Tobias Granberg

Radiologically isolated syndrome--incidental magnetic resonance imaging findings suggestive of multiple sclerosis, a systematic review.

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.

Cerebral Microbleeds: Different Prevalence, Topography, and Risk Factors Depending on Dementia Diagnosis—The Karolinska Imaging Dementia Study

MR studies in more than 1500 patients with dementia revealed that 22% had microbleedsthat were predominantly lobar and occipital in cases of Alzheimer disease. Patients with microbleeds were older, male, and hypertensive. Prevalence, location, and risk factors of microbleeds varied depending on dementia diagnosis and may be taken into account when anticoagulating such patients. BACKGROUND AND PURPOSE: Cerebral microbleeds are thought to represent cerebral amyloid angiopathy when in lobar regions of the brain and hypertensive arteriopathy when in deep and infratentorial locations. By studying cerebral microbleeds, their topography, and risk factors, we aimed to gain an insight into the vascular and amyloid pathology of dementia diagnoses and increase the understanding of cerebral microbleeds in dementia. MATERIALS AND METHODS: We analyzed 1504 patients (53% women; mean age, 63 ± 10 years; 10 different dementia diagnoses) in this study. All patients underwent MR imaging as part of the dementia investigation, and all their clinical parameters were recorded. RESULTS: Among the 1504 patients with dementia, 22% had cerebral microbleeds. Cerebral microbleed topography was predominantly lobar (P = .01) and occipital (P = .007) in Alzheimer disease. Patients with cerebral microbleeds were significantly older (P < .001), were more frequently male (P < .001), had lower cognitive scores (P = .006), and more often had hypertension (P < .001). Risk factors for cerebral microbleeds varied depending on the dementia diagnosis. Odds ratios for having cerebral microbleeds increased with the number of risk factors (hypertension, hyperlipidemia, diabetes, male sex, and age 65 and older) in the whole patient group and increased differently in the separate dementia diagnoses. CONCLUSIONS: Prevalence, topography, and risk factors of cerebral microbleeds vary depending on the dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Because cerebral microbleeds are seen as possible predictors of intracerebral hemorrhage, their increasing prevalence with an increasing number of risk factors, as shown in our study, may require taking the number of risk factors into account when deciding on anticoagulant therapy in dementia.

The neuroinflammatory component of gray matter pathology in multiple sclerosis

In multiple sclerosis (MS), using simultaneous magnetic resonance–positron emission tomography (MR‐PET) imaging with 11C‐PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal‐appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation.

SWI or T2*: Which MRI Sequence to Use in the Detection of Cerebral Microbleeds? The Karolinska Imaging Dementia Study

The prevalence of cerebral microbleeds was evaluated in 246 patients using T2* and SWI. Microbleeds were detected in 21% by SWI vs. 17% by T2* imaging. SWI performed well with both thin and thick sections. Thus, SWI is better than T2* for this purpose and robust enough to permit comparison across studies. 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.

Clinical Feasibility of Synthetic MRI in Multiple Sclerosis: A Diagnostic and Volumetric Validation Study

SyMRI is a quantitative synthetic MR imaging method where a single saturation recovery TSE sequence is used to estimate the proton density, longitudinal relaxation rate, and transverse relaxation rate and allows for a free range of synthetic weightings. Twenty patients with MS and 20 healthy controls were enrolled and synthetic MR imaging was implemented on a Siemens 3T scanner. Diagnostic accuracy, lesion detection, and artifacts were assessed by blinded neuroradiologic evaluation, and CNR by manual tracing. Synthetic PD-, T1-, and T2-weighted images were of sufficient or good quality and were acquired in 7% less time than with conventional MRI. Synthetic FLAIR images suffered from artifacts. Also, synthetic MRI provided segmentations with the shortest processing time (16 seconds) and the lowest repeatability error for brain volume. Synthetic MRI can be an alternative to conventional MRI for generating diagnostic PD-, T1-, and T2-weighted images in patients with MS with fast and robust volumetric measurements. BACKGROUND AND PURPOSE: Quantitative MR imaging techniques are gaining interest as methods of reducing acquisition times while additionally providing robust measurements. This study aimed to implement a synthetic MR imaging method on a new scanner type and to compare its diagnostic accuracy and volumetry with conventional MR imaging in patients with MS and controls. MATERIALS AND METHODS: Twenty patients with MS and 20 healthy controls were enrolled after ethics approval and written informed consent. Synthetic MR imaging was implemented on a Siemens 3T scanner. Comparable conventional and synthetic proton-density–, T1-, and T2-weighted, and FLAIR images were acquired. Diagnostic accuracy, lesion detection, and artifacts were assessed by blinded neuroradiologic evaluation, and contrast-to-noise ratios, by manual tracing. Volumetry was performed with synthetic MR imaging, FreeSurfer, FMRIB Software Library, and Statistical Parametric Mapping. Repeatability was quantified by using the coefficient of variance. RESULTS: Synthetic proton-density–, T1-, and T2-weighted images were of sufficient or good quality and were acquired in 7% less time than with conventional MR imaging. Synthetic FLAIR images were degraded by artifacts. Lesion counts and volumes were higher in synthetic MR imaging due to differences in the contrast of dirty-appearing WM but did not affect the radiologic diagnostic classification or lesion topography (P = .50–.77). Synthetic MR imaging provided segmentations with the shortest processing time (16 seconds) and the lowest repeatability error for brain volume (0.14%), intracranial volume (0.12%), brain parenchymal fraction (0.14%), and GM fraction (0.56%). CONCLUSIONS: Synthetic MR imaging can be an alternative to conventional MR imaging for generating diagnostic proton-density–, T1-, and T2-weighted images in patients with MS and controls while additionally delivering fast and robust volumetric measurements suitable for MS studies.

Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study

Background: Cognitive impairment is common in multiple sclerosis (MS) and may be subtle. The corpus callosum is essential for connectivity-demanding cognitive tasks and is significantly affected in MS, therefore it may serve as a marker for cognitive function. Objective: The objective of this paper is to longitudinally study the normalized corpus callosum area (nCCA) as a marker of cognitive function and disability in MS. Methods: Thirty-seven MS patients were followed from 1996 with follow-ups in 2004 and 2013. A healthy matched control group was recruited. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed. The nCCA was measured on T2-weighted images. Volumetry was performed with FreeSurfer. Results: Disease duration spanned five decades (1.6–46 years). Annual corpus callosal atrophy rate decreased with disease duration. nCCA was strongly correlated with SDMT (r = 0.793, p < 0.001) and moderately correlated with EDSS (r = −0.545, p < 0.001) after adjusting for disease duration, age and sex. The correlations of brain parenchymal fraction, white matter fraction, gray matter fraction and normalized lesion volume were less strong. Conclusions: The nCCA correlates well with physical and cognitive disability in time perspectives close to two decades, outperforming volumetric measurements. The nCCA is fast and could be feasible for clinical implementation where it may help identify patients in need of neuropsychological evaluation.

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society.

Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.

Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer’s disease and mild cognitive impairment (p < 0.05). CSF/serum albumin ratios were high with multiple CMBs (p < 0.001), reflecting accompanying blood–brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer’s patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer’s disease (p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

MRI‐Defined Corpus Callosal Atrophy in Multiple Sclerosis: A Comparison of Volumetric Measurements, Corpus Callosum Area and Index

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.

Cortical superficial siderosis: Prevalence and biomarker profile in a memory clinic population

Objective: To gain further insight into cortical superficial siderosis (cSS), a new hemorrhagic neuroimaging marker of cerebral amyloid angiopathy (CAA), and to investigate the clinical, neuroimaging, genetic, and CSF biomarker profile of cSS in a large, consecutive memory clinic series. Methods: We included 1,504 memory clinic patients undergoing dementia investigation including a brain MRI in our center. Routine CSF biomarker analysis was performed in 1,039 patients and APOE genotyping in 520 patients. MRIs were systematically evaluated for presumed marker of small vessel disease: cSS, cerebral microbleeds, enlarged perivascular spaces, white matter hyperintensities, and lacunes. Results: cSS was detected in 40 patients (2.7%; 95% confidence interval [CI] 1.9–3.6); cSS was focal in 33 cases (2.2%; 95% CI 1.5–3.1) and disseminated in 7 (0.5%; 95% CI 0.2–1). Vascular dementia had the highest cSS prevalence (13%; 95% CI 5.4–24.9), followed by Alzheimer disease (5%; 95% CI 3.1–7.5). The most commonly affected area was the occipital lobe (70%; 95% CI 53.5–83.4). cSS was associated with lobar cerebral microbleeds (odds ratio [OR] 7.9; 95% CI 3.4–18.1; p < 0.001), high-degree centrum semiovale perivascular spaces (OR 1.7; 95% CI 1.2–2.6; p = 0.008), and white matter hyperintensities (OR 1.5; 95% CI 1.0–2.2; p = 0.062). APOE ε4/4 genotype was more common in cSS cases compared to those without. CSF β-amyloid 42 was lower in patients with cSS (coefficient −0.09; 95% CI −0.15 to −0.03; p = 0.004). Conclusions: Our large series of memory clinic patients provides evidence that cSS is related to cerebrovascular disease and may be a manifestation of severe CAA, even in patients without intracerebral hemorrhage.