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BJOG : An International Journal of... Jul 2024To utilise combined diffusion-relaxation MRI techniques to interrogate antenatal changes in the placenta prior to extreme preterm birth among both women with PPROM and...
OBJECTIVE
To utilise combined diffusion-relaxation MRI techniques to interrogate antenatal changes in the placenta prior to extreme preterm birth among both women with PPROM and membranes intact, and compare this to a control group who subsequently delivered at term.
DESIGN
Observational study.
SETTING
Tertiary Obstetric Unit, London, UK.
POPULATION
Cases: pregnant women who subsequently spontaneously delivered a singleton pregnancy prior to 32 weeks' gestation without any other obstetric complications.
CONTROLS
pregnant women who delivered an uncomplicated pregnancy at term.
METHODS
All women consented to an MRI examination. A combined diffusion-relaxation MRI of the placenta was undertaken and analysed using fractional anisotropy, a combined T2*-apparent diffusion coefficient model and a combined T2*-intravoxel incoherent motion model, in order to provide a detailed placental phenotype associated with preterm birth. Subgroup analyses based on whether women in the case group had PPROM or intact membranes at time of scan, and on latency to delivery were performed.
MAIN OUTCOME MEASURES
Fractional anisotropy, apparent diffusion coefficients and T2* placental values, from two models including a combined T2*-IVIM model separating fast- and slow-flowing (perfusing and diffusing) compartments.
RESULTS
This study included 23 women who delivered preterm and 52 women who delivered at term. Placental T2* was lower in the T2*-apparent diffusion coefficient model (p < 0.001) and in the fast- and slow-flowing compartments (p = 0.001 and p < 0.001) of the T2*-IVIM model. This reached a higher level of significance in the preterm prelabour rupture of the membranes group than in the membranes intact group. There was a reduced perfusion fraction among the cases with impending delivery.
CONCLUSIONS
Placental diffusion-relaxation reveals significant changes in the placenta prior to preterm birth with greater effect noted in cases of preterm prelabour rupture of the membranes. Application of this technique may allow clinically valuable interrogation of histopathological changes before preterm birth. In turn, this could facilitate more accurate antenatal prediction of preterm chorioamnionitis and so aid decisions around the safest time of delivery. Furthermore, this technique provides a research tool to improve understanding of the pathological mechanisms associated with preterm birth in vivo.
PubMed: 38956748
DOI: 10.1111/1471-0528.17901 -
Human Genomics Jul 2024Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive...
BACKGROUND
Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles.
RESULTS
We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging.
CONCLUSIONS
These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.
Topics: Humans; DNA Methylation; Female; Male; Multifactorial Inheritance; Aged; Genome-Wide Association Study; Middle Aged; Cognitive Aging; Cross-Sectional Studies; White Matter; Risk Factors; Magnetic Resonance Imaging; Aging; Brain; Genetic Risk Score
PubMed: 38956648
DOI: 10.1186/s40246-024-00640-6 -
Molecular Imaging 2024To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (H-MRS) parameters in predicting the...
OBJECTIVE
To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (H-MRS) parameters in predicting the immunohistochemistry (IHC) biomarkers of glioma.
METHODS
Patients with glioma confirmed by pathology from March 2015 to September 2019 were analyzed, the preoperative DTI and H-MRS images were collected, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), in the lesion area were measured, the relative values relative ADC (rADC) and relative FA (rFA) were obtained by the ratio of them in the lesion area to the contralateral normal area. The peak of each metabolite in the lesion area of H-MRS image: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), and metabolite ratio: NAA/Cho, NAA/(Cho + Cr) were selected and calculated. The preoperative IHC data were collected including CD34, Ki-67, p53, S-100, syn, vimentin, NeuN, Nestin, and glial fibrillary acidic protein.
RESULTS
One predicting parameter of DTI was screened, the rADC of the Ki-67 positive group was lower than that of the negative group. Two parameters of H-MRS were found to have significant reference values for glioma grades, the NAA and Cr decreased as the grade of glioma increased, moreover, Ki-67 Li was negatively correlated with NAA and Cr.
CONCLUSION
NAA and Cr have potential application value in predicting glioma grades and tumor proliferation activity. Only rADC has predictive value for Ki-67 expression among DTI parameters.
Topics: Humans; Glioma; Male; Female; Middle Aged; Adult; Immunohistochemistry; Brain Neoplasms; Diffusion Tensor Imaging; Magnetic Resonance Imaging; Aged; Proton Magnetic Resonance Spectroscopy; Young Adult
PubMed: 38952400
DOI: 10.1177/15353508241261583 -
Annals of Clinical and Translational... Jul 2024The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it...
OBJECTIVE
The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach.
METHODS
MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross-sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison.
RESULTS
Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted.
INTERPRETATION
Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex.
PubMed: 38952134
DOI: 10.1002/acn3.52048 -
NPJ Parkinson's Disease Jun 2024Idiopathic rapid eye movement sleep behaviour disorder (iRBD)-a Parkinson's disease (PD) prodrome-might exhibit neural changes similar to those in PD. Substantia nigra...
Idiopathic rapid eye movement sleep behaviour disorder (iRBD)-a Parkinson's disease (PD) prodrome-might exhibit neural changes similar to those in PD. Substantia nigra pars compacta (SNc) degeneration underlies motor symptoms of PD. In iRBD and early PD (ePD), we measured diffusion MRI (dMRI) in the caudal motor SNc, which overlaps the nigrosome-1-the earliest-degenerating dopaminergic neurons in PD-and in the striatum. Nineteen iRBD, 26 ePD (1.7 ± 0.03 years), and 46 age-matched healthy controls (HCs) were scanned at Western University, and 47 iRBD, 115 ePD (0.9 ± 0.01 years), and 56 HCs were scanned through the Parkinson's Progression Markers Initiative, using 3T MRI. We segmented the SNc and striatum into subregions using automated probabilistic tractography to the cortex. We measured mean diffusivity (MD) and fractional anisotropy (FA) along white-matter bundles and subregional surfaces. We performed group-level and classification analyses. Increased caudal motor SNc surface MD was the only iRBD-HCs and ePD-HCs difference replicating across datasets (p < 0.05). No iRBD-ePD differences emerged. Caudal motor SNc surface MD classified patient groups from HCs at the single-subject level with good-to-excellent balanced accuracy in an independent sample (0.91 iRBD and 0.86 iRBD and ePD combined), compared to fair performance for total SNc surface MD (0.72 iRBD and ePD). Caudal motor SNc surface MD correlated significantly with MDS-UPDRS-III scores in ePD patients. Using dMRI and automated segmentation, we detected changes suggesting altered microstructural integrity in iRBD and ePD in the nigrostriatal subregion known to degenerate first in PD. Surface MD of the caudal motor SNc presents a potential measure for inclusion in neuroimaging biomarkers of iRBD and PD.
PubMed: 38951528
DOI: 10.1038/s41531-024-00731-0 -
Scientific Reports Jul 2024Diffusion tensor imaging (DTI) metrics and tractography can be biased due to low signal-to-noise ratio (SNR) and systematic errors resulting from image artifacts and...
Diffusion tensor imaging (DTI) metrics and tractography can be biased due to low signal-to-noise ratio (SNR) and systematic errors resulting from image artifacts and imperfections in magnetic field gradients. The imperfections include non-uniformity and nonlinearity, effects caused by eddy currents, and the influence of background and imaging gradients. We investigated the impact of systematic errors on DTI metrics of an isotropic phantom and DTI metrics and tractography of a rat brain measured at high resolution. We tested denoising and Gibbs ringing removal methods combined with the B matrix spatial distribution (BSD) method for magnetic field gradient calibration. The results showed that the performance of the BSD method depends on whether Gibbs ringing is removed and the effectiveness of stochastic error removal. Region of interest (ROI)-based analysis of the DTI metrics showed that, depending on the size of the ROI and its location in space, correction methods can remove systematic bias to varying degrees. The preprocessing pipeline proposed and dedicated to this type of data together with the BSD method resulted in an even - 90% decrease in fractional anisotropy (FA) (globally and locally) in the isotropic phantom and - 45% in the rat brain. The largest global changes in the rat brain tractogram compared to the standard method without preprocessing (sDTI) were noticed after denoising. The direction of the first eigenvector obtained from DTI after denoising, Gibbs ringing removal and BSD differed by an average of 56 and 10 degrees in the ROI from sDTI and from sDTI after denoising and Gibbs ringing removal, respectively. The latter can be identified with the amount of improvement in tractography due to the elimination of systematic errors related to imperfect magnetic field gradients. Based on the results, the systematic bias for high resolution data mainly depended on SNR, but the influence of non-uniform gradients could also be seen. After denoising, the BSD method was able to further correct both the metrics and tractography of the diffusion tensor in the rat brain by taking into account the actual distribution of magnetic field gradients independent of the examined object and uniquely dependent on the scanner and sequence. This means that in vivo studies are also subject to this type of errors, which should be taken into account when processing such data.
Topics: Animals; Diffusion Tensor Imaging; Rats; Brain; Signal-To-Noise Ratio; Phantoms, Imaging; Artifacts; Image Processing, Computer-Assisted; Anisotropy; Male
PubMed: 38951163
DOI: 10.1038/s41598-024-66076-z -
MedRxiv : the Preprint Server For... Jun 2024Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative....
IMPORTANCE
Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD.
OBJECTIVE
To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL).
DESIGN
Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined).
SETTING
The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively.
PARTICIPANTS
Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women).
INTERVENTION
Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals.
MAIN OUTCOMES AND MEASURES
Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance).
RESULTS
Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1- p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=- 0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance.
CONCLUSIONS AND RELEVANCE
Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.
KEY POINTS
Does white matter (WM) microstructure change with medication-assisted treatment in individuals with heroin use disorder (iHUD)? In this longitudinal cohort study, diffusion MRI was acquired in 34 inpatient iHUD and 25 healthy controls (CTL) twice, separated by a mean of 13.9 weeks. We found HUD- specific WM microstructure changes with time, characterized by increased anisotropy and decreased diffusivity in fronto-striatal WM pathways. These changes were correlated with decreased baseline drug craving with treatment. Frontal WM changes and associated drug craving decreases suggest brain-behavior recovery with inpatient treatment in iHUD, potentially contributing to reduced drug use and sustained abstinence.
PubMed: 38946983
DOI: 10.1101/2024.06.10.24308719 -
Biological Psychiatry Jun 2024Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently...
OBJECTIVE
Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure detection of involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes.
METHODS
Structural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of mood and personality traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age and sex evaluated group differences in structural connectivity strength, indicated by fractional anisotropy, streamline volume density and mean diffusivity, and evaluated within three different atlases.
RESULTS
Insomnia subtypes showed differentiating profiles of deviating structural connectivity which concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes: highly distressed, moderately distressed reward sensitive, slightly distressed low reactive and slightly distressed high reactive. Connectivity deviation profile significance ranged from p= 0.001 to p=0.049 for different resolutions of brain parcellation and connectivity weight.
CONCLUSIONS
Our results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.
PubMed: 38944140
DOI: 10.1016/j.biopsych.2024.06.014 -
Ecotoxicology and Environmental Safety Jun 2024Studies have highlighted a possible link between air pollution and cerebral small vessel disease (CSVD) imaging markers. However, the exact association and effects of...
Studies have highlighted a possible link between air pollution and cerebral small vessel disease (CSVD) imaging markers. However, the exact association and effects of polygenic risk score (PRS) defined genetic susceptibility remains unclear. This cross-sectional study used data from the UK Biobank. Participants aged 40-69 years were recruited between the year 2006 and 2010. The annual average concentrations of NO, NO, PM, PM, PM absorbance, and PM, were estimated, and joint exposure to multiple air pollutants was reflected in the air pollution index (APEX). Air pollutant exposure was classified into the low (T1), intermediate (T2), and high (T3) tertiles. Three CSVD markers were used: white matter hyper-intensity (WMH), mean diffusivity (MD), and fractional anisotropy (FA). The first principal components of the MD and FA measures in the 48 white matter tracts were analysed. The sample consisted of 44,470 participants from the UK Biobank. The median (T1-T3) concentrations of pollutants were as follows: NO, 25.5 (22.4-28.7) μg/m; NOx, 41.3 (36.2-46.7) μg/m; PM, 15.9 (15.4-16.4) μg/m; PM, 9.9 (9.5-10.3) μg/m; PM absorbance, 1.1 (1.0-1.2) per metre; and PM, 6.1 (5.9-6.3) μg/m. Compared with the low group, the high group's APEX, NO, and PM levels were associated with increased WMH volumes, and the estimates (95 %CI) were 0.024 (0.003, 0.044), 0.030 (0.010, 0.050), and 0.032 (0.011, 0.053), respectively, after adjusting for potential confounders. APEX, PM, PM absorbance, and PM exposure in the high group were associated with increased FA values compared to that in the low group. Sex-specific analyses revealed associations only in females. Regarding the combined associations of air pollutant exposure and PRS-defined genetic susceptibility with CSVD markers, the associations of NO, NO, PM, and PM with WMH were more profound in females with low PRS-defined genetic susceptibility, and the associations of PM, PM, and PM absorbance with FA were more profound in females with higher PRS-defined genetic susceptibility. Our study demonstrated that air pollutant exposure may be associated with CSVD imaging markers, with females being more susceptible, and that PRS-defined genetic susceptibility may modify the associations of air pollutants.
PubMed: 38944013
DOI: 10.1016/j.ecoenv.2024.116638 -
European Journal of Paediatric... Jun 2024Music therapy (MT) is proposed to enrich the acoustic environment of very preterm infants (VPT) on the neonatal intensive care unit during a vulnerable period of brain...
OBJECTIVE
Music therapy (MT) is proposed to enrich the acoustic environment of very preterm infants (VPT) on the neonatal intensive care unit during a vulnerable period of brain development. The objective of this study was to investigate the effect of MT on the white matter (WM) microstructure. It is hypothesized that MT affects WM integrity in VPT.
METHODS
Randomized controlled trial enrolling infants born <32 weeks' gestation. Infants were randomized to MT or standard care. Live MT was provided twice weekly from the second postnatal week onwards by a trained music therapist. At term equivalent age, participants underwent a cranial magnetic resonance imaging scan including sequences for diffusion tensor imaging analysis. Differences in WM microstructure were assessed using tract based spatial statistics with fractional anisotropy.
RESULTS
Of 80 infants enrolled, 42 were eligible for diffusion tensor imaging analysis (MT: n = 22, standard care: n = 20). While primary tract based spatial statistics analysis revealed no significant differences between groups, post hoc analysis with uncorrected p-values and a significance threshold of p < 0.01 revealed significant fractional anisotropy differences in several WM tracts including the bilateral superior longitudinal fasciculus, the left forceps minor and left fasciculus uncinatus, the corpus callosum, the left external capsule, and the right corticospinal tract.
CONCLUSION
Post hoc analysis results suggest an effect of MT on WM integrity in VPT. Larger studies including long-term outcome are necessary to confirm these effects of MT on WM microstructure and to assess its impact on clinical neurodevelopment.
CLINICAL TRIAL REGISTRATION
Clinical trial number DRKS00025753.
PubMed: 38941879
DOI: 10.1016/j.ejpn.2024.06.009