Repair of oesophageal atresia by consultants and supervised trainees results in similar outcomes.

INTRODUCTION: Consultants and trainees require exposure to complex cases for maintaining and gaining operative experience. Oesophageal atresia (OA) repair is a neonatal surgical procedure with indicative numbers for completion of training. A conflict of interest may exist between adequate training, maintaining consultant experience and achieving good outcomes. We aimed to review outcomes of procedures performed primarily by trainees and those performed by consultants. METHODS: We carried out a retrospective case note review of all consecutive infants who underwent surgical repair of OA with distal tracheooesophageal fistula (TOF) between January 1994 and December 2014 at our institution. Only cases that underwent primary oesophageal anastomosis were included. Surgical outcomes were compared between cases that had a trainee and those that had a consultant listed as the primary operator. RESULTS: One hundred and twenty-two cases were included. A total of 52 procedures were performed by trainees, and 68 by consultants. Two cases were undeterminable and excluded. Infant demographics, clinical characteristics and duration of follow-up were similar between groups. All infants survived to discharge. Procedures performed by trainees and those performed by consultants as primary operators had a similar incidence of postoperative pneumothorax (trainees 4, consultants 3; p=0.46), anastomotic leak (trainees 5, consultants 3; p=0.29) and recurrent TOF (trainees 0, consultants 2; p=0.5). Overall 52% of cases had an anastomotic dilatation during follow-up, with no difference between the trainee and consultant groups (50% vs 53%; p=0.85). CONCLUSIONS: Surgical outcomes for repair of OA/TOF are not adversely affected by trainee operating. Trainees with appropriate skills should perform supervised OA/TOF repair. These data are important for understanding the interrelationship between provision of training and surgical outcomes.

The effectiveness of influenza vaccination in pregnancy in relation to child health outcomes: Systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of influenza vaccination during pregnancy on child health outcomes. DESIGN: Systematic review/meta-analysis. DATA SOURCES: Clinical Trials.gov, Cochrane Library, EMBASE, Medline, Medline in process, PubMed and Web of Science, from 1st January 1996 to 29th June 2018. An updated Medline search was performed 30th June 2018 to 31st October 2019. METHODS: Randomised controlled trials (RCTs) and observational studies reporting health outcomes of infants and children born to women who received inactivated influenza vaccine during pregnancy. The primary outcome was infant laboratory confirmed influenza (LCI). Secondary outcomes included influenza-like illness (ILI), other respiratory illnesses, primary care, clinic visit or hospitalisations due to influenza illness and long-term respiratory childhood outcomes. RESULTS: 19 studies were included; 15 observational studies and 4 primary RCTs with an additional 3 papers reporting secondary outcomes of these RCTs. In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15-50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old. Two RCTs were excluded from the meta-analysis for the outcome of LCI in infants (different controls used). Both of these studies showed a protective effect for infants from LCI, with a vaccine efficacy of up to 70%. Overall observational studies showed an inverse (protective) association between maternal influenza vaccination and infant LCI, hospitalisation and clinic visits due to LCI or ILI in infants and other respiratory illness in infants ≤6 months old. CONCLUSIONS: This systematic review supports maternal influenza vaccination as a strategy to reduce LCI and influenza-related hospitalisations in young infants. Communicating these benefits to pregnant women may support their decision to accept influenza vaccination in pregnancy and increase vaccine coverage in pregnant women. REGISTRATION: PROSPERO CRD42018102776.

Improving paediatric antimicrobial stewardship in hospital-based settings: why, where and how?

BACKGROUND: Antimicrobial resistance (AMR) is being recognized as a priority by healthcare organizations across the world. However, many children are managed on IV antimicrobials in hospital with very little consideration of antimicrobial stewardship issues. OBJECTIVES: A nurse-led paediatric ambulatory outpatient parenteral antimicrobial therapy (OPAT) service, managing children with common infections being ambulated on short courses of IV antimicrobials, was introduced within Southampton Children's Hospital in January 2018. We evaluated the impact of this service in terms of the quality of antimicrobial prescribing and timing of ambulation in children presenting with common infections. METHODS: All cases managed within the service were reviewed in two separate 2 month time periods: prior to introduction of the service (September-October 2016) and then prospectively after its introduction (September-October 2018). RESULTS: A total of 96% of IV antibiotic management decisions at 48 h were deemed appropriate in 2018, compared with 75% in 2016. A total of 64% of patients were ambulated on IV antibiotics at some point during their treatment course in 2018, compared with 19% in 2016. However, a significant proportion of antimicrobial decisions made at the point of presentation to hospital remained suboptimal in 2018. CONCLUSIONS: Children are commonly managed with IV antibiotics in hospital. We demonstrate marked improvements in appropriate antimicrobial use through the introduction of a nurse-led ambulatory OPAT service. In addition, such a service can promote a greater proportion of children being ambulated from hospital, freeing up valuable inpatient beds and potentially delivering cost savings that can be used to fund such services.

Integral small field output factor measurements using a transmission ionisation chamber.

Previous studies describe the use of a large area parallel-plate chamber, the PTW Bragg Peak chamber, for measuring dose-area product (DAP) and output factors in small megavoltage photon fields. However, in radiotherapy departments without protons, this detector would have to be purchased separately for this purpose. This work investigated the feasibility of alternatively using a large transmission ionisation chamber, the IBA round Stealth chamber (SC), for output factor measurements of stereotactic fields. This type of detector is more commonly found in radiotherapy departments as a reference chamber for water tank scanning of small fields, and hence DAP could be performed without an additional purchase. The SC's large sensitive area (diameter of 94 mm) measures the integral dose, also known as DAP, over the whole two-dimensional (2D) dose distribution of the small field. The measurements were performed using a 6 MV beam from an Elekta Infinity linear accelerator. Conversion of DAP to central axis point dose was performed using 2D dose maps from Gafchromic EBT3 films. The field sizes measured ranged from side length of 5 mm to 50 mm (all square). The resultant output factors were compared against measurements with a stereotactic diode. The small field output factors measured using SC + film were in good agreement with the stereotactic diode (within 2% for field sizes as small as 6 mm; 3% difference at 5 mm). The new proposed method showed that a transmission chamber like SC is a good alternative large-area parallel plate chamber to measure DAP and derive small field OFs. Furthermore, the feasibility of using 2D reconstructed dose maps from water tank profiles and hence filmless approach was investigated. Results showed that filmless conversion of DAP to central axis point dose is feasible using profiles. However, a large number of profiles are required (i.e. 15° increments (star pattern) are required for accurate 2D dose reconstruction), and hence the water tank scanning for this approach may be prohibitively time-consuming.

Spaceborne Synthetic Aperture Radar Survey of Subsidence in Hampton Roads, Virginia (USA).

Over the past century, the Hampton Roads area of the Chesapeake Bay region has experienced one of the highest rates of relative sea level rise on the Atlantic coast of the United States. This rate of relative sea level rise results from a combination of land subsidence, which has long been known to be present in the region, and rising seas associated with global warming on long timescales and exacerbated by shifts in ocean dynamics on shorter timescales. An understanding of the current-day magnitude of each component is needed to create accurate projections of future relative sea level rise upon which to base planning efforts. The objective of this study is to estimate the land component of relative sea level rise using interferometric synthetic aperture radar (InSAR) analysis applied to ALOS-1 synthetic aperture radar data acquired during 2007-2011 to generate high-spatial resolution (20-30 m) estimates of vertical land motion. Although these results are limited by the uncertainty associated with the small set of available historical SAR data, they highlight both localized rates of high subsidence and a significant spatial variability in subsidence, emphasizing the need for further measurement, which could be done with Sentinel-1 and NASA's upcoming NISAR mission.

The atmospheric chemistry of trace gases and particulate matter emitted by different land uses in Borneo.

We report measurements of atmospheric composition over a tropical rainforest and over a nearby oil palm plantation in Sabah, Borneo. The primary vegetation in each of the two landscapes emits very different amounts and kinds of volatile organic compounds (VOCs), resulting in distinctive VOC fingerprints in the atmospheric boundary layer for both landscapes. VOCs over the Borneo rainforest are dominated by isoprene and its oxidation products, with a significant additional contribution from monoterpenes. Rather than consuming the main atmospheric oxidant, OH, these high concentrations of VOCs appear to maintain OH, as has been observed previously over Amazonia. The boundary-layer characteristics and mixing ratios of VOCs observed over the Borneo rainforest are different to those measured previously over Amazonia. Compared with the Bornean rainforest, air over the oil palm plantation contains much more isoprene, monoterpenes are relatively less important, and the flower scent, estragole, is prominent. Concentrations of nitrogen oxides are greater above the agro-industrial oil palm landscape than over the rainforest, and this leads to changes in some secondary pollutant mixing ratios (but not, currently, differences in ozone). Secondary organic aerosol over both landscapes shows a significant contribution from isoprene. Primary biological aerosol dominates the super-micrometre aerosol over the rainforest and is likely to be sensitive to land-use change, since the fungal source of the bioaerosol is closely linked to above-ground biodiversity.

Methylation profiling of rectal cancer identifies novel markers of early-stage disease.

BACKGROUND: Radical surgery is the de facto treatment for early rectal cancer. Conservative surgery with transanal endoscopic microsurgery can achieve high rates of cure but the histopathological measures of outcome used to select local treatment lack precision. Biomarkers associated with disease progression, particularly mesorectal nodal metastasis, are urgently required. The aim was to compare patterns of gene-specific hypermethylation in radically excised rectal cancers with histopathological stage. METHODS: Locus-specific hypermethylation of 24 tumour suppressor genes was measured in 105 rectal specimens (51 radically excised adenocarcinomas, 35 tissues adjacent to tumour and 19 normal controls) using the methylation-specific multiplex ligation-dependent probe assay (MS-MLPA). Methylation values were correlated with histopathological indices of disease progression and validated using bisulphite pyrosequencing. RESULTS: Five sites (ESR1, CDH13, CHFR, APC and RARB) were significantly hypermethylated in cancer compared with adjacent tissue and normal controls (P < 0·050). Methylation at these sites was higher in Dukes' A than Dukes' 'D' cancers (P = 0·013). Methylation at two sites (GSTP1 and RARB) was individually associated with localized disease (N0 and M0 respectively; P = 0·006 and P = 0·008). Hypermethylation of at least two of APC, RARB, TIMP3, CASP8 and GSTP1 was associated with early (N0 M0) disease (N0, P = 0·002; M0, P = 0·044). Methylation levels detected by MS-MLPA and pyrosequencing were concordant. CONCLUSION: Locus-specific hypermethylation was more prevalent in early- than late-stage disease. Hypermethylation of two or more of a panel of five tumour suppressor genes was associated with localized disease.

Survey of fungi and yeast in polymicrobial infections in chronic wounds.

OBJECTIVE: To assess the incidence, abundance and species diversity of fungi in chronic wounds, as well as to describe the associations of major fungi populations. METHOD: Comprehensive molecular diagnostic reports were evaluated from a total of 915 chronic wounds in a retrospective study. RESULTS: Of the 915 clinical specimens, 208 (23%) were positive for fungal species. These samples were further compared in a compiled dataset, and sub-classified among the four major chronic wound types (decubitus ulcer, diabetic foot ulcer, non-healing surgical wound, and venous leg ulcer). The most abundant fungi were yeasts in the genus Candida; however, Curvularia, Malessezia, Aureobasidium, Cladosporium, Ulocladium, Engodontium and Trichtophyton were also found to be prevalent components of these polymicrobial infections. A notable bacterial/fungal negative correlation was found to be apparent between Staphylococcus and Candida. There were also significant relationships between both bacterial and fungal genera and patient metadata including gender, diabetes status and cardiovascular comorbidities. CONCLUSION: This microbial survey shows that fungi are more important wound pathogens and opportunistic pathogens than previously reported, exemplifying the impact of these under-reported pathogens. With the application of modern cost-effective and comprehensive molecular diagnostics, clinicians can now identify and address this significant component of chronic wound bioburden with targeted therapies, thereby improving healing trajectories.

Wnt signalling in adenomas of familial adenomatous polyposis patients.

BACKGROUND: Epigenetic silencing of Wnt antagonists and expression changes in genes associated with Wnt response pathways occur in early sporadic colorectal tumourigenesis, indicating that tumour cells are more sensitive to Wnt growth factors and respond differently. In this study, we have investigated whether similar changes occur in key markers of the Wnt response pathways in the genetic form of the disease, familial adenomatous polyposis (FAP). METHODS: We investigated epigenetic and expression changes using pyrosequencing and real-time RT-PCR in samples from seven patients without neoplasia, and matched normal and tumour tissues from 22 sporadic adenoma and 14 FAP patients. RESULTS: We found that 17 out of 24 (71%) FAP adenomas were hypermethylated at sFRP1, compared with 20 out of 22 (91%) of sporadic cases. This was reflected at the level of sFRP1 transcription, where 73% of FAP and 100% of sporadic cases were down-regulated. Increased expression levels of c-myc and FZD3 were less common in FAP (35 and 46% respectively) than sporadic tumours (78 and 67% respectively). CONCLUSION: Overall, the changes in expression and methylation were comparable, although the degree of change was generally lower in the FAP adenomas. Molecular heterogeneity between multiple adenomas from individual FAP patients may reflect different developmental fates for these premalignant tumours.

Nitrogen management is essential to prevent tropical oil palm plantations from causing ground-level ozone pollution.

More than half the world's rainforest has been lost to agriculture since the Industrial Revolution. Among the most widespread tropical crops is oil palm (Elaeis guineensis): global production now exceeds 35 million tonnes per year. In Malaysia, for example, 13% of land area is now oil palm plantation, compared with 1% in 1974. There are enormous pressures to increase palm oil production for food, domestic products, and, especially, biofuels. Greater use of palm oil for biofuel production is predicated on the assumption that palm oil is an "environmentally friendly" fuel feedstock. Here we show, using measurements and models, that oil palm plantations in Malaysia directly emit more oxides of nitrogen and volatile organic compounds than rainforest. These compounds lead to the production of ground-level ozone (O(3)), an air pollutant that damages human health, plants, and materials, reduces crop productivity, and has effects on the Earth's climate. Our measurements show that, at present, O(3) concentrations do not differ significantly over rainforest and adjacent oil palm plantation landscapes. However, our model calculations predict that if concentrations of oxides of nitrogen in Borneo are allowed to reach those currently seen over rural North America and Europe, ground-level O(3) concentrations will reach 100 parts per billion (10(9)) volume (ppbv) and exceed levels known to be harmful to human health. Our study provides an early warning of the urgent need to develop policies that manage nitrogen emissions if the detrimental effects of palm oil production on air quality and climate are to be avoided.

Association of gastroesophageal reflux and O2 desaturation: a novel study of simultaneous 24-h MII-pH and continuous pulse oximetry.

BACKGROUND: Proof of the relationship between gastroesophageal reflux disease (GERD) and respiratory symptoms remains a challenge. Our aim was to determine the association between reflux events and O(2) desaturation in GERD patients with primary respiratory symptoms (RS) compared to those with primary esophageal symptoms (ES) using ambulatory monitoring systems. METHODS: One thousand eight hundred fifty-one reflux episodes were detected by multichannel intraluminal impedance (MII)-pH testing in 30 patients with symptoms of GERD (20 RS, ten ES.) All patients underwent simultaneous 24-h MII-pH and continuous O(2) saturation monitoring via pulse oximetry. Reflux-associated desaturation events were determined by correlating synchronized 24-h esophageal pH and/or impedance and O(2) desaturation. RESULTS: One thousand one hundred seventeen reflux events occurred in patients with RS and 734 in those with ES. Nearly 60% of these 1,851 reflux events were associated with O(2) desaturation. Markedly more events were associated with O(2) desaturation in patients with RS (74.5%, 832/1,117) than in patients with ES (30.4%, 223/734, p < 0.0001). The difference in reflux desaturation association was more profound with proximal reflux--80.3% with RS vs. 29.4% with ES (p < 0.0001). CONCLUSIONS: A remarkably high prevalence of O(2) desaturation associated with gastroesophageal reflux was noted in patients with RS. Given further study, simultaneous combined esophageal reflux and O(2) saturation monitoring may prove a useful diagnostic tool in this difficult group of patients.

Effects of biofilm treatments on the multi-species Lubbock chronic wound biofilm model.

OBJECTIVE: To evaluate the efficacy of several biofilm effectors in inhibiting biofilm formation in an in vitro multi-species chronic wound biofilm model. METHOD: The Lubbock Chronic Wound Biofilm (LCWB) model has been described in detail elsewhere. Pathogens used in the model are Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus. These are three of the most important species associated with biofilms. Here, the model was exposed to the following biofilm effectors: xylitol, salicylic acid, farnesol, erythritol and two proprietary, semi-solid, wound-dressing formulations currently under development (Sanguitec gels). RESULTS: Biofilm formation was completely inhibited in the LCWB model following treatment with 20% xylitol, 10% erythritol, 1,000 microg/ml farnesol, 20mM salicylic acid or 0.1% of either of the two Sanguitec gel formulations. Salicylic acid specifically inhibited S. aureus (p<0.01) at 10mM and 20mM, consequently increasing the ratios of P. aeruginosa and E. faecalis within the biofilm. Xylitol had an increasing inhibitory effect on P. aeruginosa (p<0.01) at all concentrations evaluated. Erythritol had an inhibitory effect on P. aeruginosa and S. aureus growth (p<0.01) at over 5% concentrations. The inhibitory effect of both Sanguitec gel formulations was more broadly effective, with an increasingly inhibitory effect on all LCWB species (p<0.01). CONCLUSION: The LCWB model provides a multi-species format with which to evaluate the effect of biofilm effectors on wound flora in a biofilm phenotype. These results suggest that different treatments can target specific populations within a biofilm. Salicylic acid preferentially targeted S. aureus, xylitol preferentially targeted P. aeruginosa, while erythritol preferentially targeted both P. aeruginosa and S. aureus. In contrast, the two Sanguitec gel formulations provided a broad, less preferential, inhibition of biofilm development. DECLARATION OF INTEREST: Research and Testing Laboratory is a for-profit enterprise that develops molecular methods and performs service research work on biofilms. Sanguitec gel was developed by JPK and CEJ.

Allelic diversity within the high frequency Mamu-A2*05/Mane-A2*05 (Mane-A*06)/Mafa-A2*05 family of macaque MHC-A loci.

Macaque species serve as important animal models of human infection and immunity. To more fully scrutinize their potential in both the analysis of disease pathogenesis and vaccine development, it is necessary to characterize the major histocompatibility complex (MHC) class I loci of Macaca mulatta (Mamu), Macaca nemestrina (Mane), and Macaca fascicularis (Mafa) at the genomic level. The oligomorphic Mamu-A2*05/Mane-A2*05 (previously known as Mane-A*06) family of macaque MHC-A alleles has recently been shown to be present at high frequency in both Indian rhesus and pig-tailed macaque populations. Using a locus-specific amplification and direct DNA typing methodology, we have additionally found that the locus encoding this family is very prevalent (75%) among a sampling of 182 Chinese rhesus macaques and has a high prevalence (80%) within a larger, independent cohort of 309 pig-tailed macaques. Interestingly, among the Chinese rhesus macaques, only six alleles previously identified in Indian-origin animals were observed, while three recently identified in Chinese-origin animals and 25 new alleles were characterized. Among the pig-tailed macaques, we observed 1 previously known (Mane-A*06) and 19 new alleles. Examination of the orthologous locus in a preliminary sampling of 30 cynomolgus macaques showed an even higher presence (87%) of Mafa-A2*05 family alleles, with 5 previously identified and 15 new alleles characterized. The continued discovery of novel alleles and thus further diversity within the Mamu-A2*05/Mane-A2*05/Mafa-A2*05 family indicates that this MHC-A locus, although highly conserved across the three species of macaques, has remained a dynamic entity during evolution.

Reorganisation of Wnt-response pathways in colorectal tumorigenesis.

In most colorectal tumours, APC mutation stabilises beta-catenin and mimics elements of Wnt growth factor signalling, but the high frequency of epigenetic loss of Wnt antagonists indicates an additional role for ligand-mediated Wnt signalling. Here, we have investigated the expression of key components of beta-catenin-independent Wnt response pathways to determine whether their profiles change during the transition from normal mucosa to colorectal adenomas. Transcription of the Wnt/planar cell polarity pathway determinant NKD1 (naked cuticle homologue 1) was induced in adenomas by a median 135-fold and in cancers by 7.4-fold. While some Frizzleds (FZDs) were downregulated in adenomas, the Wnt/Ca(2+) receptors FZD3 and FZD6 were induced by a median factor of 6.5 and 4.6, respectively. Naked cuticle homologue 1, FZD3 and FZD6 expression were coordinated in pre-malignant disease, but this relationship was lost in invasive cancers, where FZD induction was seen less frequently. Naked cuticle homologue 1 expression was associated with nuclear localisation of phospho-c-Jun in adenomas. In cultured cells, NKD1 transcription was induced by lithium chloride but FZD3 expression required Wnt growth factor treatment. These data show that Wnt responses are consistently directed towards both beta-catenin-independent routes in early colorectal tumorigenesis and elements of this are retained in more advanced cancers. These beta-catenin-independent Wnt signalling pathways may provide novel targets for chemoprevention of early colorectal tumours.

Anion photoelectron spectroscopy and density functional investigation of diniobium-carbon clusters.

Experimental photoelectron and computational results show diniobium-carbon (Nb(2)C(n)) clusters to coexist in multiple structural isomers: three-dimensional geometries, planar rings, and linear chains. Three-dimensional clusters having up to five carbons are formed preferentially with Nb-Nb bonding, whereas only Nb-C bonding is observed experimentally at six carbons. Clusters consisting of an odd number of atoms are also observed with linear geometries. The larger binary clusters (n > or = 7) display properties similar to those of pure carbon clusters. We provide evidence for niobium substitution of carbon atoms.

Anion photoelectron spectroscopy and density functional investigation of vanadium carbide clusters.

The influence of source conditions on vanadium-carbon cluster formation in a methane-vanadium plasma is explored and analyzed by photoelectron spectroscopy, revealing that the metal-carbon ratio has substantial influence over the cluster products. Experiments that employ large methane content produce carbon-rich mono- and divanadium carbides. The carbon-rich clusters show a preference for the formation of cyclic neutral and linear ionic structures. When the methane concentration is decreased, VmCn clusters are formed with m = 1-4 and n = 2-8. The photoelectron spectra of clusters formed under these conditions are indicative of a three-dimensional network. We have measured a significantly lower vertical electron affinity for the VC2, V2C3, and V4C6 clusters compared with proximate species. Interestingly, the VC2 species is a proposed building block of the M8C12 Met-Car cluster, and the 2,3 and 4,6 clusters correspond to the 1/4 and 1/2 Met-Car cages, respectively. This correlation is taken as evidence of their importance in the formation of the larger Met-Car species. These results are supported by density functional theory (DFT) calculations carried out at the PBE/GGA level.

The Wnt antagonist sFRP1 is downregulated in premalignant large bowel adenomas.

Our previous studies have implicated the Wnt antagonist, sFRP1, as a tumour suppressor gene in advanced colorectal cancer. In this study, we set out to investigate the relationship between sFRP1 expression and large bowel adenomas, a precursor of colorectal cancer. The induction of beta-catenin/TCF mediated transcription is both a frequent early event in colorectal neoplasia, and a key downstream effect of wnt growth factor signalling. Lithium treatment of a small bowel mucosal cell line (FHs 74 int) induced sFRP1 within 8 h, indicating that this gene is positively regulated by beta-catenin, contrasting with the suppression of sFRP1 expression, we saw previously in advanced colorectal cancers. We therefore investigated a series of 12 adenomas and matched large bowel mucosa samples. Real-time RT-PCR analysis showed a reduction in sFRP1 expression in all 12 dysplastic lesions (median 485-fold, IQR 120- to 1500-fold), indicating factors other than beta-catenin influence sFRP1 levels. In a second series of 11 adenomas, we identified methylation of the sFRP1 promotor region in all 11 samples, and this was increased compared with the surrounding normal mucosa in seven cases. Immunohistochemical analysis using a polyclonal antibody supported these findings, with sFRP1 expression reduced in many of the adenoma samples examined. sFRP1 staining in normal mucosa adjacent to the dysplastic tissue was also reduced compared with the normal controls, suggesting that sFRP1 expression may be suppressed in a field of mucosa rather than in individual cells. This study identifies sFRP1 inactivation at the premalignant stage of colorectal cancer development, indicating that these pathways may be useful targets for chemoprevention strategies in this common solid tumour.

Structural MRI of carotid artery atherosclerotic lesion burden and characterization of hemispheric cerebral blood flow before and after carotid endarterectomy.

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.