Combination of complementary imaging techniques, like hybrid PET/MRI, allows protocols to be developed that exploit the best features of both. In order to get the best of these combinations the use of dual probes is highly desirable. On this sense the combination of biocompatible iron oxide nanoparticles and 68Ga isotope is a powerful development for the new generation of hybrid systems and multimodality approaches. Our objective was the synthesis and application of a chelator-free 68Ga-iron oxide nanotracer with improved stability, radiolabeling yield and in vivo performance in dual PET/MRI. We carried out the core doping of iron oxide nanoparticles, without the use of any chelator, by a microwave-driven protocol. The synthesis allowed the production of extremely small (2.5 nm) 68Ga core-doped iron oxide nanoparticles. The microwave approach allowed an extremely fast synthesis with a 90% radiolabeling yield and T1 contrast in MRI. With the same microwave approach the nano-radiotracer was functionalized in a fast and efficient way. We finally evaluated these dual targeting nanoparticles in an angiogenesis murine model by PET/MR imaging. Copyright © 2016 John Wiley & Sons, Ltd.

People with normal hearing thresholds can nonetheless have difficulty with understanding speech in noisy backgrounds. The origins of such supra-threshold hearing deficits remain largely unclear. Previously we showed that the auditory brainstem response to running speech is modulated by selective attention, evidencing a subcortical mechanism that contributes to speech-in-noise comprehension. We observed, however, significant variation in the magnitude of the brainstem's attentional modulation between the different volunteers. Here we show that this variability relates to the ability of the subjects to understand speech in background noise. In particular, we assessed 43 young human volunteers with normal hearing thresholds for their speech-in-noise comprehension. We also recorded their auditory brainstem responses to running speech when selectively attending to one of two competing voices. To control for potential peripheral hearing deficits, and in particular for cochlear synaptopathy, we further assessed noise exposure, the temporal sensitivity threshold, the middle-ear muscle reflex, and the auditory-brainstem response to clicks in various levels of background noise. These tests did not show evidence for cochlear synaptopathy amongst the volunteers. Furthermore, we found that only the attentional modulation of the brainstem response to speech was significantly related to speech-in-noise comprehension. Our results therefore evidence an impact of topdown modulation of brainstem activity on the variability in speech-in-noise comprehension amongst the subjects.Understanding speech in noisy backgrounds such as other competing speakers is a challenging task at which humans excel 1,2 It requires the separation of different sound sources, selective attention to the target speaker, and the processing of degraded signals 3-5 Hearing impairment such as resulting from noise exposure often leads to an increase of hearing thresholds, a reduction in the information conveyed about a sound to the central auditory system, and thus to greater difficulty in understanding speech in noise 6-8 However, even listeners with normal hearing thresholds can have problems with understanding speech in noisy environments 9,10 .An extensive neural network of efferent fibers can feed information from the central auditory cortex back to the auditory brainstem and even to the cochlea 11,12 . Research on the role of these neural feedback loops for speech-in-noise listening has mostly focused on the medial olivocochlear reflex (MOCR), in which stimulation of the medial olivocochlear fibers that synapse on the outer hair cells in the cochlea reduces cochlear amplification across a wide frequency band 13 . Computational modelling as well as animal studies have shown that such reduced broad-band amplification can improve the signal-to-noise ratio of a transient signal embedded in background noise [14][15][16][17] . However, it remains debated whether the reduction of cochlear amplification through the MOCR contributes to better speech-in-noise comprehe...

Objective. The auditory brainstem response can be recorded non-invasively from scalp electrodes and serves as an important clinical measure of hearing function. We have recently shown how the brainstem response at the fundamental frequency of continuous, non-repetitive speech can be measured, and have used this measure to demonstrate that the response is modulated by selective attention. However, different parts of the speech signal as well as several parts of the brainstem contribute to this response. Here we employ a computational model of the brainstem to elucidate the influence of these different factors. Approach. We developed a computational model of the auditory brainstem by combining a model of the middle and inner ear with a model of globular bushy cells in the cochlear nuclei and with a phenomenological model of the inferior colliculus. We then employed the model to investigate the neural response to continuous speech at different stages in the brainstem, following the methodology developed recently by ourselves for detecting the brainstem response to running speech from scalp recordings. We compared the simulations with recordings from healthy volunteers. Main results. We found that the auditory-nerve fibers, the cochlear nuclei and the inferior colliculus all contributed to the speech-evoked brainstem response, although the dominant contribution came from the inferior colliculus. The delay of the response corresponded to that observed in experiments. We further found that a broad range of harmonics of the fundamental frequency, up to about 8 kHz, contributed to the brainstem response. The response declined with increasing fundamental frequency, although the signal-to-noise ratio was largely unaffected. Significance. Our results suggest that the scalp-recorded brainstem response at the fundamental frequency of speech originates predominantly in the inferior colliculus. They further show that the response is shaped by a large number of higher harmonics of the fundamental frequency, reflecting highly nonlinear processing in the auditory periphery and illustrating the complexity of the response.

The human auditory system is exceptional at comprehending an individual speaker even in complex acoustic environments. Because the inner ear, or cochlea, possesses an active mechanism that can be controlled by subsequent neural processing centers through descending nerve fibers, it may already contribute to speech processing. The cochlear activity can be assessed by recording otoacoustic emissions (OAEs), but employing these emissions to assess speech processing in the cochlea is obstructed by the complexity of natural speech. Here we develop a novel methodology to measure otoacoustic emissions that are related to the time-varying harmonic structure of speech (speech-DPOAEs). We then employ the method to investigate the effect of selective attention on the speech-DPOAEs. We provide tentative evidence that the speech-DPOAEs are larger when the corresponding speech signal is attended than when it is ignored. Our development of speech-DPOAEs opens up a path to further investigations of the contribution of the cochlea to the processing of complex realworld signals.