Deep Learning-based Hierarchical Brain Segmentation with Preliminary Analysis of the Repeatability and Reproducibility

Quantitative comparisons of three automated methods for estimating intracranial volume: A study of 270 longitudinal magnetic resonance images

This study aimed to investigate the resting-state functional connectivity of the hypothalamus and its relationships with gonadal steroid hormones and depression symptoms in perimenopausal women. Total 66 perimenopausal women voluntarily participated in this study from October 2012 to June 2013. Zung Self-rating Depression Scale (ZSDS) was used to assess depression symptoms. Plasma gonadal steroid hormones including estradiol, testosterone, and progesterone were determined by the chemiluminescence immunoassay. A 3.0 Tesla magnetic resonance imaging (MRI) scanner was utilized to acquire resting-state functional MRI data. The z-value functional connectivity map of each participant was calculated voxel-wisely based on the seed region of the hypothalamus. One sample t test of Statistical Parametric Mapping (SPM) were used to determine the brain areas with statistically significant functional connectivity to the hypothalamus, then multiple regression of SPM was used to calculate the correlated areas with 3 gonadal steroid hormones, respectively. Finally, Pearson correlation was performed to analyze bivariate correlations between mean z-values and ZSDS scores. Significant functional connectivity to the hypothalamus were found in brain areas as follows:the lateral inferior frontal gyrus, medial prefrontal cortex, dorsal lateral prefrontal cortex, orbitofrontal cortex, subgenual cortex, anterior cingulate cortex, posterior cingulate cortex, cuneus and precuneus, hippocampus and parahippocampal gyrus, and angular gyrus (False Discovery Rate q<0.05). Among these areas, the plasma testosterone level was positively related to the functional connectivity strength of the right angular gyrus, and negatively related to the strengths of the right subgenual cortex and bilateral medial superior frontal gyrus to the hypothalamus (PAlphaSim<0.05). Especially, mean z-value in the subgenual cortex was positively related to the ZSDS index score (r=0.279, P=0.023), and factor scores of the core depression symptoms (r=0.278, P=0.024) and somatic symptoms (r=0.357, P=0.003). In perimenopausal women, the hypothalamus has resting-state functional connectivity with widespread areas involved in the brain depression-related network and default mode network, and the plasma androgen level may modulate the functional connectivity strengths of the hypothalamus and decrease the susceptibility of perimenopausal women to depression.

Autism Spectrum Disorder (ASD) encompasses a range of neurodevelopmental disorders, and early detection is crucial. This study aims to identify the Regions of Interest (ROIs) with significant differences between healthy controls and individuals with autism, as well as evaluate the agreement between FreeSurfer 6 (FS6) and Computational Anatomy Toolbox (CAT12) methods. Surface-based and volume-based features were extracted from FS software and CAT12 toolbox for Statistical Parametric Mapping (SPM) software to estimate ROI-wise biomarkers. These biomarkers were compared between 18 males Typically Developing Controls (TDCs) and 40 male subjects with ASD to assess group differences for each method. Finally, agreement and regression analyses were performed between the two methods for TDCs and ASD groups. Both methods revealed ROIs with significant differences for each parameter. The Analysis of Covariance (ANCOVA) showed that both TDCs and ASD groups indicated a significant relationship between the two methods (p<0.001). The R2 values for TDCs and ASD groups were 0.692 and 0.680, respectively, demonstrating a moderate correlation between CAT12 and FS6. Bland-Altman graphs showed a moderate level of agreement between the two methods. The moderate correlation and agreement between CAT12 and FS6 suggest that while some consistency is observed in the results, CAT12 is not a superior substitute for FS6 software. Further research is needed to identify a potential replacement for this method.

The present study aims to assess the prevalence, associated clinical symptoms, longitudinal changes, and imaging correlates of Loss of Insight (LOI), which is still unexplored in syndromes associated with Frontotemporal Lobar Degeneration (FTLD). Retrospective longitudinal cohort study, from Oct 2009 to Feb 2023. Tertiary Frontotemporal Dementia research clinic. A sample of 712 FTLD patients, 331 of whom had follow-up evaluation. LOI was assessed by interview with the primary caregiver. Univariate and multiple logistic regression and linear mixed models were used to estimate predictors and longitudinal changes over time associated with LOI. Voxel-based morphometry and structural covariance analyses of brain structural MRI images were implemented in Statistical Parametric Mapping. LOI was reported in 45% of patients (321/712, 95%CI = 41-49), with progressively increased prevalence from prodromal to severe dementia stages. LOI was more prevalent in the behavioural variant FTD, in the semantic variant of Primary Progressive Aphasia (svPPA) and FTD with Amyotrophic Lateral Sclerosis than in other phenotypes (all p-values<0.001). LOI severity increased over time only in patients with svPPA (β = +0.59, p <0.001) and clustered with other behavioral symptoms (all p-values <0.05). Finally, LOI was significantly associated with greater atrophy in the right medial orbital gyrus (p <0.001 uncorrected). Structural covariance analysis demonstrated loss of negative correlation between right medial orbital gyrus and regions belonging to the Default Mode Network (DMN), such as the left precuneus and the left angular gyrus (p ≤0.05 family-wise error-corrected) in FTLD patients with LOI. A better comprehension of LOI mechanisms could lead to more effective interventions and healthcare policies.

To use both whole-brain and normal-appearing brain tissue (NABT) T1 relaxation time histograms to investigate abnormalities in early relapsing-remitting (RR) multiple sclerosis (MS). In patients with established MS, both lesions and NABT exhibit an increase in T1 relaxation time. By using T1 histogram analysis, it is hoped that such changes in early disease can be detected. Twenty-seven patients and 14 age- and sex-matched controls underwent magnetic resonance imaging (MRI) of the brain, which included the following sequences: 1) proton density (PD)- and T2-weighted fast spin echo (FSE) to measure T2 lesion load, 2) PD- and T1-weighted gradient echos from which T1 relaxation was calculated, and 3) T1-weighted SE imaging pre- and post-triple dose (0.3 mmol/kg) gadolinium (Gd-DTPA) to measure T1 hypointense and gadolinium-enhancing lesion loads, respectively. All patients had RR MS with disease duration <3 years (median 1.7 years). Statistical parametric mapping (SPM) 99 was used to segment brain from cerebrospinal fluid (CSF), and lesions were segmented using a local thresholding technique. Both whole-brain and NABT histograms were abnormal for all six T1 histogram parameters that were measured. For NABT, the mean T1 was 1,027 (+/- 74) ms in patients and 969 (+/- 41) ms in controls (p=0.003). There was little difference between the global and NABT histograms, which indicates that most of the whole-brain histogram abnormality derives from normal-appearing tissues. There was a correlation between the Nine-Hole Peg Test and NABT T1 measures. There are widespread abnormalities of NABT in early RR MS, which were sensitively detected by T1 relaxation time histogram analysis. As such, T1 histogram analysis appears promising for studying the natural history of early RR MS, and in the monitoring of response to treatment

Enhancing reproducibility of fMRI statistical maps using generalized canonical correlation analysis in NPAIRS framework

Objective To explore the significance of language proficiency in bilingual perception in Chinese-English late bilingual subjects with block-design functional magnetic resonance imaging (bfMRI). Methods Thirteen right-handed Chinese Han healthy male late bilinguists who had limited English proficiency were scanned while listening to short sentences in Chinese and English. Based on blood oxygenation level-dependent (BOLD) signal efficacy, functional images were collected using a 1.5-T MRI. Statistical parametric mapping 2 (SPM2) was used to analyze the data of functional images (P 100). Results For Chinese familiar voices, more significant activation was observed in the right superior temporal gyrus than that for English familiar voices. On the contrary, more significant activations for English familiar voices were observed in the left precuneus, middle frontal gyrus and left posterior cingulate cortex compared with that for Chinese familiar voices.For Chinese unfamiliar voices, more significant activations were observed in the right middle temporal gyrus and right medial frontal gyrus than that for English unfamiliar voices. In contrast, more significant activations by English unfamiliar voices were observed in the right inferior frontal gyrus, middle frontal gyrus and left middle temporal gyrus compared with that for Chinese unfamiliar voices. Conclusion Language proficiency may play an important role in different language perception from auditory level. Key words: Language proficiency; Block design; Functional MRI

The primary objective of this study was to identify the metabolic pattern in the brains of betel quid dependent (BQD) individuals using 18 F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (18 F-FDG-PET). A total of 42 individuals (16 BQD individuals and 26 healthy controls, HCs) enrolled at the Department of Nuclear Medicine of Xiangya Hospital underwent brain 18 F-FDG-PET. Group comparisons using statistical parametric mapping (SPM) were performed to identify the 18 F-FDG-PET patterns. Standardized uptake value ratios of anterior cingulate, frontal, thalamus, parietal, occipital, temporal and cerebellum were calculated by SPM. The characteristics of abnormal metabolism in brain regions were quantified using the xjView toolbox, and a 3-D brain map was drawn using BrainNet Viewer. We found significant metabolic reduction in the bilateral middle prefrontal cortex (PFC) and the left orbital frontal gyrus (OFC). In contrast, hypermetabolism was observed in the inferior cerebellum, fusiform, superior cerebellum, parahippocampal, vermis, lingual and thalamus. However, we found no significant difference between the BQD and HC group in the anterior cingulate, thalamus, cerebellum and frontal, temporal, parietal and occipital lobes. In summary, we found abnormal 18 F-FDG-PET metabolic pattern in BQD individuals, and this pattern may help the treatment of BQD.

Measurement of brain atrophy in subcortical vascular disease: A comparison of different approaches and the impact of ischaemic lesions

Objective To explore the changes of rest-state functional MRI (fMRI) features in patients with Parkinson's disease. Methods Twelve patients with Parkinson's disease, collected in our hospital from September 2013 to March 2014, and 12 volunteers (controls) were recruited. The fMRI based on blood oxygen level dependent (BOLD) was performed at resting state; the differences of amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) were statistically analyzed; and the correlations of values of ALFF and ReHo with uniformed Parkinsonism rating scale (UPDRS) scores and Hoehn-Yahr (H-Y) grading were analyzed. Results PD patients exhibited increased ALFF values in the limbic lobe, the right parahippocampal gyrus and the right middle temporal pole, and reduced ALFF values in the left thalamus as compared with the controls. PD patients exhibited increased ReHo values in the superior medial frontal gyrus, the left middle frontal gyrus, brodmann area (BA) 9 and medial frontal gyrus, and reduced ReHo values in the left rolandic, the left superior temporal gyrus and insula lobe as compared with the controls. ALFF values were positively correlated with the UPDRS III scores in the right posterior cerebellum lobe and cerebellar tonsil. ALFF values and H-Y grading were negatively correlated on the left superior frontal gyrus. Negative correlation was noted between the ReHo values and UPDRS III scores in the right superior temporal gyrus and insular lobe. Positive correlation was noted between the ReHo values and H-Y grading in medial frontal gyrus, limbic lobe, anterior cingulate, medial orbitofrontal area, middle superior frontal gyrus, BA32, left superior frontal gyrus and BA10. Conclusion By resting-state fMRI, abnormal brain function in Parkinson's disease was noted; ReHo and ALFF showed abnormal changes in the connection of neuronal networks, and the compensatory response may lead to the increased brain function. Key words: Parkinson’s disease; Functional MR imaging; Regional homogeneity; Amplitude of low frequency fluctuation

This study presents a visual rating scale for the assessment of cerebral [(18)F]fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) scans to characterize typical findings in dementias associated with frontotemporal lobar degeneration (FTLD) and to differentiate individual patients with FTLD compared to Alzheimer's disease (AD) and mild cognitive impairment (MCI). A total of 43 cerebral PET scans from patients with FTLD (n = 16, mean age 58.4 years), AD (n = 16, 59.9 years) and MCI (n = 11, 57.9 years) were analysed. Every PET data set was visually rated for seven brain regions on each hemisphere (frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, thalamus and cerebellum). The extent of the impairment in metabolism was classified as absent, mild, medium or strong. Using this four-stage visual rating scale, characteristic profiles of metabolic impairment in FTLD, AD, MCI and the FTLD-subgroup FTD (n = 9) could be demonstrated. Patients with FTLD showed a significantly lower metabolism in the left frontal lobe and in the left basal ganglia when compared to AD and to MCI. Complementary analyses using statistical parametric mapping (SPM2) supported the findings of the visual analysis. In detecting FTLD with visual rating, sensitivity/specificity was 81/94% compared to AD and 81/64% compared to MCI. Patients with FTD were correctly attributed to a diagnosis of FTLD with a sensitivity of 89%. This visual rating scale may facilitate the differential diagnosis of FTLD in clinical routine.

Loss of noradrenergic neurons in a small brainstem nucleus, the locus coeruleus (LC), is a common characteristic in the development of age‐related neurodegenerative diseases such as Alzheimer's disease (AD) and other dementias. The noradrenergic system (NS) projects from the locus coeruleus (LC) throughout the brain to modulate neurophysiology for memory, learning and cognition, for regulation of sleep and circadian rhythm, and in response to stress and reward. Thus dysregulation of NS activity, i.e., blunted or tonic firing of LC neurons and its resultant effect on neural activity, is considered a significant factor in development and progression of neurodegenerative diseases as well as of psychiatric disorders. Our hypothesis is that tonic activation of LC neurons acutely discoordinates neuronal firing patterns across the brain, and ultimately provokes a prolonged abnormal brain state. We test this hypothesis via brain‐wide manganese‐enhanced MRI (MEMRI) in parallel with recordings of naturalistic behavior before, during, and long after chemogenetic (hM3Dq) stimulation of LC neurons. After systemic delivery, paramagnetic Mn(II) ions (0.3 mmol/kg, i.p.) accumulate in active neurons of awake‐behaving mice, highlighting neural activity by T1‐weighted MRI. Adult mice (3‐6 months) were subjected either to longitudinal MEMRI (n = 18) or to open field behavior (n = 8), ± hM3Dq expression; and ± designer drug – clozapine‐N‐oxide (CNO). For behavior naïve C57BL/6 mice were video recorded and behavioral parameters tracked by Noldus Ethovision XT15, before and after administration of CNO (5 mg/kg, i.p.). Mice then underwent stereotactic injection of CAV2‐PRS‐hM3D(Gq)‐mCherry targeting the LC (AP = ‐5.4, ML = ±0.80, DV = ‐3.80). At 4‐8 weeks after transfection the effect of CNO ± hM3Dq on LC neurons was monitored in live animals by pupillary light response. Pre‐ and post‐CNO behavior was again recorded. For MEMRI two groups ± hM3Dq were imaged before and after CNO. MEMRI images were analyzed for Mn(II)‐dependent intensity increases by statistical parametric mapping (SPM), segment‐wise cross‐correlation and network analysis. Transgene expression was confirmed post‐mortem by microscopy of mCherry in LC brain sections, which showed transgene expression in bilateral LC. Comparison of MEMRI segment‐wise intensities revealed changes of strength and direction of correlations between time points that also diffed between groups. Hierarchical clustering of these correlations revealed 40% increase in modularity, i.e., the number of distinct clusters, after CNO only in the hM3Dq transfected group. Together our data suggest discoordination of brain regions after LC‐NS activation. In neurodegenerative disease the loss of LC input could result in the opposite effects, while none‐the‐less leading to discoordination of brain‐wide activity underlying sleep disorders and memory disturbance. This brain‐wide imaging strategy with chemogenetic LC manipulation provides critical insight into NS modulation of neural activity under both normal and pathological conditions.

Generalizing deep learning brain segmentation for skull removal and intracranial measurements

EFFECT OF MEMANTINE ON BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA (BPSD) OF ALZHEIMER'S DISEASE - STUDY OF CHANGES IN CEREBRAL BLOOD FLOW BY SPECT IMAGING-

Neuroimage phenotyping for psychiatric and neurological disorders is performed using voxelwise analyses also known as voxel based analyses or morphometry (VBM). A typical voxelwise analysis treats measurements at each voxel (e.g., fractional anisotropy, gray matter probability) as outcome measures to study the effects of possible explanatory variables (e.g., age, group) in a linear regression setting. Furthermore, each voxel is treated independently until the stage of correction for multiple comparisons. Recently, multi-voxel pattern analyses (MVPA), such as classification, have arisen as an alternative to VBM. The main advantage of MVPA over VBM is that the former employ multivariate methods which can account for interactions among voxels in identifying significant patterns. They also provide ways for computer-aided diagnosis and prognosis at individual subject level. However, compared to VBM, the results of MVPA are often more difficult to interpret and prone to arbitrary conclusions. In this paper, first we use penalized likelihood modeling to provide a unified framework for understanding both VBM and MVPA. We then utilize statistical learning theory to provide practical methods for interpreting the results of MVPA beyond commonly used performance metrics, such as leave-one-out-cross validation accuracy and area under the receiver operating characteristic (ROC) curve. Additionally, we demonstrate that there are challenges in MVPA when trying to obtain image phenotyping information in the form of statistical parametric maps (SPMs), which are commonly obtained from VBM, and provide a bootstrap strategy as a potential solution for generating SPMs using MVPA. This technique also allows us to maximize the use of available training data. We illustrate the empirical performance of the proposed framework using two different neuroimaging studies that pose different levels of challenge for classification using MVPA.