Metabolic MRI with Hyperpolarized Pyruvate for Traumatic Brain Injury
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Maryland, Baltimore
Disqualifiers: Inability to undergo MRI, others
No Placebo Group
Approved in 2 Jurisdictions
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.
12345Is 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.
12367How 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.
12468Eligibility 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.
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Metabolic MRI in traumatic brain injury patientsExperimental Treatment1 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 patientsExperimental Treatment1 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 volunteersExperimental Treatment1 Intervention
Perform metabolic magnetic resonance imaging on healthy volunteers to understand early brain metabolism changes in this population
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Maryland BaltimoreBaltimore, MD
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Who Is Running the Clinical Trial?
University of Maryland, BaltimoreLead Sponsor
References
Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. [2023]Hyperpolarized (HP) 13C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-13C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire 13C-labeled volumetric and dynamic images of [2-13C]pyruvate and downstream metabolites [5-13C]glutamate and [2-13C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (kPL) and pyruvate-to-glutamate (kPG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.
First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism. [2022]We developed methods for the preparation of hyperpolarized (HP) sterile [2-13C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-13C]pyruvate to [2-13C]lactate and [5-13C]glutamate in the brain of four healthy volunteers. Metabolite kinetics, signal-to-noise (SNR) and area-under-curve (AUC) ratios, and calculated [2-13C]pyruvate to [2-13C]lactate conversion rates (kPL) were measured and showed similar but not identical inter-subject values. The kPL measurements were equivalent with prior human HP [1-13C]pyruvate measurements.
Parahydrogen-Polarized [1-13 C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging. [2023]Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1-13 C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70-160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.
Investigating cerebral perfusion with high resolution hyperpolarized [1-13 C]pyruvate MRI. [2023]Label="PURPOSE">To investigate high-resolution hyperpolarized (HP) 13 C pyruvate MRI for measuring cerebral perfusion in the human brain.
Longitudinal assessment of mitochondrial dysfunction in acute traumatic brain injury using hyperpolarized [1-13 C]pyruvate. [2023]Label="PURPOSE">[13 C]Bicarbonate formation from hyperpolarized [1-13 C]pyruvate via pyruvate dehydrogenase, a key regulatory enzyme, represents the cerebral oxidation of pyruvate and the integrity of mitochondrial function. The present study is to characterize the chronology of cerebral mitochondrial metabolism during secondary injury associated with acute traumatic brain injury (TBI) by longitudinally monitoring [13 C]bicarbonate production from hyperpolarized [1-13 C]pyruvate in rodents.
Considering whole-body metabolism in hyperpolarized MRI through 13 C breath analysis-An alternative way to quantification and normalization? [2023]Label="PURPOSE">Hyperpolarized [1-13 C]pyruvate MRI is an emerging clinical tool for metabolic imaging. It has the potential for absolute quantitative metabolic imaging. However, the method itself is not quantitative, limiting comparison of images across both time and between individuals. Here, we propose a simple signal normalization to the whole-body oxidative metabolism to overcome this limitation.
Cerebral dynamics and metabolism of hyperpolarized [1-(13)C]pyruvate using time-resolved MR spectroscopic imaging. [2021]Dynamic hyperpolarized [1-(13)C]pyruvate metabolic imaging in the normal anesthetized rat brain is demonstrated on a clinical 3-T magnetic resonance imaging scanner. A 12-second bolus injection of hyperpolarized [1-(13)C]pyruvate is imaged at a 3-second temporal resolution. The observed dynamics are evaluated with regard to cerebral blood volume (CBV), flow, transport, and metabolic exchange with the cerebral lactate pool. A model for brain [1-(13)C]lactate, based on blood-brain transport kinetics, CBV, and the observed pyruvate dynamics is described.
Kinetic analysis of multi-resolution hyperpolarized 13 C human brain MRI to study cerebral metabolism. [2023]Label="PURPOSE">To investigate multi-resolution hyperpolarized (HP) 13 C pyruvate MRI for measuring kinetic conversion rates in the human brain.