Background: Membrane protein functional dynamics are sensitive to the detergent host. Results: Three functional states of the ␤ 2 -adrenoreceptor (␤ 2 AR) are identified in maltose-neopentyl glycol, whereas all states exchange rapidly in dodecyl maltoside. Conclusion: ␤ 2 AR converts between inactive and active states on a time scale that depends on the detergent off-rate. Significance: G protein-coupled receptor functional dynamics are understood by considering topology changes and corresponding rearrangements of associated detergents.

Poly(acrylic acid) consisting of 25 monomer units (PAA 25 ) was used to stabilize nanoparticle aggregates (NPAs) consisting of either NaGdF 4 or 50/50 mixtures of GdF 3 and CeF 3 . The resulting polymer-stabilized nanoparticle aggregates (NPAs) were developed and tested for their application as contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT). The PAA 25 -stabilized NPAs exhibit low polydispersity and are colloidally stable at concentrations of 40 mg/mL, while their sizes can be be controlled by choosing a specific ratio of Gd 3þ to Ce 3þ . Scanning transmission electron microscopy (STEM) reveals that NaGdF 4 NPAs possess an average diameter of 400 nm. High-resolution STEM and powder X-ray diffraction (XRD) both show that these NPAs consist of a stable aggregate of smaller NPs, whose diameters are 20-22 nm. PAA 25stabilized NPAs consisting of a 50/50 mixture of GdF 3 and CeF 3 possess an average diameter of 70 nm, while the fundamental unit size is estimated to be 10-12 nm in diameter. The PAA 25 -stabilized GdF 3 /CeF 3 NPAs possess mass relaxivities of 40 ( 2 and 30 ( 2 s -1 (mg/mL) -1 at 1.5 T and 3.0 T, respectively. Their effectiveness as contrast agents for CT X-ray imaging at various X-ray energies was also tested and compared to that of equivalent mass concentrations of Gd 3þ -diethylene triamine pentaacetic acid (Gd 3þ -DTPA) and iopromide. Gd-based NPAs exhibit superior CT contrast to equal-mass concentrations of either iopromide or Gd 3þ -DTPA below 30 keV and above 50 keV. Finally, PAA 25 was functionalized by folic acid to explore targeted imaging. Confocal microscopy revealed that, by functionalizing the PAA 25 -stabilized NaGdF 4 :Tb 3þ NPAs with ∼0.8 folates per polymer, binding and endocytosis occurred in SK-BR-3 human breast cancer cells. The utility of the PAA 25 -stabilized GdF 3 /CeF 3 NPAs for MRI is demonstrated in rat perfusion MRI experiments, where T 1 -weighted MRI images of equivalent concentrations of either Gd 3þ -DTPA or the above NPAs are directly compared. The high relaxivities provide an opportunity to conduct perfusion MRI experiments with significantly lower concentrations than those needed for current commercial agents.

This study demonstrated that the use of neat [1-(13) C]lactic acid as the DNP sample is a potential alternative to [1-(13) C]pyruvic acid for cardiac hyperpolarized (13) C MR studies. Hyperpolarized [1-(13) C]lactate may enable noninvasive assessment of cardiac PDH flux in cardiac patients in the near future.

Magnetic resonance imaging (MRI) provides superior resolution of anatomical features and the best soft tissue contrast, and is one of the predominant imaging modalities. With this technique, contrast agents are often used to aid discrimination by enhancing specific features. Over the years, a rich diversity of such agents has evolved and with that, so has a need to systematically sort contrast agents based on their efficiency, which directly determines sensitivity. Herein, we present a scale to rank MRI contrast agents. The scale is based on analytically determining the minimum detectable concentration of a contrast agent, and employing a ratiometric approach to standardize contrast efficiency to a benchmark contrast agent. We demonstrate the approach using several model contrast agents and compare the relative sensitivity of these agents for the first time. As the first universal metric of contrast agent sensitivity, this scale will be vital to easily assessing contrast agent efficiency and thus important to promoting use of some of the elegant and diverse contrast agents in research and clinical practice.