Technology Development for Intracellular Metabolites at 7 Tesla

Study ID
STU 092010-054

Cancer Related
Yes

Healthy Volunteers
Yes

Study Sites

Contact
Jeannie Baxter
214-645-2726
jeannie.baxter@utsouthwestern.edu

Principal Investigator
Craig Malloy

Summary

We anticipate enrolling 2,000 study participants over the course of the study to optimize magnetic resonance imaging (MRi) and magnetic resonance spectroscopy (MRS) of brain, forearm muscle, calf muscle, or other specific organ in the body such as liver, breast, or kidney, in a high field magnet. as some metabolites are better detected after exercise, some volunteers who do/do not regularly exercise may be asked to exercise prior to the MRS. exercise will be limited to up to one hour, during which the subject's vital signs and blood oxygen will be monitored. Some subjects exercising for forearm or calf scans may exercise with or without the inflation of a BP cuff to induce ischemia. The BP cuff may also be used to induce ischemia on subjects who are not exercising. The BP cuff on the upper arm/leg will be inflated with enough air pressure to prevent blood from flowing to the arm/leg. Cuff inflation with exercise will last no more than 5 minutes and 10 minutes for those not exercising. For the scan, the subject will be asked to lie still on the table of the MR machine for 5-15 minute periods of time during data collection. Fasting may also affect the measurement of metabolites during MR spectroscopy. Thus, subjects may be asked to fast 4 to 24 hours prior to a calf or liver scan. During the scan, the subject's heart rate and respiratory rate may be monitored.
Screening Visit Prior to infusion Protocol: Subjects will be instructed to fast overnight prior to the screening laboratory tests for safety and study eligibility.
infusion Protocol: a sterile, pyrogen-free solution of sodium acetate added to 0.45% naCl will infuse at a rate of 2.9 to 3.0 mg/kg/min. For an 80 kg person, this corresponds to 232 mg/min or about 8 ml/min. The solution will infuse for approximately 90 minutes, during which time blood will be drawn from the iV in the opposite arm.
Pilot Breast Contrast Protocol: The target nuclei are 1H for detecting choline (most prior studies of cancer metabolism utilized this approach) and 13C and 31P as additional methods for probing metabolism. Regardless of the approach, localizing the breast lesion must be achieved. This generally requires an FDa approved standard clinical contrast agent such as Magnevist or another FDa approved equivalent iV contrast. Ten subjects (normal, with breast mass, or known breast cancer) will be given the opportunity to participate by having an MRi scan with contrast at the advanced imaging Research Center (aiRC) at uTSW. The experience for the subject is very similar to routine magnetic resonance imaging (MRi). approximately one-third way through the MR examination, iV contrast will be administered at the FDa recommended dose and rate (Magnevist: 0.1 mmol/kg not to exceed 10ml/15sec) and MRS will commence. Total time in the magnet will be limited to approximately 90 minutes. once pilot data has been collected and analyzed on up to ten subjects with contrast, further studies if indicated will be designed using the separate submission of a new iRB study.
Hypercapnia Protocol: The purpose of this phosphorus spectroscopy study is to test, in five healthy subjects, whether pH value of the brain tissue would decrease, increase, or stay unchanged when the participant inhales (5%) Co2 enriched air, comparing to room-air breathing. The MRS will be performed using a surface coil positioned under the head. During the MR scan, the inhaled air will be controlled with a gas inhalation system that we have used extensively ([Greater Than]300 subjects) on 3T. For most of the time while they are inside the magnet, the participants will breathe room-air. During two periods of 7 minute blocks, they will be breathing 5% Co2, 21% o2 and 74% n2.

Participant Eligibility

Criteria for Inclusion of Subjects:
- Adults, age 18-70
- In good health (evidenced by normal vital signs and no signs or symptoms of acute illness)
- Willing to participate under the conditions described in the informed consent form (ICF).
- Must be able to sign the ICF and applicable HIPAA forms.
- Must be willing to undergo screening for MR procedures

Additional Criteria for Inclusion of Subjects in hypercapnia protocol: Only young healthy subjects 18 to 40 years old will be included.