Imaging of Traumatic Brain Injury Metabolism Using Hyperpolarized Carbon-13 Pyruvate (HPTBI)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Hyperpolarized [1-13C] Pyruvate; Drug: Hyperpolarized [2-13C] Pyruvate

Detailed Description

Aim 1:

Investigators will quantify changes in [1-13C]lactate and H13CO3- labeling following a bolus injection of hyperpolarized [1-13C]pyruvate during the time window of secondary injury to assess upregulated glycolysis. Due to heterogeneous presence and severity of damage by TBI, defining the injured brain region can be difficult. Therefore, the metabolite ratio maps ([product]/[pyruvate]) of TBI patients (n = 5) will be compared with those of healthy-controls (n = 3).

Hyperpolarized [2-13C]pyruvate will be examined in a separate group of TBI cohorts (n = 5) and healthy controls (n = 3), and [5-13C]glutamate, [1-13C]acetyl-carnitine, [1-13C]acetoacetate, and [1-13C]citrate from [2-13C]pyruvate will be quantified for assessing the altered mitochondrial metabolism. Imaging procedure with [2-13C]pyruvate is the same as the imaging with hyperpolarized [1-13C]pyruvate.

For both [1-13C]pyruvate and [2-13C]pyruvate studies, each subject will be imaged twice with a 45min interval for confirming the reproducibility of the methods and/or averaging to enhance the signal-to-noise ratios of 13C-metabolite maps.

Aim 2:

After the feasibility study (aim1) is completed, an intra-subject comparison study of [1-13C]pyruvate and [2-13C]pyruvate will be performed. Similar to the aim1, patients with post-TBI neurological disorders having normal or near-normal CT results (n = 6 patients) as well as normal brains of age/gender-matching healthy volunteers (n = 3) will be recruited. Each patient will be imaged twice (one with [1-13C]pyruvate and one with [2-13C]pyruvate with a 45min interval). PDH activity and the TCA cycling will be assessed from measured H13CO3- from hyperpolarized [1-13C]pyruvate and [5-13C]glutamate from [2-13C]pyruvate, respectively. The comparison of [1-13C]pyruvate and [2-13C]pyruvate will identify the detailed information of how pyruvate (and converted acetyl-CoA) is utilized in the mitochondria, and assess the utility and necessity of imaging hyperpolarized [2-13C]pyruvate in TBI, providing critical data for future grant applications and larger clinical trials.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern - Advanced Imaging Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

TBI Patients

• Injury occurred within 30 days
• Documented and verified TBI by Glascow coma scal 10-15 and/or Loss of Consciousness >10 minutes.
• Head Computed Tomography at admission.

ALL Subjects:

• 18 through 60 years of age.
• Ability to understand the the willingness to sign a writteninformed consent.
• All races and ethnicities will be included; subjects must be able to read and speak either the English or Spanish language.

Exclusion Criteria:

• Non-traumatic structural brain abnormality identified on head CT.
• Metallic foreign bodies on the scalp or cranium which may interfere with MRI acquisitions.
• Penetrating TBI.
• Significant anatomic distortion of the brain identified on CT images, such as large hematomas, herniation, intraventricular hemorrhage, extensive subarachnoid hemorrhage, hydrocephalus.
• Significant polytrauma that would interfere with follow-up and outcome assessment.
• Patients on psychiatric hold.
• Major debilitating mental health disorders including, but not limited to schizophrenia and bipolar disorder that would limit compliance with study requirements.
• Major debilitating neurological disease including, but not limited to, stroke, CVA, dementia and tumor that would limit compliance with study requirements.
• Under influence of illicit drugs which are known to alter brain physiology/metabolism including, but not limited to cocaine, lysergic acid diethylamide (LSD), and marijuana at the time of MRI/MRSI scanning.
• Any contraindication per MRI Screening Form including
• Implants contraindicated at 3T, pacemakers
• Implantable Cardioverter Defibrillator (ICD)
• Claustrophobia
• Prisoners or patients in custody.
• Medically unstable including
• Heart failure
• Severe left ventricular outflow tract (LVOT) obstruction
• Unstable angina
• Pregnancy
• Lactating
• Subjects who are receiving any other investigational agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperpolarized [1-13C] Pyruvate; Injection with hyperpolarized [1-13C] Pyruvate during MRI.	Drug: Hyperpolarized [1-13C] Pyruvate; Bolus injection of study drug; Other Names: HP Pyruvate Injection
Experimental: Hyperpolarized [2-13C] Pyruvate; Injection with hyperpolarized [2-13C] Pyruvate during MRI.	Drug: Hyperpolarized [2-13C] Pyruvate; Bolus injection of study drug; Other Names: HP Pyruvate Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[1-13C]lactate-to-H13CO3- ratio from [1-13C]pyruvate or [2-13C]lactate-to-[5-13C]glutamate ratio from [2-13C]pyruvate	Product ratio maps of lactate from pyruvate in the brain of TBI patients as compared to those of healthy controls.	One visit of three hours: 2 bolus injections during MRI with 45 minute rest period between the two

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: April 11, 2018
• First Posted (Actual): April 19, 2018

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: TBI; Traumatic Brain Injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Organic Chemicals; Carboxylic Acids; Pyruvates; Keto Acids; Pyruvic Acid
• Other Study ID Numbers: STU 072017-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No