new ICEMED publication

Tracking live brain activity with the new NeuBtracker open-source microscope

A team of scientists from the Helmholtz Zentrum München and the Technical University of Munich (TUM) has successfully developed a new type of microscope. The so-called NeuBtracker is an open source microscope that allows to observe neuronal activities of zebrafish without perturbing their behavior. This is opening up completely new perspectives for science, because now it will be possible to track natural behavior while simultaneously imaging neuronal activity in the brain. NeuBtracker* is equipped with two cameras: One tracks the unrestrained behavior of the zebrafish larva while the other automatically remains pointed at the transparent head, and consequently the brain, to record fluorescence images. “This approach makes it possible to observe neuronal activity during unrestrained behavior. We can test the larvae in different environmental conditions and can immediately analyze the effects,” says Prof. Dr. Gil Westmeyer from the Institutes of Biological and Medical Imaging (IBMI) and Developmental Genetics (IDG) at...

Prospective MR Image Alignment Between Breath-Holds: Application to Renal BOLD MRI

Abstract PURPOSE To present an image registration method for renal blood oxygen level-dependent (BOLD) measurements that enables semiautomatic assessment of parenchymal and medullary R2* changes under a functional challenge. METHODS In a series of breath-hold acquisitions, three-dimensional data were acquired initially for prospective image registration of subsequent BOLD measurements. An algorithm for kidney alignment for BOLD renal imaging (KALIBRI) was implemented to detect the positions of the left and right kidney so that the kidneys were acquired in the subsequent BOLD measurement at consistent anatomical locations. Residual in-plane distortions were corrected retrospectively so that semiautomatic dynamic R2* measurements of the renal cortex and medulla become feasible. KALIBRI was tested in six healthy volunteers during a series of BOLD experiments, which included a 600- to 1000-mL water challenge. RESULTS Prospective image registration and BOLD imaging of each kidney was achieved within a total measurement time of about 17 s, enabling its...

Near-Infrared Photoacoustic Imaging Probe Responsive to Calcium

Near-Infrared Photoacoustic Imaging Probe Responsive to Calcium Abstract: Photoacoustic imaging (PAI) is an attractive imaging modality that can volumetrically map the distribution of photoabsorbing molecules with deeper tissue penetration than multiphoton microscopy. To enable dynamic sensing of divalent cations via PAI, we have engineered a new reversible near-infrared probe that is more sensitive to calcium as compared to other biologically relevant cations. The metallochromic compound showed a strong reduction of its peak absorbance at 765 nm upon addition of calcium ions that was translated into robust signal changes in photoacoustic images. Therefore, the heptamethine cyanine dye will be an attractive scaffold to create a series of metallochromic sensors for molecular PAI. Authors: Anurag Mishra, Yuanyuan Jiang, Sheryl Roberts, Vasilis Ntziachristos, and Gil G. Westmeyer Link: http://pubs.acs.org/doi/abs/10.1021/acs.analchem.6b03039

Hyperpolarized Multi-Metal 13C-Sensors for Magnetic Resonance Imaging

Hyperpolarized Multi-Metal ¹³C-Sensors for Magnetic Resonance Imaging Abstract: We introduce hyperpolarizable ¹³C-labeled probes that identify multiple biologically important divalent metals via metal-specific chemical shifts. These features enable NMR measurements of calcium concentrations in human serum in the presence of magnesium. In addition, signal enhancement through dynamic nuclear polarization (DNP) increases the sensitivity of metal detection to afford measuring micromolar concentrations of calcium as well as simultaneous multi-metal detection by chemical shift imaging. The hyperpolarizable ¹³C-MRI sensors presented here enable sensitive NMR measurements and MR imaging of multiple divalent metals in opaque biological samples. Authors: Anurag Mishra, Giorgio Pariani, Thomas Oerther, Markus Schwaiger, and Gil G. Westmeyer Link: http://pubs.acs.org/doi/abs/10.1021/acs.analchem.6b03546

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity.

Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity. Heni M, Kullmann S, Ahlqvist E, Wagner R, Machicao F, Staiger H, Häring HU, Almgren P, Groop LC, Small DM, Fritsche A, Preissl H. Abstract AIMS/HYPOTHESIS: Variations in FTO are the strongest common genetic determinants of adiposity, and may partly act by influencing dopaminergic signalling in the brain leading to altered reward processing that promotes increased food intake. Therefore, we investigated the impact of such an interaction on body composition, and peripheral and brain insulin sensitivity. METHODS: Participants from the Tübingen Family study (n = 2245) and the Malmö Diet and Cancer study (n = 2921) were genotyped for FTO SNP rs8050136 and ANKK1 SNP rs1800497. Insulin sensitivity in the caudate nucleus, an important reward area in the brain, was assessed by fMRI in 45 participants combined with intranasal insulin administration. RESULTS: We found evidence of an interaction...

STAT3-Ser/Hes3 Signaling: A New Molecular Component of the Neuroendocrine System?

STAT3-Ser/Hes3 Signaling: A New Molecular Component of the Neuroendocrine System? The endocrine system involves communication among different tissues in distinct organs, includ- ing the pancreas and components of the Hypo- thalamic-Pituitary-Adrenal Axis. The molecular mechanisms underlying these complex interac- tions are a subject of intense study as they may hold clues for the progression and treatment of a variety of metabolic and degenerative diseases. A plethora of signaling pathways, activated by hor- mones and other endocrine factors have been implicated in this communication. Recent advances in the stem cell field introduce a new level of complexity: adult progenitor cells appear to utilize distinct signaling pathways than the more mature cells in the tissue they co-reside. It is therefore important to elucidate the signal transduction requirements of adult progenitor cells in addition to those of mature cells. Recent evidence suggests that a common non-canonical signaling pathway regulates adult progenitors in several...

Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology

Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology Loss of insulin-producing pancreatic islet b-cells is a hallmark of type 1 diabetes. Several experimental para- digms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these path- ways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling path- ways should not be seen as “on” or “off” but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play im- portant roles. Thus, a pathway, once considered as “off” or “low” may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A...

Orientation dependence of magnetization transfer parameters in human white matter

Quantification of magnetization-transfer (MT) experiments is typically based on a model comprising a liquid pool “a” of free water and a semisolid pool “b” of motionally restricted macromolecules or membrane compounds. By a comprehensive fitting approach, high qualityMT parameter maps of the human brain are obtained. In particular, a distinct correlation between the diffusion-tensor orientation with respect to the B0-magnetic field and the apparent transverse relaxation time, T2 b , of the semisolid pool (i.e., thewidth of its absorption line) is observed. This orientation dependence is quantitatively explained by a refined dipolar lineshape for pool b that explicitly considers the specific geometrical arrangement of lipid bilayers wrapped around a cylindrical axon. The model inherently reduces themyelinmembrane to its lipid constituents, which ismotivated by previous studies on efficient interaction sites (e.g., cholesterol or galactocerebrosides) in themyelinmembrane and on the origin of ultrashort T2 signals in cerebral white matter. The agreement betweenMT orientation effects and corresponding forward simulations using empirical diffusion imaging...