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 β-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 Aβ 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.

Background: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder. However, its diagnosis and effective treatment present challenges. Understanding neurotransmitter impairments may offer new perspectives into the mechanisms underlying ASD and the potential therapeutic targets for this condition. This study aimed to investigate the spatial associations of ASD‐related brain activity patterns and multiple specific neurotransmitter distributions to identify abnormal neurotransmitter alterations in patients with ASD, and to assess how these spatial associations relate to clinical features. Methods: We included 44 patients with ASD and 132 typically developing controls (TDCs) and compared the regional homogeneity (ReHo) differences between the two groups. Associations between the spatial patterns of ReHo alterations and specific neurotransmitter receptor/transporter densities in patients with ASD were evaluated, and the correlations of these associations with the clinical characteristics were analyzed. Results: In comparison with TDCs, patients with ASD exhibited specific brain activity abnormalities in the visuomotor network, cerebro‐cerebellar circuits, angular gyrus, and limbic areas. These atypical brain activity patterns were significantly co‐localized with the serotonergic, glutamatergic, GABAergic, dopaminergic, noradrenergic, cholinergic, and cannabinoid neurotransmitter systems in patients with ASD, and the results showed good reproducibility between different neurotransmitter maps. Additionally, the awareness score in the Social Responsiveness Scale ( ρ = −0.475, p = 0.009) and the social score in the Autism Diagnostic Observation Schedule ( ρ = −0.415, p = 0.049) exhibited negative correlations with the strength of ReHo co‐localization of serotonin 5‐hydroxytryptamine receptor subtype 2a. Conclusions: This is the first systematic analysis of multiple neurotransmitter systems to show abnormalities in these systems in patients with ASD. These results will enhance the existing understanding of the mechanisms underlying ASD and may provide the foundation for identifying therapeutic targets.

Objective: Cocaine Use Disorder (CUD) poses a major public health challenge, with no Food and Drug Administration-approved pharmacotherapies currently available. A deeper understanding of Morphometric Similarity Network (MSN) alterations and their associations with neurotransmitter systems in CUD may facilitate the development of targeted therapeutic strategies. We aimed to investigate the aberrant MSN patterns and their relationships with neurotransmitter distributions in CUD. Methods: This case-control study enrolled 70 patients with CUD and 57 age- and sex-matched healthy controls (HCs). Individual-level MSNs were constructed for each participant, and regional morphometric similarity (MS) strength was computed. Group differences in MSN connectivity and regional MS strength were compared between the CUD and HC groups. The JuSpace toolbox was employed to assess spatial correlations between regional MS alterations and specific neurotransmitter maps. results: Network-based statistic analysis revealed disrupted MSN connectivity in patients with CUD, primarily involving the prefrontal cortex, striatum, thalamus, frontoparietal control network, and insula. Regional MS strength abnormalities demonstrated significant spatial correlations with the neurotransmitter density distributions of the serotonergic, dopaminergic, glutamatergic, GABAergic, and cholinergic systems. These spatial correlations were further associated with CUD severity and weekly cocaine dose. Results: Network-based statistic analysis revealed disrupted MSN connectivity in patients with CUD, primarily involving the prefrontal cortex, striatum, thalamus, frontoparietal control network, and insula. Regional MS strength abnormalities demonstrated significant spatial correlations with the neurotransmitter density distributions of the serotonergic, dopaminergic, glutamatergic, GA-BAergic, and cholinergic systems. These spatial correlations were further associated with CUD severity and weekly cocaine dose. Discussion: These findings provide novel insights into the neuropathological mechanisms of CUD from the perspectives of gray matter morphometric covariance patterns and neurotransmitter systems. The consistency with existing findings further supports the clinical translational value of the neurotransmitter targets we have identified. Conclusion: Our findings revealed co-altered patterns of gray matter morphometric covariance and neurotransmitter interactions in CUD, providing novel insights into the neuropathological mechanisms of CUD and identifying potential therapeutic targets.