Semiautomated Detection of Early Infarct Signs on Noncontrast CT Improves Interrater Agreement.

BACKGROUND: Acute ischemic infarct identification on noncontrast computed tomography (NCCT) is highly variable between raters. A semiautomated method for segmentation of acute ischemic lesions on NCCT may improve interrater reliability. METHODS: Patients with successful endovascular reperfusion from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) were included. We created relative NCCT (rNCCT) color-gradient overlays by comparing the density of a voxel on NCCT to the homologous region in the contralateral hemisphere. Regions with a relative hypodensity of at least 5% were visualized. We coregistered baseline and follow-up images. Two neuroradiologists and 6 nonradiologists segmented the acute ischemic lesion on the baseline scans with 2 methods: (1) manually outlining hypodense regions on the NCCT (unassisted segmentation) and (2) manually excluding areas deemed outside of the ischemic lesion on the rNCCT color map (rNCCT-assisted segmentation). Voxelwise interrater agreement was quantified using the Dice similarity coefficient and volumetric agreement between raters with the detection index (DI), defined as the true positive volume minus the false positive volume. RESULTS: From a total of 92, we included 61 patients. Median age was 59 (64-77), and 57% were female. Stroke onset was known in 39%. Onset to NCCT was median, 8.5 hours (7-11) and median 10 hours (8.4-11.5) in patients with known and unknown onset, respectively. Compared with unassisted NCCT segmentation, rNCCT-assisted segmentation increased the Dice similarity coefficient by >50% for neuroradiologists (Dice similarity coefficient, 0.38 versus 0.83; P<0.001) and nonradiologists (Dice similarity coefficient, 0.14 versus 0.84; P<0.001), and improved the DI among nonradiologists (mean improvement, 5.8 mL [95% CI, 3.1-8.5] mL, P<0.001) but not among neuroradiologists. CONCLUSIONS: The high variability of manual segmentations of the acute ischemic lesion on NCCT is greatly reduced using semiautomated rNCCT. The rNCCT map may therefore aid acute infarct detection and provide more reliable infarct estimates for clinicians with less experience.

Feeding state sculpts a circuit for sensory valence in Caenorhabditis elegans.

Hunger affects the behavioral choices of all animals, and many chemosensory stimuli can be either attractive or repulsive depending on an animal's hunger state. Although hunger-induced behavioral changes are well documented, the molecular and cellular mechanisms by which hunger modulates neural circuit function to generate changes in chemosensory valence are poorly understood. Here, we use the CO2 response of the free-living nematode Caenorhabditis elegans to elucidate how hunger alters valence. We show that CO2 response valence shifts from aversion to attraction during starvation, a change that is mediated by two pairs of interneurons in the CO2 circuit, AIY and RIG. The transition from aversion to attraction is regulated by biogenic amine signaling. Dopamine promotes CO2 repulsion in well-fed animals, whereas octopamine promotes CO2 attraction in starved animals. Biogenic amines also regulate the temporal dynamics of the shift from aversion to attraction such that animals lacking octopamine show a delayed shift to attraction. Biogenic amine signaling regulates CO2 response valence by modulating the CO2-evoked activity of AIY and RIG. Our results illuminate a new role for biogenic amine signaling in regulating chemosensory valence as a function of hunger state.

Olfactory circuits and behaviors of nematodes.

Over one billion people worldwide are infected with parasitic nematodes. Many parasitic nematodes actively search for hosts to infect using volatile chemical cues, so understanding the olfactory signals that drive host seeking may elucidate new pathways for preventing infections. The free-living nematode Caenorhabditis elegans is a powerful model for parasitic nematodes: because sensory neuroanatomy is conserved across nematode species, an understanding of the microcircuits that mediate olfaction in C. elegans may inform studies of olfaction in parasitic nematodes. Here we review circuit mechanisms that allow C. elegans to respond to odorants, gases, and pheromones. We also highlight work on the olfactory behaviors of parasitic nematodes that lays the groundwork for future studies of their olfactory microcircuits.

O2-sensing neurons control CO2 response in C. elegans.

Sensory behaviors are often flexible, allowing animals to generate context-appropriate responses to changing environmental conditions. To investigate the neural basis of behavioral flexibility, we examined the regulation of carbon dioxide (CO2) response in the nematode Caenorhabditis elegans. CO2 is a critical sensory cue for many animals, mediating responses to food, conspecifics, predators, and hosts (Scott, 2011; Buehlmann et al., 2012; Chaisson and Hallem, 2012). In C. elegans, CO2 response is regulated by the polymorphic neuropeptide receptor NPR-1: animals with the N2 allele of npr-1 avoid CO2, whereas animals with the Hawaiian (HW) allele or an npr-1 loss-of-function (lf) mutation appear virtually insensitive to CO2 (Hallem and Sternberg, 2008; McGrath et al., 2009). Here we show that ablating the oxygen (O2)-sensing URX neurons in npr-1(lf) mutants restores CO2 avoidance, suggesting that NPR-1 enables CO2 avoidance by inhibiting URX neurons. URX was previously shown to be activated by increases in ambient O2 (Persson et al., 2009; Zimmer et al., 2009; Busch et al., 2012). We find that, in npr-1(lf) mutants, O2-induced activation of URX inhibits CO2 avoidance. Moreover, both HW and npr-1(lf) animals avoid CO2 under low O2 conditions, when URX is inactive. Our results demonstrate that CO2 response is determined by the activity of O2-sensing neurons and suggest that O2-dependent regulation of CO2 avoidance is likely to be an ecologically relevant mechanism by which nematodes navigate gas gradients.