[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

The significance of PDGF expression in serum of colorectal carcinoma patients--correlation with Duke's classification. Can PDGF become a potential biomarker?

BACKGROUND: The expression of serum angiogenic factors has been associated with tumor dissemination and poor prognosis in multiple cancer types. However, it is still unclear whether these angiogenic molecules can be used as an independent molecular marker or in correlation with other parameters for predicting the prognosis of colorectal carcinoma (CRC)patients. METHODS: Protein expression was evaluated in 28 CRC and 10 control cases using Angiogenesis Fast Quant technology. RESULTS: In this study, we found downregulation of PDGF-bb protein expression in the serum of patients with colorectal cancer compared with the control group. Thus, PDGF-bb might play an essential function in the progression of CRC. CONCLUSIONS: Our study indicated that the PDGF-bb protein expression might be an independent prognostic marker or in association with other parameters for CRC patients.

Nonrigid PET motion compensation in the lower abdomen using simultaneous tagged-MRI and PET imaging.

PURPOSE: We propose a novel approach for PET respiratory motion correction using tagged-MRI and simultaneous PET-MRI acquisitions. METHODS: We use a tagged-MRI acquisition followed by motion tracking in the phase domain to estimate the nonrigid deformation of biological tissues during breathing. In order to accurately estimate motion even in the presence of noise and susceptibility artifacts, we regularize the traditional HARP tracking strategy using a quadratic roughness penalty on neighboring displacement vectors (R-HARP). We then incorporate the motion fields estimated with R-HARP in the system matrix of an MLEM PET reconstruction algorithm formulated both for sinogram and list-mode data representations. This approach allows reconstruction of all detected coincidences in a single image while modeling the effect of motion both in the emission and the attenuation maps. At present, tagged-MRI does not allow estimation of motion in the lungs and our approach is therefore limited to motion correction in soft tissues. Since it is difficult to assess the accuracy of motion correction approaches in vivo, we evaluated the proposed approach in numerical simulations of simultaneous PET-MRI acquisitions using the NCAT phantom. We also assessed its practical feasibility in PET-MRI acquisitions of a small deformable phantom that mimics the complex deformation pattern of a lung that we imaged on a combined PET-MRI brain scanner. RESULTS: Simulations showed that the R-HARP tracking strategy accurately estimated realistic respiratory motion fields for different levels of noise in the tagged-MRI simulation. In simulations of tumors exhibiting increased uptake, contrast estimation was 20% more accurate with motion correction than without. Signal-to-noise ratio (SNR) was more than 100% greater when performing motion-corrected reconstruction which included all counts, compared to when reconstructing only coincidences detected in the first of eight gated frames. These results were confirmed in our proof-of-principle PET-MRI acquisitions, indicating that our motion correction strategy is accurate, practically feasible, and is therefore ready to be tested in vivo. CONCLUSIONS: This work shows that PET motion correction using motion fields measured with tagged-MRI in simultaneous PET-MRI acquisitions can be made practical for clinical application and that doing so has the potential to remove motion blur in whole-body PET studies of the torso.

Solution of the conformation and alignment tensors for the binding of trimethoprim and its analogs to dihydrofolate reductase: 3D-quantitative structure-activity relationship study using molecular shape analysis, 3-way partial least-squares regression, and 3-way factor analysis.

Molecular recognition is the basis of rational drug design, and for this reason it has been extensively studied. However, the process by which a ligand recognizes and binds to its receptor is complex and not well understood. For the case in which the geometries (conformation and alignment) of the ligand and receptor are known from X-ray crystal structure data, the problem is simplified. The receptor-bound conformation and alignment of the ligand is assumed, and those of additional ligands are inferred. For the general case in which the geometries of the ligand(s) and receptor are unknown, no general treatment or solution is available and receptor-ligand geometries must be obtained indirectly from structure-activity studies or synthesis and evaluation of rigid analogs. A general treatment for solving for the receptor-bound geometry of a series of ligands is presented here. Using molecular shape analysis, for ligand description, tensor analysis of N-way arrays by partial least-squares (PLS) regression, and 3-way factor analysis, the receptor-bound geometries of trimethoprim and a series of trimethoprim-like dihydrofolate reductase inhibitors are correctly predicted.