3D Masked Modelling Advances Lesion Classification in Axial T2w Prostate MRI

Masked Image Modelling (MIM) has been shown to be an efficient self-supervised learning (SSL) pre-training paradigm when paired with transformer architectures and in the presence of a large amount of unlabelled natural images. The combination of the difficulties in accessing and obtaining large amounts of labeled data and the availability of unlabelled data in the medical imaging domain makes MIM an interesting approach to advance deep learning (DL) applications based on 3D medical imaging data. Nevertheless, SSL and, in particular, MIM applications with medical imaging data are rather scarce and there is still uncertainty around the potential of such a learning paradigm in the medical domain. We study MIM in the context of Prostate Cancer (PCa) lesion classification with T2 weighted (T2w) axial magnetic resonance imaging (MRI) data. In particular, we explore the effect of using MIM when coupled with convolutional neural networks (CNNs) under different conditions such as different masking strategies, obtaining better results in terms of AUC than other pre-training strategies like ImageNet weight initialization.publishedVersio

Out-of-distribution multi-view auto-encoders for prostate cancer lesion detection

Traditional deep learning (DL) approaches based on supervised learning paradigms require large amounts of annotated data that are rarely available in the medical domain. Unsupervised Out-of-distribution (OOD) detection is an alternative that requires less annotated data. Further, OOD applications exploit the class skewness commonly present in medical data. Magnetic resonance imaging (MRI) has proven to be useful for prostate cancer (PCa) diagnosis and management, but current DL approaches rely on T2w axial MRI, which suffers from low out-of-plane resolution. We propose a multi-stream approach to accommodate different T2w directions to improve the performance of PCa lesion detection in an OOD approach. We evaluate our approach on a publicly available data-set, obtaining better detection results in terms of AUC when compared to a single direction approach (73.1 vs 82.3). Our results show the potential of OOD approaches for PCa lesion detection based on MRI.Comment: Accepted and presented in ISBI 2023. To be published in Proceeding

White Matter Hyperintensities and the Course of Depressive Symptoms in Elderly People with Mild Dementia

Objectives: To explore the relationship between white matter hyperintensities (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer’s disease (AD) and Lewy body dementia. Design: This is a prospective cohort study conducted in secondary care outpatient clinics in western Norway. Subjects: The study population consisted of 77 elderly people with mild dementia diagnosed according to standardised criteria. Methods: Structured clinical interviews and physical, neurological, psychiatric, and neuropsychological examinations were performed and routine blood tests were taken. Depression was assessed using the depression subitem of the Neuropsychiatric Inventory and the Montgomery-Åsberg Depression Rating Scale (MADRS). A standardised protocol for magnetic resonance imaging scan was used, and the volumes of WMH were quantified using an automated method, followed by manual editing. Results: The volumes of total and frontal deep WMH were significantly and positively correlated with baseline severity of depressive symptoms, and depressed patients had significantly higher volumes of total and frontal deep WMH than non-depressed patients. Higher volumes of WMH were also associated with having a high MADRS score and incident and persistent depression at follow-up. After adjustment for potential confounders, frontal deep WMH, in addition to prior depression and non-AD dementia, were still significantly associated with baseline depressive symptoms (p = 0.015, OR 3.703, 95% CI 1.294–10.593). Similar results emerged for total WMH. Conclusion: In elderly people with mild dementia, volumes of WMH, in particular frontal deep WMH, were positively correlated with baseline severity of depressive symptoms, and seemed to be associated with persistent and incident depression at follow-up. Further studies of the mechanisms that determine the course of depression in mild dementia are needed

European DLB consortium: diagnostic and prognostic biomarkers in dementia with Lewy bodies, a multicenter international initiative

Q3247-250As the population ages, the incidence of chronic diseases such as dementia increases. Dementia with Lewy bodies(DLB) is the second most common neurodegenerative dementia after Alzheimer’s disease (AD) and even thoughboth diseases are clinically separate entities

Effects of purified anthocyanins in people at risk for dementia: Study protocol for a phase II randomized controlled trial

Background: The number of people with dementia is increasing, with huge challenges for society and health-care systems. There are no disease-modifying therapies available. There is, therefore, an urgent need to identify strategies to reduce the risk of developing dementia. Anthocyanins are a class of compounds found in dark berries and fruits with some effects that might reduce the risk for cognitive decline and the development of dementia in older people. Aim: This phase II three-center, randomized, 24-week, placebo-controlled study, ongoing in Norway, aims to evaluate the safety, and efficacy of anthocyanins in modifying key dementia-related mechanisms and maintain cognitive functioning in older people at risk for dementia. Methods: Participants (220 individuals aged 60–80 years) who meet the inclusion criteria (either mild cognitive impairment or two or more cardiometabolic disorders) are being enrolled in this study at three different centers in Norway. Participants are block randomized to identically appearing capsules containing 80 mg of naturally purified anthocyanins or placebo 1:1. Dosage is 2 + 2 capsules per day for 24 weeks. The primary outcome will be the quality of episodic memory score, a composite measure from the extensively validated online cognitive test battery CogTrack®, which is administered at baseline and monthly for the next 6 months. Secondary outcomes include other major scores from CogTrack, as well as a range of neuroimaging and other biomarkers. Anthocyanin metabolites will be measured in blood and cerebrospinal fluid. The change from baseline scores will be subject to a mixed model for repeated measures analysis of covariance. The primary comparison will be the contrast (difference in the least-square means) between active and placebo at the end of the study (week 24). The primary study population will be a modified intention-to-treat population (ClinicalTrials.gov, NCT03419039). Discussion: This study aims to demonstrate whether there are beneficial effects of purified anthocyanins on cognition and relevant biological functions in people at increased risk for dementia. Forthcoming results may contribute to further improvement of intervention strategies to prevent or delay the onset of dementia, including a potential decision to take anthocyanins toward phase III trials.publishedVersio

A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia

Importance Identifying nutritional compounds which can reduce cognitive decline in older people is a hugely important topic. Objective To study the safety and effect of anthocyanins in maintaining cognitive functioning in people at increased risk for dementia. Design, setting, and participants Participants (206 individuals, aged 60–80 years) diagnosed with either mild cognitive impairment (MCI) or two or more cardiometabolic disorders (i.e., diabetes, hypertension, obesity) were enrolled at three different centres in Norway. Intervention Participants were randomly assigned to four capsules with a total of 320 mg/d of naturally purified anthocyanins or placebo 1:1 for 24 weeks. Main outcomes and measures The primary outcome was the Quality of Episodic Memory composite measure (0–100) from an online cognitive test battery CogTrack, which was administered at baseline and monthly for the next 24 weeks. Secondary outcomes included other cognitive scores from the CogTrack battery. We applied mixed effects models with a baseline test score, group, time and their interaction as fixed effects, as well as other predefined baseline covariates. The primary comparison was the group difference at week 24 based on a modified intention-to-treat principle. Results : The primary analysis did not show a significant group difference at 24 weeks (78.2 versus 76.8; adjusted mean difference 1.4 (95% confidence interval -0.9–3.7); effect size 0.15; p = 0.23). However, there was a significant difference in slopes during weeks 8–24 (p = 0.007); the anthocyanin group improved while the placebo group worsened. No differences were found for the secondary cognitive outcomes. Anthocyanin capsules were well-tolerated and safe to use. Conclusion Anthocyanin supplementation for 24 weeks was safe and well tolerated in people with MCI or cardiometabolic disorders. We found no significant group difference in episodic memory at the end of the study but statistically significant differences in slopes. Further studies are warranted to explore whether anthocyanins supplementation can reduce cognitive decline in people at increased risk of dementia.publishedVersio

Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data

Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features. We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions. We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-β and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores. This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials. The online version contains supplementary material available at 10.1186/s13195-021-00946-w

Sex differences in brain atrophy in dementia with Lewy bodies

Publisher Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Highlights: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.Peer reviewe

White Matter Lesions and Pattern Recognition in MRI of Neurodegenerative Dementia

PhD thesis in Information technologyIntroduction Expected age is increasing globally and dementia is a common outcome for an increasing number of people. Dementia is a demanding syndrome for the patient and the environment as well as it is costly for society. Damaging changes to the cerebral blood flow also called white matter lesions (WML) are common in the elderly and is expected to increase as age advances. It has been reported that these types of lesions affect cognition in healthy elderly. They are also associated to Alzheimer’s disease but have not been much studied in DLB. Quantitative analysis and machine learning have a potential to contribute in understanding the disease process as well as aid in diagnosis. Methods Quantitative analysis of WML volumes were calculated using an automatic segmentation routine on magnetic resonance images (MRI) of subjects with Alzheimer’s disease (AD), Lewy body dementia (LBD), and normal controls (NC). Statistical tests were performed to compare groups as well as to investi- gate relations to cognition. Additionally, WML volumes were used as features in a machine learning (ML) environment to check whether WML volume were able to classify subjects with AD and LBD from NC. Texture analysis (TA) may be able to document changes at a microstructural level and was performed in WML an non-WML regions of the different types of MRI’s (FLAIR and T1). 2D- and 3D TA features were calculated and used in classification with the aim to serve as a tool for computer aided diagnosis (CAD) in dementia. The dataset used was imbalanced meaning that the number of subjects in each group were very different. Two methods for handling the imbalanced data were tested, namely upsampling and cost-sensitive classification. Results and conclusions Severity of WML did neither differ significantly between subjects with dementia and NC nor between mildly demented patients with AD and LBD. WML severity were associated with cognitive decline in AD, but not LBD suggesting that WML contributes to cognitive decline in AD, but not LBD. More studies of the potential clinical impact of WML in patients with LBD are needed. The best classification results obtained using WML volumes as features in an ML framework discerning subjects with dementia from healthy controls were an area under curve (AUC) of 0.73 and 95% confidence interval of 0.57 to 0.83. We experienced better classification results when using TA features compared to WML volumes in classification and better results when performing classifi- cation on TA features calculated from T1 MRI compared to FLAIR MRI. A total accuracy, reported as mean with standard deviation in brackets over cross validation folds, of 0.97(0.07) or higher was reported for the dementia vs. NC, AD vs. NC, and LBD vs. NC classification problems for both the 2D- and 3D texture analysis approaches. In the AD vs. LBD case a total accuracy of 0.73(0.16) was reported using the 2D TA approach slightly exceeded by the 3D TA approach were 0.79(0.15) was reported. It seems like the results do not differ much when performing analysis in different regions of the brain and that the results vary in an inconsistent way. Using upsampling increased classification accuracy to a large extent in the LBD class at the expense of total accuracy and the accuracy of the AD class. In both the two-class problems NC vs. AD and NC vs. LBD, adding cost- sensitivity increased classification performance in many of the tests, but upsam- pling increased accuracy even more in most of the tests. High classification performance was achieved when classifying dementia groups from NC’s. The classification performance reached when classifying AD from LBD did not reach the same level. Further research with the aim of developing methods with a higher sensitivity to the different brain changes going on in AD and LBD are needed.Helse Ves