Metabolic MRI with Hyperpolarized Pyruvate for Traumatic Brain Injury

Overseen By Rosy Linda Njonkou Tchoquessi

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

Disqualifiers: Inability to undergo MRI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method of using MRI scans to examine the brain after a head injury, such as a concussion (a type of traumatic brain injury or TBI). Researchers seek to determine if using a special compound, hyperpolarized 13C-pyruvate, during the MRI can help identify changes in brain metabolism (how the brain uses energy) immediately after an injury. The study will compare results from individuals with TBI, those with subarachnoid hemorrhage (a type of bleeding in the brain), and healthy volunteers. The trial seeks participants who have recently experienced a head injury that might have caused a concussion and can undergo an MRI. As a Phase 1 trial, this research focuses on understanding how this new approach works in people, offering participants the chance to be among the first to experience this innovative technique.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that hyperpolarized metabolic MRI is safe for studying brain metabolism changes?

Research has shown that hyperpolarized 13C-pyruvate MRI is generally safe. In studies with healthy volunteers, researchers used this technique without causing serious side effects. Participants tolerated the injection of hyperpolarized pyruvate well. Safety data supports its use, even at normal levels.

Although researchers continue to study this imaging method, its use in humans has not raised major safety concerns so far. This suggests it is well-tolerated in healthy individuals and those with certain brain injuries. However, more research is needed to fully understand its safety across different populations and conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Metabolic MRI with Hyperpolarized 13C-Pyruvate for traumatic brain injury because it offers a novel way to visualize brain metabolism in real-time. Unlike traditional imaging methods like CT or standard MRI that show structural damage, this technique provides insight into how the brain's metabolism is functioning after an injury. This could lead to earlier and more precise interventions. By understanding metabolic changes, doctors might tailor treatments more effectively, potentially improving recovery outcomes for patients with traumatic brain injuries.

What evidence suggests that hyperpolarized 13C-pyruvate MRI is effective for diagnosing traumatic brain injury?

Research has shown that a special type of MRI, called hyperpolarized 13C-pyruvate metabolic MRI, can detect changes in brain energy use after a traumatic brain injury (TBI). In this trial, participants will undergo metabolic MRI to understand early brain metabolism changes. Studies suggest this technique could enhance the detection and understanding of TBI, potentially aiding in predicting patient outcomes. This method is practical for observing changes in brain metabolism in TBI patients, indicating its potential use in hospitals. For subarachnoid hemorrhage (SAH), this imaging technique reveals changes in the brain's energy use, providing valuable insights. Overall, hyperpolarized 13C-pyruvate MRI shows promise for safely monitoring brain metabolism in both TBI and SAH without requiring surgery. ^{1 2 5 6 7}

Who Is on the Research Team?

Dirk Mayer, Dr. rer. nat.

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for up to 15 people with a recent head injury suspected of non-penetrating traumatic brain injury (TBI), including those who can safely have an MRI with contrast and are not pregnant. It excludes individuals who cannot undergo MRI scans, have had severe reactions or kidney issues preventing them from receiving IV MRI contrast agents, or are pregnant.

Inclusion Criteria

I have had a recent head injury without an open wound.

You have to have a negative blood test for pregnancy.

I can safely have an MRI with contrast.

Exclusion Criteria

You are pregnant.

I cannot have IV MRI contrast due to a severe reaction or kidney issues.

You cannot have an MRI scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Metabolic MRI

Perform metabolic magnetic resonance imaging on participants to understand early brain metabolism changes

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized 13C-Pyruvate

Trial Overview The study tests the safety and feasibility of using a special type of metabolic MRI scan called hyperpolarized 13C-Pyruvate (HP 13C-pyruvate) to detect changes in brain metabolism after TBI. It will compare results from TBI patients, subarachnoid hemorrhage patients, and healthy volunteers at UMB.

How Is the Trial Designed?

Group I: Metabolic MRI in traumatic brain injury patients Experimental Treatment 1 Intervention

Perform metabolic magnetic resonance imaging on patients who have traumatic brain injury to understand early brain metabolism changes in this population

Group II: Metabolic MRI in subarachnoid hemorrhage patients Experimental Treatment 1 Intervention

Perform metabolic magnetic resonance imaging on patients who have subarachnoid hemorrhage to understand early brain metabolism changes in this population

Group III: Metabolic MRI in healthy volunteers Experimental Treatment 1 Intervention

Perform metabolic magnetic resonance imaging on healthy volunteers to understand early brain metabolism changes in this population

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

The study monitored mitochondrial metabolism in male Wistar rats after traumatic brain injury (TBI) by measuring [13C]bicarbonate production from hyperpolarized [1-13C]pyruvate, revealing significantly reduced bicarbonate levels at the injury site, indicating impaired mitochondrial function.

Bicarbonate production peaked at 24 hours post-injury and returned to normal by day 10, suggesting that [13C]bicarbonate could serve as a sensitive in-vivo biomarker for assessing secondary injury processes following TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of mitochondrial dysfunction in acute traumatic brain injury using hyperpolarized [1-13 C]pyruvate. Hackett, EP., Chen, J., Ingle, L., et al.[2023]

Using multi-resolution hyperpolarized 13C pyruvate MRI in 6 subjects improved the measurement of kinetic conversion rates in the human brain, particularly by enhancing spatial resolution and reducing partial volume effects.

Higher resolution images (7.5 × 7.5 mm2) led to more accurate calculations of pyruvate-to-lactate conversion rates, especially in areas near blood vessels, indicating that finer resolution can significantly enhance metabolic data quality in brain imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism. Hu, JY., Kim, Y., Autry, AW., et al.[2023]

A new method for normalizing hyperpolarized [1-13 C]pyruvate MRI signals using expired 13 CO2 significantly reduces variability in metabolic measurements, improving the accuracy of metabolic imaging in clinical settings.

In a study involving 11 pigs with induced renal hypoperfusion, this normalization technique led to a 25% reduction in variance for certain metabolic ratios, enhancing the specificity of the imaging results without significantly affecting other ratios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considering whole-body metabolism in hyperpolarized MRI through 13 C breath analysis-An alternative way to quantification and normalization? Sejersen, S., Rasmussen, CW., Bøgh, N., et al.[2023]

The study successfully developed methods to prepare hyperpolarized [2-13C]pyruvate for the first human NMR studies, demonstrating its feasibility for investigating brain energy metabolism in four healthy volunteers.

Results showed that the conversion of hyperpolarized [2-13C]pyruvate to [2-13C]lactate and [5-13C]glutamate can be measured, with conversion rates comparable to previous studies using [1-13C]pyruvate, indicating the potential for this technique in metabolic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism. Chung, BT., Chen, HY., Gordon, J., et al.[2022]

High-resolution hyperpolarized 13C pyruvate MRI can effectively measure cerebral perfusion in the human brain, showing significant positive correlations with traditional arterial spin labeling (ASL) methods across different brain regions.

This study, involving five healthy volunteers, demonstrates that hyperpolarized pyruvate MRI not only provides detailed spatial imaging of brain structures but also allows for simultaneous assessment of cerebral metabolism and perfusion, enhancing our understanding of brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating cerebral perfusion with high resolution hyperpolarized [1-13 C]pyruvate MRI. Hu, JY., Vaziri, S., Bøgh, N., et al.[2023]

Dynamic hyperpolarized [1-(13)C]pyruvate metabolic imaging successfully demonstrated the ability to visualize metabolic processes in the normal anesthetized rat brain using a clinical 3-T MRI scanner, with a rapid imaging capability of 3-second intervals after a 12-second bolus injection.

The study developed a model to understand the dynamics of brain lactate production based on factors like cerebral blood volume and transport kinetics, which could enhance our understanding of metabolic exchanges in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral dynamics and metabolism of hyperpolarized [1-(13)C]pyruvate using time-resolved MR spectroscopic imaging. Hurd, RE., Yen, YF., Tropp, J., et al.[2021]

A new hyperpolarization technique using parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) can produce highly hyperpolarized [1-13 C]pyruvate solutions quickly and efficiently, achieving concentrations of 70-160 mM in just 85 seconds.

In a study with 48 animals, the safety and image quality of PHIP-SAH were found to be comparable to the established dissolution dynamic nuclear polarization (d-DNP) method, suggesting that PHIP-SAH could be a practical alternative for metabolic MRI applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parahydrogen-Polarized [1-13 C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging. Nagel, L., Gierse, M., Gottwald, W., et al.[2023]

This study is the first to use hyperpolarized 13C MRI to visualize and measure how the human brain processes [2-13C]pyruvate, providing insights into cerebral energy metabolism.

In a trial involving 5 healthy volunteers, the technique allowed for the simultaneous assessment of glycolytic and oxidative metabolism by quantifying the conversion rates of pyruvate to lactate and glutamate, highlighting its potential for advanced metabolic imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. Chung, BT., Kim, Y., Gordon, JW., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06103201

Hyperpolarized 13C-pyruvate Metabolic MRI With ... The purpose of this study is to examine the safety and feasibility of using hyperpolarized metabolic MRI to study early brain metabolism changes.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10462249/

Hyperpolarized 13C metabolic imaging detects long- ... Our study demonstrates the potential of metabolic imaging to improve detection, classification and outcome prediction of previously undetected rTBI.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589004220310828

Imaging Acute Metabolic Changes in Patients with Mild ... This study reports the feasibility of imaging altered metabolism using hyperpolarized pyruvate in patients with TBI, demonstrating the translatability and ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/mrm.29875

Current methods for hyperpolarized [1‐13C]pyruvate MRI ... MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10530049/

Hyperpolarized [2–13C]pyruvate MR molecular imaging ... HP [2–13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition ...

6. elifesciences.org elifesciences.org/reviewed-preprints/106736

Hyperpolarized 13 C metabolic imaging detects long ... This study presents a valuable finding on the perturbed pyruvate metabolism in models of repetitive traumatic brain injury.

7. trialx.com trialx.com/clinical-trials/listings/264845/hyperpolarized-13c-pyruvate-metabolic-mri-with-traumatic-brain-injury/?&geo_lat=39.4072&geo_lng=-76.6038&radius=10&place=Towson&user_country=United%20States

Hyperpolarized 13C-pyruvate Metabolic MRI With ... The purpose of this study is to examine the safety and feasibility of using hyperpolarized metabolic MRI to study early brain metabolism changes ...