fMRI visualization of transient activations in the rat olfactory bulb using short odor stimulations

International audienceOdor-evoked activity in the olfactory bulb displays both spatial and temporal organization. The difficulty when assessing spatio-temporal dynamics of olfactory representation is to find a method that reconciles the appropriate resolution for both dimensions. Imaging methods based on optical recordings can reach high temporal and spatial resolution but are limited to the observation of the accessible dorsal surface. Functional magnetic resonance imaging (fMRI) may be useful to overcome this limitation as it allows recording from the whole brain. In this study, we combined ultra fast imaging sequence and short stimulus duration to improve temporal resolution of odor-evoked BOLD responses. Short odor stimulations evoked high amplitude BOLD responses and patterns of activation were similar to those obtained in previous studies using longer stimulations. Moreover, short odor exposures prevented habituation processes. Analysis of the BOLD signal time course in the different areas of activation revealed that odorant response maps are not static entities but rather are temporally dynamic as reported by recent studies using optical imaging. These data demonstrated that fMRI is a non-invasive method which could represent a powerful tool to study not only the spatial dimension of odor representation but also the temporal dimension of information processing

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Accomplishments and challenges in stem cell imaging in vivo.

Stem cell therapies have demonstrated promising preclinical results, but very few applications have reached the clinic owing to safety and efficacy concerns. Translation would benefit greatly if stem cell survival, distribution and function could be assessed in vivo post-transplantation, particularly in patients. Advances in molecular imaging have led to extraordinary progress, with several strategies being deployed to understand the fate of stem cells in vivo using magnetic resonance, scintigraphy, PET, ultrasound and optical imaging. Here, we review the recent advances, challenges and future perspectives and opportunities in stem cell tracking and functional assessment, as well as the advantages and challenges of each imaging approach

Intersubject Regularity in the Intrinsic Shape of Human V1

Previous studies have reported considerable intersubject variability in the three-dimensional geometry of the human primary visual cortex (V1). Here we demonstrate that much of this variability is due to extrinsic geometric features of the cortical folds, and that the intrinsic shape of V1 is similar across individuals. V1 was imaged in ten ex vivo human hemispheres using high-resolution (200 μm) structural magnetic resonance imaging at high field strength (7 T). Manual tracings of the stria of Gennari were used to construct a surface representation, which was computationally flattened into the plane with minimal metric distortion. The instrinsic shape of V1 was determined from the boundary of the planar representation of the stria. An ellipse provided a simple parametric shape model that was a good approximation to the boundary of flattened V1. The aspect ration of the best-fitting ellipse was found to be consistent across subject, with a mean of 1.85 and standard deviation of 0.12. Optimal rigid alignment of size-normalized V1 produced greater overlap than that achieved by previous studies using different registration methods. A shape analysis of published macaque data indicated that the intrinsic shape of macaque V1 is also stereotyped, and similar to the human V1 shape. Previoud measurements of the functional boundary of V1 in human and macaque are in close agreement with these results

Iron oxide nanoparticles and derivatives for biomedical imaging and application in cancer diagnosis and siRNA therapy

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.Our studies have focused on the application of imaging-capable nanoparticulate agents for the delivery of small RNA-based tumor therapy. One example includes magnetic nanoparticles (MN), which have traditionally been utilized as contrast agents for magnetic resonance imaging. The probes typically consist of a dextran-coated superparamagnetic iron oxide core (for magnetic resonance imaging), labeled with Cy5.5 dye (for near-infrared in vivo optical imaging), and conjugated to synthetic small interfering RNA (siRNA) molecules targeting model or therapeutic genes. We have explored the potential of these nanoparticles as delivery modules for small interfering RNA to tumors. Furthermore, we have investigated the feasibility of combining the imaging and delivery capabilities of these nanoparticles for the tracking of siRNA bioavailability. The versatile functionalization potential of MN has allowed us to control properties of the agents, such as uptake mechanism and target organ distribution. The tumoral accumulation of MNsiRNA results in a remarkable level of target-gene down-regulation. Repeated treatment with MN-siBIRC5, targeting the tumor-specific anti-apoptotic gene, birc5, leads to the induction of apoptosis in the tumors and an overall reduction in tumor growth rate. More recently, we have synthesized a second generation of nanoparticles, which combine the capability for high-resolution magnetic resonance imaging with detection by ultrasensitive surface enhanced Raman scattering

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined

Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T

Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in ‘arterial’ and ‘venous’ blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between ‘arterial’ and ‘venous’ contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms

Microtesla MRI of the human brain combined with MEG

One of the challenges in functional brain imaging is integration of complementary imaging modalities, such as magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). MEG, which uses highly sensitive superconducting quantum interference devices (SQUIDs) to directly measure magnetic fields of neuronal currents, cannot be combined with conventional high-field MRI in a single instrument. Indirect matching of MEG and MRI data leads to significant co-registration errors. A recently proposed imaging method - SQUID-based microtesla MRI - can be naturally combined with MEG in the same system to directly provide structural maps for MEG-localized sources. It enables easy and accurate integration of MEG and MRI/fMRI, because microtesla MR images can be precisely matched to structural images provided by high-field MRI and other techniques. Here we report the first images of the human brain by microtesla MRI, together with auditory MEG (functional) data, recorded using the same seven-channel SQUID system during the same imaging session. The images were acquired at 46 microtesla measurement field with pre-polarization at 30 mT. We also estimated transverse relaxation times for different tissues at microtesla fields. Our results demonstrate feasibility and potential of human brain imaging by microtesla MRI. They also show that two new types of imaging equipment - low-cost systems for anatomical MRI of the human brain at microtesla fields, and more advanced instruments for combined functional (MEG) and structural (microtesla MRI) brain imaging - are practical.Comment: 8 pages, 5 figures - accepted by JM

Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties