We present a clustering method to extract the depth of interaction (DOI) information from an 8 mm thick crystal version of our continuous miniature crystal element (cMiCE) small animal PET detector. This clustering method, based on the maximum-likelihood (ML) method, can effectively build look-up tables (LUT) for different DOI regions. Combined with our statistics-based positioning (SBP) method, which uses a LUT searching algorithm based on the ML method and two-dimensional mean-variance LUTs of light responses from each photomultiplier channel with respect to different gamma ray interaction positions, the position of interaction and DOI can be estimated simultaneously. Data simulated using DETECT2000 were used to help validate our approach. An experiment using our cMiCE detector was designed to evaluate the performance. Two and four DOI region clustering were applied to the simulated data. Two DOI regions were used for the experimental data. The misclassification rate for simulated data is about 3.5% for two DOI regions and 10.2% for four DOI regions. For the experimental data, the rate is estimated to be approximately 25%. By using multi-DOI LUTs, we also observed improvement of the detector spatial resolution, especially for the corner region of the crystal. These results show that our ML clustering method is a consistent and reliable way to characterize DOI in a continuous crystal detector without requiring any modifications to the crystal or detector front end electronics. The ability to characterize the depth-dependent light response function from measured data is a major step forward in developing practical detectors with DOI positioning capability.

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SUMMARY Inflammatory activation of myeloid cells is accompanied by increased glycolysis, which is required for the surge in cytokine production. Although in vitro studies suggest that increased macrophage glucose metabolism is sufficient for cytokine induction, the pro-inflammatory effects of increased myeloid cell glucose flux in vivo and the impact on atherosclerosis, a major complication of diabetes, are unknown. We therefore tested the hypothesis that increased glucose uptake in myeloid cells stimulates cytokine production and atherosclerosis. Overexpression of the glucose transporter GLUT1 in myeloid cells caused increased glycolysis and flux through the pentose phosphate pathway, but did not induce cytokines. Moreover, myeloid cell-specific overexpression of GLUT1 in LDL receptor-deficient mice was ineffective in promoting atherosclerosis. Thus, increased glucose flux is insufficient for inflammatory myeloid cell activation and atherogenesis. If glucose promotes atherosclerosis by increasing cellular glucose flux, myeloid cells do not appear to be the key targets.

[(11)C]-RSV can be used to dynamically and noninvasively quantify hepatobiliary transport and hepatic concentration of the drug, in the absence and presence of drug interactions, in rats and could be used for the same purpose in humans.

Crows pay close attention to people and can remember specific faces for several years after a single encounter. In mammals, including humans, faces are evaluated by an integrated neural system involving the sensory cortex, limbic system, and striatum. Here we test the hypothesis that birds use a similar system by providing an imaging analysis of an awake, wild animal's brain as it performs an adaptive, complex cognitive task. We show that in vivo imaging of crow brain activity during exposure to familiar human faces previously associated with either capture (threatening) or caretaking (caring) activated several brain regions that allow birds to discriminate, associate, and remember visual stimuli, including the rostral hyperpallium, nidopallium, mesopallium, and lateral striatum. Perception of threatening faces activated circuitry including amygdalar, thalamic, and brainstem regions, known in humans and other vertebrates to be related to emotion, motivation, and conditioned fear learning. In contrast, perception of caring faces activated motivation and striatal regions. In our experiments and in nature, when perceiving a threatening face, crows froze and fixed their gaze (decreased blink rate), which was associated with activation of brain regions known in birds to regulate perception, attention, fear, and escape behavior. These findings indicate that, similar to humans, crows use sophisticated visual sensory systems to recognize faces and modulate behavioral responses by integrating visual information with expectation and emotion. Our approach has wide applicability and potential to improve our understanding of the neural basis for animal behavior.A variety of species are able to discriminate between human faces (1-3), and this ability appears to be linked to neural integration of perception, emotion, and memory. Brain imaging studies have revealed that humans use a core recognition system in their sensory cortex (the posterior superior temporal sulcus, the inferior occipital gyrus, and the fusiform gyrus) networked with two extended systems that convey the historical (anterior paracingulate, posterior superior temporal sulcus/temporoparietal junction, anterior temporal cortex, precuneus, and posterior cingulate) and emotional (amygdala, insula, and striatum) significance of the person (4). This network of brain regions that perceive and analyze faces is informed by ventral and dorsal visual pathways-the ventral enabling fine discrimination and the dorsal providing rapid, but coarse, emotional assessment (3). Brain mapping investigations on other species capable of human recognition are extremely limited; however, electrophysiological recordings in the visual cortex of domestic sheep and nonhuman primates have indicated the presence of neurons that respond to human facial information (5).We demonstrated previously that free-ranging American crows (Corvus brachyrhynchos) discriminate among humans based on facial characteristics, but we could only speculate on the neural basis for this behavior (1, 6). Because bi...

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Hepatocellular carcinoma (HCC) is a devastating malignancy in which imperfect imaging plays a primary role in diagnosis. Glypican-3 (GPC3) is an HCC-specific cell surface proteoglycan overexpressed in most HCCs. This paper presents the use of 89Zr-conjugated monoclonal antibody against GPC3 (89Zr-αGPC3) for intrahepatic tumor localization using PET. Methods Polymerase chain reaction confirmed relative GPC3 expression in cell lines. In vitro binding, in vivo biodistribution, and small-animal PET studies were performed on GPC3-expressing HepG2 and non–GPC3-expressing HLF and RH7777 cells and orthotopic xenografts. Results 89Zr-αGPC3 demonstrated antibody-dependent, antigen-specific tumor binding. HepG2 liver tumors exhibited high peak uptake (836.6 ± 86.6 percentage injected dose [%ID]/g) compared with background liver (27.5 ± 1.6 %ID/g). Tumor-to-liver contrast ratio was high and peaked at 32.5. The smallest HepG2 tumor (<1 mm) showed lower peak uptake (42.5 ± 6.4 %ID/g) and tumor-to-liver contrast (1.57) but was still clearly visible on PET. Day 7 tissue activity was still substantial in HepG2 tumors (466.4 ± 87.6 %ID/g) compared with control RH7777 tumors (3.9 ± 1.3 %ID/g, P < 0.01), indicating antigen specificity by 89Zr-αGPC3. HepG2 tumor treated with unlabeled αGPC3 or heat-denatured 89Zr-αGPC3 demonstrated tumor activity (2.1 %ID/g) comparable to that of control xenografts, confirming antibody dependency. Conclusion This study demonstrated the feasibility of using 89Zr-αGPC3 to image HCC in the liver, as well as the qualitative determination of GPC3 expression via small-animal PET. The ability to clarify the identity of small liver lesions with an HCC-specific PET probe would provide clinicians with vital information that could significantly alter patient management, warranting further investigation for clinical translation.

Social animals encountering natural dangers face decisions such as whether to freeze, flee or harass the threat. The American crow, Corvus brachyrhynchos, conspicuously mobs dangers. We used positron emission tomography to test the hypothesis that distinct neuronal substrates underlie the crow's consistent behavioural response to different dangers. We found that crows activated brain regions associated with attention and arousal (nucleus isthmo-opticus/locus coeruleus), and with motor response (arcopallium), as they fixed their gaze on a threat. However, despite this consistent behavioural and neural response, the sight of a person who previously captured the crow, a person holding a dead crow and a taxidermy-mounted hawk activated distinct forebrain regions (amygdala, hippocampus and portion of the caudal nidopallium, respectively). We suggest that aspects of mobbing behaviour are guided by unique neural circuits that respond to differences in mental processing-learning, memory formation and multisensory discrimination-required to appropriately nuance a risky behaviour to specific dangers.