Biomedical

MATERIALS SCIENCE BIOMEDICAL FOOD & AGRICULTURE HETERONUCLEI

MATERIALS SCIENCE

FFC NMR relaxometry has found applications in some key industries, such as oil and polymers, as well as in basic research. Herein are some examples of the most popular materials FFC applications.

Please contact Stelar if you would like information on any application not listed here or you would like to try a new application.

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BIOMEDICAL APPLICATIONS

FFC NMR relaxometry can offer a range of solutions in healthcare, pharmaceutical, cosmetic and preclinical and clinical research applications, in particular in biomedical detection with clinical MR imaging contrast agents.

Please contact Stelar if you would like information on any application not listed here or you would like to try a new application.

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FOOD & AGRICULTURE

FFC NMR relaxometry can offer solutions for the food and agriculture industries, particularly for quality control, shelf-life and denomination of origin. The NMRD profile is sensitive to dehydration, oxidation, spoilage, and the addition of additives including adulterants that may lead to fraudulent products. Below are some examples of these applications.

Please contact Stelar if you would like information on any application not listed here or you would like to try a new application.

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HETERONUCLEI

FFC NMR relaxometry is mostly used for proton-based analyses (1H nucleus), as detailed in the other applications pages. It is however possible to study dispersion curves or simpler decay curves of T1 for other nuclei, such as deuterium (2H), fluorine (19F), lithium (7Li), compounds enriched in carbon-13 (13C) and more.

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Biomedical detection
DESIGN AND APPLICATION OF PRECLINICAL & CLINICAL MRI CONTRAST AGENTS

Design and application of MRI contrast agents for biomedical detection of various pathologies is an evolving field of research. Relaxivity profiles produced by application of the FFC technique to MRI contrast agents are essential in showing the effectiveness of the contrast agent and optimizing its design, particularly at the magnetic fields of clinical MRI scanners. Parameters involved in relaxation can be estimated by fitting the FFC relaxivity profiles with the appropriate physical relaxation models through a dedicated software.

1H NMRD profiles of magnetic iron oxide nanoparticles with increasing core sizes. [ See ]

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Preclinical research
"IN VIVO" CANCER DIAGNOSES

Conventional magnetic resonance imaging (MRI) techniques have focused on the improvement of the spatial resolution by using high magnetic fields (1-7T). High field allows the visualization of small tumour masses but cannot give a precise evaluation of important hallmarks of the disease such as tumour grading, oxygenation, pH and metastasization, which may affect the type of therapy chosen. New work aims at developing an innovative diagnostic strategy, based on the measurements of longitudinal relaxation times at low and ultra-low magnetic fields with FFC NMR relaxometry to obtain quantitative information on tumour characteristics, due to different water content and mobility, that is invisible to standard MRI.

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SPINMASTER "DUO"

1 TESLA & 0,5

TESLA WIDE BORE

Preliminary results on mice have shown that the endogenous contrast between normal and diseased tissue, due to differences in T1, is much greater at low field and the shape of the relaxation dispersion profiles may be used as a method for reporting the molecular dynamical processes of water (i.e. the exchange rate across membranes) that dominate the relaxation mechanism at low fields.

This MRI image shows the difference between normal and tumour-bearing mouse leg.

Mouse in the wide bore probe.

Melanoma tumours have shorter T1 than normal tissue due to the higher iron content in melanin aggregates. T1 differences are proportional to the tumour size (132 and 180 mm3 for tumour 1 and 2 respectively)

Quadrupolar peaks arising from protein amidic groups can be seen very clearly, centred at proton NMR frequencies of 0.65, 2.10 and 2.75 MHz. This is a phenomenon that is completely invisible to conventional (fixed-field) MRI but fully exploitable by FFC-NMR.

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See application note

Quality assurance
THERAPEUTIC PROTEINS

The aggregation of therapeutic proteins (e.g. monoclonal antibodies) is an important problem in the bio-pharmaceutical industry. It is well documented that protein product aggregates are potent inducers of immune responses to therapeutic protein products, thus manufacturers of therapeutic protein products should ensure that their products contain minimal product aggregates. Currently size exclusion chromatography (SEC) is primarily used in combination with orthogonal methods to confirm aggregate sizes present. There is a real need for new and improved analytical methods for defining protein aggregates for the benefit of the patient, to avoid constraining the production capacity of therapeutic proteins over the coming years and to prevent loss of therapeutic proteins through aggregation during the manufacturing process and storage. FFC NMR relaxometry shows considerable promise for making routine assessments of protein aggregation and denaturation.

1H NMRD profiles of a therapeutic monoclonal antibody in its monomeric (non-aggregated) and an artifcially aggregated states. From Stelar in-house data.

1H NMRD profiles of a monomeric therapeutic protein at different temperatures corresponding to unfolding dynamics. From Stelar in-house data.

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See application note

Medicine authentication

The market of counterfeit medicines has grown in many countries and these uncontrolled medicines, which contain not only the active principal but other derivatives of this, are potentially damaging to health, at best, and could, at worst, cost lives. It is therefore important to find reliable methods of analysis to reveal these non-authentic products. FFC NMR relaxometry has been tested as a method of differentiation between authentic and counterfeit Viagra®. It was demonstrated that relaxation was bi-exponential in the whole frequency range for the counterfeit medicine, while for the original Viagra® the relaxation process was always a single exponential.

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Clinical diagnosis
DISEASED TISSUE INVESTIGATIONS

FFC NMR relaxometry has been used in combination with fixed field NMR techniques to evaluate the severity of osteoarthritis in human cartilage samples. Features in the NMRD profile (quadrupolar dips), as well as cartilage thickness obtained from profile measurements, were indeed found to correlate with the severity of osteoarthritis. Another significant correlation was also identified by the authors of the study. [ See ]


Cosmetic formulations
DERMAL FILLERS

Dermal fillers such as hyaluronic acid are used in the cosmetic industry for treatment of scars, atrophy, wrinkles, facial rejuvenation and tissue augmentation. A crosslinking process is applied to hyaluronic acid to optimize its rheological properties for specific cosmetic uses. FFC NMR relaxometry is able to assess the formation of networks of hyaluronic acid hydrogels and thus the rheology of these dermal fillers.

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Forensics
POST-MORTEM DECOMPOSITION

FFC NMR relaxometry and FFC-MRI techniques have been used as non-invasive techniques to investigate post-mortem decomposition changes (and thus post-mortem interval, PMI) in porcine muscle, fatty tissue and bone marrow. PMI is critical for the forensic pathologist and investigators probing crimes and suspicious deaths. NMRD profiles allow qualitative and quantitative analysis of tissue status through features known as “quadrupolar peaks”. [ See ]