Monitoring of Brain Metabolites Using Proton and Deuterium MR Techniques

NCT06705010 | Not Yet Recruiting DMC

• 2 other identifiers: 2023-D0060SNCTP000006108
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

MR pulse for whole brain optimal Deuterium (2H) Metabolic Imaging and EPSI (echo planar spectroscopic imaging) based SLOW-edited 1H-MRSI will be developed and optimized for use at an UHF scanner at 7 Tesla. The study has 4 phases. Phase I: The 2H and 1H MRSI sequences are developed and optimized in vitro (phantoms) Phase II: Sequences are applied in vivo in healthy volunteers and further optimized Phase III: Optimal 2H 1H pulse sequences are applied in 4 cohorts of healthy volunteers, to study the effect of aging with whole brain 2H and 1H MRSI. Phase IV: application of the sequences in 4 patient groups with different diseases: Alzheimer's diseases (AD) patients, diabetes mellitus type II (DM) patients, mild cognitive impaired (MCI) patients, and high grade carotid stenosis patients (HGCS). The ultimate aim is to create for individual patient specific 3dimensional spatial resolved z-score maps (similar to FDG-PET) based on the healthy control data of phase III of the trial.

Conditions

Aging; Brain Metabolic Disorder; Carotid Stenosis; Alzheimer Disease; Diabetes Type 2; Mild Cognitive Impairment; Brain Disease

Outcome Measures

Primary Outcomes (6)

• 3D spatial resolved Deuterium metabolite imaging (DMI)

  Coregistered deuterium metabolite distributions (glucose, glutamate) is measured in a young healthy control group of 20 person (\<40 years) is obtained, as well as coregistered deuterium metabolic images of metabolite distribution in a elder healthy control group of 20 person (\>40 years) is obtained.

  36 months

• 3D spatial resolved SLOW-EPSI MRSI metabolite mapping

  Coregistered neuro-metabolite distributions (e.g. GABA, glutamate) distribution in a young healthy control group of 20 persons (age \< 40 years) are measured, as well as coregistered neuro-metabolite distributions (e.g. GABA, glutamate, ..) are measured in healthy control group of 20 persons (age \> 40 years).

  36 months

• 3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Alzheimer's disease (AD) patient group

  Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in an Alzheimer's disease (AD) patient group of 10 persons are obtained.

  48 months

• 3D spatial resolved 3D DMI and 3D SLOW-EPSI MRSI mapping in Mild Cognitive Impairment (MCI) patient group

  Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Mild Cognitive Impairment (MCI) patient group of 10 persons are obtained.

  48 months

• 3D DMI and 3D SLOW-EPSI MRSI mapping in a Diabetes Mellitus (DM) Type II patient group

  Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained

  48 months

• 3D DMI and 3D SLOW-EPSI MRSI mapping in a High Grade Carotid Stenosis (HGCS) patient group

  Coregistered DMI (glucose, glutamate) maps and neuro-metabolite images (e.g. GABA, glutamate, ..) distribution in a Diabetes Mellitus (DM) Type II patient group of 10 persons is obtained

  48 months

Study Arms (2)

Application of novel MRSI pulse sequences to healthy persons

ACTIVE COMPARATOR

Optimized MR-pulse sequences are applied to three healthy person groups after glucose solution ingestion to obtain healthy control 3D metabolic reference data.

Device: Application of new pulse sequence package SIGNATURES2023 to healthy controls

Application of novel MRSI pulse sequences to four patient groups

EXPERIMENTAL

Optimized MR-pulse sequences are applied to four groups of 10 patients after glucose solution ingestion followed by patient level comparison of patient 3D metabolic data to healthy control data by z-score mapping.

Device: Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot)

Interventions

Application of new pulse sequence package SIGNATURES2023 to healthy controls DEVICE

One or more novel or further optimized non CE-marked pulse MRSI sequence is/are applied to 100 healthy subjects to determined reference metabolite maps of the whole brain

Application of novel MRSI pulse sequences to healthy persons

Application of new pulse sequence package SIGNATURES2023 to 4 groups of patients (pilot) DEVICE

One or more novel or further optimized non CE-marked pulse MRSI sequence is/are applied to 4 time 10 patients with AD, MCI, DM and HGCS to determine metabolite maps of the whole brain.

Application of novel MRSI pulse sequences to four patient groups

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent by the participant.
• Ability to lie still in the MR scanner for at least one hour.
• No current or lifetime history of drug or alcohol abuse.
• No medications that interfere with cognition.
• Normal or corrected-to-normal vision.
• I. Type 2 Diabetes Patients group (PG-IV-2H-DM):
• Diagnosis of Type 2 diabetes according to the ADA classification.
• Treatment with lifestyle modification and/or non-insulin agents.
• II. High-Grade Carotid Stenosis Patient Group (PG-IV-1H-HGCS):
• ≥50% stenosis of the carotid artery.
• III. Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) Patients (PG-IV-2H-AD/MCI):
• Diagnosis of Mild Cognitive Impairment (MCI) or early Alzheimer's disease (AD).
• Age range between 60-80 years.
• Fluent in German.
• Normal or corrected-to-normal vision and hearing.

You may not qualify if:

• Under 18 years of age.
• Claustrophobia.
• Pregnancy or current state of lactation.
• Active implants (e.g., pacemakers, neuro-stimulators).
• Passive ferromagnetic implants.
• Passive non-ferromagnetic metallic implants \> 4 cm in 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.
• Underweight \<30 kg body weight.
• Body mass index (BMI) \> 30.
• Overweight \>135 kg
• Persons with extreme big head circumference or extreme astigmatism, which cannot be corrected by MR-compatible eyeglasses.
• Persons not able to understand the informed consent form.
• Not agreeing with the institute's policy to inform the subject on incidental findings discovered during the examination.
• Visual and auditory acuity impairing neuropsychological testing (if relevant).

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Translational Imaging Center / Sitem

Bern, 3010, Switzerland

Location

Related Publications (4)

• Weng G, Radojewski P, Sheriff S, Kiefer C, Schucht P, Wiest R, Maudsley AA, Slotboom J. SLOW: A novel spectral editing method for whole-brain MRSI at ultra high magnetic field. Magn Reson Med. 2022 Jul;88(1):53-70. doi: 10.1002/mrm.29220. Epub 2022 Mar 28.

  PMID: 35344608 BACKGROUND

• Weng G, Ermis E, Maragkou T, Krcek R, Reinhardt P, Zubak I, Schucht P, Wiest R, Slotboom J, Radojewski P. Accurate prediction of isocitrate dehydrogenase -mutation status of gliomas using SLOW-editing magnetic resonance spectroscopic imaging at 7 T MR. Neurooncol Adv. 2023 Jan 3;5(1):vdad001. doi: 10.1093/noajnl/vdad001. eCollection 2023 Jan-Dec.

  PMID: 36875625 BACKGROUND

• Weng G, Slotboom J, Schucht P, Ermis E, Wiest R, Kloppel S, Peter J, Zubak I, Radojewski P. Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T. Neuroimage. 2024 Feb 1;286:120511. doi: 10.1016/j.neuroimage.2024.120511. Epub 2024 Jan 5.

  PMID: 38184158 BACKGROUND

• Rakic M, Turco F, Weng G, Maes F, Sima DM, Slotboom J. Deep learning pipeline for quality filtering of MRSI spectra. NMR Biomed. 2024 Jul;37(7):e5012. doi: 10.1002/nbm.5012. Epub 2023 Jul 30.

  PMID: 37518942 BACKGROUND

Related Links

• Website where a description of a MRSI processing tool is described and can be downloaded

MeSH Terms

Conditions

Brain Diseases, Metabolic; Carotid Stenosis; Alzheimer Disease; Diabetes Mellitus, Type 2; Cognitive Dysfunction; Brain Diseases

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Carotid Artery Diseases; Cerebrovascular Disorders; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Dementia; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Endocrine System Diseases; Cognition Disorders

Study Officials

• Johannes Slotboom, PhD

  University Hospital / Inselspital /University Bern / 3010 Bern / Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Johannes Slotboom, PhD

CONTACT

+41316327469; johannes.slotboom@insel.ch

Piotr Radojewski, MD

CONTACT

+41316641467; piotr.radojewski@insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2H-MRSI and 1H-MRSI pulse sequences will be developed and protocols optimized in vitro. Suitable MR-protocols will be further optimized in vivo. These DMI-MRSI protocols will be applied after 1H/2H-glucose supplementation: 1. in a group of 20 healthy persons younger that 40 years old after deuterated glucose intake 2. in a group of 20 healthy person elder 40 years old after deuterated glucose intake 3. in a group of 10 young healthy persons to measure task based functional 2H-MRSI response. 4. in a group of 10 Alzheimer's disease patients after deuterated glucose intake 5. in a group of 10 mild cognitive impairment patients after deuterated glucose intake 6. in a group of 10 diabetes mellitus patients after deuterated glucose intake 7. in a group of 10 high grade carotid stenosis patients after alpha-D-glucose intake

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: November 26, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)