A 3D pseudo-continuous arterial spin labeling study of altered cerebral blood flow correlation networks in mild cognitive impairment and Alzheimer's disease.

Objective: To investigate the abnormalities of the three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) based cerebral blood flow (CBF) correlation networks in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: 3D PCASL images of 53 cognitive normal (CN) subjects, 43 subjects with MCI, and 30 subjects with AD were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Whole-brain CBF maps were calculated using PCASL and proton density-weighted images (PDWI). The 246 regional CBF values, including the cortex and subcortex, were obtained after registering the Brainnetome Atlas to the individual CBF maps. The Pearson correlation coefficient between every two regions across subjects was calculated to construct the CBF correlation network. Then the topologies of CBF networks with regard to global properties (global network efficiency, clustering coefficient, characteristic path length, and small-world properties), hub regions, nodal properties (betweenness centrality, BC), and connections were compared among CN, MCI, and AD. Significant changes in the global and nodal properties were observed in the permutation tests, and connections with significant differences survived after the z-statistic and false discovery rate (FDR) correction. Results: The CBF correlation networks of CN, MCI, and AD all showed small-world properties. Compared with CN, global efficiency decreased significantly in AD. Significant differences in nodal properties and a loss of hub regions are noted in the middle temporal lobe in both MCI and AD. In the frontal lobe, BC is reduced in MCI while it is increased in the occipital lobe in AD. The identified altered hub regions with significant differences in MCI and AD were mainly distributed in the hippocampus and entorhinal cortex. In addition, disrupted hub regions in AD with significantly decreased connections were mainly found in the precuneus/posterior cingulate cortex (PCC) and hippocampus-cortical cortex. Conclusions: Noninvasive 3D PCASL-based CBF correlation networks are capable of showing changes in topological organization in subjects with MCI and AD, and the observed disruption in the topological organization may underlie cognitive decline in MCI and AD.

Disrupted white matter microstructure correlates with impulsivity in children and adolescents with bipolar disorder.

Altered white matter (WM) microstructure likely occurs in children with bipolar disorder (BD) with impulsivity representing one of the core features. However, altered WM microstructures and their age-related trendlines in children with BD and those at high-risk of developing BD, as well as correlations of WM microstructures with impulsivity, have been poorly investigated. In this study, diffusion MRI, cognitive, and impulsivity assessments were obtained from children/adolescents diagnosed with BD, offspring of individuals with BD (high-risk BD) and age-matched healthy controls. A novel atlas-based WM skeleton measurement approach was used to quantify WM microstructural integrity with all diffusion-tensor-imaging (DTI) metrics including fractional anisotropy, axial, mean and radial diffusivity to survey entire WM tracts and ameliorate partial volume effects. Among all DTI-derived metric measures, radial diffusivity quantifying WM myelination was found significantly higher primarily in corpus callosum and in the corona radiata in children with BD compared to controls. Distinguished from age-related progressively decreasing diffusivities and increasing fractional anisotropy in healthy controls, flattened age-related trendlines were found in BD group, and intermediate developmental rates were observed in high-risk group. Larger radial diffusivity in the corpus callosum and corona radiata significantly correlated with shorter response times to affective words that indicate higher impulsivity in the BD group, whereas no such correlation was found in the healthy control group. This work corroborates the progressive nature of pediatric BD and suggests that WM microstructural disruption involved in affective regulation and sensitive to impulsivity may serve as a biomarker of pediatric BD progression.

Single-direction diffusion-weighted imaging may be a simple complementary sequence for evaluating fetal corpus callosum.

OBJECTIVES: To explore the feasibility of single-direction diffusion-weighted imaging (DWI) for assessing the fetal corpus callosum (CC). METHODS: This prospective study included 67 fetuses with normal CC and 35 fetuses suspected with agenesis of the corpus callosum (ACC). The MR protocols included HASTE, TrueFISP, and single-direction DWI. Two radiologists independently evaluated the optimal visibility and the contrast ratio (CR) of the normal fetal CC. The Chi-squared test or Fisher's exact test was used to compare the proportions of "good" visibility (score ≥ 3, and the CC was almost/entirely visible) between single-direction DWI and HASTE/TrueFISP. The CR difference between single-direction DWI and HASTE/TrueFISP was detected using the paired t-test. The diagnostic accuracies were determined by comparison with postnatal imaging. In fetuses suspected of ACC, we measured and compared the length and area of the mid-sagittal CC in the single-direction DWI images. RESULTS: The proportion of "good" visibility in single-direction DWI was higher than that in HASTE/TrueFISP, with p < 0.0001. The mean CR from single-direction DWI was also higher than that of TrueFISP and HASTE (both with p < 0.0001). The diagnostic accuracy of the single-direction DWI combined with HASTE/TrueFisp (97.1%, 34/35) was higher than that of the Haste/TrueFISP (74.3%, 26/35) (p = 0.013). The length and area of the PACC (p < 0.001, p = 0.001, respectively) and HCC (p < 0.001, p = 0.018, respectively) groups were significantly lower than those of the normal group. CONCLUSIONS: The single-direction DWI is feasible in displaying fetal CC and can be a complementary sequence in diagnosing ACC. KEY POINTS: • We suggest a simple method for the display of the fetal CC. • The optimal visibility and contrast ratio from single-direction DWI were higher than those from HASTE and TrueFISP. • The diagnostic accuracy of the single-direction DWI combined with HASTE/TrueFISP sequences (97.1%, 34/35) was higher than that of the Haste/TrueFISP (74.3%, 26/35).

Neuroanatomical underpinning of diffusion kurtosis measurements in the cerebral cortex of healthy macaque brains.

PURPOSE: To investigate the neuroanatomical underpinning of healthy macaque brain cortical microstructure measured by diffusion kurtosis imaging (DKI), which characterizes non-Gaussian water diffusion. METHODS: High-resolution DKI was acquired from 6 postmortem macaque brains. Neurofilament density (ND) was quantified based on structure tensor from neurofilament histological images of a different macaque brain sample. After alignment of DKI-derived mean kurtosis (MK) maps to the histological images, MK and histology-based ND were measured at corresponding regions of interests characterized by distinguished cortical MK values in the prefrontal/precentral-postcentral and temporal cortices. Pearson correlation was performed to test significant correlation between these cortical MK and ND measurements. RESULTS: Heterogeneity of cortical MK across different cortical regions was revealed, with significantly and consistently higher MK measurements in the prefrontal/precentral-postcentral cortex compared to those in the temporal cortex across all six scanned macaque brains. Corresponding higher ND measurements in the prefrontal/precentral-postcentral cortex than in the temporal cortex were also found. The heterogeneity of cortical MK is associated with heterogeneity of histology-based ND measurements, with significant correlation between cortical MK and corresponding ND measurements (P < .005). CONCLUSION: These findings suggested that DKI-derived MK can potentially be an effective noninvasive biomarker quantifying underlying neuroanatomical complexity inside the cerebral cortical mantle for clinical and neuroscientific research.

Flattened Structural Network Changes and Association of Hyperconnectivity With Symptom Severity in 2-7-Year-Old Children With Autism.

Understanding the brain differences present at the earliest possible diagnostic age for autism spectrum disorder (ASD) is crucial for delineating the underlying neuropathology of the disorder. However, knowledge of brain structural network changes in the early important developmental period between 2 and 7 years of age is limited in children with ASD. In this study, we aimed to fill the knowledge gap by characterizing age-related brain structural network changes in ASD from 2 to 7 years of age, and identify sensitive network-based imaging biomarkers that are significantly correlated with the symptom severity. Diffusion MRI was acquired in 30 children with ASD and 21 typically developmental (TD) children. With diffusion MRI and quantified clinical assessment, we conducted network-based analysis and correlation between graph-theory-based measurements and symptom severity. Significant age-by-group interaction was found in global network measures and nodal efficiencies during the developmental period of 2-7 years old. Compared with significant age-related growth of the structural network in TD, relatively flattened maturational trends were observed in ASD. Hyper-connectivity in the structural network with higher global efficiency, global network strength, and nodal efficiency were observed in children with ASD. Network edge strength in ASD also demonstrated hyper-connectivity in widespread anatomical connections, including those in default-mode, frontoparietal, and sensorimotor networks. Importantly, identified higher nodal efficiencies and higher network edge strengths were significantly correlated with symptom severity in ASD. Collectively, structural networks in ASD during this early developmental period of 2-7 years of age are characterized by hyper-connectivity and slower maturation, with aberrant hyper-connectivity significantly correlated with symptom severity. These aberrant network measures may serve as imaging biomarkers for ASD from 2 to 7 years of age.