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Having gained a tremendous amount of popularity since its introduction in 2006, tract-based spatial statistics (TBSS) can now be considered as the standard approach for voxel-based analysis (VBA) of diffusion tensor imaging (DTI) data. Aiming to improve the sensitivity, objectivity, and interpretability of multi-subject DTI studies, TBSS includes a skeletonization step that alleviates residual image misalignment and obviates the need for data smoothing. Although TBSS represents an elegant and user-friendly framework that tackles numerous concerns existing in conventional VBA methods, it has limitations of its own, some of which have already been detailed in recent literature. In this work, we present general methodological considerations on TBSS and report on pitfalls that have not been described previously. In particular, we have identified specific assumptions of TBSS that may not be satisfied under typical conditions. Moreover, we demonstrate that the existence of such violations can severely affect the reliability of TBSS results. With TBSS being used increasingly, it is of paramount importance to acquaint TBSS users with these concerns, such that a well-informed decision can be made as to whether and how to pursue a TBSS analysis. Finally, in addition to raising awareness by providing our new insights, we provide constructive suggestions that could improve the validity and increase the impact of TBSS drastically. •We investigate tract-based spatial statistics (TBSS) considering potential pitfalls.•TBSS is not tract-specific and we show how this may falsify results.•User defined parameters strongly influence the final TBSS-derived results.•We provide suggestions that improve the validity and increase the impact of TBSS.

Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

Lacunar lesions (LLs) and white matter lesions (WMLs) affect cognition. We assessed whether lesions located in specific white matter tracts were associated with cognitive performance taking into account total lesion burden. Within the Second Manifestations of ARTerial disease Magnetic Resonance (SMART-MR) study, cross-sectional analyses were performed on 516 patients with manifest arterial disease. We applied an assumption-free voxel-based lesion-symptom mapping approach to investigate the relation between LL and WML locations on 1.5 Tesla brain MRI and compound scores of executive functioning, memory and processing speed. Secondly, a multivariable linear regression model was used to relate the regional volume of LLs and WMLs within specific white matter tracts to cognitive functioning. Voxel-based lesion-symptom mapping identified several clusters of voxels with a significant correlation between WMLs and executive functioning, mostly located within the superior longitudinal fasciculus and anterior thalamic radiation. In the multivariable linear regression model, a statistically significant association was found between regional LL volume within the superior longitudinal fasciculus and anterior thalamic radiation and executive functioning after adjustment for total LL and WML burden. These findings identify the superior longitudinal fasciculus and anterior thalamic radiation as key anatomical structures in executive functioning and emphasize the role of strategically located vascular lesions in vascular cognitive impairment.

Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognised as an important comorbidity and complication of diabetes that affects an individual’s well-being and diabetes management, and is associated with diabetes treatment-related complications. Recent guidelines therefore recommend screening for cognitive impairment in older individuals with diabetes. In addition, these guidelines suggest that glucose-lowering treatment should be tailored in those diagnosed with cognitive impairment, to reduce the risk of hypoglycaemia and improve treatment adherence. This review gives an overview of cognitive dysfunction in people with diabetes, briefly describing the clinical features of different stages of cognitive dysfunction and their epidemiology. In particular, it addresses essential additional steps that need to be taken to fully implement the emerging guidelines on screening and management of cognitive dysfunction in diabetes into daily practice.

Background High body temperatures after ischemic stroke have been associated with larger infarct size, but the temporal profile of this relation is unknown. We assess the relation between temporal profile of body temperature and infarct size and functional outcome in patients with acute ischemic stroke. Methods In 419 patients with acute ischemic stroke we assessed the relation between body temperature on admission and during the first 3 days with both infarct size and functional outcome. Infarct size was measured in milliliters on CT or MRI after 3 days. Poor functional outcome was defined as a modified Rankin Scale score ≥3 at 3 months. Results Body temperature on admission was not associated with infarct size or poor outcome in adjusted analyses. By contrast, each additional 1.0 °C in body temperature on day 1 was associated with 0.31 ml larger infarct size (95% confidence interval (CI) 0.04–0.59), on day 2 with 1.13 ml larger infarct size(95% CI, 0.83–1.43), and on day 3 with 0.80 ml larger infarct size (95% CI, 0.48–1.12), in adjusted linear regression analyses. Higher peak body temperatures on days two and three were also associated with poor outcome (adjusted relative risks per additional 1.0 °C in body temperature, 1.52 (95% CI, 1.17–1.99) and 1.47 (95% CI, 1.22–1.77), respectively). Conclusions Higher peak body temperatures during the first days after ischemic stroke, rather than on admission, are associated with larger infarct size and poor functional outcome. This suggests that prevention of high temperatures may improve outcome if continued for at least 3 days.

Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days. Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94-1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase.

Objectives Intracranial vessel wall magnetic resonance imaging (MRI) may improve the diagnosis of vessel wall abnormalities. Current methods are hampered by limited coverage and few contrast weightings. We present a multi-sequence protocol with whole-brain coverage for vessel wall imaging on 7.0-T MRI. Methods A modified magnetisation-preparation inversion recovery turbo-spin-echo (MPIR-TSE) sequence was used to obtain proton density (PD)-, T 1 -, and T 2 -weighting with 190-mm whole-brain coverage. Three observers independently scored the visibility of arterial vessel walls in five healthy volunteers, and compared the conspicuity and image contrast of all sequences. Clinical applicability was demonstrated in 17 patients with cerebrovascular disease. Results Conspicuity was good for all acquisitions, with best scores for the original limited-coverage sequence, followed by whole-brain coverage T 2 - , PD- and T 1 -weighted sequences, respectively. Mean vessel wall/background MR signal intensity ratios for all whole-brain sequences were similar, with higher scores for the limited-coverage MPIR-TSE sequence. Signal intensity ratios were highest in patients, for the whole-brain T 1 -weighted sequence. Conclusions The whole-brain multi-sequence vessel wall protocol can assess intracranial arterial vessel walls with full brain coverage, for different image contrast weightings. These sequences could eventually characterise intracranial vessel wall abnormalities similar to current techniques for assessing carotid artery plaques. Key points - Intracranial vessel wall imaging using MRI improves diagnosis of cerebrovascular diseases. - Conventional 7-T MRI sequences cannot image the whole cerebral arterial tree. - New whole-brain 7-T MRI sequences compare favourably with smaller-coverage sequences. - These whole-brain sequences can demonstrate the entire cerebral arterial tree. - These sequences should help in the diagnosis of vessel wall abnormalities.

Little is known about structural brain changes in type 1 diabetes (T1D) and whether there are early manifestations of a neurodegenerative condition like Alzheimer disease (AD) or evidence of premature brain aging. To evaluate neuroimaging markers of brain age and AD-like atrophy in participants with T1D in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, identify which brain regions are associated with the greatest changes in patients with T1D, and assess the association between cognition and brain aging indices. This cohort study leveraged data collected during the combined DCCT (randomized clinical trial, 1983-1993) and EDIC (observational study, 1994 to present) studies at 27 clinical centers in the US and Canada. A total of 416 eligible EDIC participants and 99 demographically similar adults without diabetes were enrolled in the magnetic resonance imaging (MRI) ancillary study, which reports cross-sectional data collected in 2018 to 2019 and relates it to factors measured longitudinally in DCCT/EDIC. Data analyses were performed between July 2020 and April 2022. T1D diagnosis. Psychomotor and mental efficiency were evaluated using verbal fluency, digit symbol substitution test, trail making part B, and the grooved pegboard. Immediate memory scores were derived from the logical memory subtest of the Wechsler memory scale and the Wechsler digit symbol substitution test. MRI and machine learning indices were calculated to predict brain age and quantify AD-like atrophy. This study included 416 EDIC participants with a median (range) age of 60 (44-74) years (87 of 416 [21%] were older than 65 years) and a median (range) diabetes duration of 37 (30-51) years. EDIC participants had consistently higher brain age values compared with controls without diabetes, indicative of approximately 6 additional years of brain aging (EDIC participants: β, 6.16; SE, 0.71; control participants: β, 1.04; SE, 0.04; P < .001). In contrast, AD regional atrophy was comparable between the 2 groups. Regions with atrophy in EDIC participants vs controls were observed mainly in the bilateral thalamus and putamen. Greater brain age was associated with lower psychomotor and mental efficiency among EDIC participants (β, -0.04; SE, 0.01; P < .001), but not among controls. The findings of this study suggest an increase in brain aging among individuals with T1D without any early signs of AD-related neurodegeneration. These increases were associated with reduced cognitive performance, but overall, the abnormal patterns seen in this sample were modest, even after a mean of 38 years with T1D.

Objectives Carotid siphon calcification is often visible on unenhanced head CT (UCT), but the relation to proximal carotid artery stenosis (CAS) is unclear. We investigated the association of carotid siphon calcification with the presence of CAS. Methods This IRB-waived retrospective study included 160 consecutive patients suspected of stroke (age 64 ± 14 years, 63 female) who underwent head UCT and CTA of the head and neck. CAS was rated on CTA as not present or present with non-significant (<50 %), moderate (50–69 %) or significant (≥70 %) stenosis. Presence, shape (on UCT) and volume (on CTA) of carotid siphon calcifications were related to CAS. Results Carotid siphon calcification was absent in 41 % of patients and bilateral in 94 % of those with calcifications. Presence, shape and volume of calcification resulted in odds ratios for having significant CAS of 10.1, 3.9 and 8.4, with 95 % CIs of 1.3–79.6, 1.1–14.1 and 2.6–26.8, respectively. Corresponding NPVs were 0.98, 0.98 and 0.96, while PPVs were 0.14, 0.07 and 0.29, respectively. Conclusion Absence of calcification in the carotid artery siphon on UCT has high negative predictive value for carotid artery stenosis in patients with suspected stroke. However, siphon calcification is not a reliable indicator of significant carotid artery stenosis. Key Points • Many stroke patients do not have calcification in the carotid artery siphon . • Carotid stenosis ≥ 50  % is unlikely in stroke patients without siphon calcification . • Carotid siphon calcium is a poor indicator of significant carotid artery stenosis .

Abstract There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status.