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Introduction: Type 1 diabetes has been linked to brain volume reductions as well as to cerebral small vessel disease (cSVD). This study concerns the relationship between normalized brain volumes (volume fractions) and cSVD, which has not been examined previously. Methods: We subjected brain magnetic resonance imaging studies of 187 adults of both sexes with Type 1 diabetes and 30 matched controls to volumetry and neuroradiological interpretation. Results: Participants with Type 1 diabetes had smaller thalami compared to controls without diabetes ( p = 0.034). In subgroup analysis of the Type 1 diabetes group, having any sign of cSVD was associated with smaller cortical ( p = 0.031) and deep gray matter volume fractions ( p = 0.029), but a larger white matter volume fraction ( p = 0.048). After correcting for age, the smaller putamen volume remained significant. Conclusions: We found smaller thalamus volume fractions in individuals with Type 1 diabetes as compared to those without diabetes, as well as reductions in brain volume fractions related to signs of cSVD in individuals with Type 1 diabetes., Competing Interests: T.T. is an advisory board member of Boehringer Ingelheim, Bayer, Bristol Myers Squibb, and Portola and has received speaker honoraria from the University of Donau (Austria). P.-H.G. has received lecture honoraria from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, ELO Water, Genzyme, Medscape, MSD, Novartis, Novo Nordisk, Sanofi, and SCI-Arc, and he is an advisory board member of AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Nestlé, Novartis, Novo Nordisk, and Sanofi. J.M. has received lecture honoraria from Santen. D.G. has received lecture or advisory honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Delta Medical Communications, EASD eLearning, GE Healthcare, Kidney and Liver Foundation in Finland, and Novo Nordisk. The other authors declare no conflict of interest., (Copyright © 2024 Tor-björn Claesson et al.)

Objectives: A third of asymptomatic individuals with type 1 diabetes (T1D) show signs of cerebrovascular disease in brain MRI. These signs associate with advanced stages of diabetic retinal disease, but not in mild or moderate retinopathy. We aimed to evaluate a wider spectrum of retinal changes by exploring the relationship between quantitative measures of retinal vessel parameters (RVP) and cerebrovascular changes in T1D., Methods: We included 146 neurologically asymptomatic individuals with T1D [51% women, median age 40 (33.0-45.1) years] and 24 healthy, sex-matched and age-matched controls. All individuals underwent a clinical and biochemical work-up and brain MRI, which was evaluated for cerebral microbleeds (CMBs), white matter hyperintensities, and lacunar infarcts. RVPs, including central retinal arteriole (CRAE) and central retinal vein (CRVE) equivalents and the ratio of the two variables (arteriovenous ratio, AVR) were assessed quantitatively by a computer-assisted method (IVAN software, version 3.2.6) from fundus images., Results: Among T1D participants, those with CMBs had a lower arteriovenous ratio (AVR) compared with those without CMBs ( P  = 0.023). AVR was inversely associated with the amount of CMBs ( r  = -0.063, P  = 0.035). CMB prevalence was higher in those with AVR below the median (31%) compared with above the median (16%, P  < 0.001), and this difference was significant also after individuals with only no-to-mild retinopathy were included (28 vs. 16%, P  = 0.005). A correlation between blood pressure and CRAE ( r  = -0.19, P  = 0.025) appeared among those with T1D., Conclusion: Regardless of the severity of diabetic retinopathy, AVR is associated with the existence of CMBs in T1D., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: Cortical lesions are common in multiple sclerosis and are included in the latest diagnostic criteria. The limited sensitivity of cortical MS lesions on conventional MR imaging can be improved by phase-sensitive inversion recovery. Synthetic MR imaging could provide phase-sensitive inversion recovery without additional scanning, but the use of synthetic phase-sensitive inversion recovery remains to be validated. We aimed to compare the ability and clinical value of detecting leukocortical lesions with conventional and synthetic phase-sensitive inversion recovery in MS., Materials and Methods: Twenty-one patients with MS prospectively underwent conventional and synthetic phase-sensitive inversion recovery, 3D T1-weighted, and T2 FLAIR imaging. Two neuroradiologists independently performed blinded phase-sensitive inversion recovery lesion assessments; a consensus rating with all sequences was considered the criterion standard. Lesion volumes were segmented. All participants underwent standardized cognitive and physical examinations and Fatigue Severity Scale assessment. Results were analyzed with multiple linear regressions., Results: Interrater and criterion standard agreement for leukocortical lesions was excellent for both conventional and synthetic phase-sensitive inversion recovery (intraclass correlation coefficient = 0.79-0.97). Leukocortical lesion volumes for both sequences were associated with lower information-processing speed ( P ≤ .01) and verbal fluency ( P ≤ .02). Both phase-sensitive inversion recovery sequences showed a positive effect on the association when combining volumes of leukocortical lesions and white matter lesions with information-processing speed ( P ≤ .005) and verbal fluency ( P ≤ .03). No associations were found between leukocortical lesion volumes and physical disability or fatigue., Conclusions: Synthetic and conventional phase-sensitive inversion recovery have a sensitivity similar to that of leukocortical MS lesions. The detected leukocortical lesions are associated with cognitive dysfunction and thus provide clinically relevant information, which encourages assessment of cortical MS involvement at conventional field strengths., (© 2018 by American Journal of Neuroradiology.)

Background: Magnetic resonance imaging-visible perivascular spaces (PVS) are related to interstitial fluid clearance pathways (including amyloid-β) in the brain and are suggested to be a marker of cerebral small vessel disease. We investigated the role, topography, and possible implications of PVS in cognitive impairment., Methods and Results: A total of 1504 patients undergoing memory clinic investigation and an associated brain magnetic resonance imaging scan were included in this cross-sectional study. Magnetic resonance images were assessed for markers of small vessel disease. Additionally, 1039 patients had cerebrospinal fluid analysis of amyloid-β 42, total tau (T-tau), and phosphorylated tau ( P -tau); 520 patients had apoE genotyping done. Results were analyzed with generalized linear models. A total of 289 (19%; 95% confidence interval, 17-21) had a high-grade PVS in the centrum semiovale (CSO) and 65 (4%; 95% confidence interval: 3%-5%) in the basal ganglia (BG). Centrum semiovale- and BG-PVS were both associated with high age ( P <0.001), hypertension ( P <0.001), probable cerebral amyloid angiopathy ( P <0.05), moderate-to-severe white matter hyperintensities ( P <0.001), cortical superficial siderosis ( P <0.001), cerebral microbleeds ( P <0.001), and PVS. centrum semiovale-PVS was separately associated with strictly lobar cerebral microbleeds ( P =0.057). BG-PVS was associated with strictly deep cerebral microbleeds ( P <0.001), lacunes ( P <0.001), and vascular dementia ( P =0.04). BG-PVS showed a tendency to be associated with high cerebrospinal fluid tau (B=0.002, P =0.04) in the whole cohort and in Alzheimer's disease (B=0.005; P =0.02). No other associations with cerebrospinal fluid or the apoE e4 allele was observed., Conclusions: Centrum semiovale-PVS and BG-PVS have different underlying etiology, being associated with cerebral amyloid angiopathy and hypertensive vasculopathy, respectively, although a significant overlap between these pathologies is likely to exist., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: To compare corpus callosum area (CCA) and corpus callosum index (CCI) in terms of feasibility and their performance as biomarkers for cognitive and physical disability in multiple sclerosis (MS). A secondary aim was to compare these two methods with volumetric measurements., Methods: This study was based on a cohort of 37 MS patients and a group of age- and gender-matched healthy controls. Physical disability was assessed with the expanded disability status scale (EDSS) and cognitive disability with the symbol digit modalities test (SDMT). CCA and CCI were assessed on midsagittal brain MRI by 3 raters with varying radiological experience. Volumes of the brain, gray and white matter, corpus callosum, and MS lesions were acquired with Freesurfer and Lesion Segmentation Toolbox for Statistical Parametric Mapping., Results: CCA and CCI were obtained within seconds with excellent intra- and inter-rater agreement, and outperformed volumetric measurements. CCA had the strongest correlations with both SDMT (r = .82, P < .001) and EDSS (r = -.56, P < .001), and the highest accuracy in differentiating patients from controls (95%) and relapse-remitting MS from progressive forms of MS (77%). CCI performed less well (r = .73, P < .001; r = -.45, P < .001; 94%; 71%). CCA also outperformed the volumetric measurements in these regards., Conclusions: CCA is a time-effective and robust biomarker that has stronger correlations with both EDSS and information processing speed than CCI and volumetric measurements that are commonly used as outcome measures in MS research and clinical trials., (Copyright © 2015 by the American Society of Neuroimaging.)

Background and Purpose: Cerebral microbleeds are thought to have potentially important clinical implications in dementia and stroke. However, the use of both T2* and SWI MR imaging sequences for microbleed detection has complicated the cross-comparison of study results. We aimed to determine the impact of microbleed sequences on microbleed detection and associated clinical parameters., Materials and Methods: Patients from our memory clinic (n = 246; 53% female; mean age, 62) prospectively underwent 3T MR imaging, with conventional thick-section T2*, thick-section SWI, and conventional thin-section SWI. Microbleeds were assessed separately on thick-section SWI, thin-section SWI, and T2* by 3 raters, with varying neuroradiologic experience. Clinical and radiologic parameters from the dementia investigation were analyzed in association with the number of microbleeds in negative binomial regression analyses., Results: Prevalence and number of microbleeds were higher on thick-/thin-section SWI (20/21%) compared with T2*(17%). There was no difference in microbleed prevalence/number between thick- and thin-section SWI. Interrater agreement was excellent for all raters and sequences. Univariate comparisons of clinical parameters between patients with and without microbleeds yielded no difference across sequences. In the regression analysis, only minor differences in clinical associations with the number of microbleeds were noted across sequences., Conclusions: Due to the increased detection of microbleeds, we recommend SWI as the sequence of choice in microbleed detection. Microbleeds and their association with clinical parameters are robust to the effects of varying MR imaging sequences, suggesting that comparison of results across studies is possible, despite differing microbleed sequences., (© 2015 by American Journal of Neuroradiology.)

Magnetic resonance imaging of the brain is currently the most sensitive method in detecting the lesions caused by multiple sclerosis. Assessment of the immunological treatment response used in the treatment of multiple sclerosis should be based on the clinical picture and brain MRI. T2-, flair- and T1-biased images, gadolinium enhancement and assessment of atrophy are required for MRI monitoring. In the first-line immune therapy MRI is taken at 6 to 12 months after starting the drug therapy, in fingolimod therapy after 6 to 12 months and 1 to 2 years, respectively, and in alemtuzumab and natalizumab therapy after one and two years.

With increasing availability of magnetic resonance imaging (MRI), there is also an increase in incidental abnormal findings. MRI findings suggestive of multiple sclerosis in persons without typical multiple sclerosis symptoms and with normal neurological findings are defined as radiologically isolated syndrome (RIS). Half of the persons with RIS have their initial MRI because of headache, and some have a subclinical cognitive impairment similar to that seen in multiple sclerosis. Radiological measurements also show a similarity between RIS and multiple sclerosis. Approximately two-thirds of persons with RIS show radiological progression and one-third develop neurological symptoms during mean follow-up times of up to five years. Cervical cord lesions are important predictors of clinical conversion. Management has to be individualised, but initiation of disease modifying therapy is controversial and not recommended outside of clinical trials since its effects have not been studied in RIS. Future studies should try to establish the prevalence and long-term prognosis of RIS, its impact on quality of life, and define the role of disease modifying therapy in RIS.

Introduction: Multiple sclerosis (MS) has a variable progression with an early onset of atrophy. Individual longitudinal radiological evaluations (over decades) are difficult to perform due to the limited availability of magnetic resonance imaging (MRI) in the past, patients lost in follow-up, and the continuous updating of scanners. We studied a cohort with widespread disease duration at baseline. The observed individual atrophy rates over time of 10 years represented four decades of disease span., Methods: Thirty-seven MS patients (age range 24-65 years with disease duration 1-33 years) were consecutively selected and evaluated with MRI at baseline 1995 and in 1996. They were followed up for a decade (mean of 9.25 years, range 7.3-10 years) up to 2003-2005. Brain parenchymal volume and volumes of the supratentorial ventricles were analyzed with semi-automated volumetric measurements at three time points (1995, 1996, and 2003-2005)., Results: Volumetric differences were found over shorter periods of time (1-7 months); however, differences vanished by the end of follow-up. A uniform longitudinal decrease in brain volume and increase in ventricle volumes were found. Frontal horn width (1D) correlated strongest to 3D measures. No statistical differences of atrophy rates between MS courses were found. Supratentorial ventricular volumes were associated with disability and this association persisted during follow-up., Conclusion: Despite variable clinical courses, the degenerative effects of MS progression expressed in brain atrophy seem to uniformly progress over longer periods of time. These volumetric changes can be detected using 1D and 2D measurements performed on a routine PACS workstation.

Background: For decades, normalized one-dimensional (1D) measures have been used in the evaluation of brain atrophy. In multiple sclerosis (MS), the use of normalized linear measures over longitudinal follow-up remains insufficiently documented., Purpose: To evaluate the association between different regional atrophy measures and disability in MS patients over four decades in a longitudinal cross-sectional study., Material and Methods: 37 consecutively selected MS patients were included. At baseline, patients had a range of disease duration (1-33 years) and age (24-65 years). Each patient was followed by magnetic resonance imaging (MRI) for a mean of 9.25 years (range 7.3-10 years). Four 1D measures were applied at three time points on axial 5-mm T1-weighted images. Three clinical MS subgroups were represented: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS)., Results: There were significant changes in all 1D ratios during follow-up. The Evans ratio (ER) and the bifrontal ratio (BFR) were associated with the development of disability. Changes of ER and BFR reflected more aggressive disease progression, as expressed by MS severity score (MSSS)., Conclusion: All four normalized ratios showed uniform atrophy progression, suggesting a consistent rate of atrophy over long-term disease duration independent of MS course. Disability status correlated with 1D measures, suggesting that serial evaluation of Evans and bifrontal ratios might contribute to the radiological evaluation of MS patients.

Background: In multiple sclerosis (MS), brain atrophy assessed by linear measurements of ventricular widths has been reported to be well correlated with three-dimensional (3D) measurements. Therefore, serial linear measurements with no need for advanced 3D evaluation may be proven to be robust markers of irreversible, destructive changes., Purpose: To evaluate the rate of supratentorial ventricular enlargement representing four decades of disease span., Material and Methods: 37 MS patients with disease duration at baseline ranging from 1 to 33 years were included. The mean time of the individual magnetic resonance imaging (MRI) follow-up was 9.25 years (range 7.3-10 years). Enlargement rate of the third and lateral ventricles was studied over time by applying three linear measurements on axial 5-mm T1-weighted MRI images., Results: Progression of supratentorial ventricular widths during 9 years' follow-up was found. The mean annual width increase of the third ventricle was 0.20 mm (P<0.001, 95% confidence interval [CI] 0.15-0.25), for the frontal horn width 0.32 mm (P<0.001, 95% CI 0.23-0.40), and increase of the intercaudate distance was 0.26 mm (P<0.001, 95% CI 0.19-0.33). The association between these three measurements and disability status persisted at the time of follow-up., Conclusion: We found uniform ventricular enlargement progression during four decades of disease span, suggesting unchanging total brain atrophy progression over time.

Aim: Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles' association with SVD. Methods: This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts). Results: SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74–83], 75 [70–80], and 75 [72–81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46–2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy. Conclusions: Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype. [ABSTRACT FROM AUTHOR]