Repurposing of the PET Probe Prototype PiB for Label and Radiation-Free CEST MRI Molecular Imaging of Amyloid.

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 ß-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 Aß 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.

The value of a shorter-delay arterial spin labeling protocol for detecting cerebrovascular impairment.

BACKGROUND: The aim of this study was to determine the relationship between blood oxygen level dependent (BOLD) cerebrovascular reactivity (CVR) and cerebral blood flow (CBF) obtained from arterial spin labeling (ASL) using different post labeling delays (PLD). METHODS: Forty-two patients with steno-occlusive diseases and impaired CVR were divided into two groups, one scanned with a 1.5-second (1.5-s) and the other with a 2.5-second (2.5-s) PLD ASL protocol. For all patients, a region of interest (ROI) was drawn around the CVR impairment. This affected ROI was then left-right flipped across the brain midline to obtain the control ROI. For both groups, the difference in grey matter CVR between affected and control ROI was first tested to confirm significance. The average grey matter CBF of affected and control ROIs were then compared. The same analysis method was used to compare affected and control hemispheres. RESULTS: In both groups of 1.5-s and 2.5-s PLD, CVR values in the affected ROI (-0.049±0.055 and -0.042±0.074%/mmHg, respectively) were significantly lower compared to that in the control ROI (0.152±0.054 and 0.152±0.053%/mmHg, respectively, P<0.0001). In the group with the 1.5-s PLD, CBF in the affected ROI (37.62±11.37 mL/100 g/min) was significantly lower compared to CBF in the control ROI (44.13±11.58 mL/100 g/min, P<0.05). However, in the group with the 2.5-s PLD, no significant differences could be seen between CBF in the affected ROI (40.50±14.82 mL/100 g/min) and CBF in the control ROI (39.68±12.49 mL/100 g/min, P=0.73). In the hemisphere-based analysis, CBF was significantly lower in the affected side than in the control side for the group with the 1.5-s PLD (P<0.05) when CVR was impaired (P<0.0001), but not for the group with the 2.5-s PLD (P=0.49). CONCLUSIONS: In conclusion, our study reveals and highlights the value of a shorter-PLD ASL protocol, which is able to reflect CVR impairment. At the same time, we offer a better understanding of the relationship between BOLD CVR and CBF obtained from ASL.

Noninvasive Detection of Extracellular pH in Human Benign and Malignant Liver Tumors Using CEST MRI.

PURPOSE: In this study, we aimed to use 3T magnetic resonance imaging (MRI), which is clinically available, to determine the extracellular pH (pHe) of liver tumors and prospectively evaluate the ability of chemical exchange saturation transfer (CEST) MRI to distinguish between benign and malignant liver tumors. METHODS: Different radiofrequency irradiation schemes were assessed for ioversol-based pH measurements at 3T. CEST effects were quantified in vitro using the asymmetric magnetization transfer ratio (MTRasym) at 4.3 ppm from the corrected Z spectrum. Generalized ratiometric analysis was conducted by rationing resolved ioversol CEST effects at 4.3 ppm at a flip angle of 60 and 350°. Fifteen patients recently diagnosed with hepatic carcinoma and five patients diagnosed with hepatic hemangioma [1 male; mean age, 48.6 (range, 37-59) years] were assessed. RESULTS: By conducting dual-power CEST MRI, the pH of solutions was determined to be 6.0-7.2 at 3T in vitro. In vivo, ioversol signal intensities in the tumor region showed that the extracellular pH in hepatic carcinoma was acidic(mean ± standard deviation, 6.66 ± 0.19), whereas the extracellular pH was more physiologically neutral in hemangioma (mean ± standard deviation, 7.34 ± 0.09).The lesion size was similar between CEST pH MRI and T2-weighted imaging. CONCLUSION: dual-power CEST MRI can detect extracellular pH in human liver tumors and can provide molecular-level diagnostic tools for differentiating benign and malignant liver tumors at 3T.

Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI.

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.

Updated incidence rates and risk factors of esophageal cancer in Nan'ao Island, a coastal high-risk area in southern China.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.