Grant Mair

Airway dimensions in COPD: Relationships with clinical variables

BACKGROUND COPD patients have varying degrees of airways disease and emphysema. CT scanning can differentiate these pathological subtypes. We evaluated airway dimensions and emphysema severity with low dose CT scanning in COPD patients to determine relationships with clinical features of the disease. METHODS Fifty six patients with COPD had a low dose thoracic CT scan. Airways were analysed using novel software as either proximal (1st and 2nd generation) or distal (3rd to 6th generation); the extent of emphysema was assessed as the percentage of pixels less than -950 Hounsfield units. CT measures were related to clinical features of COPD. RESULTS Thicker walls in the proximal airways were associated with clinical features that may represent a bronchitic phenotype (MRC Bronchitis Score; β = 0.20, p = 0.003, Frequent Exacerbations; β = 0.14, p = 0.017, Total St Georges Score; β = 0.50, p = 0.001 and body mass index [BMI]; β = 0.26, p = 0.049); these associations were independent of emphysema. BMI was negatively correlated with the degree of emphysema (β = -0.41, p = 0.001). Airway wall thickness was negatively correlated with CT measured emphysema for both proximal and more distal airways (r = -0.30, p = 0.025 and r = -0.32, p = 0.015). CONCLUSIONS CT measured airway dimensions are associated with several clinical measures of COPD; these are related to a bronchitic phenotype and the effect is independent of emphysema.

Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers

Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema. A total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance). Emphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George’s Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution. Distribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.

Sensitivity and Specificity of the Hyperdense Artery Sign for Arterial Obstruction in Acute Ischemic Stroke

Background and Purpose— In acute ischemic stroke, the hyperdense artery sign (HAS) on noncontrast computed tomography (CT) is thought to represent intraluminal thrombus and, therefore, is a surrogate of arterial obstruction. We sought to assess the accuracy of HAS as a marker of arterial obstruction by thrombus. Methods— The Third International Stroke Trial (IST-3) was a randomized controlled trial testing the use of intravenous thrombolysis for acute ischemic stroke in patients who did not clearly meet the prevailing license criteria. Some participating IST-3 centers routinely performed CT or MR angiography at baseline. One reader assessed all relevant scans independently, blinded to all other data; we checked observer reliability. We combined IST-3 data with a systematic review and meta-analysis of all studies that assessed the accuracy of HAS using angiography (any modality). Results— IST-3 had 273 patients with baseline CT or MR angiography and was the largest study of HAS accuracy. The meta-analysis (n=902+273=1175, including IST-3) found sensitivity and specificity of HAS for arterial obstruction on angiography to be 52% and 95%, respectively. HAS was more commonly identified in proximal than distal arteries (47% versus 37%; P=0.015), and its sensitivity increased with thinner CT slices (r=−0.73; P=0.001). Neither extent of obstruction nor time after stroke influenced HAS accuracy. Conclusions— When present in acute ischemic stroke, HAS indicates a high likelihood of arterial obstruction, but its absence indicates only a 50/50 chance of normal arterial patency. Thin-slice CT improves sensitivity of HAS detection. Clinical Trial Registration— URL: http://www.controlled-trials.com/ISRCTN25765518. Unique identifier: ISRCTN25765518.

Cerebral White Matter Hypoperfusion Increases with Small-Vessel Disease Burden. Data From the Third International Stroke Trial

BACKGROUND Leukoaraiosis is associated with impaired cerebral perfusion, but the effect of individual and combined small-vessel disease (SVD) features on white matter perfusion is unclear. METHODS We studied patients recruited with perfusion imaging in the Third International Stroke Trial. We rated individual SVD features (leukoaraiosis, lacunes) and brain atrophy on baseline plain computed tomography or magnetic resonance imaging. Separately, we assessed white matter at the level of the lateral ventricles in the cerebral hemisphere contralateral to the stroke for visible areas of hypoperfusion (present or absent) on 4 time-based perfusion imaging parameters. We examined associations between SVD features (individually and summed) and presence of hypoperfusion using logistic regression adjusted for age, sex, baseline National Institutes of Health Stroke Scale, hypertension, and diabetes. RESULTS A total of 115 patients with median (interquartile range) age of 81 (72-86) years, 78 (52%) of which were male, had complete perfusion data. Hypoperfusion was most frequent on mean transit time (MTT; 63 patients, 55%) and least frequent on time to maximum flow (19 patients, 17%). The SVD score showed stronger independent associations with hypoperfusion (e.g., MTT, odds ratio [OR] = 2.80; 95% confidence interval [CI] = 1.56-5.03) than individual SVD markers (e.g., white matter hypoattenuation score, MTT, OR = 1.49, 95% CI = 1.09-2.04). Baseline blood pressure did not differ by presence or absence of hypoperfusion or across strata of SVD score. Presence of white matter hypoperfusion increased with SVD summed score. CONCLUSIONS The SVD summed score was associated with hypoperfusion more consistently than individual SVD features, providing validity to the SVD score concept. Increasing SVD burden indicates worse perfusion in the white matter.

Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke

Objective: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). Methods: All prerandomization and follow-up (24–48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). Results: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). Conclusions: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. Classification of evidence: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.

Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke

Background and Purpose— Computed tomographic angiography and magnetic resonance angiography are used increasingly to assess arterial patency in patients with ischemic stroke. We determined which baseline angiography features predict response to intravenous thrombolytics in ischemic stroke using randomized controlled trial data. Methods— We analyzed angiograms from the IST-3 (Third International Stroke Trial), an international, multicenter, prospective, randomized controlled trial of intravenous alteplase. Readers, masked to clinical, treatment, and outcome data, assessed prerandomization computed tomographic angiography and magnetic resonance angiography for presence, extent, location, and completeness of obstruction and collaterals. We compared angiography findings to 6-month functional outcome (Oxford Handicap Scale) and tested for interactions with alteplase, using ordinal regression in adjusted analyses. We also meta-analyzed all available angiography data from other randomized controlled trials of intravenous thrombolytics. Results— In IST-3, 300 patients had prerandomization angiography (computed tomographic angiography=271 and magnetic resonance angiography=29). On multivariable analysis, more extensive angiographic obstruction and poor collaterals independently predicted poor outcome (P<0.01). We identified no significant interaction between angiography findings and alteplase effect on Oxford Handicap Scale (P≥0.075) in IST-3. In meta-analysis (5 trials of alteplase or desmoteplase, including IST-3, n=591), there was a significantly increased benefit of thrombolytics on outcome (odds ratio>1 indicates benefit) in patients with (odds ratio, 2.07; 95% confidence interval, 1.18–3.64; P=0.011) versus without (odds ratio, 0.88; 95% confidence interval, 0.58–1.35; P=0.566) arterial obstruction (P for interaction 0.017). Conclusions— Intravenous thrombolytics provide benefit to stroke patients with computed tomographic angiography or magnetic resonance angiography evidence of arterial obstruction, but the sample was underpowered to demonstrate significant treatment benefit or harm among patients with apparently patent arteries. Clinical Trial Registration— URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518.

Survey of UK radiology trainees in the aftermath of 'Modernising Medical Careers'

BackgroundFollowing implementation of Modernising Medical Careers (MMC) in the UK, potential radiology trainees must decide on their career and apply sooner than ever before. We aimed to determine whether current trainees were sufficiently informed to make an earlier career decision by comparing the early radiology experiences of Traditional and Foundation Trainees.Methods344 radiology trainees were appointed through MMC in 2007/08. This cohort was surveyed online.ResultsResponse rate was 174/344 (51%). Traditional Trainees made their career decision 2.6 years after graduation compared with 1.2 years for Foundation Trainees (57/167, 34%). Nearly half of responders (79/169, 47%) experienced no formal radiology teaching as undergraduates. Most trainees regularly attended radiology meetings, spent time in a radiology department and/or performed radiology research. Many trainees received no career advice specific to radiology (69/163, 42%) at any point prior to entering the specialty; this includes both formal and informal advice. Junior doctor experiences were more frequently cited as influencing career choice (98/164, 60%). An earlier career decision was associated with; undergraduate radiology projects (-0.72 years, p = 0.018), career advice (-0.63 years, p = 0.009) and regular attendance at radiology meetings (-0.65 years, p = 0.014).ConclusionEarly experience of radiology enables trainees to make an earlier career decision, however current radiology trainees were not always afforded relevant experiences prior to entering training. Radiologists need to be more proactive in encouraging the next generation of trainees.

Penumbra and re-canalization acute computed tomography in ischemic stroke evaluation: PRACTISE study protocol

Rationale Multimodal imaging, including computed tomography angiography and computed tomography perfusion imaging, yields additional information on intracranial vessels and brain perfusion and can differentiate between ischemic core and penumbra which may affect patient selection for intravenous thrombolysis. Hypothesis The use of multimodal imaging will increase the number of patients receiving intravenous thrombolysis and lead to better treatment outcomes. Sample size 400 patients. Methods and design PRACTISE is a prospective, multicenter, randomized, controlled trial in which patients presenting within 4.5 h of symptom onset are randomized to either the current evidence-based imaging (NCCT alone) or additional multimodal computed tomography imaging (NCCT + computed tomography angiography + computed tomography perfusion). Clinical decisions on intravenous recombinant tissue plasminogen activator are documented. Total imaging time in both arms and time to initiation of treatment delivery in those treated with intravenous recombinant tissue plasminogen activator, is recorded. Follow-up will include brain imaging at 24 h to document infarct size, the presence of edema and the presence of intra-cerebral hemorrhage. Clinical evaluations include NIHSS score at baseline, 24 h and day 7 ± 2, and mRS at day 90 to define functional outcomes. Study outcomes The primary outcome is the proportion of patients receiving intravenous recombinant tissue plasminogen activator. Secondary end-points evaluate times to decision-making, comparison of different image processing software and clinical outcomes at three months. Discussion Multimodal computed tomography is a widely available tool for patient selection for revascularization therapy, but it is currently unknown whether the use of additional imaging in all stroke patients is beneficial. The study opened for recruitment in March 2015 and will provide data on the value of multimodal imaging in treatment decisions for acute stroke.

Effect of X-Ray Attenuation of Arterial Obstructions on Intravenous Thrombolysis and Outcome after Ischemic Stroke

Objective To assess whether the x-ray attenuation of intra-arterial obstruction measured on non-contrast CT in ischemic stroke can predict response to thrombolysis and subsequent functional outcome. Methods The Third International Stroke Trial (IST-3) was a multicenter randomized-controlled trial of intravenous thrombolysis (rt-PA) given within six hours of ischemic stroke. Ethical approval and informed consent were obtained. In a subgroup of 109 IST-3 patients (38 men, median age 82 years), a single reader, masked to all clinical and other imaging data, manually measured x-ray attenuation (Hounsfield Units, HU) on non-contrast CT at the location of angiographically-proven intra-arterial obstructions, pre-randomization and at 24–48 hour follow-up. We calculated change in attenuation between scans. We assessed the impact of pre-randomization arterial obstruction attenuation on six-month functional outcome. Results Most arterial obstructions (64/109, 59%) were hyperattenuating (mean 51.0 HU). Compared with control, treatment with rt-PA was associated with a greater, but non-significant, reduction in obstruction attenuation at follow-up (-8.0 HU versus -1.4 HU in patients allocated control, p = 0.117). In multivariable ordinal regression analysis controlled for patient age, stroke severity, location and extent of obstruction, time from stroke onset to baseline scan and rt-PA treatment allocation, the attenuation of pre-randomization arterial obstruction was not independently associated with six-month outcome (odds ratio = 0.99, 95% confidence interval = 0.94–1.03, p = 0.516). Conclusions In ischemic stroke, the x-ray attenuation of the arterial obstruction may decline more rapidly from baseline to 24–48 hours following treatment with thrombolysis but we found no evidence that baseline arterial obstruction attenuation predicts six-month outcome.

Blood pressure variability and leukoaraiosis in acute ischemic stroke

Higher blood pressure, blood pressure variability, and leukoaraiosis are risk factors for early adverse events and poor functional outcome after ischemic stroke, but prior studies differed on whether leukoaraiosis was associated with blood pressure variability, including in ischemic stroke. In the Third International Stroke Trial, blood pressure was measured in the acute phase of ischemic stroke immediately prior to randomization, and at 0.5, 1, and 24 h after randomization. Masked neuroradiologists rated index infarct, leukoaraiosis, and atrophy on CT using validated methods. We characterized blood pressure variation by coefficient of variance and three other standard methods. We measured associations between blood pressure, blood pressure variability, and leukoaraiosis using generalized estimating equations, adjusting for age, and a number of covariates related to treatment and stroke type/severity. Among 3017 patients, mean (±SD) systolic and diastolic blood pressure decreased from 155(±24)/82(±15) mmHg pre-randomization to 146(±23)/78(±14) mmHg 24 h later (P < 0.005). Mean within-subject coefficient of variance was 0.09 ± 0.05 for systolic and 0.11 ± 0.06 for diastolic blood pressure. Patients with most leukoaraiosis were older and had higher blood pressure than those with least (P < 0.0001). Although statistically significant in simple pairwise comparisons, no measures of blood pressure variability were associated with leukoaraiosis when adjusting for confounding variables (P > 0.05), e.g. age. Our results suggest that blood pressure variability is not a potential mechanism to explain the association between leukoaraiosis and poor outcome after acute stroke.