Development and validation of a perivascular space segmentation method in multi-center datasets.

BACKGROUND: Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) are significant markers associated with various neurological diseases. Although quantitative analysis of PVS may enhance sensitivity and improve consistency across studies, the field lacks a universally validated method for analyzing images from multi-center studies. METHODS: We annotated PVS on multi-center 3D T1-weighted (T1w) images acquired using scanners from three major vendors (Siemens, General Electric, and Philips). A neural network, mcPVS-Net (multi-center PVS segmentation network), was trained using data from 40 subjects and then tested in a separate cohort of 15 subjects. We assessed segmentation accuracy against ground truth masks tailored for each scanner vendor. Additionally, we evaluated the agreement between segmented PVS volumes and visual scores for each scanner. We also explored correlations between PVS volumes and various clinical factors such as age, hypertension, and white matter hyperintensities (WMH) in a larger sample of 1020 subjects. Furthermore, mcPVS-Net was applied to a new dataset comprising both T1w and T2-weighted (T2w) images from a United Imaging scanner to investigate if PVS volumes could discriminate between subjects with differing visual scores. We also compared the mcPVS-Net with a previously published method that segments PVS from T1 images. RESULTS: In the test dataset, mcPVS-Net achieved a mean DICE coefficient of 0.80, with an average Precision of 0.81 and Recall of 0.79, indicating good specificity and sensitivity. The segmented PVS volumes were significantly associated with visual scores in both the basal ganglia (r = 0.541, p < 0.001) and white matter regions (r = 0.706, p < 0.001), and PVS volumes were significantly different among subjects with varying visual scores. Segmentation performance was consistent across different scanner vendors. PVS volumes exhibited significant associations with age, hypertension, and WMH. In the United Imaging scanner dataset, PVS volumes showed good associations with PVS visual scores evaluated on either T1w or T2w images. Compared to a previously published method, mcPVS-Net showed a higher accuracy and improved PVS segmentation in the basal ganglia region. CONCLUSION: The mcPVS-Net demonstrated good accuracy for segmenting PVS from 3D T1w images. It may serve as a useful tool for future PVS research.

Higher intracranial arterial pulsatility is associated with presumed imaging markers of the glymphatic system: An explorative study.

BACKGROUND: Arterial pulsation has been suggested as a key driver of paravascular cerebrospinal fluid flow, which is the foundation of glymphatic clearance. However, whether intracranial arterial pulsatility is associated with glymphatic markers in humans has not yet been studied. METHODS: Seventy-three community participants were enrolled in the study. 4D phase-contrast magnetic resonance imaging (MRI) was used to quantify the hemodynamic parameters including flow pulsatility index (PIflow) and area pulsatility index (PIarea) from 13 major intracerebral arterial segments. Three presumed neuroimaging markers of the glymphatic system were measured: including dilation of perivascular space (PVS), diffusivity along the perivascular space (ALPS), and volume fraction of free water (FW) in white matter. We explored the relationships between PIarea, PIflow, and the presumed glymphatic markers, controlling for related covariates. RESULTS: PIflow in the internal carotid artery (ICA) C2 segment (OR, 1.05; 95 % CI, 1.01-1.10, per 0.01 increase in PI) and C4 segment (OR, 1.05; 95 % CI, 1.01-1.09) was positively associated with the dilation of basal ganglia PVS, and PIflow in the ICA C4 segment (OR, 1.06, 95 % CI, 1.02-1.10) was correlated with the dilation of PVS in the white matter. ALPS was associated with PIflow in the basilar artery (ß, -0.273, p, 0.046) and PIarea in the ICA C2 (ß, -0.239, p, 0.041) and C7 segments (ß, -0.238, p, 0.037). CONCLUSIONS: Intracranial arterial pulsatility was associated with presumed neuroimaging markers of the glymphatic system, but the results were not consistent across different markers. Further studies are warranted to confirm these findings.

Oxygen Vacancies-Induced Antifouling Photoelectrochemical Aptasensor for Highly Sensitive and Selective Determination of α-Fetoprotein.

Accurate measurement of cancer markers in urine is a convenient method for tumor monitoring. However, the concentration of cancer markers in urine is so low that it is difficult to achieve their measurement. Photoelectrochemical (PEC) sensors are a promising technology to realize the detection of trace cancer markers due to their high sensitivity. Currently, the interference of nonspecific biomolecules in urine is the main reason affecting the high sensitivity and selectivity of PEC sensors in detecting cancer markers. In this work, a strategy of oxygen vacancy (OV) modulation is proposed to construct a fouling-resistant PEC aptamer sensing platform for the detection of α-fetoprotein (AFP), a liver cancer marker. The introduction of OVs induces the formation of intermediate localized states in the photoelectric material, which not only facilitates the separation of photogenerated carriers but also leads to the redshift of the light absorption edge. More importantly, OVs with positive electrical properties can be employed to modify the antifouling layer (C-PEG) with negatively charged groups through an electrostatic interaction. The synergistic effect of OVs, antifouling layer, and aptamer resulted in a TiO2/OVs/C-PEG-based PEC sensor achieves a wide linear range from 1 pg/mL to 100 ng/mL and a low detection limit of 0.3 pg/mL for AFP. In addition, the sensor successfully realized the determination of AFP in urine samples and accurately differentiated between normal people and liver cancer patients in the early and advanced stages. This project is of great significance in advancing the application of photoelectrochemical bioanalytical technology to achieve the detection of cancer markers in urine by investigating the construction of an OVs-regulated fouling-resistant sensing interface.

Small vessel disease and cognitive reserve oppositely modulate global network redundancy and cognitive function: A study in middle-to-old aged community participants.

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community-dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity-related CR (CRI-leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI-leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD.

Engineering probiotic Escherichia coli Nissle 1917 to block transfer of multiple antibiotic resistance genes by exploiting a type I CRISPR-Cas system.

Many multidrug-resistant (MDR) bacteria have evolved through the accumulation of antibiotic resistance genes (ARGs). Although the potential risk of probiotics as reservoirs of ARGs has been recognized, strategies for blocking the transfer of ARGs while using probiotics have rarely been explored. The probiotic Escherichia coli Nissle 1917 (EcN) has long been used for treating intestinal diseases. Here, we demonstrate frequent transfer of ARGs into EcN both in vitro and in vivo, raising concerns about its potential risk of accumulating antibiotic resistance. Given that no CRISPR-Cas system was found in natural EcN, we integrated the type I-E CRISPR-Cas3 system derived from E. coli BW25113 into EcN. The engineered EcN was able to efficiently cleave multiple ARGs [i.e., mcr-1, blaNDM-1, and tet(X)] encoding enzymes for degrading last-resort antibiotics. Through co-incubation of EcN expressing Cas3-Cascade and that expressing Cas9, we showed that the growth of the former strain outcompeted the latter strain, demonstrating a better clinical application prospect of EcN expressing the type I-E CRISPR-Cas3 system. In the intestine of a model animal (i.e., zebrafish), the engineered EcN exhibited immunity against the transfer of CRISPR-targeted ARGs. Our work equips EcN with immunity against the transfer of multiple ARGs by exploiting the exogenous type I-E CRISPR-Cas3 system, thereby reducing the risk of the spread of ARGs while using it as a probiotic chassis for generating living therapeutics. IMPORTANCE: To reduce the development of antibiotic resistance, probiotics have been considered as a substitute for antibiotics. However, probiotics themselves are reservoirs of antibiotic resistance genes (ARGs). This study introduces a new strategy for limiting the spread of ARGs by engineering the typical probiotic strain Escherichia coli Nissle 1917 (EcN), which has been used for treating intestinal diseases and developed as living therapeutics. We also demonstrate that the type I CRISPR-Cas system imposes a lower growth burden than the type II CRISPR-Cas system, highlighting its promising clinical application potential. Our work not only provides a new strategy for restricting the transfer of ARGs while using probiotics but also enriches the genetic engineering toolbox of EcN, paving the way for the safe use and development of probiotics as living therapeutics.

An Investigation of Cerebral Vascular Functional Properties in Middle-to-Old Age Community People With High Vascular Risk Profiles.

BACKGROUND: Vascular degeneration is an important cause of brain damage in aging. Assessing the functional properties of the cerebral vascular system may aid early diagnosis and prevention. PURPOSE: To investigate the relationships between potential vascular functional markers and vascular risks, brain parenchymal damage, and cognition. STUDY TYPE: Retrospective. SUBJECTS: Two hundred two general community subjects (42-80 years, males/females: 127/75). FIELD STRENGTH/SEQUENCE: 3 T, spin echo T1W/T2W/FLAIR, resting-state functional MRI with an echo-planar sequence (rsfMRI), pseudo-continuous arterial spin labeling (pCASL) with a three-dimensional gradient-spin echo sequence. ASSESSMENT: Cerebral blood flow (CBF) in gray matter calculated using pCASL, blood transit times calculated using rsfMRI, and the SD of internal carotid arteries signal (ICAstd) calculated using rsfMRI; visual assessment for lacunes; quantification of white matter hyperintensity volume; permutation test for quality control; collection of demographic and clinical data, Montreal Cognitive Assessment, Mini-Mental State Examination. STATISTICAL TESTS: Kolmogorov-Smirnov test; Spearman rank correlation analysis; Multivariable linear regression analysis controlling for covariates; The level of statistical significance was set at P < 0.05. RESULTS: Age was negatively associated with ICAstd (ß = -0.180). Diabetes was associated with longer blood transit time from large arteries to capillary bed (ß = 0.185, adjusted for age, sex, and intracranial volume). Larger ICAstd was associated with less presence of lacunes (odds ratio: 0.418, adjusted for age and sex). Higher gray matter CBF (ß = 0.154) and larger ICAstd (ß = 0.136) were associated with better MoCA scores (adjusted for age, sex, and education). DATA CONCLUSION: Prolonged blood transit time, decreased ICAstd, and diminished CBF were associated with vascular dysfunction and cognitive impairment. They may serve as vascular functional markers in future studies. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Potency analysis of twelve cannabinoids in industrial hemp via ultrahigh-performance liquid chromatography-tandem mass spectrometry.

RATIONALE: With an increasing appreciation for the unique pharmacological properties associated with distinct, individual cannabinoids of Cannabis sativa, there is demand for accurate and reliable quantification for a growing number of them. In this study, we developed rapid, sensitive, selective, accurate, and validated liquid chromatography-tandem mass spectrometry for the quantification of cannabinoids. METHODS: Crushed industrial hemp flower and leaf sample was extracted by 95% methanol aqueous, sonicated for 30 min. UPLC-MS/MS analysis using Waters Acquity BEH-C18 column and electrospray ionization(ESI) mass spectrometry detector. RESULTS: The method was validated to demonstrate its reproducibility and precision, linearity, recovery investigation, and investigation of matrix effect. The concentration-response relationship for all analyzed cannabinoids were linear with R2 values >0.99, with intra- and inter-day precision and relative errors below 12%. The recovery and matrix effect were measured as 66.1%-104.1% and 70.42%-110.75%. CONCLUSIONS: This study established a UHPLC-MS/MS method for the simultaneous and rapid quantitative determination of twelve cannabinoids in industrial hemp flowers and leaves in 11 min. The method was used to analyze 43 industrial hemp flower and leaf samples, with the data being statistically analyzed. Based on the statistical analysis of the cannabinoids, hemp from different regions and different varieties were well distinguished by the PLS-DA model, with the main contributing substances being cannabidiol, Δ9-tetrahydrocannabinol, and Δ8-tetrahydrocannabinol.

A shifted ratio spectrum strategy for effective subtraction of fluorescence interference in Raman spectra.

Raman spectroscopy is an important technique for analyzing the chemical composition of samples in many fields. A severe challenge often encountered in Raman measurements is the presence of a concurrent fluorescence background, especially in biological samples. In order to obtain accurate Raman spectra, the fluorescence background must be subtracted from the original Raman spectra. We proposed a shifted ratio spectrum method to subtract the strong fluorescence background from the original Raman spectrum. First, the original Raman spectrum is divided into multiple regions according to the spectral shape of the shifted ratio spectra, and then, Gaussian fitting is performed in each region. The fitting results are stitched together in order to obtain the complete fluorescence background. Finally, this fluorescence background is subtracted from the original spectrum to obtain a pure Raman spectrum. This method can accurately subtract the fluorescence background of Rhodamine 6G (R6G)/ethanol solution and serum. This highlights the great potential of this method for applications in both biological and non-biological samples.

Synthesis, Thermal Stability and Antifungal Evaluation of Two New Pyrrole Esters.

To develop new chemicals that are stable at high temperatures with biological activity, a pyrrole intermediate was firstly synthesized using glucosamine hydrochloride as raw materials through cyclization and oxidation. Further, two novel pyrrole ester derivatives were prepared via Steglich esterification from pyrrole intermediate with vanillin and ethyl maltol, respectively. Nuclear magnetic resonance (1 H-NMR, 13 C NMR), infrared spectroscopy (IR) and high resolution mass spectrometry (HRMS) were used to confirm the target compounds. Thermal behavior of the compounds was investigated by thermogravimetry (TG), differential scanning calorimeter (DSC) and the pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) methods. The plausible pyrolytic mechanism was proposed. Additionally, their biological activities against the pathogens Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Phytophthora nicotianae, and Rhizoctonia solani were assessed. These target compounds showed outstanding antifungal activities and the highest inhibitor rates of 62.50 % and 68.75 % against R. solani with EC50 values of 0.0296 and 0.0200 mg mL-1 , respectively. SDHI protein sequence was molecularly docked to identify the binding mechanisms in the active pocket and examine the interactions between both the molecules and the SDHI protein.

Nucleic acid aptamer-based electrochemical sensor for the detection of serum P-tau231 and the instant screening test of Alzheimer's disease.

The instant screening of patients with a tendency towards developing Alzheimer's disease (AD) is significant for providing preventive measures and treatment. However, the current imaging-based technology cannot meet the requirements in the early stage. Developing biosensor-based liquid biopsy technology could be overcoming this bottleneck problem. Herein, we developed a simple, low-cost, and sensitive electrochemical aptamer biosensor for detecting phosphorylated tau protein threonine 231 (P-tau231), the earliest and one of the most efficacious abnormally elevated biomarkers of AD. Gold nanoparticles (AuNPs) were electrochemically synthesized on a glassy carbon electrode as the transducer, exhibiting excellent conductivity, and were applied to amplify the electrochemical signal. A nucleic acid aptamer was designed as the receptor to capture the P-tau231 protein, specifically through the formation of an aptamer-antigen complex. The proposed biosensor showed excellent sensitivity in detecting P-tau 231, with a broad linear detection range from 10 to 107 pg/mL and a limit of detection (LOD) of 2.31 pg/mL. The recoveries of the biosensor in human serum ranged from 97.59 to 103.26%, demonstrating that the biosensor could be used in complex practical samples. In addition, the results showed that the developed biosensor has good repeatability, reproducibility, and stability, which provides a novel method for the early screening of AD.

"Building bridges"-communication education for residents in radiology: a scoping review.

BACKGROUND: Good communication is an important professional attribute for radiologists. However, explorations of communication education and their outcomes in radiology residents are sparse. This scoping review aims to evaluate the existing literature on communication education for radiology residents, identify gaps in current practices, and suggest directions for future studies. METHODS: A scoping review following the six-step approach of Arksey and O'Malley was undertaken. We searched through PubMed, Embase, ERIC, and Web of Science databases, focusing on communication education in radiology residents. RESULTS: Sixteen of the 3096 identified articles were included in the analysis. Most studies (13/16) originated from the United States. The studies varied in study design, including quantitative, qualitative and mixed-methods approaches. The sample sizes of most studies were small to moderate, with more than half of the studies had fewer than 30 participants. The identified studies predominantly focused on communication with patients and healthcare professionals. The need for communication education, the efficacy of specific communication education programs, and the capability of some assessment tools for evaluating residents' communication skills were investigated. CONCLUSIONS: This scoping review reveals the gap between the need for communication education and the lack of comprehensive education programs in radiology residents globally. Future studies should develop tailored interventions and use reliable assessment tools, engaging more participants with extended follow-up periods, and expand the scope of communication training to include all relevant stakeholders.

[Effect of Peitu Yifei Granules on autophagy mechanism in rats with idiopathic pulmonary fibrosis based on PI3K/Akt/mTOR signaling pathway].

To investigate the mechanism by which Peitu Yifei Granules inhibit idiopathic pulmonary fibrosis(IPF) in rats, fifty specific-pathogen-free(SPF) grade male Wistar rats were randomly divided into blank group and modeling group. IPF was induced in the modeling group rats by tracheal infusion of 5 mg·kg~(-1) bleomycin(BLM) and then randomly divided into model group, pirfenidone group, and high-dose, medium-dose, and low-dose groups treated with Peitu Yifei Granules. After 24 hours of modeling, the treatment groups received intragastric administration of either Peitu Yifei Granules or pirfenidone as a positive control drug; meanwhile, the model group received an equal volume of normal saline. After 21 days of treatment administration, lung tissue samples were collected for analysis. Pathological changes in lung tissues were assessed using hematoxylin-eosin(HE) staining and Masson's trichrome staining. The expression levels of protein kinase B(Akt), mammalian target of rapamycin(mTOR), their phosphorylated forms, and sequestosome 1(p62) were determined through Western blot(WB). Fluorescent quantitative real-time polymerase chain reaction(RT-qPCR) was used to measure messenger ribonucleic acid(mRNA) expression levels of Beclin-1, microtubule-associated proteins 1A/1B light chain 3B(LC3B), and p62. Immunohistochemistry was performed to assess protein expression levels of Beclin-1 and LC3B in lung tissue samples. RESULTS:: demonstrated that lung tissue structure appeared normal without significant collagen deposition in the blank group rats. In contrast, rats from the model group exhibited thickened alveolar septa along with evident inflammatory changes and collagen deposition. Compared to the model group rats, those treated with Peitu Yifei Granules or pirfenidone showed significantly improved lung tissue structure with reduced inflammation and collagen deposition observed histologically. Furthermore, compared with those of the blank group, the expressions of p62 and its mRNA, p-Akt and p-mTOR protein in lung tissues of the model group were significantly increased, while Beclin-1, LC3B and their mRNA levels were significantly decreased. Compared with those of the model group, the expressions of p62 and its mRNA, p-Akt and p-mTOR in lung tissues of the pirfenidone group and Peitu Yifei Granules high-dose and medium-dose groups were significantly decreased, while Beclin-1, LC3B and their mRNA expressions were significantly increased. The above results indicate that Peitu Yifei Granules can improve autophagy levels in lung tissues by inhibiting the phosphoinositide 3-kinase(PI3K)/Akt/mTOR signaling pathway and delay the development of IPF disease.

Re enhances anthocyanin and proanthocyanidin accumulation to produce red foliated cotton and brown fiber.

Red foliated cotton is a typical dominant mutation trait in upland cotton (Gossypium hirsutum). Although mutants have been described, few responsible genes have been identified and characterized. In this study, we performed map-based cloning of the red foliated mutant gene (Re) derived from the cross between G. hirsutum cv. Emian22 and G. barbadense acc. 3-79. Through expression profiling, metabolic pathway analysis, and sequencing of candidate genes, Re was identified as an MYB113 transcription factor. A repeat sequence variation in the promoter region increased the activity of the promoter, which enhanced the expression of Re. Re expression driven by the 35S promoter produced a red foliated phenotype, as expected. When the gene was driven by a fiber elongation-specific promoter, promoter of α-expansin 2 (PGbEXPA2), Re was specifically expressed in 5- to 10-day post-anthesis fibers rather than in other tissues, resulting in brown mature fibers. Re responded to light through phytochrome-interacting factor 4 and formed a dimer with transparent testa 8, which increased its expression as well as that of anthocyanin synthase and UDP-glucose:flavonoid 3-o-glucosyl transferase, and thus activated the entire anthocyanin metabolism pathway. Our research has identified the red foliated mutant gene in cotton, which paves the way for detailed studies of anthocyanin and proanthocyanidin metabolism and pigment accumulation in cotton and provides an alternative strategy for producing brown fiber.

Visualizing Cerebral Small Vessel Degeneration During Aging and Diseases Using Magnetic Resonance Imaging.

Cerebral small vessel disease is a major contributor to brain disorders in older adults. It is associated with a much higher risk of stroke and dementia. Due to a lack of clinical and fluid biomarkers, diagnosing and grading small vessel disease are highly dependent on magnetic resonance imaging. In the past, researchers mostly used brain parenchymal imaging markers to represent small vessel damage, but the relationships between these surrogate markers and small vessel pathologies are complex. Recent progress in high-resolution magnetic resonance imaging methods, including time-of-flight MR angiography, phase-contrast MR angiography, black blood vessel wall imaging, susceptibility-weighted imaging, and contrast-enhanced methods, allow for direct visualization of cerebral small vessel structures. They could be powerful tools for understanding aging-related small vessel degeneration and improving disease diagnosis and treatment. This article will review progress in these imaging techniques and their application in aging and disease studies. Some challenges and future directions are also discussed. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: 3.

White Matter Tract Injury by MRI in CADASIL Patients is Associated With Iron Accumulation.

BACKGROUND: Widespread white matter (WM) injury is a hallmark feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, controversies about the mechanism of WM tract injury exist persistently. Excessive iron accumulation, frequently reported in CADASIL patients, might cause WM tract injury. PURPOSE: To test the association between iron accumulation and WM tract injury in CADASIL patients. STUDY TYPE: Retrospective. POPULATION: A total of 35 CADASIL patients (age = 50.4 ± 6.4, 62.9% female) and 48 healthy controls (age = 55.7 ± 8.0, 68.8% female). FIELD STRENGTH/SEQUENCE: Diffusion-weighted spin-echo echo-planar sequence; enhanced susceptibility-weighted angiography (ESWAN) gradient echo sequence on a 3 T scanner. ASSESSMENT: The phase images acquired by ESWAN were used to calculate quantitative susceptibility mapping (QSM). Iron accumulation was evaluated in deep gray matters using QSM. WM tract injury was quantified by diffusion metrics based on WM major tracts skeleton. We compared iron deposition between groups and analyzed the correlation between WM tract injury and iron deposition in regions showing significant differences from healthy controls. Exploratory analysis was carried out to investigate whether WM tract injury mediated the relationship between iron deposition and cognitive impairment evaluated by Mini-Mental State Examination (MMSE). STATISTICAL TESTS: General linear model (GLM), partial correlation, stepwise linear regression and mediation analysis were used. The threshold of statistical significance was set as p < 0.05. RESULTS: Compared with healthy controls, CADASIL patients had significantly increased iron deposition in the caudate and putamen. Aberrant iron deposition in these two regions was significantly associated with decreased WM fractional anisotropy (FA) (caudate, r = -0.373； putamen, r = - 0.421), and increased radial diffusivity (RD) (caudate, r = 0.372; putamen, r = 0.386). Furthermore, WM tract injury mediated the relationship between iron deposition and cognitive impairment. DATA CONCLUSION: Patients with CADASIL show increased iron deposition in the caudate and putamen that is correlated to WM tract injury, which may in turn mediate the association with cognitive impairment. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Associations of Alzheimer's Disease Pathology and Small Vessel Disease With Cerebral White Matter Degeneration: A Tract-Based MR Diffusion Imaging Study.

BACKGROUND: White matter (WM) degeneration is a key feature of Alzheimer's disease (AD). However, the underlying mechanism remains unclear. PURPOSE: To investigate how amyloid-ß (Aß), tau, and small vascular disease (SVD) jointly affect WM degeneration in subjects along AD continuum. STUDY TYPE: Retrospective. SUBJECTS: 152 non-demented participants (age: 55.8-91.6, male/female: 66/86) from the ADNI database were included, classified into three groups using the A (Aß)/T (tau)/N pathological scheme (Group 1: A-T-; Group 2: A+T-; Group 3: A+T+) based on positron emission tomography data. FIELD STRENGTH/SEQUENCE: 3T; T1-weighted images, T2-weighted fluid-attenuated inversion recovery images, T2*-weighted images, diffusion-weighted spin-echo echo-planar imaging sequence (54 diffusion directions). ASSESSMENT: Free-water diffusion model (generated parameters: free water, FW; tissue fractional anisotropy, FAt; tissue mean diffusivity, MDt); SVD total score; Neuropsychological tests. STATISTICAL TESTS: Linear regression analysis was performed to investigate the independent contribution of AD (Aß and tau) and SVD pathologies to diffusion parameters in each fiber tract, first in the entire population and then in each subgroup. We also investigated associations between diffusion parameters and cognitive functions. The level of statistical significance was set at p < 0.05 (false discovery rate corrected). RESULTS: In the entire population, we found that: 1) Increased FW was significantly associated with SVD and tau, while FAt and MDt were significantly associated with Aß and tau; 2) The spatial pattern of fiber tracts related to a certain pathological marker is consistent with the known distribution of that pathology; 3) Subgroup analysis showed that Group 2 and 3 had more alterations of FAt and MDt associated with Aß and tau; 4) Diffusion imaging indices showed significant associations with cognitive score in all domains except memory. DATA CONCLUSION: WM microstructural injury was associated with both AD and SVD pathologies, showing compartment-specific, tract-specific, and stage-specific WM patterns. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Presumed periventricular venous infarction on magnetic resonance imaging and its association with increased white matter edema in CADASIL.

OBJECTIVES: Venous pathology could contribute to the development of parenchymal lesions in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aim to identify presumed periventricular venous infarction (PPVI) in CADASIL and analyze the associations between PPVI, white matter edema, and microstructural integrity within white matter hyperintensities (WMHs) regions. METHODS: We included forty-nine patients with CADASIL from a prospectively enrolled cohort. PPVI was identified according to previously established MRI criteria. White matter edema was evaluated using the free water (FW) index derived from diffusion tensor imaging (DTI), and microstructural integrity was evaluated using FW-corrected DTI parameters. We compared the mean FW values and regional volumes with different levels of FW (ranging from 0.3 to 0.8) in WMHs regions between the PPVI and non-PPVI groups. We used intracranial volume to normalize each volume. We also analyzed the association between FW and microstructural integrity in fiber tracts connected with PPVI. RESULTS: We found 16 PPVIs in 10 of 49 CADASIL patients (20.4%). The PPVI group had larger WMHs volume (0.068 versus 0.046, p = 0.036) and higher FW in WMHs (0.55 versus 0.52, p = 0.032) than the non-PPVI group. Larger areas with high FW content were also found in the PPVI group (threshold: 0.7, 0.47 versus 0.37, p = 0.015; threshold: 0.8, 0.33 versus 0.25, p = 0.003). Furthermore, higher FW correlated with decreased microstructural integrity (p = 0.009) in fiber tracts connected with PPVI. CONCLUSIONS: PPVI was associated with increased FW content and white matter degeneration in CADASIL patients. CLINICAL RELEVANCE STATEMENT: PPVI is an important factor related with WMHs, and therefore, preventing the occurrence of PPVI would be beneficial for patients with CADASIL. KEY POINTS: •Presumed periventricular venous infarction is important and occurs in about 20% of patients with CADASIL. •Presumed periventricular venous infarction was associated with increased free water content in the regions of white matter hyperintensities. •Free water correlated with microstructural degenerations in white matter tracts connected with the presumed periventricular venous infarction.

Superficial white matter microstructure affects processing speed in cerebral small vessel disease.

White matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD), which contributes to about 50% of dementias worldwide. Microstructural alterations in deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In 141 CSVD patients, processing speed was assessed using Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (volume on T2-FLAIR) and diffusion MRI measures. SWM imaging measures had a large contribution to processing speed, despite a relatively low SWM WMH burden. Across all imaging measures, SWM free water (FW) had the strongest association with processing speed, followed by SWM mean diffusivity (MD). SWM FW was the only marker to significantly increase between two subgroups with the lowest WMH burdens. When comparing two subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Mediation analysis revealed that SWM FW fully mediated the association between WMH volume and processing speed, while no mediation effect of MD or DWM FW was observed. Overall, results suggest that the SWM has an important contribution to processing speed, while SWM FW is a sensitive imaging marker associated with cognition in CSVD. This study extends the current understanding of CSVD-related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes.

Altered brain structural and functional connectivity in schizotypy.

BACKGROUND: Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of 'brain disconnection' and 'brain connectivity compensation' to 'brain connectivity decompensation'. METHODS: In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated. RESULTS: We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network. CONCLUSIONS: These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.

Fine-mapping and candidate gene analysis of qFL-c10-1 controlling fiber length in upland cotton (Gossypium hirsutum L.).

KEY MESSAGE: A fiber length QTL, qFL-c10-1, was fine-mapped to a 96.5-kb region containing one gene that has not been characterized in plants. Fiber length is an important component of cotton fiber quality, which is associated with other quality properties such as fiber strength, fiber maturity, and fineness. In our previous studies, a stable QTL qFL-c10-1 controlling fiber length had been identified on chromosome A10 in an upland cotton recombinant inbred line (RIL) population from a cross between Jimian5 and DH962. To fine-map qFL-c10-1, an F2 population with 1081 individual plants from a cross between a recombinant line DJ61 and Jimian5 was established. Using linkage analysis and progeny recombination experiment, qFL-c10-1 was mapped into a 96.5-kb genomic region that just contained one proper transcript Ghir_A10G022020 (described as GhFL10), an undescribed gene in plants. One 214-bp deletion was identified in the promoter region of DJ61 compared with Jimian5. Quantitative real-time PCR (qRT-PCR) and comparative analysis of parental sequences suggested that GhFL10 was the most promising candidate gene for qFL-c10-1. According to RNA-seq, yeast two-hybrid assay and bimolecular fluorescence complementation (BiFC), we speculate that GhFL10 interacts with NF-YA transcription factors to negatively regulate fiber elongation.