Search

The current report describes the development of a dual modality tomographic agent for both positron emission tomography and magnetic resonance imaging (PET/MRI). The dual-modality agent in this study was based on a 124I (PET) radiolabeled tri-gadolinium endohedral metallofullerene Gd3N@C80 (MRI) nanoprobe platform. The outer surface of the fullerene cage of the Gd3N@C80 metallofullerenes was surface functionalized with carboxyl and hydroxyl groups (f-Gd3N@C80) using previously developed procedures and subsequently iodinated with 124I to produce 124I-f-Gd3N@C80 nanoprobe. Orthotopic tumor-bearing rats were infused intratumorally by convection-enhanced delivery (CED) with the 124I-f-Gd3N@C80 agent and imaged by MRI or micro PET. The anatomical positioning and distribution of the 124I-f-Gd3N@C80 agent were comparable between the MRI and PET scans. The 124I-f-Gd3N@C80­ dual-agent distribution and infusion site within the tumor was clearly evident in both T1- and T2-weighted MR images. The results demonstrate the successful preparation of a dual-modality imaging agent, 124I-f-Gd3N@C80, which could ultimately be used for simultaneous PET/MR imaging.

Background: Generalized anxiety disorder (GAD) is a common chronic condition that is relatively understudied compared to other psychiatric syndromes. Neuroimaging studies have begun to implicate particular neural structures and circuitry in its pathophysiology; however, no genetically informative research has examined the potential sources of reported brain differences., Methods: We acquired spectroscopic, volumetric, and diffusion tensor magnetic resonance imaging data from a pilot study of 34 female subjects selected from monozygotic twin pairs based upon their affection status for GAD, and examined brain regions previously implicated in fear and anxiety for their relationship with affection status and genetic risk., Results: Lifetime GAD associated with increased creatine levels in the amygdala, smaller left hippocampal volume, and lower fractional anisotropy in the uncinate fasciculus which connects amygdala and frontal cortex. In addition, GAD genetic risk predicted increases in myo-inositol in the amygdala and, possibly, glutamate/glutamine/GABA alterations in the hippocampus. The association of lifetime GAD with smaller hippocampal volume was independent of major depression and might represent a common genetic risk marker for internalizing disorders., Conclusions: These preliminary data suggest that GAD and its genetic risk factors are likely correlated with volumetric and spectroscopic changes in fear-related limbic structures and their connections with the frontal cortex., (© 2011 Wiley-Liss, Inc.)

Background: We believe that in traumatic brain injury (TBI), the reduction of N-acetyl aspartate (NAA) occurs in the presence of adequate cerebral blood flow (CBF) which would lend support to the concept of mitochondrial impairment. The objective of this study was to test this hypothesis in severely injured patients (GCS 8 or less) by obtaining simultaneous measures of CBF and NAA., Methods: Fourteen patients were studied of which six patients presented as diffuse injury at admission CT, while focal lesions were present in eight patients. CBF using stable xenon method was measured at the same time that NAA was measured by magnetic resonance proton spectroscopy (1HMRS) in the MR suite. Additionally, diffusion weighted imaging (DWI) and maps of the apparent diffusion coefficient (ADC) were assessed., Findings: In diffuse injury, NAA/Cr reduction occurred uniformly throughout the brain where the values of CBF in all patients were well above ischemic threshold. In focal injury, we observed ischemic CBF values in the core of the lesions. However, in areas other than the core, CBF was above ischemic levels and NAA/Cr levels were decreased., Conclusions: Considering the direct link between energy metabolism and NAA synthesis in the mitochondria, this study showed that in the absence of an ischemic insult, reductions in NAA concentration reflects mitochondrial dysfunction.

Object: After traumatic brain injury (TBI), S100B protein is released by astrocytes. Furthermore, cerebrospinal fluid (CSF) and serum S100B levels have been correlated to outcome. Given that no data exist about the temporal profile of cerebral S100B levels following TBI and their correlation to serum levels, the authors examined whether proton magnetic resonance (MR) spectroscopy is capable of measuring S100B., Methods: Results of in vitro proton MR spectroscopy experiments (2.35-tesla magnet, 25 G/cm, point-resolved spatially localized spectroscopy) revealed an Sl00B-specific peak at 4.5 ppm and confirmed a positive correlation between different S100B concentrations (10 nM-1 microM) and the area under the curve (AUC) for the S100B peak (r = 0.991, p < 0.001). Thereafter, proton MR spectroscopy was performed in male Sprague-Dawley rats (7 X 5 X 5-mm voxel in each hemisphere, TR 3000 msec, TE 30 msec, 256 acquisitions). Exogenously increased CSF S100B levels (approximately 200 ng/ml) through the intraventricular infusion of S100B increased the AUC of the S100B peak from 0.06 +/- 0.02 to 0.44 +/- 0.06 (p < 0.05), whereas serum S100B levels remained normal. Two hours after lateral fluid-percussion injury, serum S100B levels increased to 0.61 +/- 0.09 ng/ml (p < 0.01) and rapidly returned to normal levels, whereas the AUC of the S100B peak increased to 0.19 +/- 0.04 at 2 hours postinjury and 0.41 +/- 0.07 (p < 0.05) on Day 5 postinjury., Conclusions: Proton MR spectroscopy proves a strong correlation between the AUC of the S100B peak and S100B concentrations. Following experimental TBI, serum S100B levels increased for only a very short period, whereas cerebral S100B levels were increased up to Day 5 postinjury. Given that experimental data indicate that S100B is actively released following TBI, proton MR spectroscopy may represent a new tool to identify increased cerebral S100B levels in patients after injury, thus allowing its biological function to be better understood.