Association between long-term PM2.5 exposure and risk of Kawasaki disease in children: A nationwide longitudinal cohort study.

BACKGROUND: Based on previous studies suggesting air pollution as a potential risk factor for Kawasaki Disease (KD), we examined the association of long-term exposure to childhood fine particulate matter (PM2.5) with the risk of KD. METHODS: We used National Health Insurance Service-National Sample Cohort data from 2002 to 2019, which included beneficiaries aged 0 years at enrollment and followed-up until the onset of KD or age 5 years. The onset of KD was defined as the first hospital visit record with a primary diagnostic code of M30.3, based on the 10th revision of the International Classification of Diseases, and with an intravenous immunoglobulin (IVIG) prescription. We assigned PM2.5 concentrations to 226 districts, based on mean annual predictions from a machine learning-based ensemble prediction model. We performed Cox proportional-hazards modeling with time-varying exposures and confounders. RESULTS: We identified 134,634 individuals aged five or less at enrollment and, of these, 1220 individuals who had a KD onset and an IVIG prescription during study period. The average annual concentration of PM2.5 exposed to the entire cohort was 28.2 µg/m³ (Standard Deviation 2.9). For each 5 µg/m³ increase in annual PM2.5 concentration, the hazard ratio of KD was 1.21 (95% CI 1.05-1.39). CONCLUSIONS: In this nationwide, population-based, cohort study, long-term childhood exposure to PM2.5 was associated with an increased incidence of KD in children. The study highlights plausible mechanisms for the association between PM2.5 and KD, but further studies are needed to confirm our findings.

Iron Oxide Nanoparticle-Incorporated Mesenchymal Stem Cells for Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is a neurodegenerative disease with multifactorial pathogenesis. However, most current therapeutic approaches for AD target a single pathophysiological mechanism, generally resulting in unsatisfactory therapeutic outcomes. Recently, mesenchymal stem cell (MSC) therapy, which targets multiple pathological mechanisms of AD, has been explored as a novel treatment. However, the low brain retention efficiency of administered MSCs limits their therapeutic efficacy. In addition, autologous MSCs from AD patients may have poor therapeutic abilities. Here, we overcome these limitations by developing iron oxide nanoparticle (IONP)-incorporated human Wharton's jelly-derived MSCs (MSC-IONPs). IONPs promote therapeutic molecule expression in MSCs. Following intracerebroventricular injection, MSC-IONPs showed a higher brain retention efficiency under magnetic guidance. This potentiates the therapeutic efficacy of MSCs in murine models of AD. Furthermore, human Wharton's jelly-derived allogeneic MSCs may exhibit higher therapeutic abilities than those of autologous MSCs in aged AD patients. This strategy may pave the way for developing MSC therapies for AD.

Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine.

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.

Risk of Dementia in Newly Diagnosed Glaucoma: A Nationwide Cohort Study in Korea.

PURPOSE: To investigate the risk of dementia in participants with newly diagnosed glaucoma. DESIGN: A nationwide cohort study using authorized data provided by the Korean National Health Insurance Service (NHIS). PARTICIPANTS: A total of 788 961 participants aged ≥ 45 years in 2006, who did not have dementia or glaucoma between 2002 and 2005, were included. METHODS: Data were collected from a nationwide population-based retrospective cohort study using the Korean NHIS database. From January 2006 to December 2017, participants were tracked for the diagnosis of glaucoma or dementia using claims data. The prospective association between newly diagnosed glaucoma and the risk of dementia was investigated using a multivariable Cox proportional hazard model adjusted for age, sex, behavioral factors, and systemic and ocular comorbidities. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia development according to the parameters, including glaucoma diagnosis. RESULTS: Overall, 7.0% of the participants developed dementia after an average of 7.4 years. Newly diagnosed glaucoma was associated with a higher risk of dementia (HR, 1.89, 95% CI, 1.57-2.27) independent of age, sex, body mass index, income, smoking and drinking status, visual acuity, and other systemic comorbidities, such as diabetes, hypertension, stroke, and depression. Newly diagnosed glaucoma was associated with higher risk of AD but not VD. The risk of dementia in relation to glaucoma was higher in older participants (HR, 3.15 [≥ 65 years] vs. 1.56 [< 65 years], P < 0.0001). CONCLUSIONS: This nationwide cohort study found that individuals with newly diagnosed glaucoma were at a higher risk of developing dementia, particularly AD. This association was greater among older individuals in the studied population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Emerging role of vascular burden in AT(N) classification in individuals with Alzheimer's and concomitant cerebrovascular burdens.

OBJECTIVES: Alzheimer's disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. METHODS: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. RESULTS: In A+ category, compared with the frequency of Alzheimer's pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p<0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimer's pathological changes (A-T+, A-N+; p=0.002) and Alzheimer's pathological changes (p<0.001) categories. CONCLUSION: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system.

Outcome of epidural blood patch for imaging-negative spontaneous intracranial hypotension.

BACKGROUND: Spontaneous intracranial hypotension is diagnosed by an abnormal finding in brain MRI, spinal imaging, or lumbar puncture. However, the sensitivity of each test is low. We investigated whether patients with suspected spontaneous intracranial hypotension and negative imaging findings would respond to epidural blood patch. METHODS: We prospectively recruited patients with new-onset orthostatic headache admitted at the Samsung Medical Center from January 2017 to July 2021. In patients without abnormal imaging findings and no history of prior epidural blood patch, treatment outcome-defined as both 50% response in maximal headache intensity and improvement of orthostatic component-was collected at discharge and three months after epidural blood patch. RESULTS: We included 21 treatment-naïve patients with orthostatic headache and negative brain and spinal imaging results who received epidural blood patch. After epidural blood patch (mean 1.3 times, range 1-3), 14 (66.7%) and 19 (90.5%) patients achieved both 50% response and improvement of orthostatic component at discharge and three months post-treatment, respectively. Additionally, complete remission was reported in 11 (52.4%) patients at three-month follow-up, while most of the remaining patients had only mild headaches. Among nine (42.9%) patients who underwent lumbar puncture, none had an abnormally low opening pressure (median 13.8 cm H2O, range 9.2-21.5). CONCLUSION: Given the high responder rates of epidural blood patch in our study, empirical epidural blood patch should be considered to treat new-onset orthostatic headache, even when brain and spinal imaging are negative. The necessity of lumbar puncture is questionable considering the high response rate of epidural blood patch and low rate of "low pressure."

Association of long-term exposure to air pollution with chronic sleep deprivation in South Korea: A community-level longitudinal study, 2008-2018.

BACKGROUND AND OBJECTIVE: Although there are many findings about the effects of fine particulate matter (PM2.5) and sleep deprivation on health respectively, the association between PM2.5 and chronic sleep deprivation has rarely been investigated. Thus, we aimed to investigate this association using a nationwide survey in South Korea. METHOD: We examined the association between long-term exposure to PM2.5 and chronic sleep deprivation using a national cross-sectional health survey covering the entire 226 districts in inland South Korea from 2008 to 2018, with a machine learning-based national air pollution prediction model with 1 km2 spatial resolution. RESULTS: Chronic sleep deprivation was positively associated with PM2.5 in the total population (odds ratio (OR): 1.09, 95% confidence interval (CI): 1.05-1.13) and sub-population (low, middle, high population density areas with OR: 1.127, 1.09, and 1.059, respectively). The association was consistently observed in both sexes (males with OR: 1.09, females with OR: 1.09)) and was more pronounced in the elderly population (OR: 1.12) than in the middle-aged (OR: 1.07) and young (OR: 1.09) populations. CONCLUSIONS: Our results are consistent with the hypothesis regarding the relationship between long-term PM2.5 exposure and chronic sleep deprivation, and the study provides quantitative evidence for public health interventions to improve air quality that can affect chronic sleep conditions.

Independent effects of amyloid and vascular markers on long-term functional outcomes: An 8-year longitudinal study of subcortical vascular cognitive impairment.

BACKGROUND AND PURPOSE: Subcortical vascular cognitive impairment (SVCI) is characterized by the presence of cerebral small vessel disease (CSVD) markers. Some SVCI patients also show Alzheimer's disease and cerebral amyloid angiopathy markers. However, the effects of these imaging markers on long-term clinical outcomes have not yet been established. The present study, therefore, aimed to determine how these imaging markers influence functional disability and/or mortality. METHODS: We recruited 194 participants with SVCI from the memory clinic and followed them up. All participants underwent brain magnetic resonance imaging at baseline, and 177 (91.2%) participants underwent beta-amyloid (Aß) positron emission tomography. We examined the occurrence of ischemic or hemorrhagic strokes. We also evaluated functional disability and mortality using the modified Rankin scale. To determine the effects of imaging markers on functional disability or mortality, we used Fine and Gray competing regression or Cox regression analysis. RESULTS: During a 8.6-year follow-up period, 46 of 194 patients (23.7%) experienced a stroke, 110 patients (56.7%) developed functional disabilities and 75 (38.6%) died. Aß positivity (subdistribution hazard ratio [SHR] = 2.73), greater white matter hyperintensity (WMH) volume (SHR = 3.11) and ≥3 microbleeds (SHR = 2.29) at baseline were independent predictors of functional disability regardless of the occurrence of stroke. Greater WMH volume (hazard ratio = 2.07) was an independent predictor of mortality. CONCLUSIONS: Our findings suggest that diverse imaging markers may predict long-term functional disability and mortality in patients with SVCI, which in turn may provide clinicians with a more insightful understanding of the long-term outcomes of SVCI.

Association between Baseline Cognitive Function and Longitudinal Functional Outcome Change after Ischemic Stroke.

INTRODUCTION: Ischemic stroke can cause impairment of daily function and cognitive function. Higher cognitive function is reported in many studies to be associated with better functional outcomes; however, evidence from longitudinal study is lacking. Therefore, in the present study, the association between cognitive function and longitudinal changes of functional outcome was investigated based on stroke severity. Furthermore, whether the effect of cognitive function remained consistent after controlling for depression was investigated. METHODS: The data of 423 stroke patients (292 minor strokes, 93 moderate strokes, and 38 severe strokes) were collected. Baseline Mini-Mental State Examination (MMSE) score was considered a predictor, and change of modified Rankin Scale (mRS) score during 12 months of follow-up was the outcome. First, the association between the baseline MMSE score and longitudinal change in the mRS score was analyzed using linear mixed-effects models. Fixed effects were MMSE score group, time, and MMSE score group × time interaction. Additional adjustment was made for the Geriatric Depression Scale (GDS) score. RESULTS: Among the 423 subjects, the mean age was 73.5 years, and 43.4% were female. In the minor stroke group, the high MMSE score group had a decreased mRS score, and the low MMSE score group had an increased mRS score (p < 0.001). This association remained after additional adjustment of the GDS score. Association was not observed between cognitive function and functional recovery in the moderate or severe stroke group. CONCLUSION: After ischemic stroke, higher baseline global cognitive function was a predictive factor for better functional recovery regardless of depression symptoms in the minor stroke group.

Suicide rate and social environment characteristics in South Korea: the roles of socioeconomic, demographic, urbanicity, general health behaviors, and other environmental factors on suicide rate.

BACKGROUND: Suicide is a serious worldwide public health concern, and South Korea has shown the highest suicide rate among Organisation for Economic Co-operation and Development (OECD) countries since 2003. Nevertheless, most previous Korean studies on suicide had limitations in investigating various social environment factors using long-term nationwide data. Thus, this study examined how various social environment characteristics are related to the suicide rate at the district-level, using nationwide longitudinal data over 11 years. METHODS: We used the district-level age-standardized suicide rate and a total of 12 annual social environment characteristics that represented socioeconomic, demographic, urbanicity, general health behaviors, and other environmental characteristics from 229 administrative districts in South Korea. A Bayesian hierarchical model with integrated Laplace approximations (INLA) was used to examine the spatiotemporal association between the rate of suicide and the social environment indicators selected for the study. RESULTS: In the total population, the indicators "% of population aged 65 and older eligible for the basic pension", "% vacant houses in the area", "% divorce", "% single elderly households", "% detached houses", "% current smokers", and "% of population with obesity" showed positive associations with the suicide rate. In contrast, "% of people who regularly participated in religious activities" showed negative associations with suicide rate. The associations between these social environment characteristics and suicide rate were generally more statistically significant in males and more urbanized areas, than in females and less urbanized areas; however, associations differed amongst age groups, depending on the social environment characteristic variable under study. CONCLUSIONS: This study investigated the complex role of social environments on suicide rate in South Korea and revealed that higher suicide rates were associated with lower values of socioeconomic status, physical exercise, and religious activities, and with higher social isolation and smoking practice. Our results can be used in the development of targeted suicide prevention policies.

IntraBrain Injector (IBI): A Stereotactic-Guided Device for Repeated Delivery of Therapeutic Agents Into the Brain Parenchyma.

BACKGROUND: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. METHODS: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. RESULTS: We compared the planned vs. insertion trajectory of IBI to the hippocampus. With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. CONCLUSION: Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.

Interaction between Alzheimer's Disease and Cerebral Small Vessel Disease: A Review Focused on Neuroimaging Markers.

Alzheimer's disease (AD) is characterized by the presence of ß-amyloid (Aß) and tau, and subcortical vascular cognitive impairment (SVCI) is characterized by cerebral small vessel disease (CSVD). They are the most common causes of cognitive impairment in the elderly population. Concurrent CSVD burden is more commonly observed in AD-type dementia than in other neurodegenerative diseases. Recent developments in Aß and tau positron emission tomography (PET) have enabled the investigation of the relationship between AD biomarkers and CSVD in vivo. In this review, we focus on the interaction between AD and CSVD markers and the clinical effects of these two markers based on molecular imaging studies. First, we cover the frequency of AD imaging markers, including Aß and tau, in patients with SVCI. Second, we discuss the relationship between AD and CSVD markers and the potential distinct pathobiology of AD markers in SVCI compared to AD-type dementia. Next, we discuss the clinical effects of AD and CSVD markers in SVCI, and hemorrhagic markers in cerebral amyloid angiopathy. Finally, this review provides both the current challenges and future perspectives for SVCI.

Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aß1-42.

Honeybee venom has recently been considered an anti-neurodegenerative agent, primarily due to its anti-inflammatory effects. The natural accumulation of amyloid-beta (Aß) in the brain is reported to be the natural cause of aging neural ability downfall, and oxidative stress is the main route by which Aß ignites its neural toxicity. Anti-neural oxidative stress is considered an effective approach for neurodegenerative therapy. To date, it is unclear how bee venom ameliorates neuronal cells in oxidative stress induced by Aß. Here, we evaluated the neuroprotective effect of bee venom on Aß-induced neural oxidative stress in both HT22 cells and an animal model. Our results indicate that bee venom protected HT22 cells against apoptosis induced by Aß1-42. This protective effect was explained by the increased nuclear translocation of nuclear factor erythroid 2-like 2 (Nrf2), consequently upregulating the production of heme oxygenase-1 (HO-1), a critical cellular instinct antioxidant enzyme that neutralizes excessive oxidative stress. Furthermore, bee venom treatment activated the tropomyosin-related kinase receptor B (TrkB)/cAMP response element-binding (CREB)/brain-derived neurotrophic factor (BDNF), which is closely related to the promotion of cellular antioxidant defense and neuronal functions. A mouse model with cognitive deficits induced by Aß1-42 intracerebroventricular (ICV) injections was also used. Bee venom enhanced animal cognitive ability and enhanced neural cell genesis in the hippocampal dentate gyrus region in a dose-dependent manner. Further analysis of animal brain tissue and serum confirmed that bee venom reduced oxidative stress, cholinergic system activity, and intercellular neurotrophic factor regulation, which were all adversely affected by Aß1-42. Our study demonstrates that bee venom exerts antioxidant and neuroprotective actions against neural oxidative stress caused by Aß1-42, thereby promoting its use as a therapeutic agent for neurodegenerative disorders.

Harmonisation of PET imaging features with different amyloid ligands using machine learning-based classifier.

PURPOSE: In this study, we used machine learning to develop a new method derived from a ligand-independent amyloid (Aß) positron emission tomography (PET) classifier to harmonise different Aß ligands. METHODS: We obtained 107 paired 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) PET images at the Samsung Medical Centre. To apply the method to FMM ligand, we transferred the previously developed FBB PET classifier to test similar features from the FMM PET images for application to FMM, which in turn developed a ligand-independent Aß PET classifier. We explored the concordance rates of our classifier in detecting cortical and striatal Aß positivity. We investigated the correlation of machine learning-based cortical tracer uptake (ML-CTU) values quantified by the classifier between FBB and FMM. RESULTS: This classifier achieved high classification accuracy (area under the curve = 0.958) even with different Aß PET ligands. In addition, the concordance rate of FBB and FMM using the classifier (87.5%) was good to excellent, which seemed to be higher than that in visual assessment (82.7%) and lower than that in standardised uptake value ratio cut-off categorisation (93.3%). FBB and FMM ML-CTU values were highly correlated with each other (R = 0.903). CONCLUSION: Our findings suggested that our novel classifier may harmonise FBB and FMM ligands in the clinical setting which in turn facilitate the biomarker-guided diagnosis and trials of anti-Aß treatment in the research field.

Honorific Speech Impairment: A Characteristic Sign of Frontotemporal Dementia.

BACKGROUND: Individuals with the behavioral variant of frontotemporal dementia (bvFTD) exhibit various levels of abulia, disinhibition, impaired judgment, and decline in executive function. Empirical evidence has shown that individuals with bvFTD also often exhibit difficulty using honorific speech, which expresses respect to another party or addressee. OBJECTIVE: To analyze differences in the ability to use honorific speech among individuals with bvFTD, individuals with dementia of the Alzheimer type (AD dementia), and individuals with normal cognition (NC). METHOD: A total of 53 native Korean speakers (13 bvFTD, 20 AD dementia, and 20 NC) completed an experimental honorific speech task (HST) that involved both expressive and receptive tasks. We analyzed the number of correct responses and error patterns separately for an expressive task and for a receptive task. RESULTS: The bvFTD group had significantly fewer correct responses on the HST compared with the AD dementia and NC groups. The bvFTD group exhibited more misjudgment errors in identifying nonhonorific speech as honorific speech in the expressive task, and significantly longer response times in the receptive task, than the AD dementia and NC groups. Significant associations were identified between HST scores and cortical atrophy in the temporal and frontotemporal lobes. CONCLUSION: A decline in the ability to use honorific speech may be a diagnosable behavioral and psychiatric symptom for bvFTD in Korean-speaking individuals. This decline in individuals with bvFTD could be attributed to multiple factors, including social manners (politeness) and impaired social language use ability (pragmatics).

Feasibility of MRI for the evaluation of interosseous ligament vertical segment via subtalar arthroscopy correlation: comparison of 2D and 3D MR images.

BACKGROUND: Interosseous ligament vertical segment (IOLV) and calcaneofibular ligament (CFL) have been reported to be important in stabilizing the subtalar joint. Unlike CFL, there is not much information regarding the comparison of MRI results with surgical evaluation of IOLV and the comparison between 2D and 3D MRI on IOLV evaluation. The feasibility of MRI in IOLV evaluation has yet to be reported. The purpose of this study was to evaluate the validity and reliability of MRI in IOLV tear detection via correlation with arthroscopic results. We also compared the diagnostic performance of 2D and 3D MR images. METHODS: In this retrospective study, 52 patients who underwent subtalar arthroscopy after ankle MRI were enrolled. Arthroscopic results confirmed IOLV tear in 25 cases and intact IOLV in 27 cases. Two radiologists independently evaluated the IOLV tears using only conventional 2D images, followed by isotropic 3D images, and comparison with arthroscopic results. RESULTS: Only the 2D sequences interpreted by two readers showed a sensitivity of 64.0-96.0%, a specificity of 29.6-44.4%, a positive predictive value of 51.6-56.4%, and a negative predictive value of 57.1-88.9%. Addition of isotropic 3D sequences changed the sensitivity to 60.0-80.0%, specificity to 63.0-77.8%, positive predictive value to 64.3-76.9%, and negative predictive value to 66.7-80.8%. The overall diagnostic performance of isotropic 3D sequences (AUC values: 0.679-0.816) was higher than that of 2D sequences (AUC values: 0.568-0.647). Inter-observer and intra-observer agreement between the two readers was moderate-to-good for both 2D and 3D sequences. The diagnostic accuracy in 19 patients with tarsal sinus fat obliteration tended to increase from 26.3-42.1% to 57.9-73.7% with isotropic 3D sequences compared with 2D sequences. CONCLUSIONS: Isotropic 3D MRI was feasible for the assessment of IOLV tear prior to subtalar arthroscopy. Additional 3D sequences showed higher diagnostic accuracy compared with conventional 2D sequences in IOLV evaluation. Isotropic 3D sequences may be more valuable in detecting IOLV tear in case of tarsal sinus fat obliteration.

Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments.

BACKGROUND AND PURPOSE: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. METHODS: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aß (amyloid-ß) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. RESULTS: The frequency of Aß positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P=0.047). The lobar cerebellar group had a higher Aß positivity (75% versus 28.6%, P=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P=0.041) than the dentate group. CONCLUSIONS: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

Correction to: Staging and quantification of florbetaben PET images using machine learning: impact of predicted regional cortical tracer uptake and amyloid stage on clinical outcomes.

Incorrect acknowledgments.

Staging and quantification of florbetaben PET images using machine learning: impact of predicted regional cortical tracer uptake and amyloid stage on clinical outcomes.

PURPOSE: We developed a machine learning-based classifier for in vivo amyloid positron emission tomography (PET) staging, quantified cortical uptake of the PET tracer by using a machine learning method, and investigated the impact of these amyloid PET parameters on clinical and structural outcomes. METHODS: A total of 337 18F-florbetaben PET scans obtained at Samsung Medical Center were assessed. We defined a feature vector representing the change in PET tracer uptake from grey to white matter. Using support vector machine (SVM) regression and SVM classification, we quantified the cortical uptake as predicted regional cortical tracer uptake (pRCTU) and categorised the scans as positive and negative. Positive scans were further classified into two stages according to the striatal uptake. We compared outcome parameters among stages and further assessed the association between the pRCTU and outcome variables. Finally, we performed path analysis to determine mediation effects between PET variables. RESULTS: The classification accuracy was 97.3% for cortical amyloid positivity and 91.1% for striatal positivity. The left frontal and precuneus/posterior cingulate regions, as well as the anterior portion of the striatum, were important in determination of stages. The clinical scores and magnetic resonance imaging parameters showed negative associations with PET stage. However, except for the hippocampal volume, most outcomes were associated with the stage through the complete mediation effect of pRCTU. CONCLUSION: Using a machine learning algorithm, we achieved high accuracy for in vivo amyloid PET staging. The in vivo amyloid stage was associated with cognitive function and cerebral atrophy mostly through the mediation effect of cortical amyloid.

Correction to: Staging and quantification of florbetaben PET images using machine learning: impact of predicted regional cortical tracer uptake and amyloid stage on clinical outcomes.

The Table 2 in the original version of this article contained a mistake in the alignment. Correct Table 2 presentation is presented here.