The present invention discloses indicator fluids, reference indicator fluid, and usage thereof, and systems and methods for assessing movement of molecular substances within, to or from a cerebrospinal fluid, brain or spinal cord compartment of a human cranio-spinal cavity. Indicator fluid moving from the cerebrospinal fluid compartment enables measurements of levels of indicator fluid in blood or urine and assessment of the cranio-spinal cavity's ability to remove molecular substances. The indicator fluids may be contrast agents used for imaging, such as by computed tomography imaging, and magnetic resonance imaging, or imaging utilizing radioactive substances by positron emission tomography, single-photon emission computed tomography or scintigraphy. Using these imaging modalities, the invention describes indicator fluids, systems and methods enabling assessment of movement of substances within, to or from a cerebrospinal fluid, brain or spinal cord compartment of a cranio-spinal cavity, and from the human cranio-spinal cavity to lymphatic pathways or kidneys.

The present invention relates to a complex of formula (II) constituted of at least 80% of a diastereoisomeric excess comprising a mixture of isomers II-RRR and II-SSS of formulae:

##STR00001##

The present invention also relates to a process for preparing said complex of formula (II), and also to two synthetic intermediates.

Gadolinium based contrast agents (GCA) incorporating linear ligand chelation are fundamentally different from GCAs incorporating macrocyclic ligands. The macrocyclic\GCAs are synthesized by pathways characterized by the formation of a sequence of metastable complexes before obtaining the final stable complex. The synthesis of linear GCAs do not form metastable complexes. Commercial macrocyclic GCAs contain unstable metastable complexes. These metastable species are not regulated and quickly release free Gd3+ ions upon administration into the body. Gadolinium based contrast agents with near zero metastable species content and methods of synthesizing the same are disclosed. Gadolinium based contrast agents with long dissociation time in the body, and low free Gd3+ ion formation are obtained using a synthesis method which departs in novel ways from the traditional free Gd3+-based synthesis methods.

The present invention relates to a complex of formula (II) constituted of at least 90% of a diastereoisomeric excess comprising a mixture of isomers II-RRR and II-SSS of formulae:

##STR00001##

The present invention also relates to a process for preparing and purifying said complex of formula (II), and also to a composition comprising said complex.

The present invention refers to pharmaceutical compositions comprising a macrocyclic gadolinium complex and a water-soluble polyarylene additive useful in diagnostic imaging as diagnostic agents, in particular as contrast agents, specifically in Magnetic Resonance Imaging (MRI).

In some aspects, the present disclosure provides compounds of the formula: ##STR00001##
wherein the variables are defined herein. In some aspects, the present disclosure provides methods of preparing imaging agents, compositions thereof, and methods of imaging using said imaging agents or compositions thereof.

Methods of ex vivo labeling of a biological material for in vivo imaging, methods of labeling a biological material in vivo, methods for preparing a labeling agent, and methods for in vivo imaging of a subject using a biological material labeled with a labeling agent are disclosed. In one non-limiting example, the biological material is selected from cells and the labeling agent is a .sup.89Zr-Desferrioxamine-NCS labeling agent.

An in-case stand for a musical instrument that supports a musical instrument in the open musical instrument case, such as a guitar, in an inclined position making the headstock and the neck readily accessible for string changes, cleaning or light maintenance.

Systems, methods and related devices used to produce and collect polarized noble gas to inhibit, suppress, detect or filter alkali metal nanoclusters to preserve or increase a polarization level thereof. The systems can include a pre-sat chamber that has an Area Ratio between 20 and 500.

A process is provided in which the resulting Fe-tCDTA contrast agent has a reduced osmolality. The process according to the invention comprises the following steps: a) preparing an aqueous solution of tCDTA and FeO(OH), tCDTA and FeO(OH) being present in a molar ratio of from 1:1 to 1:1.4; b) b.1) adjusting a pH of the aqueous solution to between pH 2.5 and pH 4.5 by adding a base, preferably meglumine, and separating the precipitate; or b.2) precipitating the Fe-tCDTA contrast agent from the aqueous solution by adding acetone, separating the precipitate, and preparing an aqueous solution from the precipitate; and c) adjusting a pH of the aqueous solution to between pH 6.5 and pH 8.0 by adding a base, preferably meglumine, and separating the precipitated FeO(OH).