Mean Fractional Anisotropy Research Articles

Investigation into white matter microstructure differences in visual training by using an automated fiber tract subclassification segmentation quantification method

Visual training has emerged as a useful framework for investigating training-related brain plasticity, a highly complex task involving the interaction of visual orientation, attention, reasoning, and cognitive functions. However, the effects of long-term visual training on microstructural changes within white matter (WM) is poorly understood. Therefore, a set of visual training programs was designed, and automated fiber tract subclassification segmentation quantification based on diffusion magnetic resonance imaging was performed to obtain the anatomical changes in the brains of visual trainees. First, 40 healthy matched participants were randomly assigned to the training group or the control group. The training group underwent 10 consecutive weeks of visual training. Then, the fiber tracts of the subjects were automatically identified and further classified into fiber clusters to determine the differences between the two groups on a detailed scale. Next, each fiber cluster was divided into segments that can analyze specific areas of a fiber cluster. Lastly, the diffusion metrics of the two groups were comparatively analyzed to delineate the effects of visual training on WM microstructure. Our results showed that there were significant differences in the fiber clusters of the cingulate bundle, thalamus frontal, uncinate fasciculus, and corpus callosum between the training group compared and the control group. In addition, the training group exhibited lower mean fractional anisotropy, higher mean diffusivity and radial diffusivity than the control group. Therefore, the long-term cognitive activities, such as visual training, may systematically influence the WM properties of cognition, attention, memory, and processing speed.

Sleep loss, caffeine, sleep aids and sedation modify brain abnormalities of mild traumatic brain injury

Little evidence exists about how mild traumatic brain injury (mTBI) is affected by commonly encountered exposures of sleep loss, sleep aids, and caffeine that might be potential therapeutic opportunities. In addition, while propofol sedation is administered in severe TBI, its potential utility in mild TBI is unclear. Each of these exposures is known to have pronounced effects on cerebral metabolism and blood flow and neurochemistry. We hypothesized that they each interact with cerebral metabolic dynamics post-injury and change the subclinical characteristics of mTBI. MTBI in rats was produced by head rotational acceleration injury that mimics the biomechanics of human mTBI. Three mTBIs spaced 48 h apart were used to increase the likelihood that vulnerabilities induced by repeated mTBI would be manifested without clinically relevant structural damage. After the third mTBI, rats were immediately sleep deprived or administered caffeine or suvorexant (an orexin antagonist and sleep aid) for the next 24 h or administered propofol for 5 h. Resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were performed 24 h after the third mTBI and again after 30 days to determine changes to the brain mTBI phenotype. Multi-modal analyses on brain regions of interest included measures of functional connectivity and regional homogeneity from rs-fMRI, and mean diffusivity (MD) and fractional anisotropy (FA) from DTI. Each intervention changed the mTBI profile of subclinical effects that presumably underlie healing, compensation, damage, and plasticity. Sleep loss during the acute post-injury period resulted in dramatic changes to functional connectivity. Caffeine, propofol sedation and suvorexant were especially noteworthy for differential effects on microstructure in gray and white matter regions after mTBI. The present results indicate that commonplace exposures and short-term sedation alter the subclinical manifestations of repeated mTBI and therefore likely play roles in symptomatology and vulnerability to damage by repeated mTBI.

Aging of reward dopamine tracts in the human brain: A diffusion tensor imaging study.

The mesocortical tract (MCT) and mesolimbic tract (MLT) are reward dopaminergic tracts that have been shown to play a role in regulating reward stimuli, including both incentive salience and social stimuli. In the current study, we examined aging of the MCT and MLT in normal human participants to explain human brain structures using diffusion tensor tractography (DTT). Sixty-four healthy participants were recruited for this study and allocated to 3 groups based on participants' age. Diffusion tensor imaging was performed, and MCTs and MLTs were reconstructed using the probabilistic tractography method. A significant negative correlation was observed between age and fractional anisotropy and tract volume of the MCT and MLT, whereas a positive correlation was observed between age and mean diffusivity. The mean fractional anisotropy value of the MCT was significantly lower in the old group than in the young and middle-aged groups (P < .05). The mean diffusivity values of the MCT and MLT were significantly higher in the old group than in the young and middle-aged groups (P < .05). The mean tract volume values of the MCT and MLT were significantly lower in the old group than in the young group (P < .05). We found that degenerative changes in the MCT and MLT began in participants in the 20s-30s, progressed steadily throughout life, and accelerated in the 60s.

Brain white matter alterations in young adult male patients with childhood-onset growth hormone deficiency: a diffusion tensor imaging study.

This study aimed to detect white matter changes and different effects of thyroid hormone on the white matter integrity in young adult male patients with childhood-onset growth hormone deficiency (CO-GHD), compared with healthy people. Magnetic resonance imaging (structural imaging and diffusion tensor imaging) was performed in 17 young adult male patients with CO-GHD and 17 healthy male controls. The white matter volume, mean diffusivity (MD) values and fractional anisotropy (FA) values were quantified and compared between two groups (CO-GHD group vs. control group). We assessed the interaction effects between thyroid hormone and groups (CO-GHD group vs. control group) on white matter integrity. Patients with CO-GHD exhibited similar white matter volumes compared with controls. However, compared with the controls, patients with CO-GHD showed a significant reduction in FA values in six clusters and a substantial increase in MD values in four clusters, mainly involving the corticospinal tracts, corpus callosum and so on. Moreover, after correcting for insulin-like growth factor-1 levels, the significant interaction effects between groups (CO-GHD group vs. control group) and serum free thyroxine levels on MD values were noted in three clusters, mainly involving in superior longitudinal fasciculus and sagittal stratum. In conclusion, young males with CO-GHD showed white matter changes in multiple brain regions and different effects of thyroid hormone on the white matter integrity.

Microstructural abnormalities of white matter in the cingulum bundle of adolescents with major depression and non-suicidal self-injury.

Non-suicidal self-injury (NSSI) is prevalent in major depressive disorder (MDD) during adolescence, but the underlying neural mechanisms are unclear. This study aimed to investigate microstructural abnormalities in the cingulum bundle associated with NSSI and its clinical characteristics. 130 individuals completed the study, including 35 healthy controls, 47 MDD patients with NSSI, and 48 MDD patients without NSSI. We used tract-based spatial statistics (TBSS) with a region of interest (ROI) analysis to compare the fractional anisotropy (FA) of the cingulum bundle across the three groups. receiver-operating characteristics (ROC) analysis was employed to evaluate the ability of the difficulties with emotion regulation (DERS) score and mean FA of the cingulum to differentiate between the groups. MDD patients with NSSI showed reduced cingulum integrity in the left dorsal cingulum compared to MDD patients without NSSI and healthy controls. The severity of NSSI was negatively associated with cingulum integrity (r = -0.344, p = 0.005). Combining cingulum integrity and DERS scores allowed for successful differentiation between MDD patients with and without NSSI, achieving a sensitivity of 70% and specificity of 83%. Our study highlights the role of the cingulum bundle in the development of NSSI in adolescents with MDD. The findings support a frontolimbic theory of emotion regulation and suggest that cingulum integrity and DERS scores may serve as potential early diagnostic tools for identifying MDD patients with NSSI.

6 Racial Discrimination and White Matter Integrity Among Black Older Adults

Objective:Non-Hispanic Black older adults experience a disproportionate burden of Alzheimer’s Disease and related dementias (ADRD) risk compared to non-Hispanic White older adults. It is necessary to identify mechanisms that may be contributing to inequities in cognitive aging. Psychosocial stressors that disproportionately affect Black adults (e.g., discrimination) have the potential to impact brain health through stress pathways. The brain’s white matter, which appears to be particularly important for ADRD risk among Black older adults, may be uniquely vulnerable to stress-related physiological dysfunction. To further understand whether and how discrimination can affect ADRD risk, this study aimed to examine associations between multiple forms of racial discrimination and white matter integrity, operationalized through diffusion tensor imaging.Participants and Methods:Cross-sectional data were obtained from 190 non-Hispanic Black residents aged 65+ without dementia in northern Manhattan. Racial discrimination was self-reported using the Everyday Discrimination and Major Experiences of Lifetime Discrimination scales. Example items from the Everyday Discrimination Scale include: “You are treated with less respect than other people”; “You are called names or insulted.” Example items from the Major Experiences of Lifetime Discrimination Scale include: “At any time in your life, have you ever been unfairly fired from a job?”; “Have you ever been unfairly denied a bank loan?” Racial discrimination was operationalized as experiences attributed to “race” or “skin color.” White matter integrity was assessed using fractional anisotropy (FA) via diffusion tensor imaging. Multivariable regression models evaluated the unique effects of everyday and major experiences of lifetime racial discrimination on mean FA in the whole brain and specific regions. Initial models controlled for age, sex/gender, intracranial volume, and white matter hyperintensities. Subsequent models additionally controlled for socioeconomic and health factors to consider potential confounders or mediators of the relationship between discrimination and white matter integrity.Results:Major experiences of lifetime discrimination were negatively associated with mean FA within the left cingulum cingulate gyrus and the right inferior fronto-occipital fasciculus. These associations persisted when controlling for additional covariates (i.e., education, depression, and cardiovascular diseases). In contrast, major experiences of lifetime discrimination were positively associated with mean FA within the right superior longitudinal fasciculus (temporal part). This association was attenuated when controlling for additional covariates. Everyday racial discrimination was not associated with mean FA in any regions.Conclusions:These results extend prior work linking racial discrimination to brain health and provide evidence for both risk and resilience among Black older adults. Major experiences of lifetime racial discrimination, a proxy for institutional racism, may have a stronger effect on white matter integrity than everyday racial discrimination, a proxy for interpersonal racism. Educational opportunities and cardiovascular risk factors may represent mediators between racial discrimination and white matter integrity. White matter integrity within specific brain regions may be a mechanism through which racially patterned social stressors contribute to racial disparities in ADRD. Future research should characterize within-group heterogeneity in order to identify factors that promote resilience among Black older adults.

7 P-Tau and Education as Moderators of the Relation between APOE4 and Memory Performance in Older Adults with Varying Cognitive Status

Objective:White matter microstructure (WMM) potentially mediates the relation between APOE4 and memory performance. This study’s purpose was to understand whether p-tau effects this mediation model and whether education level differentially impacts the relations between these genetic and biological biomarkers’ influence on memory.Participants and Methods:Participants included 161 older adults (M=74 years, 40.4% female, 92% White, 74 e4 non-carriers, 87 e4 carriers) with subjective and objective cognitive impairment from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A composite memory score created by ADNI was used as the outcome variable. Mean fractional anisotropy (FA) and radial diffusivity (RD) values of white matter tracts within regions of interest (i.e., fornix (FX), hippocampal cingulum (CGH)) were individually used as the measures of WMM. A moderated mediation was run to examine whether p-tau was a moderator of the mediation between APOE4, white matter microstructure, and memory. An exploratory dual moderated mediation analysis examined education as a moderator of the moderated mediation. Indirect effects were tested using bootstrapping procedures.Results:In the FA moderated mediation model, APOE4 was significantly related to FA of the fornix and memory performance. FA of the CGH and FX were also related to memory performance. With FA of the fornix as the mediator, the conditional indirect effect was not significant (95% CI[-.0009, .0070]). There was a trend suggesting at low (95% CI[-.2421, -.0140]) and average (95% CI[-.1658, -.0083]) levels of p-tau, FA of the fornix was a significant mediator but was non-significant at high levels of p-tau (95% CI [-.1322, .0341]). The RD moderated mediation model was non-significant. The FA and RD exploratory dual moderated mediation models were non-significant. However, the APOE4 x p-tau interaction with FA of the fornix as the mediator suggested a trend. At low levels of p-tau, increased education was related to a significant moderated mediation.Conclusions:Results suggest that FA of the fornix is a significant mediator between the relation of APOE4 and memory, and this may be dependent upon p-tau levels. When p-tau burden load was high, the path by which APOE4 impacts memory performance was not through white matter microstructure degradation. Additionally, the potential buffering effects of education may be most robust at lower levels of p-tau burden.

54 Exploring the Impact of Stria Terminalis Connectivity and Family Income on Depressive Symptoms Throughout Development

Objective:The stria terminalis (ST) is a white matter tract with connections to limbic and autonomic brain structures that is implicated in affective functioning. Recent works suggests that ST functional integrity and connectivity is associated with faster responses to emotional cues (Dzafic et al., 2019) and may be influenced by environmental factors including socioeconomic status (SES) and childhood adversity (Banihashemi et al., 2020). The role of the ST in the experience of more daily affective experiences, such as depressive symptoms, remains unexplored. Therefore, the present study examined the role of the ST and SES, as assessed by household income, in the relationship between age and depressive symptoms in typically developing children and adolescents.Participants and Methods:Participants include 64 typically developing children and adolescents age 8-21 (Mage=13.27, SD=3.15) who participated in an ongoing study of development of neurocognitive and social-cognitive skills. Participants completed imaging on a 3Tesla MR Siemens PRISMA scanner. Tractography was executed via ENIGMA tract-based spatial statistics to quantify WM integrity and provided values for mean fractional anisotropy (mFA) of the ST. Depressive symptoms were measured with the Behavior Assessment Scale for Children-Third Edition (BASC-3) parent report scale, and annual family income was obtained per parent report. Mediation and moderation analyses were conducted using Process version 4.1 (Hayes, 2022) in SPSS version 28. As depression symptoms are often higher in early adolescence than later, we examined the indirect effect of age on depressive symptoms through ST mFA and evaluated this relationship at different levels of family income.Results:Age was associated with lower levels of depressive symptoms (b=-.98, t=-2.18, p&lt;.05), whereas greater right ST mFA was associated with higher levels of depressive symptoms (b=42.05, t=2.50, p&lt;.05). Right ST mFA explained significant variance in the relationship between age and parent-reported depression (ab=.13, 95% CI [.02, .29]). The conditional indirect effect of family income was significant for children with annual family incomes between 25-50k (effect=.16, 95% CI [.01, .38]) and 75-100k (effect=.13, 95% CI [.001, .31]), but not for 100k+ (effect=.11, 95% CI [-.05, .33]).Conclusions:The present study revealed a significant, positive relationship between white matter integrity in the right ST and parent-reported depressive symptoms in healthy children and young adults. Finding extend on prior work implicating the ST in threat responsivity (Dzafic et al., 2019). Moreover,results suggest the role of the ST in the relationship between age and depression depends on level of family income, such that ST mFA explains more variance at lower income levels, and is no longer significant for children from families with income greater than 100k. These findings support the notion that environmental stressors (such as lower family income) may strengthen ST pathways via activity-dependent plasticity and repeated, coordinated activation (Rinaman et al., 2011). Future studies should examine these brain-behavior associations, as they may replicate in a larger sample, with more nuanced indicators of environmental stress.

MRI of brachial plexus using diffusion tensor imaging: a pilot study for the use of resolve sequence surgical and radiologic anatomy.

Clinical exam is the goldstandard for surgical indication. ENMG and conventional MRI are insufficient to understand the highly variable clinical presentation of brachial plexus (BP) lesions. DTI is based on motion of water molecules and can explore nerve function. This pilot study of healthy subjects aimed to develop RESOLVE sequence for BP exploration using diffusion MRI. The main objective was to provide complete precise information from DTI cartography associated with anatomical data. Six healthy volunteers were scanned using 3T PRISMA scanner with anatomic 3D STIR SPACE and RESOLVE diffusion sequences. Diffusion parametric maps of fractional anisotropy (FA) were extracted from RESOLVE acquisitions. A reproducible method for roots volumes and angles measurements was created using 3DSlicer. ROI were segmented on Mean B0 sequences. FA measurements were obtained with ROI on Mean B0 sequences. RESOLVE sequence was adapted to the BP. Mean FA was 0.30. Angles measurements on 3D STIR SPACE sequences showed increasing values from proximal to distal roots with an 0.6 ICC. Volume measurements on anatomic sequences varied widely from one root to another but did not show any significant difference on laterality. A new and reproducible method for BP exploration was developed, using MRI RESOLVE DTI sequences. Complete mapping was obtained but a low resolution of track density imaging did not allow to exploit distal nerves. Deterministic tractography principal limit was the lack of resolution. Extraction of diffusion, volumetric and angular parameters of the plexus roots, and scripts creation for image processing was adapted to the healthy BP.

Role of diffusion tensor imaging in stenotic and non-stenotic spinal canal

Background and purposeCervical Spondylotic Myelopathy (CSM) is a gradually escalating spinal cord disturbance set in motion by the degenerative narrowing of the vertebral canal. Routine MRI may fail to detect the subtle early alterations of the cord. MRI Diffusion Tensor Imaging (DTI) possesses the potential to detect these changes. This study intends to estimate the potential of the DTI technique in non-stenotic & stenotic spinal canals in individuals affected with CSM. MethodologySixty-four subjects who met the requirements of the inclusion criteria were incorporated into the investigation. All subjects underwent routine MRI sequences in addition to DTI of the cervical spine region. Scalars such as Fractional Anisotropy (FA), besides Apparent Diffusion Coefficient (ADC), were computed at each cervical intervertebral fibrocartilaginous disc level for all subjects. DTI fiber tractography was then performed to qualitatively assess the microstructural integrity of the tracts. ResultsA noteworthy difference (p<0.05) was seen in the FA parameter and ADC parameter values between the stenotic and non-stenotic groups, with the non-stenotic group having a higher mean FA and a lower ADC than the stenotic group (at the level of stenosis). A significant difference in age was seen between both groups, with most of the patients in the stenotic group belonging to 40 years and above. Tractography helped in demonstrating the morphology of the fiber tracts. ConclusionDTI parameters, namely FA and ADC, are sensitive to damage to the white matter and can be used to detect microstructural changes in the cord. However, standardization of the protocol is necessary when imaging the spinal canal.

Disturbed white matter integrity on diffusion tensor imaging in young children with epilepsy

To evaluate whether abnormalities in white matter (WM) integrity are present in young children with epilepsy. Twelve children (3-6 years old) with epilepsy and six matched healthy controls were recruited for brain diffusion tensor imaging (DTI). Track-based spatial statistics (TBSS) was used to analyse and compare DTI indices of mean diffusivity (MD), fractional anisotropy (FA), axial and radial diffusivity (AD/RD) between patients and controls, and correlations between clinical variables and DTI parameters were analysed. Compared with controls, patients showed increased FA in the left superior corona radiata and increased AD in the bilateral superior corona radiata. In children with generalised epilepsy, FA was increased in the left external capsule, while AD was decreased in the body of the corpus callosum, the left external capsule and the left superior longitudinal fasciculus. In those with focal epilepsy, FA was increased in the genu and body of the corpus callosum, and RD was decreased in the genu of the corpus callosum and left external capsule. Compared with partial epilepsy, generalised epilepsy was associated with increased FA in the right anterior corona radiata and decreased RD in the right anterior corona radiata and the genu and body of the corpus callosum. No significant correlations were observed between clinical variables and DTI parameters. The results of this study indicate that the microstructure of the white matter is disturbed by epileptic discharges and a compensatory response occurs during early brain development.

Effects of Damage to the Integrity of the Left Dual-Stream Frontotemporal Network Mediated by the Arcuate Fasciculus and Uncinate Fasciculus on Acute/Subacute Post-Stroke Aphasia.

(1) Background: To investigate the correlation between the integrity of the left dual-stream frontotemporal network mediated by the arcuate fasciculus (AF) and uncinate fasciculus (UF), and acute/subacute post-stroke aphasia (PSA). (2) Methods: Thirty-six patients were recruited and received both a language assessment and a diffusion tensor imaging (DTI) scan. Correlations between diffusion indices in the bilateral LSAF/UF and language performance assessment were analyzed with correlation analyses. Multiple linear regression analysis was also implemented to investigate the effects of the integrity of the left LSAF/UF on language performance. (3) Results: Correlation analyses showed that the diffusion indices, including mean fractional anisotropy (FA) values and the fiber number of the left LSAF rather than the left UF was significantly positively associated with language domain scores (p < 0.05). Multiple linear regression analysis revealed an independent and positive association between the mean FA value of the left LSAF and the percentage score of language subsets. In addition, no interaction effect of the integrity of the left LSAF and UF on language performance was found (p > 0.05). (4) Conclusions: The integrity of the left LSAF, but not the UF, might play important roles in supporting residual language ability in individuals with acute/subacute PSA; simultaneous disruption of the dual-stream frontotemporal network mediated by the left LSAF and UF would not result in more severe aphasia than damage to either pathway alone.

Diffusion tensor imaging in trigeminal neuralgia: beyond the normal morphology

BackgroundTrigeminal neuralgia (TN) is an electric-like recurrent pain of a sudden onset and is localized to the area supplied by the trigeminal nerve, and the patients are usually free in between the attacks. It’s one of the most common causes of facial pain and is commonly induced by mechanical irritation, and there’s strong evidence suggesting an insult at the trigeminal nerve root which is usually caused by a neurovascular compression. The aim of the study was to evaluate the role of diffusion tensor imaging (DTI) in the detection of microstructural changes of normal appearing trigeminal nerve in patients with trigeminal neuralgia and the correlation between DTI parameters and pain severity.ResultsThirty one cases were included in the study (16 patients with TN and 15 healthy controls) underwent MRI with diffusion tensor imaging. The fractional anisotropy (FA) values of the trigeminal nerves were recorded and then comparison between the affected and unaffected sides in TN patients and healthy controls was done, also the degree of FA reduction was correlated with the pain severity in TN groups. The mean FA value of the affected trigeminal nerves was 0.43 ± 0.083, while that of the unaffected sides was 0.56 ± 0.058. The mean FA value of the trigeminal nerves in the healthy controls was 0.54 ± 0.057. A significant statistical differences was found between affected and unaffected sides (P < 0.00001) and between the affected sides and healthy controls (P < 0.0003), while no statistically significant difference was detected between the unaffected side and the healthy controls. A strong negative correlation was found between the pain score and the degree of FA reduction (P < 0.001).ConclusionsDiffusion tensor imaging is a functional MRI technique which can detect the microstructural changes in the normal appearing trigeminal nerves in patients with trigeminal neuralgia with a strong negative correlation between the severity of pain and the degree of FA reduction of the affected trigeminal nerve.

Anxiety in Parkinson's Disease Is Associated with Changes in Brain Structural Connectivity.

Anxiety in Parkinson's disease (PD) has been associated with grey matter changes and functional changes in anxiety-related neuronal circuits. So far, no study has analyzed white matter (WM) changes in patients with PD and anxiety. The aim of this study was to identify WM changes by comparing PD patients with and without anxiety, using diffusion-tensor imaging (DTI). 108 non-demented PD patients with (n = 31) and without (n = 77) anxiety as defined by their score on the Parkinson Anxiety Scale participated. DTI was used to determine the fractional anisotropy (FA) and mean diffusivity (MD) in specific tracts within anxiety-related neuronal circuits. Mean FA and MD were compared between groups and correlated with the severity of anxiety adjusted by sex, center, Hoehn & Yahr stage, levodopa equivalent daily dosage, and Hamilton depression rating scale. Compared to patients without anxiety, PD patients with anxiety showed lower FA within the striato-orbitofrontal, striato-cingulate, cingulate-limbic, and caudate-thalamic tracts; higher FA within the striato-limbic and accumbens-thalamic tracts; higher MD within the striato-thalamic tract and lower MD within the striato-limbic tract. Anxiety in PD is associated with microstructural alterations in anxiety-related neuronal circuits within the WM. This result reinforces the view that PD-related anxiety is linked to structural alteration within the anxiety-related brain circuits.

Noninvasive Prediction of Sperm Retrieval Using Diffusion Tensor Imaging in Patients with Nonobstructive Azoospermia.

Microdissection testicular sperm extraction (mTESE) is the first-line treatment plan for nonobstructive azoospermia (NOA). However, studies reported that the overall sperm retrieval rate (SRR) was 43% to 63% among men with NOA, implying that nearly half of the patients fail sperm retrieval. This study aimed to evaluate the diagnostic performance of parameters derived from diffusion tensor imaging (DTI) in predicting SRR in patients with NOA. Seventy patients diagnosed with NOA were enrolled and classified into two groups based on the outcome of sperm retrieval during mTESE: success (29 patients) and failure (41 patients). Scrotal magnetic resonance imaging was performed, and the DTI parameters, including mean diffusivity and fractional anisotropy, were analyzed between groups. The results showed that there was a significant difference in mean diffusivity values between the two groups, and the area under the curve for mean diffusivity was calculated as 0.865, with a sensitivity of 72.2% and a specificity of 97.5%. No statistically significant difference was observed in fractional anisotropy values and sex hormone levels between the two groups. This study demonstrated that the mean diffusivity value might serve as a useful noninvasive imaging marker for predicting the SRR of NOA patients undergoing mTESE.

Cerebellar growth, volume and diffusivity in children cooled for neonatal encephalopathy without cerebral palsy

Children cooled for HIE and who did not develop cerebral palsy (CP) still underperform at early school age in motor and cognitive domains and have altered supra-tentorial brain volumes and white matter connectivity. We obtained T1-weighted and diffusion-weighted MRI, motor (MABC-2) and cognitive (WISC-IV) scores from children aged 6–8 years who were cooled for HIE secondary to perinatal asphyxia without CP (cases), and controls matched for age, sex, and socioeconomic status. In 35 case children, we measured cerebellar growth from infancy (age 4–15 days after birth) to childhood. In childhood, cerebellar volumes were measured in 26 cases and 23 controls. Diffusion properties (mean diffusivity, MD and fractional anisotropy, FA) were calculated in 24 cases and 19 controls, in 9 cerebellar regions. Cases with FSIQ ≤ 85 had reduced growth of cerebellar width compared to those with FSIQ > 85 (p = 0.0005). Regional cerebellar volumes were smaller in cases compared to controls (p < 0.05); these differences were not significant when normalised to total brain volume. There were no case–control differences in MD or FA. Interposed nucleus volume was more strongly associated with IQ in cases than in controls (p = 0.0196). Other associations with developmental outcome did not differ between cases and controls.

Detection of recurrent high-grade glioma using microstructure characteristics of distinct metabolic compartments in a multimodal and integrative 18F-FET PET/fast-DKI approach

ObjectivesDifferentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-18F-fluoroethyl)-l-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping.MethodsFifty-nine participants with neuropathologically confirmed recurrent HGG (n = 39) or PTRE (n = 20) were investigated using static 18F-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80–100% and 60–75% areas of 18F-FET uptake) compartments were assessed. Comparative analysis was performed using Mann–Whitney U tests with Holm-Šídák multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman’s correlation analysis were used for statistical evaluations.ResultsCompared to PTRE, recurrent HGG presented increased 18F-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p < .05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance — most pronounced for FA60 (AUC = 0.86, p < .001), which presented similar benefit to 18F-FET PET (AUC = 0.86, p < .001) and was negatively correlated with amino acid uptake (rs = − 0.46, p < .001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax + FA60 showed highest diagnostic accuracy (AUC = 0.93, p < .001), which improved the detection of relapse compared to PET alone (difference in AUC = 0.069, p = .04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting.ConclusionDetection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone.Clinical relevance statementA multimodal and integrative 18F-FET PET/fast-DKI approach for the non-invasive microstructural characterization of metabolic compartments provided improved diagnostic capability for differentiation between recurrent glioma and post-treatment-related changes, suggesting a role for the diagnostic workup of patients in post-treatment settings.Key Points• Multimodal PET/MRI with integrative analysis of 18F-FET PET and fast-DKI presents clinical benefit for the assessment of CNS cancer, particularly for the detection of recurrent high-grade glioma.• Microstructure markers of the metabolic periphery yielded biologically pertinent estimates characterising the tumour microenvironment, and, thereby, presented improved diagnostic accuracy with similar accuracy to amino acid PET.• Combined 18F-FET PET/fast-DKI achieved the best diagnostic performance for detection of high-grade glioma relapse with significant benefit to the assessment based on PET alone.

Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury

BackgroundIt is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI.MethodsNinety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups.ResultsThe levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001—p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found.ConclusionIn patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.

Spherical means-based free-water volume fraction from diffusion MRI increases non-linearly with age in the white matter of the healthy human brain

The term free-water volume fraction (FWVF) refers to the signal fraction that could be found as the cerebrospinal fluid of the brain, which has been demonstrated as a sensitive measure that correlates with cognitive performance and various neuropathological processes. It can be quantified by properly fitting the isotropic component of the magnetic resonance (MR) signal in diffusion-sensitized sequences. Using N=287 healthy subjects (178F/109M) aged 25-94, this study examines in detail the evolution of the FWVF obtained with the spherical means technique from multi-shell acquisitions in the human brain white matter across the adult lifespan, which has been previously reported to exhibit a positive trend when estimated from single-shell data using the bi-tensor signal representation. We found evidence of a noticeably non-linear gain after the sixth decade of life, with a region-specific variate and varying change rate of the spherical means-based multi-shell FWVF parameter with age, at the same time, a heteroskedastic pattern across the adult lifespan is suggested. On the other hand, the FW corrected diffusion tensor imaging (DTI) leads to a region-dependent flattened age-related evolution of the mean diffusivity (MD) and fractional anisotropy (FA), along with a considerable reduction in their variability, as compared to the studies conducted over the standard (single-component) DTI. This way, our study provides a new perspective on the trajectory-based assessment of the brain and explains the conceivable reason for the variations observed in FA and MD parameters across the lifespan with previous studies under the standard diffusion tensor imaging.

Properties of white matter tract diffusivity in children with developmental dyslexia and comorbid attention deficit/hyperactivity disorder

BackgroundDevelopmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored.MethodsParticipants were 3rd and 4th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants.ResultsDD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found.ConclusionsFindings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD.