In vivo co-registered hybrid-contrast imaging by successive photoacoustic tomography and magnetic resonance imaging.

Magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) offer two distinct image contrasts. To integrate these two modalities, we present a comprehensive hardware-software solution for the successive acquisition and co-registration of PAT and MRI images in in vivo animal studies. Based on commercial PAT and MRI scanners, our solution includes a 3D-printed dual-modality imaging bed, a 3-D spatial image co-registration algorithm with dual-modality markers, and a robust modality switching protocol for in vivo imaging studies. Using the proposed solution, we successfully demonstrated co-registered hybrid-contrast PAT-MRI imaging that simultaneously displays multi-scale anatomical, functional and molecular characteristics on healthy and cancerous living mice. Week-long longitudinal dual-modality imaging of tumor development reveals information on size, border, vascular pattern, blood oxygenation, and molecular probe metabolism of the tumor micro-environment at the same time. The proposed methodology holds promise for a wide range of pre-clinical research applications that benefit from the PAT-MRI dual-modality image contrast.

Diminished treatment response in relapsed versus first-episode schizophrenia as revealed by a panel of blood-based biomarkers: A combined cross-sectional and longitudinal study.

There is a paucity of biomarkers for the prediction of treatment response in schizophrenia. In this study, we aimed to investigate whether diminished antipsychotic treatment response in relapsed versus first-episode schizophrenia can be revealed and predicted by a panel of blood-based biomarkers. A cross-sectional cohort consisting of 655 schizophrenia patients at different episodes and 606 healthy controls, and a longitudinal cohort including 52 first-episode antipsychotic-naïve schizophrenia patients treated with the same antipsychotic drugs during the 5-year follow-up of their first three episodes were enrolled. Plasma biomarker changes and symptom improvement were compared between the drug-free phase of psychosis onset and after 4 weeks of atypical antipsychotic drug (AAPD) treatment. In response to treatment, the extent of changes in the biomarkers of bioenergetic, purinergic, phospholipid and neurosteroid metabolisms dwindled down as number of episode and illness duration increased in relapsed schizophrenia. The changes of creatine, inosine, progesterone, allopregnanolone, cortisol and PE(16:0/22:6) were significantly correlated with the improvement of symptomatology. Inosine and progesterone at baseline were shown to be strong predictive biomarkers of treatment response. The results suggest that AAPD treatment response is diminished in the context of relapse, and our findings open new avenues for understanding the pathophysiology of treatment-resistance schizophrenia.

Automatic 3-D segmentation and volumetric light fluence correction for photoacoustic tomography based on optimal 3-D graph search.

Preclinical imaging with photoacoustic tomography (PAT) has attracted wide attention in recent years since it is capable of providing molecular contrast with deep imaging depth. The automatic extraction and segmentation of the animal in PAT images is crucial for improving image analysis efficiency and enabling advanced image post-processing, such as light fluence (LF) correction for quantitative PAT imaging. Previous automatic segmentation methods are mostly two-dimensional approaches, which failed to conserve the 3-D surface continuity because the image slices were processed separately. This discontinuity problem further hampers LF correction, which, ideally, should be carried out in 3-D due to spatially diffused illumination. Here, to solve these problems, we propose a volumetric auto-segmentation method for small animal PAT imaging based on the 3-D optimal graph search (3-D GS) algorithm. The 3-D GS algorithm takes into account the relation among image slices by constructing a 3-D node-weighted directed graph, and thus ensures surface continuity. In view of the characteristics of PAT images, we improve the original 3-D GS algorithm on graph construction, solution guidance and cost assignment, such that the accuracy and smoothness of the segmented animal surface were guaranteed. We tested the performance of the proposed method by conducting in vivo nude mice imaging experiments with a commercial preclinical cross-sectional PAT system. The results showed that our method successfully retained the continuous global surface structure of the whole 3-D animal body, as well as smooth local subcutaneous tumor boundaries at different development stages. Moreover, based on the 3-D segmentation result, we were able to simulate volumetric LF distribution of the entire animal body and obtained LF corrected PAT images with enhanced structural visibility and uniform image intensity.

Clozapine Induced Disturbances in Hepatic Glucose Metabolism: The Potential Role of PGRMC1 Signaling.

Newly emerging evidence has implicated that progesterone receptor component 1 (PGRMC1) plays a novel role not only in the lipid disturbance induced by atypical antipsychotic drugs (AAPD) but also in the deterioration of glucose homoeostasis induced by clozapine (CLZ) treatment. The present study aimed to investigate the role of PGRMC1 signaling on hepatic gluconeogenesis and glycogenesis in male rats following CLZ treatment (20 mg/kg daily for 4 weeks). Recombinant adeno-associated viruses (AAV) were constructed for the knockdown or overexpression of hepatic PGRMC1. Meanwhile, AG205, the specific inhibitor of PGRMC1 was also used for functional validation of PGRMC1. Hepatic protein expressions were measured by western blotting. Meanwhile, plasma glucose, insulin and glucagon, HbA1c and hepatic glycogen were also determined by assay kits. Additionally, concentrations of progesterone (PROG) in plasma, liver and adrenal gland were measured by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Our study demonstrated that CLZ promoted the process of gluconeogenesis and repressed glycogenesis, respectively mediated by PI3K-Akt-FOXO1 and GSK3ß signaling via inhibition of PGRMC1-EGFR/GLP1R in rat liver, along with an increase in fasting blood glucose, HbA1c levels and a decrease in insulin and hepatic glycogen levels. Furthermore, through PGRMC1-EGFR/GLP1R-PI3K-Akt pathway, knockdown or inhibition (by AG205) of PGRMC1 mimics, whereas its overexpression moderately alleviates CLZ-induced glucose disturbances. Potentially, the PGRMC1 target may be regarded as a novel therapeutic strategy for AAPD-induced hepatic glucose metabolism disorder.

Photoacoustic imaging of living mice enhanced with a low-cost contrast agent.

One of the advantages of photoacoustic imaging (PAI) is that its image contrast may come from exogenous agents. Such advantage leads to the development of a great number of exogenous probes. However, the biosafety of most of these contrast agents has not yet been confirmed, thus hindering their clinical translation. In this work, we report on the utilization of a clinically commonly used nutritional medicine, the Intralipid, as a new contrast agent for photoacoustic imaging. Intralipid consists of soybean oil, lecithin and glycerin and has long been adapted in clinical practices, mainly as a parenteral nutrition. In our study, we found that with Intralipid, the imaging sensitivity of PAI can be effectively enhanced, as demonstrated in in vivo imaging of different organs of nude mice. Further imaging studies on cancerous mice showed not only a twofold PA signal enhancement, but also a strong and long-lasting signal aggregation in the tumor region. Our result revealed the potential of Intralipid to be used in clinical PAI applications, since it is clinically safe, and can be easily prepared at very low cost.

[Clinical Significance of P53, C-MYC and BCL-6 Abnormality in Patients with Diffuse Large B Cell Lymphoma].

OBJECTIVE: To study the clinical significance of P53, C-MYC and BCL-6 abnormality in the patients with diffuse large B cell lymphoma (DLBCL). METHODS: From July 2011 to January 2013, 80 patients with DLBCL were admitted in our hospital and were chosen as study objects, their clinical data were collected. The abnormality of P53, C-MYC and BCL-6 was examined by using I-FISH for all the patients. The correlation of abnormality of P53, C-MYC and BCL-6 with clinical staging, curative efficacy and prognosis of the patients were analyzed. RESULTS: Out of 80 patients 27 patients (33.75%) had P53 deletion, 24 patients (30.00%) had C-MYC rearrangement/amplification, and 46 patients (57.50%) had BCL-6 rearrangement. The P53 deletion, C-MYC rearrangement/amplification and BCL-6 rearrangement significantly correlated with staging, curative effect and prognosis of the patients (P < 0.05). CONCLUSION: The curative efficacy and prognosis of the DLBCL patients with abnormality of P53, C-MYC and BCL-6 have been confirmed to be unsatisfactory.