Multimodal data fusion reveals functional and neurochemical correlates of Parkinson's disease.

BACKGROUND: Neurotransmitter deficits and spatial associations among neurotransmitter distribution, brain activity, and clinical features in Parkinson's disease (PD) remain unclear. Better understanding of neurotransmitter impairments in PD may provide potential therapeutic targets. Therefore, we aimed to investigate the spatial relationship between PD-related patterns and neurotransmitter deficits. METHODS: We included 59 patients with PD and 41 age- and sex-matched healthy controls (HCs). The voxel-wise mean amplitude of the low-frequency fluctuation (mALFF) was calculated and compared between the two groups. The JuSpace toolbox was used to test whether spatial patterns of mALFF alterations in patients with PD were associated with specific neurotransmitter receptor/transporter densities. RESULTS: Compared to HCs, patients with PD showed reduced mALFF in the sensorimotor- and visual-related regions. In addition, mALFF alteration patterns were significantly associated with the spatial distribution of the serotonergic, dopaminergic, noradrenergic, glutamatergic, cannabinoid, and acetylcholinergic neurotransmitter systems (p < 0.05, false discovery rate-corrected). CONCLUSIONS: Our results revealed abnormal brain activity patterns and specific neurotransmitter deficits in patients with PD, which may provide new insights into the mechanisms and potential targets for pharmacotherapy.

Repurposing of the PET Probe Prototype PiB for Label and Radiation-Free CEST MRI Molecular Imaging of Amyloid.

Positron emission tomography (PET) probes are specific and sensitive while suffering from radiation risk. It is worthwhile to explore the chemical emission saturation transfer (CEST) effects of the probe prototypes and repurpose them for CEST imaging to avoid radiation. In this study, we used 11C-PiB as an example of a PET probe for detecting amyloid and tested the feasibility of repurposing this PET probe prototype, PiB, for CEST imaging. After optimizing the parameters through preliminary phantom experiments, we used APP/PS1 transgenic mice and age-matched C57 mice for in vivo CEST magnetic resonance imaging (MRI) of amyloid. Furthermore, the pathological assessment was conducted on the same brain slices to evaluate the correlation between the CEST MRI signal abnormality and ß-amyloid deposition detected by immunohistochemical staining. In our results, the Z-spectra revealed an apparent CEST effect that peaked at approximately 6 ppm. APP/PS1 mice as young as 9 months injected with PiB showed a significantly higher CEST effect compared to the control groups. The hyperintense region was correlated with the Aß deposition shown by pathological staining. In conclusion, repurposing the PET probe prototype for CEST MRI imaging is feasible and enables label- and radiation-free detection of the amyloid while maintaining the sensitivity and specificity of the ligand. This study opens the door to developing CEST probes based on PET probe prototypes.

Alteration of intracerebral metabolites and subjective sleepiness by acute caffeine administration in adults.

Background: Caffeine is the most widely consumed psychostimulant. Despite this, the effects of acute caffeine intake on brain metabolite levels remain largely unknown. We aimed to investigate the effect of acute caffeine intake on brain metabolite concentrations in different caffeine consumption habit groups and to explore the association between metabolite changes and sleepiness. Methods: Forty-five healthy adults were divided into groups based on their daily caffeine consumption: ≥1 cup/day, <1 cup/day, and no consumption. The exclusion criteria were the presence of neurological disorder, habitual consumption of mind-altering substances, and individuals who were unable to undergo magnetic resonance imaging. Mescher-Garwood point resolved spectroscopy and conventional spectroscopy data were acquired at 3 Tesla from voxels in the thalamus and posterior cingulate cortex (PCC). Subjective sleepiness was measured with the Karolinska Sleepiness Scale. Results: The results of two-way repeated measures analysis of variance indicated a significant interaction effect between time and group for glutamate, glycerylphosphocholine and phosphocholine (GPC + PCH), myo-inositol, glutamate + glutamine (Glx), and creatine and phosphocreatine (Cr + PCr) of the thalamus (all P<0.01), and glutamate (P<0.0001), GPC + PCH (P=0.016), and Glx (P<0.0001) of the PCC. The change between pre- and post-caffeine intake results with significant reductions in γ-aminobutyric acid-positive macromolecule (GABA+) (thalamus, P=0.011), Glx (thalamus, P=0.002), glutamate (PCC, P<0.0001), and significant increments in GPC + PCH (thalamus, P=0.012 and PCC, P<0.0001), myo-inositol (thalamus, P=0.009), and Glx (PCC, P<0.0001). The change among the groups, with the ≥1 cup/day was significantly higher than the <1 cup/day or no consumption for glutamate (PCC, P=0.028), GPC (thalamus, P=0.001; PCC, P=0.026), and Cr + PCr (PCC, P=0.035); ≥1 cup/day was significantly lower than <1 cup/day and no consumption for glutamate (thalamus, P<0.0001), Cr + PCr (thalamus, P=0.003), Glx (thalamus, P=0.014), and myo-inositol (PCC, P=0.009). Bivariate correlation analysis revealed that GABA+ in the thalamus voxel (r=-0.7676; P<0.0001) was negatively correlated with subjective sleepiness. Conclusions: Higher caffeine consumption had a significant impact on brain metabolites. Magnetic resonance spectroscopy was sensitive in measuring brain metabolite fluctuations after caffeine intake, particularly the levels of GABA+ in the thalamus, which was significantly correlated with sleepiness.

γ-Aminobutyric acid as a biomarker of the lateralizing and monitoring drug effect in patients with magnetic resonance imaging-negative temporal lobe epilepsy.

Introduction: Despite verifying proton magnetic resonance spectroscopy (1H-MRS) for focal localization in magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE), it is necessary to illustrate metabolic changes and screen for effective biomarkers for monitoring therapeutic effect. We used 1H-MRS to investigate the role of metabolic levels in MRI-negative TLE. Materials and methods: Thirty-seven patients (n = 37, 14 women) and 20 healthy controls (n = 20, 11 women) were investigated by 1H-MRS. We compared the metabolite level changes in the epileptic and contralateral sides on the mesial temporal and dorsolateral prefrontal cortices and analyzed their association with clinical symptoms. Results: γ-Aminobutyric acid (GABA) levels were significantly lower on the epileptic side (2.292 ± 0.890) than in the contralateral side (2.662 ± 0.742, p = 0.029*) in patients on the mesial temporal lobe. N-acetylaspartate (NAA) levels were significantly lower on the epileptic side (7.284 ± 1.314) than on the contralateral side (7.655 ± 1.549, p = 0.034*). NAA + N-acetylaspartylglutamate levels were significantly lower on the epileptic side (7.668 ± 1.406) than on the contralateral side (8.086 ± 1.675, p = 0.032*). Glutamate levels were significantly lower on the epileptic side (7.773 ± 1.428) than on the contralateral side (8.245 ± 1.616, p = 0.040*). Moreover, a significant negative correlation was found between GABA levels in the epileptic mesial temporal lobe and tonic-clonic seizure frequency (r = -0.338, p = 0.046*). Conclusion: γ-Aminobutyric acid (GABA) is a potential biomarker for lateralization and monitoring seizure frequency in MRI-negative TLE.

Combination of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Provides Potential Biomarkers for Early-Stage Parkinson's Disease.

Purpose: This study aimed to detect changes in iron deposition and neural microstructure in the substantia nigra (SN), red nucleus (RN), and basal ganglia of Parkinson's disease (PD) patients at different stages using quantitative susceptibility mapping and diffusion kurtosis imaging to identify potential indicators of early-stage PD. Methods: We enrolled 20 early-stage and 15 late-stage PD patients, as well as 20 age- and sex-matched controls. All participants underwent quantitative susceptibility mapping and diffusion kurtosis imaging to determine magnetic susceptibility (MS), fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) in several brain regions. Results: Compared with the control group, MS and MK values in the SN were significantly increased in the early- and late-stage PD group, whereas MS values in the red nucleus (RN), globus pallidus (GP), and caudate nucleus (CN), FA value in the CN and GP, and MK value in the CN and putamen (PU) were significantly increased in the late-stage PD group. There were positive correlations between MS and MK values in the CN and MS and FA values in the GP. Furthermore, the combination of MS and MK values in the SN provided high accuracy for distinguishing early-stage PD patients from controls. Conclusions: This study identified MS and MK in the SN as potential indicators of early-stage PD.

Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function. Chronic inflammation has been demonstrated to be the pathological basis of fibrosis. Emerging studies have revealed that most interleukin-17 (IL-17) isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity. Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes, including the initiation and exacerbation of IPF. Here, we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.

Clinical value and application of preoperative CT-guided hookwire localization of solitary pulmonary nodules for video-assisted thoracic surgery.

BACKGROUND: Video-assisted thoracic surgery (VATS) is a minimally invasive technique for the diagnosis and management of small pulmonary nodular lesions However, the identification of some lung nodules remains difficult. OBJECTIVE: This research aimed to investigate the clinical value of preoperative computed tomography (CT)-guided hookwire localization of solitary pulmonary nodules (SPNs) for thoracoscopic resection. METHODS: Seventy-one patients with 74 SPNs underwent VATS wedge resection after CT-guided hookwire localization. The mean diameter of the SPNs was 8.50 ± 4.53 mm,,besides, the mean distance from the SPNs to the parietal pleura was 16.81 ± 5.23 mm. RESULTS: Sixty-nine of the 74 nodules were successfully localized using a CT-guided hookwire. The success rate of CT-guided localization was 93.2%. The average localization time was 15.23 ± 7.21 min per lesion. Seven patients (9.5%) had asymptomatic pneumothorax and 10 (13.5%) had minimal needle tract parenchymal hemorrhages after localization no clinical intervention was required for these patients. The rate of success for VATS wedge resection of the SPNs was 100%. Histological analysis of the SPNs revealed malignant disease in 67.4% of the patients. CONCLUSIONS: Preoperative CT-guided hookwire localization for thoracoscopic resection is a safe and effective operation for the identification and stable fixation of SPNs.