MR Imaging Reveals Dynamic Aggregation of Multivalent Glycoconjugates in Aqueous Solution.

Glycoconjugates forming from the conjugation of carbohydrates to other biomolecules, such as proteins, lipids, or other carbohydrates, are essential components of mammalian cells and are involved in numerous biological processes. Due to the capability of sugars to form multiple hydrogen bonds, many synthetic glycoconjugates are desirable biocompatible platforms for imaging, diagnostics, drugs, and supramolecular self-assemblies. Herein, we present a multimeric galactose functionalized paramagnetic gadolinium (Gd(III)) chelate that displays spontaneous dynamic aggregation in aqueous conditions.

Distribution of MRI-derived T2 values as a biomarker for in vivo rapid screening of phenotype severity in mdx mice.

Background: The pathology in Duchenne muscular dystrophy (DMD) is characterized by degenerating muscle fibers, inflammation, fibro-fatty infiltrate, and edema, and these pathological processes replace normal healthy muscle tissue. The mdx mouse model is one of the most commonly used preclinical models to study DMD. Mounting evidence has emerged illustrating that muscle disease progression varies considerably in mdx mice, with inter-animal differences as well as intra-muscular differences in pathology in individual mdx mice.

New semi-automated tool for the quantitation of MR imaging to estimate in vivo muscle disease severity in mice.

The pathology in Duchenne muscular dystrophy (DMD) is characterized by degenerating muscle fibers, inflammation, fibro-fatty infiltrate, and edema, and these pathological processes replace normal healthy muscle tissue. The mouse model is one of the most commonly used preclinical models to study DMD. Mounting evidence has emerged illustrating that muscle disease progression varies considerably in mice, with inter-animal differences as well as intra-muscular differences in pathology in individual mice.

Wireless multi-lateral optofluidic microsystems for real-time programmable optogenetics and photopharmacology.

In vivo optogenetics and photopharmacology are two techniques for controlling neuronal activity that have immense potential in neuroscience research. Their applications in tether-free groups of animals have been limited in part due to tools availability. Here, we present a wireless, battery-free, programable multilateral optofluidic platform with user-selected modalities for optogenetics, pharmacology and photopharmacology.

Wireless implantable optical probe for continuous monitoring of oxygen saturation in flaps and organ grafts.

Continuous, real-time monitoring of perfusion after microsurgical free tissue transfer or solid organ allotransplantation procedures can facilitate early diagnosis of and intervention for anastomotic thrombosis. Current technologies including Doppler systems, cutaneous O-sensing probes, and fluorine magnetic resonance imaging methods are limited by their intermittent measurements, requirements for skilled personnel, indirect interfaces, and/or their tethered connections. This paper reports a wireless, miniaturized, minimally invasive near-infrared spectroscopic system designed for uninterrupted monitoring of local-tissue oxygenation.

A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy.

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control.

The Therapeutic and Diagnostic Potential of Amyloid β Oligomers Selective Antibodies to Treat Alzheimer's Disease.

Improvements have been made in the diagnosis of Alzheimer's disease (AD), manifesting mostly in the development of imaging methods that allow for the detection of pathological changes in AD by magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Many of these imaging methods, however, use agents that probe amyloid fibrils and plaques-species that do not correlate well with disease progression and are not present at the earliest stages of the disease. Amyloid β oligomers (AβOs), rather, are now widely accepted as the Aβ species most germane to AD onset and progression.

Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices.

Bioresorbable, Wireless, Passive Sensors as Temporary Implants for Monitoring Regional Body Temperature.

Measurements of regional internal body temperatures can yield important information in the diagnosis of immune response-related anomalies, for precisely managing the effects of hyperthermia and hypothermia therapies and monitoring other transient body processes such as those associated with wound healing. Current approaches rely on permanent implants that require extraction surgeries after the measurements are no longer needed. Emerging classes of bioresorbable sensors eliminate the requirements for extraction, but their use of percutaneous wires for data acquisition leads to risks for infection at the suture site.

Wireless, battery-free subdermally implantable photometry systems for chronic recording of neural dynamics.

Recording cell-specific neuronal activity while monitoring behaviors of freely moving subjects can provide some of the most significant insights into brain function. Current means for monitoring calcium dynamics in genetically targeted populations of neurons rely on delivery of light and recording of fluorescent signals through optical fibers that can reduce subject mobility, induce motion artifacts, and limit experimental paradigms to isolated subjects in open, two-dimensional (2D) spaces. Wireless alternatives eliminate constraints associated with optical fibers, but their use of head stages with batteries adds bulk and weight that can affect behaviors, with limited operational lifetimes.

Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models.

Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance.

Self-Immolative Activation of β-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models.

Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β-galactosidase (β-gal). We investigated two molecular architectures to create agents that detect β-gal activity by modulating the coordination of water to Gd . The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions.

Whole-body Imaging of Cell Death Provides a Systemic, Minimally Invasive, Dynamic, and Near-real Time Indicator for Chemotherapeutic Drug Toxicity.

Purpose: Response to toxicity in chemotherapies varies considerably from tissue to tissue and from patient to patient. An ability to monitor the tissue damage done by chemotherapy may have a profound impact on treatment and prognosis allowing for a proactive management in understanding and mitigating such events. For the first time, we investigated the feasibility of using whole-body imaging to map chemotherapeutic drug-induced toxicity on an individual basis.

Ratiometric quantitation of redox status with a molecular Fe magnetic resonance probe.

We demonstrate the ability of a molecular Fe complex to enable magnetic resonance (MR)-based ratiometric quantitation of redox status, namely through redox-dependent paramagnetic chemical exchange saturation transfer (PARACEST). Metalation of a tetra(carboxamide) ligand with Fe and/or Fe in the presence of etidronate ion affords analogous FeII2, FeFe, and FeIII2 complexes. Both FeII2 and FeFe complexes give highly-shifted, sharp, and non-overlapping NMR spectra, with multiple resonances for each complex corresponding to exchangeable carboxamide protons.

Experimental Modeling Supports a Role for MyBP-HL as a Novel Myofilament Component in Arrhythmia and Dilated Cardiomyopathy.

Background: Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy and associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing.

Methods: Whole-genome sequencing and induced pluripotent stem cells were used to examine a family with dilated cardiomyopathy and atrial and ventricular arrhythmias.

Nanodiamond-Gadolinium(III) Aggregates for Tracking Cancer Growth In Vivo at High Field.

The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth, and metastatic potential within the intact organism. Magnetic resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and the absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies.

Multimeric Near IR-MR Contrast Agent for Multimodal In Vivo Imaging.

Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety.

Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in vivo.

Bioactive supramolecular nanostructures are of great importance in regenerative medicine and the development of novel targeted therapies. In order to use supramolecular chemistry to design such nanostructures, it is extremely important to track their fate in vivo through the use of molecular imaging strategies. Peptide amphiphiles (PAs) are known to generate a wide array of supramolecular nanostructures, and there is extensive literature on their use in areas such as tissue regeneration and therapies for disease.

Synthesis and characterization of a porphyrazine-Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model.

Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu-Pz-Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or 'click' chemistry between an azide functionalized Pz and alkyne functionalized DOTA-Gd(III) analog for use as an MRI contrast agent. This agent, Cu-Pz-Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1  = 11.

High-resolution magnetic resonance imaging of ankle joints in murine arthritis discriminates inflammation and bone destruction in a quantifiable manner.

Objective: The ability to noninvasively monitor the development of inflammatory arthritis longitudinally has become increasingly important in experimental rheumatology. Magnetic resonance imaging (MRI) allows for detailed examination of anatomic structures, as well as the assessment of joint and soft tissue inflammation. The aim of this study was to extend the use of MRI to include quantitative measurements of bone destruction in murine ankle joints.

A novel mouse model that develops spontaneous arthritis and is predisposed towards atherosclerosis.

Objectives: Patients with rheumatoid arthritis (RA) have a reduced life expectancy due to increased cardiovascular disease. The lack of a suitable animal model resembling both RA and atherosclerosis has hindered studies demonstrating a direct link between systemic inflammation in RA and the development of atherosclerosis. Our objective was to overcome this barrier by generating an animal model (K/BxA(g7)) that spontaneously develops both RA-like disease and atherosclerosis.

Synthesis and characterization of new porphyrazine-Gd(III) conjugates as multimodal MR contrast agents.

Magnetic resonance imaging (MRI) has long been used clinically and experimentally as a diagnostic tool to obtain three-dimensional, high-resolution images of deep tissues. These images are enhanced by the administration of contrast agents such as paramagnetic Gd(III) complexes. Herein, we describe the preparation of a series of multimodal imaging agents in which paramagnetic Gd(III) complexes are conjugated to a fluorescent tetrapyrrole, namely, a porphyrazine (pz).

Protein polymer MRI contrast agents: Longitudinal analysis of biomaterials in vivo.

Despite recent advances in tissue engineering to regenerate biological function by combining cells with material supports, development is hindered by inadequate techniques for characterizing biomaterials in vivo. Magnetic resonance imaging is a tomographic technique with high temporal and spatial resolution and represents an excellent imaging modality for longitudinal noninvasive assessment of biomaterials in vivo. To distinguish biomaterials from surrounding tissues for magnetic resonance imaging, protein polymer contrast agents were developed and incorporated into hydrogels.

Multivalent protein polymer MRI contrast agents: controlling relaxivity via modulation of amino acid sequence.

Magnetic resonance imaging is a noninvasive imaging modality with high spatial and temporal resolution. Contrast agents (CAs) are frequently used to increase the contrast between tissues of interest. To increase the effectiveness of MR agents, small molecule CAs have been attached to macromolecules.