NIMM_MRS: Non-Invasive Monitoring Of Metabolite Levels Using Novel And Adapted MR Spectroscopy Techniques

Sponsor

University Hospital Inselspital, Berne (Other)

Overall Status

Recruiting

CT.gov ID

NCT05165537

Collaborator

(none)

100

Enrollment

Location

Arm

Anticipated Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Swiss National Science Foundation (SNF) funded project and the linked European project aim

to improve magnetic resonance (MR) methods, specifically MR spectroscopy and metabolic imaging (making them more sensitive and accurate - also less dependent on motion),
to extend them (making previously unobservable metabolites visible) and also
to make them more stable (suitable for routine clinical use).

Magnetic resonance spectroscopy (MRS) is closely related to the widely used magnetic resonance imaging (MRI). Both methods are based on the same physical effect and are performed on the same equipment. However, while MRI mainly images the anatomy inside the body, MRS gives us information about the metabolism of the tissue. The main goal of this study is to develop and improve methods of MRS to better measure the concentrations of endogenous substances without actual intervention. MRS methodology development is performed in 4 steps:

A new method is developed and optimized theoretically and in sample preparations (solutions of chemicals).
The new methodology is evaluated in single healthy volunteers and optimized step by step for the conditions of use in the human body.
The methodology in evaluated in small groups of healthy volunteers (measurement accuracy and range of variation in healthy volunteers).
Feasibility is studied in different situations with possibly different metabolic situations (e.g. awake versus asleep or before and after muscular exertion).

For this purpose, about 100 subjects will be measured for different subprojects. Thus, among other things, one determines the measurement accuracy and also normal values in healthy subjects for the assessment of diseases in future studies.

Condition or Disease	Intervention/Treatment	Phase
Magnetic Resonance Spectroscopy	Device: NIMM_MRS	N/A

Detailed Description

Magnetic resonance imaging (MRI) and spectroscopy (MRS) provide non-invasive modalities to explore human morphology, function and metabolism. MRS methods are in widespread use in clinical research and to some degree in clinical applications. MRS methodology has been continuously extended for the last 30 years. All extensions employing novel MR pulse sequences (acquisition software), acquisition hardware capabilities of MRI scanners or post-processing methods have to be validated in theory, and in practice, where they are first tested in vitro and then in healthy subjects. The proposed project is based on a SNF project and a Horizon 2020 project of the sponsor-investigator, where multiple methodological extensions of MRS sequences are implemented for improved measurements of metabolite levels, characteristics and maps.

The intended study uses MRI-scanners which have a Conformité Européenne (CE) label for diagnostic use. The manufacturer of the MR scanner provides a "research-license mode" with the very same hardware; however, since the flexibility of this mode of operation makes a CE process prohibitively long and complex, no CE label was aimed at for the research-license mode.

The methodological developments within the proposed study aim at novel or improved sequences, which have the potential to observe previously undetectable metabolites and to evaluate metabolite changes as function of time-of-day or previous exercise. The sequences are applied in investigations of healthy adult subjects in everyday physiological situations to document the potential of the novel methods in terms of accuracy, precision, robustness. Without such investigations on healthy subjects the methodological advances cannot be verified in a valid situation and thus not ported to more specific research trials or clinical applications.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Evaluation of Novel and Adapted MR Spectroscopy and Metabolic Imaging Techniques for Non-invasive Monitoring of Metabolite Levels in Humans in Physiologic States of Everyday Life

Actual Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NIMM_MRS testing of new MRS methods	Device: NIMM_MRS evaluation of new MRS methods

Arm

Intervention/Treatment

Experimental: NIMM_MRS

testing of new MRS methods

Device: NIMM_MRS

evaluation of new MRS methods

Outcome Measures

Primary Outcome Measures

healthy-cohort signal intensity characteristics for metabolites of interest (MOI) [2 months]
healthy-cohort signal intensity characteristics for MOI as targeted by newly developed/optimized MRS sequences. Novel MRS sequences will be administered in a small cohort of healthy subjects and each sequence will provide detection/quantification of one or multiple specific metabolites (or metabolite characteristics (e.g. diffusivity)). Respective cohort averages and standard deviations of those signal intensities relative to the averaged signal noise per subject are the prime outcomes

Secondary Outcome Measures

healthy-cohort signal resolution and uncertainty characteristics for metabolites of interest (MOI) [2 months]
cohort characteristics of the resolution parameters (full width at half maximum intensity) and (where a fitting model is available) the uncertainties of the model fit from single subjects

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

signed informed consent
healthy (no neuronal or metabolic diseases as stated by the study participant)
able to lie still in the MR scanner for at least one hour

Exclusion Criteria:

<18 yrs of age
pregnancy or current state of lactation
active implants
passive ferromagnetic implants
passive non-ferromagnetic metallic implants > 4 cm inside a region covered by the active radio-frequency (RF) coils
large tattoos inside a region covered by the active RF coils
known or suspected non-compliance,
under-weight (<35 kg body weight)