The Role of the Glymphatic System in Perioperative Neurocognitive Disorders.

BACKGROUND: The glymphatic system plays a crucial role in clearing metabolic waste from the central nervous system and is most active during sleep. Patients with obstructive sleep apnea (OSA) have a dysfunctional glymphatic system that correlates with disease severity. In addition, these patients have worse outcomes after surgery. The status of the glymphatic system during the perioperative period is unclear and can be examined with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI). This study assessed perioperative glymphatic system changes in OSA surgical patients and possible relationships with perioperative neurocognitive disorders. METHODS: DTI data from 13 OSA patients having laparoscopic abdominal surgery with general anesthesia were acquired and analyzed using a 3.0-T MRI scanner. Diffusivity maps in the x-axis (Dxx), y-axis (Dyy), z-axis (Dzz), x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated. Diffusion values for the projection and association fibers were extracted, and DTI analysis along the perivascular space (ALPS) was performed. The patients' cognition was assessed using the Montreal Cognitive Assessment tool. Evaluations were carried out within 5 days before surgery and within the first 48 hours after surgery. RESULTS: The ALPS index decreased after surgery, and this correlated with a decrease in general cognition scores and specific memory domains, including visuospatial and delayed recall. CONCLUSIONS: The glymphatic system in OSA patients is worsened after surgery and this may contribute to an increased risk for long-term postoperative cognitive disorders. This study suggest that the glymphatic system might play a role in the pathophysiology of perioperative neurocognitive disorders and be a potential therapeutic target.

Heart failure-induced brain myelin changes and differences between sexes.

Heart failure (HF) leads to brain injury in autonomic, respiratory, mood, and cognitive control sites, revealed as tissue volume loss, altered metabolites, and impaired diffusion tissue properties. The extent of myelin changes in HF and variations within sexes are unclear. Our aim was to examine regional brain subcortical and white matter myelin integrity in HF patients over control subjects, as well as differences between sexes using T1- and T2-weighted clinical images. We acquired T1- and T2-weighted images from 63 HF patients and 129 controls using a 3.0-Tesla MRI scanner. Using T1- and T2-weighted images, ratio maps were computed, normalized to a common space, smoothed, and compared between groups (ANCOVA; covariates: age and sex; SPM12, false discovery rate, p < .010), as well as between male versus female HF (ANCOVA; covariate: age; SPM12, uncorrected p < .005). Multiple brain areas in HF showed decreased myelin integrity, including the amygdala, hippocampus, cingulate, insula, cerebellum, prefrontal cortices, and multiple white matter areas, compared to controls. Female HF patients showed more brain injuries in the parietal, prefrontal and frontal, hippocampus, amygdala, pons, cerebellar, insula, and corpus callosum compared to male HF patients. HF subjects showed compromised subcortical and white matter myelin integrity, especially in sites regulating autonomic, respiratory, mood, and cognition, with more changes in females over males. These findings provide a structural basis for the enhanced symptoms identified in female over male HF patients with similar disease severity.

Microstructural brain tissue changes contribute to cognitive and mood deficits in adults with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) patients show brain tissue changes in mood and cognitive regulatory sites, but the nature and extent of tissue injury and their associations with symptoms are unclear. Our aim was to examine brain tissue damage in T2DM over controls using mean diffusivity (MD) computed from diffusion tensor imaging (DTI), and assess correlations with mood and cognitive symptoms in T2DM. We collected DTI series (MRI), mood, and cognitive data, from 169 subjects (68 T2DM and 101 controls). Whole-brain MD-maps were calculated, normalized, smoothed, and compared between groups, as well as correlated with mood and cognition scores in T2DM subjects. Type 2 diabetes patients showed altered cognitive and mood functions over control subjects. Multiple brain sites in T2DM patients showed elevated MD values, indicating chronic tissue changes, including the cerebellum, insula, and frontal and prefrontal cortices, cingulate, and lingual gyrus. Associations between MD values and mood and cognition scores appeared in brain sites mediating these functions. Type 2 diabetes patients show predominantly chronic brain tissue changes in areas mediating mood and cognition functions, and tissue changes from those regions correlate with mood and cognitive symptoms suggesting that the microstructural brain changes may account for the observed functional deficits.

Brain Changes Linked to Cognitive Symptomatology in Homeless Youth.

Youth impacted by homelessness experience diminished cognition due to a variety of reasons including mental health symptoms, alcohol and substance use, and adverse childhood experiences. However, the status of specific brain regions which could impact important cognitive functions in homeless youth remains unclear. In this pilot comparative and correlational study, a series of demographic, psychological, cognitive assessments, and brain magnetic resonance imaging were performed in 10 male youth experiencing homelessness and 9 age-matched healthy male controls (age range: 18-25 years). Participants experiencing homelessness had significantly decreased regional brain gray matter tissue in comparison to the controls. Moreover, there were strong inverse correlations between the brain regions classically associated with executive decision-making (prefrontal cortices), depression (insular lobes), and conflict resolution (anterior cingulate), and the level of the symptoms detected by their questionnaires.

Machine learning approach for obstructive sleep apnea screening using brain diffusion tensor imaging.

Patients with obstructive sleep apnea (OSA) show autonomic, mood, cognitive, and breathing dysfunctions that are linked to increased morbidity and mortality, which can be improved with early screening and intervention. The gold standard and other available methods for OSA diagnosis are complex, require whole-night data, and have significant wait periods that potentially delay intervention. Our aim was to examine whether using faster and less complicated machine learning models, including support vector machine (SVM) and random forest (RF), with brain diffusion tensor imaging (DTI) data can classify OSA from healthy controls. We collected two DTI series from 59 patients with OSA [age: 50.2 ± 9.9 years; body mass index (BMI): 31.5 ± 5.6 kg/m2 ; apnea-hypopnea index (AHI): 34.1 ± 21.2 events/h 23 female] and 96 controls (age: 51.8 ± 9.7 years; BMI: 26.2 ± 4.1 kg/m2 ; 51 female) using a 3.0-T magnetic resonance imaging scanner. Using DTI data, mean diffusivity maps were calculated from each series, realigned and averaged, normalised to a common space, and used to conduct cross-validation for model training and selection and to predict OSA. The RF model showed 0.73 OSA and controls classification accuracy and 0.85 area under the curve (AUC) value on the receiver-operator curve. Cross-validation showed the RF model with comparable fitting over SVM for OSA and control data (SVM; accuracy, 0.77; AUC, 0.84). The RF ML model performs similar to SVM, indicating the comparable statistical fitness to DTI data. The findings indicate that RF model has similar AUC and accuracy over SVM, and either model can be used as a faster OSA screening tool for subjects having brain DTI data.

Functional comorbidities and brain tissue changes before and after lung transplant in adults.

Background: Adults undergoing lung transplant, as a lifesaving treatment for end stage lung disease, exhibit high levels of peri-operative neurocognitive dysfunction in multiple domains, including delirium, cognition, and autonomic deficits. These complications impact healthcare costs, quality of life, and patient outcomes. Post-operative symptoms likely result from loss of brain tissue integrity in sites mediating such regulatory functions. Our aim in this study was to examine peri-operative neurocognitive dysfunction and brain tissue changes after lung transplant in adults. Methods: We retrospectively examined the UCLA lung transplant database to identify 114 lung transplant patients with pre-operative clinical and neurocognitive data. Of 114 patients, 9 lung transplant patients had pre- and post-transplant brain magnetic resonance imaging. Clinical and neurocognitive data were summarized for all subjects, and brain tissue volume changes, using T1-weighted images, before and after transplant were examined. T1-weighted images were partitioned into gray matter (GM)-tissue type, normalized to a common space, smoothed, and the smoothed GM-volume maps were compared between pre- and post-transplant (paired t-tests; covariate, age; SPM12, p < 0.005). Results: Increased comorbidities, including the diabetes mellitus (DM), hypertension, kidney disease, and sleep disordered breathing, as well as higher rates of neurocognitive dysfunction were observed in the lung transplant patients, with 41% experiencing post-operative delirium, 49% diagnosed with a mood disorder, and 25% of patients diagnosed with cognitive deficits, despite incomplete documentation. Similarly, high levels of delirium, cognitive dysfunction, and mood disorder were noted in a subset of patients used for brain MRI evaluation. Significantly decreased GM volumes emerged in multiple brain regions, including the frontal and prefrontal, parietal, temporal, bilateral anterior cingulate and insula, putamen, and cerebellar cortices. Conclusion: Adults undergoing lung transplant often show significant pre-operative comorbidities, including diabetes mellitus, hypertension, and chronic kidney disease, as well as neurocognitive dysfunction. In addition, patients with lung transplant show significant brain tissue changes in regions that mediate cognition, autonomic, and mood functions. The findings indicate a brain structural basis for many enhanced post-operative symptoms and suggest a need for brain tissue protection in adults undergoing lung transplant to improve health outcomes.

Brain tissue integrity mapping in adults with obstructive sleep apnea using T1-weighted and T2-weighted images.

Background: Obstructive sleep apnea (OSA) is accompanied by both gray and white matter differences in brain areas that regulate autonomic, cognitive, and mood functions, which are deficient in the condition. Such tissue changes have been examined through diffusion tensor and diffusion kurtosis imaging-based procedures. However, poor in-plane spatial resolution of these techniques precludes precise determination of the extent of tissue injury. Tissue texture maps derived from the ratio of T1-weighted and T2-weighted images can provide more adequate in-plane assessment of brain tissue differences. Objectives: To examine brain tissue integrity in recently diagnosed, treatment-naïve OSA subjects, relative to age- and sex-comparable control subjects using T1-weighted and T2-weighted images. Design: A cross-sectional study. Methods: We examined the extent of tissue changes in 106 OSA over 115 control subjects using high-resolution T1- and T2-weighted images collected from a 3.0-Tesla scanner (analysis of covariance; covariates: age, sex, body-mass-index, Pittsburgh sleep quality index, Epworth sleepiness scale, Beck Anxiety Inventory, and Beck Depression Inventory II; false discovery rate corrected; p < 0.01). Results: OSA subjects showed significantly lowered tissue integrity in several brain regions, including the frontal, cingulate and insular cortices, cingulum bundle, thalamus, corpus callosum, caudate and putamen, pons, temporal, occipital, and parietal sites, cerebellar peduncles, and medial medullary sites, compared with controls. Conclusion: OSA subjects show widespread lowered tissue integrity in autonomic, mood, and cognitive control sites over healthy controls. The pathological processes contributing to the alterations may include repetitive hypoxic and hypercarbic processes and excitotoxic injury, leading to altered brain tissue integrity in OSA.

Regional variation in brain tissue texture in patients with tonic-clonic seizures.

Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) seizures and 53 healthy controls; images were bias-corrected, entropy maps calculated, normalized to a common space, smoothed, and compared between groups (TC patients and controls using ANCOVA; covariates, age and sex; SPM12, family-wise error correction for multiple comparisons, p<0.01). Decreased entropy, indicative of increased tissue homogeneity, appeared in major autonomic (ventromedial prefrontal cortex, hippocampus, dorsal and ventral medulla, deep cerebellar nuclei), motor (sensory and motor cortex), or both motor and autonomic regulatory sites (basal-ganglia, ventral-basal cerebellum), and external surfaces of the pons. The anterior and posterior thalamus and midbrain also showed entropy declines. Only a few isolated regions showed increased entropy. Among the spared autonomic regions was the anterior cingulate and anterior insula; the posterior insula and cingulate were, however, affected. The entropy alterations overlapped areas of tissue changes found earlier with volumetric measures, but were more extensive, and indicate widespread injury to tissue within critical autonomic and breathing regulatory areas, as well as prominent damage to more-rostral sites that exert influences on both breathing and cardiovascular regulation. The entropy measures provide easily-collected supplementary information using only T1-weighted images, showing aspects of tissue integrity other than volume change that are important for assessing function.

Relationships between brain tissue damage, oxygen desaturation, and disease severity in obstructive sleep apnea evaluated by diffusion tensor imaging.

STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) show brain injury in sites responsible for autonomic, cognitive, and respiratory functions. Brain changes in OSA may vary with disease severity as assessed by the apnea-hypopnea index (AHI), which does not provide information about the apnea depth and length in contrast to oxygen desaturation. Although significant associations with brain injury and AHI are known in OSA, it is unclear whether AHI or the extent of oxygen desaturations better correlate with brain damage. We evaluated associations between brain changes, AHI, and oxygen desaturation using diffusion tensor imaging-based measures. METHODS: We acquired diffusion tensor imaging data from 19 patients with OSA using a 3.0-Tesla MRI scanner and calculated, normalized, and smoothed mean, axial, and radial diffusivity maps that were used for correlations between brain changes, oxygen desaturation, and AHI values. RESULTS: Positive correlations with extent of injury (mean, axial, and radial diffusivity values) and AHI appeared in the frontal areas, cingulate and insula, amygdala, hippocampus, and basal pons, and negative associations emerged in the putamen, internal-capsule, globus-pallidus, and cerebellar cortices. Regional diffusivity values and oxygen desaturation showed positive correlations in the cingulate, frontal, putamen, and cerebellar sites, and negative relationships in several areas, including the occipital cortex. CONCLUSIONS: Patients with OSA show negative and positive correlations, indicated by increased and decreased diffusivity values, resulting from chronic and acute changes in those areas. The extent of injury in OSA partially depends on the extent of AHI and oxygen desaturation, with the effects representing continued development from acute to chronic processes. CITATION: Sahib A, Roy B, Kang D, Aysola RS, Wen E, Kumar R. Relationships between brain tissue damage, oxygen desaturation, and disease severity in obstructive sleep apnea evaluated by diffusion tensor imaging. J Clin Sleep Med. 2022;18(12):2713-2721.

Impaired Glymphatic System Actions in Obstructive Sleep Apnea Adults.

Study Objectives: Obstructive sleep apnea (OSA) is accompanied by sleep fragmentation and altered sleep architecture, which can potentially hinder the glymphatic system, increasing risks for Alzheimer's disease (AD), but the status is unclear in OSA. Our aim was to investigate the glymphatic system in OSA subjects and examine the relationships between OSA disease severity, sleep symptoms, and glymphatic system indices in OSA using diffusion tensor imaging (DTI). Methods: We acquired DTI data from 59 OSA and 62 controls using a 3.0-Tesla MRI and examined OSA disease severity and sleep symptoms with the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Diffusivity maps in the x-axis (Dxx), y-axis (Dyy), and z-axis (Dzz), as well as in x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated, diffusion values for the projection and association fibers extracted, and the DTI analyses along the perivascular space (DTI-ALPS index) were performed. The glymphatic system indices were compared between groups and correlated with disease severity and sleep symptoms in OSA subjects. Results: Dzz values, derived from projection fiber areas, Dyy and Dzz values from association fiber areas, as well as ALPS and Dyzmean values were significantly reduced in OSA over controls. Significant correlations emerged between disease severity, sleep symptoms, and Dxy, Dxx, and Dzz values in OSA subjects. Conclusion: OSA patients show abnormal glymphatic system function that may contribute to increased risks for AD. The findings suggest that the APLS method can be used to assess the glymphatic system in OSA patients.

Brain regional homogeneity changes after short-term positive airway pressure treatment in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) reveal functional changes in brain sites involved in autonomic, cognitive, and mood regulations. However, it is unclear whether these brain changes reverse with short-term positive airway pressure (PAP) treatment. Our aim was to examine brain functional changes in response to 3-months of PAP treatment using regional homogeneity (ReHo) measures, where increased and decreased ReHo value indicates hyper- and hypo-local neural activities, respectively, and considered as functional deficits. We collected brain magnetic resonance imaging data as well as mood, cognitive, and sleep variables from 17 treatment-naïve OSA at baseline and after 3-months of PAP treatment and 25 age- and gender-matched healthy controls. Whole-brain ReHo maps were calculated and compared between OSA and controls and OSA subjects before and after PAP treatment. At baseline, treatment-naïve OSA subjects showed higher ReHo in the bilateral thalamus, putamen, postcentral gyrus, paracentral lobule, supplementary motor area, and right insula, and lower ReHo in the frontal and parietal cortices, compared to controls. After 3-months of PAP treatment, abnormal sleep and mood scores decreased significantly to normal levels. ReHo decreased in the autonomic and somatosensory control areas, including the thalamus, putamen, postcentral gyrus, and insula, and increased in the cognitive and affective regulatory parietal regions. The normalized ReHo was correlated with improved sleep quality and reduced anxiety symptoms. These findings suggest that 3-months of PAP use can improve sleep, mood issues, and partly recover brain activities, however, longer PAP treatment may be required to fully and permanently reverse brain functional deficits.

Regional brain tissue changes in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) patients present with a variety of symptoms, including mood and cognition deficits, in addition to classical respiratory, and autonomic issues. This suggests that brain injury, which can be examined with non-invasive magnetic resonance imaging (MRI), is a manifestation of this condition. However, brain tissue integrity in sites that regulate cognitive, autonomic, respiratory, and mood functions in CF patients is unclear. Our aim was to assess regional brain changes using high-resolution T1-weighted images based gray matter (GM) density and T2-relaxometry procedures in CF over control subjects. METHODS: We acquired high-resolution T1-weighted images and proton-density (PD) and T2-weighted images from 5 CF and 15 control subjects using a 3.0-Tesla MRI. High-resolution T1-weighted images were partitioned to GM-tissue type, normalized to a common space, and smoothed. Using PD- and T2-weighted images, whole-brain T2-relaxation maps were calculated, normalized, and smoothed. The smoothed GM-density and T2-relaxation maps were compared voxel-by-voxel between groups using analysis of covariance (covariates, age and sex; SPM12, p < 0.001). RESULTS: Significantly increased GM-density, indicating tissues injury, emerged in multiple brain regions, including the cerebellum, hippocampus, amygdala, basal forebrain, insula, and frontal and prefrontal cortices. Various brain areas showed significantly reduced T2-relaxation values in CF subjects, indicating predominant acute tissue changes, in the cerebellum, cerebellar tonsil, prefrontal and frontal cortices, insula, and corpus callosum. CONCLUSIONS: Cystic fibrosis subjects show predominant acute tissue changes in areas that control mood, cognition, respiratory, and autonomic functions and suggests that tissue changes may contribute to symptoms resulting from ongoing hypoxia accompanying the condition.

Brain Structural Changes in Patients with Pulmonary Arterial Hypertension.

BACKGROUND AND PURPOSE: Patients with pulmonary arterial hypertension (PAH) frequently present with anxiety, depression, autonomic, and cognitive deterioration, which may indicate brain changes in regions that control these functions. However, the precise regional brain-injury in sites that regulate cognitive, autonomic, and mood functions in PAH remains unclear. We examined the shifts in regional gray matter (GM) volume, using high-resolution T1-weighted images, and brain tissue alterations, using T2-relaxometry procedures, in PAH compared to healthy subjects. METHODS: We collected two high-resolution T1-weighted series, and proton-density and T2-weighted images using a 3.0-Tesla magnetic resonance imaging scanner from 9 PAH and 19 healthy subjects. Both high-resolution T1-weighted images were realigned and averaged, partitioned to GM tissue type, normalized to a common space, and smoothed. Using proton-density and T2-weighted images, T2-relaxation maps were calculated, normalized to a common space, and smoothed. Whole-brain GM volume and T2-relaxation maps were compared between PAH and controls using analysis of covariance (covariates, age, sex, and total-brain-volume; false discover rate corrections). RESULTS: Significantly decreased GM volumes, indicating tissue injury, emerged in multiple brain regions, including the hippocampus, insula, cerebellum, parahippocampus, temporal, frontal, and occipital gyri, cingulate, amygdala, and thalamus. Higher T2-relaxation values, suggesting tissue damage, appeared in the cerebellum, hippocampus, parahippocampus, frontal, lingual, and temporal and occipital gyri, and cingulate areas in PAH compared to healthy subjects. CONCLUSIONS: PAH patients showed significant GM injury and brain tissue changes in sites that regulate cognition, autonomic, and mood functions. These findings indicate a brain structural basis for functional deficits in PAH patients.

Reduced hippocampal volumes and memory deficits in adolescents with single ventricle heart disease.

INTRODUCTION: Adolescents with single ventricle congenital heart disease (SVHD) show functional deficits, particularly in memory and mood regulation. Hippocampi are key brain structures that regulate mood and memory; however, their tissue integrity in SVHD is unclear. Our study aim is to evaluate hippocampal volumes and their associations with memory, anxiety, and mood scores in adolescents with SVHD compared to healthy controls. METHODS: We collected brain magnetic resonance imaging data from 25 SVHD (age 15.9 ± 1.2 years; 15 male) and 38 controls (16.0 ± 1.1 years; 19 male) and assessed memory (Wide Range Assessment of Memory and Learning 2, WRAML2), anxiety (Beck Anxiety Inventory, BAI), and mood (Patient Health Questionnaire 9, PHQ-9) functions. Both left and right hippocampi were outlined and global volumes, as well as three-dimensional surfaces were compared between groups using ANCOVA and associations with cognitive and behavioral scores with partial correlations (covariates: age and total brain volume). RESULTS: The SVHD group showed significantly higher BAI (p = .001) and PHQ-9 (p < .001) scores, indicating anxiety and depression symptoms and significantly reduced WRAML2 scores (p < .001), suggesting memory deficits compared with controls. SVHD group had significantly reduced right global hippocampal volumes (p = .036) compared with controls, but not the left (p = .114). Right hippocampal volume reductions were localized in the CA1, CA4, subiculum, and dentate gyrus. Positive correlations emerged between WRAML2 scores and left (r = 0.32, p = .01) and right (r = 0.28, p = .03) hippocampal volumes, but BAI and PHQ-9 did not show significant correlations. CONCLUSION: Adolescents with SVHD show reduced hippocampal volumes, localized in several sites (CA1, CA4, subiculum, and dentate gyrus), which are associated with memory deficits. The findings indicate the need to explore ways to improve memory to optimize academic achievement and ability for self-care in the condition.

Poor Sleep Quality Linked to Decreased Brain Gray Matter Density in Adults with Type 2 Diabetes.

BACKGROUND: Poor sleep is common in adults with Type 2 Diabetes Mellitus (T2DM), which may contribute to brain tissue changes. However, the impact of sleep quality on brain tissue in T2DM individuals is unclear. We aimed to evaluate differential sleep quality with brain changes, and brain tissue integrity in T2DM patients. METHODS: Data were collected from 34 patients with T2DM and included sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], and high-resolution T1-weighted brain images using a 3.0-Tesla MRI scanner. Gray matter density (GMD) maps were compared between subjects with good vs poor sleep quality as assessed by PSQI (covariates: age, sex, BMI). RESULTS: Of 34 T2DM patients, 17 showed poor sleep quality. Multiple brain sites, including the hippocampus, cerebellum, prefrontal, amygdala, thalamus, hypothalamus, insula, cingulate, and temporal areas, showed reduced gray matter in T2DM patients with poor sleep quality over patients with good sleep quality. Negative associations emerged between PSQI scores and gray matter density in multiple areas. CONCLUSIONS: T2DM patients with poor sleep quality show brain tissue changes in sites involved in sleep regulation. Findings indicate that improving sleep may help mitigate brain tissue damage, and thus, improve brain function in T2DM patients.

T1-weighted and T2-weighted Subtraction MR Images for Glioma Visualization and Grading.

BACKGROUND AND PURPOSE: To evaluate the performance of multiparametric MR images in differentiation of different regions of the gross tumor area and for assessment of glioma grade. METHODS: Forty-six glioma subjects (18 grade II, 11 grade III, and 17 grade IV) underwent a comprehensive MR and spectroscopic imaging procedure. Maps were generated by subtraction of T1-weighted images from contrast-enhanced T1-weighted images (ΔT1 map) and T1-weighted images from T2-weighted images (ΔT2 map). Regions of interest (ROIs) were positioned in normal-appearing white matter (NAWM), enhancing tumor, hyperintense T2, necrotic region, and immediate and distal peritumoral regions (IPR and DPR). Relative signal contrast was estimated as difference between mean intensities in ROIs and NAWM. Classification using support vector machines was applied to all image series to determine the efficacy of regional contrast measures for differentiation of low- and high-grade lesions and grade III and IV lesions. RESULTS: ΔT1 and ΔT2 maps offered higher contrast as compared to other parametric maps in differentiating enhancing tumor and edematous regions, respectively, and provided the highest classification accuracy for differentiating low- and high-grade tumors, of 91% and 90.4%. Choline/N-acetylaspartate maps provided significant contrast for delineating IPR and DPR. For differentiating high-grade gliomas, ΔT2 and ΔT1 maps provided a mean accuracy of 90.9% and 88.2%, which was lower than that obtained using cerebral blood volume (93.7%) and choline/creatine (93.3%) maps. CONCLUSION: This study showed that subtraction maps provided significant contrast in differentiating several regions of the gross tumor area and are of benefit for accurate tumor grading.

Regional Brain Gray Matter Changes in Patients with Type 2 Diabetes Mellitus.

Patients with Type 2 diabetes mellitus (T2DM) show cognitive and mood impairment, indicating potential for brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites, and their associations with these functional deficits in T2DM subjects remain unclear. We examined gray matter (GM) changes in 34 T2DM and 88 control subjects using high-resolution T1-weighted images, collected from a 3.0-Tesla magnetic resonance imaging scanner, and assessed anxiety [Beck Anxiety Inventory], depressive symptoms [Beck Depression Inventory-II], and cognition [Montreal Cognitive Assessment]. We also investigated relationships between GM status of cognitive and mood control sites and these scores in T2DM. Significantly increased anxiety (p = 0.003) and depression (p = 0.001), and reduced cognition (p = 0.002) appeared in T2DM over controls. Decreased GM volumes appeared in several regions in T2DM patients, including the prefrontal, hippocampus, amygdala, insular, cingulate, cerebellum, caudate, basal-forebrain, and thalamus areas (p < 0.01). GM volumes were significantly associated with anxiety (r = -0.456,p = 0.009), depression (r = -0.465,p = 0.01), and cognition (r = 0.455,p = 0.009) scores in regions associated with those regulations (prefrontal cortices, hippocampus, para hippocampus, amygdala, insula, cingulate, caudate, thalamus, and cerebellum) in T2DM patients. Patients with T2DM show brain damage in regions that are involved in cognition, anxiety, and depression control, and these tissue alterations are associated with functional deficits. The findings indicate that mood and cognitive deficits in T2DM patients has brain structural basis in the condition.

Caudate nuclei volume alterations and cognition and mood dysfunctions in adolescents with single ventricle heart disease.

Adolescents with single ventricle heart disease (SVHD) exhibit mood and cognitive deficits, which may result from injury to the basal ganglia structures, including the caudate nuclei. However, the integrity of the caudate in SVHD adolescents is unclear. Our aim was to examine the global and regional caudate volumes, and evaluate the relationships between caudate volumes and cognitive and mood scores in SVHD and healthy adolescents. We acquired two high-resolution T1-weighted images from 23 SVHD and 37 controls using a 3.0-Tesla MRI scanner, as well as assessed mood (Patient Health Questionnaire-9 [PHQ-9]; Beck Anxiety Inventory [BAI]) and cognition (Montreal Cognitive Assessment [MoCA]; Wide Range Assessment of Memory and Learning-2; General Memory Index [GMI]) functions. Both left and right caudate nuclei were outlined, which were then used to calculate and compare volumes between groups using ANCOVA (covariates: age, gender, and head-size), as well as perform 3D surface morphometry. Partial correlations (covariates: age, gender, and head-size) were used to examine associations between caudate volumes, cognition, and mood scores in SVHD and controls. SVHD subjects showed significantly higher PHQ-9 and BAI scores, indicating more depressive and anxiety symptoms, as well as reduced GMI scores, suggesting impaired cognition, compared to controls. SVHD patients showed significantly reduced caudate volumes (left, 3,198.8 ± 490.1 vs. 3,605.0 ± 480.4 mm3 , p < 0.004; right, 3,162.1 ± 475.4 vs. 3,504.8 ± 465.9 mm3 , p < 0.011) over controls, and changes were localized in the rostral, mid-dorsolateral, and caudal areas. Significant negative correlations emerged between caudate volumes with PHQ-9 and BAI scores and positive correlations with GMI and MoCA scores in SVHD and controls. SVHD adolescents show significantly reduced caudate volumes, especially in sites that have projections to regulate mood and cognition, which may result from developmental and/or hypoxia-/ischemia-induced processes.

Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure.

BACKGROUND: Adolescents with single ventricle heart disease (SVHD) who have undergone the Fontan procedure show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls. METHODS: Brain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total brain volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV). RESULTS: SVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls. CONCLUSION: Adolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory.

Prefrontal cortex brain damage and glycemic control in patients with type 2 diabetes.

BACKGROUND: This study examined brain tissue integrity in sites that controls cognition (prefrontal cortices; PFC) and its relationships to glycemic outcomes in adults with type 2 diabetes mellitus (T2DM). METHODS: We examined 28 T2DM patients (median age 57.1 years; median body mass index [BMI] 30.6 kg/m2 ;11 males) and 47 healthy controls (median age 55.0 years; median BMI 25.8 kg/m2 ; 29 males) for cognition (Montreal Cognitive Assessment [MoCA]), glycemic control (hemoglobin A1c [HbA1c]), and PFC tissue status via brain magnetic resonance imaging (MRI). High-resolution T1-weighted images were collected using a 3.0-Tesla MRI scanner, and PFC tissue changes (tissue density) were examined with voxel-based morphometry procedures. RESULTS: Reduced PFC density values were observed in T2DM patients compared to controls (left, 0.41 ± 0.02 mm3 /voxel vs 0.44 ± 0.02 mm3 /voxel, P < 0.001; right, 0.41 ± 0.03 mm3 /voxel vs 0.45 ± 0.02 mm3 /voxel, P < 0.001). PFC density values were positively correlated with cognition; left PFC region (r = 0.53, P = 0.005) and right PFC region (r = 0.56, P = 0.003), with age and sex as covariates. Significant negative correlations were found between PFC densities and HbA1c values; left PFC region (r = -0.39, P = 0.049) and right PFC region (r = -0.48, P = 0.01), with age and sex as covariates. CONCLUSIONS: T2DM patients showed PFC brain tissue damage, which is associated with cognitive deficits and poor glycemic control. Further research is needed to identify causal relationships between HbA1c, cognition, and brain changes in T2DM and to evaluate the impact of interventions to prevent brain tissue injury or neuroregeneration in this high-risk patient population, to eventually preserve or enhance cognition and improve glucose outcomes.