Diffusion Tensor Tractrography Visualizes Partial Nerve Laceration Severity as Early as 1 Week After Surgical Repair in a Rat Model Ex Vivo.

Background: Previous studies in our laboratory have demonstrated that a magnetic resonance imaging method called diffusion tensor imaging (DTI) can differentiate between crush and complete transection peripheral nerve injuries in a rat model ex vivo. DTI measures the directionally dependent effect of tissue barriers on the random diffusion of water molecules. In ordered tissues such as nerves, this information can be used to reconstruct the primary direction of diffusion along fiber tracts, which may provide information on fiber tract continuity after nerve injury and surgical repair.

Relating structural and functional brainstem connectivity to disease measures in epilepsy.

Objective: While epilepsy studies rarely examine brainstem, we sought to examine the hypothesis that temporal lobe epilepsy (TLE) leads to subcortical arousal center dysfunction, contributing to neocortical connectivity and neurocognitive disturbances.

Methods: In this case-control study of 26 adult patients with TLE and 26 controls, we used MRI to measure structural and functional connectivity of the cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus, and ventral tegmental area. Ascending reticular activating system connectivity patterns were related to neuropsychological and disease measures.

On the Use of DSC-MRI for Measuring Vascular Permeability.

Background And Purpose: Contrast agent extravasation has been shown to confound brain tumor perfusion measurements with DSC-MR imaging, necessitating the use of correction techniques (eg, Weisskoff, Bjornerud). Leakage parameters (K2 and K(a)) postulated to reflect vessel permeability can be extracted from these correction methods; however, the biophysical interpretation of these parameters and their relationship to commonly used MR imaging measures of vascular permeability (eg, contrast agent volume transfer constant, [K(trans)]) remain unclear. Given that vascular density, as assessed by blood volume, and vascular permeability, as reflected by K(trans) (and potentially K2 or K(a)), report on unique and clinically informative vascular characteristics, there is a compelling interest to simultaneously assess these features.

3'-Deoxy-3'-[18F]-Fluorothymidine PET imaging reflects PI3K-mTOR-mediated pro-survival response to targeted therapy in colorectal cancer.

Biomarkers that predict response to targeted therapy in oncology are an essential component of personalized medicine. In preclinical treatment response studies that featured models of wild-type KRAS or mutant BRAF colorectal cancer treated with either cetuximab or vemurafenib, respectively, we illustrate that [(18)F]-FLT PET, a non-invasive molecular imaging readout of thymidine salvage, closely reflects pro-survival responses to targeted therapy that are mediated by PI3K-mTOR activity. Activation of pro-survival mechanisms forms the basis of numerous modes of resistance.

18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer.

Purpose: To evaluate 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography imaging ((18)FDG-PET) as a predictive, noninvasive, pharmacodynamic (PD) biomarker of response following administration of a small-molecule insulin-like growth factor-1 receptor and insulin receptor (IGF-1R/IR) inhibitor, OSI-906.

Experimental Design: In vitro uptake studies of (3)H-2-deoxy glucose following OSI-906 exposure were conducted evaluating correlation of dose with inhibition of IGF-1R/IR as well as markers of downstream pathways and glucose metabolism. Similarly, in vivo PD effects were evaluated in human tumor cell line xenografts propagated in athymic nude mice by (18)FDG-PET at 2, 4, and 24 hours following a single treatment of OSI-906 for the correlation of inhibition of receptor targets and downstream markers.