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Aims: Acute kidney injury (AKI) has been associated with a variety of neurological problems, while the neurobiological mechanism remains unclear. In the present study, we utilized resting‐state functional magnetic resonance imaging (rs‐fMRI) to detect brain injury at an early stage and investigated the impact of microglia on the neuropathological mechanism of AKI. Methods: Rs‐fMRI data were collected from AKI rats and the control group with a 9.4‐Tesla scanner at 24, 48, and 72 h post administration of contrast medium or saline. The amplitude of low‐frequency fluctuations (ALFF) was then compared across the groups at each time course. Additionally, flow cytometry and SMART‐seq2 were employed to evaluate microglia. Furthermore, pathological staining and Western blot were used to analyze the samples. Results: MRI results revealed that AKI led to a decreased ALFF in the hippocampus, particularly in the 48 h and 72 h groups. Additionally, western blot suggested that AKI‐induced the neuronal apoptosis at 48 h and 72 h. Flow cytometry and confocal microscopy images demonstrated that AKI activated the aggregation of microglia into neurons at 24 h, with a strong upregulation of M1 polarization at 48 h and peaking at 72 h, accompanying with the release of proinflammatory cytokines. The ALFF value was strongly correlated with the proportion of microglia (|r| > 0.80, p < 0.001). Conclusions: Our study demonstrated that microglia aggregation and inflammatory factor upregulation are significant mechanisms of AKI‐induced neuronal apoptosis. We used fMRI to detect the alterations in hippocampal function, which may provide a noninvasive method for the early detection of brain injury after AKI. [ABSTRACT FROM AUTHOR]

Early detection of pulmonary fibrosis is a critical yet insufficiently met clinical necessity. This study evaluated the effectiveness of FAPI-LM3, a 68 Ga-radiolabeled heterobivalent molecular probe that targets fibroblast activating protein (FAP) and somatostatin receptor 2 (SSTR2), in the early detection of pulmonary fibrosis, leveraging its potential for early disease identification. A bleomycin-induced early pulmonary fibrosis model was established in C57BL/6 mice for 7 days. FAP and SSTR2 expression levels were quantitatively assessed in human idiopathic pulmonary fibrosis lung tissue samples and bleomycin-treated mouse lung tissues by using western blotting, real-time quantitative PCR (RT-qPCR), and immunofluorescence techniques. The diagnostic performance of FAPI-LM3 was investigated by synthesizing monomeric radiotracers 68 Ga-FAPI-46 and 68 Ga-DOTA-LM3 alongside the heterobivalent probe 68 Ga-FAPI-LM3. These imaging radiopharmaceuticals were used in small-animal PET to compare their uptake in fibrotic and normal lung tissues. Results indicated significant upregulation of FAP and SSTR2 at both RNA and protein levels in fibrotic lung tissues compared with that in normal controls. PET imaging demonstrated significantly enhanced uptake of the 68 Ga-FAPI-LM3 probe in fibrotic lung tissues, with superior visual effects compared to monomeric tracers. At 60 min postinjection, early stage fibrotic tissues (day 7) demonstrated low-to-medium uptake of monomeric probes, including 68 Ga-DOTA-LM3 (0.45 ± 0.04% ID/g) and 68 Ga-FAPI-46 (0.78 ± 0.09% ID/g), whereas the uptake of the heterobivalent probe 68 Ga-FAPI-LM3 (1.90 ± 0.10% ID/g) was significantly higher in fibrotic lesions than in normal lung tissue. Blockade experiments confirmed the specificity of 68 Ga-FAPI-LM3 uptake, which was attributed to synergistic targeting of FAP and SSTR2. This study demonstrates the potential of 68 Ga-FAPI-LM3 for early pulmonary fibrosis detection via molecular imaging, offering significant benefits over monomeric tracers 68 Ga-FAPI-46 and 68 Ga-DOTA-LM3. This strategy offers new possibilities for noninvasive and precise early detection of pulmonary fibrosis.