A branched polymer-based agent for efficient and precise targeting of fibrosis diseases by magnetic resonance imaging.

Herein, we synthesized and characterized gadolinium-based hyperbranched polymers, POADGd and PODGd, through RAFT polymerization as magnetic resonance imaging (MRI) contrast agents for detecting fibrosis. POADGd and PODGd contain biocompatible short-chain OEGMA to prolong blood circulation, and they can be decomposed in response to ROS after MRI examination to prevent potential accumulation. The relaxivities of POADGd and PODGd are 9.81 mM-1 s-1 and 9.58 mM-1 s-1 respectively, which are significantly higher than that of DTPA-Gd, a clinically used agent (3.74 mM-1 s-1). In comparison with PODGd, POADGd can specifically target allysine in fibrosis tissues through its oxyamine groups. Therefore, it displays a sharp spatial resolution and a high signal-to-noise ratio in the liver and lung fibrosis tissue at a field strength of 3.0 T or 7.0 T, and the morphology of these fibrosis tissues is accurately delineated. Our MRI diagnosis results based on POADGd are highly aligned with those from pathological examinations, while MRI diagnosis could avoid invasive biopsy. In addition, POADGd shows excellent biosafety and low toxicity. Therefore, POADGd could be applied to non-invasively and accurately diagnose liver and lung fibrosis diseases.

Abnormal large-scale brain functional network dynamics in social anxiety disorder.

AIMS: Although static abnormalities of functional brain networks have been observed in patients with social anxiety disorder (SAD), the brain connectome dynamics at the macroscale network level remain obscure. We therefore used a multivariate data-driven method to search for dynamic functional network connectivity (dFNC) alterations in SAD. METHODS: We conducted spatial independent component analysis, and used a sliding-window approach with a k-means clustering algorithm, to characterize the recurring states of brain resting-state networks; then state transition metrics and FNC strength in the different states were compared between SAD patients and healthy controls (HC), and the relationship to SAD clinical characteristics was explored. RESULTS: Four distinct recurring states were identified. Compared with HC, SAD patients demonstrated higher fractional windows and mean dwelling time in the highest-frequency State 3, representing "widely weaker" FNC, but lower in States 2 and 4, representing "locally stronger" and "widely stronger" FNC, respectively. In State 1, representing "widely moderate" FNC, SAD patients showed decreased FNC mainly between the default mode network and the attention and perceptual networks. Some aberrant dFNC signatures correlated with illness duration. CONCLUSION: These aberrant patterns of brain functional synchronization dynamics among large-scale resting-state networks may provide new insights into the neuro-functional underpinnings of SAD.

Harnessing and Mimicking Bacterial Features to Combat Cancer: From Living Entities to Artificial Mimicking Systems.

Bacterial-derived micro-/nanomedicine has garnered considerable attention in anticancer therapy, owing to the unique natural features of bacteria, including specific targeting ability, immunogenic benefits, physicochemical modifiability, and biotechnological editability. Besides, bacterial components have also been explored as promising drug delivery vehicles. Harnessing these bacterial features, cutting-edge physicochemical and biotechnologies have been applied to attenuated tumor-targeting bacteria with unique properties or functions for potent and effective cancer treatment, including strategies of gene-editing and genetic circuits. Further, the advent of bacteria-inspired micro-/nanorobots and mimicking artificial systems has furnished fresh perspectives for formulating strategies for developing highly efficient drug delivery systems. Focusing on the unique natural features and advantages of bacteria, this review delves into advances in bacteria-derived drug delivery systems for anticancer treatment in recent years, which has experienced a process from living entities to artificial mimicking systems. Meanwhile, a summary of relative clinical trials is provided and primary challenges impeding their clinical application are discussed. Furthermore, future directions are suggested for bacteria-derived systems to combat cancer.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Genes associated with cortical thickness alterations in behavioral addiction.

Behavioral addiction (BA) is a conceptually new addictive phenotype characterized by compulsive reward-seeking behaviors despite adverse consequences. Currently, its underlying neurogenetic mechanism remains unclear. Here, this study aimed to investigate the association between cortical thickness (CTh) and genetic phenotypes in BA. We conducted a systematic search in five databases and extracted gene expression data from the Allen Human Brain Atlas. Meta-analysis of 10 studies (343 addicted individuals and 355 controls) revealed that the BA group showed thinner CTh in the precuneus, postcentral gyrus, orbital-frontal cortex, and dorsolateral prefrontal cortex (P < 0.005). Meta-regression showed that the CTh in the precuneus and postcentral gyrus were negatively associated with the addiction severity (P < 0.0005). More importantly, the CTh phenotype of BA was spatially correlated with the expression of 12 genes (false discovery rate [FDR] < 0.05), and the dopamine D2 receptor had the highest correlation (rho = 0.55). Gene enrichment analysis further revealed that the 12 genes were involved in the biological processes of behavior regulation and response to stimulus (FDR < 0.05). In conclusion, our findings demonstrated the thinner CTh in cognitive control-related brain areas in BA, which could be associated with the expression of genes involving dopamine metabolism and behavior regulation.

Altered cerebellar effective connectivity in first-episode schizophrenia and long-term changes after treatment.

AIM: Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ. METHODS: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom. RESULTS: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission. CONCLUSION: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (ß = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

Biomarker-driven molecular imaging probes in radiotherapy.

Background: Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use of molecular imaging probes, including nanoprobes, have been explored in radiotherapy imaging to precisely and noninvasively monitor spatiotemporal distribution of biomarkers, potentially revealing tumor-killing mechanisms and therapy-induced adverse effects during radiation treatment. Methods: We summarized literature reports from preclinical studies and clinical trials, which cover two main parts: 1) Clinically-investigated and emerging imaging biomarkers associated with radiotherapy, and 2) instrumental roles, functions, and activatable mechanisms of molecular imaging probes in the radiotherapy workflow. In addition, reflection and future perspectives are proposed. Results: Numerous imaging biomarkers have been continuously explored in decades, while few of them have been successfully validated for their correlation with radiotherapeutic outcomes and/or radiation-induced toxicities. Meanwhile, activatable molecular imaging probes towards the emerging biomarkers have exhibited to be promising in animal or small-scale human studies for precision radiotherapy. Conclusion: Biomarker-driven molecular imaging probes are essential for precision radiotherapy. Despite very inspiring preliminary results, validation of imaging biomarkers and rational design strategies of probes await robust and extensive investigations. Especially, the correlation between imaging biomarkers and radiotherapeutic outcomes/toxicities should be established through multi-center collaboration involving a large cohort of patients.

The associations of peripheral interleukin alterations and hippocampal subfield volume deficits in schizophrenia.

The hippocampus is one of the brain regions most vulnerable to inflammatory insults, and the relationships between peripheral inflammation and hippocampal subfields in patients with schizophrenia remain unclear. In this study, forty-six stably medicated patients with schizophrenia and 48 demographically matched healthy controls (HCs) were recruited. The serum levels of IL - 1ß, IL-6, IL-10, and IL-12p70 were measured, and 3D high-resolution T1-weighted magnetic resonance imaging was performed. The IL levels and hippocampal subfield volumes were both compared between patients and HCs. The associations of altered IL levels with hippocampal subfield volumes were assessed in patients. Patients with schizophrenia demonstrated higher serum levels of IL-6 and IL-10 but lower levels of IL-12p70 than HCs. In patients, the levels of IL-6 were positively correlated with the volumes of the left granule cell layer of the dentate gyrus (GCL) and cornu Ammonis (CA) 4, while the levels of IL-10 were negatively correlated with the volumes of those subfields. IL-6 and IL-10 might have antagonistic roles in atrophy of the left GCL and CA4. This suggests a complexity of peripheral cytokine dysregulation and the potential for its selective effects on hippocampal substructures, which might be related to the pathophysiology of schizophrenia.

Elucidating trauma-related and disease-related regional cortical activity in post-traumatic stress disorder.

Trauma exposure may precipitate a cascade of plastic modifications within the intrinsic activity of brain regions, but it remains unclear which regions could be responsible for the development of post-traumatic stress disorder based on intrinsic activity. To elucidate trauma-related and post-traumatic stress disorder-related alterations in cortical intrinsic activity at the whole-brain level, we recruited 47 survivors diagnosed with post-traumatic stress disorder, 64 trauma-exposed controls from a major earthquake, and 46 age- and sex-matched healthy controls. All subjects were scanned with an echo-planar imaging sequence, and 5 parameters including the amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, regional homogeneity, degree centrality, and voxel-mirrored homotopic connectivity were calculated. We found both post-traumatic stress disorder patients and trauma-exposed controls exhibited decreased amplitude of low-frequency fluctuations in the bilateral posterior cerebellum and inferior temporal gyrus, decreased fractional amplitude of low-frequency fluctuation and regional homogeneity in the bilateral anterior cerebellum, and decreased fractional amplitude of low-frequency fluctuation in the middle occipital gyrus and cuneus compared to healthy controls, and these impairments were more severe in post-traumatic stress disorder patients than in trauma-exposed controls. Additionally, fractional amplitude of low-frequency fluctuation in left cerebellum was positively correlated with Clinician-Administered PTSD Scale scores in post-traumatic stress disorder patients. We identified brain regions that might be responsible for the emergence of post-traumatic stress disorder, providing important information for the treatment of this disorder.

Linked patterns of symptoms and cognitive covariation with functional brain controllability in major depressive disorder.

BACKGROUND: Controllability analysis is an approach developed for evaluating the ability of a brain region to modulate function in other regions, which has been found to be altered in major depressive disorder (MDD). Both depressive symptoms and cognitive impairments are prominent features of MDD, but the case-control differences of controllability between MDD and controls can not fully interpret the contribution of both clinical symptoms and cognition to brain controllability and linked patterns among them in MDD. METHODS: Sparse canonical correlation analysis was used to investigate the associations between resting-state functional brain controllability at the network level and clinical symptoms and cognition in 99 first-episode medication-naïve patients with MDD. FINDINGS: Average controllability was significantly correlated with clinical features. The average controllability of the dorsal attention network (DAN) and visual network had the highest correlations with clinical variables. Among clinical variables, depressed mood, suicidal ideation and behaviour, impaired work and activities, and gastrointestinal symptoms were significantly negatively associated with average controllability, and reduced cognitive flexibility was associated with reduced average controllability. INTERPRETATION: These findings highlight the importance of brain regions in modulating activity across brain networks in MDD, given their associations with symptoms and cognitive impairments observed in our study. Disrupted control of brain reconfiguration of DAN and visual network during their state transitions may represent a core brain mechanism for the behavioural impairments observed in MDD. FUNDING: National Natural Science Foundation of China (82001795 and 82027808), National Key R&D Program (2022YFC2009900), and Sichuan Science and Technology Program (2024NSFSC0653).

Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: Alterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder. METHODS: We recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC. RESULTS: First-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance. LIMITATIONS: The relatively large "pure" MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions. CONCLUSION: These findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

Neural activation signatures in individuals with subclinical depression: A task-fMRI meta-analysis.

BACKGROUND: Previous task-related functional magnetic resonance imaging (task-fMRI) investigations have documented abnormal brain activation associated with subclinical depression (SD), defined as a clinically relevant level of depressive symptoms that does not meet the diagnostic criteria for major depressive disorder. However, these task-fMRI studies have not reported consistent conclusions. Performing a voxel-based meta-analysis of task-fMRI studies may yield reliable findings. METHODS: We extracted the peak coordinates and t values of included studies and analyzed brain activation between individuals with SD and healthy controls (HCs) using anisotropic effect-size signed differential mapping (AES-SDM). RESULTS: A systematic literature search identified eight studies, including 266 individuals with SD and 281 HCs (aged 14 to 25). The meta-analysis showed that individuals with SD exhibited significantly greater activation in the right lenticular nucleus and putamen according to task-fMRI. The meta-regression analysis revealed a negative correlation between the proportion of females in a group and activation in the right striatum. LIMITATIONS: The recruitment criteria for individuals with SD, type of tasks and MRI acquisition parameters of included studies were heterogeneous. The results should be interpreted cautiously due to insufficient included studies. CONCLUSION: Our findings suggest that individuals with SD exhibit increased activation in the right lenticular nucleus, putamen and striatum, which may indicate a compensatory increase in response to an impairment of insular and striatal function caused by depression. These results provide valuable insights into the potential pathophysiology of brain dysfunction in SD.

Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Body Satisfaction, Exercise Dependence, and White Matter Microstructure in Young Adults.

BACKGROUND: Self-body satisfaction is considered a psychological factor for exercise dependence (EXD). However, the potential neuropsychological mechanisms underlying this association remain unclear. PURPOSE: To investigate the role of white matter microstructure in the association between body satisfaction and EXD. STUDY TYPE: Prospective. POPULATION: One hundred eight regular exercisers (age 22.11 ± 2.62 years; 58 female). FIELD STRENGTH/SEQUENCE: 3.0 Tesla; diffusion-weighted echo planar imaging with 30 directions. ASSESSMENT: The Body Shape Satisfaction (BSS) and Exercise Dependence Scale (EDS); whole-brain tract-based spatial statistics (TBSS) and correlational tractography analyses; average fractional anisotropy (FA) and quantitative anisotropy (QA) values of obtained tracts. STATISTICAL TESTS: The whole-brain regression model, mediation analysis, and simple slope analysis. P values <0.05 were defined as statistically significant. RESULTS: The BSS and EDS scores were 37.33 ± 6.32 and 68.22 ± 13.88, respectively. TBSS showed negative correlations between EDS and FA values in the bilateral corticospinal tract (CST, r = -0.41), right cingulum (r = -0.41), and left superior thalamic radiation (STR, r = -0.50). Correlational tractography showed negative associations between EDS and QA values of the left inferior frontal occipital fasciculus (r = -0.35), STR (r = -0.42), CST (r = -0.31), and right cingulum (r = -0.28). The FA values, rather than QA values, mediated the BSS-EDS association (indirect effects = 0.30). The BSS was significantly associated with the EDS score at both low (ß = 1.02) and high (ß = 0.43) levels of FA value, while the association was significant only at the high level of QA value (ß = 1.26). DATA CONCLUSION: EXD was correlated with white matter in frontal-subcortical and sensorimotor networks, and these tracts mediated the body satisfaction-EXD association. White matter microstructure could be a promising neural signature for understanding the underlying neuropsychological mechanisms of EXD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Facile Synthesis of Rigid Binuclear Manganese Complexes for Magnetic Resonance Angiography and SLC39A14-Mediated Hepatic Imaging.

Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.

Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia.

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.

Porphyrin-Based Self-Assembled Nanoparticles for PET/MR Imaging of Sentinel Lymph Node Metastasis.

Diagnosing of lymph node metastasis is challenging sometimes, and multimodal imaging offers a promising method to improve the accuracy. This work developed porphyrin-based nanoparticles (68Ga-F127-TAPP/TCPP(Mn) NPs) as PET/MR dual-modal probes for lymph node metastasis imaging by a simple self-assembly method. Compared with F127-TCPP(Mn) NPs, F127-TAPP/TCPP(Mn) NPs synthesized by amino-porphyrins (TAPP) doping can not only construct PET/MR bimodal probes but also improve the T1 relaxivity (up to 456%). Moreover, T1 relaxivity can be adjusted by altering the molar ratio of TAPP/TCPP(Mn) and the concentration of F127. However, a similar increase in T1 relaxivity was not observed in the F127-TCPP/TCPP(Mn) NPs, which were synthesized using carboxy-porphyrins (TCPP) doping. In a breast cancer lymph node metastasis mice model, subcutaneous injection of 68Ga-F127-TAPP/TCPP(Mn) NPs through the hind foot pad, the normal lymph nodes and metastatic lymph nodes were successfully distinguished based on the difference of PET standard uptake values and MR signal intensities. Furthermore, the dark brown F127-TAPP/TCPP(Mn) NPs demonstrated the potential for staining and mapping lymph nodes. This study provides valuable insights into developing and applying PET/MR probes for lymph node metastasis imaging.

A novel transcranial MR Guided focused ultrasound method based on the ultrashort echo time skull acoustic model and phase retrieval techniques.

Transcranial ultrasound stimulation (TUS) has been clinically applied as a neuromodulation tool. Particularly, the phase array ultrasound can be applied in TUS to non-invasively focus on the cortex or deep brain. However, the vital phase distortion of the ultrasound induced by the skull limits its clinical application. In the current study, we aimed to develop a hybrid method that combines the ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences with the prDeep technique to achieve focusing ventral intermediate thalamic nucleus (VIM). The time-reversal (TR) approach of the UTE numerical acoustic model of the skull combined with the prDeep algorithm was used to reduce the number of iterations. The skull acoustic model simulation therapy process was establish to valid this method's prediction and focus performance, and the classical TR method were considered as the gold standard (GS). Our approach could restore 75% of the GS intensity in 25 iteration steps, with a superior the noise immunity. Our findings demonstrate that the phase aberration caused by the skull can be estimated using phase retrieval techniques to achieve a fast and accurate transcranial focus. The method has excellent adaptability and anti-noise capacity for satisfying complex and changeable scenarios.