Researchers at the University of California, Irvine have developed a tri-modality system that combines fluorescence tomography (FT), diffuse optical tomography (DOT), and x-ray tomography (XCT). This tri-modality imaging system can be used to obtain quantitatively accurate 3D in vivo fluorescence concentration images. It may be utilized in small animal research for a wide variety of applications ranging from imaging of gene expression to biodistribution of targeted fluorescent molecular probes. (more...)

Incorporating positron emitting fluorine-18 into aromatic ring systems plays a very important role in the development of novel biomarkers for use in Positron Emission Tomography (PET). Current methods of preparing biomarkers include nucleophilic fluorine substitution reactions, however the yield obtained by this reaction drops drastically as the complexity of the aromatic ring system increases. UCLA researchers have developed a novel nucleophilic fluorination reaction of aromatic compounds with a no-carrier-added [F-18] fluoride ion. This reaction is suitable for the preparation of F-18 labeled biomarkers containing a variety of substituents and allows for the synthesis of biomarkers and molecular imaging probes for PET with higher yields and purity than currently used methods. The reaction can be expanded to a multitude of labeled and unlabeled molecules. (more...)

The improved resolution and amount of detail afforded by emerging electron microscopy techniques, such as serial block-face scanning electron microscopy (SBFSEM) enable researchers to explore previously unaddressed scientific questions. SBFSEM technique can reveal cell boundaries, e.g. sites of synapses, and intracellular components, such as synaptic vesicles and mitochondria. However, segmentation of the images generated by SBSFEM requires a trained expert to use automated algorithms or manually going through each slice to trace contours around the region of interest, thereby making it a time consuming and labor intensive effort. (more...)

Hydrogen peroxide (H2O2) is a toxic byproduct of many physiologic and pathological reactions, and elevated in a variety of conditions in which free radicals have been implicated, such as inflammation, infection, cancer, diabetes, aging, and cardiovascular disease. Most conventional methods for H2O2 detection are limited to in vitro use. Being able to detect and image elevated H2O2 levels in vivo and in situ provides accurate and real time diagnosis and monitoring of many pathologies and body’s response to perturbation. (more...)

Quantum dots (QDs) are highly sensitive cellular imaging tools with unique photophysical properties that have become powerful reagents for both basic and translational biomedical research. Emerging applications for QDs include biological imaging, detection of specific molecules for cancer diagnostics and monitoring the effects of stem cell therapies. However, use of commercially available multivalent QDs for imaging purposes remains limited, because multivalent QDs can perturb cell function, and purification of monovalent QDs is a very labor-intensive process that often results in low yields. Therefore, novel methods to develop biologically inert monovalent QDs amenable for large-scale development are critical. (more...)

Positron emission tomography (PET) is a medical imaging technique that follows radioactive tracers to produce a 3D image of functional processes in the body. The most prominent use of PET is in clinical oncology; by following the glucose surrogate fluorodeoxyglucose, physicians can visualize the uptake of this sugar, thereby facilitating tumor diagnosis and staging. In the liver, ribose is metabolized extensively. Thus, monitoring the state of this organ would be greatly aided by a PET tracer that specifically follows ribose. Such a probe could be used to not only diagnose liver cancer, cirrhosis, and hepatitis, but also to assess side effects of therapeutics on liver function. The potential market for tools to assess liver health is tremendous. The CDC places liver disease in the top 10 leading causes of death in the United States. With the ever-worsening obesity epidemic, the prevalence of associated liver maladies will only increase in the coming years. (more...)

Researchers at the University of California, Berkeley have developed an invention that consists of an angular interferometer able to measure angle variations of a coherent, collimated light source with an accuracy below 30 nrad. The optical setup is compact and consists of a few simple optical components. The novelty of this innovation lies in the use of a simple, cost-effect technique to amplify the sensitivity of the instrument. The disclosed invention is in principle capable of being integrated into more compact, high-sensitivity commercial instruments for a fraction of the cost of current, state-of-the-art instruments (currently exceeding $30,000).   Commercial devices used to measure the angular deviation of a single beam include autocollimators and interferometers. The highest resolution offered by a commercial system is 25 nrad. The disclosed angular interferometer is able to measure relative angle variations (of a sample beam relative to a reference beam) below 30 nrad, though the resolution is known to currently be limited by the specific details of the current application and can therefore be further reduced with minor, inexpensive improvements. (more...)

Two of the most commonly used humidity control methods employed today use either the air/water vapor flow method, or saturated salt method. With the water vapor flow method, the relative humidity (RH) accuracy is usually +/-1% in a humidity range from 0% to 95%. With the saturated salt method, one can obtain a discrete number of humidities depending on the choice of salt. A limitation with these two methods is the requirement of a uniform temperature environment. Even small fluctuations in temperature or an offset in temperature gradient would result in +/- 1-2% error in relative humidity. Overcoming the present-day limitations on attaining high-precision humidity control, especially for high humidity, promises to open up a new window to imaging research, enabling new experiments which were previously impossible (e.g. X-ray scattering studies of soft materials, bio-mimetic systems and biological systems). (more...)

The method is a novel and convenient method to chemically modify the exterior surface of enveloped viruses so that such viruses can be easily purified. This chemical modification on the envelope of the virus is reversible. (more...)

Researchers at the University of California, Irvine have developed a novel high resolution imaging technique, referred to as Photo-Magnetic Imaging (PMI), that combines the abilities of optical and magnetic resonance (MR) imaging systems. Images are created with PMI by heating tissue with a light (e.g. laser) and measuring the resulting temperature change with MR Thermometry. This change in temperature can then be related to a tissue’s absorption, scattering, and metabolic properties. PMI addresses the limitations of current optical imaging techniques by providing a repeatable, non-contact, high resolution optical image with increased quantitative accuracy. This technique can be used for a wide-range of applications including but not limited to imaging of small animals for research purposes. This technique may also be used in imaging the tissue and organs of a patient. (more...)

Small animal imaging modalities, such as micro-CT, micro-PET, and micro-MR, are frequently used in preclinical studies. The laboratory mouse is the most widely used small animal model for cancer, immunology, neurodegenerative, and metabolic disease studies. In order to extract anatomical information from mouse images, it is necessary to perform organ segmentation from the 3D images. Human operator-based processing of 3D images is tedious and subject to bias. Therefore, it is desirable to develop a computerized approach to accomplish this task. A promising solution involves registration of a digital mouse atlas to an acquired image. Organ labeling by the atlas can define organ regions in the mouse image. With this strategy, an atlas can give a more accurate, more reliable, and easier estimation of organ region of a preclinical mouse subject. (more...)

Single-photon emission computed topography (SPECT) imaging generates functional 3D images of internal organs, such as the brain or heart (cardiac imaging).  Radioactive nuclides bound to a targeting ligand are injected into the bloodstream; SPECT cameras measure the levels of emitted gamma radiation to provide information on local physiologic changes in tissues or organs.  Measurements are compared under normal and stressful or pathological conditions.  This technique is widely used for myocardial perfusion imaging of the heart, as well as for detecting changes in local brain blood flow and the regional dopamine transporter distribution in the striatal region of the brain.  Indeed, SPECT imaging can differentiate between causal pathologies of dementia, such as the loss of cortical metabolism due to Alzheimer's disease or stroke, as well as different pathologies of Parkinson's disease marked by the reduction of dopaminergic neurons. Collimators are used to filter the stream of gamma rays and improve image resolution.  Currently available SPECT cameras are designed with parallel-hole collimators to focus gamma rays orginiating from within the patient; only gamma rays that run parallel to a specificed direction are allowed through.  However, this also reduces the diagnostic sensitivity of the technique.  Another current limitation of SPECT imaging is that procedures cannot be performed dynamically because rotation of cameras is required. (more...)

3D molecular imaging is a powerful tool for the analysis of biological samples. Methods like positron emission tomography share the limitations inherited from their dependence on biomarkers. Magnetic resonance imaging requires costly equipment and has limited specificity. Researchers at University of California, Davis have developed a novel device and method for creating 3D molecular composition images that overcomes the limitations of these prior technologies. Additionally, the device is suitable for the analysis of a wide range of molecular weights and requires minimal sample preparation. (more...)

Researchers at the University of California, Irvine have developed a novel, label-free imaging and evalution method that enables users to track cell metabolism in vivo.The technique is a novel phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM), a multi-photon microscopy technique that excites cells and then detects their fluorescence activity over time. In this approach, the data from these images is transformed mathematically into a phasor representation. The subsequent analysis identifies, locates, and calculates the concentration of important metabolic cell components, such as: collagen, FAD, free and bound NADH, retinol, and retinoic acid.Overall, this novel method provides a straightforward and quantitative interpretation of the physiological processes occurring in tissues. It enables users to visualize cellular metabolism and retinoid gradients, distinguish between the unique metabolic states of cells, and map their level of differentiation. (more...)

Researchers at the University of California, Irvine have developed a novel device for generating stiffness gradients in naturally derived extracellular matrices (ECM) where stiffness is tuned by inducing strain rather than increasing the concentration of the molecules that make-up the ECM or adding exogenous molecules or cross-linking agents. The strain may be applied as a non-uniform or a uniform force. (more...)

Molecular imaging plays an instrumental role in cancer research, clinical trials and medical practice. Bioluminescence imaging enables the visualization of genetic expression and physiological processes at the molecular level in living tissues by using a bioluminescence reporter, which is usually a genetic transfect from a firefly. This imaging ability opens possibilities for accelerating basic research and drug discovery by allowing in vivo imaging of various disease processes. Currently, the commercial bioluminescence imaging systems developed by Caliper Life Sciences (Xenogen), Kodak and Berthold are for planar imaging and qualitative analyses, and cannot accurately reconstruct a bioluminescent source distribution inside a living animal. Our proposed BLT techniques will allow reliable and accurate analyses on the bioluminescence probe distribution within a living small animal, and offer an excellent instrument to identify disease pathways, clarify mechanisms of action, evaluate efficacy of drug compounds, and monitor their effects on disease progression in animal models. (more...)

Researchers at the University of California, Irvine have developed a dual modality magnetic resonance (MR)/nuclear imaging system for diagnosing prostate cancer. A novel MR prostate radiofrequency (RF) coil built for high field MRI may be combined with single photon emission tomography (SPECT) detectors that enable the medical practitioner to perform co-registered prostate MR and nuclear imaging. (more...)

Background: Human stem cells provide an unprecedented opportunity for the study of human tissue development and the development of cell-based therapies for human disease. For example, research is underway to develop stem cell therapies for major conditions such as cardiac disease, cancer, and diabetes. Many of these proposed therapies involve the controlled differentiation of pluripotent stem cells into a tissue of interest (i.e. a heart muscle, or pancreatic beta-cells) that can then be transplanted into a patient. While these therapies offer exciting promise, significant technical hurdles remain. One important hurdle is the ability to monitor the controlled differentiation of stem cells into the desired tissue type and to isolate pure populations of cells with the potential to form a single tissue type. While reporter constructs have been designed to facilitate this process, the resulting cells have limited potential for human therapeutics because the reporter either integrates into the cells’ genomic DNA, or exists in the cell’s cytoplasm indefinitely. To realize the potential of cell-based therapies for human disease, it is therefore imperative that methods are developed to monitor and isolate pure populations of live human stem cells without altering cellular properties.  Invention: Prominent UCSF scientists have developed a novel method to monitor and isolate live human embryonic stem cells (hESCs) based upon the expression of intracellular proteins. The method involves the design of dual fluoresce resonance energy transfer (FRET) molecular beacons to monitor the expression of specific proteins. Crucially, the beacons used do not alter the functional or genomic characteristics of hESCs. In a major innovative step, the team has adapted this FRET-based reporter system for a high-throughput fluorescence-activated cell sorting (FACS) apparatus. Therefore, not only can protein expression be analyzed using standard confocal microscopy techniques, but pure populations of cells expressing particular tissue-specific proteins can be isolated for clinical applications. To validate this approach, the team monitored the expression of Oct4 (a nuclear transcription factor associated with pluripotency) and successfully demonstrated that Oct-4 expressing hESCs could be isolated via FRET-based FACS. Importantly, FRET-positive hESCs demonstrated pluripotency in culture and in vivo, and molecular beacons are reliably shed from the cell after use. (more...)

Researchers at the University of California, Irvine have developed an RF coil with integrated collimators. This combination coil has a greater internal volume and an object of interest, such as a small animal, may be placed within the coil for MRI and SPECT imaging. (more...)

The use of antibodies to target tumor cell-associated antigens for diagnostic and therapeutic purposes has been a critical step forward in cancer research. As protein engineering capabilities grow, researchers modify antibodies to alter inherent characteristics, such as affinity and immunogenicity, for enhanced imaging and tumor response. One example of this is in the conjugation of various radionuclides to small recombinant antibody fragments (i.e. diabodies and minibodies) for in vivo tumor cell targeting applications. However, it is not always advantageous to use radioactivity, and thus alternative detection systems are necessary. To that end, the search for high-sensitivity and high-specificity probes that circumvent the limitations of organic dyes and fluorescent proteins has led to the discovery and utilization of quantum dots, nanometer-sized semiconductor particles. Quantum dots are brighter than traditional chromophores, have greater stability, and can be used in multiplex imaging due to size-tunable emission wavelengths. To date, bioconjugates with quantum dots are coupled to intact antibodies whose large size makes it difficult to penetrate tissues and tumors. Therefore, it would be advantageous to monitor tumors with a robust, but small, bioconjugate for tandem in vivo monitoring and treatment. (more...)

Inflammation is a central occurrence in many neurodegenerative disease states such as Alzheimer's and cancer. It is said that sulfotransferases (SULT), a diverse group of enzymes important for the bioprocessing of both endogenous and xenobiotic compounds, play an active and pivotal role during inflammation. Therefore, monitoring of SULT activity during inflammation may serve as a diagnostic for disease states.  A common feature in the brain of patient with Alzheimer's disease is beta-amyloid plaques. Thus, Alzheimer's disease may then be monitored and detected by dyes that label beta-amyloid plaques in the brain. However, dyes developed to detect the advancement of Alzheimer's (i.e. Congo red) have demonstrated very limited BBB permeability. Also, no current methodologies allow for the examination of SULT activity in vivo. Therefore, there is a need for both a method and compounds that will allow detection and monitoring of Alzheimer's disease. (more...)

Researchers at the University of California, Irvine have developed novel polydimethylsiloxane shelled microbubbles that may be functionalized with a variety of ligands to selectively target treatment or diagnosis. These microbubbles may be used as a stand-alone application in biological applications such as medical imaging and drug delivery. (more...)

The present invention is related generally to a method for screening subjects to determine those subjects more likely to develop diabetes by quantization of insulin producing cells. The present invention is also related to the diagnosis of diabetes to monitor disease progression or treatment efficacy of candidate drugs. (more...)

New materials and methods that enable the simple inclusion of 18F into cancer-targeting peptides that can be used as radiolabels for PET imaging (more...)