Assessing Metabolic Changes in Multiple Sclerosis Using Hyper-polarized Carbon 13 MRI
Ari Green
Summary
The main purpose of this study is to assess whether hyperpolarized carbon imaging in relapsing remitting multiple sclerosis (MS) patients can be used to predict response to anti-CD20 disease modifying therapy. Study procedures will include magnetic resonance imaging (MRI) assessments with a hyperpolarized pyruvate sequence, clinical assessment as well as blood markers of disease progression. This method of imaging utilizes the Warburg effect, where innate immune cells utilize a metabolic shift to glycolysis instead of oxidative phosphorylation. In pre-clinical data, increased hyperpolarized lactate production has been found to be associated with increased microglial/macrophage infiltration in the brain. Although hyperpolarized carbon imaging in humans has been established and used in the field of oncology, this will be one of the first applications of hyperpolarized carbon the study of neuroinflammation in humans. We predict that hyperpolarized carbon imaging may have the potential to monitor and evaluate neuroinflammation in MS, and in particular the innate immune activation state that plays a role in MS progression. This imaging method may provide non-invasive monitoring of disease progression and therapy response for MS patients.
Description
This is a prospective investigational study to evaluate the utility of HP 13C pyruvate MRI for assessing metabolism in MS lesions and monitoring response to treatment. A total of 40 relapse-remitting (RRMS) patients naïve to DMT and starting on an anti-CD20 therapy as part of their routine MS clinical care will be recruited. In a preliminary cohort, 8 patients will be imaged once to optimize HP 13C MR parameters for improved spatial and temporal resolution. Using these sequence parameters, we will then image 32 RRMS patients who will undergo a baseline anatomic and HP 13C pyruvate MRI scan pri…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Subjects must be 18 years or older. 2. Relapsing remitting MS, naïve to DMTs for the past two years minimum 3. Patients must be naive to anti-CD20 therapy with plans to begin the therapy as part of their physician's multiple sclerosis treatment plan. The patients must remain on a form of anti-CD20 therapy for the entirety of their enrollment in the study. 4. Patients enrolled will be screened for at least one MS lesion with a 10mm diameter in one plane. Exclusi…
Interventions
- DrugHP 13C pyruvate injection
Each participant will receive HP 13C pyruvate injection at a dosage of 0.43 mL/kg body weight during the MRI scan. A subset of subjects will undergo a repeatability study with a second HP 13C pyruvate injection at the same dosage. 13C is a stable, non-radioactive isotope of carbon with approximately 1% natural abundance. \[1-13C\] pyruvate has the same chemical characteristics as pyruvate. In \[1-13C\] pyruvate, the C-1 carbonyl has been replaced by a 13C-nucleus. These enriched isotopes have a magnetic moment and can be hyperpolarized in the presence of an EPA, i.e., AH111501 sodium salt (a stable trityl radical) by dynamic nuclear polarization (DNP) technique. As \[1-13C\] pyruvate has the same chemical characteristics as pyruvate, it is metabolized the same way. The polarization procedure allows MR imaging to rapidly detect the hyperpolarized 13C-label in \[1-13C\] pyruvate and its metabolites, \[1-13C\] lactate, \[1-13C\] alanine, and \[13C\] bicarbonate.
- DeviceMRI Scanner
MRI Brain scan
Location
- Byers HallSan Francisco, California