Trevor Wade, Abstract Co-Author: Nothing to Disclose

Hyla Allouche-Arnon, Abstract Co-Author: Former Employee, Brainwatch Ltd

Lanette Friesen Waldner, Abstract Co-Author: Nothing to Disclose

Kundan Thind, Abstract Co-Author: Nothing to Disclose

Alexei V. Ouriadov, Abstract Co-Author: Nothing to Disclose

Albert Chen, Abstract Co-Author: Employee, General Electric Company

J. Moshe Gomori, Presenter: Scientific Advisor, Brainwatch Ltd

Charles A. McKenzie PhD, Abstract Co-Author: Research Grant, General Electric Company

Rachel Katz-Brull PhD, Abstract Co-Author: Shareholder, BrainWatch Ltd

To image choline distribution and metabolism in the live rat by MRI, non-invasively and non-radioactively.

The animal study protocol was approved by the Institutional Animal Use Subcommittee. Anesthetized male Sprague-Dawley rats, 400+/-20 g (n=6), underwent MRI and MRS in a 3T clinical MRI scanner. Coronal projection 13C imaging was performed using a variable flip angle gradient echo sequence within 1 s. Hyperpolarized media containing Choline Molecular Probe 1(CMP1, [1,1,2,2-D4, 1-13C]choline chloride) were produced in a DNP polarizer and injected via a tail vein catheter as a 12s bolus. Images were acquired 15-45 s after the start of the bolus injection. Time resolved 13C spectra were acquired every 3 s. 2D 13C chemical shift imaging was acquired as a 12 x 12 matrix (in-plane resolution of 1.0 cm) within 19 s.

CMP1 polarization in liquid state in the scanner reached 36%. The T1 of CMP1 at 3T was 30 s. Imaging of hyperpolarized CMP1 demonstrated a time dependent distribution in the rats' body. At 15 s post start of injection the signal appeared to be largely vascular. By 30 s, signal from the heart and vasculature was greatly reduced, while signal from the kidneys was even larger than that at 15 s, suggesting rapid choline uptake by the kidneys. At 45 s, the strongest signal was still from the kidneys. Whole-body dynamic spectroscopy showed two distinct signals assigned to choline (CMP1) and [1,1,2,2-D4,1-13C]phosphocholine during the bolus. At the end of the bolus, the signal from phosphocholine was already higher than CMP1, and by 18 s from the start of injection, phosphocholine was the predominant signal, suggesting complete conversion of CMP1 to phosphocholine. The T1 of phosphocholine in vivo was found to be 22 s. Chemical shift imaging showed that the phosphocholine signal arises from the kidneys.

The first non-radioactive images of choline distribution were obtained by hyperpolarized MRI. A rapid uptake in kidneys was observed in normal healthy rats. Hyperpolarized MRS showed that the label accumulated in the kidneys is dominated by phosphocholine metabolized from the injected choline.

Radioactive choline analogs are being used today as PET imaging agents for cancer. Here we show a non-radioactive imaging approach for choline uptake with added information on its metabolic fate.

Wade, T, Allouche-Arnon, H, Friesen Waldner, L, Thind, K, Ouriadov, A, Chen, A, Gomori, J, McKenzie, C, Katz-Brull, R, In Vivo Magnetic Resonance Imaging of Hyperpolarized Choline and Monitoring of Metabolism.  Radiological Society of North America 2012 Scientific Assembly and Annual Meeting, November 25 - November 30, 2012 ,Chicago IL. http://archive.rsna.org/2012/12028393.html