Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. However, attaining consistently high performance of these functions in vivo in one single nano-construct remains extremely challenging. Here we demonstrate the use of one single polymer to develop a smart “all-in-one” nanoporphyrin platform that conveniently integrates a broad range of clinically relevant functions. Nanoporphyrins can be used as amplifiable multimodality nanoprobes for near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), positron emission tomography (PET) and dual modal PET-MRI. Nanoporphyrins greatly increase the imaging sensitivity for tumor detection through background suppression in blood, as well as preferential accumulation and signal amplification in tumors. Nanoporphyrins also function as multiphase nanotransducers that can efficiently convert light to heat inside tumors for photothermal-therapy (PTT), and light to singlet oxygen for photodynamic-therapy (PDT). Furthermore, nanoporphyrins act as programmable releasing nanocarriers for targeted delivery of drugs into tumors.

Articular cartilage is a load bearing and lubricating tissue in animal joints. Heterogeneous deformations arise in the structured and zonal tissue under the application of mechanical load. The character of these deformations is altered by degenerative joint disease. Here, we document an MRI-based technique for determining deformations throughout the volume of the tissue based on displacement encoding with stimulated echoes (DENSE) and a fast spin echo (FSE) readout. A DENSE-FSE technique was designed to image cartilage at 9.4 Tesla in a deformed state during the application of cyclic mechanical loading. Artifact elimination arising from stimulated echoes and FSE was accomplished by radio frequency pulse phase cycling. The articular cartilage of animal joints functions to support load during locomotion and reduce friction and wear at the articular surface (1). Cartilage has a unique zonal structure that varies dramatically in terms of biochemical content (2) and mechanical context (3) through the depth of the thin (i.e., less than 5 mm thick) tissue. Tissue homeostasis and function is altered during degenerative joint diseases such as osteoarthritis (4), which afflicts greater than 10% of the U.S. population (5).Measurement of cartilage deformation under applied mechanical loading by MRI is critical in several research applications. First, MRI provides a tool for the noninvasive and nondestructive evaluation of cartilage mechanical function in normal, diseased, and regenerated tissue. Second, the computed deformations allow for the characterization and estimation of the mechanical environment (which depends on spatial location; 3,6) experienced by chondrocytes, and thus may be important in terms of documenting physical signals for mechanical signal transduction. Third, deformation data permit verification and development of material models for cartilage mechanical behavior. Ultimately, the development of MR techniques at the tissue explant level may be appropriately modified and extended for use at the whole joint or in vivo level with the goal of evaluating the mechanical function of cartilage regeneration or repair techniques. The unique ability of MRI to differentiate between soft tissues, coupled with the ability to determine functional aspects such as mechanical deformations, allow for noninvasive measurements of cartilage deformation at the tissue explant and potentially whole-joint levels.The study of the deformation throughout the volume of cartilage in response to applied loading requires the use of specialized MR-based measurement techniques. One recent cartilage deformation by tag registration (CDTR) technique characterized deformation in cartilage using a loading apparatus with a specialized tagging-based MRI pulse sequence (7). This technique provides a precise description of three-dimensional (3D) strains in cartilage at physiologically relevant loading rates. However, a primary limitation of the CDTR technique was the use of spline fitting to represent tissue motion, which led to a determination of...

It is conventionally thought that multiplication of the xylem-limited bacterium Xylella fastidiosa (Xf) within xylem vessels is the sole factor responsible for the blockage of water movement in grapevines (Vitis vinifera) affected by Pierce's disease. However, results from our studies have provided substantial support for the idea that vessel obstructions, and likely other aspects of the Pierce's disease syndrome, result from the grapevine's active responses to the presence of Xf, rather than to the direct action of the bacterium. The use of magnetic resonance imaging (MRI) to observe the distribution of water within the xylem has allowed us to follow nondestructively the development of vascular system obstructions subsequent to inoculation of grapevines with Xf. Because we have hypothesized a role for ethylene produced in vines following infection, the impact of vine ethylene exposure on obstruction development was also followed using MRI. In both infected and ethylene-exposed plants, MRI shows that an important proportion of the xylem vessels become progressively air embolized after the treatments. The loss of xylem water-transporting function, assessed by MRI, has been also correlated with a decrease in stem-specific hydraulic conductivity (K  S) and the presence of tyloses in the lumens of obstructed water conduits. We have observed that the ethylene production of leaves from infected grapevines is greater than that from healthy vines and, therefore, propose that ethylene may be involved in a series of cellular events that coordinates the vine's response to the pathogen.

Distance-dependent magnetic resonance tuning (MRET) technology enables the sensing and quantitative imaging of biological targets in vivo, with the advantage of deep tissue penetration and less interactions with the surroundings as compared to fluorescence-based Förster resonance energy transfer (FRET). However, applications of MRET technology in vivo are currently limited by the moderate contrast enhancement and stability of T 1 -based MRET probes. Here we report a new two-way magnetic resonance tuning (t-MRET) nanoprobe with dually activatable T 1 and T 2 magnetic resonance signals that is coupled with dual-contrast enhanced subtraction imaging (DESI). This integrated platform achieves substantially improved contrast enhancement with minimal background signal and can be used to quantitatively image molecular targets in tumours and to sensitively detect very small intracranial brain tumours in patient-derived xenograft models. The high tumour-to-normal tissue ratio offered by t-MRET in combination with DESI provides new opportunities for molecular diagnostics and image-guided biomedical applications.

Cerebral edema forms in the early hours of ischemic stroke by processes involving increased transport of Na and Cl from blood into brain across an intact blood-brain barrier (BBB). Our previous studies provided evidence that the BBB Na-K-Cl cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema and infarct in rats subjected to permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP. The present study was conducted to further investigate the possibility that a BBB Na/H exchanger also participates in edema formation during ischemic stroke. Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic resonance spectroscopy Na spectroscopy, respectively, for up to 210 minutes. We found that intravenous administration of the specific Na/H exchange inhibitor HOE-642 significantly decreased brain Na uptake and reduced cerebral edema, brain swelling, and infarct volume. These findings support the hypothesis that edema formation and brain Na uptake during the early hours of cerebral ischemia involve BBB Na/H exchanger activity as well as Na-K-Cl cotransporter activity.

Articular cartilage is critical to the normal function of diarthrodial joints. Despite the importance of the tissue and the prevalence of cartilage degeneration (e.g., osteoarthritis), the technology required to noninvasively describe nonuniform deformations throughout the volume of the tissue has not been available until recently. The objectives of the work reported in this paper were to 1) describe a noninvasive technique (termed the cartilage deformation by tag registration (CDTR) technique) to determine nonuniform deformations in articular cartilage explants with the use of specialized MRI tagging and image processing methods, 2) evaluate the strain error of the CDTR technique using a custom MRI-compatible phantom material, and 3) demonstrate the applicability of the CDTR technique to articular cartilage by determining 3D strain fields throughout the volume of a bovine articular cartilage explant. A custom MRI pulse sequence was designed to tag and image articular cartilage explants at 7 Tesla in undeformed and deformed states during the application of multiple load cycles. The custom pulse sequence incorporated the "delays alternating with nutations for tailored excitation" (DANTE) pulse sequence to apply tags. This was followed by a "fast spin echo" (FSE) pulse sequence to create images of the tags. The error analysis using the phantom material indicated that deformations can be determined with an error, defined as the strain precision, better than 0.83% strain.

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The temperature dependence of the chemical shift of 'axe dissolved in polymers is examined in the context of the van der Waals interaction. It is found that above the glass transition temperature for the polymers studied herein, the laXe chemical shift can be described by a 6-12 Lennard-Jones potential. The cell model of DiBenedetto is used to describe the average local environment of the amorphous polymer and s u m over the pairwise interactions of the potential. We show the van der Waals shift model agrees reasonably well with the "Xe chemical shifts and provides the potential to determine solubility parameters and van der Waals radii of polymers. IntroductionThe l29Xe chemical shift is particularly sensitive to the environment of the atom. Xenon is a noble gas and therefore interacts with ita surroundings primarily through the van der Waals interaction. However, because xenon has a large number of electrons, even this small interaction produces a chemical shift relatively large in magnitude and with a strong temperature dependence. 129Xe is 26% abundant and has a relatively large magnetogyric ratio, y, so dilute amounts can be detected. For these reasons, 129Xe NMR has been widely used to study solid materials including zeolites2 and clathrate compound^.^^^ More recently, the NMR of lmXe dissolved in polymers has been investigated."1° In these studies, the 129Xe chemical shift is generally correlated with a molecular parameter such as pore size or density through semiphenomenological theories which usually involve xenon-wall collision rates or the residence times of xenon atoms on the cavity walls. The NMR of xenon in liquids has also been used to test theories of solute-solvent interactions.11J2 We note that resonance shifts due to solute-solvent interactions arise from the physical interactions of the solute with its surroundings and are distinct from and additive with the more familiar chemical shifts which arise from the chemical structure of the solute. Xenon dissolved in polymers above the glass transition is in a more liquid-like environment; therefore it is appropriate to attribute the lSXe chemical shift to solute-solvent interactions.We first briefly review the present understanding of the origin of resonance shifts due to solute-solvent interactions. In the van der Waals Shift Model section we introduce a new model of the van der Waals shifts applicable to polymers. We then describe in detail how the parameters necessary to implement the model are calculated in the Calculation of Parameters section. Finally, in the Results and Discussion section we present the results and discuss how a number of the assumptions made in the model affect the results.The theory of resonance shifts due to solute-solvent interactions has received much attention over the years.13 (Throughout this paper we will refer to the calculated values as resonance or van der Waals shifts and the measured values as chemical shifts.) The resonance shift of a solute molecule due to solute-solvent interactions is the sum of se...