Accuracy of Automated Computer-Aided Diagnosis for Stroke Imaging: A Critical Evaluation of Current Evidence.

There is increasing interest in computer applications, using artificial intelligence methodologies, to perform health care tasks previously performed by humans, particularly in medical imaging for diagnosis. In stroke, there are now commercial artificial intelligence software for use with computed tomography or MR imaging to identify acute ischemic brain tissue pathology, arterial obstruction on computed tomography angiography or as hyperattenuated arteries on computed tomography, brain hemorrhage, or size of perfusion defects. A rapid, accurate diagnosis may aid treatment decisions for individual patients and could improve outcome if it leads to effective and safe treatment; or conversely, to disaster if a delayed or incorrect diagnosis results in inappropriate treatment. Despite this potential clinical impact, diagnostic tools including artificial intelligence methods are not subjected to the same clinical evaluation standards as are mandatory for drugs. Here, we provide an evidence-based review of the pros and cons of commercially available automated methods for medical imaging diagnosis, including those based on artificial intelligence, to diagnose acute brain pathology on computed tomography or magnetic resonance imaging in patients with stroke.

Automatic segmentation of white matter hyperintensities from brain magnetic resonance images in the era of deep learning and big data - A systematic review.

BACKGROUND: White matter hyperintensities (WMH), of presumed vascular origin, are visible and quantifiable neuroradiological markers of brain parenchymal change. These changes may range from damage secondary to inflammation and other neurological conditions, through to healthy ageing. Fully automatic WMH quantification methods are promising, but still, traditional semi-automatic methods seem to be preferred in clinical research. We systematically reviewed the literature for fully automatic methods developed in the last five years, to assess what are considered state-of-the-art techniques, as well as trends in the analysis of WMH of presumed vascular origin. METHOD: We registered the systematic review protocol with the International Prospective Register of Systematic Reviews (PROSPERO), registration number - CRD42019132200. We conducted the search for fully automatic methods developed from 2015 to July 2020 on Medline, Science direct, IEE Explore, and Web of Science. We assessed risk of bias and applicability of the studies using QUADAS 2. RESULTS: The search yielded 2327 papers after removing 104 duplicates. After screening titles, abstracts and full text, 37 were selected for detailed analysis. Of these, 16 proposed a supervised segmentation method, 10 proposed an unsupervised segmentation method, and 11 proposed a deep learning segmentation method. Average DSC values ranged from 0.538 to 0.91, being the highest value obtained from an unsupervised segmentation method. Only four studies validated their method in longitudinal samples, and eight performed an additional validation using clinical parameters. Only 8/37 studies made available their methods in public repositories. CONCLUSIONS: We found no evidence that favours deep learning methods over the more established k-NN, linear regression and unsupervised methods in this task. Data and code availability, bias in study design and ground truth generation influence the wider validation and applicability of these methods in clinical research.

Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke.

BACKGROUND: Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association. METHODS: We included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24-48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation. RESULTS: Among 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47). CONCLUSION: Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase.

Clinical diagnosis of TIA or minor stroke and prognosis in patients with neurological symptoms: A rapid access clinic cohort.

BACKGROUND: The long-term risk of stroke or myocardial infarction (MI) in patients with minor neurological symptoms who are not clinically diagnosed with transient ischaemic attack (TIA) or minor stroke is uncertain. METHODS: We used data from a rapid access clinic for patients with suspected TIA or minor stroke and follow-up from four overlapping data sources for a diagnosis of ischaemic or haemorrhagic stroke, MI, major haemorrhage and death. We identified patients with and without a clinical diagnosis of TIA or minor stroke. We estimated hazard ratios of stroke, MI, major haemorrhage and death in early and late time periods. RESULTS: 5,997 patients were seen from 2005-2013, who were diagnosed with TIA or minor stroke (n = 3604, 60%) or with other diagnoses (n = 2392, 40%). By 5 years the proportion of patients who had a subsequent ischaemic stroke or MI, in patients with a clinical diagnosis of minor stroke or TIA was 19% [95% confidence interval (CI): 17-20%], and in patients with other diagnoses was 10% (95%CI: 8-15%). Patients with clinical diagnosis of TIA or minor stroke had three times the hazard of stroke or MI compared to patients with other diagnoses [hazard ratio (HR)2.83 95%CI:2.13-3.76, adjusted age and sex] by 90 days post-event; however from 90 days to end of follow up, this difference was attenuated (HR 1.52, 95%CI:1.25-1.86). Older patients and those who had a history of vascular disease had a high risk of stroke or MI, whether or not they were diagnosed with minor stroke or TIA. CONCLUSIONS: Careful attention to vascular risk factors in patients presenting with transient or minor neurological symptoms not thought to be due to stroke or TIA is justified, particularly those who are older or have a history of vascular disease.

Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

OBJECTIVE: To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke. METHODS: The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging. RESULTS: Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, p < 0.001; OR = 0.73, 95% CI 0.66-0.79, p < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, p < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, p = 0.004). CONCLUSION: Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.

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.

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.

Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study.

BACKGROUND: Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension. METHODS: Patients with inadequate biochemical control (GH ≥2.5 µg/L and/or IGF-1 > ULN) at end of core study (month 12) were eligible to switch to pasireotide LAR 40 mg/28 days (n = 81) or octreotide LAR 20 mg/28 days (n = 38). One dose escalation to pasireotide LAR 60 mg/28 days or octreotide LAR 30 mg/28 days was permitted, but not mandatory, at month 17 or 20. RESULTS: Twelve months after crossover, 17.3 % of pasireotide LAR and 0 % of octreotide LAR patients achieved GH <2.5 µg/L and normal IGF-1 (main outcome measure); 27.2 and 5.3 % of pasireotide LAR and octreotide LAR patients achieved normal IGF-1, respectively; 44.4 and 23.7 % of pasireotide LAR and octreotide LAR patients achieved GH <2.5 µg/L, respectively. Mean (±SD) tumor volume further decreased from the end of the core study by 25 % (±25) and 18 % (±28); 54.3 % of pasireotide LAR and 42.3 % of octreotide LAR patients achieved significant (≥20 %) tumor volume reduction during the extension. The safety profile of pasireotide LAR was similar to that of octreotide LAR, with the exception of the frequency and degree of hyperglycemia-related adverse events. CONCLUSIONS: Pasireotide LAR is a promising treatment option for patients with acromegaly inadequately controlled with the first-generation somatostatin analogue octreotide LAR. TRIAL REGISTRATION: clinicaltrials.gov, NCT00600886 . Registered 14 January 2008.

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.

Hemispheric association and dissociation of voice and speech information processing in stroke.

As we listen to someone speaking, we extract both linguistic and non-linguistic information. Knowing how these two sets of information are processed in the brain is fundamental for the general understanding of social communication, speech recognition and therapy of language impairments. We investigated the pattern of performances in phoneme versus gender categorization in left and right hemisphere stroke patients, and found an anatomo-functional dissociation in the right frontal cortex, establishing a new syndrome in voice discrimination abilities. In addition, phoneme and gender performances were most often associated than dissociated in the left hemisphere patients, suggesting a common neural underpinnings.

Consent for Brain Tissue Donation after Intracerebral Haemorrhage: A Community-Based Study.

BACKGROUND: Spontaneous intracerebral haemorrhage is a devastating form of stroke and its incidence increases with age. Obtaining brain tissue following intracerebral haemorrhage helps to understand its cause. Given declining autopsy rates worldwide, the feasibility of establishing an autopsy-based collection and its generalisability are uncertain. METHODS: We used multiple overlapping sources of case ascertainment to identify every adult diagnosed with intracerebral haemorrhage between 1st June 2010-31st May 2012, whilst resident in the Lothian region of Scotland. We sought consent from patients with intracerebral haemorrhage (or their nearest relative if the patient lacked mental capacity) to conduct a research autopsy. RESULTS: Of 295 adults with acute intracerebral haemorrhage, 110 (37%) could not be approached to consider donation. Of 185 adults/relatives approached, 91 (49%) consented to research autopsy. There were no differences in baseline demographic variables or markers of intracerebral haemorrhage severity between consenters and non-consenters. Adults who died and became donors (n = 46) differed from the rest of the cohort (n = 249) by being older (median age 80, IQR 76-86 vs. 75, IQR 65-83, p = 0.002) and having larger haemorrhages (median volume 23 ml, IQR 13-50 vs. 13 ml, IQR 4-40; p = 0.002). CONCLUSIONS: Nearly half of those approached consent to brain tissue donation after acute intracerebral haemorrhage. The characteristics of adults who gave consent were comparable to those in an entire community, although those who donate early are older and have larger haemorrhage volumes.

Influence of intracerebral hemorrhage location on incidence, characteristics, and outcome: population-based study.

BACKGROUND AND PURPOSE: The characteristics of intracerebral hemorrhage (ICH) may vary by ICH location because of differences in the distribution of underlying cerebral small vessel diseases. Therefore, we investigated the incidence, characteristics, and outcome of lobar and nonlobar ICH. METHODS: In a population-based, prospective inception cohort study of ICH, we used multiple overlapping sources of case ascertainment and follow-up to identify and validate ICH diagnoses in 2010 to 2011 in an adult population of 695 335. RESULTS: There were 128 participants with first-ever primary ICH. The overall incidence of lobar ICH was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7-12.4] versus 8.6 [95% confidence interval, 6.7-11.1] per 100 000 adults/y). At baseline, adults with lobar ICH were more likely to have preceding dementia (21% versus 5%; P=0.01), lower Glasgow Coma Scale scores (median, 13 versus 14; P=0.03), larger ICHs (median, 38 versus 11 mL; P<0.001), subarachnoid extension (57% versus 5%; P<0.001), and subdural extension (15% versus 3%; P=0.02) than those with nonlobar ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH (adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21; 95% confidence interval, 0.07-0.63; P=0.006, after adjustment for known predictors of outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8%; 95% confidence interval, 4.6%-28.5% versus 0% after nonlobar ICH; log-rank P=0.04). CONCLUSIONS: The baseline characteristics and outcome of lobar ICH differ from other locations.

Observer reliability of CT angiography in the assessment of acute ischaemic stroke: data from the Third International Stroke Trial.

INTRODUCTION: CT angiography (CTA) is often used for assessing patients with acute ischaemic stroke. Only limited observer reliability data exist. We tested inter- and intra-observer reliability for the assessment of CTA in acute ischaemic stroke. METHODS: We selected 15 cases from the Third International Stroke Trial (IST-3, ISRCTN25765518) with various degrees of arterial obstruction in different intracranial locations on CTA. To assess inter-observer reliability, seven members of the IST-3 expert image reading panel (>5 years experience reading CTA) and seven radiology trainees (<2 years experience) rated all 15 scans independently and blind to clinical data for: presence (versus absence) of any intracranial arterial abnormality (stenosis or occlusion), severity of arterial abnormality using relevant scales (IST-3 angiography score, Thrombolysis in Cerebral Infarction (TICI) score, Clot Burden Score), collateral supply and visibility of a perfusion defect on CTA source images (CTA-SI). Intra-observer reliability was assessed using independently repeated expert panel scan ratings. We assessed observer agreement with Krippendorff's-alpha (K-alpha). RESULTS: Among experienced observers, inter-observer agreement was substantial for the identification of any angiographic abnormality (K-alpha = 0.70) and with an angiography assessment scale (K-alpha = 0.60-0.66). There was less agreement for grades of collateral supply (K-alpha = 0.56) or for identification of a perfusion defect on CTA-SI (K-alpha = 0.32). Radiology trainees performed as well as expert readers when additional training was undertaken (neuroradiology specialist trainees). Intra-observer agreement among experts provided similar results (K-alpha = 0.33-0.72). CONCLUSION: For most imaging characteristics assessed, CTA has moderate to substantial observer agreement in acute ischaemic stroke. Experienced readers and those with specialist training perform best.

Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study.

Pasireotide has a broader somatostatin receptor binding profile than other somatostatin analogues. A 16-week, Phase II trial showed that pasireotide may be an effective treatment for acromegaly. An extension to this trial assessed the long-term efficacy and safety of pasireotide. This study was an open-label, single-arm, open-ended extension study (primary efficacy and safety evaluated at month 6). Patients could enter the extension if they achieved biochemical control (GH ≤ 2.5 µg/L and normal IGF-1) or showed clinically relevant improvements during the core study. Thirty of the 60 patients who received pasireotide (200-900 µg bid) in the core study entered the extension. At extension month 6, of the 26 evaluable patients, six were biochemically controlled, of whom five had achieved control during the core study. Normal IGF-1 was achieved by 13/26 patients and GH ≤ 2.5 µg/L by 12/26 at month 6. Nine patients received pasireotide for ≥24 months in the extension; three who were biochemically controlled at month 24 had achieved control during the core study. Of 29 patients with MRI data, nine had significant (≥20%) tumor volume reduction during the core study; an additional eight had significant reduction during the extension. The most common adverse events were transient gastrointestinal disturbances; hyperglycemia-related events occurred in 14 patients. Twenty patients had fasting plasma glucose shifted to a higher category during the extension. However, last available glucose measurements were normal for 17 patients. Pasireotide has the potential to be an effective, long-term medical treatment for acromegaly, providing sustained biochemical control and significant reductions in tumor volume.

CT and Clinical Predictors of Fatigue at One Month after Stroke.

BACKGROUND: Fatigue is a common and distressing consequence of stroke, and the aetiology of post-stroke fatigue (PSF) is poorly understood. It is unclear whether chronic brain changes [cerebral atrophy and white matter lesions (WML)], stroke lesion location or certain clinical features are related to its development. The aim of this study was to identify, in patients with acute stroke, whether features in different brain regions on routine CT imaging or routinely collected clinical features predicted PSF at 1 month. METHODS: In total, 107 patients (62% male) with acute ischaemic or haemorrhagic stroke were assessed for fatigue (Fatigue Assessment Scale), anxiety and depression (Hospital Anxiety and Depression Scale) at 1 month. Admission brain CT was rated using a structured scoring system for (i) severity of atrophy and (ii) severity of WML in different regions of the brain, and (iii) site of acute and previous vascular lesions. RESULTS: Cerebral atrophy of mild or greater severity was present in 84 patients (77.5%) and WML of mild or greater severity was present in 54 patients (50.5%) in at least one of the evaluated brain regions. There was no association between PSF and severity of atrophy or WML, or presence of acute or previous vascular lesions. We used the Oxfordshire Community Stroke Project (OCSP) classification to explore the possible influence of lesion location because a minority of the patients (37.4%) had visible acute lesions. Fatigue scores were higher in patients with clinically diagnosed posterior strokes (p = 0.046), in females (p = 0.05) and in those with higher depression and anxiety scores (ρ = 0.52; p < 0.001 and ρ = 0.49; p < 0.001, respectively). Structural CT variables were not significant predictors of fatigue (log FAS) in a linear regression which controlled for age, sex, pre-stroke fatigue, OCSP classification, depression and anxiety. The significant predictors of fatigue were depression (ß = 0.30; p = 0.007) and anxiety (ß = 0.28; p = 0.013; adjusted R(2) = 0.254). Stroke subtype (according to the OCSP classification) was marginally predictive (ß = 0.17; p = 0.05) and sex was not statistically significant (ß = 0.15; p = 0.08). CONCLUSIONS: Features on routine post-stroke CT do not appear to associate with fatigue at 1 month. However, clinically diagnosed posterior strokes as well as female gender, anxiety and depression may be linked with fatigue. Therefore, clinical vigilance rather than CT features should be used to predict fatigue early after stroke. Further research is needed in this area to establish whether biological mechanisms underlie the development of PSF.

A systematic review of the utility of 1.5 versus 3 Tesla magnetic resonance brain imaging in clinical practice and research.

OBJECTIVE: MRI at 3 T is said to be more accurate than 1.5 T MR, but costs and other practical differences mean that it is unclear which to use. METHODS: We systematically reviewed studies comparing diagnostic accuracy at 3 T with 1.5 T. We searched MEDLINE, EMBASE and other sources from 1 January 2000 to 22 October 2010 for studies comparing diagnostic accuracy at 1.5 and 3 T in human neuroimaging. We extracted data on methodology, quality criteria, technical factors, subjects, signal-to-noise, diagnostic accuracy and errors according to QUADAS and STARD criteria. RESULTS: Amongst 150 studies (4,500 subjects), most were tiny, compared old 1.5 T with new 3 T technology, and only 22 (15 %) described diagnostic accuracy. The 3 T images were often described as "crisper", but we found little evidence of improved diagnosis. Improvements were limited to research applications [functional MRI (fMRI), spectroscopy, automated lesion detection]. Theoretical doubling of the signal-to-noise ratio was not confirmed, mostly being 25 %. Artefacts were worse and acquisitions took slightly longer at 3 T. CONCLUSION: Objective evidence to guide MRI purchasing decisions and routine diagnostic use is lacking. Rigorous evaluation accuracy and practicalities of diagnostic imaging technologies should be the routine, as for pharmacological interventions, to improve effectiveness of healthcare. KEY POINTS : • Higher field strength MRI may improve image quality and diagnostic accuracy. • There are few direct comparisons of 1.5 and 3 T MRI. • Theoretical doubling of the signal-to-noise ratio in practice was only 25 %. • Objective evidence of improved routine clinical diagnosis is lacking. • Other aspects of technology improved images more than field strength.

Use of dynamic contrast-enhanced MRI to measure subtle blood-brain barrier abnormalities.

There is growing interest in investigating the role of subtle changes in blood-brain barrier (BBB) function in common neurological disorders and the possible use of imaging techniques to assess these abnormalities. Some studies have used dynamic contrast-enhanced MR imaging (DCE-MRI) and these have demonstrated much smaller signal changes than obtained from more traditional applications of the technique, such as in intracranial tumors and multiple sclerosis. In this work, preliminary results are presented from a DCE-MRI study of patients with mild stroke classified according to the extent of visible underlying white matter abnormalities. These data are used to estimate typical signal enhancement profiles in different tissue types and by degrees of white matter abnormality. The effect of scanner noise, drift and different intrinsic tissue properties on signal enhancement data is also investigated and the likely implications for interpreting the enhancement profiles are discussed. No significant differences in average signal enhancement or contrast agent concentration were observed between patients with different degrees of white matter abnormality, although there was a trend towards greater signal enhancement with more abnormal white matter. Furthermore, the results suggest that many of the factors considered introduce uncertainty of a similar magnitude to expected effect sizes, making it unclear whether differences in signal enhancement are truly reflective of an underlying BBB abnormality or due to an unrelated effect. As the ultimate aim is to achieve a reliable quantification of BBB function in subtle disorders, this study highlights the factors which may influence signal enhancement and suggests that further work is required to address the challenging problems of quantifying contrast agent concentration in healthy and diseased living human tissue and of establishing a suitable model to enable quantification of relevant physiological parameters. Meanwhile, it is essential that future studies use an appropriate control group to minimize these influences.

A large web-based observer reliability study of early ischaemic signs on computed tomography. The Acute Cerebral CT Evaluation of Stroke Study (ACCESS).

BACKGROUND: Early signs of ischaemic stroke on computerised tomography (CT) scanning are subtle but CT is the most widely available diagnostic test for stroke. Scoring methods that code for the extent of brain ischaemia may improve stroke diagnosis and quantification of the impact of ischaemia. METHODOLOGY AND PRINCIPAL FINDINGS: We showed CT scans from patients with acute ischaemic stroke (n = 32, with different patient characteristics and ischaemia signs) to doctors in stroke-related specialties world-wide over the web. CT scans were shown twice, randomly and blindly. Observers entered their scan readings, including early ischaemic signs by three scoring methods, into the web database. We compared observers' scorings to a reference standard neuroradiologist using area under receiver operator characteristic curve (AUC) analysis, Cronbach's alpha and logistic regression to determine the effect of scales, patient, scan and observer variables on detection of early ischaemic changes. Amongst 258 readers representing 33 nationalities and six specialties, the AUCs comparing readers with the reference standard detection of ischaemic signs were similar for all scales and both occasions. Being a neuroradiologist, slower scan reading, more pronounced ischaemic signs and later time to CT all improved detection of early ischaemic signs and agreement on the rating scales. Scan quality, stroke severity and number of years of training did not affect agreement. CONCLUSIONS: Large-scale observer reliability studies are possible using web-based tools and inform routine practice. Slower scan reading and use of CT infarct rating scales improve detection of acute ischaemic signs and should be encouraged to improve stroke diagnosis.

Lacunar stroke is associated with diffuse blood-brain barrier dysfunction.

OBJECTIVE: Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood-brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke. METHODS: We recruited patients with lacunar and mild cortical stroke. We assessed BBB leak in gray matter, white matter, and cerebrospinal fluid, at least 1 month after stroke, using magnetic resonance imaging before and after intravenous gadolinium. We measured tissue enhancement for 30 minutes after intravenous gadolinium by two image analysis approaches (regions of interest and tissue segmentation). We compared the enhancement (leak) between lacunar and cortical patients, and associations with key variables, using general linear modeling. RESULTS: We recruited 51 lacunar and 46 cortical stroke patients. Signal enhancement after gadolinium was higher in lacunar than cortical stroke patients in white matter (p < 0.001) and cerebrospinal fluid (p < 0.003) by both analysis methods, independent of other variables. Signal enhancement after gadolinium was also associated with increasing age and enlarged perivascular spaces, but these did not explain the lacunar-cortical difference. INTERPRETATION: Patients with lacunar stroke have subtle, diffuse BBB dysfunction in white matter. Further studies are required to determine the relative contributions of BBB dysfunction and/or ischemia to the microvascular and brain abnormalities in lacunar stroke.