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Background and Objective: Brain metastases are common in lung cancer and increasingly treated using targeted radiotherapy techniques such as stereotactic radiosurgery (SRS). Using MRI, post-SRS changes may be difficult to distinguish from progressive brain metastasis. Contrast clearance analysis (CCA) uses T1-weighted MRI images to assess the clearance of gadolinium and can be thus used to assess vascularity and active tumours., Design and Methods: We retrospectively assessed CCAs in 62 patients with non-small cell lung cancer (NSCLC) undergoing 104 CCA scans in a single centre., Results: The initial CCA suggested the aetiology of equivocal changes on standard MRI in 80.6% of patients. In all patients whose initial CCA showed post-SRS changes and who underwent serial CCAs, the initial diagnosis was upheld with the serial imaging. In only two cases of a presumed progressive tumour on the initial CCA, subsequent treatment for radionecrosis was instigated; a retrospective review and re-evaluation of the CCAs show that progression was reported where a thin rim of rapid contrast clearance was seen, and this finding has been subsequently recognised as a feature of post-treatment change on CCAs. The lack of concordance with CCA findings in those who underwent surgical resection was also found to be due to the over-reporting of the thin blue rim as disease in the early cases of CCA use and, in three cases, potentially related to timelines longer than 7 days prior to surgery, both factors being unknown during the early implementation phase of CCA at our centre but subsequently learned., Conclusions: Our single-centre experience shows CCA to be feasible and useful in patients with NSCLC in cases of diagnostic uncertainty in MRI. It has helped guide treatment in the majority of patients, with subsequent outcomes following the implementation of the treatment based on the results, suggesting correct classification. Recommendations from our experience of the implementation include the careful consideration of the thin rim of the rapid contrast clearance and the timing of the CCA prior to surgery for suspected brain metastasis progression.

7 Tesla-field-strength (7 T) Magnetic Resonance Imaging allows the small perforating arteries in the brain to be visualised, and this modality may allow visualisation of the arterial pathology in cerebral small vessel disease. Most studies have used standard Time-of-Flight (ToF) Magnetic Resonance Angiography (MRA). Whether the use of contrast enhancement improves perforating artery visualisation at 7 T remains unclear. In a prospective study, we compared standard ToF MRA with contrast-enhanced (CE) ToF MRA at 7 T for the visualisation of the lenticulostriate arteries (LSAs). Ten patients with symptomatic lacunar stroke were recruited (mean age, SD, 64 ± 9.9 years). Visualisation was assessed using a visual rating scale administered by two independent expert readers and length of the LSAs visible. Visualisation of the LSAs was improved with CE ToF MRA. The mean Visibility and Sharpness Score was higher for CE ToF MRA over standard ToF MRA (2.55 ± 0.64 vs. 1.75 ± 0.68; P = 0.0008). The mean length of LSA visualised was significantly longer with CE ToF MRA compared to standard ToF MRA (24.4 ± 4.5 vs. 21.9 ± 4.0 mm; P = 0.01). CE ToF MRA offers improved visualisation of the LSAs over standard ToF MRA. The addition of contrast may improve the ability to visualise cerebral small vessel disease arterial pathology., (© 2022. The Author(s).)

Background and Aim: Whether cerebral microbleeds cause cognitive impairment remains uncertain. We analyzed whether cerebral microbleeds are associated with cognitive dysfunction in patients with symptomatic cerebral small vessel disease, and whether this association is independent of other neuroimaging markers of cerebral small vessel disease., Methods: We analyzed consecutive patients with MRI-confirmed lacunar stroke included in DNA-Lacunar-2 multicenter study. Cerebral microbleeds were graded using the Brain Observer Microbleed Rating Scale (BOMBS). Neuropsychological assessment was performed using the Brief Memory and Executive Test (BMET). We analyzed the association between cerebral microbleeds, BMET, and the following subdomains: executive function/processing speed and orientation/memory. We also searched for an independent association between cerebral microbleeds and vascular cognitive impairment, defined as BMET ≤ 13., Results: Out of 688 included patients, cerebral microbleeds were detected in 192 (27.9%). After adjusting for white matter hyperintensities severity, lacune count, and other confounders, both the presence and the number of cerebral microbleeds were significantly associated with impaired cognitive performance [β = -13.0; 95% CI = (-25.3, -0.6) and β = -13.1; 95% CI = (-19.8, -6.4), respectively]. On analysis of specific cognitive domains, associations were present for executive function/processing speed [β = -5.8; 95% CI = (-9.3, -2.2) and β = -4.3; 95% CI = (-6.2, -2.4), respectively] but not for orientation/memory [β = -0.4; 95% CI = (-4.0, 3.2) and β = -2.1; 95% CI = (-4.0, 0.1), respectively]. We also found an independent association between the presence and the number of cerebral microbleeds and vascular cognitive impairment [adjusted OR = 1.48; 95% CI = (1.01, 2.18) and OR = 1.43; 95% CI = (1.15, 1.79), respectively]., Conclusion: In a large cohort of symptomatic cerebral small vessel disease patients, after controlling for other neuroimaging markers of cerebral small vessel disease severity, cerebral microbleeds were associated with cognitive dysfunction. Executive function and processing speed were predominantly impaired. This might suggest a causal role of cerebral microbleeds in determining vascular cognitive impairment.

Background and Objectives: To determine the prevalence of and risk factors for cerebral microbleeds (CMBs) at different locations in a large healthy community population., Methods: A total of 8,159 participants from the UK Biobank with MRI scans suitable for CMB analysis were included. Brain susceptibility-weighted imaging data were acquired on 2 identical 3.0T scanners. The Microbleed Anatomical Rating Scale was used to identify definite CMBs. Generalized linear models were used to determine independent associations with all CMBs and lobar, deep, and infratentorial CMBs., Results: The mean age at scan was 62.1 ± 7.4 years. One or more definite CMBs were detected in 572 (7.0%) participants. Of those with CMBs, 439 (76.7%) had lobar CMBs, 103 (18.0%) had deep CMBs, and 83 (14.5%) had infratentorial CMBs. Age was an independent risk factor for CMBs in all locations. APOE4 and male sex were positively associated and higher body mass index was negatively associated with lobar CMBs. Hypertension, smoking, and alcohol consumption were associated with deep CMBs, but not with lobar CMBs. Only age was associated with infratentorial CMBs. The associations were unchanged after controlling for white matter hyperintensity lesion volume as a marker of small vessel disease severity., Discussion: In this large population-based study, CMB prevalence detected using a low sensitivity and high specificity system was 7%. There were distinct risk factor profiles for CMBs in lobar and deep locations consistent with different underlying pathophysiologic processes., Trial Registration Information: Clinical Trial registration number: UK Biobank application number 19463., (© 2021 American Academy of Neurology.)

Objective: To identify common genetic variants associated with the presence of brain microbleeds (BMBs)., Methods: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs., Results: BMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR] any BMB [95% confidence interval (CI)] 1.33 [1.21-1.45]; p = 2.5 × 10 -10 ). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19-1.50]; p = 1.0 × 10 -6 ) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86-1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB., Conclusions: Genetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Bone marrow composition varies with stage of development., Purpose: To assess differences in apparent diffusion coefficient (ADC) derived from clivus bone marrow in healthy children by age, pubertal status, and gender as a benchmark when monitoring local and systemic treatment-induced effects., Material and Methods: Non-oncological pediatric patients (30 pre-pubertal [15 girls, 15 boys] and 30 post-pubertal [15 girls, 15 boys]) with previous normal magnetic resonance imaging (MRI) of the brain including diffusion-weighted magnetic resonance imaging (DW-MRI; 1.5-T Philips Achieva-Ingenia, b-values 0 and 1000s/mm 2 ) were studied. A 4-6 mm diameter region of interest (ROI), drawn within the clivus on two or three DW-MRI slices, yielded mean and centile ADC values. Pubertal status was recognized from imaging appearances of the pituitary gland and from fusion of the spheno-occipital synchondrosis. Correlations between ADC and age were assessed (Pearson's coefficient). Mann-Whitney U tests compared ADC by age, pubertal status, and gender., Results: Age and ADC were significantly negatively correlated (median ADC r=-0.48, mean ADC r=-0.42, P =0.0001 and 0.0008, respectively) which held true when divided by gender. Mean and median ADC differed significantly before and after puberty for the whole population ( P =0.0001 and 0.0001, respectively). There was a left shift of the ADC histogram after puberty with significant differences in centile values. ADC differences before and after puberty remained when divided by gender (girls: P =0.04 and 0.009, respectively; boys: P =0.005 and 0.0002, respectively)., Conclusion: ADC of clivus bone marrow correlates with age in children. ADC decreases significantly after puberty, likely due to replacement of hypercellular marrow with fat. There are no gender-related differences in clivus bone-marrow ADC before or after puberty.

Acute stroke is often superimposed on chronic damage from previous cerebrovascular events. This background will inevitably modulate the impact of acute injury on clinical outcomes to an extent that will depend on the precise anatomical pattern of damage. Previous attempts to quantify such modulation have employed only reductive models that ignore anatomical detail. The combination of automated image processing, large-scale data, and machine learning now enables us to quantify the impact of this with high-dimensional multivariate models sensitive to individual variations in the detailed anatomical pattern. We introduce and validate a new automated chronic lesion segmentation routine for use with non-contrast CT brain scans, combining non-parametric outlier-detection score, Zeta, with an unsupervised 3-dimensional maximum-flow, minimum-cut algorithm. The routine was then applied to a dataset of 1,704 stroke patient scans, obtained at their presentation to a hyper-acute stroke unit (St George's Hospital, London, UK), and used to train a support vector machine (SVM) model to predict between low (0-2) and high (3-6) pre-admission and discharge modified Rankin Scale (mRS) scores, quantifying performance by the area under the receiver operating curve (AUROC). In this single center retrospective observational study, our SVM models were able to differentiate between low (0-2) and high (3-6) pre-admission and discharge mRS scores with an AUROC of 0.77 (95% confidence interval of 0.74-0.79), and 0.76 (0.74-0.78), respectively. The chronic lesion segmentation routine achieved a mean (standard deviation) sensitivity, specificity and Dice similarity coefficient of 0.746 (0.069), 0.999 (0.001), and 0.717 (0.091), respectively. We have demonstrated that machine learning models capable of capturing the high-dimensional features of chronic injuries are able to stratify patients-at the time of presentation-by pre-admission and discharge mRS scores. Our fully automated chronic stroke lesion segmentation routine simplifies this process, and utilizes routinely collected CT head scans, thereby facilitating future large-scale studies to develop supportive clinical decision tools., (Copyright © 2020 Mah, Nachev and MacKinnon.)

Background and Purpose- Cerebral small vessel disease (SVD) is the most common cause of vascular cognitive impairment, with a significant proportion of cases going on to develop dementia. We explore the extent to which diffusion tensor image segmentation technique (DSEG; which characterizes microstructural damage across the cerebrum) predicts both degree of cognitive decline and conversion to dementia, and hence may provide a useful prognostic procedure. Methods- Ninety-nine SVD patients (aged 43-89 years) underwent annual magnetic resonance imaging scanning (for 3 years) and cognitive assessment (for 5 years). DSEG- θ was used as a whole-cerebrum measure of SVD severity. Dementia diagnosis was based Diagnostic and Statistical Manual of Mental Disorders V criteria. Cox regression identified which DSEG measures and vascular risk factors were related to increased risk of dementia. Linear discriminant analysis was used to classify groups of stable versus subsequent dementia diagnosis individuals. Results- DSEG- θ was significantly related to decline in executive function and global cognition ( P <0.001). Eighteen (18.2%) patients converted to dementia. Baseline DSEG- θ predicted dementia with a balanced classification rate=75.95% and area under the receiver operating characteristic curve=0.839. The best classification model included baseline DSEG- θ , change in DSEG- θ , age, sex, and premorbid intelligence quotient (balanced classification rate of 79.65%; area under the receiver operating characteristic curve=0.903). Conclusions- DSEG is a fully automatic technique that provides an accurate method for assessing brain microstructural damage in SVD from a single imaging modality (diffusion tensor imaging). DSEG- θ is an important tool in identifying SVD patients at increased risk of developing dementia and has potential as a clinical marker of SVD severity.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare autosomal recessive disorder of nucleoside metabolism that is caused by mutations in the nuclear thymidine phosphorylase gene ( TYMP ) gene, encoding for the enzyme thymidine phosphorylase. There are currently no approved treatments for MNGIE. The aim of this study was to investigate the safety, tolerability, and efficacy of an enzyme replacement therapy for the treatment of MNGIE. In this single centre study, three adult patients with MNGIE received intravenous escalating doses of erythrocyte encapsulated thymidine phosphorylase (EE-TP; dose range: 4 to 108 U/kg/4 weeks). EE-TP was well tolerated and reductions in the disease-associated plasma metabolites, thymidine, and deoxyuridine were observed in all three patients. Clinical improvements, including weight gain and improved disease scores, were observed in two patients, suggesting that EE-TP is able to reverse some aspects of the disease pathology. Transient, non-serious adverse events were observed in two of the three patients; these did not lead to therapy discontinuation and they were managed with pre-medication prior to infusion of EE-TP. To conclude, enzyme replacement therapy with EE-TP demonstrated biochemical and clinical therapeutic efficacy with an acceptable clinical safety profile.

Striking MRI brain changes resembling leukoencephalopathy are rarely seen in classical homocystinuria. Our case suggests that reversible white matter changes (WMC) are linked to elevated plasma methionine levels arising during treatment.A 6-year-old boy with learning difficulties and a normal MRI brain scan was diagnosed with homocystinuria (initial total homocysteine 344 μmol/L and methionine 64 μmol/L). At the age of 6.5 years, he developed superior sagittal sinus (SSS) thrombosis. Antithrombotic and homocysteine-lowering treatments were started. Due to poor dietary compliance and betaine treatment, his methionine level reached 1,285 μmol/L, and left side weakness developed. Repeat MRI scan revealed new confluent WMC in previously myelinated brain areas. Further 3-month treatment with tighter dietary control significantly dropped his methionine level (233 μmol/L) with resolution of his neurological deficit and of radiological changes.We suggest a reversible toxicity from hypermethioninaemia as a possible source of cerebral WMC (secondary to a demyelinating process) in patients with homocystinuria. It highlights the importance of homocysteine-lowering treatment as a prevention and complete resolution of neurological complications. It also demonstrates the need to consider homocystinuria in a differential diagnosis of paediatric leukoencephalopathy.

Diffusion-weighted imaging (DWI) is a well-established technique in neuroimaging, but the diagnostic value of DWI outside the setting of acute infarct and abscess is sometimes under-recognised particularly in paediatric neuroimaging. DWI also plays an important role in the evaluation of intracranial infection, brain tumours, demyelinating diseases, and metabolic disorders. DWI can assist in the early detection and characterisation of intraocular and skull-base pathology. The cases presented in this article demonstrate the utility of DWI in paediatric neuroimaging. DWI can improve diagnostic sensitivity and in conjunction with other magnetic resonance imaging (MRI) sequences can aid in early diagnosis and management. Obtaining an early diagnosis may avoid potential complications and improve patient outcome., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Glucose transporter type 1 (GLUT1) deficiency syndrome is a well recognised genetic neurometabolic disorder typically presenting with progressive encephalopathy, acquired microcephaly and drug-resistant epilepsy. Imaging is normal in the majority. Here we describe a 5-month-old boy who presented with motor delay, myoclonic jerks and tonic-clonic seizures. His MRI brain scan revealed confluent symmetrical T2 hyperintense signal abnormality in both anterior frontal lobes and delayed myelination. Neurometabolic screen revealed low CSF glucose and lactate levels. A pathogenic de novo heterozygous mutation in SLC2A1 (c.275+1G > A) confirmed the diagnosis of GLUT1 deficiency. Ketogenic diet resulted in a dramatic termination of his seizures at 72 h. At 15 months, he continued to be seizure free with marked developmental catch up. Repeat imaging revealed a significant resolution of the previously seen changes. This case suggests that GLUT1 deficiency should be considered in the differential diagnosis of infants with suspected genetic leukoencephalopathies with important treatment implications., (Copyright © 2018. Published by Elsevier Ltd.)

Sporadic cerebral small vessel disease is an important cause of vascular dementia, a syndrome of cognitive impairment together with vascular brain damage. At post-mortem pure vascular dementia is rare, with evidence of co-existing Alzheimer's disease pathology in 95% of cases. This work used MRI to characterize structural abnormalities during the preclinical phase of vascular dementia in symptomatic small vessel disease. 121 subjects were recruited into the St George's Cognition and Neuroimaging in Stroke study and followed up longitudinally for five years. Over this period 22 individuals converted to dementia. Using voxel-based morphometry, we found structural abnormalities present at baseline in those with preclinical dementia, with reduced grey matter density in the left striatum and hippocampus, and more white matter hyperintensities in the frontal white-matter. The lacunar data revealed that some of these abnormalities may be due to lesions within the striatum and centrum semiovale. Using support vector machines, future dementia could be best predicted using hippocampal and striatal Jacobian determinant data, achieving a balanced classification accuracy of 73%. Using cluster ward linkage we identified four anatomical subtypes. Successful predictions were restricted to groups with lower levels of vascular damage. The subgroup that could not be predicted were younger, further from conversion, had the highest levels of vascular damage, with milder cognitive impairment at baseline but more rapid deterioration in processing speed and executive function, consistent with a primary vascular dementia. In contrast, the remaining groups had decreasing levels of vascular damage and increasing memory impairment consistent with progressively more Alzheimer's-like pathology. Voxel-wise rates of hippocampal atrophy supported these distinctions, with the vascular group closely resembling the non-dementing cohort, whereas the Alzheimer's like group demonstrated global hippocampal atrophy. This work reveals distinct anatomical endophenotypes in preclinical vascular dementia, forming a spectrum between vascular and Alzheimer's like pathology. The latter group can be identified using baseline MRI, with 73% converting within 5 years. It was not possible to predict the vascular dominant dementia subgroup, however 19% of negative predictions with high levels of vascular disease would ultimately develop dementia. It may be that techniques more sensitive to white matter damage, such as diffusion weighted imaging, may prove more useful for this vascular dominant subgroup in the future. This work provides a way to accurately stratify patients using a baseline MRI scan, and has utility in future clinical trials designed to slow or prevent the onset of dementia in these high-risk cohorts.

Background and Purpose: Cerebral small-vessel disease is a major cause of cognitive impairment. Perivascular spaces (PvS) occur in small-vessel disease, but their relationship to cognitive impairment remains uncertain. One reason may be difficulty in distinguishing between lacunes and PvS. We determined the relationship between baseline PvS score and PvS volume with change in cognition over a 5-year follow-up. We compared this to the relationship between baseline lacune count and total lacune volume with cognition. In addition, we examined change in PvS volume over time., Methods: Data from the prospective SCANS study (St Georges Cognition and Neuroimaging in Stroke) of patients with symptomatic lacunar stroke and confluent leukoaraiosis were used (n=121). Multimodal magnetic resonance imaging was performed annually for 3 years and neuropsychological testing annually for 5 years. Lacunes were manually identified and distinguished from PvS. PvS were rated using a validated visual rating scale, and PvS volumes calculated using T1-weighted images. Linear mixed-effect models were used to determine the impact of PvS and lacunes on cognition., Results: Baseline PvS scores or volumes showed no association with cognitive indices. No change was detectable in PvS volumes over the 3 years. In contrast, baseline lacunes associated with all cognitive indices and predicted cognitive decline over the 5-year follow-up., Conclusions: Although a feature of small-vessel disease, PvS are not a predictor of cognitive decline, in contrast to lacunes. This study highlights the importance of carefully differentiating between lacunes and PvS in studies investigating vascular cognitive impairment., (© 2018 The Authors.)

Background and Purpose: The frequency, clinical correlates, and risk factors of cerebral microbleeds (CMB) in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) are still poorly known. We aimed at determining the location and number of CMB and their relationship with clinical manifestations, vascular risk factors, drugs, and other neuroimaging features in CADASIL patients., Methods: We collected clinical data by means of a structured proforma and centrally evaluated CMB on magnetic resonance gradient echo sequences applying the Microbleed Anatomical Rating Scale in CADASIL patients seen in 2 referral centers in Italy and United Kingdom., Results: We evaluated 125 patients. CMB were present in 34% of patients and their presence was strongly influenced by the age. Twenty-nine percent of the patients had CMB in deep subcortical location, 22% in a lobar location, and 18% in infratentorial regions. After adjustment for age, factors significantly associated with a higher total number of CMB were hemorrhagic stroke, dementia, urge incontinence, and statins use (this latter not confirmed by multivariate analysis). Infratentorial and deep CMB were associated with dementia and urge incontinence, lobar CMB with hemorrhagic stroke, dementia, and statins use. Unexpectedly, patients with migraine, with or without aura, had a lower total, deep, and lobar number of CMB than patients without migraine., Discussion: CMB formation in CADASIL seems to increase with age. History of hemorrhagic stroke, dementia, urge incontinence, and statins use are associated with a higher number of CMB. However, these findings need to be confirmed by longitudinal studies.

Objective: To determine whether MRI markers, including diffusion tensor imaging (DTI), can predict cognitive decline and dementia in patients with cerebral small vessel disease (SVD)., Methods: In the prospective St George's Cognition and Neuroimaging in Stroke study, multimodal MRI was performed annually for 3 years and cognitive assessments annually for 5 years in a cohort of 99 patients with SVD, defined as symptomatic lacunar stroke and confluent white matter hyperintensities (WMH). Progression to dementia was determined in all patients. Progression of WMH, brain volume, lacunes, cerebral microbleeds, and a DTI measure (the normalized peak height of the mean diffusivity histogram distribution) as a marker of white matter microstructural damage were determined., Results: Over 5 years of follow-up, 18 patients (18.2%) progressed to dementia. A significant change in all MRI markers, representing deterioration, was observed. The presence of new lacunes, and rate of increase in white matter microstructural damage on DTI, correlated with both decline in executive function and global functioning. Growth of WMH and deterioration of white matter microstructure on DTI predicted progression to dementia. A model including change in MRI variables together with their baseline values correctly classified progression to dementia with a C statistic of 0.85., Conclusions: This longitudinal prospective study provides evidence that change in MRI measures including DTI, over time durations during which cognitive change is not detectable, predicts cognitive decline and progression to dementia. It supports the use of MRI measures, including DTI, as useful surrogate biomarkers to monitor disease and assess therapeutic interventions., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Variations of normal development and benign incidental anomalies are frequently observed on diagnostic neuroimaging. It is important these are recognised for what they are, as misinterpretation may result in unnecessary further investigation, follow-up imaging and anxiety. In this article, we review benign intracranial anomalies commonly referred to our unit for specialist neuroradiology advice or multidisciplinary discussion, concerning cysts of the pineal gland and pituitary fossa, vascular anomalies, and perivascular spaces. This article outlines the embryology and development, the various imaging features as well as the clinical relevance and differential diagnoses of each normal neuroanatomical variant., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS). Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline. Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity. Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period. 98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years. DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue. By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain. Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters. The impact of brain change on cognition was explored using linear mixed-effects models. Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials. Changes in brain structure described by DSEG θ were related to change in EF and IPS ( p  < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ. Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models ( p  = 0.002). Change in DSEG θ was also related to change in all other MRI markers ( p  < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum. Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity. DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for. DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change. Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials. As such it may provide a marker of SVD severity from a single imaging modality (i.e. DTIs).

Diffusion-weighted imaging (DWI) has transformed the radiological assessment of a variety of cerebral pathologies, in particular acute stroke. In neuroimaging studies, DWI can also be used to evaluate pathology outside the brain parenchyma, although it is sometimes underutilized for this purpose. In this pictorial review, the principles of DWI are outlined, and 13 cases of abnormal diffusion outside the brain parenchyma are illustrated in order to show DWI as a useful sequence for the evaluation of the following recommended review areas: the dural venous sinuses, internal carotid arteries, meninges, ventricles, cavernous sinus and orbits, skull base and lymph nodes.

Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George’s Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used (n = 121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.

Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive decline. Magnetic resonance imaging (MRI) currently plays a central role in diagnosis, and advanced MRI techniques are widely used in research but are limited by spatial resolution. Human 7 Tesla (7T) MRI has recently become available offering the ability to image at higher spatial resolution. This may provide additional insights into both the vascular pathology itself as well as parenchymal markers which could only previously be examined post mortem. In this review we cover the advantages and limitations of 7T MRI, review studies in SVD performed to date, and discuss potential future insights into SVD which 7T MRI may provide., (© 2015 World Stroke Organization.)

Background: Rosai-Dorfman disease (RDD), otherwise known as sinus histiocytosis with massive lymphadenopathy (SHML), usually affects young adults and commonly presents with massive painless cervical lymphadenopathy. Extranodal disease is present in a third of patients, and it is recognised that this can involve the central nervous system. Intracranial RDD is rare in adults and fewer than 10 paediatric cases have been reported., Case: A 10-year-old boy with isolated intracranial RDD presents with a painless forehead mass. The management is discussed and the literature reviewed., Conclusion: This case of isolated intracranial RDD highlights the importance of considering RDD in the differential of paediatric intracranial mass lesions and outlines the diagnostic and treatment challenges faced when managing this rare condition.

Objectives: Lacunes are an important disease feature of cerebral small vessel disease (SVD) but their relationship to cognitive impairment is not fully understood. To investigate this we determined (1) the relationship between lacune count and total lacune volume with cognition, (2) the spatial distribution of lacunes and the cognitive impact of lacune location, and (3) the whole brain anatomical covariance associated with these strategically located regions of lacune damage., Methods: One hundred and twenty one patients with symptomatic lacunar stroke and radiological leukoaraiosis were recruited and multimodal MRI and neuropsychological data acquired. Lacunes were mapped semi-automatically and their volume calculated. Lacune location was automatically determined by projection onto atlases, including an atlas which segments the thalamus based on its connectivity to the cortex. Lacune locations were correlated with neuropsychological results. Voxel based morphometry was used to create anatomical covariance maps for these 'strategic' regions., Results: Lacune number and lacune volume were positively associated with worse executive function (number p < 0.001; volume p < 0.001) and processing speed (number p < 0.001; volume p < 0.001). Thalamic lacunes, particularly those in regions with connectivity to the prefrontal cortex, were associated with impaired processing speed (Bonferroni corrected p = 0.016). Regions of associated anatomical covariance included the medial prefrontal, orbitofrontal, anterior insular cortex and the striatum., Conclusion: Lacunes are important predictors of cognitive impairment in SVD. We highlight the importance of spatial distribution, particularly of anteromedial thalamic lacunes which are associated with impaired information processing speed and may mediate cognitive impairment via disruption of connectivity to the prefrontal cortex.

An 80 year old man presented subacutely with drowsiness and confusion. Subsequent MRI brain imaging demonstrated multiple posterior circulation infarcts. Extracranial vasculitis was suspected when his ESR was found to be high and vascular imaging showed multifocal irregular narrowing of both vertebral arteries. This was confirmed by targeted temporal artery biopsy, which showed chronic granulomatous inflammation typical of giant cell arteritis (GCA). The patient made a significant recovery following treatment with prednisolone.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD.

Aim: To determine the negative predictive value of 16 channel multisection computed tomography angiography (CTA) for detecting aneurysms in spontaneous subarachnoid haemorrhage (SAH), using digital subtraction angiography (DSA) as the reference standard., Materials and Methods: The prospectively collected cerebral angiogram database of Department of Neuroradiology, Atkinson Morley Regional Neuroscience Centre was used to identify 200 consecutive patients who had undergone DSA for SAH. Of these, 176 had undergone CTA prior to DSA. Clinical details and radiology reports were correlated and images of positive investigations reviewed., Results: DSA showed one or more cerebral aneurysms in 105 (60%) patients. These were correctly reported on CTA in 100. CTA was reported negative for aneurysms in 74 patients. Of these five were false negative and had aneurysms detected on DSA. In the CTA/DSA negative group, 11 (16%) patients had classical perimesencephalic clinical syndrome and blood distribution. There were two false positives at CTA. For ruptured cerebral aneurysms, CTA had 95.2% sensitivity, 97.2% specificity, 98.1% positive predictive value, and 93.2% negative predictive value., Conclusion: The sensitivity and negative predictive value of CTA for ruptured aneurysms remains imperfect. Continued use of DSA is recommended in most patients with a negative CTA after acute SAH. Confirmation of a negative CTA result with DSA may not be routinely required in patients with perimesencephalic syndrome., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Cerebral microbleeds (CMBs) are common in cerebral small vessel disease. They may cause cognitive impairment, possibly via white matter tract disruption but previous studies have produced inconsistent results. We determined whether CMB number and location are associated with impaired cognition in symptomatic small vessel disease and whether any association was independent of other magnetic resonance imaging markers of small vessel disease., Methods: One hundred sixteen patients with lacunar stroke and radiological leukoaraiosis were studied. Neuropsychological assessment was performed. CMBs on gradient echo images were assessed using the Brain Observer Microbleed Rating Scale criteria. Magnetic resonance imaging measures, including diffusion tensor imaging, were also analyzed. Associations between cognitive function and the presence, number, and location of CMBs were determined., Results: CMBs were present in 46 (39.7%) patients. CMB number correlated weakly with executive function (r=0.22; P=0.022) but not with other cognitive indices. CMBs count in the top decile (≥ 9 CMB, N=12) was more strongly associated with poor executive function; this association remained significant after controlling for T2-lesion load, brain volume, lacune count, and mean diffusivity (b=-0.51; P=0.043)., Conclusions: In symptomatic small vessel disease, CMB number was weakly associated with executive dysfunction. There seemed to be a threshold effect with the association being largely accounted for by an association of impaired executive function with high CMB count. No association of CMBs with other cognitive domains, including processing speed, was found.

Hearing disturbances are not commonly reported in stroke or transient ischemic attack. We describe a case of a 60-year-old man with fluctuating brainstem ischemia with basilar artery thrombosis where the patient has consistently described hearing "white noise," bilaterally becoming progressively louder over 10 minutes that prevented him from hearing surrounding noise including the radio. These episodes were transient and preceded episodes of hemiparesis or reduced conscious level. We correlate this to the sequential imaging findings from the patient. We discuss how this case provides in vivo evidence for localization of auditory hallucinations in the context of the auditory pathways and their blood supply, and review 25 previous cases of auditory hallucinations and possible mechanisms.

Background and Purpose: Carotid IMT is widely used as a surrogate marker for atherosclerosis. Prospective studies in largely white populations demonstrate that it is strongly associated with carotid plaque and is an independent predictor of stroke. There are few data from black populations. In a previous study, we showed that carotid IMT is increased in black individuals in the UK. The purpose of this study was to confirm this with a larger sample size and to establish whether raised IMT in black stroke-free individuals is associated with increased carotid plaque., Materials and Methods: High-resolution sonography was used to measure the CCA-, BIF-, and ICA-IMT and plaque in 306 black and 281 white healthy individuals recruited by random community sampling from London, U.K. Mean CCA-IMT was determined by using a semiautomated computer program that detects the blood/intima borderline and the media/adventitia borderline with the use of a gray-value algorithm., Results: CCA-IMT was higher in black compared with white individuals after controlling for cardiovascular risk factors and socioeconomic status (β = 0.050; 95%CI, 0.024-0.076; P < .001). BIF- and ICA-IMT were also increased in black subjects. In contrast, carotid plaque was more common in white individuals (OR, 2.90; 95%CI, 1.41-5.96; P = .004)., Conclusions: The lack of correlation between increased IMT and carotid plaque in black individuals implies that IMT should not currently be used as a surrogate marker of atherosclerosis in black populations. It suggests that the increased IMT seen in black individuals may not represent early atherosclerosis.

Aim: To evaluate the impact of picture archiving and communications systems (PACS) on reporting times and productivity in a large teaching hospital., Materials and Methods: Reporting time, defined as the time taken from patient registration to report availability, and productivity, defined as the number of reports issued per whole time equivalent (WTE) radiologist per month, were studied for 2 years pre- and 3 years post-PACS installation. Mean reporting time was calculated for plain radiographs and specialist radiology techniques [computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine]. Productivity, total department workload, and unreported film rates were also assessed. Pre- and post-PACS findings were compared., Results: Between 2002-2006 the number of radiological patient episodes increased by 30% from 11,531/month to 15,057/month. This was accompanied by a smaller increase in WTE reporting radiologists, from 32 to 37 (15%). Mean reporting times have improved substantially post-PACS, plain radiograph reporting time decreased by 26% (from 6.8 to 5 days; p=0.002) and specialty modalities by 24% (4.1 to 3.1 days; p<0.001). Radiologist productivity has increased by 18% (337 films to 407 films/WTE radiologist/month). Unreported films have decreased from 5 to 4% for plain radiographs and are steady for specialty modalities (< 1%). In most areas improvements have been sustained over a 3-year period., Conclusion: Since the introduction of PACS, reporting times have decreased by 25% and the productivity improved by 18%. Sustained improvements are felt to reflect the efficiencies and cultural change that accompanied the introduction of PACS and digital dictation.

Background and Purpose: Transcranial Doppler (TCD) ultrasound can detect asymptomatic emboli in carotid stenosis. Current systems are nonportable and can only record for short durations. A novel ambulatory TCD system allows prolonged recording. We applied this to patients with symptomatic and asymptomatic carotid stenosis to determine patterns of embolization in the 2 conditions and optimal recording protocols., Methods: Ambulatory TCD recordings were performed in 12 symptomatic and 15 asymptomatic carotid stenosis (> or =50%) patients for 8 hours and then repeated on a second occasion., Results: Nine (75%) of symptomatic subjects had embolic signals during the first recording. In this group, repeating the recording did not increase the proportion of positive patients. In asymptomatic patients, 4 (26.7%) had embolic signals on 1 recording, and this proportion increased to 46.7% after 2 recordings. There was significant clustering of embolic signals demonstrating that the process was nonrandom., Conclusions: Ambulatory TCD is possible in patients with carotid artery stenosis. By increasing the duration of recording, additional information is provided, particularly in asymptomatic patients. Our results also demonstrate clustering of embolic signals. Our study provides baseline data to allow studies in both asymptomatic and symptomatic carotid stenosis to be planned.

Background and Purpose: Carotid intima-media thickness (IMT) progression rates are increasingly used as an intermediate outcome for vascular risk. The carotid bifurcation (BIF) and internal carotid artery (ICA) are predilection sites for atherosclerosis. IMT measures from these sites may be a better estimate of atherosclerosis than common carotid artery (CCA) IMT. The study aim was to evaluate site-specific IMT progression rates and their relationships to vascular risk factors compared with baseline IMT measurements., Methods: In a community population (n=3383), ICA-IMT, BIF-IMT, CCA-IMT, and vascular risk factors were evaluated at baseline and at 3-year follow-up., Results: Mean (SD) IMT progression was significantly greater at the ICA (0.032 [0.109] mm/year) compared with the BIF (0.023 [0.108] mm/year) and the CCA (0.001 [0.040] mm/year) (P<0.001). Only ICA-IMT progression significantly correlated with baseline vascular risk factors (age, male gender, hypertension, diabetes, and smoking). Change in risk factor profile over follow-up, estimated using the Framingham risk score, was a predictor of IMT progression only. For all arterial sites, correlations were stronger, by a factor of 2 to 3, for associations with baseline IMT compared with IMT progression., Conclusions: Progression rates at the ICA rather than the CCA yield greater absolute changes in IMT and better correlations with vascular risk factors. Vascular risk factors correlate more strongly with baseline IMT than with IMT progression. Prospective data on IMT progression and incident vascular events are required to establish the true value of progression data as a surrogate measure of vascular risk.

Background and Purpose: Transcranial Doppler (TCD) monitoring for asymptomatic cerebral emboli is currently limited to short recordings by equipment size, restricting its clinical usefulness. We have developed a first ambulatory TCD system, evaluated it in at-risk patient groups, and used it to study the pattern of embolization in patients with symptomatic carotid stenosis., Methods: The system comprises an 18x11.5x3.2 cm battery-powered Doppler unit (425 g) and a 13-mm servo-controlled 2 MHz transducer probe. The quadrature raw Doppler signal is stored on flash-disk. An autosearch algorithm restores vessel insonation should signal quality fall. Initial evaluation was in 20 ambulatory stroke patients. Subsequently, 12 recently symptomatic carotid patients had recordings for > or =5 hours., Results: Recordings were well tolerated and a median of 96% of Doppler signal was suitable for analysis. Embolic signals were detected in 11 of the 12 symptomatic carotid patients. There was marked temporal variability in embolization and prolonging the recording increased the yield of embolic signal positive patients from 58% at 30 minutes to 92% at 150 minutes. In 3 subjects with frequent embolic signals, significant temporal clustering of embolic signals was observed., Conclusions: We have developed the first ambulatory TCD system. Good-quality recordings of > or =5 hours can be obtained. In view of the demonstrated temporal variability in embolization, this technique is likely to improve the predictive value of recording for asymptomatic embolic signals and may be particularly useful in patients in whom embolic signals are relatively infrequent, such as those with asymptomatic carotid stenosis and atrial fibrillation.