Infusion-based manganese-enhanced MRI: a new imaging technique to visualize the mouse brain

Manganese-enhanced magnetic resonance imaging is a technique that employs the divalent ion of the paramagnetic metal manganese (Mn²⁺) as an effective contrast agent to visualize, in vivo, the mammalian brain. As total achievable contrast is directly proportional to the net amount of Mn²⁺ accumulated in the brain, there is a great interest in optimizing administration protocols to increase the effective delivery of Mn²⁺ to the brain while avoiding the toxic effects of Mn²⁺ overexposure. In this study, we investigated outcomes following continuous slow systemic infusion of manganese chloride (MnCl₂) into the mouse via mini-osmotic pump administration. The effects of increasing fractionated rates of Mn²⁺ infusion on signal enhancement in regions of the brain were analyzed in a three-treatment study. We acquired whole-brain 3-D T1-weighted images and performed region of interest quantitative analysis to compare mean normalized signal in Mn²⁺ treatments spanning 3, 7, or 14 days of infusion (rates of 1, 0.5, and 0.25 μL/h, respectively). Evidence of Mn²⁺ transport at the conclusion of each infusion treatment was observed throughout the brains of normally behaving mice. Regions of particular Mn²⁺ accumulation include the olfactory bulbs, cortex, infralimbic cortex, habenula, thalamus, hippocampal formation, amygdala, hypothalamus, inferior colliculus, and cerebellum. Signals measured at the completion of each infusion treatment indicate comparable means for all examined fractionated rates of Mn²⁺ infusion. In this current study, we achieved a significantly higher dose of Mn²⁺ (180 mg/kg) than that employed in previous studies without any observable toxic effects on animal physiology or behavior.     

A new approach to visualize ecosystem health by using parasites

A new approach is chosen to visualize ecosystem health by using parasite bioindicators in Segara Anakan Lagoon, a brackish water ecosystem at the southern Java coast, Indonesia. Three fish species (Mugil cephalus, Scatophagus argus, Epinephelus coioides) were collected in two different years and sampling sites and studied for ecto- and endoparasites. Additional data were taken for E. coioides from two further sites in Lampung Bay, Sumatra, and for E. fucoguttatus out of floating cages from a mariculture facility in the Thousand Islands, Jakarta Bay, North Java. The parasite fauna of fishes inside the lagoon was characterized by a high number of ecto- and a low number of endoparasites, the endoparasite diversity was relatively low and the prevalence of ectocommensalistic trichodinid ciliates was high. These parameters were chosen to indicate the biological conditions inside the lagoon. In E. coioides during rainy season, the prevalence of trichodinid ciliates was highest inside the lagoon (55%) compared with 27% in an open-net-cage mariculture and 5.7% in free-living specimens in Lampung Bay. The endoparasite diversity (Shannon-Wiener) was lowest in fish from Segara Anakan lagoon (0.66) compared with fish from an open-net-cage mariculture (0.71) and free-living specimens (1.39). Results for E. fuscoguttatus from the mariculture site in the Thousand Islands, a relatively undisturbed marine environment, demonstrated high parasite diversity (1.58) in the cultivated fish, a high number of endoparasites, and no trichodinids. A star graph is used to visualize the parasite composition for the different fishes, sampling sites, and conditions, using (1) the prevalence of trichodinid ciliates, (2) the ecto/endoparasite ratio and (3) the endoparasite diversity as bioindicators. The application of the star graph is suggested to be a suitable tool to visualize and monitor environmental health under high parasite biodiversity conditions within tropical ecosystems. It can also support a better communication to stake holders and decision makers in order to monitor environmental impact and change.     

X-ray diffraction enhanced imaging as a novel method to visualize low-density scaffolds in soft tissue engineering

Scaffold visualization is challenging yet essential to the success of various tissue engineering applications. The aim of this study was to explore the potential of X-ray diffraction enhanced imaging (DEI) as a novel method for the visualization of low density engineered scaffolds in soft tissue. Imaging of the scaffolds made from poly(L-lactide) (PLLA) and chitosan was conducted using synchrotron radiation-based radiography, in-line phase-contrast imaging (in-line PCI), and DEI techniques as well as laboratory-based radiography. Scaffolds were visualized in air, water, and rat muscle tissue. Compared with the images from X-ray radiography and in-line PCI techniques, DEI images more clearly show the structure of the low density scaffold in air and have enhanced image contrast. DEI was the only technique able to visualize scaffolds embedded in unstained muscle tissue; this method could also define the microstructure of muscle tissue in the boundary areas. At a photon energy of 20?KeV, DEI had the capacity to image PLLA/chitosan scaffolds in soft tissue with a sample thickness of up to 4?cm. The DEI technique can be applied at high X-ray energies, thus facilitating lower in vivo radiation doses to tissues during imaging as compared to conventional radiography.     

The use of computer imaging techniques to visualize cardiac muscle cells in three dimensions

Atrial muscle cells and atrioventricular bundle cells were reconstructed using a computer-assisted three-dimensional reconstruction system. This reconstruction technique permitted these cells to be viewed from any direction. The cell surfaces were approximated using triangular tiles, and this optimization technique for cell reconstruction allowed for the computation of cell surface area and cell volume. A transparent mode is described which enables the investigator to examine internal cellular features such as the shape and location of the nucleus. In addition, more than one cell can be displayed simultaneously, and, therefore, spatial relationships are preserved and intercellular relationships viewed directly. The use of computer imaging techniques allows for a more complete collection of quantitative morphological data and also the visualization of the morphological information gathered.     

Molecular imaging: spawning a new melting-pot for biomedical imaging

Predicting the future is a dangerous undertaking at best, and not meant for the faint-hearted. However, viewing the advances in molecular medicine, genomics and proteomics, it is easy to comprehend those who believe that molecular imaging methods will open up new vistas for medical imaging. The knock on effect will impact our capacity to diagnose and treat diseases. Anatomically detectable abnormalities, which have historically been the basis of the practice of radiology, will soon be replaced by molecular imaging methods that will reflect the under expression or over expression of certain genes which occur in almost every disease. Molecular imaging can then be resorted to so that early diagnosis and characterisation of disease can offer improved specificity. Given the growing importance of molecular medicine, imagers will find it profitable to educate themselves on molecular targeting, molecular therapeutics and the role of imaging in both areas.     

Metal-enhanced emission from indocyanine green: a new approach to in vivo imaging

Indocyanine green (ICG) is widely used in medical imaging and testing. Its complex spectral behavior and low quantum yield limits some applications. We show that proximity of ICG to a metallic silver particle increases its intensity approximately 20-fold and decreases the decay time. Since the rate of photobleaching is not increased, our results suggest that ICG-silver particle complexes can yield at least 20-fold more photons per ICG molecule for improved medical imaging.     

Kinetic magnetic resonance imaging analysis of swallowing: a new approach to pharyngeal function

The emergence of turbo-FLASH MR sequences allows us to acquire five 10-mm sections each second and thus to catch images of the soft tissues during function. One can trace the pathway of a liquid between the tongue, the soft palate, the epiglottis and the pharyngeal apparatus and analysis the role of the anatomic structures during swallowing. Restricted to the sagittal plane for the purpose of this preliminary study, this technique can be extended to the other planes to provide a three-dimensional analysis of oropharyngeal function or dysfunction.     

Ten good reasons to consider biological processes in prevention and intervention research

Most contemporary accounts of psychopathology acknowledge the importance of both biological and environmental influences on behavior. In developmental psychopathology, multiple etiological mechanisms for psychiatric disturbance are well recognized, including those operating at genetic, neurobiological, and environmental levels of analysis. However, neuroscientific principles are rarely considered in current approaches to prevention or intervention. In this article, we explain why a deeper understanding of the genetic and neural substrates of behavior is essential for the next generation of preventive interventions, and we outline 10 specific reasons why considering biological processes can improve treatment efficacy. Among these, we discuss (a) the role of biomarkers and endophenotypes in identifying those most in need of prevention; (b) implications for treatment of genetic and neural mechanisms of homotypic comorbidity, heterotypic comorbidity, and heterotypic continuity; (c) ways in which biological vulnerabilities moderate the effects of environmental experience; (d) situations in which Biology x Environment interactions account for more variance in key outcomes than main effects; and (e) sensitivity of neural systems, via epigenesis, programming, and neural plasticity, to environmental moderation across the life span. For each of the 10 reasons outlined we present an example from current literature and discuss critical implications for prevention.     

Multispectral fluorescence imaging to assess pH in biological specimens

Simple, quantitative assays to measure pH in tissue could improve the study of complicated biological processes and diseases such as cancer. We evaluated multispectral fluorescence imaging (MSFI) to quantify extracellular pH (pHe) in dye-perfused, surgically-resected tumor specimens with commercially available instrumentation. Utilizing a water-soluble organic dye with pH-dependent fluorescence emission (SNARF-4F), we used standard fluorimetry to quantitatively assess the emission properties of the dye as a function of pH. By conducting these studies within the spectroscopic constraints imposed by the appropriate imaging filter set supplied with the imaging system, we determined that correction of the fluorescence emission of deprotonated dye was necessary for accurate determination of pH due to suboptimal excitation. Subsequently, employing a fluorimetry-derived correction factor (CF), MSFI data sets of aqueous dye solutions and tissuelike phantoms could be spectrally unmixed to accurately quantify equilibrium concentrations of protonated (HA) and deprotonated (A-) dye and thus determine solution pH. Finally, we explored the feasibility of MSFI for high-resolution pHe mapping of human colorectal cancer cell-line xenografts. Data presented suggest that MSFI is suitable for quantitative determination of pHe in ex vivo dye-perfused tissue, potentially enabling measurement of pH across a variety of preclinical models of disease.     

Single-phased luminescent mesoporous nanoparticles for simultaneous cell imaging and anticancer drug delivery

Multifunctional materials for biological use have mostly been designed with composite or hybrid nanostructures in which two or more components are incorporated. The present work reports on a multifunctional biomaterial based on single-phased luminescent mesoporous lanthanide oxide nanoparticles that combine simultaneous drug delivery and cell imaging. A simple strategy based on solid-state-chemistry thermal decomposition process was employed to fabricate the spherical mesoporous Gd(2)O(3):Eu nanoparticles with homogeneous size distribution. The porous nanoparticles developed by this strategy possess well-defined mesopores, large pore size and volume, and high specific surface area. The mesoporous features of nanoparticles impart the material with capabilities of loading and releasing the drug with a relatively high loading efficiency and a sustained release behavior of drugs. The DOX-loaded porous Gd(2)O(3) nanoparticles are able to kill the cancer cells efficiently upon incubation with the human cervical carcinoma (HeLa) cells, indicating the potential for treatment of cancer cells. Meanwhile, the intrinsic luminescence of Gd(2)O(3):Eu nanoparticles gives the function of optical imaging. Therefore, the drug release activity and effect of drugs on the cells can be effectively monitored via luminescence of nanoparticles themselves, realizing multifunctionality of simultaneous cell imaging and anticancer drug delivery in a single-phased nanoparticle.     

A mathematical model platform for optimizing a multiprojection breast imaging system

Multiprojection imaging is a technique in which a plurality of digital radiographic images of the same patient are acquired within a short interval of time from slightly different angles. Information from each image is combined to determine the final diagnosis. Projection data are either reconstructed into slices as in the case of tomosynthesis or analyzed directly as in the case of multiprojection correlation imaging technique, thereby avoiding reconstruction artifacts. In this study, the authors investigated the optimum geometry of acquisitions of a multiprojection breast correlation imaging system in terms of the number of projections and their total angular span that yield maximum performance in a task that models clinical decision. Twenty-five angular projections of each breast from 82 human subjects in our breast tomosynthesis database were each supplemented with a simulated 3 mm mass. An approach based on Laguerre-Gauss channelized Hotelling observer was developed to assess the detectability of the mass in terms of receiver operating characteristic (ROC) curves. Two methodologies were developed to integrate results from individual projections into one combined ROC curve as the overall figure of merit. To optimize the acquisition geometry, different components of acquisitions were changed to investigate which one of the many possible configurations maximized the area under the combined ROC curve. Optimization was investigated under two acquisition dose conditions corresponding to a fixed total dose delivered to the patient and a variable dose condition, based on the number of projections used. In either case, the detectability was dependent on the number of projections used, the total angular span of those projections, and the acquisition dose level. In the first case, the detectability approximately followed a bell curve as a function of the number of projections with the maximum between 8 and 16 projections spanning angular arcs of about 23 degrees-45 degrees, respectively. In the second case, the detectability increased with the number of projections approaching an asymptote at 11-17 projections for an angular span of about 45 degrees. These results indicate the inherent information content of the multi-projection image data reflecting the relative role of quantum and anatomical noise in multiprojection breast imaging. The optimization scheme presented here may be applied to any multiprojection imaging modalities and may be extended by including reconstruction in the case of digital breast tomosynthesis and breast computed tomography.     

Development of a platform for co-registered ultrasound and MR contrast imaging in vivo

Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.