UCSQ Method Applied on 3D Photogrammetry: Non-Invasive Objective Differentiation Between Synostotic and Positional Plagiocephaly.

OBJECTIVE: Objective differentiation between unilateral coronal synostosis (UCS) and positional posterior plagiocephaly (PPP) based on 3D photogrammetry according to Utrecht Cranial Shape Quantificator (UCSQ). DESIGN: Retrospective study. SETTING: Primary craniofacial center. PATIENTS, PARTICIPANTS: Thirty-two unoperated patients (17 UCS; 15 PPP) (age < 1 year). INTERVENTIONS: Extraction of variables from sinusoid curves derived using UCSQ: asymmetry ratio forehead and occiput peak, ratio of gradient forehead and occiput peak, location forehead and occiput peak. MAIN OUTCOME MEASURE(S): Variables, derived using 3D photogrammetry, were analyzed for differentiation between UCS and PPP. RESULTS: Frontal peak was shifted to the right side of the head in left-sided UCS (mean x-value 207 [192-220]), and right-sided PPP (mean x-value 210 [200-216]), and to the left in right-sided UCS (mean x-value 161 [156-166]), and left-sided PPP (mean x-value 150 [144-154]). Occipital peak was significantly shifted to the right side of the head in left-sided PPP (mean x-value 338 [336-340]) and to the left in right-sided PPP (mean x-value 23 [14-32]). Mean x-value of occipital peak was 9 (354-30) in left- and 2 (350-12) in right-sided UCS. Calculated ratio of gradient of the frontal peak is, in combination with the calculated asymmetry ratio of the frontal peak, a distinctive finding. CONCLUSIONS: UCSQ objectively captures shape of synostotic and positional plagiocephaly using 3D photogrammetry, we therefore developed a suitable method to objectively differentiate UCS from PPP using radiation-free methods.

Classification of Skull Shape Deformities Related to Craniosynostosis on 3D Photogrammetry.

Implementation of the Utrecht Cranial Shape Quantificator (UCSQ) classification method on 3D photogrammetry in patients with different types of craniosynostosis is the aim of the present study. Five children (age <1 year) of every group of the common craniosynostoses (scaphocephaly, brachycephaly, trigonocephaly, right-sided and left-sided anterior plagiocephaly) were randomly included. The program 3-Matic (v13.0) was used to import and analyze the included 3dMD photos. Three external landmarks were placed. Using the landmarks, a base plane was created, as well as a plane 4 cm superior to the base plane. Using UCSQ, we created sinusoid curves of the patients, the resulting curves were analyzed and values were extracted for calculations. Results per patient were run through a diagnostic flowchart in order to determine correctness of the flowchart when using 3D photogrammetry. Each of the patients (n=25) of the different craniosynostosis subgroups is diagnosed correctly based on the different steps in the flowchart. This study proposes and implements a diagnostic approach of craniosynostosis based on 3D photogrammetry. By using a diagnostic flowchart based on specific characteristics for every type of craniosynostosis related to specific skull deformities, diagnosis can be established. All variables are expressed in number and are therefore objective.

Diabetes and hypertension are related to amyloid-beta burden in the population-based Rotterdam Study.

Higher vascular disease burden increases the likelihood of developing dementia, including Alzheimer's disease. Better understanding the association between vascular risk factors and Alzheimer's disease pathology at the predementia stage is critical for developing effective strategies to delay cognitive decline. In this work, we estimated the impact of six vascular risk factors on the presence and severity of in vivo measured brain amyloid-beta (Aß) plaques in participants from the population-based Rotterdam Study. Vascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, physical inactivity and smoking) were assessed 13 (2004-2008) and 7 years (2009-2014) prior to 18F-florbetaben PET (2018-2021) in 635 dementia-free participants. Vascular risk factors were associated with binary amyloid PET status or continuous PET readouts (standard uptake value ratios, SUVrs) using logistic and linear regression models, respectively, adjusted for age, sex, education, APOE4 risk allele count and time between vascular risk and PET assessment. Participants' mean age at time of amyloid PET was 69 years (range: 60-90), 325 (51.2%) were women and 190 (29.9%) carried at least one APOE4 risk allele. The adjusted prevalence estimates of an amyloid-positive PET status markedly increased with age [12.8% (95% CI 11.6; 14) in 60-69 years versus 35% (36; 40.8) in 80-89 years age groups] and APOE4 allele count [9.7% (8.8; 10.6) in non-carriers versus 38.4% (36; 40.8) to 60.4% (54; 66.8) in carriers of one or two risk allele(s)]. Diabetes 7 years prior to PET assessment was associated with a higher risk of a positive amyloid status [odds ratio (95% CI) = 3.68 (1.76; 7.61), P < 0.001] and higher standard uptake value ratios, indicating more severe Aß pathology [standardized beta = 0.40 (0.17; 0.64), P = 0.001]. Hypertension was associated with higher SUVr values in APOE4 carriers (mean SUVr difference of 0.09), but not in non-carriers (mean SUVr difference 0.02; P = 0.005). In contrast, hypercholesterolaemia was related to lower SUVr values in APOE4 carriers (mean SUVr difference -0.06), but not in non-carriers (mean SUVr difference 0.02). Obesity, physical inactivity and smoking were not related to amyloid PET measures. The current findings suggest a contribution of diabetes, hypertension and hypercholesterolaemia to the pathophysiology of Alzheimer's disease in a general population of older non-demented adults. As these conditions respond well to lifestyle modification and drug treatment, further research should focus on the preventative effect of early risk management on the development of Alzheimer's disease neuropathology.

The Associations Between Intracranial Stenosis, Brain Amyloid-beta, and Cognition in a Memory Clinic Sample.

BACKGROUND: Intracranial stenosis (ICS) and brain amyloid-beta (Aß) have been associated with cognition and dementia. We aimed to investigate the association between ICS and brain Aß and their independent and joint associations with cognition. METHODS: We conducted a cross-sectional study of 185 patients recruited from a memory clinic. ICS was measured on 3-dimensional time-of-flight magnetic resonance angiography and defined as stenosis ≥50%. Brain Aß was measured with [ 11 C] Pittsburgh compound B-positron emission tomography imaging. Cognition was assessed with a locally validated neuropsychological battery. RESULTS: A total of 17 (9.2%) patients had ICS, and the mean standardized uptake value ratio was 1.4 (±0.4 SD). ICS was not significantly associated with brain Aß deposition. ICS was significantly associated with worse global cognition (ß: -1.26, 95% CI: -2.25; -0.28, P =0.013), executive function (ß: -1.04, 95% CI: -1.86; -0.22, P =0.015) and visuospatial function (ß: -1.29, 95% CI: -2.30; -0.27, P =0.015). Moreover, in ICS patients without dementia (n=8), the presence of Aß was associated with worse performance on visuomotor speed. CONCLUSIONS: ICS was significantly associated with worse cognition and showed interaction with brain Aß such that patients with both pathologies performed worse on visuomotor speed specifically in those without dementia. Further studies may clarify if ICS and brain Aß deposition indeed have a synergistic association with cognition.

A Diffusion Tensor Imaging Analysis of Frontal Lobe White Matter Microstructure in Trigonocephaly Patients.

BACKGROUND: Children with trigonocephaly are at risk for neurodevelopmental disorders. The aim of this study is to investigate white matter properties of the frontal lobes in young, unoperated patients with metopic synostosis as compared to healthy controls using diffusion tension imaging (DTI). METHODS: Preoperative DTI data sets of 46 patients with trigonocephaly with a median age of 0.49 (interquartile range: 0.38) years were compared with 21 controls with a median age of 1.44 (0.98) years. White matter metrics of the tracts in the frontal lobe were calculated using FMRIB Software Library (FSL). The mean value of tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were estimated for each subject and compared to healthy controls. By linear regression, FA and MD values per tract were assessed by trigonocephaly, sex, and age. RESULTS: The mean FA and MD values in the frontal lobe tracts of untreated trigonocephaly patients, younger than 3 years, were not significantly different in comparison to controls, where age showed to be a significant associated factor. CONCLUSIONS: Microstructural parameters of white matter tracts of the frontal lobe of patients with trigonocephaly are comparable to those of controls aged 0-3 years.

Cerebral cortex maldevelopment in syndromic craniosynostosis.

AIM: To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis. METHOD: Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo-24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls). MRIs were processed via FreeSurfer pipeline to determine total ICV and cortical surface area (CSA). Scaling coefficients were calculated from log-transformed data via mixed regression to account for multiple measurements, sex, syndrome, and age. Educational outcomes were reported by syndrome. RESULTS: Mean ICV was greater in patients with FGFR (1519cm3 , SD 269cm3 , p=0.016) than in patients with TWIST1 (1304cm3 , SD 145cm3 ) or controls (1405cm3 , SD 158cm3 ). CSA was related to ICV by a scaling law with an exponent of 0.68 (95% confidence interval [CI] 0.61-0.76) in patients with FGFR compared to 0.81 (95% CI 0.50-1.12) in patients with TWIST1 and 0.77 (95% CI 0.61-0.93) in controls. Lobar analysis revealed reduced scaling in the parietal (0.50, 95% CI 0.42-0.59) and occipital (0.67, 95% CI 0.54-0.80) lobes of patients with FGFR compared with controls. Modified learning environments were needed more often in patients with FGFR. INTERPRETATION: Despite adequate ICV in FGFR-mediated craniosynostosis, CSA development is reduced, indicating maldevelopment, particularly in parietal and occipital lobes. Modified education is also more common in patients with FGFR.

New diagnostic approach of the different types of isolated craniosynostosis.

In this study, we diagnose skull shape deformities by analysing sinusoid curves obtained from standardized computed tomography (CT) slices of the skull for the common craniosynostoses (scaphocephaly, brachycephaly, trigonocephaly, right- and left-sided anterior plagiocephaly). Scaphocephaly has a high forehead peak and low troughs, in contrast to brachycephaly. Anterior plagiocephaly has asymmetry and shifting of the forehead peak. Trigonocephaly has a high and narrow frontal peak. Control patients have a symmetrical skull shape with low troughs and a high and broader frontal peak. Firstly, we included 5 children of every group of the common craniosynostoses and additionally 5 controls for extraction and calculation of characteristics. A diagnostic flowchart was developed. Secondly, we included a total of 51 craniosynostosis patients to validate the flowchart. All patients were correctly classified using the flowchart.Conclusion: Our study proposes and implements a new diagnostic approach of craniosynostosis. We describe a diagnostic flowchart based on specific characteristics for every type of craniosynostosis related to the specific skull deformities and control patients. All variables are expressed in number; therefore, we are able to use these variables in future research to quantify the different types of craniosynostosis. What is Known: • Premature fusion of one or more cranial sutures results in a specific cranial shape. • Clinical diagnosis is relatively simple; however, objective diagnosis based on distinctive values is difficult. What is New: • Using external landmarks and curve analysis, distinctive variables, and values for every type of craniosynostosis related to the specific skull deformities were determined and used to create a diagnostic flowchart for diagnosis. • Validation with an independent data set of 51 patients showed that all patients were correctly classified.

Quantification of Severity of Unilateral Coronal Synostosis.

OBJECTIVES: Severity of unilateral coronal synostosis (UCS) can vary. Quantification is important for treatment, expectations of treatment and natural outcome, and education of the patient and parents. DESIGN: Retrospective study. SETTING: Primary craniofacial center. PATIENTS, PARTICIPANTS: Twenty-three preoperative patients with unilateral coronal craniosynostosis (age < 2 years). INTERVENTION: Utrecht Cranial Shape Quantifier (UCSQ) was used to quantify severity using the variables: asymmetry ratio of frontal peak and ratio of frontal peak gradient. MAIN OUTCOME MEASURES(S): The UCSQ variables were combined and related to visual score using Pearson correlation coefficient; UCSQ and visual score were additionally compared to Di Rocco classification by one-way analysis of variance or Kruskal-Wallis test. All measurements were made on computed tomography scans. RESULTS: Good correlation between UCSQ and visual score was found (r = 0.67). No statistically significant differences were found between group means of UCSQ in the 3 categories of Di Rocco classification (F2,20 = 0.047; P > .05). Kruskal-Wallis test showed no significant differences between group means of visual score in the 3 categories of Di Rocco classification (Kruskal-Wallis H (2) = 0.871; P > .05). CONCLUSIONS: Using UCSQ, we can quantify UCS according to severity using characteristics, it outperforms traditional methods and captures the whole skull shape. In future research, we can apply UCSQ to 3D-photogrammetry due to the utilization of external landmarks.

Cortical Thickness in Crouzon-Pfeiffer Syndrome: Findings in Relation to Primary Cranial Vault Expansion.

BACKGROUND: Episodes of intracranial hypertension are associated with reductions in cerebral cortical thickness (CT) in syndromic craniosynostosis. Here we focus on Crouzon-Pfeiffer syndrome patients to measure CT and evaluate associations with type of primary cranial vault expansion and synostosis pattern. METHODS: Records from 34 Crouzon-Pfeiffer patients were reviewed along with MRI data on CT and intracranial volume to examine associations. Patients were grouped according to initial cranial vault expansion (frontal/occipital). Data were analyzed by multiple linear regression controlled for age and brain volume to determine an association between global/lobar CT and vault expansion type. Synostosis pattern effect sizes on global/lobar CT were calculated as secondary outcomes. RESULTS: Occipital expansion patients demonstrated 0.02 mm thicker cortex globally (P = 0.81) with regional findings, including: thicker cortex in frontal (0.02 mm, P = 0.77), parietal (0.06 mm, P = 0.44) and occipital (0.04 mm, P = 0.54) regions; and thinner cortex in temporal (-0.03 mm, P = 0.69), cingulate (-0.04 mm, P = 0.785), and, insula (-0.09 mm, P = 0.51) regions. Greatest effect sizes were observed between left lambdoid synostosis and the right cingulate (d = -1.00) and right lambdoid synostosis and the left cingulate (d = -1.23). Left and right coronal synostosis yielded effect sizes of d = -0.56 and d = -0.42 on respective frontal lobes. CONCLUSIONS: Both frontal and occipital primary cranial vault expansions correlate to similar regional CT in Crouzon-Pfeiffer patients. Lambdoid synostosis appears to be associated with cortical thinning, particularly in the cingulate gyri.

Introducing a new method for classifying skull shape abnormalities related to craniosynostosis.

We present a novel technique for classification of skull deformities due to most common craniosynostosis. We included 5 children of every group of the common craniosynostoses (scaphocephaly, brachycephaly, trigonocephaly, and right- and left-sided anterior plagiocephaly) and additionally 5 controls. Our outline-based classification method is described, using the software programs OsiriX, MeVisLab, and Matlab. These programs were used to identify chosen landmarks (porion and exocanthion), create a base plane and a plane at 4 cm, segment outlines, and plot resulting graphs. We measured repeatability and reproducibility, and mean curves of groups were analyzed. All raters achieved excellent intraclass correlation scores (0.994-1.000) and interclass correlation scores (0.989-1.000) for identifying the external landmarks. Controls, scaphocephaly, trigonocephaly, and brachycephaly all have the peak of the forehead in the middle of the curve (180°). In contrary, in anterior plagiocephaly, the peak is shifted (to the left of graph in right-sided and vice versa). Additionally, controls, scaphocephaly, and trigonocephaly have a high peak of the forehead; scaphocephaly has the lowest troughs; in brachycephaly, the width/frontal peak ratio has the highest value with a low frontal peak.Conclusion: We introduced a preliminary study showing an objective and reproducible methodology using CT scans for the analysis of craniosynostosis and potential application of our method to 3D photogrammetry. What is Known: • Diagnosis of craniosynostosis is relatively simple; however, classification of craniosynostosis is difficult and current techniques are not widely applicable. What is New: • We introduce a novel technique for classification of skull deformities due to craniosynostosis, an objective and reproducible methodology using CT scans resulting in characteristic curves. The method is applicable to all 3D-surface rendering techniques. • Using external landmarks and curve analysis, specific and characteristic curves for every type of craniosynostosis related to the specific skull deformities are found.

Intracranial hypertension and cortical thickness in syndromic craniosynostosis.

AIM: To evaluate the impact of risk factors for intracranial hypertension (ICH) on cerebral cortex thickness in syndromic craniosynostosis. METHOD: ICH risk factors including papilloedema, hydrocephalus, obstructive sleep apnea (OSA), cerebellar tonsillar position, occipitofrontal circumference (OFC) curve deflection, age, and sex were collected from the records of patients with syndromic craniosynostosis (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen syndromes) and imaging. Magnetic resonance images were analysed and exported for statistical analysis. A linear mixed model was developed to determine correlations with cerebral cortex thickness changes. RESULTS: In total, 171 scans from 107 patients (83 males, 88 females [including repeated scans], mean age 8y 10mo, range 1y 1mo-34y, SD 5y 9mo) were evaluated. Mean cortical thickness in this cohort was 2.78mm (SD 0.17). Previous findings of papilloedema (p=0.036) and of hydrocephalus (p=0.007) were independently associated with cortical thinning. Cortical thickness did not vary significantly by sex (p=0.534), syndrome (p=0.896), OSA (p=0.464), OFC (p=0.375), or tonsillar position (p=0.682). INTERPRETATION: Detection of papilloedema or hydrocephalus in syndromic craniosynostosis is associated with significant changes in cortical thickness, supporting the need for preventative rather than reactive treatment strategies. WHAT THIS PAPER ADDS: Papilloedema is associated with thinning of the cerebral cortex in syndromic craniosynostosis, independently of hydrocephalus.

Hipertensión intracraneal y grosor cortical en craneosinostosis sindrómica OBJETIVO: Evaluar el impacto de los factores de riesgo de hipertensión intracraneal (HIC) en el grosor de la corteza cerebral en la craneosinostosis sindrómica. MÉTODO: La neuroimagen, y, los factores de riesgo para HIC que incluyeron papiledema, hidrocefalia, apnea obstructiva del sueño (SAOS), posición de la tonsila cerebelosa, edad de desviación de la curva de circunferencia occipitofrontal (CFO) y el sexo, se recogieron de los registros de pacientes con craneosinostosis sindrómica (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzensis). Las imágenes de resonancia magnética fueron analizadas y exportadas para análisis estadístico. Se desarrolló un modelo mixto lineal para determinar las correlaciones con los cambios en el espesor de la corteza cerebral. RESULTADOS: En total se evaluaron 171 exploraciones de 107 pacientes (83 varones, 88 mujeres [incluyendo escaneos repetidos], edad media 8 años 10 meses, rango 1 año 1 mes - 34 años, DE 5 años 9 meses). El espesor medio cortical en esta cohorte fue de 2,78 mm (DS 0,17). Los hallazgos anteriores de papiledema (p=0,036) y de hidrocefalia (p=0,007) se asociaron de forma independiente con el adelgazamiento cortical. El grosor cortical no varió significativamente por sexo (p=0,534), síndrome (p=0,896), SAOS (p=0,464), CFO (p=0,375), o posición tonsilar (p=0,682). INTERPRETACIÓN: La detección de papiledema o hidrocefalia en la craneosinostosis sindrómica, se asocia con cambios significativos en el grosor cortical. Esto apoya la necesidad de estrategias de tratamiento preventivo en lugar de tratamientos reactivos.

Hipertensão intracrianiana e espessura cortical na craniossinostose sindrômica OBJETIVO: Avaliar o impacto de fatores de risco para hipertensão intracraniana (HIC) na espessura cortical em craniossinostose sindrômica. MÉTODO: Fatores de risco para HIC incluindo papiloedema, hidrocefalia, apnéia obstrutiva do sono (AOS), posição das tonsilas do cerebelo, idade de deflexão da curva da circunferência occipitofrontal (COF), e sexo foram coletados dos registros de pacientes com craniossinostose sindrômica (síndromes de Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen) e imagens. As imagens de ressonância magnética foram analisadas e exportadas para análise estatística. Um modelo linear misto foi desenvolvido para determinar correlações com mudanças na espessura do córtex cerebral. RESULTADOS: No total, 171 imagens de 107 pacientes (83 do sexo masculino, 88 do sexo feminino [incluindo varreduras repetidas], média de idade 8a 10m, variação 1a 1m-34a, DP 5a 9m) foram avaliados. A espessura cortical média nesta coorte foi 2,78mm (DP 0,17). Achados prévios de papiloedema (p=0,036) e de hidrocefalia (p=0,007) foram independentemente associados com a redução cortical. A espessura cortical não variou significativamente com o sexo (p=0,534), síndrome (p=0,896), AOS (p=0,464), COF (p=0,375), ou posição tonsilar (p=0,682). INTERPRETAÇÃO: A detecção do papiloedema ou hidrocefalia na craniossinostose sindrômica se associa com mudanças significativas na espessura cortical, sustentando a necessidade de estratégias de tratamento preventivas e não reativas.

Patterns of functional connectivity in an aging population: The Rotterdam Study.

Structural brain markers are studied extensively in the field of neurodegeneration, but are thought to occur rather late in the process. Functional measures such as functional connectivity are gaining interest as potentially more subtle markers of neurodegeneration. However, brain structure and function are also affected by 'normal' brain ageing. More information is needed on how functional connectivity relates to aging, particularly in the absence of overt neurodegenerative disease. We investigated the association of age with resting-state functional connectivity in 2878 non-demented persons between 50 and 95 years of age (54.1% women) from the population-based Rotterdam Study. We obtained nine well-known resting state networks using data-driven methodology. Within the anterior default mode network, ventral attention network, and sensorimotor network, functional connectivity was significantly lower with older age. In contrast, functional connectivity was higher with older age within the visual network. Between resting state networks, we found patterns of both increases and decreases in connectivity in approximate equal proportions. Our results reinforce the notion that the aging brain undergoes a reorganization process, and serves as a solid basis for exploring functional connectivity as a preclinical marker of neurodegenerative disease.

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

OBJECTIVES: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). METHOD: MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. RESULTS: We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. CONCLUSIONS: Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. KEY POINTS: • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

Small cortical infarcts: prevalence, determinants, and cognitive correlates in the general population.

BACKGROUND: Cortical brain infarcts are defined as infarcts involving cortical gray matter, but may differ considerably in size. It is unknown whether small cortical infarcts have a similar clinical phenotype as larger counterparts. We investigated prevalence, determinants, and cognitive correlates of small cortical infarcts in the general population and compared these with large cortical infarcts and lacunar infarcts. METHODS: Four thousand nine hundred five nondemented individuals (age 63·95 ± 10·99) from a population-based study were included. Infarcts were rated on magnetic resonance imaging and participants were classified according to mean infarct diameter into small (≤15 mm in largest diameter) or large (>15 mm) cortical infarcts, lacunar infarcts, or a combination of subtypes. Spatial distribution maps were created for manually labeled small and large infarcts. Participants underwent cognitive testing. Analyses were performed using multinomial regression and analysis of covariance. RESULTS: Three hundred eighty-one (7·8%) persons had any infarct on magnetic resonance imaging, among whom 54 with small (1·1%) and 77 (1·6%) with large cortical infarcts. Small cortical infarcts were mainly localized in external watershed areas, whereas large cortical infarcts were localized primarily in large arterial territories. Age (odds ratio = 1·06; 95% confidence interval = 1·02, 1·09), male gender (1·98; 1·01, 3·92), and smoking (2·55; 1·06, 6·14) were determinants of small cortical infarcts. Participants with these infarcts had worse scores in delayed memory, processing speed, and attention tests than persons without infarcts, even after adjustment for cardiovascular risk factors. CONCLUSIONS: In the elderly, small cortical infarcts appear as frequent as large infarcts but in different localization. Our results suggest that small cortical infarcts share cardiovascular risk factors and cognitive correlates with large cortical, but also with lacunar infarcts.

IT Infrastructure to support the secondary use of routinely acquired clinical imaging data for research.

We propose an infrastructure for the automated anonymization, extraction and processing of image data stored in clinical data repositories to make routinely acquired imaging data available for research purposes. The automated system, which was tested in the context of analyzing routinely acquired MR brain imaging data, consists of four modules: subject selection using PACS query, anonymization of privacy sensitive information and removal of facial features, quality assurance on DICOM header and image information, and quantitative imaging biomarker extraction. In total, 1,616 examinations were selected based on the following MRI scanning protocols: dementia protocol (246), multiple sclerosis protocol (446) and open question protocol (924). We evaluated the effectiveness of the infrastructure in accessing and successfully extracting biomarkers from routinely acquired clinical imaging data. To examine the validity, we compared brain volumes between patient groups with positive and negative diagnosis, according to the patient reports. Overall, success rates of image data retrieval and automatic processing were 82.5 %, 82.3 % and 66.2 % for the three protocol groups respectively, indicating that a large percentage of routinely acquired clinical imaging data can be used for brain volumetry research, despite image heterogeneity. In line with the literature, brain volumes were found to be significantly smaller (p-value <0.001) in patients with a positive diagnosis of dementia (915 ml) compared to patients with a negative diagnosis (939 ml). This study demonstrates that quantitative image biomarkers such as intracranial and brain volume can be extracted from routinely acquired clinical imaging data. This enables secondary use of clinical images for research into quantitative biomarkers at a hitherto unprecedented scale.

MRBrainS Challenge: Online Evaluation Framework for Brain Image Segmentation in 3T MRI Scans.

Many methods have been proposed for tissue segmentation in brain MRI scans. The multitude of methods proposed complicates the choice of one method above others. We have therefore established the MRBrainS online evaluation framework for evaluating (semi)automatic algorithms that segment gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) on 3T brain MRI scans of elderly subjects (65-80 y). Participants apply their algorithms to the provided data, after which their results are evaluated and ranked. Full manual segmentations of GM, WM, and CSF are available for all scans and used as the reference standard. Five datasets are provided for training and fifteen for testing. The evaluated methods are ranked based on their overall performance to segment GM, WM, and CSF and evaluated using three evaluation metrics (Dice, H95, and AVD) and the results are published on the MRBrainS13 website. We present the results of eleven segmentation algorithms that participated in the MRBrainS13 challenge workshop at MICCAI, where the framework was launched, and three commonly used freeware packages: FreeSurfer, FSL, and SPM. The MRBrainS evaluation framework provides an objective and direct comparison of all evaluated algorithms and can aid in selecting the best performing method for the segmentation goal at hand.

Intracranial stenosis, cerebrovascular diseases, and cognitive impairment in chinese.

Extracranial carotid artery disease has been shown to be related to cognitive deficits. However, limited data are available on intracranial stenosis (ICS) and cognitive impairment. We investigate the association between ICS and cognitive impairment in Chinese. Subjects (n=278), recruited from the Epidemiology of Dementia in Singapore Study, underwent comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI), including 3-dimensional-time-of-flight magnetic resonance angiography (MRA). Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment no dementia and dementia were diagnosed according to internationally accepted diagnostic criteria. Linear and logistic regression models were adjusted for age, sex, education, vascular risk factors, and other MRI markers. A total of 29 (10.4%) persons had ICS on MRA, which was significantly associated with both composite cognitive Z-scores [mean difference in Z-score, presence vs. absence of ICS: -0.37 (95% confidence interval: -0.63, -0.12)] and specific domains including executive function, language, visuomotor speed, verbal memory, and visual memory. ICS was also related to significant cognitive impairment (odds ratio: 5.10 [1.24 to 21.02]). With respect to other MRI markers, adjusted for the presence of lacunar infarcts, the associations of ICS with both composite and domain-specific Z-scores, and significant cognitive impairment became nonsignificant; however, adjustment for other MRI markers did not alter these associations. In this Chinese population, presence of ICS was associated with cognitive impairment independent of vascular risk factors. These associations may be mediated through the presence of infarcts.

TMEM106B influences volume of left-sided temporal lobe and interhemispheric structures in the general population.

BACKGROUND: Frontotemporal lobar degeneration is a neurodegenerative disease characterized by brain atrophy of the frontal and anterior temporal lobes. The associated frontotemporal dementia syndromes are clinically heterogeneous, and the pattern of affected cortical regions varies among subtypes. The TMEM106B rs1990622 polymorphism is associated with frontotemporal lobar degeneration, but little is known about how it affects the brain. METHODS: We investigated the rs1990622 polymorphism in relation to regional brain volumes to identify potential structures through which TMEM106B confers risk for frontotemporal lobar degeneration. In 4413 nondemented and stroke-free participants from the population-based Rotterdam Study, 150 cortical brain structures and 6 commissural regions were segmented from magnetic resonance imaging. RESULTS: A distinct pattern of association was found between rs1990622 and gray matter volume of left-sided temporal brain regions important for language processing, including the superior temporal gyrus (ß=-88.8 µL per risk allele, p=7.64×10(-5)), which contains Wernicke's area. The risk allele was also associated with a smaller anterior commissure cross-sectional area (ß=-.167 mm2 per risk allele, p=4.90×10(-5)) and posterior part of the corpus callosum (ß=-15.3 µL per risk allele, p=1.23×10(-5)), both of which contain temporal lobe commissural tracts. CONCLUSIONS: The asymmetric, predominantly left-sided involvement suggests an effect of TMEM106B on functions lateralized to the dominant hemisphere, such as language. These results show that, in nondemented persons, TMEM106B influences the volume of temporal brain regions that are important for language processing.

Apolipoprotein E genotype influences spatial distribution of cerebral microbleeds.

In cerebral amyloid angiopathy patients, microbleeds often cluster, mostly occipital, and are associated with apolipoprotein E (APOE) genotype. Microbleeds also frequently occur in the asymptomatic, general population. In this population, we investigated spatial distribution of microbleeds and whether this is influenced by APOE genotype. In 292 persons with microbleeds, we labeled microbleeds on baseline and follow-up magnetic resonance images. We calculated distance between incident and prevalent microbleeds within and between persons and performed lobar segmentation on the magnetic resonance images. Subsequently, we investigated proximity and lobar distribution in strata of APOE genotype. Microbleeds occurred closer within persons than between persons (-42.2 mm, 95% confidence interval, -44.6 to -39.9; p < 0.001). Microbleeds within APOE ε2 and ε4 carriers occurred closer than those in persons with ε3ε3 genotype (-11.9 mm, 95% confidence interval, -24.4 to 0.6; p = 0.06). Persons with ε2 and ε4 alleles had a larger proportion of microbleeds in the occipital lobe than persons with ε3ε3 genotype. Similar to cerebral amyloid angiopathy patients, microbleeds in the general population cluster and the distribution is affected by APOE genotype.

Cerebral microbleeds and cognition: the epidemiology of dementia in Singapore study.

Cerebral microbleeds (CMBs) are considered to be a novel marker of cerebral small vessel disease. However, the link with cognitive impairment remains unclear. We investigated whether CMBs-independent of other traditional markers of cerebral small vessel disease-are related to cognition. Chinese subjects from the population-based Singapore Chinese Eye Study, who failed an initial cognitive screening and were recruited into the ongoing Epidemiology of Dementia in Singapore Study, underwent neuropsychological testing and 3 T brain magnetic resonance imaging. The presence and number of CMBs were graded using Brain Observer Microbleed Scale on susceptibility-weighted images. Other magnetic resonance imaging lesions that were graded included presence of lacunes, white matter lesion, and total brain volumes. A comprehensive neuropsychological battery was administered and cognitive function was summarized as composite and domain-specific Z-scores. Among 282 subjects, 91 had any CMBs (32.3%), of whom 36 (12.8%) had multiple CMBs. CMBs were-independent of cardiovascular risk factors and other markers of cerebral small vessel disease-significantly associated with poorer cognitive function as reflected by composite Z-score (mean difference per CMB increase: -0.06; 95% confidence interval: -0.11, -0.01] and with domain-specific Z-scores including executive function, attention, and visuoconstruction. Among Chinese subjects CMBs were, independent of other concomitant markers of cerebral small vessel disease, associated with poorer cognitive function.