Objective: To develop an effective method for phase correction of magnetic resonance spectroscopic imaging (MRSI) data. Methods: In many MRSI applications, it is desirable to generate absorption-mode spectra, which requires correction of phase errors in the measured MRSI data. Conventional phase correction methods are sensitive to measurement noise and baseline distortion, often resulting in distorted absorption-mode spectra from MRSI data with low-SNR and long acquisition dead time. This paper proposed a novel model-based method for improved phase correction of MRSI data. The proposed method determined the zeroth-order phase and acquisition dead time using a Lorentzian-based spectral model and performed signal extrapolation using a generalized series model. Absorption-mode spectra were then generated from the phase-corrected and extrapolated MRSI data. Results: The proposed method was evaluated using both simulated data and experimental data acquired from human subjects in multi-nuclei (31P, 2H, and 1H) MRSI experiments. Simulation results demonstrated improved parameter estimation accuracy by the proposed method under various noise levels and dead times. The proposed method also consistently generated high-quality absorption-mode spectra with minimal spectral distortions from experimental data. The proposed method was compared with state-of-the-art methods (including the entropy method and LCModel method) and showed more robust phase correction performance with less spectral distortions. Conclusion: This paper introduced a novel method for phase correction of MRSI data. Results from simulated and in vivo data demonstrated that high-quality absorption-mode spectra could be obtained using the proposed method. Significance: This method will provide a useful tool for processing MRSI data.

Fatigue is a pervasive and difficult-to-treat symptom of major depressive disorder (MDD) that contributes to disability. Understanding this problem in its earlier stages will be critical for averting long-term negative outcomes. To investigate the molecular roots of fatigue in early-stage depression, the current work measured bioenergetic mechanisms, with a focus on adenosine triphosphate (ATP), in brain and blood cells in young adults with MDD versus healthy controls (HC). To measure ATP concentration and ATP production rate in the visual cortex, we utilized 31P magnetic resonance spectroscopy imaging with magnetization transfer (31P MRSI-MT) at 7 Tesla, with and without gamma-ATP resonance saturation. ATP level was also measured in peripheral blood mononuclear cells (PBMCs) at rest and after serial addition of mitochondrial inhibitors. Out of 25 participants (mean age 21.8 years), usable data were available for 18 participants for imaging (9 per group); 24 for PBMCs (13 HC; 11 MDD). The MDD group demonstrated higher ATP production rate in the visual cortex than HC, which correlated positively with Fatigue Severity Scale (FSS) scores. ATP concentrations in PBMCs were higher in MDD than HC, and also correlated with FSS scores. After mitochondrial uncoupling, PBMCs in the MDD group had a lower capacity for ATP production than HC. For the first time, we demonstrate an ATP biosignature of fatigue in young adults with MDD that is visible in both brain and peripheral blood. The findings suggest a compensatory mechanism that occurs early in the disease stage.

Brain connectomes are insightful models that describe the connectivity of different regions throughout the brain. These connectomes are traditionally generated through temporal correlation of blood oxygen level dependent (BOLD) signals detected by functional magnetic resonance imaging (fMRI). Photoacoustic ultrasound (PAU) can also detect oxygenation levels while being more accessible and cost effective than fMRI. We propose the use of PAU to generate brain connectomes as an alternative to fMRI. In this study we successfully developed a pipeline for processing PAU data from whole brain scans of mice models and found that the connectomes it produced were comparable to those generated by fMRI, particularly, in detecting connections previously documented in the literature. Our findings suggest that PAU is a promising alternative to fMRI for mapping brain connectome, offering advantages in sensitivity and accessibility, making it a valuable tool for future research on brain connectivity.

Deuterium (2H) magnetic resonance spectroscopic imaging (DMRSI) is a newly developed technology for assessing glucose metabolism by simultaneously measuring deuterium-labeled glucose and its downstream metabolites (1) and has a potential to provide a powerful neurometabolic imaging tool for quantitative studies of cerebral glucose metabolism involving multiple metabolic pathways in the human brain. In this work, we developed a dynamic DMRSI method that combines advanced radiofrequency coil and postprocessing techniques to substantially improve the imaging signal-to-noise ratio for detecting deuterated metabolites and enable robust dynamic DMRSI of the human brain at 7 T with very high resolution (HR; 0.7 cc nominal voxel and 2.5 min/image) and whole-brain coverage. Utilizing this capability, we were able to map and differentiate metabolite contents and dynamics throughout the human brain following oral administration of deuterated glucose. Furthermore, by introducing a sophisticated kinetic model, we demonstrated that three key cerebral metabolic rates of glucose consumption (CMRGlc), lactate production (CMRLac), and tricarboxylic acid (TCA) cycle (V TCA), as well as the maximum apparent rate of forward glucose transport (T max) can be simultaneously imaged in the human brain through a single dynamic DMRSI measurement. The results clearly show that the glucose transport, neurotransmitter turnover, CMRGlc, and V TCA are significantly higher in gray matter than in white matter in the human brain; and the mean metabolic rates and their ratios measured in this study are consistent with the values reported in the literature. The HR dynamic DMRSI methodology presented herein is of great significance and value for the quantitative assessment of human brain glucose metabolism, aerobic glycolysis, and metabolic reprogramming under physiopathological conditions.

Liver fibrosis is a dynamic and complex process characterized by the excessive accumulation of extracellular matrix (ECM) components, driven by a heterogeneous population of hepatic myofibroblasts (MFs). Current treatments for liver fibrosis primarily include pharmacological interventions such as antiviral and anti-fibrotic therapies, alongside lifestyle modifications, including dietary changes and alcohol abstinence. However, the therapeutic outcomes remain suboptimal. Existing anti-fibrotic medications are unable to fully reverse liver fibrosis, particularly in its advanced stages, and some drugs may even induce adverse effects. Recently, the challenge of combating liver fibrosis has attracted increasing attention from both the academic community and the general public, leading to extensive research efforts and several significant discoveries. Hepatocyte senescence, an irreversible and inevitable process, plays a crucial role in the onset and progression of various liver diseases. It serves as a key regulatory factor in the development of liver fibrosis, exerting a considerable impact on its progression. Senescent hepatocytes secrete the senescence-associated secretory phenotype (SASP), which interacts with hepatic stellate cells (HSCs), promoting their transformation into MFs. Additionally, SASP fosters a cellular microenvironment conducive to the advancement of hepatic fibrosis, thereby accelerating its progression. This review comprehensively examines the natural flavonoid compound Oroxylin A (OA), which regulates hepatocyte senescence in the context of liver fibrosis. The paper also discusses the current research landscape, trends, and critical challenges related to hepatocyte senescence in liver fibrosis, along with the mechanisms through which OA influences hepatocyte senescence, either promoting or delaying its onset.

Purpose Phosphorus-31 (P-31) MR spectroscopy imaging (MRSI) at 7 T is a powerful tool for investigating high-energy phosphate metabolism in human brains with significantly improved signal-to-noise ratio (SNR) and spectral resolution. However, this imaging technique requires dual-frequency radiofrequency coil for performing brain anatomical imaging and B-0 shimming at proton (H-1) operation frequency, and P-31 MRSI at lower operation frequency. Herein, we introduce a novel P-31-H-1 dual-frequency radiofrequency coil design using a double-tuned and double-matched (DODO) coil that does not require complex circuitry or two coil layers and exhibits similar imaging performance as to single-frequency control coils for both P-31 and H-1 imaging operations. Methods We constructed an eight-element P-31-H-1 dual-frequency DODO transceiver array and compared its performance with a quadrature-driven dual-tuned eight-element P-31 and eight-element H-1 transverse electromagnetic volume coil for both phantom and in vivo human-brain P-31-MRSI studies at 7 T. Results The DODO transceiver array achieved high spatiotemporal resolution P-31 MRSI with 2.5-cc nominal voxel size and 22-min scan time covering the entire human brain, showing excellent SNR for mapping cerebral phosphorous metabolites such as phosphocreatine, adenosine triphosphate, and other low-concentration metabolites. Compared with the transverse electromagnetic volume coil, the DODO array demonstrated large improvements in P-31-MRSI SNR in both phantom and human brain studies, with over 5-fold SNR gain in peripheral regions and over 2-fold SNR gain in central brain regions. Conclusion This simple and cost-effective array design and excellent performance can greatly benefit human-brain P-31-MRSI applications at 7 T.

Neural activity in the delta range (1.0-4.5 Hz) during non-rapid eye movement (NREM) sleep is crucial for brain plasticity and overall brain health. Recent research has shown that changes in NREM delta activity can occur locally, and activity can vary across different brain regions. Ischemic stroke results in focal brain injury and long-term disability. While sleep disruption during the acute phase of stroke is known to hinder recovery, the relationship between region-specific changes in NREM delta activity and functional recovery remains poorly understood. To investigate these localized changes in NREM delta activity with high spatial resolution, we utilized wide-field optical imaging (WFOI) in mice that expressed GCaMP6f, a fluorescent calcium indicator, in cortical excitatory pyramidal neurons. Sleep was longitudinally recorded before and at 24 hours, 1 week, and 4 weeks after photothrombotic stroke in the left somatosensory forepaw cortex. In the acute phase of stroke (24 hours post-stroke), mice exhibited decreased delta activity in the infarct and peri-infarct regions during NREM sleep. Increased delta activity in the contralesional hemisphere and decreased delta activity in the perilesional region during NREM sleep in the acute phase were associated with poor behavioral recovery, as measured by performance on the cylinder rearing test. These findings suggest that region-specific NREM delta activity may play a crucial role in stroke recovery and warrant further investigation to determine whether modulating delta activity in targeted brain areas during NREM sleep could aid recovery.

We proposed a simple approach to optimize a concentric-loops RF coil, consisting of an inner primary coil as the driving coil and an outer secondary coil as a passive resonator. By adjusting the tuning capacitor in the secondary loop to raise its self-resonance frequency to be slightly above the operating Larmor frequency, we enabled the preferred operation condition (additive mode), where both secondary and primary loops contributed to the largely enhanced RF coil transmit and receive magnetic fields (B1) within the area enclosed by the primary loop as compared to a single-loop secondary coil. Compared to a single secondary loop coil as control, electromagnetic (EM) simulations and phantom MRS/MRI at 10.5 Tesla (T) 17O (60.6 MHz), 7 T 31P (120.7 MHz), and 1.5 T 1H (63.8 MHz) operating frequencies show that the concentric-loops coil (8 cm diameter for the secondary loop coil) provides 1.2 to 1.4-fold higher B1 and coil detection sensitivity in the near-coil region (0-3 cm). In the far region, it offers slightly enhanced B1 and coil sensitivity, which becomes similar to the control coil at 9 cm away from the coil plane. Additionally, the concentric-loops coil reduces imaging noise by 15-30 %, collectively, resulting in an ∼1.7-fold signal-to-noise ratio (SNR) gain at the near-coil region. The concentric-loops coil with the presented optimization strategy provides an effective and simple coil design with largely improved imaging SNR compared to a conventional single-loop coil for a broad range of MRS/MRI applications across different field strengths.

Partial sleep deprivation (PSD) alters neural activity of intrinsic brain networks involved in cognitive functions. However, the age-related time-varying properties of large-scale brain functional networks after PSD remain unknown. Our study applied energy landscape analysis to resting-state functional magnetic resonance imaging data to characterize the dominant brain activity patterns in 36 healthy young (19 females, 23.53 ± 2.36 years) and 33 healthy older (18 females, 68.81 ± 2.41 years) adults after full sleep (FS) and PSD. Dynamic properties of these patterns, including appearance probability, duration and transitions, were then calculated. Finally, a 105 steps numerical simulation was performed on each energy landscape. We found that the energy landscapes of the younger and older groups had similar hierarchical structures, including two major states and two minor states. The two major states showed complementary spontaneous activation patterns. But the PSD has altered the temporal evolution of these major brain states in younger participants, manifested by significantly higher appearance frequency of the major states and the direct transitions between major states than FS. These changes were not significant in older participants. Additionally, the weaker functional segregation between two modules assigned by two complementary major states was found during PSD than FS in young group. We further demonstrated that such abnormal brain network functional coordination was associated with the atypical brain dynamics and behaviors. These findings suggested a low-dimensional and restricted dynamic landscape of brain activity in young adults after PSD and provided new insight into understand the neural effects of PSD.

Multiple sclerosis (MS) is a chronic and progressive autoimmune disease affecting the central nervous system. It is characterized by damage to neurons myelin protective sheath, which results in impaired nervous communication and consequently in deterioration of physical, cognitive and mental capacities. Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) regulates key signaling pathways involved in pro-inflammatory immune response. Selective ROCK2 inhibition has been shown to dampen inflammation – notably autoimmune Th17 and innate immune responses, in various tissues and pathologies, but not in MS. Here, we show that therapeutic oral administration of novel BBB-penetrant selective ROCK2 inhibitor ameliorates limb paralysis and significantly reduces the clinical scores in an Experimental Autoimmune Encephalomyelitis (EAE) murine model of MS, consistent with efficient target engagement in the brain. ROCK2 inhibition improves the demyelination score, decreases inflammatory foci and Th17 cells while increasing Treg and microglia populations in the spinal cord. Ex vivo, ROCK2 targeting directly promotes both myelin expression and myelinating capacity in oligodendrocytes and upregulates phagocytosis of myelin residues by microglia, two crucial aspects for effective remyelination. These data underscore the therapeutic potential of selective ROCK2 inhibition in MS by concurrently rebalancing disease-associated inflammation and promoting remyelination. Neuroimmunology (NEUR)

Marine geomagnetic survey plays a pivotal role in the study of submarine tectonics, but existing technology lacks the ability to acquire the magnetic mineral composition of marine bottom sediments, which is crucial for the accurate analysis and interpretation of magnetic anomalies. To address this problem, we have developed an ocean floor magnetic property measurement system (OFMPMS), which is capable of in situ measurement of isothermal remanent magnetization (IRM) acquisition curves and alternating field demagnetization (AFD) curves in deep-sea environments. The subsea unit of the OFMPMS consists of three modules: a magnetic field generator, a system controller, and a measuring unit, all of which are enclosed in three sealed cabins to withstand the high-pressure environment of the deep sea. The OFMPMS is equipped with five anisotropic magnetoresistance (AMR) magnetometers, enabling it to effectively detect the magnetic inhomogeneity of samples. Two sea trials were completed in South China Sea. During the first sea trial, the OFMPMS performed in situ detection of marine bottom sediments at a depth of 1385 m. However, no valuable IRM and AFD data were obtained because the sediments in this area were predominantly paramagnetic. During the second sea trial, at a depth of 4500 m, an iron ore sample was subjected to testing. The test results showed that in situ data matched laboratory data under high applied fields but differed significantly under low applied fields, which was attributed to the pressure exerted by seawater on the sample. This discovery highlights the limitations of ex situ measurement methods (measurements taken at normal pressure on land) for analyzing marine bottom sediment magnetic properties. OFMPMS provides an approach for in situ identification of magnetic minerals in marine bottom sediments and is expected to provide an accurate interpretation of submarine magnetic anomalies.

Objective: To develop a high-resolution magnetic resonance (MR) metabolic imaging method for mapping human brain metabolite distributions at ultrahigh field (7T). Methods: In data acquisition, a free-induction-decay (FID) based MR spectroscopic imaging (MRSI) sequence was implemented. To achieve high spatial resolution, the sequence used fast echo-planar spectroscopic imaging (EPSI) trajectories with echo-spacings larger than the Nyquist sampling interval. Using this sequence, 3D MRSI signals at isotropic nominal resolutions of 3.0 mm and 1.8 mm were acquired within scan times of 4.8 and 14.2 minutes, respectively. In data processing, model-based methods integrating subspace learning, spectral modeling, and generalized series modeling were developed to address key challenges, including spectral ghosting, low signal-to-noise ratio, and spectral aliasing. Results: The proposed acquisition and processing methods successfully generated high-resolution, high-quality metabolite maps of the human brain at 7T. Experimental results from phantom and in vivo scans validated the proposed method and showed its capability to capture detailed brain metabolite distributions. Conclusion: This work demonstrates the feasibility of high-resolution brain metabolic imaging at ultrahigh field using MRSI acquisition sequence and model-based processing methods. Significance: By providing high-resolution spatial mapping of brain metabolites within clinically feasible scan times, the proposed method promises to offer a powerful imaging tool for investigating brain metabolism, which is expected to be useful for various brain imaging applications.

Cerebral glucose and oxygen metabolism and blood perfusion play key roles in neuroenergetics and oxidative phosphorylation to produce adenosine triphosphate (ATP) energy molecules in supporting cellular activity and brain function. Their impairments have been linked to numerous brain disorders. This study aimed to develop an in vivo magnetic resonance spectroscopy (MRS) method capable of simultaneously assessing and quantifying the major cerebral metabolic rates of glucose (CMRGlc) and oxygen (CMRO2) consumption, lactate formation (CMRLac), and tricarboxylic acid (TCA) cycle (VTCA); cerebral blood flow (CBF); and oxygen extraction fraction (OEF) via a single dynamic MRS measurement using an interleaved deuterium (2H) and oxygen-17 (17O) MRS approach. We introduced a single-loop multifrequency radio-frequency (RF) surface coil that can be used to acquire proton (1H) magnetic resonance imaging (MRI) or interleaved low-γ X-nuclei 2H and 17O MRS. By combining this RF coil with a modified MRS pulse sequence, 17O-isotope-labeled oxygen gas inhalation, and intravenous 2H-isotope-labeled glucose administration, we demonstrate for the first time the feasibility of simultaneously and quantitatively measuring six important physiological parameters, CMRGlc, CMRO2, CMRLac, VTCA, CBF, and OEF, in rat brains at 16.4 T. The interleaved 2H-17O MRS technique should be readily adapted to image and study cerebral energy metabolism and perfusion in healthy and diseased brains.

IntroductionNicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging.MethodsIn this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method.ResultsThe processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age.DiscussionThese results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.

The pathogenesis of hepatic fibrosis is driven by dysregulated metabolism precipitated by chronic inflammation. Rho-associated coiled-coil-containing protein kinases (ROCKs) have been implicated in these processes, however the ability of selective ROCK2 inhibition to target simultaneously profibrotic, pro-inflammatory and metabolic pathways remains undocumented. Here we show that therapeutic administration of GV101, a selective ROCK2 inhibitor with more than 1000-fold selectivity over ROCK1, attenuates established liver fibrosis induced by thioacetamide (TAA) in combination with high-fat diet in mice. GV101 treatment significantly reduces collagen levels in liver, associated with downregulation of pCofilin, pSTAT3, pAkt, while pSTAT5 and pAMPK levels are increased in tissues of treated mice. In vitro, GV101 inhibits profibrogenic markers expression in fibroblasts, adipogenesis in primary adipocytes and TLR-induced cytokine secretion in innate immune cells via targeting of Akt-mTOR-S6K signaling axis, further uncovering the ROCK2-specific complex mechanism of action and therapeutic potential of highly selective ROCK2 inhibitors in liver fibrosis.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disorder that causes syndromes characterized by physiological dysfunction in many organs and tissues. Despite the recognizable morphological and behavioral deficits associated with MPS I, neither the underlying alterations in functional neural connectivity nor its restoration following gene therapy have been shown. By employing high-resolution resting-state fMRI (rs-fMRI), we found significant reductions in functional neural connectivity in the limbic areas of the brain that play key roles in learning and memory in MPS I mice, and that adeno-associated virus (AAV)-mediated gene therapy can reestablish most brain connectivity. Using logistic regression in MPS I and treated animals, we identified functional networks with the most alterations. The rs-fMRI and statistical methods should be translatable into clinical evaluation of humans with neurological disorders.