Imperatorin Suppresses Aberrant Hedgehog Pathway and Overcomes Smoothened Antagonist Resistance via STAT3 Inhibition.

Background: Hyperactive Hedgehog (Hh) signaling initiates and drives the progression of various tumors. Despite the clinical success of Hh inhibitors targeting Smoothened (SMO), drug resistance, often stemming from SMO mutations, remains a formidable obstacle in cancer therapy. Here, we investigated the potential of imperatorin (IMP), a Chinese herbal medicine, to overcome drug resistance and revealed the potential mechanisms.

Radiosynthesis and evaluation of a novel F-labeled tracer for PET imaging of glycogen synthase kinase 3.

Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase family that regulates diverse biological processes including glucose metabolism, insulin activity and energy homeostasis. Dysregulation of GSK3 is implicated in the development of several diseases such as type 2 diabetes mellitus, Alzheimer's disease (AD), and various cancer types. In this study, we report the synthesis and evaluation of a novel positron emission tomography (PET) ligand compound 28 (codenamed [F]GSK3-2209).

Radiosynthesis and preclinical evaluation of a carbon-11 labeled PET ligand for imaging metabotropic glutamate receptor 7.

Metabotropic glutamate receptor 7 (mGlu) is a G protein-coupled receptor that is preferentially found in the active zone of neurotransmitter release in the central nervous system (CNS). mGlu plays a vital role in memory, learning, and neuronal development, rendering it a potential target for treating epilepsy, depression, and anxiety. The development of noninvasive imaging ligands targeting mGlu could help elucidate the functional significance of mGlu and accelerate drug discovery for neurological and psychiatric disorders.

Altered representation of peripersonal and interpersonal space in psychopathology.

The space surrounding the body, and the regulation of this buffer zone play a central role in adaptive behavior, with direct implications for psychopathology. The physical distance that we choose to maintain between ourselves and others for social comfort is known as Interpersonal Distance (IPD), whereas the action space that marks the perceptual border between the self and the external world is known as Peripersonal Space (PPS ). While both IPD and PPS represent personal space, they are distinct constructs, each associated with different methodologies.

Multi-task magnetic resonance imaging reconstruction using meta-learning.

Using single-task deep learning methods to reconstruct Magnetic Resonance Imaging (MRI) data acquired with different imaging sequences is inherently challenging. The trained deep learning model typically lacks generalizability, and the dissimilarity among image datasets with different types of contrast leads to suboptimal learning performance. This paper proposes a meta-learning approach to efficiently learn image features from multiple MRI datasets.

Ga labeled Olmutinib: Design, synthesis, and evaluation of a novel PET EGFR probe.

Radiolabeled tyrosine kinase inhibitors (TKIs) offer a promising approach for molecular imaging of EGFR-positive cancers. Despite the development of various EGFR small-molecule probes, none of the Ga-labeled small-molecule probes based on the chelator DOTA have shown tumor-specific uptake. To address this challenge, we selected Olmutinib, a third-generation EGFR covalent inhibitor, as a PET imaging tracer for EGFR-positive tumors.

Cerebral microvascular physiology associated with white matter lesion burden differs by level of vascular risk in typically aging older adults.

White matter lesions (WMLs) are prevalent with aging, and higher WML burden has been observed in older adults with vascular diseases. While the physiology underlying the formation of WMLs is not known, various risk factors are associated with high WML burden. Here, we investigated the relationship between vascular risk factors and microvascular physiology (i.

Blip-up blip-down circular EPI (BUDA-cEPI) for distortion-free dMRI with rapid unrolled deep learning reconstruction.

Purpose: BUDA-cEPI has been shown to achieve high-quality, high-resolution diffusion magnetic resonance imaging (dMRI) with fast acquisition time, particularly when used in conjunction with S-LORAKS reconstruction. However, this comes at a cost of more complex reconstruction that is computationally prohibitive. In this work we develop rapid reconstruction pipeline for BUDA-cEPI to pave the way for its deployment in routine clinical and neuroscientific applications.

Mindfulness Meditation and Network Neuroscience: Review, Synthesis, and Future Directions.

Network neuroscience is an interdisciplinary field, which can be used to understand the brain by examining the connections between its constituent elements. In recent years, the application of network neuroscience approaches to study the intricate nature of the structural and functional relationships within the human brain has yielded unique insights into its organization. In this review, we begin by defining network neuroscience and providing an overview of the common metrics that describe the topology of human structural and functional brain networks.

"Neuroinflammation": does it have a role in chronic pain? Evidence from human imaging.

Despite hundreds of studies demonstrating the involvement of neuron-glia-immune interactions in the establishment and/or maintenance of persistent pain behaviors in animals, the role (or even occurrence) of so-called "neuroinflammation" in human pain has been an object of contention for decades. Here, I present the results of multiple positron emission tomography (PET) studies measuring the levels of the 18 kDa translocator protein (TSPO), a putative neuroimmune marker, in individuals with various pain conditions. Overall, these studies suggest that brain TSPO PET signal: (1) is elevated, compared to healthy volunteers, in individuals with chronic low back pain (with additional elevations in spinal cord and neuroforamina), fibromyalgia, migraine and other conditions characterized by persistent pain; (2) has a spatial distribution exhibiting a degree of disorder specificity; (3) is parametrically linked to pain characteristics or comorbid symptoms (eg, nociplastic pain, fatigue, depression), as well as measures of brain function (ie, functional connectivity), in a regionally-specific manner.

Altered Neural Processing of Interoception in Patients With Functional Neurological Disorder: A Task-Based fMRI Study.

Objective: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND.

Methods: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients.

Romer-EPTI: Rotating-view motion-robust super-resolution EPTI for SNR-efficient distortion-free in-vivo mesoscale diffusion MRI and microstructure imaging.

Purpose: To overcome the major challenges in diffusion MRI (dMRI) acquisition, including limited SNR, distortion/blurring, and susceptibility to motion artifacts.

Theory And Methods: A novel Romer-EPTI technique is developed to achieve SNR-efficient acquisition while providing distortion-free imaging, minimal spatial blurring, high motion robustness, and simultaneous multi-TE imaging. It introduces a ROtating-view Motion-robust supEr-Resolution technique (Romer) combined with a distortion/blurring-free Echo Planar Time-resolved Imaging (EPTI) readout.

Paramagnetic salt and agarose recipes for phantoms with desired T1 and T2 values for low-field MRI.

Tissue-mimicking reference phantoms are indispensable for the development and optimization of magnetic resonance (MR) measurement sequences. Phantoms have greatest utility when they mimic the MR signals arising from tissue physiology; however, many of the properties underlying these signals, including tissue relaxation characteristics, can vary as a function of magnetic field strength. There has been renewed interest in magnetic resonance imaging (MRI) at field strengths less than 1 T, and phantoms developed for higher field strengths may not be physiologically relevant at these lower fields.

Multi-institutional Evaluation and Training of Breast Density Classification AI Algorithm Using ACR Connect and AI-LAB.

Objective: To demonstrate and test the capabilities of the American College of Radiology (ACR) Connect and AI-LAB software platform by implementing multi-institutional artificial intelligence (AI) training and validation for breast density classification.

Methods: In this proof-of-concept study, six U.S.

Mapping the 9-year sleep trajectory and its implications for chronic disease risks among middle-aged and older adults.

Objective: To identify the 9-year trajectories of sleep duration and to assess the relationship between time-dependent sleep duration and sleep trajectories with 14 chronic diseases in adults.

Methods: This study used five waves of data of the China Health and Retirement Longitudinal Survey. Participants with complete sleep duration data and at least one record of 14 chronic diseases were included.

Altered parasympathetic outflow and central sensitization response to continuous pain in cyclic vomiting syndrome: a functional magnetic resonance imaging study.

Cyclic vomiting syndrome (CVS) is a disorder of brain-gut interaction characterized by recurrent episodes of nausea and vomiting interspersed with asymptomatic periods and associated with autonomic nervous system dysfunction. We examined the dysautonomic response to noxious stimuli seen in CVS patients using our previously validated approach to integrate peripheral autonomic outflow metrics, temporal summation of pain, and brain fMRI. BOLD fMRI and ECG were acquired from CVS patients and healthy adults during a rest condition and a sustained cuff pressure pain stimulus at the leg.

[C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain.

Our laboratory recently developed [C]PS13 as a PET radioligand to selectively measure cyclooxygenase-1 (COX-1). The cyclooxygenase enzyme family converts arachidonic acid into prostaglandins and thromboxanes, which mediate inflammation. The total brain uptake of [C]PS13, which is composed of both specific binding and background uptake, can be accurately quantified with gold standard methods of compartmental modeling.

Development of a Candidate C-Labeled Selective Phosphodiesterase 1 Radioligand for Positron Emission Tomography.

Phosphodiesterases (PDEs) constitute a superfamily of phosphohydrolytic enzymes that regulate intracellular second messenger signaling by hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate. Among the 11 subfamilies of PDEs, phosphodiesterase 1 (PDE1) stands out due to its broad implications in central and peripheral pathologies. There are three subtypes of PDE1: PDE1A, PDE1B, and PDE1C.

Selective Functional Connectivity between Ocular Dominance Columns in the Primary Visual Cortex.

The primary visual cortex (V1) in humans and many animals is comprised of fine-scale neuronal ensembles that respond preferentially to the stimulation of one eye over the other, also known as the ocular dominance columns (ODCs). Despite its importance in shaping our perception, to date, the nature of the functional interactions between ODCs has remained poorly understood. In this work, we aimed to improve our understanding of the interaction mechanisms between fine-scale neuronal structures distributed within V1.

Neuropathological Correlates of White Matter Hyperintensities in Cerebral Amyloid Angiopathy.

Background: White matter hyperintensities (WMHs) are frequently observed on magnetic resonance imaging (MRI) in patients with cerebral amyloid angiopathy (CAA). The neuropathological substrates that underlie WMHs in CAA are unclear, and it remains largely unexplored whether the different WMH distribution patterns associated with CAA (posterior confluent and subcortical multispot) reflect alternative pathophysiological mechanisms.

Methods And Results: We performed a combined in vivo MRI-ex vivo MRI-neuropathological study in patients with definite CAA.

Sleep oscillations and their relations with sleep-dependent memory consolidation in early course psychosis and first-degree relatives.

Sleep spindles mediate sleep-dependent memory consolidation, particularly when coupled to neocortical slow oscillations (SOs). Schizophrenia is characterized by a deficit in sleep spindles that correlates with reduced overnight memory consolidation. Here, we examined sleep spindle activity, SO-spindle coupling, and both motor procedural and verbal declarative memory consolidation in early course, minimally medicated psychosis patients and non-psychotic first-degree relatives.

Within-individual organization of the human cognitive cerebellum: Evidence for closely juxtaposed, functionally specialized regions.

Specific regions in the cognitive cerebellum are connected to distinct cerebral association networks. Do these cerebellar regions exhibit functional specialization similar to the cerebral cortex? Here, we mapped the cerebellum within intensively studied participants ( = 15) first using connectivity to estimate regions linked to specific networks and then prospectively testing functional response properties in task data within each individual's own idiosyncratic anatomy. A large megacluster extending across Crus I/II was consistently found with subregions linked to five higher-order association networks.

Identifying the bioimaging features of Alzheimer's disease based on pupillary light response-driven brain-wide fMRI in awake mice.

Pupil dynamics has emerged as a critical non-invasive indicator of brain state changes. In particular, pupillary-light-responses (PLR) in Alzheimer's disease (AD) patients show potential as biomarkers for brain degeneration. To investigate AD-specific PLR and its underlying neuromodulatory sources, we combine high-resolution awake mouse fMRI with real-time pupillometry to map brain-wide event-related correlation patterns based on illumination-driven pupil constriction ( ) and post-illumination pupil dilation recovery (amplitude, , and time, T).