Future imaging modalities for the assessment of pancreas allografts a scan of the horizon.

Pancreas transplantation (PT) allows improved glycaemic control for patients with complicated type 1 diabetes mellitus and is most commonly performed simultaneously with a renal transplant. Imaging modalities are critical for the assessment of pancreatic graft dysfunction, as clinical assessment and hyperglycaemia lack robust sensitivity for the transplant clinician. Biopsy represents the most conclusive standard of PT graft assessment but is challenging due to its invasive nature and the potential morbidity associated with the procedure. Innovative imaging technologies offer the opportunity to apply these modalities to improve PT outcomes while using non-invasive technologies to provide a diagnostic sensitivity that traditionally only biopsies can provide. Early graft dysfunction has traditionally been investigated with Computed tomography (CT) and ultrasound (US) scans. We explore adjuncts to these modalities including the application of contrast enhanced ultrasound (CEUS) for routine post-operative graft assessment to inform post-operative treatment strategies. There is currently a dearth of imaging modalities to reliably monitor long term graft function, but the use of innovative functional imaging techniques and how they can be applied to PT is discussed. Perfusion CT and glucose stimulated magnetic resonance imaging (MRI) to detect whole organ function are examined. In addition, early phase developments in beta-cell specific imaging methods to quantify beta-cell mass longitudinally are described. The clinical applications of such tools including Mn2+-enhanced MR and GLP-1R targeted PET/CT are reviewed and may demonstrate opportunities to provide the transplant clinician with greater information to support improved patient care.

OVERVIEW OF NEUTRON MEASUREMENTS IN JET FUSION DEVICE.

The design and operation of ITER experimental fusion reactor requires the development of neutron measurement techniques and numerical tools to derive the fusion power and the radiation field in the device and in the surrounding areas. Nuclear analyses provide essential input to the conceptual design, optimisation, engineering and safety case in ITER and power plant studies. The required radiation transport calculations are extremely challenging because of the large physical extent of the reactor plant, the complexity of the geometry, and the combination of deep penetration and streaming paths. This article reports the experimental activities which are carried-out at JET to validate the neutronics measurements methods and numerical tools used in ITER and power plant design. A new deuterium-tritium campaign is proposed in 2019 at JET: the unique 14 MeV neutron yields produced will be exploited as much as possible to validate measurement techniques, codes, procedures and data currently used in ITER design thus reducing the related uncertainties and the associated risks in the machine operation.

Absence of PO2 change in fetal brain despite PO2 increase in placenta in response to maternal oxygen challenge.

OBJECTIVE: Magnetic resonance imaging allows the noninvasive observation of PO2 changes between air breathing and oxygen breathing through quantification of the magnetic longitudinal relaxation time T1. Changes in PO2 are proportional to changes in the longitudinal relaxation rate ΔR1 (where ΔR1=1/T1oxygen-1/T1air). Knowledge of this response could inform clinical interventions using maternal oxygen administration antenatally to treat fetal growth restriction. We present in vivo measurements of the response of the fetal-placental unit to maternal hyperoxia. DESIGN: Prospective cohort. SETTING: Large tertiary maternity hospital. SAMPLE: Nine women undergoing low-risk pregnancy (21-33 weeks of gestation) and five nonpregnant adults. METHODS: During imaging the air supply to mothers was changed from medical air (21% oxygen) to medical oxygen (100% oxygen) and T1 was monitored over time in both the placenta and fetal brain using a periodically repeated magnetic resonance imaging sequence. To demonstrate that the method could detect a brain response, brain responses from five normal adult volunteers were measured using a similar imaging protocol. MAIN OUTCOME MEASURE: Changes in T1 following oxygen challenge. RESULTS: No significant ΔR1 (P=0.42, paired t-test) was observed in fetal brains. A significant placental ΔR1 (P=0.0002, paired t-test) of 0.02±0.01/s (mean±SD) was simultaneously observed in the same participants. In the brains of the nonpregnant adults, a significant ΔR1 (P=0.01, paired t-test) of 0.005±0.002/s was observed. CONCLUSION: Short-term maternal oxygen administration does not improve fetal brain oxygenation, in contrast to the response observed in the adult brain.

Mutual information as a measure of image quality for 3D dynamic lung imaging with EIT.

We report on a pilot study of dynamic lung electrical impedance tomography (EIT) at the University of Manchester. Low-noise EIT data at 100 frames per second were obtained from healthy male subjects during controlled breathing, followed by magnetic resonance imaging (MRI) subsequently used for spatial validation of the EIT reconstruction. The torso surface in the MR image and electrode positions obtained using MRI fiducial markers informed the construction of a 3D finite element model extruded along the caudal-distal axis of the subject. Small changes in the boundary that occur during respiration were accounted for by incorporating the sensitivity with respect to boundary shape into a robust temporal difference reconstruction algorithm. EIT and MRI images were co-registered using the open source medical imaging software, 3D Slicer. A quantitative comparison of quality of different EIT reconstructions was achieved through calculation of the mutual information with a lung-segmented MR image. EIT reconstructions using a linear shape correction algorithm reduced boundary image artefacts, yielding better contrast of the lungs, and had 10% greater mutual information compared with a standard linear EIT reconstruction.

Comparison of dynamic contrast-enhanced MRI and dynamic contrast-enhanced CT biomarkers in bladder cancer.

Dynamic contrast-enhanced MRI (DCE-MRI) is frequently used to provide response biomarkers in clinical trials of novel cancer therapeutics but assessment of their physiological accuracy is difficult. DCE-CT provides an independent probe of similar pharmacokinetic processes and may be modeled in the same way as DCE-MRI to provide purportedly equivalent physiological parameters. In this study, DCE-MRI and DCE-CT were directly compared in subjects with primary bladder cancer to assess the degree to which the model parameters report modeled physiology rather than artefacts of the measurement technique and to determine the interchangeability of the techniques in a clinical trial setting. The biomarker K(trans) obtained by fitting an extended version of the Kety model voxelwise to both DCE-MRI and DCE-CT data was in excellent agreement (mean across subjects was 0.085 ± 0.030 min(-1) for DCE-MRI and 0.087 ± 0.033 min(-1) for DCE-CT, intermodality coefficient of variation 9%). The parameter v(p) derived from DCE-CT was significantly greater than that derived from DCE-MRI (0.018 ± 0.006 compared to 0.009 ± 0.008, P = 0.0007) and v(e) was in reasonable agreement only for low values. The study provides evidence that the biomarker K(trans) is a robust parameter indicative of the underlying physiology and relatively independent of the method of measurement.

Multiple-bolus dynamic contrast-enhanced MRI in the pancreas during a glucose challenge.

PURPOSE: To assess the feasibility of multiple-bolus dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the pancreas; to optimize the analysis; and to investigate application of the method to a glucose challenge in type 2 diabetes. MATERIALS AND METHODS: A 4-bolus DCE-MRI protocol was performed on five patients with type 2 diabetes and 11 healthy volunteers during free-breathing. Motion during the dynamic time series was corrected for using a model-driven nonlinear registration. A glucose challenge was administered intravenously between the first and second DCE-MRI acquisition in all patients and in seven of the healthy controls. RESULTS: Image registration improved the reproducibility of the DCE-MRI model parameters across the repeated bolus-acquisitions in the healthy controls with no glucose challenge (eg, coefficient of variation for K(trans) improved from 38% to 28%). Native tissue T(1) was significantly lower in patients (374 +/- 68 msec) compared with volunteers (519 +/- 41 msec) but there was no significant difference in any of the baseline DCE-MRI parameters. No effect of glucose challenge was observed in either the patients or healthy volunteers. CONCLUSION: Multiple bolus DCE-MRI is feasible in the pancreas and is improved by nonlinear image registration but is not sensitive to the effects of an intravenous glucose challenge.

MR measurement of articular cartilage thickness distribution in the hip.

OBJECTIVE: To develop a method to determine the distribution of articular cartilage in the hip and to evaluate the potential of the method in a study of normal weight-bearing effects in asymptomatic young volunteers. DESIGN: Six volunteers were scanned after periods of standing and lying supine, using 3D gradient-echo magnetic resonance imaging (MRI). The protocol was repeated for two successive weeks to determine reproducibility. The femoral and acetabular cartilage layers were segmented as a single unit and thickness distribution maps were calculated using a spherical bone model as a frame of reference. Thickness maps were combined over the population using the bone model and post-weight-bearing and post-resting maps were compared. RESULTS: Mean thickness values were compared using an analysis of variance and a significant increase in cartilage thickness of 0.05 mm (P=0.02) was observed. The reproducibility of the method, assessed using test-retest coefficient of variation was 2.5%. CONCLUSIONS: The technique is reproducible, sensitive to sub-millimetre changes in thickness and may be useful in monitoring changes due to disease progression in patients with arthritis of the hip.

Did the London Initiative Zone investment programme affect general practice structure and performance in East London? A time series analysis of cervical screening coverage and asthma prescribing.

A programme of incentives was set up in the London Initiative Zones to improve primary care in inner London based on the findings of the Tomlinson Enquiry in 1992. This descriptive study is a 4-y time series analysis of changes in general practice structure in East London as the result of London Initiative Zone investment, and an exploration of the possible effect of investment on practice performance. We used routinely available administrative data for the whole analysis. General practice characteristics and two selected performance indicators: the asthma prophylaxis to bronchodilator ratio and cervical cytology screening rate, for all practices in the East London and the City Health Authority for 4 y, 1993-1996, were used. Both reflect practice efficiency, but relate to different aspects of practice performance. The prescribing indicator is more indicative of the quality of clinical practise, whereas cervical screening coverage relates more to the characteristics of the practice population and to practice organisation. Repeated measures analyses were used to identify trends and to explore the relationship between changes in practice characteristics and performance. Graphical methods were used to compare East London trends with the rest of England. There were significant improvements in practice structure as the consequence of London Initiative Zone investment. There was a positive association with improvements in practice performance, but East London still lagged some way behind national patterns. The findings suggest that while improvements in asthma prescribing follow the national trend, practices have difficulty in achieving and sustaining the 80% target for cervical cytology screening, and that an overall population coverage of 80% may be in doubt.Increased investment in practice staffing may be influential in improving some aspects of performance. However, in common with other inner cities, a greater effort and more innovative strategies may be needed to achieve a standard of performance equal to the best.

Do practice-based preventive child health services affect the use of hospitals? A cross-sectional study of hospital use by children in east London.

BACKGROUND: Acute paediatric admissions have risen steadily over the past 20 years. During the same period, practice-based child health clinics have increased, although provision is less common in areas of deprivation where hospital use is greatest. AIM: To investigate the contribution of practice-based, preventive child health services to rates of hospital utilisation in children under five years of age. METHOD: A cross-sectional retrospective study examining practice variations in paediatric acute admissions, outpatient referrals, and accident and emergency (A&E) department attendances in the East London and the City Health authority, including all 164 practices in the inner-city boroughs of Hackney, Newham, Tower Hamlets, and the City of London. The main outcome measures were practice-based paediatric hospital attendance rates, for discrete age and sex bands, for the year to 31 March 1996. RESULTS: Hospital use varied with age and sex, with the rates being highest for the youngest children and for boys. The median A&E attendance rate (including reattendances) for boys up to one year of age was 897 per thousand children per practice. In east London, 62% of practices are registered for child health surveillance and 71% provide a child health clinic. Practice approval for child health surveillance, and the provision of child health clinics, did not account for differences between practices in hospital use, but proportionally greater health visiting hours were significantly related to lower rates of emergency hospital admission by young children. Multivariate analyses revealed that up to 23% of the variation between practice admission rates could be explained by health visiting hours. CONCLUSIONS: We found significant associations between the amount of health visiting time available to the practice population and rates of acute admission and outpatient referral among children up to five years of age. These findings suggest that increasing health visitor provision could contribute to lower paediatric emergency admission and outpatient referral rates. A small change would have a significant effect, particularly among the youngest children, given that during the study year 10,000 children under two years of age in east London were either admitted or referred to hospital.

Prescribing for persistent cough in children.

To identify the medications general practitioners consider for the treatment of persistent isolated cough, we undertook a postal questionnaire survey of a sample of general practitioners in east London. Fewer than 10% indicated that they never prescribed for such cough. About 70% sometimes considered antibiotics and/or bronchodilators in all age groups. Inhaled steroids and cromoglycate were considered by about 30% of prescribers for infants compared with over 60% for older age groups. As yet there is no evidence that medication is beneficial for persistent isolated cough. The role of asthma drugs for children with this symptom needs to be evaluated so that we can better identify those who are likely to benefit.