Diffusion model enables quantitative CBF analysis of Alzheimer's Disease.

Objectives: Cerebral blood flow (CBF) measured by arterial spin labeling (ASL) is a promising biomarker for Alzheimer's Disease (AD). ASL data from multiple vendors were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. However, the M0 images were missing in Siemens ASL data, prohibiting CBF quantification. Here, we utilized a generative diffusion model to impute the missing M0 and validated generated CBF data with acquired data from GE. Methods: A conditional latent diffusion model was trained to generate the M0 image and validate it on an in-house dataset ( N =55) based on image similarity metrics, accuracy of CBF quantification, and consistency with the physical model. This model was then applied to the ADNI dataset (Siemens: N =211) to impute the missing M0 for CBF calculation. We further compared the imputed data (Siemens) and acquired data (GE) regarding regional CBF differences by AD stages, their classification accuracy for AD prediction, and CBF trajectory slopes estimated by a mixed effect model. Results: The trained diffusion model generated the M0 image with high fidelity (Structural similarity index, SSIM=0.924±0.019; peak signal-to-noise ratio, PSNR=33.348±1.831) and caused minimal bias in CBF values (mean difference in whole brain is 1.07±2.12ml/100g/min). Both generated and acquired CBF data showed similar differentiation patterns by AD stages, similar classification performance, and decreasing slopes with AD progression in specific AD-related regions. Generated CBF data also improved accuracy in classifying AD stages compared to qualitative perfusion data. Interpretation/Conclusion: This study shows the potential of diffusion models for imputing missing modalities for large-scale studies of CBF variation with AD.

Ethnic differences in the effects of apolipoprotein E ɛ4 and vascular risk factors on accelerated brain aging.

The frequency of the apolipoprotein E ɛ4 allele and vascular risk factors differs among ethnic groups. We aimed to assess the combined effects of apolipoprotein E ɛ4 and vascular risk factors on brain age in Korean and UK cognitively unimpaired populations. We also aimed to determine the differences in the combined effects between the two populations. We enrolled 2314 cognitively unimpaired individuals aged ≥45 years from Korea and 6942 cognitively unimpaired individuals from the UK, who were matched using propensity scores. Brain age was defined using the brain age index. The apolipoprotein E genotype (ɛ4 carriers, ɛ2 carriers and ɛ3/ɛ3 homozygotes) and vascular risk factors (age, hypertension and diabetes) were considered predictors. Apolipoprotein E ɛ4 carriers in the Korean (ß = 0.511, P = 0.012) and UK (ß = 0.302, P = 0.006) groups had higher brain age index values. The adverse effects of the apolipoprotein E genotype on brain age index values increased with age in the Korean group alone (ɛ2 carriers × age, ß = 0.085, P = 0.009; ɛ4 carriers × age, ß = 0.100, P < 0.001). The apolipoprotein E genotype, age and ethnicity showed a three-way interaction with the brain age index (ɛ2 carriers × age × ethnicity, ß = 0.091, P = 0.022; ɛ4 carriers × age × ethnicity, ß = 0.093, P = 0.003). The effects of apolipoprotein E on the brain age index values were more pronounced in individuals with hypertension in the Korean group alone (ɛ4 carriers × hypertension, ß = 0.777, P = 0.038). The apolipoprotein E genotype, age and ethnicity showed a three-way interaction with the brain age index (ɛ4 carriers × hypertension × ethnicity, ß=1.091, P = 0.014). We highlight the ethnic differences in the combined effects of the apolipoprotein E ɛ4 genotype and vascular risk factors on accelerated brain age. These findings emphasize the need for ethnicity-specific strategies to mitigate apolipoprotein E ɛ4-related brain aging in cognitively unimpaired individuals.

Long-term night-shift work is associated with accelerates brain aging and worsens N3 sleep in female nurses.

BACKGROUND: Shift work disrupts circadian rhythms and alters sleep patterns, resulting in various health problems. To quantitatively assess the impact of shift work on brain health, we evaluated the brain age index (BAI) derived from sleep electroencephalography (EEG) results in night-shift workers and compared it with that in daytime workers. METHODS: We studied 45 female night shift nurses (mean age: 28.2 ± 3.3 years) and 44 female daytime workers (30.5 ± 4.7 years). Sleep EEG data were analyzed to calculate BAI. The BAI of night shift workers who were asleep during the daytime with those of daytime workers who were asleep at night were statistically compared to explore associations between BAI, duration of shift work, and sleep quality. RESULTS: Night-shift workers exhibited significantly higher BAI (2.14 ± 6.04 vs. 0 ± 5.35), suggesting accelerated brain aging and altered sleep architecture, including reduced delta and sigma wave frequency activity during non-rapid eye movement sleep than daytime workers. Furthermore, poor deep sleep quality, indicated by a higher percentage of N1, lower percentage of N3, and higher arousal index, was associated with increased BAI among shift workers. Additionally, a longer duration of night-shift work was correlated with increased BAI, particularly in older shift workers. CONCLUSION: Night-shift work, especially over extended periods, may be associated with accelerated brain aging, as indicated by higher BAI and alterations in sleep architecture. Interventions are necessary to mitigate the health impacts of shift work. Further research on the long-term effects and potential strategies for sleep improvement and mitigating brain aging in shift workers is warranted.

Palsy of Both the Tibial Nerve and Common Peroneal Nerve Caused by a Ganglion Cyst in the Popliteal Area.

A ganglion cyst is a benign mass consisting of high-viscosity mucinous fluid. It can originate from the sheath of a tendon, peripheral nerve, or joint capsule. Compressive neuropathy caused by a ganglion cyst is rarely reported, with the majority of documented cases involving peroneal nerve palsy. To date, cases demonstrating both peroneal and tibial nerve palsies resulting from a ganglion cyst forming on a branch of the sciatic nerve have not been reported. In this paper, we present the case of a 74-year-old man visiting an outpatient clinic complaining of left-sided foot drop and sensory loss in the lower extremity, a lack of strength in his left leg, and a decrease in sensation in the leg for the past month without any history of trauma. Ankle dorsiflexion and great toe extension strength on the left side were Grade I. Ankle plantar flexion and great toe flexion were Grade II. We suspected peroneal and tibial nerve palsy and performed a screening ultrasound, which is inexpensive and rapid. In the operative field, several cysts were discovered, originating at the site where the sciatic nerve splits into peroneal and tibial nerves. After successful surgical decompression and a series of rehabilitation procedures, the patient's neurological symptoms improved. There was no recurrence.

Spatiotemporal Progression Patterns of Dopamine Availability and Deep Gray Matter Volume in Parkinson Disease-Related Cognitive Impairment.

BACKGROUND AND OBJECTIVES: Cognitive impairment is a frequent nonmotor symptom in patients with Parkinson disease (PD), and early cognitive decline is often attributed to dopaminergic system dysfunction. We aimed to explore spatiotemporal progression patterns of striatal dopamine availability and regional brain volume based on cognitive status among patients with PD. METHODS: This retrospective, cross-sectional study included patients with newly diagnosed PD who were not taking medication for this condition who visited a university-affiliated hospital in Seoul between January 2018 and December 2020. Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or PD dementia (PDD) based on Seoul Neuropsychological Screening Battery-II, which includes 31 subsets covering activities of daily living and 5 cognitive domains. They all had brain imaging with MRI and PET with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane at baseline. Subsequently, standardized uptake value ratios (SUVRs) for regional dopamine availability and regional gray matter volumes were obtained using automated segmentation. These metrics were compared across cognitive status groups, and spatiotemporal progression patterns were analyzed using the Subtype and Stage Inference machine learning technique. RESULTS: Among 168 patients (mean age, 73.3 ± 6.1 years; 81 [48.2%] women), 65 had PD-NC, 65 had PD-MCI, and 38 had PDD. Patients with PD-MCI exhibited lower SUVRs (3.61 ± 1.31, p < 0.001) in the caudate than patients with PD-NC (4.43 ± 1.21) but higher SUVRs than patients with PDD (2.39 ± 1.06). Patients with PD-NC had higher thalamic SUVRs (1.55 ± 0.16, p < 0.001) than patients with both PD-MCI (1.45 ± 0.16) and PDD (1.38 ± 0.19). Regional deep gray matter volumes of the caudate (p = 0.015), putamen (p = 0.012), globus pallidus (p < 0.001), thalamus (p < 0.001), hippocampus (p < 0.001), and amygdala (p < 0.001) were more reduced in patients with PD-MCI or PDD than in patients with PD-NC, and the SUVR of the caudate correlated with caudate volume (r = 0.187, p = 0.015). Hippocampal atrophy was the initial change influencing cognitive impairment. The reduced dopamine availability of the thalamus preceded reductions in volume across most deep gray matter regions. DISCUSSION: Our finding underscores the association between decreased dopamine availability and volume of the caudate and thalamus with cognitive dysfunction in PD. The dopamine availability of the caudate and thalamus was reduced before the volume of the caudate and thalamus was decreased, highlighting the spatiotemporal association between dopaminergic and structural pathology in cognitive impairment in PD.

Static and dynamic brain morphological changes in isolated REM sleep behavior disorder compared to normal aging.

Objective/background: To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms. Patients/methods: In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time. Results: None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified. Conclusion: Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson's disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive.

Are there effects of light exposure on daytime sleep for rotating shift nurses after night shift?: an EEG power analysis.

Introduction: Night-shift workers often face various health issues stemming from circadian rhythm shift and the consequent poor sleep quality. We aimed to study nurses working night shifts, evaluate the electroencephalogram (EEG) pattern of daytime sleep, and explore possible pattern changes due to ambient light exposure (30 lux) compared to dim conditions (<5 lux) during daytime sleep. Moethods: The study involved 31 participants who worked night shifts and 24 healthy adults who had never worked night shifts. The sleep macro and microstructures were analyzed, and electrophysiological activity was compared (1) between nighttime sleep and daytime sleep with dim light and (2) between daytime sleep with dim and 30 lux light conditions. Results: The daytime sleep group showed lower slow or delta wave power during non-rapid eye movement (NREM) sleep than the nighttime sleep group. During daytime sleep, lower sigma wave power in N2 sleep was observed under light exposure compared to no light exposure. Moreover, during daytime sleep, lower slow wave power in N3 sleep in the last cycle was observed under light exposure compared to no light exposure. Discussion: Our study demonstrated that night shift work and subsequent circadian misalignment strongly affect sleep quality and decrease slow and delta wave activities in NREM sleep. We also observed that light exposure during daytime sleep could additionally decrease N2 sleep spindle activity and N3 waves in the last sleep cycle.

The Outcomes of Mini-Plate Fixation for Unstable Wagstaffe Tubercle Fracture, an Indirect Syndesmosis Injury in Rotational Ankle Fracture.

Background: Wagstaffe fracture constitutes an indirect injury to the AITFL and can precipitate syndesmotic instability. The prevailing fixation methods often involve the use of mini-screws or K-wires, with absorbable suture repair reserved for cases with small or comminuted fragments exhibiting instability. In this study, we devised a mini-plate fixation method capable of securing the fracture fragment irrespective of its size or condition. Methods: A retrospective chart review was conducted on patients who underwent surgery for ankle fractures between May 2022 and October 2023. The surgical technique involved direct fixation of the Wagstaffe fracture using mini-plate fixation. Radiologic evaluation was performed using postoperative CT images, and clinical outcomes were assessed using the OMAS and VAS. Results: Fourteen patients with an average age of 62.5 years were included. Most fractures were associated with the supination-external rotation type. The average preoperative OMAS significantly improved from 5.95 to 83.57 postoperatively. The average VAS score decreased from 7.95 preoperatively to 0.19 postoperatively. Conclusions: The mini-plate technique for Wagstaffe fractures exhibited dependable fixation strength, effective fracture reduction, a minimal complication rate, and judicious surgical procedure duration.

Predicting the impact of CPAP on brain health: A study using the sleep EEG-derived brain age index.

OBJECTIVE: This longitudinal study investigated potential positive impact of CPAP treatment on brain health in individuals with obstructive sleep Apnea (OSA). To allow this, we aimed to employ sleep electroencephalogram (EEG)-derived brain age index (BAI) to quantify CPAP's impact on brain health and identify individually varying CPAP effects on brain aging using machine learning approaches. METHODS: We retrospectively analyzed CPAP-treated (n = 98) and untreated OSA patients (n = 88) with a minimum 12-month follow-up of polysomnography. BAI was calculated by subtracting chronological age from the predicted brain age. To investigate BAI changes before and after CPAP treatment, we compared annual ΔBAI between CPAP-treated and untreated OSA patients. To identify individually varying CPAP effectiveness and factors influencing CPAP effectiveness, machine learning approaches were employed to predict which patient displayed positive outcomes (negative annual ΔBAI) based on their baseline clinical features. RESULTS: CPAP-treated group showed lower annual ΔBAI than untreated (-0.6 ± 2.7 vs. 0.3 ± 2.6 years, p < 0.05). This BAI reduction with CPAP was reproduced independently in the Apnea, Bariatric surgery, and CPAP study cohort. Patients with more severe OSA at baseline displayed more positive annual ΔBAI (=accelerated brain aging) when untreated and displayed more negative annual ΔBAI (=decelerated brain aging) when CPAP-treated. Machine learning models achieved high accuracy (up to 86%) in predicting CPAP outcomes. INTERPRETATION: CPAP treatment can alleviate brain aging in OSA, especially in severe cases. Sleep EEG-derived BAI has potential to assess CPAP's impact on brain health. The study provides insights into CPAP's effects and underscores BAI-based predictive modeling's utility in OSA management.

Low-threshold 2†µm InAs/InP quantum dash lasers enabled by punctuated growth.

2 µm photonics and optoelectronics is promising for potential applications such as optical communications, LiDAR, and chemical sensing. While the research on 2 µm detectors is on the rise, the development of InP-based 2 µm gain materials with 0D nanostructures is rather stalled. Here, we demonstrate low-threshold, continuous wave lasing at 2 µm wavelength from InAs quantum dash/InP lasers enabled by punctuated growth of the quantum structure. We demonstrate low threshold current densities from the 7.1 µm width ridge-waveguide lasers, with values of 657, 1183, and 1944 A/cm2 under short pulse wave (SPW), quasi-continuous wave (QCW), and continuous wave operation. The lasers also exhibited good thermal stability, with a characteristic temperature T0 of 43 K under SPW mode. The lasing spectra is centered at 1.97 µm, coinciding with the ground-state emission observed from photoluminescence studies. We believe that the InAs quantum dash/InP lasers emitting near 2 µm will be a key enabling technology for 2 µm communication and sensing.

Age-Related Decline in Blood-Brain Barrier Function is More Pronounced in Males than Females in Parietal and Temporal Regions.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.

Deep learning of sleep apnea-hypopnea events for accurate classification of obstructive sleep apnea and determination of clinical severity.

BACKGROUND: /Objective: Automatic apnea/hypopnea events classification, crucial for clinical applications, often faces challenges, particularly in hypopnea detection. This study aimed to evaluate the efficiency of a combined approach using nasal respiration flow (RF), peripheral oxygen saturation (SpO2), and ECG signals during polysomnography (PSG) for improved sleep apnea/hypopnea detection and obstructive sleep apnea (OSA) severity screening. METHODS: An Xception network was trained using main features from RF, SpO2, and ECG signals obtained during PSG. In addition, we incorporated demographic data for enhanced performance. The detection of apnea/hypopnea events was based on RF and SpO2 feature sets, while the screening and severity categorization of OSA utilized predicted apnea/hypopnea events in conjunction with demographic data. RESULTS: Using RF and SpO2 feature sets, our model achieved an accuracy of 94 % in detecting apnea/hypopnea events. For OSA screening, an exceptional accuracy of 99 % and an AUC of 0.99 were achieved. OSA severity categorization yielded an accuracy of 93 % and an AUC of 0.91, with no misclassification between normal and mild OSA versus moderate and severe OSA. However, classification errors predominantly arose in cases with hypopnea-prevalent participants. CONCLUSIONS: The proposed method offers a robust automatic detection system for apnea/hypopnea events, requiring fewer sensors than traditional PSG, and demonstrates exceptional performance. Additionally, the classification algorithms for OSA screening and severity categorization exhibit significant discriminatory capacity.

Transformer-based deep learning denoising of single and multi-delay 3D arterial spin labeling.

PURPOSE: To present a Swin Transformer-based deep learning (DL) model (SwinIR) for denoising single-delay and multi-delay 3D arterial spin labeling (ASL) and compare its performance with convolutional neural network (CNN) and other Transformer-based methods. METHODS: SwinIR and CNN-based spatial denoising models were developed for single-delay ASL. The models were trained on 66 subjects (119 scans) and tested on 39 subjects (44 scans) from three different vendors. Spatiotemporal denoising models were developed using another dataset (6 subjects, 10 scans) of multi-delay ASL. A range of input conditions was tested for denoising single and multi-delay ASL, respectively. The performance was evaluated using similarity metrics, spatial SNR and quantification accuracy of cerebral blood flow (CBF), and arterial transit time (ATT). RESULTS: SwinIR outperformed CNN and other Transformer-based networks, whereas pseudo-3D models performed better than 2D models for denoising single-delay ASL. The similarity metrics and image quality (SNR) improved with more slices in pseudo-3D models and further improved when using M0 as input, but introduced greater biases for CBF quantification. Pseudo-3D models with three slices achieved optimal balance between SNR and accuracy, which can be generalized to different vendors. For multi-delay ASL, spatiotemporal denoising models had better performance than spatial-only models with reduced biases in fitted CBF and ATT maps. CONCLUSIONS: SwinIR provided better performance than CNN and other Transformer-based methods for denoising both single and multi-delay 3D ASL data. The proposed model offers flexibility to improve image quality and/or reduce scan time for 3D ASL to facilitate its clinical use.

Brain age predicted using graph convolutional neural network explains neurodevelopmental trajectory in preterm neonates.

OBJECTIVES: Dramatic brain morphological changes occur throughout the third trimester of gestation. In this study, we investigated whether the predicted brain age (PBA) derived from graph convolutional network (GCN) that accounts for cortical morphometrics in third trimester is associated with postnatal abnormalities and neurodevelopmental outcome. METHODS: In total, 577 T1 MRI scans of preterm neonates from two different datasets were analyzed; the NEOCIVET pipeline generated cortical surfaces and morphological features, which were then fed to the GCN to predict brain age. The brain age index (BAI; PBA minus chronological age) was used to determine the relationships among preterm birth (i.e., birthweight and birth age), perinatal brain injuries, postnatal events/clinical conditions, BAI at postnatal scan, and neurodevelopmental scores at 30 months. RESULTS: Brain morphology and GCN-based age prediction of preterm neonates without brain lesions (mean absolute error [MAE]: 0.96 weeks) outperformed conventional machine learning methods using no topological information. Structural equation models (SEM) showed that BAI mediated the influence of preterm birth and postnatal clinical factors, but not perinatal brain injuries, on neurodevelopmental outcome at 30 months of age. CONCLUSIONS: Brain morphology may be clinically meaningful in measuring brain age, as it relates to postnatal factors, and predicting neurodevelopmental outcome. CLINICAL RELEVANCE STATEMENT: Understanding the neurodevelopmental trajectory of preterm neonates through the prediction of brain age using a graph convolutional neural network may allow for earlier detection of potential developmental abnormalities and improved interventions, consequently enhancing the prognosis and quality of life in this vulnerable population. KEY POINTS: •Brain age in preterm neonates predicted using a graph convolutional network with brain morphological changes mediates the pre-scan risk factors and post-scan neurodevelopmental outcomes. •Predicted brain age oriented from conventional deep learning approaches, which indicates the neurodevelopmental status in neonates, shows a lack of sensitivity to perinatal risk factors and predicting neurodevelopmental outcomes. •The new brain age index based on brain morphology and graph convolutional network enhances the accuracy and clinical interpretation of predicted brain age for neonates.

White matter microstructure and connectivity changes after surgery in male adults with obstructive sleep apnea: recovery or reorganization?

Study objectives: Obstructive sleep apnea (OSA) is a prevalent clinical problem significantly affecting cognitive functions. Surgical treatment is recommended for those unable to use continuous positive airway pressure. We aimed to investigate the therapeutic effect of upper airway surgery on the white matter (WM) microstructure and brain connectivity in patients with OSA. Methods: Twenty-one male patients with moderate-to-severe OSA were recruited for multi-level upper airway surgery. Overnight polysomnography (PSG), neuropsychiatric tests, and brain MRI scans were acquired before and 6.1 ± 0.8 months after surgery. Nineteen male patients with untreated OSA were also included as a reference group. We calculated the longitudinal changes of diffusion tensor imaging (DTI) parameters, including fractional anisotropy (ΔFA) and mean/axial/radial diffusivity (ΔMD/AD/RD). We also assessed changes in network properties based on graph theory. Results: Surgically treated patients showed improvement in PSG parameters and verbal memory after surgery. Globally, ΔFA was significantly higher and ΔRD was lower in the surgery group than in the untreated group. Especially ΔFA of the tracts involved in the limbic system was higher after surgery. In network analysis, higher Δbetweenness and lower Δclustering coefficients were observed in the surgical group than in the untreated group. Finally, the improvement of verbal memory after surgery positively correlated with ΔFA in superior thalamic radiation (p = 0.021), fronto aslant tracts (p = 0.027), and forceps minor tracts (p = 0.032). Conclusion: Surgical treatment of OSA can alleviate alterations in WM integrity and disruptions in local networks, particularly for the tracts involved in the limbic system. These findings may further explain the cognitive improvement observed after the treatment of OSA.

Style transfer generative adversarial networks to harmonize multisite MRI to a single reference image to avoid overcorrection.

Recent work within neuroimaging consortia have aimed to identify reproducible, and often subtle, brain signatures of psychiatric or neurological conditions. To allow for high-powered brain imaging analyses, it is often necessary to pool MR images that were acquired with different protocols across multiple scanners. Current retrospective harmonization techniques have shown promise in removing site-related image variation. However, most statistical approaches may over-correct for technical, scanning-related, variation as they cannot distinguish between confounded image-acquisition based variability and site-related population variability. Such statistical methods often require that datasets contain subjects or patient groups with similar clinical or demographic information to isolate the acquisition-based variability. To overcome this limitation, we consider site-related magnetic resonance (MR) imaging harmonization as a style transfer problem rather than a domain transfer problem. Using a fully unsupervised deep-learning framework based on a generative adversarial network (GAN), we show that MR images can be harmonized by inserting the style information encoded from a single reference image, without knowing their site/scanner labels a priori. We trained our model using data from five large-scale multisite datasets with varied demographics. Results demonstrated that our style-encoding model can harmonize MR images, and match intensity profiles, without relying on traveling subjects. This model also avoids the need to control for clinical, diagnostic, or demographic information. We highlight the effectiveness of our method for clinical research by comparing extracted cortical and subcortical features, brain-age estimates, and case-control effect sizes before and after the harmonization. We showed that our harmonization removed the site-related variances, while preserving the anatomical information and clinical meaningful patterns. We further demonstrated that with a diverse training set, our method successfully harmonized MR images collected from unseen scanners and protocols, suggesting a promising tool for ongoing collaborative studies. Source code is released in USC-IGC/style_transfer_harmonization (github.com).

Obstructive Sleep Apnea and Striatal Dopamine Availability in Parkinson's Disease.

BACKGROUND: Sleep disorders are frequently associated with Parkinson's disease. Obstructive sleep apnea syndrome is one of these sleep disorders and is associated with the severity of motor symptoms in Parkinson's disease. Obstructive sleep apnea can lead to dopaminergic neuronal cell degeneration and may impair the clearance of α-synuclein in Parkinson's disease. Striatal dopamine uptake is a surrogate marker of nigral dopaminergic cell damage. OBJECTIVE: We aimed to investigate the differences in striatal dopamine availability between Parkinson's disease patients with or without obstructive sleep apnea. METHODS: A total of 85 de novo and nonmedicated Parkinson's disease patients were enrolled. Full-night polysomnography was performed for all patients, and obstructive sleep apnea was diagnosed as apnea/hypopnea index ≥5. Positron emission tomography was performed with 18 F-N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane, and the regional standardized-uptake values were analyzed using a volume-of-interest template and compared between groups with or without obstructive sleep apnea. RESULTS: Dopamine availability in the caudate nucleus of the obstructive sleep apnea group was significantly lower than that of the nonobstructive sleep apnea group. On subgroup analysis, such association was found in female but not in male patients. In other structures (putamen, globus pallidus, and thalamus), dopamine availability did not differ between the two groups. CONCLUSION: This study supports the proposition that obstructive sleep apnea can contribute to reduced striatal dopamine transporter availability in Parkinson's disease. Additional studies are needed to assess the causal association between obstructive sleep apnea and the neurodegenerative process in Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004). DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

More extensive white matter disruptions present in untreated obstructive sleep apnea than we thought: A large sample diffusion imaging study.

Obstructive sleep apnea (OSA) may lead to white mater (WM) disruptions and cognitive deficits. However, no studies have investigated the full extent of the brain WM, and its associations with cognitive deficits in OSA remain unclear. We thus applied diffusion tensor imaging (DTI) tractography with multi-fiber models and used atlas-based bundle-specific approach to investigate the WM abnormalities for various tracts of the cerebral cortex, thalamus, brainstem, and cerebellum in patients with untreated OSA. We enrolled 100 OSA patients and 63 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values mapped on 33 regions of interest including WM tracts of cortex, thalamus, brainstem, and cerebellum were obtained from tractography-based reconstructions. We compared FA/MD values between groups and correlated FA/MD with clinical data in the OSA group after controlling for age and body mass index. OSA patients showed significantly lower FA values in multiple WM fibers including corpus callosum, inferior fronto-occipital fasciculus, middle/superior longitudinal fasciculi, thalamic radiations, and uncinate (FDR <0.05). Higher FA values were found in medial lemniscus of patients compared to controls (FDR <0.05). Lower FA values of rostrum of corpus callosum correlated with lower visual memory performance in OSA group (p < .005). Our quantitative DTI analysis demonstrated that untreated OSA could negatively impact the integrity of pathways more broadly, including brainstem structures such as medial lemniscus, in comparison to previous findings. Fiber tract abnormalities of the rostral corpus callosum were associated with impaired visual memory in untreated OSA may provide insights into the related pathomechanism.

Different effects of cardiometabolic syndrome on brain age in relation to gender and ethnicity.

BACKGROUND: A growing body of evidence shows differences in the prevalence of cardiometabolic syndrome (CMS) and dementia based on gender and ethnicity. However, there is a paucity of information about ethnic- and gender-specific CMS effects on brain age. We investigated the different effects of CMS on brain age by gender in Korean and British cognitively unimpaired (CU) populations. We also determined whether the gender-specific difference in the effects of CMS on brain age changes depending on ethnicity. METHODS: These analyses used de-identified, cross-sectional data on CU populations from Korea and United Kingdom (UK) that underwent brain MRI. After propensity score matching to balance the age and gender between the Korean and UK populations, 5759 Korean individuals (3042 males and 2717 females) and 9903 individuals from the UK (4736 males and 5167 females) were included in this study. Brain age index (BAI), calculated by the difference between the predicted brain age by the algorithm and the chronological age, was considered as main outcome and presence of CMS, including type 2 diabetes mellitus (T2DM), hypertension, obesity, and underweight was considered as a predictor. Gender (males and females) and ethnicity (Korean and UK) were considered as effect modifiers. RESULTS: The presence of T2DM and hypertension was associated with a higher BAI regardless of gender and ethnicity (p < 0.001), except for hypertension in Korean males (p = 0.309). Among Koreans, there were interaction effects of gender and the presence of T2DM (p for T2DM*gender = 0.035) and hypertension (p for hypertension*gender = 0.046) on BAI in Koreans, suggesting that T2DM and hypertension are each associated with a higher BAI in females than in males. In contrast, among individuals from the UK, there were no differences in the effects of T2DM (p for T2DM*gender = 0.098) and hypertension (p for hypertension*gender = 0.203) on BAI between males and females. CONCLUSIONS: Our results highlight gender and ethnic differences as important factors in mediating the effects of CMS on brain age. Furthermore, these results suggest that ethnic- and gender-specific prevention strategies may be needed to protect against accelerated brain aging.