Validation study of machine-learning chest radiograph software in primary and emergency medicine.

AIM: To evaluate the performance of a machine learning based algorithm tool for chest radiographs (CXRs), applied to a consecutive cohort of historical clinical cases, in comparison to expert chest radiologists. MATERIALS AND METHODS: The study comprised 1,960 consecutive CXR from primary care referrals and the emergency department (992 and 968 cases respectively), obtained in 2015 at a UK hospital. Two chest radiologists, each with >20 years of experience independently read all studies in consensus to serve as a reference standard. A chest artificial intelligence (AI) algorithm, Lunit INSIGHT CXR, was run on the CXRs, and results were correlated with those by the expert readers. The area under the receiver operating characteristic curve (AUROC) was calculated for the normal and 10 common findings: atelectasis, fibrosis, calcification, consolidation, lung nodules, cardiomegaly, mediastinal widening, pleural effusion, pneumothorax, and pneumoperitoneum. RESULTS: The ground truth annotation identified 398 primary care and 578 emergency department datasets containing pathologies. The AI algorithm showed AUROC of 0.881-0.999 in the emergency department dataset and 0.881-0.998 in the primary care dataset. The AUROC for each of the findings between the primary care and emergency department datasets did not differ, except for pleural effusion (0.954 versus 0.988, p<0.001). CONCLUSIONS: The AI algorithm can accurately and consistently differentiate normal from major thoracic abnormalities in both acute and non-acute settings, and can serve as a triage tool.

New possibilities for ST analysis - A post-hoc analysis on the Dutch STAN RCT.

BACKGROUND: The diagnostic value of ST analysis of the fetal electrocardiogram (fECG) during labor is uncertain. False alarms (ST events) may be explained by physiological variation of the fetal electrical heart axis. Adjusted ST events, based on a relative rather than an absolute rise from baseline, correct for this variation and may improve the diagnostic accuracy of ST analysis. AIMS: Determine the optimal cut-off for relative ST events in fECG to detect fetal metabolic acidosis. STUDY DESIGN: Post-hoc analysis on fECG tracings from the Dutch STAN trial (STAN+CTG branch). SUBJECTS: 1328 term singleton fetuses with scalp ECG tracing during labor, including 10 cases of metabolic acidosis. OUTCOME MEASURES: Cut-off value for relative ST events at the point closest to (0,1) in the receiver operating characteristic (ROC) curve with corresponding sensitivity and specificity. RESULTS: Relative baseline ST events had an optimal cut-off at an increment of 85% from baseline. Relative ST events had a sensitivity of 90% and specificity of 80%. CONCLUSIONS: Adjusting the current definition of ST events may improve ST analysis, making it independent of CTG interpretation.

Coronary artery calcification is associated with mortality independent of pulmonary embolism severity: a retrospective cohort study.

AIM: To assess coronary artery calcification (CAC) and vascular calcification in patients with pulmonary embolism (PE) and correlate this with mortality. MATERIALS AND METHODS: PE severity was quantified using computed tomography pulmonary angiography (CTPA) in 400 consecutive cases using the modified Miller score (1-5, mild; 6-11, moderate; 12-16, severe). Right ventricle strain was assessed using the right/left ventricle diameter (RV/LV) ratio. CAC score (CACS) was assessed using a four-point scale (CACS mild 1-3, moderate 4-8, severe 9-12) for each vessel and summed to give the total CACS. Follow-up for mortality was obtained at 3 years. RESULTS: PE severity was classified as mild in 48%, moderate in 21%, and severe in 32% of cases. The median modified Miller score was 6 (Interquartile range [IQR] 2, 14) and median total CACS was 2 (IQR 0, 7). All-cause mortality occurred in 128 (32%) patients. Patients with CAC were three times more likely to die than patients without CAC (Hazard ratio [HR] 2.96; 95% CI 1.84, 4.77; p<0.001), and patients with severe CAC were at the highest risk (HR 4.62; 95% CI 2.73, 7.83, p<0.001). Gender, modified Miller score and RV/LV ratio were not predictive of mortality. In multivariate analysis both CACS and age were independent predictors of 3-year all-cause mortality. Of the patients with CAC who died, the presence of coronary artery disease was only documented in 34 (32%). CONCLUSION: CACS is an independent predictor of all-cause mortality in patients with PE, and has important implications for subsequent patient management.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Multimodality quantitative assessments of myocardial perfusion using dynamic contrast enhanced magnetic resonance and 15O-labelled water positron emission tomography imaging.

Kinetic modelling of myocardial perfusion imaging data allows the absolute quantification of myocardial blood flow (MBF) and can improve the diagnosis and clinical assessment of coronary artery disease (CAD). Positron emission tomography (PET) imaging is considered the reference standard technique for absolute quantification, whilst oxygen-15 (15O)-water has been extensively implemented for MBF quantification. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has also been used for MBF quantification and showed comparable diagnostic performance against (15O)-water PET studies. We investigated for the first time the diagnostic performance of two different PET MBF analysis softwares PMOD and Carimas, for obstructive CAD detection against invasive clinical standard methods in 20 patients with known or suspected CAD. Fermi and distributed parameter modelling-derived MBF quantification from DCE-MRI was also compared against (15O)-water PET, in a subgroup of 6 patients. The sensitivity and specificity for PMOD was significantly superior for obstructive CAD detection in both per vessel (0.83, 0.90) and per patient (0.86, 0.75) analysis, against Carimas (0.75, 0.65), (0.81, 0.70), respectively. We showed strong, significant correlations between MR and PET MBF quantifications (r=0.83-0.92). However, DP and PMOD analysis demonstrated comparable and higher haemodynamic differences between obstructive versus (no, minor or non)-obstructive CAD, against Fermi and Carimas analysis. Our MR method assessments against the optimum PET reference standard technique for perfusion analysis showed promising results in per segment level and can support further multi-modality assessments in larger patient cohorts. Further MR against PET assessments may help to determine their comparative diagnostic performance for obstructive CAD detection.

CTPA protocol optimisation audit: challenges of dose reduction with maintained image quality.

AIM: To assess computed tomography (CT) pulmonary angiography (CTPA) dose and image quality in a large teaching hospital, and subsequently, to optimise the protocol in order to reduce the dose without affecting image quality. MATERIALS AND METHODS: Dose-length product (DLP), patient size, and objective quality parameters (contrast-to-noise ratio and signal-to-noise ratio on standardised levels) were recorded from 31 patients undergoing CTPA, where also a subjective image quality evaluation was carried out independently by three specialist cardiothoracic consultant radiologists. An equivalent objective and subjective quality assessment was carried out on a cohort of the same size in a different tertiary healthcare centre. Moreover, experimental tests using anthropomorphic chest phantoms were performed, using different scan parameters. In light of the above analysis, two of the scanner settings for CTPA were modified, i.e., the SureExposure pre-set was changed to "Standard" noise level, quantified with standard deviation (SD) of 19, and the minimum amperage setting lowered from 80 to 40 mA. A second cohort of patients using this new protocol was audited, following the same methodology. RESULTS: The average DLP of patients undergoing CTPA was initially found to be higher than both local and national dose reference levels (DRLs; 559 versus 300 mGy·cm and 400 mGy·cm, respectively). The new protocol led to a reduction in average DLP (359 mGy·cm) while the image quality, assessed by three cardiothoracic consultant radiologists, was preserved. CONCLUSION: The CTPA protocol was implemented in the Royal Infirmary of Edinburgh resulting in significant dose reduction, and is now compliant with national and local DRLs. The image quality was maintained.

Labour pain with remifentanil patient-controlled analgesia versus epidural analgesia: a randomised equivalence trial.

OBJECTIVE: To distinguish satisfaction with pain relief using remifentanil patient-controlled analgesia (RPCA) compared with epidural analgesia (EA) in low-risk labouring women. DESIGN: Randomised controlled equivalence trial. SETTING: Eighteen midwifery practices and six hospitals in the Netherlands. POPULATION: A total of 408 pregnant women at low risk for obstetric complications initially under the care of primary-care midwives. METHODS: Women randomised before active labour to receive analgesia with RPCA or EA, if requested. MAIN OUTCOME MEASURES: Primary outcome was satisfaction with pain relief measured hourly using a visual analogue scale and summed as area under the curve (AUC). Secondary outcomes were overall satisfaction with pain relief, pain intensity scores during labour, mode of delivery, and maternal and neonatal outcomes. RESULTS: We randomised 418 women, of whom 409 could be followed for the primary endpoint. Analgesia was received by 46% (94/203) in the remifentanil group and 37% (76/206) in the epidural group. The AUC for satisfaction with pain relief was 32 in the remifentanil group and 31 in the epidural group (mean difference -0.50; 95% CI -6.8 to 5.9). Among women who actually received analgesia, these values were 23 and 35, respectively (mean difference -12; 95% CI -22 to -1.5). Secondary outcomes were comparable. CONCLUSIONS: In low-risk labouring women, we could not demonstrate equivalence between a strategy with RPCA to EA with respect to satisfaction with pain relief assessed during the total duration of labour. However, once applied satisfaction was higher in women who received epidural analgesia. TWEETABLE ABSTRACT: Satisfaction with pain relief is higher in women receiving epidural analgesia compared with Remifentanil PCA.

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms.

OBJECTIVES: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. MATERIALS AND METHODS: Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. RESULTS: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. CONCLUSIONS: Both (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.

Long-term adverse effects associated with isolated below-knee deep-vein thrombosis: a 10-year follow-up study.

AIM: To assess the effect of the presence and locality of symptomatic lower-limb deep vein thrombosis (DVT) on mortality and morbidity following contrast venography (CV), the reference standard for diagnosing below-knee DVT, with a view to determining the prevalence of recurrent episodes of DVT and post-thrombotic syndrome (PTS). MATERIALS AND METHODS: Patients with clinical DVT undergoing investigation using CV were prospectively recorded. By retrospective case note examination and mortality data evaluation, 347 patients with DVT were matched with negative controls for mortality follow-up. Long-term complications were recorded. RESULTS: Fifty-one (14.7%) of the DVT patients were diagnosed with PTS and 43 (12.4%) with possible PTS in the 10 years following presentation. The relative risk for developing definite PTS was 0.544 for below- versus above-knee DVT; 9.9% with below-knee DVT had PTS, and 9% had probable PTS. Recurrent DVT occurred in 23.3% of patients with proximal DVT as opposed to 12.6% of patients with isolated below-knee DVT. CONCLUSIONS: Morbidity is greater in patients with proximal DVT; however, a significant, albeit smaller, proportion of patients with isolated below-knee DVT develop recurrent DVT and PTS. Below-knee DVT carries sufficient morbidity and mortality to warrant vigilance in diagnosis and management of this condition.

Ten years of imaging for pulmonary embolism: too many scans or the tip of an iceberg?

AIM: To examine the number and nature of investigations performed for suspected pulmonary embolism (PE) in a large teaching hospital and the change in incidence and severity of PE over a decade. MATERIALS AND METHODS: In this retrospective study, all patients investigated for suspected PE using computed tomography pulmonary angiography (CTPA) or lung scintigraphy during 10 years to March 2012 were identified and their records reviewed. In the final year, all reportedly positive CTPA cases were reviewed and PE severity calculated, for comparison with similar historical data. RESULTS: From 2002 to 2012, total annual investigations for suspected acute PE increased by 163% (805 to 2121). CTPA increased by 325% (475 to 2019). Detection of PE increased by 121% (193 to 426 per annum), with stable distribution of severity scores. The positive scan rate decreased from 24% to 20%. The mean age of patients being investigated for PE increased from 56 to 63 years. CONCLUSIONS: Increased detection of PE is not due to disproportionate increase in small PEs, but to increased detection of PE of all severities. This finding supports the hypothesis that PE is more common in the general population than previously appreciated, which may represent an iceberg phenomenon of previously undetected disease.

'Presenting CXR phenotype of H1N1' flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks'.

AIMS: To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). METHODS: We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were 'blinded' to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. RESULTS: Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p=0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p=0.001). H1N1 radiographs were more likely to be 'patchy' versus 'confluent' changes of non-H1N1 CAP (p=0.03) and more often demonstrated peripheral distribution (p=0.01). H1N1 patients tended to stay in hospital longer (not significant; p=0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p=0.02). The findings were the same for the two evaluated seasons. CONCLUSION: H1N1 patients demonstrated more extensive disease, which was more likely bilateral, 'patchy', and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients, particularly where rapid viral testing is not available.

Feasibility of radiation dose reduction using AIDR-3D in dynamic pulmonary CT perfusion.

AIM: To assess the feasibility of radiation dose reduction with adaptive iterative dose reduction (AIDR-6 3D) reconstruction in dynamic pulmonary CT perfusion. MATERIALS AND METHODS: CTP examinations of 10 patients acquired at 100 kVp/50 mAs were reconstructed with filtered back projection (FBP) and AIDR-3D. Artificial noise was added to raw data (pre-reconstruction projection data) to simulate lower tube current scanning. Radiodensity (in Hounsfield units), noise, and perfusion values were compared. RESULTS: There was no significant difference in noise between the full and simulated reduced tube current with AIDR-3D reconstruction (p = 1). There was significantly lower noise in lung tissue with AIDR-3D images when compared to reconstructions without AIDR-3D (p = 0.005) and no significant change in the radiodensity (p = 1; mean difference <6 HU). Mean perfusion values increased significantly at lower tube currents (25 and 12.5 mAs), compared to 50 mAs (p = 0.005). This effect was significantly greater in larger patients compared to thin patients. CONCLUSION: AIDR-3D produced significantly lower noise images than FBP-based algorithms and maintained consistent noise levels in lung at 12.5 mAs, indicating this algorithm is suitable for reduced dose lung perfusion imaging. Iterative reconstruction allows significant radiation dose reduction of up to fourfold in smaller patients, and up to twofold in the medium/large size patients. The increase in perfusion values at 25% simulated tube currents is attributed to attenuation bias.

Imaging of cardiovascular risk in patients with Turner's syndrome.

Turner's syndrome is a disorder defined by an absent or structurally abnormal second X chromosome and affects around 1 in 2000 newborn females. The standardised mortality ratio in Turner's syndrome is around three-times higher than in the general female population, mainly as a result of cardiovascular disorders. Most striking is the early age at which Turner's syndrome patients develop the life-threatening complications of cardiovascular disorders compared to the general population. The cardiovascular risk stratification in Turner's syndrome is challenging and imaging is not systematically used. The aim of this article is to review cardiovascular risks in this group of patients and discuss a systematic imaging approach for early identification of cardiovascular disorders in these patients.

Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions.

The black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions.

Computed tomographic measures of airway morphology in smokers and never-smoking normals.

Bronchial wall area percent (WA% = 100 × wall area/total bronchial cross sectional area) is a standard computed tomographic (CT) measure of central airway morphology utilized in smokers with chronic obstructive pulmonary disease (COPD). Although it provides significant clinical correlations, the range of reported WA% is narrow. This suggests limited macroscopic change in response to smoking or that remodeling proportionally affects the airway wall and lumen dimensions such that their ratio is preserved. The objective of this study is to assess central airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT scans of 5,179 smokers and 92 never smoking normal subjects. In smokers, WA, Ai, and Ao were positively correlated with forced expiratory volume in 1 s (FEV1) expressed as a percent of predicted (FEV1%), and the WA% was negatively correlated with FEV1% (P < 0.0001 for all comparisons). Importantly, smokers with lower FEV1% tended to have airways of smaller cross-sectional area with lower WA. The increases in the WA% across GOLD stages of chronic obstructive pulmonary disease (COPD) can therefore not be due to increases in WA. The data suggest two possible origins for the WA% increases: 1) central airway remodeling resulting in overall reductions in airway caliber in excess of the decreased WA or 2) those with COPD had smaller native airways before they began smoking. In both cases, these observations provide an explanation for the limited range of values of WA% across stages of COPD.

Iterative reconstruction and individualized automatic tube current selection reduce radiation dose while maintaining image quality in 320-multidetector computed tomography coronary angiography.

AIM: To assess the effect of two iterative reconstruction algorithms (AIDR and AIDR3D) and individualized automatic tube current selection on radiation dose and image quality in computed tomography coronary angiography (CTCA). MATERIALS AND METHODS: In a single-centre cohort study, 942 patients underwent electrocardiogram-gated CTCA using a 320-multidetector CT system. Images from group 1 (n = 228) were reconstructed with a filtered back projection algorithm (Quantum Denoising Software, QDS+). Iterative reconstruction was used for group 2 (AIDR, n = 379) and group 3 (AIDR3D, n = 335). Tube current was selected based on body mass index (BMI) for groups 1 and 2, and selected automatically based on scout image attenuation for group 3. Subjective image quality was graded on a four-point scale (1 = excellent, 4 = non-diagnostic). RESULTS: There were no differences in age (p = 0.975), body mass index (p = 0.435), or heart rate (p = 0.746) between the groups. Image quality improved with iterative reconstruction and automatic tube current selection [1.3 (95% confidence intervals (CI): 1.2-1.4), 1.2 (1.1-1.2) and 1.1 (1-1.2) respectively; p < 0.001] and radiation dose decreased [274 (260-290), 242 (230-253) and 168 (156-180) mGy cm, respectively; p < 0.001]. CONCLUSION: The application of the latest iterative reconstruction algorithm and individualized automatic tube current selection can substantially reduce radiation dose whilst improving image quality in CTCA.

Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation?

AIMS: The pathophysiology of aortic stenosis shares many similarities with atherosclerosis and skeletal bone formation. Using non-invasive imaging, we compared aortic valve calcification and inflammation activity with that measured in atherosclerosis and bone. METHODS AND RESULTS: Positron emission and computed tomography was performed using 18F-sodium fluoride (18F-NaF, calcification) and 18F-fluorodeoxyglucose (18F-FDG, inflammation) in 101 patients with calcific aortic valve disease (81 aortic stenosis and 20 aortic sclerosis). Calcium scores and positron emission tomography tracer activity (tissue-to-background ratio; TBR) were measured in the aortic valve, coronary arteries, thoracic aorta, and bone. Over 90% of the cohort had coexistent calcific atheroma, yet correlations between calcium scores were weak or absent (valve vs. aorta r(2) = 0.015, P = 0.222; valve vs. coronaries r(2) = 0.039, P = 0.049) as were associations between calcium scores and bone mineral density (BMD vs. valve r(2) = 0.000, P = 0.766; vs. aorta r(2) = 0.052, P = 0.025; vs. coronaries r(2) = 0.016, P = 0.210). 18F-NaF activity in the valve was 28% higher than in the aorta (TBR: 2.66 ± 0.84 vs. 2.11 ± 0.31, respectively, P < 0.001) and correlated more strongly with the severity of aortic stenosis (r(2) = 0.419, P < 0.001) than 18F-NaF activity outwith the valve (valve vs. aorta r(2) = 0.167, P < 0.001; valve vs. coronary arteries r(2) = 0.174, P < 0.001; valve vs. bone r(2) = 0.001, P = 0.806). In contrast, 18F-FDG activity was lower in the aortic valve than the aortic atheroma (TBR: 1.56 ± 0.21 vs. 1.81 ± 0.24, respectively, P < 0.001) and more closely associated with uptake outwith the valve (valve vs. aorta r(2) = 0.327, P < 0.001). CONCLUSION: In patients with aortic stenosis, disease activity appears to be determined by local calcific processes within the valve that are distinct from atherosclerosis and skeletal bone metabolism.

Optical imaging of cell death in traumatic brain injury using a heat shock protein-90 alkylator.

Traumatic brain injury is a major public health concern and is characterised by both apoptotic and necrotic cell death in the lesion. Anatomical imaging is usually used to assess traumatic brain injuries and there is a need for imaging modalities that provide complementary cellular information. We sought to non-invasively image cell death in a mouse model of traumatic brain injury using a near-infrared fluorescent conjugate of a synthetic heat shock protein-90 alkylator, 4-(N-(S-glutathionylacetyl) amino) phenylarsonous acid (GSAO). GSAO labels both apoptotic and necrotic cells coincident with loss of plasma membrane integrity. The optical GSAO specifically labelled apoptotic and necrotic cells in culture and did not accumulate in healthy organs or tissues in the living mouse body. The conjugate is a very effective imager of cell death in brain lesions. The optical GSAO was detected by fluorescence intensity and GSAO bound to dying/dead cells was detected from prolongation of the fluorescence lifetime. An optimal signal-to-background ratio was achieved as early as 3 h after injection of the probe and the signal intensity positively correlated with both lesion size and probe concentration. This optical GSAO offers a convenient and robust means to non-invasively image apoptotic and necrotic cell death in brain and other lesions.

Is intrapartum fever associated with ST-waveform changes of the fetal electrocardiogram? A retrospective cohort study.

OBJECTIVE: To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram. DESIGN: Retrospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(®) clinical guidelines. MAIN OUTCOME MEASURES: Number and type of ST-events. RESULTS: Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events. CONCLUSIONS: Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.

MRI of the lung (3/3)-current applications and future perspectives.

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations.