This phase I trial evaluates the feasibility of using hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing patients with primary central nervous system lymphoma. This trial aims to see whether MRI using hyperpolarized carbon-13 pyruvate is safe and useful for detecting central nervous system lymphoma and evaluating response to treatment.

PRIMARY OBJECTIVES

1. To determine the safety and tolerability of hyperpolarized 13C MR metabolic imaging as a new and unique tool in the evaluation of tumor burden and detecting early response to standard therapy in participants with PCNSL.
2. To assess the feasibility of hyperpolarized 13C as a new and unique tool in the evaluation of tumor burden and detecting early response to standard therapy in PCNSL participants.
3. To define the most appropriate imaging parameters for obtaining 13C data from PCNSL participants (Cohort 1, n=5).
4. To evaluate changes in Cohort 2 in imaging pre- and post- high-dose methotrexate, temozolomide plus rituximab (MTX-R) based therapy using the parameters found in Cohort 1

EXPLORATORY OBJECTIVES

1. To test the hypothesis that genetic markers of nuclear factor kappa light chain enhancer of activated B cells (NF-kB) activation in PCNSL diagnostic specimens correlate with high lactate signal on metabolic imaging and with high cerebrospinal fluid (CSF) lactate concentration on baseline pre-treatment CSF evaluation.
2. To test the hypothesis that genetic markers of NF-kB activation correlate with a smaller decrease in lactate on repeat metabolic magnetic resonance (MR) imaging and in repeat CSF evaluation after standard induction methotrexate-based therapy and that genetic markers of NF-kB activation and high lactate signals correlate with lower rate of complete radiographic response on conventional MRI and shorter progression-free survival (PFS).

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan.

COHORT II: Patients receive hyperpolarized carbon C 13 pyruvate IV and undergo MRI at baseline, up to 2 weeks after finishing 3 cycles of standard high-dose methotrexate, temozolomide plus rituximab therapy, and at disease progression (if applicable). An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan.

Participants are followed for 1 hours after injection for adverse events. After completion of study, patients in Cohort 2 are followed up every 3 months for 2 years after completion of therapy, every 6 months for the next 3 years, and then annually for the next 5 years.

Inclusion Criteria:

• For Patients in Cohort 1: Histologically proven PCNSL who have evidence of evaluable disease based on a prior MR scan: measurable disease based on MRI is defined as gadolinium enhancement of a central nervous system (CNS) lymphoma lesion (at least one centimeter (cm) diameter).
• For Patients in Cohort 2: Histologically proven newly diagnosed PCNSL who will receive standard treatment with high-dose methotrexate, temozolomide plus rituximab (MT-R). These criteria will ensure validity of this study in terms of safety, evaluation of clinically and radiographically relevant disease.

To be included in the study all subjects must also meet the following criteria:

1. Patients must be > 18 years old and with a life expectancy > 12 weeks.
2. Patients are eligible provided the participant had histologic confirmation of CNS non-Hodgkin lymphoma (NHL), DLBCL-type.
3. Measurable disease based on MRI that shows gadolinium enhancement of CNS lymphoma lesion, (at least one cm diameter) within two weeks of enrollment, is mandatory. Recent MRI must be eligible for review.
4. Concomitant involvement of cerebrospinal fluid/leptomeninges and intraocular compartments is allowed.
5. Patients must have adequate renal function (creatinine >50 ml/min) before starting therapy. These tests must be performed within 21 days prior to Hyperpolarized Imaging scan.
6. Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to participate in this study or any disease that will obscure toxicity or dangerously impact response to the imaging agent.
7. Patients must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure
8. Patients must be eligible for treatment with high-dose methotrexate (dose between 1 gm/m^2 - 8 gm/m^2).
9. Each participant must sign an institutional review board-approved informed consent document in accordance with federal and institutional guidelines. Patients must sign an authorization for release of their protected health information.
10. This study was designed to include women and minorities but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate. No exclusion to this study will be based on race.
11. Patients must not have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for >3 yrs.
12. Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of Hyperpolarized Imaging scan. Effective contraception (men and women) must be used in subjects of childbearing potential.

Exclusion Criteria:

1. Subjects must be excluded from participating in this study if are not able to comply with study and/or follow-up procedures.