Ximin Shi

Neuronal regeneration and protection by collagen-binding BDNF in the rat middle cerebral artery occlusion model

It has been well confirmed that brain-derived neurotrophic factor (BDNF) has therapeutic effects following stroke. However, it is difficult to be maintained at a sufficient concentration of BDNF in the infarcted hemisphere. We have shown in our previous work that BDNF fused with a collagen-binding domain (CBD-BDNF) could specifically bind to collagen. The ventricular ependyma of the brain is rich in collagen. Therefore, we have speculated that in the infarcted hemisphere, CBD-BDNF will bind to the collagen of the ventricular ependyma and stimulate the cell proliferation in the subventricular zone (SVZ). Using a rat middle cerebral artery occlusion model (MCAO), we injected CBD-BDNF into the lateral ventricle of MCAO rats. The results demonstrated that CBD-BDNF was retained at high levels in the infarcted hemisphere, promoted neural regeneration and angiogenesis, reduced cell loss, decreased apoptosis, and improved functional recovery. In addition, brain perfusion and metabolism, as evaluated by SPECT and PET, were improved in the CBD-BDNF treated group.

Diffuse hepatic and splenic uptake of Tc-99m methylene diphosphonate on bone scintigraphy after intravenous administration of gadolinium-containing MRI contrast.

Three patients with known lung cancer came on different days to our department to have a bone scan to evaluate possible osseous metastatic disease. The bone scan images showed increased Tc-99m methylene diphosphonate (Tc-99m MDP) activity in the liver and to a lesser degree in the spleen, whereas bone scan images from other patients on the same days showed no abnormal activity in the liver or spleen. On the same day, shortly before the bone scan, all 3 patients had a magnetic resonance imaging scan with an intravenous injection of Magnevist (Gadolinium-DTPA), which was not previously known to cause an altered Tc-99m MDP distribution. In the follow-up bone scans performed within 1 week of the initial bone scintigraphy, images from none of these 3 patients showed abnormal liver or spleen activity. The findings indicated that the increased Tc-99m MDP activity in the liver and spleen in the early studies was indeed an effect of Gadolinium-containing magnetic resonance imaging contrast. This effect was further confirmed by an animal experiment.

In vivo cell tracking via 18F-fluorodeoxyglucose labeling: a review of the preclinical and clinical applications in cell-based diagnosis and therapy

The rising interest in using functional cells for diagnosis and treatment has created an urgent need for in vivo cell-tracking techniques. Certain advanced techniques, such as those involving reporter genes or nanoparticles, are still awaiting confirmation of their safety and feasibility in human patients. Tracking cells by labeling them with (18)F-fluorodeoxyglucose, a tracer clinically used in positron emission tomography (PET), may be one way to rapidly translate some of these principles from bench to bedside. The preliminary results are exciting, although further development, optimization, and validation are required. Here, several applications of the technique are surveyed: finding inflammatory foci, targeting cancer immunotherapies, tracking transplanted islet cells, and monitoring cardiac stem cells. Advantages, limitations, and prospects of the technique are discussed. These early experiences only highlight the existing need to improve cell-labeling techniques using PET tracers. This method may finally lead to the development of effective and convenient methods for clinical cell-tracking techniques involving PET/computed tomography.

Clinical Applications of 18 F-FDG PET/CT in Monitoring Anti-cancer Therapies

Cancer is becoming the largest threat to human health. Apart from classical anti-cancer therapies such as surgery, chemotherapies, and radiotherapy, many new therapies are being developed or translated into clinical use. These therapies include various neoadjuvant chemotherapies, minimally invasive treatments, and molecular-targeted therapies. However, none of these methods benefit all patients because treatment should be personalized according to the response of each patient. A futile therapy makes a patient miss the optimum time for treatment and increases the medical burden to the society. Thus, a great challenge is encountered in monitoring such therapies. Classical methods based on anatomical changes such as computed tomography (CT) and magnetic resonance imaging (MRI) have well-known limitations in early response evaluation. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) as tracer is a promising method especially when integrated with CT or MRI in one system. This article reviews the current status of monitoring anti-cancer therapies, including the evolution of evaluation criteria from the World Health Organization to the Response Evaluation Criteria in Solid Tumor and the PET Response Criteria in Solid Tumor. The advantages of 18F-FDG PET/CT for response evaluation are analyzed in various malignant tumors, and the pertinent weaknesses are discussed. Finally, several future directions in monitoring anti-cancer therapies are prospected.

Comparison among Reconstruction Algorithms for Quantitative Analysis of 11C-Acetate Cardiac PET Imaging

Objective Kinetic modeling of dynamic 11C-acetate PET imaging provides quantitative information for myocardium assessment. The quality and quantitation of PET images are known to be dependent on PET reconstruction methods. This study aims to investigate the impacts of reconstruction algorithms on the quantitative analysis of dynamic 11C-acetate cardiac PET imaging. Methods Suspected alcoholic cardiomyopathy patients (N = 24) underwent 11C-acetate dynamic PET imaging after low dose CT scan. PET images were reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF). Standardized uptake values (SUVs) at different time points were compared among images reconstructed using the four algorithms. Time-activity curves (TACs) in myocardium and blood pools of ventricles were generated from the dynamic image series. Kinetic parameters K1 and k2 were derived using a 1-tissue-compartment model for kinetic modeling of cardiac flow from 11C-acetate PET images. Results Significant image quality improvement was found in the images reconstructed using iterative OSEM-type algorithms (OSME, TOF, and TPSF) compared with FBP. However, no statistical differences in SUVs were observed among the four reconstruction methods at the selected time points. Kinetic parameters K1 and k2 also exhibited no statistical difference among the four reconstruction algorithms in terms of mean value and standard deviation. However, for the correlation analysis, OSEM reconstruction presented relatively higher residual in correlation with FBP reconstruction compared with TOF and TPSF reconstruction, and TOF and TPSF reconstruction were highly correlated with each other. Conclusion All the tested reconstruction algorithms performed similarly for quantitative analysis of 11C-acetate cardiac PET imaging. TOF and TPSF yielded highly consistent kinetic parameter results with superior image quality compared with FBP. OSEM was relatively less reliable. Both TOF and TPSF were recommended for cardiac 11C-acetate kinetic analysis.

Primary Neuroendocrine Carcinoma of the Kidney on FDG PET/CT.

A 28-year-old woman presented gradually worsening intermittent right groin pain for 10 months. FDG PET/CT was performed to evaluate the suspected renal malignancy. The images demonstrated a large hypermetabolic tumor occupying the entire right kidney. Pathological examination demonstrated a primary neuroendocrine carcinoma of the kidney.