Highly accelerated EPI with wave encoding and multi-shot simultaneous multislice imaging.

PURPOSE: To introduce wave-encoded acquisition and reconstruction techniques for highly accelerated EPI with reduced g-factor penalty and image artifacts. THEORY AND METHODS: Wave-EPI involves application of sinusoidal gradients during the EPI readout, which spreads the aliasing in all spatial directions, thereby taking better advantage of 3D coil sensitivity profiles. The amount of voxel spreading that can be achieved by the wave gradients during the short EPI readout period is constrained by the slew rate of the gradient coils and peripheral nerve stimulation monitor. We propose to use a "half-cycle" sinusoidal gradient to increase the amount of voxel spreading that can be achieved while respecting the slew and stimulation constraints. Extending wave-EPI to multi-shot acquisition minimizes geometric distortion and voxel blurring at high in-plane resolutions, while structured low-rank regularization mitigates shot-to-shot phase variations. To address gradient imperfections, we propose to use different point spread functions for the k-space lines with positive and negative polarities, which are calibrated with a FLEET-based reference scan. RESULTS: Wave-EPI enabled whole-brain single-shot gradient-echo (GE) and multi-shot spin-echo (SE) EPI acquisitions at high acceleration factors at 3T and was combined with g-Slider encoding to boost the SNR level in 1 mm isotropic diffusion imaging. Relative to blipped-CAIPI, wave-EPI reduced average and maximum g-factors by up to 1.21- and 1.37-fold at Rin × Rsms  = 3 × 3, respectively. CONCLUSION: Wave-EPI allows highly accelerated single- and multi-shot EPI with reduced g-factor and artifacts and may facilitate clinical and neuroscientific applications of EPI by improving the spatial and temporal resolution in functional and diffusion imaging.

Blip up-down acquisition for spin- and gradient-echo imaging (BUDA-SAGE) with self-supervised denoising enables efficient T2 , T2 *, para- and dia-magnetic susceptibility mapping.

PURPOSE: To rapidly obtain high resolution T2 , T2 *, and quantitative susceptibility mapping (QSM) source separation maps with whole-brain coverage and high geometric fidelity. METHODS: We propose Blip Up-Down Acquisition for Spin And Gradient Echo imaging (BUDA-SAGE), an efficient EPI sequence for quantitative mapping. The acquisition includes multiple T2 *-, T2 '-, and T2 -weighted contrasts. We alternate the phase-encoding polarities across the interleaved shots in this multi-shot navigator-free acquisition. A field map estimated from interim reconstructions was incorporated into the joint multi-shot EPI reconstruction with a structured low rank constraint to eliminate distortion. A self-supervised neural network (NN), MR-Self2Self (MR-S2S), was used to perform denoising to boost SNR. Using Slider encoding allowed us to reach 1 mm isotropic resolution by performing super-resolution reconstruction on volumes acquired with 2 mm slice thickness. Quantitative T2 (=1/R2 ) and T2 * (=1/R2 *) maps were obtained using Bloch dictionary matching on the reconstructed echoes. QSM was estimated using nonlinear dipole inversion on the gradient echoes. Starting from the estimated R2 /R2 * maps, R2 ' information was derived and used in source separation QSM reconstruction, which provided additional para- and dia-magnetic susceptibility maps. RESULTS: In vivo results demonstrate the ability of BUDA-SAGE to provide whole-brain, distortion-free, high-resolution, multi-contrast images and quantitative T2 /T2 * maps, as well as yielding para- and dia-magnetic susceptibility maps. Estimated quantitative maps showed comparable values to conventional mapping methods in phantom and in vivo measurements. CONCLUSION: BUDA-SAGE acquisition with self-supervised denoising and Slider encoding enables rapid, distortion-free, whole-brain T2 /T2 * mapping at 1 mm isotropic resolution under 90 s.

Three-dimensional convolutional neural networks for simultaneous dual-tracer PET imaging.

Dual-tracer positron emission tomography (PET) is a promising technique to measure the distribution of two tracers in the body by a single scan, which can improve the clinical accuracy of disease diagnosis and can also serve as a research tool for scientists. Most current research on dual-tracer PET reconstruction is based on mixed images pre-reconstructed by algorithms, which restricts the further improvement of the precision of reconstruction. In this study, we present a hybrid loss-guided deep learning based framework for dual-tracer PET imaging using sinogram data, which can achieve reconstruction by naturally unifying two functions: the reconstruction of the mixed images and the separation for individual tracers. Combined with volumetric dual-tracer images, we adopted a three-dimensional (3D) convolutional neural network (CNN) to learn full features, including spatial information and temporal information simultaneously. In addition, an auxiliary loss layer was introduced to guide the reconstruction of the dual tracers. We used Monte Carlo simulations with data augmentation to generate sufficient datasets for training and testing. The results were analyzed by the bias and variance both spatially (different regions of interest) and temporally (different frames). The analysis verified the feasibility of the 3D CNN framework for dual-tracer reconstruction. Furthermore, we compared the reconstruction results with a deep belief network (DBN), which is another deep learning based technique for the separation of dual-tracer images based on time-activity curves (TACs). The comparison results provide insights into the superior features and performance of the 3D CNN. Furthermore, we tested the [11C]FMZ-[11C]DTBZ images with three total-counts levels ([Formula: see text], [Formula: see text], [Formula: see text]), which indicate different noise ratios. The analysis results demonstrate that our method can successfully recover the respective distribution of lower total counts with nearly the same accuracy as that of the higher total counts in the total counts range we applied, which also also indicates the proposed 3D CNN framework is more robust to noise compared with DBN.

Increased Serum Cystatin C in Early Parkinson's Disease with Objective Sleep Disturbances.

BACKGROUND: Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson's disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD. METHODS: We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients. RESULTS: The mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO2) <90% (r = 0.644, P < 0.001), arousal with respiratory event during sleep (r = 0.247, P = 0.013). On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO2(r = -0.323, -0.315, both P = 0.001) in PD patients. CONCLUSIONS: The level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Role of two Nomuraea rileyi transmembrane sensors Sho1p and Sln1p in adaptation to stress due to changing culture conditions during microsclerotia development.

Microsclerotia (MS) formation was successfully induced in Nomuraea rileyi in liquid amended medium (AM) culture. To investigate how N. rileyi senses growth stress and regulates MS differentiation, based on transcriptome library, sho1 and sln1 genes were cloned. The transcription levels of sho1 and sln1 were upregulated in response to the changing culture conditions. To determine the functions of sho1 and sln1, gene-silencing mutants (sholi, sln1i and shol&sln1i) were generated using RNA silencing technology. The significant phenotypic changes in the mutants included reduced conidial yields by 22.72, 40.27, and 63.67 % and virulence by 24.53, 25.74, and 59.04 %, respectively. Furthermore, the mutants presented decreased MS yields by approximately 96 % under changing culture conditions. Our results confirmed the crucial role of Sho1p and Sln1p in sensing growth stress due to changing culture conditions and regulating MS differentiation.

Downregulation of cystathionine ß-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type.

Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-α, iNOS and COX-2/PGE2 but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-ß-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500µmol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype.

[Preliminary relationship between serum cystatin C level and Parkinson's disease].

OBJECTIVE: To explore the role of serum cystatin C level in Parkinson's disease (PD) and evaluate the relationship between cystatin C level and clinical characteristics and different stages of PD. METHODS: A total of 115 PD patients and 110 healthy controls were recruited. The results of such routine laboratory tests as triglyceride, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), creatinine, urea, uric acid and cystatin C were assessed from fasting blood samples at our clinical laboratory center. They were further divided into subgroups according to Hoehn & Yahr (H&Y) staging. Statistical analysis was performed with SPSS version 17.0 software. RESULTS: Compared to controls (0.96 ± 0.16 mg/L), the mean serum level of cystatin C was significantly higher in PD patients (1.06 ± 0.20 mg/L). Spearman's correlation analyses showed a positive and significant correlation between cystatin C levels and age as well as creatinine levels. Correlation was not found between cystatin C level and triglyceride, cholesterol, LDL, HDL, urea or uric acid. ANOVA analysis showed that cystatin C had a higher level during the middle and late stages of PD than that during the early stage. CONCLUSION: Cystatin C level may play an important role in the progression of PD.