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1.
Brain Sci ; 13(9)2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37759924

ABSTRACT

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I-IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

2.
Nat Med ; 29(4): 950-962, 2023 04.
Article in English | MEDLINE | ID: mdl-37069360

ABSTRACT

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.


Subject(s)
Cerebral Small Vessel Diseases , Stroke , Humans , Endothelial Cells/pathology , Genome-Wide Association Study , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/genetics , Cerebral Small Vessel Diseases/complications , Magnetic Resonance Imaging/methods , Genomics
3.
Aging (Albany NY) ; 14(17): 6844-6858, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35852852

ABSTRACT

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) increases with age and is associated with stroke and cognitive decline. Enlarged Perivascular Spaces (ePVS) is an emerging marker of CSVD, but its prevalence over the life span remain unclear. We characterized the age and sex-specific prevalence of ePVS and relation to age-specific risk factors, in a large community-based sample. METHODS: We included 3,710 Framingham Heart Study participants with available brain MRI (average age 61.4±14.6, 46% men). ePVS burden was rated in the centrum semiovale (CSO) and basal ganglia (BG) regions. Individual vascular risk factors were related to ePVS burden in the CSO, BG, and mixed CSO-BG regions using multivariable adjusted ordinal logistic regression analysis. RESULTS: Severe ePVS prevalence increased with age in men and women, and paralleled increase in vascular risk factors, and prevention treatment use. Older age, hypertension (and resulting higher treatment use), higher systolic and diastolic blood pressure, and smoking were associated with higher burden of ePVS in the CSO, BG and mixed regions. CONCLUSIONS: Our observations reinforce the hypothesis that ePVS may be a marker of aging-driven brain vascular pathologies, and its association with vascular risk factors support their role as CSVD imaging biomarker.


Subject(s)
Cerebral Small Vessel Diseases , Aged , Aging , Biomarkers , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/epidemiology , Female , Humans , Magnetic Resonance Imaging , Male , Prevalence , Risk Factors
4.
Ann Neurol ; 92(1): 23-31, 2022 07.
Article in English | MEDLINE | ID: mdl-35373386

ABSTRACT

OBJECTIVE: Enlarged perivascular spaces have emerged as markers of cerebral small vessel disease and are linked to perivascular drainage dysfunction. The apolipoprotein E-ɛ4 (APOE-ɛ4) allele is the strongest genetic risk factor for cerebral amyloid angiopathy and Alzheimer's neuropathology, but the underlying mechanisms remain unclear. We studied the relationship between APOE-ɛ4 and the topography and burden of enlarged perivascular spaces to elucidate underlying mechanisms between APOE-ɛ4 and adverse clinical outcomes. METHODS: We included 3,564 Framingham Heart Study participants with available genotypes and magnetic resonance imaging. Enlarged perivascular spaces in the basal ganglia and centrum semiovale were rated using a validated scale. We related APOE-ɛ4 allele presence to high burden of enlarged perivascular spaces in each region and a mixed score reflecting high burden in both regions using multivariable logistic regression. Exploratory analyses incorporated presence of cerebral microbleeds and assessed effect modification by hypertension. RESULTS: Mean age was 60.7 years (SD = 14.6), 1,644 (46.1%) were men, 1,486 (41.8%) were hypertensive, and 836 (23.5%) participants were APOE-ɛ4 carriers. APOE-ɛ4 was associated with high burden of enlarged perivascular spaces in the centrum semiovale (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.16, 1.81) and mixed regions (OR = 1.37, 95% CI = 1.11, 1.68). Associations were slightly stronger in hypertensive subjects. INTERPRETATION: The APOE-ɛ4 allele plays a modest role in the burden of enlarged perivascular spaces in the centrum semiovale. Further studies are needed to clarify the underlying small vessel disease type in community-dwelling individuals with predominant centrum semiovale enlarged perivascular spaces, which may be hypertensive angiopathy in our sample. ANN NEUROL 2022;92:23-31.


Subject(s)
Cerebral Amyloid Angiopathy , Cerebral Small Vessel Diseases , Alleles , Apolipoprotein E4/genetics , Apolipoproteins E , Cerebral Amyloid Angiopathy/diagnostic imaging , Cerebral Amyloid Angiopathy/genetics , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/genetics , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged
6.
Acad Radiol ; 26(12): 1605-1617, 2019 12.
Article in English | MEDLINE | ID: mdl-30799032

ABSTRACT

OBJECTIVE: To describe the prevalence, severity, and location of ankle injuries as assessed on magnetic resonance imaging (MRI) in athletes participating in the Rio de Janeiro 2016 Summer Olympic Games. METHODS: We analyzed all ankle MRIs that were acquired for suspected injury as reported by the National Olympic Committee medical teams and the Organizing Committee medical staff during the Rio 2016 Summer Olympics. Diagnostic imaging was performed through the Olympic Village Polyclinic. Images were interpreted retrospectively according to standardized criteria. RESULTS: A total of 11,274 athletes participated in the Games, of which 89 (8.8%) were referred for an ankle MRI. Eighty-eight of the 89 (99%) had at least 1 abnormal finding, and some had as many as 27, for an average of 6.2 abnormalities per examination. Around one-fifth of all abnormal findings were considered pre-existing (21%) and 79% were assumed to be the result of an acute or subacute injury. The highest proportion of acute/subacute injuries per athlete occurred in ball sports (7.0 injuries per examination) and in the age group >30. Most pre-existing findings per athlete were identified in the group of others (no track and field or ball sports athletes) with 2.5 findings per examination and respectively in the age group >30 (1.7). CONCLUSION: Our study demonstrated a high prevalence of acute and subacute, but also pre-existing injuries in Olympic athletes undergoing ankle MRI. Tendon injuries were the most common acute injuries, found mainly in ball sports athletes. Most pre-existing ankle injuries were identified at the ligaments.


Subject(s)
Ankle Injuries/diagnosis , Athletes , Athletic Injuries/diagnosis , Magnetic Resonance Imaging/methods , Adult , Ankle Injuries/epidemiology , Athletic Injuries/epidemiology , Brazil/epidemiology , Female , Humans , Male , Prevalence , Retrospective Studies
7.
Skeletal Radiol ; 43(8): 1155-9, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24609811

ABSTRACT

Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis.


Subject(s)
Magnetic Resonance Imaging/methods , Muscle, Skeletal/pathology , Myositis/pathology , Arm/pathology , Biopsy , Contrast Media , Diagnosis, Differential , Female , Follow-Up Studies , Gadolinium , Humans , Image Enhancement/methods , Middle Aged
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