Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.
Previous neuroimaging studies have revealed cognitive dysfunction in patients with systemic lupus erythematosus (SLE) and suggested that it may be related to disrupted brain white matter (WM) connectivity. However, no study has examined the topological properties of brain WM structural networks in SLE patients, especially in patients with non-neuropsychiatric SLE (non-NPSLE). In this study, we acquired DTI datasets from 28 non-NPSLE patients and 24 healthy controls, constructed their brain WM structural networks by using a deterministic fiber tracking approach, estimated the topological parameters of their structural networks, and compared their group differences. We reached the following results: 1) At the global level, the non-NPSLE patients showed significantly increased characteristic path length, normalized clustering coefficient and small-worldness, but significantly decreased global efficiency and local efficiency compared to the controls; 2) At the nodal level, the non-NPSLE patients had significantly decreased nodal efficiency in regions related to movement control, executive control, and working memory (bilateral precentral gyri, bilateral middle frontal gyri, bilateral inferior parietal lobes, left median cingulate gyrus and paracingulate gyrus, and right middle temporal gyrus). In addition, to pinpointing the injured WM fiber tracts in the non-NPSLE patients, we reconstructed the major brain WM pathways connecting the abnormal regions at the nodal level with the corticospinal tract (CST), superior longitudinal fasciculus-parietal terminations (SLFP), and superior longitudinal fasciculus-temporal terminations (SLFT). By analyzing the diffusion parameters along these WM fiber pathways, we detected abnormal diffusion parameters in the bilateral CST and right SLFT in the non-NPSLE patients. These results seem to indicate that injured brain WM connectivity exists in SLE patients even in the absence of neuropsychiatric symptoms.
The nucleus accumbens (NAc), an important target of deep brain stimulation for some neuropsychiatric disorders, is thought to be involved in epileptogenesis, especially the shell portion. However, little is known about the exact parcellation within the NAc, and its structural abnormalities or connections alterations of each NAc subdivision in temporal lobe epilepsy (TLE) patients. Here, we used diffusion probabilistic tractography to subdivide the NAc into core and shell portions in individual TLE patients to guide stereotactic localization of NAc shell. The structural and connection abnormalities in each NAc subdivision in the groups were then estimated. We successfully segmented the NAc in 24 of 25 controls, 14 of 16 left TLE patients, and 14 of 18 right TLE patients. Both left and right TLE patients exhibited significantly decreased fractional anisotropy (FA) and increased radial diffusivity (RD) in the shell, while there was no significant alteration in the core. Moreover, relatively distinct structural connectivity of each NAc subdivision was demonstrated. More extensive connection abnormalities were detected in the NAc shell in TLE patients. Our results indicate that neuronal degeneration and damage caused by seizure mainly exists in NAc shell and provide anatomical evidence to support the role of NAc shell in epileptogenesis. Remarkably, those NAc shell tracts with increased connectivities in TLE patients were found decreased in FA, which indicates disruption of fiber integrity. This finding suggests the regeneration of aberrant connections, a compensatory and repair process ascribed to recurrent seizures that constitutes part of the characteristic changes in the epileptic network.
PurposeSystemic lupus erythematosus (SLE) is a chronic inflammatory female-predominant autoimmune disease that can affect the central nervous system and exhibit neuropsychiatric symptoms. In SLE patients without neuropsychiatric symptoms (non-NPSLE), recent diffusion tensor imaging studies showed white matter abnormalities in their brains. The present study investigated the entire brain white matter structural connectivity in non-NPSLE patients by using probabilistic tractography and connectivity-based analyses.MethodsWhole-brain structural networks of 29 non-NPSLE patients and 29 healthy controls (HCs) were examined. The structural networks were constructed with interregional probabilistic connectivity. Graph theory analysis was performed to investigate the topological properties, and network-based statistic was employed to assess the alterations of the interregional connections among non-NPSLE patients and controls.ResultsCompared with HCs, non-NPSLE patients demonstrated significantly decreased global and local network efficiencies and showed increased characteristic path length. This finding suggests that the global integration and local specialization were impaired. Moreover, the regional properties (nodal efficiency and degree) in the frontal, occipital, and cingulum regions of the non-NPSLE patients were significantly changed and negatively correlated with the disease activity index. The distribution pattern of the hubs measured by nodal degree was altered in the patient group. Finally, the non-NPSLE group exhibited decreased structural connectivity in the left median cingulate-centered component and increased connectivity in the left precuneus-centered component and right middle temporal lobe-centered component.ConclusionThis study reveals an altered topological organization of white matter networks in non-NPSLE patients. Furthermore, this research provides new insights into the structural disruptions underlying the functional and neurocognitive deficits in non-NPSLE patients.
• A radiation-free radiological method is desirable for assessing pulmonary infectious lesions • MRI at 3 T can depict lung infiltrates with good concordance to MDCT • SPAIR and e-THRIVE are favourable sequences for the detection of pulmonary lesions • The greatest benefit is for the diagnosis of lesions larger than 5 mm.
To detect the abnormal cortical thickness and disrupted brain resting-state functional connectivity (RSFC) in patients with systemic lupus erythematosus (SLE) without neuropsychiatric symptoms (non-NPSLE). Using T1-weighted 3D brain structural data, we first determined the regions with abnormal cortical thickness in a cohort of 33 adult female non-NPSLE patients. By taking brain regions with significantly reduced cortical thickness as the seeds, we calculated their RSFC based on the resting-fMRI data and detected the relationship between the RSFC and cortical thickness in the non-NPSLE patients. Compared to the controls, the non-NPSLE patients showed significantly cortical thinning in the left fusiform gyrus (FUS.L), left lingual gyrus (LING.L), right lingual gyrus (LING.R) and left superior frontal cortex (SFC.L). As for the RSFC, statistical analyses indicated that the abnormal cortical thickness in LING.L is associated with increased RSFC in the left posterior cingulate cortex (PCC.L), and cortical thinning in SFC.L associated with decreased RSFC in left cerebellum 6 (CRBL 6.L) in non-NPSLE patients. In addition, in non-NPSLE patients, the decreased cortical thickness in LING.L was correlated to the increased RSFC in PCC.L, and decreased cortical thickness in SFC.L was correlated to the decreased RSFC in CRBL 6.L. Our findings suggest that the cortical abnormalities may affect brain intrinsic connectivity in non-NPSLE patients.
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