of recurrent thrombo-embolic events. METHODS: 60 patients underwent multi-contrast imaging of their internal carotid arteries. Different plaque components were manually delineated on acquired axial images to assess the difference in prevalence of plaque hemorrhage, fibrous cap (FC) rupture and FC thickness among the three groups. RESULTS: 55% acute symptomatic patients had plaque hemorrhage vs. 35% for recently symptomatic group and 5% for asymptomatic group (p-value: group 1 vs. 3: 0.001, group 2 vs. 3: 0.04). Type 1 hemorrhage was more common in acute symptomatic patients than recently symptomatic patients (40% vs. 5%, p=0.01). Type 2 hemorrhage was more common in recently symptomatic vs. acute symptomatic patients (15% vs. 30%). FC rupture was observed in 50% of patients in group 1 vs. 35% of group 2 patients (p=0.02) but none in group 3. The mean minimum FC thickness was same in acute and recently symptomatic groups (600+/-200microm), compared to 800+/-200microm for asymptomatic patients (p-value: 0.03 and 0.007 respectively). Good correlation was present among the three MR readers (intra-class correlation coefficient=0.71). CONCLUSION: High resolution MRI can differentiate plaque components associated with increased risk of thrombo-embolic events.

Mycotic pseudoaneurysm of the superficial femoral artery in a patient with Cushing disease: case report and literature review.

Mycotic pseudoaneurysms of the peripheral arteries are rare and can occur as an extension of localized infection or from systemic sepsis. In some cases, no obvious source of infection may be identified. Both endovascular and open surgical management options are available for this important condition. We report a mycotic pseudoaneurysm of the superficial femoral artery in a patient associated with systemic immunosuppression secondary to Cushing disease that was successfully managed with open surgical repair and autologous bypass grafting. This unusual case highlights the potential for serious adverse cardiovascular sequelae of Cushing disease and the need for awareness of such complications in this patient group.