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Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes., Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific., Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males., Discussion: Older females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies., Clinical Trial Registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14., (© 2024. The Author(s).)

Introduction: Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle-stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women., Methods: Two hundred twenty-two women (mean age = 59) underwent hormone assays (E1, E2, FSH) and 3T brain magnetic resonance imaging. Associations of hormones to WMHV were tested with linear regression., Results: Higher E2 (B[standard error (SE)] = -0.17[0.06], P = 0.008) and E1 (B[SE] = -0.26[0.10], P = 0.007) were associated with lower whole-brain WMHV, and higher FSH (B[SE] = 0.26[0.07], P = 0.0005) with greater WMHV (covariates age, race, education). When additionally controlling for cardiovascular disease risk factors, associations of E1 and FSH to WMHV remained., Discussion: Reproductive hormones, particularly E1 and FSH, are important to women's cerebrovascular health., Highlights: Despite widespread belief that sex hormones are important to women's brain health, little work has considered how these hormones in women relate to white matter hyperintensities (WMH), a major indicator of cerebral small vessel disease. We considered relations of estradiol (E2), estrone (E1), and follicle-stimulating hormone (FSH) to WMH in midlife women. Higher E2 and E1 were associated with lower whole-brain WMH volume (WMHV), and higher FSH with higher whole-brain WMHV. Associations of E1 and FSH, but not E2, to WMHV persisted with adjustment for cardiovascular disease risk factors. Findings underscore the importance of E2 and FSH to women's cerebrovascular health., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: A method for adaptively optimized combination (AOC) of MR spectroscopic data from a coil array was recently introduced. The superior performance of the AOC method is evident when compared with the methods that assume uncorrelated noise between coil elements. However, it is unclear whether the AOC method represents the most optimal combination in the presence of correlated noise, when compared with the noise-decorrelated or whitened methods that specifically tackle the correlated noise between coil elements., Methods: A new, unified theoretical framework was developed to illustrate the relationship between the AOC method and three noise-decorrelated or whitened methods, namely, noise-decorrelated combination (nd-comb), whitened singular value decomposition (WSVD), and improved WSVD (WSVD+Apod). Simulation-based comparisons and in vivo human brain experiments on a 3 Tesla (T) MRI scanner were performed using an 8-channel phased-array head coil., Results: Compared with the noise-decorrelated or whitened methods, the AOC method consistently yielded the best combination in terms of the robustness against noise and maintaining the combined spectrum from distortion, and the superior performance was most evident at a low signal-to-noise ratio (SNR)., Conclusion: The AOC method represents the theoretical optimal combination in the presence of correlated noise between coil elements, whereas the three noise-decorrelated or whitened methods are asymptotically optimal. Magn Reson Med 78:848-859, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: MR spectroscopy (MRS) can benefit from multi-element coil arrays with enhanced signal-to-noise ratio (SNR). However, how to combine the MRS data in an optimized way from a multi-element coil array has been studied much less than MRI. A recently published method and routine combination methods have detrimental effects on SNR. We present herein a new method for optimal combination of multi-coil MRS data., Methods: Based on an analytical solution for maximizing the SNR of the combined spectrum, a new method called "adaptively optimized combination (AOC)" of MRS data from phased array coils was developed in which the inversion of the full noise correlation matrix was incorporated into the coil weighting coefficients. Simulations were carried out to demonstrate the superior performance of the proposed AOC method in various noise scenarios. Validation experiments on human subjects were performed with different voxel locations and sizes on a 3T MRI scanner using an eight-element phased array head coil., Results: Compared with a recently published method (i.e., weighting with the ratio of signal to the square of noise) and routine methods, our proposed AOC method adaptively and robustly produced significant SNR improvement in the combined spectra., Conclusion: The simulation and human experiments demonstrate that the proposed AOC method represents the theoretical optimal combination of MR spectroscopic data from multi-element coil arrays. Magn Reson Med 75:2235-2244, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Previous research has shown that type 2 diabetes mellitus (T2DM) is associated with white matter microstructural changes, cognitive impairment, and decreased resting-state functional connectivity and spontaneous brain activity. This study used magnetization transfer imaging to examine, for the first time, the integrity of macromolecular protein pools in fronto-striato-thalamic circuits and its clinical and cognitive correlates in patients with T2DM. T2DM patients without mood disorders (n = 20, aged 65.05 ± 11.95 years) and healthy control subjects (HCs; n = 26, aged 62.92 ± 12.71 years) were recruited. Nodes of fronto-striato-thalamic circuits-head of the caudate nucleus (hCaud), putamen, globus pallidus, thalamus-and four cortical regions-rostral and dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex-were examined. Compared with HCs, patients with T2DM had significantly lower magnetization transfer ratio (MTR) in bilateral anterior cingulate and hCaud. Reduced MTRs in the above regions showed correlations with T2DM-related clinical measures, including hemoglobin A1c level and vascular risk factors, and neuropsychological task performance in the domains of learning and memory, executive function, and attention and information processing. The impaired biophysical integrity of brain macromolecular protein pools and their local microenvironments in T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-associated clinical and cognitive deficits., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Multiple brain morphometric changes have been reported in late-life depression (LLD), mostly in studies comparing volumes of circumscribed brain areas. The aim of our study is to characterize the volumetric changes of multiple gray matter regions in relation to age of onset/duration of illness. We predicted that the association of gray matter volumes with total duration of illness and age of onset would differ depending on whether the region was susceptible to the toxic effects of chronic exposure to cortisol or to the vascular/neurodegenerative changes accompanying prodromal dementia. Seventy-one elderly depressed subjects were studied along with thirty-two comparison subjects. High-resolution T1-weighted brain MRIs were processed using an automated labeling pathway technique. To protect against type-I error, we combined the right and left hemisphere volume data. We sampled 24 regions of interest (ROIs). We used the primary visual cortex volume to normalize for individual variations in brain size. LLD Subjects had smaller volumes than non-depressed subjects in 17 of the 24 examined ROIs. Shorter duration of illness and later age of onset was correlated with smaller volumes of parahippocampal area and parietal inferior area. A later age of onset was also correlated with smaller volumes of several frontal and temporal areas, cingulum, and putamen. Our findings support a dementia prodrome model more strongly than a toxic stress model in this group of subjects. However, it remains likely that both processes as well as other factors contribute to the heterogeneity of volumetric brain changes in LLD.

Background and Purpose: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer's disease (AD) among cognitively normal older adults., Methods: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60% women, 81% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD., Results: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions., Conclusions: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.

White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy-connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P<0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies (e.g. [Taylor, W.D., MacFall, J.R., Steffens, D.C., Payne, M.E., Provenzale, J.M., Krishnan, K.R., 2003. Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (3), 539-544.]), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large NeuroImage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders.

BACKGROUND:Since the onset of combination antiretroviral therapy use, the incidence of HIV-associated dementia and of HIV encephalitis has fallen dramatically. The present study investigates the extent of white matter hyperintensities (WMHs) among individuals with HIV disease, and factors that predict their presence and their impact on psychomotor speed. METHODS:A total of 322 men participating in the Multicenter AIDS Cohort Study (185 HIV-infected, age: 57.5 ± 6.0) underwent MRI scans of the brain. T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images were obtained and processed using an automated method for identifying and measuring WMHs. WMH burden was expressed as the log10 transformed percentage of total white matter. RESULTS:There were no significant associations between WMHs and HIV disease. However, the extent of WMHs was predicted by age more than 60 (β = 0.17), non-white race (β = 0.14), glomerular filtration rate (β = -0.11), and the presence of diabetes (β = 0.12). There were no interactions between HIV status and age (β = -0.03) or between age and diabetes (β = 0.07). However, the interaction between HIV infection and diabetes was significant (β = 0.26). The extent of WMHs was significantly associated with performance on measures of psychomotor speed (β = 0.15). CONCLUSION:In today's therapeutic environment, in HIV-infected and HIV seronegative individuals, those factors which affect the cerebrovasculature are the best predictors of WMHs. Diabetes has a specific impact among HIV-infected, but not uninfected, men, suggesting the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions.

The brain's default mode network (DMN), having a high rate of basal energy metabolism, is vulnerable to altered glucose metabolism in type 2 diabetes mellitus (T2DM) due to insulin resistance and chronic hyperglycemia. Previous studies showed that functional connectivity and structural connectivity among the DMN nodal regions are compromised in T2DM. We applied magnetization transfer imaging to examine the impact of T2DM on the biophysical integrity of the DMN. The results showed that the biophysical integrity of macromolecular protein pools in the posterior cingulate cortex (PCC), a central DMN hub region, was selectively compromised in T2DM, whereas the other nodal regions of the DMN, including the medial prefrontal cortex, lateral inferior parietal cortex, precuneus, and medial and lateral temporal cortices, were biophysically intact compared with those of control subjects without diabetes. Furthermore, the degree of biophysical impairment of the PCC correlated with both hyperglycemia and vascular compromise, the two physiological hallmarks of diabetes. These new findings demonstrate that the PCC is vulnerable in the DMN and may shed light on the molecular neurobiology of T2DM and help to elucidate the pathophysiology of diabetes-related cognitive comorbidities and increased risk for dementia. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to map the pathophysiology of resting state functional connectivity accompanying structural and functional abnormalities in children with bipolar disorder. Methods: Children with bipolar disorder and demographically matched healthy controls underwent resting-state functional magnetic resonance imaging. A model-free independent component analysis was performed to identify intrinsically interconnected networks. Results: We included 34 children with bipolar disorder and 40 controls in our analysis. Three distinct resting state networks corresponding to affective, executive and sensorimotor functions emerged as being significantly different between the pediatric bipolar disorder (PBD) and control groups. All 3 networks showed hyperconnectivity in the PBD relative to the control group. Specifically, the connectivity of the dorsal anterior cingulate cortex (ACC) differentiated the PBD from the control group in both the affective and the executive networks. Exploratory analysis suggests that greater connectivity of the right amygdala within the affective network is associated with better executive function in children with bipolar disorder, but not in controls. Limitations: Unique clinical characteristics of the study sample allowed us to evaluate the pathophysiology of resting state connectivity at an early state of PBD, which led to the lack of generalizability in terms of comorbid disorders existing in a typical PBD population. Conclusion: Abnormally engaged resting state affective, executive and sensorimotor networks observed in children with bipolar disorder may reflect a biological context in which abnormal task-based brain activity can occur. Dual engagement of the dorsal ACC in affective and executive networks supports the neuroanatomical interface of these networks, and the amygdala's engagement in moderating executive function illustrates the intricate interplay of these neural operations at rest. [ABSTRACT FROM AUTHOR]

Abstract: Atlas-based segmentation of MR brain images typically uses a single atlas (e.g., MNI Colin27) for region identification. Normal individual variations in human brain structures present a significant challenge for atlas selection. Previous researches mainly focused on how to create a specific template for different requirements (e.g., for a certain population). We address atlas selection with a different approach: instead of choosing a fixed brain atlas, we use a family of brain templates for atlas-based segmentation. For each subject and each region, the template selection method automatically chooses the ‘best’ template with the highest local registration accuracy, based on normalized mutual information. The region classification performances of the template selection method and the single template method were quantified by the overlap ratios (ORs) and intraclass correlation coefficients (ICCs) between the manual tracings and the respective automated labeled results. Two groups of brain images and multiple regions of interest (ROIs), including the right anterior cingulate cortex (ACC) and several subcortical structures, were tested for both methods. We found that the template selection method produced significantly higher ORs than did the single template method across all of the 13 analyzed ROIs (two-tailed paired t-test, right ACC at t(8)=4.353, p =0.0024; right amygdala, matched paired t test t(8)>3.175, p <0.013; for the remaining ROIs, t(8)=4.36, p <0.002). The template selection method also provided more reliable volume estimates than the single template method with increased ICCs. Moreover, the improved accuracy of atlas-based segmentation using optimum templates approaches the accuracy of manual tracing, and thus is valid for automated brain imaging analyses. [Copyright &y& Elsevier]

Deficits in verbal learning and memory are a prominent feature of neurocognitive function in HIV-infected women, and are associated with high levels of perceived stress. To understand the neurobiological factors contributing to this stress-related memory impairment, we examined the association between stress, verbal memory, and brain volumes in HIV-infected women. Participants included 38 HIV-infected women (Mean age = 43.9 years) from the Chicago Consortium of the Women's Interagency HIV Study (WIHS). Participants underwent structural magnetic resonance imaging (MRI) and completed standardized measures of verbal learning and memory and stress (Perceived Stress Scale-10; PSS-10). Brain volumes were evaluated in a priori regions of interest, including the medial temporal lobe (MTL) and prefrontal cortex (PFC). Compared to HIV-infected women with lower stress (PSS-10 scores in lower two tertiles), HIV-infected women with higher stress (scores in the top tertile), performed worse on measures of verbal learning and memory and showed smaller volumes bilaterally in the parahippocampal gyrus, superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus (p's < 0.05). Reduced volumes in the inferior frontal gyrus, middle frontal gyrus, and superior frontal gyrus (all right hemisphere) were negatively associated with verbal learning and memory performance. Prefrontal cortical atrophy is associated with stress-related deficits in verbal learning and memory in HIV-infected women. The time course of these volume losses in relation to memory deficits has yet to be elucidated, but the magnitude of the volumetric differences between women with higher versus lower stress suggests a prolonged vulnerability due to chronic stress and/or early life trauma. [ABSTRACT FROM AUTHOR]