title: Perfusion and diffusion sensitive 13C stimulated-echo MRSI for metabolic imaging of cancer.
abstract: Metabolic imaging with hyperpolarized [1-(13)C]-pyruvate can rapidly probe tissue metabolic profiles in vivo and has been shown to provide cancer imaging biomarkers for tumor detection, progression, and response to therapy. This technique uses a bolus injection followed by imaging within 1-2 minutes. The observed metabolites include vascular components and their generation is also influenced by cellular transport. These factors complicate image interpretation, especially since [1-(13)C]lactate, a metabolic product that is a biomarker of cancer, is also produced by red blood cells. It would be valuable to understand the distribution of metabolites between the vasculature, interstitial space, and intracellular compartments. The purpose of this study was to better understand this compartmentalization by using a perfusion and diffusion-sensitive stimulated-echo acquisition mode (STEAM) MRSI acquisition method tailored to hyperpolarized substrates. Our results in mouse models showed that among metabolites, the injected substrate (13)C-pyruvate had the largest vascular fraction overall while (13)C-alanine had the smallest vascular fraction. We observed a larger vascular fraction of pyruvate and lactate in the kidneys and liver when compared to back muscle and prostate tumor tissue. Our data suggests that (13)C-lactate in prostate tumor tissue voxels was the most abundant labeled metabolite intracellularly. This was shown in STEAM images that highlighted abnormal cancer cell metabolism and suppressed vascular (13)C metabolite signals.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA 94158, USA. peder.larson@ucsf.edu
authors.forename: Peder E Z
authors.initials: PE
authors.lastname: Larson
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Hurd
authors.forename: Adam B
authors.initials: AB
authors.lastname: Kerr
authors.forename: John M
authors.initials: JM
authors.lastname: Pauly
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bok
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Vigneron
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003287:Contrast Media / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051379:Mice; D055420:Perfusion Imaging / Q000379:methods*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D002247:Carbon Isotopes; D003287:Contrast Media; D019275:Radiopharmaceuticals