Combining advanced MRI and EEG techniques better explains long-term motor outcome after very preterm birth.

BACKGROUND: Preterm born children are at high risk for adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and advanced magnetic resonance imaging (MRI) and electroencephalography (EEG) measures. METHODS: In a prospective cohort study of 64 very preterm born children, the motor outcome was assessed at 9.83 (SD 0.70) years. Volumetric MRI, diffusion tensor imaging (DTI), and EEG were acquired at 10.85 (SD 0.49) years. We investigated associations between motor outcome and brain volumes (white matter, deep gray matter, cerebellum, and ventricles), white matter integrity (fractional anisotropy and mean, axial and radial diffusivity), and brain activity (upper alpha (A2) functional connectivity and relative A2 power). The independence of associations with motor outcome was investigated with a final model. For each technique, the measure with the strongest association was selected to avoid multicollinearity. RESULTS: Ventricular volume, radial diffusivity, mean diffusivity, relative A2 power, and A2 functional connectivity were significantly correlated to motor outcome. The final model showed that ventricular volume and relative A2 power were independently associated with motor outcome (B = -9.42 × 10-5, p = 0.027 and B = 28.9, p = 0.007, respectively). CONCLUSIONS: This study suggests that a lasting interplay exists between brain structure and function that might underlie motor outcome at school age. IMPACT: This is the first study that investigates the relationships between motor outcome and brain volumes, DTI, and brain function in preterm born children at school age. Ventricular volume and relative upper alpha power on EEG have an independent relation with motor outcome in preterm born children at school age. This suggests that there is a lasting interplay between structure and function that underlies adverse motor outcome.

Longitudinal Follow-Up of Children Born Preterm: Neurodevelopment From 2 to 10 Years of Age.

Objective: To investigate the rate and stability of impairments in children born preterm by assessing (1) early and school-age outcome in four developmental domains and (2) individual changes in outcome at both timepoints. Design: Prospective, longitudinal cohort study in children born in 2006-2007, <32 weeks' gestation. Follow-up at 2 and 10 years of age included standardized neurological, motor, cognitive and behavioral assessments. Children were categorized as having no, mild or moderate-severe impairment in these four domains. A composite impairment score was composed and the number of domains with impairments counted. For each child, individual outcomes at both timepoints were compared. Results: Follow-up at both time-points was available in 71/113(63%) children. At group level, there were no significant changes in the severity of impairments per domain. However, at individual level, there were less children with a mild abnormal composite score at 10 years of age (44 vs. 20%; p = 0.006), and more with a moderate-severe abnormal composite score (12 vs. 35%; p = 0.001). Especially children with normal/mild outcome at 2 years were likely to shift to other outcome categories over time. Conclusions: Children with early severe impairment are likely experiencing impairments later on, but early normal/mild abnormal outcomes should be interpreted with care, considering the large individual shifts over time. Long-term follow-up in all children born very preterm should therefore be continued to at least school-age.

Associations between Neonatal Magnetic Resonance Imaging and Short- and Long-Term Neurodevelopmental Outcomes in a Longitudinal Cohort of Very Preterm Children.

OBJECTIVE: To assess associations between neonatal brain injury assessed by magnetic resonance imaging and cognitive, motor, and behavioral outcomes at 2 and 10 years of age, in a longitudinal cohort of children born very preterm. STUDY DESIGN: There were 112 children born at <32 weeks of gestation who participated in a longitudinal prospective study on brain injury and neurodevelopmental outcome. Using the Kidokoro score, neonatal brain injury and altered brain growth in white matter, cortical and deep gray matter, and the cerebellum were assessed. Cognitive, motor, and behavioral outcomes were assessed during follow-up visits at both 2 (corrected) and 10 years of age. RESULTS: After adjusting for perinatal factors and level of maternal education, the global brain abnormality score was associated with cognition (B = -1.306; P = .005), motor skills (B = -3.176; P < .001), and behavior (B = 0.666; P = .005) at 2 years of age, but was not associated with cognition at 10 years of age. In the subgroup of children with a moderate-severe global brain abnormality score, magnetic resonance imaging was independently associated with cognitive impairment at 10 years of age. For children with milder forms of brain injury, only birth weight and level of maternal education were associated with cognitive outcomes. CONCLUSIONS: Neonatal brain injury, assessed by a standardized scoring system, was associated with short-term neurodevelopmental outcomes, but only with motor skills and behavior in childhood. Environmental factors, such as level of maternal education, become more important for cognitive development as children grow older, especially for children with relatively mild neonatal brain injury.

Brain activity and connectivity changes in response to nutritive natural sugars, non-nutritive natural sugar replacements and artificial sweeteners.

INTRODUCTION: The brain plays an important regulatory role in directing energy homeostasis and eating behavior. The increased ingestion of sugars and sweeteners over the last decades makes investigating the effects of these substances on the regulatory function of the brain of particular interest. We investigated whole brain functional response to the ingestion of nutrient shakes sweetened with either the nutritive natural sugars glucose and fructose, the low- nutritive natural sugar replacement allulose or the non-nutritive artificial sweetener sucralose. METHODS: Twenty healthy, normal weight, adult males underwent functional MRI on four separate visits. In a double-blind randomized study setup, participants received shakes sweetened with glucose, fructose, allulose or sucralose. Resting state functional MRI was performed before and after ingestion. Changes in Blood Oxygen Level Dependent (BOLD) signal, functional network connectivity and voxel based connectivity by Eigenvector Centrality Mapping (ECM) were measured. RESULTS: Glucose and fructose led to significant decreased BOLD signal in the cingulate cortex, insula and the basal ganglia. Glucose led to a significant increase in eigen vector centrality throughout the brain and a significant decrease in eigen vector centrality in the midbrain. Sucralose and allulose had no effect on BOLD signal or network connectivity but sucralose did lead to a significant increase in eigen vector centrality values in the cingulate cortex, central gyri and temporal lobe. DISCUSSION: Taken together our findings show that even in a shake containing fat and protein, the type of sweetener can affect brain responses and might thus affect reward and satiety responses and feeding behavior. The sweet taste without the corresponding energy content of the non-nutritive sweeteners appeared to have only small effects on the brain. Indicating that the while ingestion of nutritive sugars could have a strong effect on feeding behavior, both in a satiety aspect as well as rewarding aspects, non-nutritive sweeteners appear to not have these effects. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov under number NCT02745730.

The degree of prematurity affects functional brain activity in preterm born children at school-age: An EEG study.

Prematurely born children are at higher risk for long-term adverse motor and cognitive outcomes. The aim of this paper was to compare quantitative measures derived from electroencephalography (EEG) between extremely (EP) and very prematurely (VP) born children at 9-10 years of age. Fifty-five children born <32 weeks' of gestation underwent EEG at 9-10 years of age and were assessed for motor development and cognitive outcome. Relative frequency power and functional connectivity, as measured by the Phase Lag Index (PLI), were calculated for all frequency bands. Per subject, power spectrum and functional connectivity results were averaged over all channels and pairwise PLI values to explore differences in global frequency power and functional connectivity between EP and VP children. Brain networks were constructed for the upper alpha frequency band using the Minimum Spanning Tree method and were compared between EP and VP children. In addition, the relationships between upper alpha quantitative EEG results and cognitive and motor outcomes were investigated. Relative power and functional connectivity were significantly higher in VP than EP children in the upper alpha frequency band, and VP children had more integrated networks. A strong positive correlation was found between relative upper alpha power and motor outcome whilst controlling for gestational age, age during EEG recording, and gender (ρ = 0.493, p = 0.004). These results suggest that 9-10 years after birth, the effects of the degree of prematurity can be observed in terms of alterations in functional brain activity and that motor deficits are associated with decreases in relative upper alpha power.

Subjective Cognitive Decline Is Associated with Greater White Matter Hyperintensity Volume.

BACKGROUND: Research in older adults with subjective cognitive decline (SCD) has mainly focused on Alzheimer's disease (AD)-related MRI markers, such as hippocampal volume. However, small vessel disease (SVD) is currently established as serious comorbidity in dementia and its preliminary stages. It is therefore important to examine SVD markers in addition to AD markers in older adults presenting with SCD. OBJECTIVE: The aim of our study was to elucidate the role of SVD markers in late middle-aged to older adults with and without SCD in addition to the commonly found role of AD markers (hippocampal volume). METHODS: 67 healthy late middle-aged to older adults participated in this study (mean age 68 years); 25 participants with SCD and 42 participants without SCD. We evaluated quantitative as well as qualitative AD markers (i.e., hippocampal volume and medial temporal lobe atrophy (MTA) scale) and SVD markers (i.e., white matter hyperintensities (WMH) volume, Fazekas scale, microbleeds, and lacunar infarcts), and neuropsychological function and amount of memory complaints. RESULTS: We found a significant effect of SCD on hippocampal atrophy, as assessed using the MTA scale, but not on hippocampal volume. In addition, we found a significant effect of SCD, and amount of memory complaints, on WMH volume and Fazekas score, suggesting larger WMH volumes in participants with SCD. CONCLUSION: SVD MRI markers are related to amount of memory complaints, in addition to the commonly observed AD MRI markers, as demonstrated by the greater WMHs in healthy late middle-aged to older adults with SCD.

The effect of consumption temperature on the homeostatic and hedonic responses to glucose ingestion in the hypothalamus and the reward system.

Background: Excessive consumption of sugar-sweetened beverages (SSBs) has been associated with obesity and related diseases. SSBs are often consumed cold, and both the energy content and temperature might influence the consumption behavior for SSBs. Objective: The main aim of this study was to elucidate whether consumption temperature and energy (i.e., glucose) content modulate homeostatic (hypothalamus) and reward [ventral tegmental area (VTA)] responses. Design: Sixteen healthy men participated in our study [aged 18-25 y; body mass index (kg/m2): 20-23]. High-resolution functional magnetic resonance imaging data were collected after ingestion of 4 different study stimuli: plain tap water at room temperature (22°C), plain tap water at 0°C, a glucose-containing beverage (75 g glucose dissolved in 300 mL water) at 22°C, and a similar glucose drink at 0°C. Blood oxygen level-dependent (BOLD) changes from baseline (7 min preingestion) were analyzed over time in the hypothalamus and VTA for individual stimulus effects and for effects between stimuli. Results: In the hypothalamus, water at 22°C led to a significantly increased BOLD response; all other stimuli resulted in a direct, significant decrease in BOLD response compared with baseline. In the VTA, a significantly decreased BOLD response compared with baseline was found after the ingestion of stimuli containing glucose at 0°C and 22°C. These responses were not significantly modulated by consumption temperature. The consumption of plain water did not have a significant VTA BOLD effect. Conclusions: Our data show that glucose at 22°C, glucose at 0°C, and water at 0°C lowered hypothalamic activity, which is associated with increased satiation. On the contrary, the consumption of water at room temperature increased activity. All stimuli led to a similar VTA response, which suggests that all drinks elicited a similar hedonic response. Our results indicate that, in addition to glucose, the low temperature at which SSBs are often consumed also leads to a response from the hypothalamus and might strengthen the response of the VTA. This trial was registered at www.clinicaltrials.gov as NCT03181217.

Grey matter volume loss is associated with specific clinical motor signs in Huntington's disease.

BACKGROUND: Motor disturbances are clinical hallmarks of Huntington's disease (HD) and involve chorea, dystonia, hypokinesia and visuomotor dysfunction. Investigating the association between specific motor signs and different regional volumes is important to understand the heterogeneity of HD. OBJECTIVE: To investigate the motor phenotype of HD and associations with subcortical and cortical grey matter volume loss. METHODS: Structural T1-weighted MRI scans of 79 HD patients and 30 healthy controls were used to calculate volumes of seven subcortical structures including the nucleus accumbens, hippocampus, thalamus, caudate nucleus, putamen, pallidum and amygdala. Multiple linear regression analyses, corrected for age, gender, CAG, MRI scan protocol and normalized brain volume, were performed to assess the relationship between subcortical volumes and different motor subdomains (i.e. eye movements, chorea, dystonia, hypokinesia/rigidity and gait/balance). Voxel-based morphometry analysis was used to investigate the relationship between cortical volume changes and motor signs. RESULTS: Subcortical volume loss of the accumbens nucleus, caudate nucleus, putamen, and pallidum were associated with higher chorea scores. No other subcortical region was significantly associated with motor symptoms after correction for multiple comparisons. Voxel-based cortical grey matter volume reductions in occipital regions were related with an increase in eye movement scores. CONCLUSION: In HD, chorea is mainly associated with subcortical volume loss, while eye movements are more related to cortical volume loss. Both subcortical and cortical degeneration has an impact on motor impairment in HD. This implies that there is a widespread contribution of different brain regions resulting in the clinical motor presentation seen in HD patients.

A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy. METHODS: We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups. RESULTS: At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls. CONCLUSION: We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found.

Differences in structural covariance brain networks between behavioral variant frontotemporal dementia and Alzheimer's disease.

Disease-specific patterns of gray matter atrophy in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) overlap with distinct structural covariance networks (SCNs) in cognitively healthy controls. This suggests that both types of dementia target specific structural networks. Here, we study SCNs in AD and bvFTD. We used structural magnetic resonance imaging data of 31 AD patients, 24 bvFTD patients, and 30 controls from two centers specialized in dementia. Ten SCNs were defined based on structural covariance of gray matter density using independent component analysis. We studied group differences in SCNs using F-tests, with Bonferroni corrected t-tests, adjusted for age, gender, and study center. Associations with cognitive performance were studied using linear regression analyses. Cross-sectional group differences were found in three SCNs (all P < 0.0025). In bvFTD, we observed decreased anterior cingulate network integrity compared with AD and controls. Patients with AD showed decreased precuneal network integrity compared with bvFTD and controls, and decreased hippocampal network and anterior cingulate network integrity compared with controls. In AD, we found an association between precuneal network integrity and global cognitive performance (P = 0.0043). Our findings show that AD and bvFTD target different SCNs. The comparison of both types of dementia showed decreased precuneal (i.e., default mode) network integrity in AD and decreased anterior cingulate (i.e., salience) network integrity in bvFTD. This confirms the hypothesis that AD and bvFTD have distinct anatomical networks of degeneration and shows that structural covariance gives valuable insights in the understanding of network pathology in dementia.

Visceral adipose tissue is associated with microstructural brain tissue damage.

OBJECTIVE: Obesity has been associated with microstructural brain tissue damage. Different fat compartments demonstrate different metabolic and endocrine behaviors. The aim was to investigate the individual associations between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and microstructural integrity in the brain. METHODS: This study comprised 243 subjects aged 65.4 ± 6.7 years. The associations between abdominal VAT and SAT, assessed by CT, and magnetization transfer imaging markers of brain microstructure for gray and white matter were analyzed and adjusted for confounding factors. RESULTS: VAT was associated with normalized MTR peak height in gray (ß -0.216) and white matter (ß -0.240) (both P < 0.01) after adjustment for confounding factors. After adjustment for sex, age, and descent, SAT was associated with normalized MTR peak height in gray and white matter, but not after additional correction for BMI, hypertension, current smoking, statin use, and type 2 diabetes (respectively, ß -0.055 and ß 0.035, both P > 0.05). Stepwise linear regression analysis showed that only VAT was associated with normalized MTR peak height in gray and white matter (both P < 0.001). CONCLUSIONS: Our data indicate that increased abdominal VAT rather than SAT is associated with microstructural brain tissue damage in elderly individuals.

An in vivo study on brain microstructure in biological and chronological ageing.

This study aimed to investigate whether magnetization transfer imaging (MTI) parameters of cortical gray and white matter and subcortical gray matter structures differ between subjects enriched for human familial longevity and control subjects to provide a thorough description of the brain phenotype of familial longevity. Moreover, we aimed to describe cerebral ageing effects on MTI parameters in an elderly cohort. All subjects were included from the Leiden Longevity Study and underwent 3 Tesla MTI of the brain. In total, 183 offspring of nonagenarian siblings, who are enriched for familial factors of longevity, were contrasted with 163 environmentally and age-matched controls. No differences in cortical and subcortical gray matter and white matter MTI parameters were found between offspring and control subjects using histogram-based and voxel-wise analyses. Cortical gray matter and white matter MTI parameters decreased with increasing chronological age (all p < 0.001). Decrease of white matter magnetization transfer ratio (MTR) was homogeneous throughout the whole mean white matter skeleton except for parts of the callosal splenium and partly the posterior limb of the internal capsule and superior region of the corona radiata (p < 0.05). Mean MTR of subcortical gray matter structures decreased with increasing age (p amygdala, caudate nucleus and putamen < 0.001; p pallidum = 0.001, p thalamus = 0.002). In conclusion, the brain phenotype of human familial longevity is - at a mean age of 66 years - not characterized by preserved macromolecular brain tissue integrity.

Longitudinal resting state fMRI analysis in healthy controls and premanifest Huntington's disease gene carriers: a three-year follow-up study.

BACKGROUND: We previously demonstrated that in the premanifest stage of Huntington's disease (preHD), a reduced functional connectivity exists compared to healthy controls. In the current study, we look at possible changes in functional connectivity occurring longitudinally over a period of 3 years, with the aim of assessing the potential usefulness of this technique as a biomarker for disease progression in preHD. METHODS: Twenty-two preHD and 17 healthy control subjects completed resting state functional magnetic resonance imaging (fMRI) scans in two visits with 3 years in between. Differences in resting state connectivity were examined for eight networks of interest using FSL with three different analysis types: a dual regression method, region of interest approach, and an independent component analysis. To evaluate a possible combined effect of gray matter volume change and the change in blood oxygenation level dependent signal, the analysis was performed with and without voxel-wise correction for gray matter volume. To evaluate possible correlations between functional connectivity change and the predicted time to disease onset, the preHD group was classed as preHD-A if ≥10.9 years and preHD-B if <10.9 years from predicted disease onset. Possible correlations between burden of pathology score and functional connectivity change in preHD were also assessed. Finally, longitudinal change in whole brain and striatal volumetric measures was assessed in the studied cohort. RESULTS: Longitudinal analysis of the resting state-fMRI (RS-fMRI) data revealed no differences in the degree of connectivity change between the groups over a period of 3 years, though a significantly higher rate of striatal atrophy was found in the preHD group compared to controls in the same period. DISCUSSION: Based on the results found in this study, the provisional conclusion is that RS-fMRI lacks sensitivity in detecting changes in functional connectivity in HD gene carriers prior to disease manifestation over a 3-year follow-up period.

Prognostic value of gradient echo T2* sequences for brain MR imaging in preterm infants.

BACKGROUND: Gradient echo T2*-W sequences are more sensitive than T2-W spin-echo sequences for detecting hemorrhages in the brain. OBJECTIVE: The aim of this study is to correlate presence of hemosiderin deposits in the brain of very preterm infants (gestational age <32 weeks) detected by T2*-W gradient echo MRI to white matter injury and neurodevelopmental outcome at 2 years. MATERIALS AND METHODS: In 101 preterm infants, presence and location of hemosiderin were assessed on T2*-W gradient echo MRI performed around term-equivalent age (range: 40-60 weeks). White matter injury was defined as the presence of >6 non-hemorrhagic punctate white matter lesions (PWML), cysts and/or ventricular dilatation. Six infants with post-hemorrhagic ventricular dilatation detected by US in the neonatal period were excluded. Infants were seen for follow-up at 2 years. Univariate and regression analysis assessed the relation between presence and location of hemosiderin, white matter injury and neurodevelopmental outcome. RESULTS: In 38/95 (40%) of the infants, hemosiderin was detected. Twenty percent (19/95) of the infants were lost to follow-up. There was a correlation between hemosiderin in the ventricular wall with >6 PWML (P < 0.001) and cysts (P < 0.001) at term-equivalent age, and with a lower psychomotor development index (PDI) (P=0.02) at 2 years. After correcting for known confounders (gestational age, gender, intrauterine growth retardation and white matter injury), the correlation with PDI was no longer significant. CONCLUSION: The clinical importance of detecting small hemosiderin deposits is limited as there is no independent association with neurodevelopmental outcome.

Preserved white matter integrity is a marker of familial longevity.

OBJECTIVE: Brain tissue integrity is highly heritable, and its decline is a common phenomenon of ageing. This study aimed to determine whether the phenotype of familial longevity is marked by a relative preservation of brain tissue microstructure. METHODS: Participants were enrolled in the Leiden Longevity Study. In total, 185 middle-aged to elderly offspring of nonagenarian siblings, who were enriched for familial factors of longevity, were contrasted with 171 environment- and age-matched controls. All subjects underwent 3T whole brain magnetic resonance diffusion tensor imaging. RESULTS: Voxel-wise analysis revealed widespread age-related decrease of white matter fractional anisotropy and increases of axial, radial, and mean diffusivity (all p < 0.003). Offspring showed higher mean white matter fractional anisotropy (mean [standard error]: offspring, 0.3232 [0.0009]; controls, 0.3212 [0.0009]; p = 0.04) compared to control subjects independent of cardiovascular risk factors. When differences in white matter diffusion parameters between offspring and control subjects were assessed voxel-wise, offspring showed higher white matter fractional anisotropy and lower white matter radial diffusivity predominantly in the callosal genu and body (both p < 0.003). With the effect of chronological age on white matter microstructure taken into account, offspring can be considered 4.5 years "biologically younger" compared to control subjects with regard to white matter integrity. INTERPRETATION: Both middle-aged to elderly offspring of nonagenarian siblings and control subjects show common age-related decline of white matter integrity, but it is less marked in the callosal genu and body in the offspring. This corresponds to a biological age benefit of 4.5 years of the offspring as compared to the control subjects.

Small cerebellar hemorrhage in preterm infants: perinatal and postnatal factors and outcome.

The objective of the study is to determine perinatal and postnatal factors that may affect the occurrence of small cerebellar hemorrhage (CBH) and to evaluate the effect of small CBH on neurodevelopmental outcome in very preterm infants. This prospective study in an unselected cohort of very preterm infants was approved by the medical ethics committee, and informed parental consent was obtained. Presence of small CBH (<4 mm) was assessed with magnetic resonance imaging around term equivalent age in 108 preterm infants (<32 weeks gestation). We compared infants with and without small CBH for perinatal and postnatal factors, supratentorial brain injury, and for neurodevelopmental outcome at 2 years corrected age. Follow-up consisted of a neurological examination, mental and developmental assessment (Bayley Scales of Infant Development), and behavior checklist. Univariate and multivariate logistic regression analyses were performed to examine the relationships between variables. Small CBH was diagnosed in 16/108 very preterm infants. Univariate analyses identified gestational age, high-frequency oscillation (HFO) ventilation, and grade 3-4 intraventricular hemorrhage (IVH) as factors associated with small CBH. HFO ventilation and severe IVH were independent predictors of small CBH. We found no association between small CBH and neurodevelopmental outcome at 2 years of age. Small CBH is a frequent finding in preterm infants. These hemorrhages are independently associated with HFO ventilation and severe supratentorial hemorrhage and seem to have a favorable short-term prognosis.

Tractography of white-matter tracts in very preterm infants: a 2-year follow-up study.

AIM: The aim of this study was to determine whether tractography of white-matter tracts can independently predict neurodevelopmental outcome in very preterm infants. METHOD: Out of 84 very preterm infants admitted to a neonatal intensive care unit, 64 (41 males, 23 females; median gestational age 29.1 weeks [range 25.6-31.9]; birthweight 1163 g [range 585-1960]) underwent follow-up at 2 years. Diffusion tensor imaging (DTI) values obtained around term were associated with a neurological examination and mental and psychomotor developmental index scores at 2 years based on the Bayley Scales of Infant Development (version 3). Univariate and logistic regression analyses tested for associations between DTI values and follow-up parameters. Cut-off values predicting motor delay and cerebral palsy (CP) were determined for fractional anisotropy, apparent diffusion coefficient (ADC), and fibre lengths. RESULTS: Infants with psychomotor delay and CP had significantly lower fractional anisotropy values (p=0.002, p=0.04 respectively) and shorter fibre lengths (p=0.02, p=0.02 respectively) of the posterior limb of the internal capsule. Infants with psychomotor delay also had significantly higher ADC values (p=0.03) and shorter fibre lengths (p=0.002) of the callosal splenium. Fractional anisotropy values of the posterior limb of the internal capsule independently predicted motor delay and CP, with sensitivity between 80 and 100% and specificity between 66 and 69%. ADC values of the splenium independently predicted motor delay with sensitivity of 100% and specificity of 65%. INTERPRETATION: Diffusion tensor imaging tractography at term-equivalent age independently predicts psychomotor delay at 2 years of age in preterm infants.

Clinical implications of MR imaging findings in the white matter in very preterm infants: a 2-year follow-up study.

PURPOSE: To explore the association between diffuse excessive high signal intensity (DEHSI), punctate white matter (WM) lesions, and ventricular dilatation around term-equivalent age (TEA) and at clinical follow-up at 2 years in very preterm infants and the effect on neurodevelopment. MATERIALS AND METHODS: Ethical approval for this prospective study was given by the institutional review board, and informed parental consent was obtained. An unselected cohort of 110 preterm infants (gestational age, < 32 weeks) was imaged around or after TEA. Clinical follow-up was performed at a corrected age of 2 years and consisted of a neurologic examination and a mental and developmental assessment (Bayley Scales of Infant Development). Univariate analyses and logistic and linear regression were performed to examine the relationships between variables. RESULTS: DEHSI was found in 58 of 65 (89%) infants imaged around TEA. DEHSI was never detected in infants imaged after postmenstrual age of 50 weeks and showed no association with neurodevelopmental outcome. Punctate WM lesions and ventricular dilatation were significantly associated with mental (P = .02 for punctate WM lesions) and psychomotor developmental delay (P < .001 and P = .03, respectively), motor delay (P = .002 and P = .02, respectively), and cerebral palsy (P = .01 and P = .03, respectively). CONCLUSION: Because of its high incidence in preterm infants around TEA, its absence after a postmenstrual age of 50 weeks, and its association with normal neurologic outcome at a corrected age of 2 years, DEHSI should not be considered part of the spectrum of WM injury, but rather a prematurity-related developmental phenomenon.

Tractography of developing white matter of the internal capsule and corpus callosum in very preterm infants.

OBJECTIVES: To investigate in preterm infants associations between Diffusion Tensor Imaging (DTI) parameters of the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) and age, white matter (WM) injury and clinical factors. METHODS: In 84 preterm infants DTI was performed between 40-62 weeks postmenstrual age on 3 T MR. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) values and fibre lengths through the PLIC and the genu and splenium were determined. WM injury was categorised as normal/mildly, moderately and severely abnormal. Associations between DTI parameters and age, WM injury and clinical factors were analysed. RESULTS: A positive association existed between FA and age at imaging for fibres through the PLIC (r = 0.48 p < 0.001) and splenium (r = 0.24 p < 0.01). A negative association existed between ADC and age at imaging for fibres through the PLIC (r = -0.65 p < 0.001), splenium (r = -0.35 p < 0.001) and genu (r = -0.53 p < 0.001). No association was found between DTI parameters and gestational age, degree of WM injury or categorical clinical factors. CONCLUSIONS: These results indicate that in our cohort of very preterm infants, at this young age, the development of the PLIC and CC is ongoing and independent of the degree of prematurity or WM injury.

Hypoxic-ischemic encephalopathy: diagnostic value of conventional MR imaging pulse sequences in term-born neonates.

PURPOSE: To retrospectively compare different magnetic resonance (MR) imaging techniques and pulse sequences for the depiction of brain injury in neonatal hypoxic-ischemic encephalopathy. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived informed consent. Term-born neonates underwent MR imaging within 10 days after birth because of perinatal asphyxia. Two investigators separately and retrospectively evaluated T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), diffusion-weighted, and T1-weighted contrast material-enhanced MR images for presence of hypoxic-ischemic injury patterns. Interobserver agreement between the raters for visualizing abnormalities on images obtained with the individual pulse sequences was analyzed. Individual assessments were compared with the consensus reading (reference standard) to determine which techniques were best for visualizing hypoxic-ischemic damage. Last, which combination of pulse sequences had the best performance for visualizing certain injury patterns was evaluated. All analyses were repeated for infants imaged within 4 days after birth and those imaged between 4 and 10 days after birth. RESULTS: Forty term-born neonates (22 boys; gestational age, 37 weeks to 42 weeks 2 days) were included. Interobserver agreement was moderate for all pulse sequences (intraclass correlation coefficient [ICC], 0.52-0.73). As compared with the reference standard, T1-weighted imaging performed best in both groups (infants imaged < or = 4 days and those imaged > 4 days after birth) for lesions in the basal ganglia, thalamus, and posterior limb of the internal capsule (ICC, 0.93), as well as for punctate white matter lesions (ICC, 0.88). For infarction, diffusion-weighted images were scored best in both groups (ICC, 0.86). For nonpunctate white matter lesions, T2-weighted images were scored as good in both groups (ICC, 0.59). Adding FLAIR and contrast-enhanced imaging to the combination of T1- and T2-weighted imaging and diffusion-weighted imaging did not contribute to detection of hypoxic-ischemic brain damage. CONCLUSION: The combination of T1- and T2-weighted MR imaging and diffusion-weighted imaging is best for detecting hypoxic-ischemic brain lesions in the early neonatal period in term-born infants.