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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the safety and feasibility of using hyperpolarized metabolic MRI to study early brain metabolism changes in subjects presenting with head injury and suspected non-penetrating traumatic brain injury (TBI). This study will also compare HP pyruvate MRI-derived metrics in TBI patients with healthy subjects as well as Subarachnoid hemorrhage (SAH) patients to better understand if metabolic Magnetic resonance imaging scan (MRI) can improve our ability to diagnose a TBI. The FDA is allowing the use of hyperpolarized \[1-13C\] pyruvate (HP 13C-pyruvate) in this study. Up to 15 patients (5 with TBI, 5 with SAH, and 5 healthy volunteers) may take part in this study at the University of Maryland, Baltimore (UMB).

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 data supports the effectiveness of the treatment Hyperpolarized 13C-Pyruvate for Traumatic Brain Injury?

Research shows that Hyperpolarized 13C-Pyruvate MRI can provide detailed images of brain metabolism, which helps in understanding energy use in the brain. This technique has been used to study brain metabolism in healthy individuals and animals, suggesting it could be useful in assessing brain function after traumatic brain injury. ^{1 2 3 4 5}

Is Hyperpolarized Pyruvate MRI safe for humans?

Studies have shown that Hyperpolarized Pyruvate MRI has been safely used in healthy human volunteers to study brain metabolism, with no reported safety issues in these trials. ^{1 2 3 6 7}

How does the treatment using hyperpolarized pyruvate differ from other treatments for traumatic brain injury?

This treatment is unique because it uses hyperpolarized pyruvate in MRI to provide detailed images of brain metabolism, allowing doctors to see how the brain processes energy after an injury. Unlike other treatments, it offers a non-invasive way to measure metabolic changes in real-time, which can help in understanding and potentially improving recovery from brain injuries. ^{1 2 4 6 8}

Research Team

Dirk Mayer, Dr. rer. nat.

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Parahydrogen-Polarized [1-13 C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Investigating cerebral perfusion with high resolution hyperpolarized [1-13 C]pyruvate MRI. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of mitochondrial dysfunction in acute traumatic brain injury using hyperpolarized [1-13 C]pyruvate. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Considering whole-body metabolism in hyperpolarized MRI through 13 C breath analysis-An alternative way to quantification and normalization? [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Cerebral dynamics and metabolism of hyperpolarized [1-(13)C]pyruvate using time-resolved MR spectroscopic imaging. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism. [2023]