Extracellular pH (pHe) decrease is associated with tumor growth, invasion, metastasis, and chemoresistance, which can be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of the liver cancer microenvironment. In in vitro studies, we firstly explored whether ioversol signal is pH-dependent, and calculated the function equation between the CEST effects of ioversol and pH values, in the range of 6.0 to 7.8, by a ratiometric method. Then we verified the feasibility of this technique and the equation in vivo by applying pHe imaging in an MMTV-Erbb2 transgenic mouse breast cancer model, which is often used in CEST pHe studies. Furthermore, in vivo ioversol CEST MRI, we were able to map relative pHe and differentiate between tumor and normal tissue in a McA-RH7777 rat hepatoma model. This suggests pHe may be a useful biomarker for human liver cancer.

Adult-onset Still's disease (AOSD), as a category of connective tissue diseases, has about 5∼9% of fever of unknown origin (FUO) cases. Diagnosis of AOSD was challenging because of its nonspecific characteristics. The present study analyzed clinical manifestations and laboratory findings in a series of patients with AOSD from eastern China. Medical records of 61 patients admitted with FUO and with a discharge diagnosis of AOSD were retrospectively evaluated and analyzed with special focus on clinical manifestations and laboratory findings. Compared with previous reports, most features of our patients had a similar incidence rate. Rash (79%), arthralgia (80%), and sore throat (84%) were the most frequent clinical manifestations in our series. Leukocytosis (80%), elevated ESR (98%) and CRP (100%), negative ANA (90%) and RF (93%), and high ferritin level (94%) were the most sensitive laboratory findings in our patients. AOSD was not a rare reason of FUO in eastern China. Fever, arthralgia, rash, sore throat, leukocytosis, neutrophilia, elevated ESR and CRP, negative ANA and RF, and high ferritin level were the most common clinical features in our series. The lack of highly specific characteristic makes the diagnosis of AOSD difficult compared with other diseases in FUO.

A correlation between the abnormal cerebral glucose metabolism and the progression of Alzheimer’s disease (AD) has been found in previous studies, suggesting that glucose alterations may be used to predict the histopathological diagnosis in AD. In this study, we investigated the dynamic changes of cerebral glucose uptake in vivo using MR glucose chemical exchange saturation transfer (glucoCEST) imaging in a rat model of AD with an intracerebroventricular (i.c.v) injection of amyloid Aβ-protein (25–35), confirmed by Morris water maze and Nissl staining. In total, 6 rats in the AD group and 6 rats in the control group that were given an injection of sterile normal saline were included. At 28 days after injection, all rats performed a 7.0 T MR exanimation, including glucoCEST, diffusion tensor imaging (DTI) and hippocampus magnetic resonance spectra (MRS), to detect the possible metabolic and structural changes in the rat brain. A significantly elevated brain glucoCEST signal in the brain of AD rats was observed, and a decreased brain glucose uptake was also explored during the progression of glucose infusion compared with those in rats of the control group. In addition, there is a significant positive correlation between glucoCEST enhancement (GCE) and myo-Inosito (Ins) in the AD group and the control group (P < 0.05). A significantly reduced number of neurons in the cortex and hippocampus in AD rats combined with the significantly longer escape and a decreased number of crossings were verified at 28 days after Aβ25–35 injection by Nissl staining and Morris water maze, respectively. Our results indicated that an abnormal brain glucose mechanism in AD rats could be detected by glucoCEST imaging, suggesting a new method to explore the occurrence and progress of diabetes-related AD or dementia.

Glutamate excitoxicity plays a crucial role in the pathophysiology of traumatic brain injury (TBI) through the initiation of secondary injuries. Glutamate chemical exchange saturation transfer (GluCEST) MRI is a newly developed technique to noninvasively image glutamate in vivo with high sensitivity and spatial resolution. The aim of the present study was to use a rat model of TBI to map changes in brain glutamate distribution and explore the capability of GluCEST imaging for detecting secondary injuries. Sequential GluCEST imaging scans were performed in adult male Sprague–Dawley rats before TBI and at 1, 3, 7, and 14 days after TBI. GluCEST% increased and peaked on day 1 after TBI in the core lesion of injured cortex and peaked on day 3 in the ipsilateral hippocampus, as compared to baseline and controls. GluCEST% gradually declined to baseline by day 14 after TBI. A negative correlation between the GluCEST% of the ipsilateral hippocampus on day 3 and the time in the correct quadrant was observed in injured rats. Immunolabeling for glial fibrillary acidic protein showed significant astrocyte activation in the ipsilateral hippocampus of TBI rats. IL-6 and TNF-α in the core lesion peaked on day 1 postinjury, while those in the ipsilateral hippocampus peaked on day 3. These subsequently gradually declined to sham levels by day 14. It was concluded that GluCEST imaging has potential to be a novel neuroimaging approach for predicting cognitive outcome and to better understand neuroinflammation following TBI.

Amyloid-β (Aβ) deposits and some proteins play essential roles in the pathogenesis of Alzheimer's disease (AD). Amide proton transfer (APT) imaging, as an imaging modality to detect tissue protein, has shown promising features for the diagnosis of AD disease. In this study, we chose 10 AD model rats as the experimental group and 10 sham-operated rats as the control group. All the rats underwent a Y-maze test before APT image acquisition, using saturation with frequency alternating RF irradiation (APT SAFARI) method on a 7.0 T animal MRI scanner. Compared with the control group, APT (3.5 ppm) values of brain were significantly reduced in AD models (p < 0.002). The APT SAFARI imaging is more significant than APT imaging (p < 0.0001). AD model mice showed spatial learning and memory loss in the Y-maze experiment. In addition, there was significant neuronal loss in the hippocampal CA1 region and cortex compared with sham-operated rats. In conclusion, we demonstrated that APT imaging could potentially provide molecular biomarkers for the non-invasive diagnosis of AD. APT SAFARI MRI could be used as an effective tool to improve the accuracy of diagnosis of AD compared with conventional APT imaging.