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Quality control of brain segmentation is a fundamental step to ensure data quality. Manual quality control strategies are the current gold standard, although these may be unfeasible for large neuroimaging samples. Several options for automated quality control have been proposed, providing potential time efficient and reproducible alternatives. However, those have never been compared side to side, which prevents consensus in the appropriate quality control strategy to use. This study aimed to elucidate the changes manual editing of brain segmentations produce in morphological estimates, and to analyze and compare the effects of different quality control strategies on the reduction of the measurement error. Structural brain MRI from 259 participants of The Maastricht Study were used. Morphological estimates were automatically extracted using FreeSurfer 6.0. Segmentations with inaccuracies were manually edited, and morphological estimates were compared before and after editing. In parallel, 12 quality control strategies were applied to the full sample. Those included: two manual strategies, in which images were visually inspected and either excluded or manually edited; five automated strategies, where outliers were excluded based on the tools "MRIQC" and "Qoala-T", and the metrics "morphological global measures", "Euler numbers" and "Contrast-to-Noise ratio"; and five semi-automated strategies, where the outliers detected through the mentioned tools and metrics were not excluded, but visually inspected and manually edited. In order to quantify the effects of each quality control strategy, the proportion of unexplained variance relative to the total variance was extracted after the application of each strategy, and the resulting differences compared. Manually editing brain surfaces produced particularly large changes in subcortical brain volumes and moderate changes in cortical surface area, thickness and hippocampal volumes. The performance of the quality control strategies depended on the morphological measure of interest. Overall, manual quality control strategies yielded the largest reduction in relative unexplained variance. The best performing automated alternatives were those based on Euler numbers and MRIQC scores. The exclusion of outliers based on global morphological measures produced an increase of relative unexplained variance. Manual quality control strategies are the most reliable solution for quality control of brain segmentation and parcellation. However, measures must be taken to prevent the subjectivity associated with these strategies. The detection of inaccurate segmentations based on Euler numbers or MRIQC provides a time efficient and reproducible alternative. The exclusion of outliers based on global morphological estimates must be avoided.
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Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Imagen por Resonancia Magnética/normas , Neuroimagen/métodos , Neuroimagen/normas , Control de Calidad , Adulto , Anciano , Estudios Transversales , Femenino , Guías como Asunto , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
Background Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matter and eventually contribute to cognitive decline. However, there is no consensus yet about the precise underlying topological mechanism. Purpose To examine whether WMH and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population. In addition, to investigate underlying local abnormalities in white matter by assessing the tract-specific WMH volumes and their tract-specific association with cognitive function. Materials and Methods In the prospective type 2 diabetes-enriched population-based Maastricht Study, structural and diffusion-tensor MRI was performed (December 2013 to February 2017). Total and tract-specific WMH volumes; network measures; cognition scores; and demographic, cardiovascular, and lifestyle characteristics were determined. Multivariable linear regression and mediation analyses were used to investigate the association of WMH volume, tract-specific WMH volumes, and network measures with cognitive function. Associations were adjusted for age, sex, education, diabetes status, and cardiovascular risk factors. Results A total of 5083 participants (mean age, 59 years ± 9 [standard deviation]; 2592 men; 1027 with diabetes) were evaluated. Larger WMH volumes were associated with stronger local (standardized ß coefficient, 0.065; P < .001), but not global, network efficiency and lower information processing speed (standardized ß coefficient, -0.073; P < .001). Moreover, lower local efficiency (standardized ß coefficient, -0.084; P < .001) was associated with lower information processing speed. In particular, the relationship between WMHs and information processing speed was mediated (percentage mediated, 7.2% [95% CI: 3.5, 10.9]; P < .05) by the local network efficiency. Finally, WMH load was larger in the white matter tracts important for information processing speed. Conclusion White matter hyperintensity volume, local network efficiency, and information processing speed scores are interrelated, and local network properties explain lower cognitive performance due to white matter network alterations. © RSNA, 2020 Online supplemental material is available for this article.
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Disfunción Cognitiva/fisiopatología , Imagen de Difusión Tensora/métodos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiopatología , Adulto , Anciano , Cognición , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
PURPOSE: Blood-brain barrier (BBB) disruption is commonly measured with DCE-MRI using continuous dynamic scanning. For precise measurement of subtle BBB leakage, a long acquisition time (>20 minutes) is required. As extravasation of the contrast agent is slow, discrete sampling at strategic time points might be beneficial, and gains scan time for additional sequences. Here, we aimed to explore the feasibility of a sparsely sampled MRI protocol at 7 T. METHODS: The scan protocol consisted of a precontrast quantitative T1 measurement, using an MP2RAGE sequence, and after contrast agent injection, a fast-sampling dynamic gradient-echo perfusion scan and two postcontrast quantitative T1 measurements were applied. Simulations were conducted to determine the optimal postcontrast sampling time points for measuring subtle BBB leakage. The graphical Patlak approach was used to quantify the leakage rate (Ki ) and blood plasma volume (vp ) of normal-appearing white and gray matter. RESULTS: The simulations showed that two postcontrast T1 maps are sufficient to detect subtle leakage, and most sensitive when the last T1 map is acquired late, approximately 30 minutes, after contrast agent administration. The in vivo measurements found Ki and vp values in agreement with other studies, and significantly higher values in gray matter compared with white matter (both p = .04). CONCLUSION: The sparsely sampled protocol was demonstrated to be sensitive to quantify subtle BBB leakage, despite using only three T1 maps. Due to the time-efficiency of this method, it will become more feasible to incorporate BBB leakage measurements in clinical research MRI protocols.
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Barrera Hematoencefálica , Sustancia Blanca , Barrera Hematoencefálica/diagnóstico por imagen , Medios de Contraste , Sustancia Gris , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to interpret the findings against the background of dysfunction of the fear circuit and limbic cortico-striato-thalamocortical circuit. METHODS: Studies assessing anxiety symptoms in PD patients and studies using magnetic resonance imaging, positron emission tomography, or single-photon emission computed tomography were included. RESULTS: The severity of anxiety was associated with changes in the fear circuit and the cortico-striato-thalamocortical limbic circuit. In the fear circuit, a reduced gray-matter volume of the amygdala and the anterior cingulate cortex (ACC); an increased functional connectivity (FC) between the amygdala and orbitofrontal cortex (OFC) and hippocampus and between the striatum and the medial prefrontal cortex (PFC), temporal cortex, and insula; and a reduced FC between the lateral PFC and the OFC, hippocampus, and amygdala were reported. In the cortico-striato-thalamocortical limbic circuit, a reduced FC between the striatum and ACC; a reduced dopaminergic and noradrenergic activity in striatum, thalamus, and locus coeruleus; and a reduced serotoninergic activity in the thalamus were reported. CONCLUSION: To conclude, anxiety is associated with structural and functional changes in both the hypothesized fear and the limbic cortico-striato-thalamocortical circuits. These circuits overlap and may well constitute parts of a more extensive pathway, of which different parts play different roles in anxiety. The neuropathology of PD may affect these circuits in different ways, explaining the high prevalence of anxiety in PD and also the associated cognitive, motor, and psychiatric symptoms. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Enfermedad de Parkinson , Amígdala del Cerebelo , Ansiedad/diagnóstico por imagen , Ansiedad/etiología , Trastornos de Ansiedad/diagnóstico por imagen , Trastornos de Ansiedad/etiología , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagenRESUMEN
Most HR-pQCT studies examining cortical bone use an automatically generated endocortical contour (AUTO), which is manually corrected if it visually deviates from the apparent endocortical margin (semi-automatic method, S-AUTO). This technique may be prone to operator-related variability and is time consuming. We examined whether the AUTO instead of the S-AUTO method can be used for cortical bone analysis. Fifty scans of the distal radius and tibia from participants of The Maastricht Study were evaluated with AUTO, and subsequently with S-AUTO by three independent operators. AUTO cortical bone parameters were compared to the average parameters obtained by the three operators (S-AUTOmean). All differences in mean cortical bone parameters between AUTO and S-AUTOmean were < 5%, except for lower AUTO cortical porosity of the radius (- 16%) and tibia (- 6%), and cortical pore volume (Ct.Po.V) of the radius (- 7%). The ICC of S-AUTOmean and AUTO was > 0.90 for all parameters, except for cortical pore diameter of the radius (0.79) and tibia (0.74) and Ct.Po.V of the tibia (0.89), without systematic errors on the Bland-Altman plots. The precision errors (RMS-CV%) of the radius parameters between S-AUTOmean and AUTO were comparable to those between the individual operators, whereas the tibia RMS-CV% between S-AUTOmean and AUTO were higher than those of the individual operators. Comparison of the three operators revealed clear inter-operator variability. This study suggests that the AUTO method can be used for cortical bone analysis in a cross-sectional study, but that the absolute values-particularly of the porosity-related parameters-will be lower.
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Hueso Cortical/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Carbon-fiber-reinforced poly-ether-ether-ketone (CFR-PEEK) has superior radiolucency compared to other orthopedic implant materials, e.g. titanium or stainless steel, thus allowing metal-artifact-free postoperative monitoring by computed tomography (CT). Recently, high-resolution peripheral quantitative CT (HRpQCT) proved to be a promising technique to monitor the recovery of volumetric bone mineral density (vBMD), micro-architecture and biomechanical parameters in stable conservatively treated distal radius fractures. When using HRpQCT to monitor unstable distal radius fractures that require volar distal radius plating for fixation, radiolucent CFR-PEEK plates may be a better alternative to currently used titanium plates to allow for reliable assessment. In this pilot study, we assessed the effect of a volar distal radius plate made from CFR-PEEK on bone parameters obtained from HRpQCT in comparison to two titanium plates. METHODS: Plates were instrumented in separate cadaveric human fore-arms (n = 3). After instrumentation and after removal of the plates duplicate HRpQCT scans were made of the region covered by the plate. HRpQCT images were visually checked for artifacts. vBMD, micro-architectural and biomechanical parameters were calculated, and compared between the uninstrumented and instrumented radii. RESULTS: No visible image artifacts were observed in the CFR-PEEK plate instrumented radius, and errors in bone parameters ranged from -3.2 to 2.6%. In the radii instrumented with the titanium plates, severe image artifacts were observed and errors in bone parameters ranged between -30.2 and 67.0%. CONCLUSIONS: We recommend using CFR-PEEK plates in longitudinal in vivo studies that monitor the healing process of unstable distal radius fractures treated operatively by plating or bone graft ingrowth.
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Placas Óseas/clasificación , Fijación Interna de Fracturas/instrumentación , Fracturas Óseas/cirugía , Radio (Anatomía)/fisiopatología , Tomografía Computarizada por Rayos X/métodos , Benzofenonas , Densidad Ósea , Femenino , Curación de Fractura , Humanos , Cetonas , Masculino , Proyectos Piloto , Polietilenglicoles , Polímeros , Radio (Anatomía)/cirugía , TitanioRESUMEN
BACKGROUND: Blood-brain barrier (BBB) integrity is presumed to be impaired in hypertension, resulting from cerebral endothelial dysfunction. Hypertension precedes various cerebrovascular diseases, such as cerebral small vessel disease, and is a risk factor for developing neurodegenerative diseases for which BBB disruption is a preceding pathophysiological process. In this cross-sectional study, we investigated the relation between hypertension, current blood pressure, and BBB leakage in human subjects. METHODS: BBB leakage was determined in 22 patients with hypertension and 19 age- and sex-matched normotensive controls (median age [range], 65 [45-80] years; 19 men) using a sparsely time-sampled contrast-enhanced 7T magnetic resonance imaging protocol. Structural cerebral small vessel disease markers were visually rated. Multivariable regression analyses, adjusted for age, sex, cardiovascular risk factors, and cerebral small vessel disease markers, were performed to determine the relation between hypertension status, systolic and diastolic blood pressure, mean arterial pressure, drug treatment, and BBB leakage. RESULTS: Both hypertensive and normotensive participants showed mild scores of cerebral small vessel disease. BBB leakage did not differ between hypertensive and normotensive participants; however, it was significantly higher for systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the cortex, and diastolic blood pressure and mean arterial pressure in the gray matter. Effectively treated patients showed less BBB leakage than those with current hypertension. CONCLUSIONS: BBB integrity in the total and cortical gray matter decreases with increasing blood pressure but is not related to hypertension status. These findings show that BBB disruption already occurs with increasing blood pressure, before the presence of overt cerebral tissue damage. Additionally, our results suggest that effective antihypertensive medication has a protective effect on the BBB. REGISTRATION: URL: https://trialsearch.who.int/; Unique identifier: NL7537.
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In population-based cohort studies, magnetic resonance imaging (MRI) is vital for examining brain structure and function. Advanced MRI techniques, such as diffusion-weighted MRI (dMRI) and resting-state functional MRI (rs-fMRI), provide insights into brain connectivity. However, biases in MRI data acquisition and processing can impact brain connectivity measures and their associations with demographic and clinical variables. This study, conducted with 5110 participants from The Maastricht Study, explored the relationship between brain connectivity and various image quality metrics (e.g., signal-to-noise ratio, head motion, and atlas-template mismatches) that were obtained from dMRI and rs-fMRI scans. Results revealed that in particular increased head motion (R2 up to 0.169, p < 0.001) and reduced signal-to-noise ratio (R2 up to 0.013, p < 0.001) negatively impacted structural and functional brain connectivity, respectively. These image quality metrics significantly affected associations of overall brain connectivity with age (up to -59%), sex (up to -25%), and body mass index (BMI) (up to +14%). Associations with diabetes status, educational level, history of cardiovascular disease, and white matter hyperintensities were generally less affected. This emphasizes the potential confounding effects of image quality in large population-based neuroimaging studies on brain connectivity and underscores the importance of accounting for it.
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BACKGROUND: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity. METHODS AND RESULTS: Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (ß per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. CONCLUSIONS: These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.
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Sustancia Blanca , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Sustancia Blanca/patología , Estudios Transversales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética , BiomarcadoresRESUMEN
PURPOSE OF REVIEW: Published data raise concerns about the use of nonselective NSAIDs and selective cyclo-oxygenase (COX)-2 inhibitors as anti-inflammatory or analgesic drugs in patients after a recent fracture or who are undergoing (uncemented) arthroplasty or osteotomy. However, clinical reports on the effect of COX-2 inhibition on fracture healing in humans have been variable and inconclusive. This review gives an overview of the published data and an advice when to avoid NSAIDs. RECENT FINDINGS: Prostaglandins play an important role as mediators of inflammation and COX are required for their production. Inflammation is an essential step in the fracture healing process in which prostaglandin production by COX-2 is involved. Data from animal studies suggest that NSAIDs, which inhibit COX-2, can impair fracture healing due to the inhibition of the endochondral ossification pathway. Animal data suggest that the effects of COX-2 inhibitors are dependent on the timing, duration, and dose, and that these effects are reversible. SUMMARY: These animal data, together with the view of limited scientifically robust clinical evidence in humans, indicate that physicians consider only short-term administration of COX-2 inhibitors or other drugs in the pain management of patients who are in the phase of fracture or other bone defect healing. COX-2-inhibitors should be considered a potential risk factor for fracture healing, and therefore to be avoided in patients at risk for delayed fracture healing.
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Antiinflamatorios no Esteroideos/farmacología , Curación de Fractura/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Inhibidores de la Ciclooxigenasa 2/farmacología , Modelos Animales de Enfermedad , Fracturas Óseas/inducido químicamente , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Cognitive behavioral therapy (CBT) reduces anxiety symptoms in patients with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to identify changes in functional connectivity in the brain after CBT for anxiety in patients with PD. METHODS: Thirty-five patients with PD and clinically significant anxiety were randomized over two groups: CBT plus clinical monitoring (10 CBT sessions) or clinical monitoring only (CMO). Changes in severity of anxiety symptoms were assessed with the Parkinson Anxiety Scale (PAS). Resting-state functional brain MRI was performed at baseline and after the intervention. Functional networks were extracted by an Independent Component Analysis (ICA). Functional connectivity (FC) changes between structures involved in the PD-related anxiety circuits, such as the fear circuit (involving limbic, frontal, and cingulate structures) and the cortico-striato-thalamo-cortical limbic circuit, and both within and between functional networks were compared between groups and regressed with anxiety symptoms changes. RESULTS: Compared to CMO, CBT reduced the FC between the right thalamus and the bilateral orbitofrontal cortices and increased the striato-frontal FC. CBT also increased the fronto-parietal FC within the central executive network (CEN) and between the CEN and the salience network. After CBT, improvement of PAS-score was associated with an increased striato-cingulate and parieto-temporal FC, and a decreased FC within the default-mode network and between the dorsal attentional network and the language network. CONCLUSION: CBT in PD-patients improves anxiety symptoms and is associated with functional changes reversing the imbalance between PD-related anxiety circuits and reinforcing cognitive control on emotional processing.
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Terapia Cognitivo-Conductual , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Ansiedad/etiología , Ansiedad/terapia , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: Cerebral small vessel disease (cSVD) involves several pathologies affecting the small vessels, including blood-brain barrier (BBB) impairment. Dynamic susceptibility contrast (DSC) MRI is sensitive to both blood perfusion and BBB leakage, and correction methods may be crucial for obtaining reliable perfusion measures. These methods might also be applicable to detect BBB leakage itself. This study investigated to what extent DSC-MRI can measure subtle BBB leakage in a clinical feasibility setting. METHODS: In vivo DCE and DSC data were collected from fifteen cSVD patients (71 (±10) years, 6F/9M) and twelve elderly controls (71 (±10) years, 4F/8M). DSC-derived leakage fractions were obtained using the Boxerman-Schmainda-Weisskoff method (K2). K2 was compared with the DCE-derived leakage rate Ki, obtained from Patlak analysis. Subsequently, differences were assessed between white matter hyperintensities (WMH), cortical gray matter (CGM), and normal-appearing white matter (NAWM). Additionally, computer simulations were performed to assess the sensitivity of DSC-MRI to BBB leakage. RESULTS: K2 showed significant differences between tissue regions (P < 0.001 for CGM-NAWM and CGM-WMH, and P = 0.001 for NAWM-WMH). Conversely, according to the computer simulations the DSC sensitivity was insufficient to measure subtle BBB leakage, as the K2 values were below the derived limit of quantification (4â10-3 min-1). As expected, Ki was elevated in the WMH compared to CGM and NAWM (P < 0.001). CONCLUSIONS: Although clinical DSC-MRI seems capable to detect subtle BBB leakage differences between WMH and normal-appearing brain tissue it is not recommended. K2 as a direct measure for subtle BBB leakage remains ambiguous as its signal effects are due to mixed T1- and T2∗-weighting. Further research is warranted to better disentangle perfusion from leakage effects.
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Enfermedades de los Pequeños Vasos Cerebrales , Sustancia Blanca , Humanos , Anciano , Barrera Hematoencefálica/diagnóstico por imagen , Estudios de Factibilidad , Medios de Contraste/farmacología , Imagen por Resonancia Magnética/métodos , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagenRESUMEN
Introduction: There is an urgent need for biomarkers identifying individuals at risk of early-stage cognitive impairment. Using cross-sectional data from The Maastricht Study, this study included 197 individuals with mild cognitive impairment (MCI) and 200 cognitively unimpaired individuals aged 40 to 75, matched by age, sex, and educational level. Methods: We assessed the association of plasma sphingolipid and ceramide transfer protein (CERT) levels with MCI and adjusted for potentially confounding risk factors. Furthermore, the relationship of plasma sphingolipids and CERTs with magnetic resonance imaging brain volumes was assessed and age- and sex-stratified analyses were performed. Results: Associations of plasma ceramide species C18:0 and C24:1 and combined plasma ceramide chain lengths (ceramide risk score) with MCI were moderated by sex, but not by age, and higher levels were associated with MCI in men. No associations were found among women. In addition, higher levels of ceramide C20:0, C22:0, and C24:1, but not the ceramide risk score, were associated with larger volume of the hippocampus after controlling for covariates, independent of MCI. Although higher plasma ceramide C18:0 was related to higher plasma CERT levels, no association of CERT levels was found with MCI or brain volumes. Discussion: Our results warrant further analysis of plasma ceramides as potential markers for MCI in middle-aged men. In contrast to previous studies, no associations of plasma sphingolipids with MCI or brain volumes were found in women, independent of age. These results highlight the importance of accounting for sex- and age-related factors when examining sphingolipid and CERT metabolism related to cognitive function.
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VERHEGGEN, I.C.M., W. Freeze, J. de Jong, J. Jansen, A. Postma, M. van Boxtel, F. Verhey and W. Backes. The application of contrast-enhanced MRI in the assessment of blood-cerebrospinal fluid barrier integrity. Choroid plexus epithelial cells form a barrier that enables active, bidirectional exchange between the blood plasma and cerebrospinal fluid (CSF), known as the blood-CSF barrier (BCSFB). Through its involvement in CSF composition, the BCSFB maintains homeostasis in the central nervous system. While the relation between blood-brain barrier disruption, aging and neurodegeneration is extensively studied using contrast-enhanced MRI, applying this technique to investigate BCSFB disruption in age-related neurodegeneration has received little attention. This review provides an overview of the current status of contrast-enhanced MRI to assess BCSFB permeability. Post-contrast ventricular gadolinium enhancement has been used to indicate BCSFB permeability. Moreover, new techniques highly sensitive to low gadolinium concentrations in the CSF, for instance heavily T2-weighted imaging with cerebrospinal fluid suppression, seem promising. Also, attempts are made at using other contrast agents, such as manganese ions or very small superparamagnetic iron oxide particles, that seem to be cleared from the brain at the choroid plexus. Advancing and applying new developments such as these could progress the assessment of BCSFB integrity.
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Barrera Hematoencefálica , Medios de Contraste , Plexo Coroideo/diagnóstico por imagen , Gadolinio , Imagen por Resonancia MagnéticaRESUMEN
The vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF). We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be without significant pathology (subjective cognitive decline). The microstructural components were quantified with spectral analysis using a non-negative least squares method. Linear regression was employed to investigate associations of these components with hippocampal and white matter hyperintensity (WMH) volumes. In the normal appearing white matter, a large fint (a proxy of ISF volume) was associated with a large WMH volume and low hippocampal volume. Likewise, a large fint value was associated with a lower hippocampal volume in the hippocampi. Large ISF volume (fint) was shown to be a prominent factor associated with both WMHs and neurodegenerative abnormalities in memory clinic patients and is argued to play a potential role in impaired glymphatic functioning.
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Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Demencia Vascular/metabolismo , Demencia Vascular/patología , Líquido Extracelular/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Sustancia Blanca/metabolismo , Sustancia Blanca/patología , Anciano , Enfermedad de Alzheimer/etiología , Disfunción Cognitiva/etiología , Demencia Vascular/etiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Tamaño de los Órganos , Análisis Espectral/métodosRESUMEN
BACKGROUND: Circumventricular organs (CVOs) are small structures without a blood-brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood-brain barrier absence. METHODS: Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. RESULTS: In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. CONCLUSIONS: Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. TRIAL REGISTRATION: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.
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Órganos Circunventriculares/diagnóstico por imagen , Órganos Circunventriculares/metabolismo , Medios de Contraste/farmacocinética , Imagen por Resonancia Magnética/métodos , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/metabolismoRESUMEN
To investigate whether blood-brain barrier (BBB) disruption is a potential mechanism of usual age-related cognitive decline, we conducted dynamic contrast-enhanced (DCE) MRI to measure BBB leakage in a healthy sample, and investigated the association with longitudinal cognitive decline. In a sample of neurologically and cognitively healthy, older individuals, BBB leakage rate in the white and grey matter and hippocampus was measured using DCE MRI with pharmacokinetic modelling. Regression analysis was performed to investigate whether the leakage rate was associated with decline in cognitive performance (memory encoding, memory retrieval, executive functioning and processing speed) over 12 years. White and grey matter BBB leakages were significantly associated with decline in memory retrieval. No significant relations were found between hippocampal BBB leakage and cognitive performance. BBB disruption already being associated with usual cognitive ageing, supports that this neurovascular alteration is a possible explanation for the cognitive decline inherent to the ageing process. More insight into BBB leakage during the normal ageing process could improve estimation and interpretation of leakage rate in pathological conditions. The current results might also stimulate the search for strategies to maintain BBB integrity and help increase the proportion people experiencing successful ageing. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.
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Barrera Hematoencefálica , Sustancia Gris , Envejecimiento , Cognición , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Blood-brain barrier (BBB) breakdown can disrupt nutrient supply and waste removal, which affects neuronal functioning. Currently, dynamic contrast-enhanced (DCE) MRI is the preferred in-vivo method to quantify BBB leakage. Dedicated DCE MRI studies in normal aging individuals are lacking, which could hamper value estimation and interpretation of leakage rate in pathological conditions. Therefore, we applied DCE MRI to investigate the association between BBB disruption and age in a healthy sample. Fifty-seven cognitively and neurologically healthy, middle-aged to older participants (mean age: 66 years, range: 47-91 years) underwent MRI, including DCE MRI with intravenous injection of a gadolinium-based contrast agent. Pharmacokinetic modeling was applied to contrast concentration time-curves to estimate BBB leakage rate in each voxel. Subsequently, leakage rate was calculated in the white and gray matter, and primary (basic sensory and motor functions), secondary (association areas), and tertiary (higher-order cognition) brain regions. A difference in vulnerability to deterioration was expected between these regions, with especially tertiary regions being affected by age. Higher BBB leakage rate was significantly associated with older age in the white and gray matter, and also in tertiary, but not in primary or secondary brain regions. Even in healthy individuals, BBB disruption was stronger in older persons, which suggests BBB disruption is a normal physiologically aging phenomenon. Age-related increase in BBB disruption occurred especially in brain regions most vulnerable to age-related deterioration, which may indicate that BBB disruption is an underlying mechanism of normal age-related decline.Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.
Asunto(s)
Barrera Hematoencefálica , Medios de Contraste , Anciano , Anciano de 80 o más Años , Envejecimiento , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
BACKGROUND: During implantation of an uncemented femoral knee implant, press-fit interference fit provides the primary stability. It is assumed that during implantation a combination of elastic and plastic deformation and abrasion of the bone will occur, but little is known about what happens at the bone-implant interface and how much press-fit interference fit is eventually achieved. METHODS: Five cadaveric femora were prepared and implantation was performed by an experienced surgeon. Micro-CT- and conventional CT-scans were obtained pre- and post-implantation for geometrical measurements and to measure bone mineral density. Additionally, the position of the implant with respect to the bone was determined by optical scanning of the reconstructions. By measuring the differences in surface geometry, assessments were made of the cutting error, the actual interference fit, the amount of bone damage, and the effective interference fit. FINDINGS: Our analysis showed an average cutting error of 0.67mm (SD 0.17mm), which pointed mostly towards bone under-resections. We found an average actual AP interference fit of 1.48mm (SD 0.27mm), which was close to the nominal value of 1.5mm. INTERPRETATION: We observed combinations of bone damage and elastic deformation in all bone specimens, which showed a trend to be related with bone density. Higher bone density tended to lead to lower bone damage and higher elastic deformation. The results of the current study indicate different factors that interact while implanting an uncemented femoral knee component. This knowledge can be used to fine-tune design criteria of femoral components to achieve adequate primary stability for all patients.