Hyperpolarized Carbon-13 Pyruvate Imaging for Traumatic Brain Injury

(HPTBI Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Illicit drugs

Disqualifiers: Schizophrenia, Bipolar, Stroke, others

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

Compensation: Varies

Number of Visits: 1

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This project is to evaluate sensitivity and specificity of hyperpolarized 13C-pyruvate as imaging agents of altered cerebral glycolysis and mitochondrial dysfunction and assess pyruvate utilization in mitochondria in Traumatic Brain Injury (TBI) patients.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are using illicit drugs that alter brain function, you cannot participate in the trial.

What data supports the effectiveness of the treatment Hyperpolarized [1-13C] Pyruvate, Hyperpolarized [2-13C] Pyruvate for traumatic brain injury?

Research shows that using hyperpolarized [1-13C] pyruvate can help map metabolic changes in the brain after a traumatic injury, which may help in understanding and monitoring brain function after such injuries. This treatment has been shown to detect changes in brain metabolism in real-time, indicating its potential usefulness in assessing brain injuries. ^{1 2 3 4 5}

Is hyperpolarized carbon-13 pyruvate imaging safe for humans?

Studies have shown that hyperpolarized carbon-13 pyruvate imaging has been tested in humans and animals, and it appears to be safe. In human studies, it was used to investigate brain metabolism without any reported safety issues. ^{1 5 6 7 8}

How does hyperpolarized carbon-13 pyruvate imaging differ from other treatments for traumatic brain injury?

Hyperpolarized carbon-13 pyruvate imaging is unique because it allows real-time mapping of metabolic changes in the brain after traumatic injury without invasive procedures. This approach uses magnetic resonance spectroscopic imaging (MRSI) to detect shifts in brain metabolism, providing insights into mitochondrial function and secondary injury processes that are not typically captured by standard imaging techniques. ^{1 2 4 6 9}

Eligibility Criteria

This trial is for adults aged 18-60 with a confirmed traumatic brain injury (TBI) based on specific criteria, including Glascow coma scale scores and CT scans. Participants must have had the injury within the last 30 days and be able to consent in English or Spanish. Excluded are those with non-TBI related brain abnormalities, metal in their head that affects MRI, severe mental health issues, drug influence at scanning time, or any MRI contraindications.

Inclusion Criteria

My traumatic brain injury happened less than 30 days ago.

Ability to understand and willingness to sign a written informed consent

You have a documented and confirmed traumatic brain injury with a Glasgow Coma Scale score of 10-15 or loss of consciousness for more than 10 minutes.

Exclusion Criteria

Any contraindication per MRI Screening Form including implants contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillator (ICD), claustrophobia

Medically unstable including heart failure, severe left ventricular outflow tract (LVOT) obstruction, unstable angina, pregnancy, lactating

Subjects who are receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Procedure

Participants undergo imaging with hyperpolarized [1-13C] and [2-13C] pyruvate to assess cerebral glycolysis and mitochondrial dysfunction

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

Treatment Details

Interventions

• Hyperpolarized [1-13C] Pyruvate
• Hyperpolarized [2-13C] Pyruvate

Trial Overview The study tests how well hyperpolarized carbon-13 pyruvate compounds work as imaging agents to show changes in brain metabolism after TBI. It aims to assess mitochondrial dysfunction and cerebral glycolysis using advanced imaging techniques in patients who've recently suffered from TBI.

Participant Groups

Group I: Hyperpolarized [2-13C] Pyruvate Experimental Treatment 1 Intervention

Injection with hyperpolarized \[2-13C\] Pyruvate during MRI.

Group II: Hyperpolarized [1-13C] Pyruvate Experimental Treatment 1 Intervention

Injection with hyperpolarized \[1-13C\] Pyruvate during MRI.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

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]

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]

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]

A stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate was successfully developed, allowing for its use in metabolic imaging studies.

In a study involving anesthetized rats, hyperpolarized [1-(13)C]-ethyl pyruvate was compared to [1-(13)C]-pyruvate, demonstrating its potential for effective uptake and metabolic imaging in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. Hurd, RE., Yen, YF., Mayer, D., et al.[2021]

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]

This study demonstrates the successful use of hyperpolarized 13C spectroscopy to detect metabolic products in the rat brain, specifically identifying [1-(13)C]lactate and [13C]bicarbonate after injecting [1-(13)C]pyruvate.

The research highlights the potential of using hyperpolarized [2-(13)C]pyruvate to detect [2-(13)C]lactate, although it did not reveal other metabolites, indicating that different pyruvate isotopes can yield varying insights into metabolic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo 13C spectroscopy in the rat brain using hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate. Marjańska, M., Iltis, I., Shestov, AA., et al.[2021]

References

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

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

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

Imaging Acute Metabolic Changes in Patients with Mild Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate. [2021]

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

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

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

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

5. 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]

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

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. [2021]

7. England pubmed.ncbi.nlm.nih.gov

In vivo metabolic imaging of Traumatic Brain Injury. [2019]

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

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

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

In vivo 13C spectroscopy in the rat brain using hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate. [2021]