Post-label delay times of ≥4 seconds are needed and may be combined with multidelay strategies for robust ASL assessment of CBF in Moyamoya disease.

Tissue hypoxia occurs in pathologic conditions such as cancer, ischemic heart disease and stroke when oxygen demand is greater than oxygen supply. An imaging method that can differentiate hypoxic versus normoxic tissue could have an immediate impact on therapy choices. In this work, the gadolinium complex of 1,4,7,10-tetraaza-1,4,7,10-tetraacetate (DOTA) having a 2-nitroimidazole attached to one carboxyl group via an amide linkage was prepared, characterized and tested as a hypoxia-sensitive MRI agent. A control complex, Gd(DO3A-monobutylamide), was also prepared in order to test whether the nitroimidazole side-chain alters either the water proton T1 relaxivity or the thermodynamic stability of the complex. The stabilities of these complexes were lower than that of Gd(DOTA)− as expected for mono-amide derivatives. The water proton T1 relaxivity (r1), bound water residence lifetime (τM) and rotational correlation time (τR) of both complexes was determined by relaxivity measurements, variable temperature 17O NMR and proton nuclear magnetic relaxation dispersion (NMRD) studies. The resulting parameters (r1 = 6.38 mm−1s−1 at 20 MHz, τM = 0.71 µs, τR = 141 ps) determined for the nitroimidazole derivative closely parallel those of other Gd(DO3A-monoamide) complexes of similar molecular size. In vitro MR imaging experiments using 9L rat glioma cells maintained under nitrogen (hypoxic) versus oxygen (normoxic) gas showed that both agents enter cells but only the nitroimidazole derivative is trapped in cells maintained under N2 as evidenced by ~2-fold decrease in T1 measured for hypoxic cells versus normoxic cells exposed to this agent. These results suggest that the nitroimidazole derivative may serve as a molecular reporter for discriminating hypoxic versus normoxic tissues by MRI.

A reliable and automated radiosynthesis for providing routine clinical-grade [F]FTC-146 for human studies was established in a modified GE TRACERlab FX. PET/MRI demonstrated the initial tracer biodistribution in humans, and clinical studies investigating different S1R-related diseases are in progress.

Hexamethyldisiloxane (HMDSO) has been identified as a sensitive proton NMR indicator of tissue oxygenation (pO 2 ) based on spectroscopic spin-lattice relaxometry. A rapid MRI approach has now been designed, implemented, and tested. The technique, proton imaging of siloxanes to map tissue oxygenation levels (PISTOL), utilizes frequency-selective excitation of the HMDSO resonance and chemical-shift selective suppression of residual water signal to effectively eliminate water and fat signals and pulse-burst saturation recovery 1 H echo planar imaging to map T 1 of HMDSO and hence pO 2 . PISTOL was used here to obtain maps of pO 2 in rat thigh muscle and Dunning prostate R3327 MAT-Lu tumor-implanted rats. Measurements were repeated to assess baseline stability and response to breathing of hyperoxic gas. Each pO 2 map was obtained in 3½ min, facilitating dynamic measurements of response to oxygen intervention. Altering the inhaled gas to oxygen produced a significant increase in mean pO 2 from 55 Torr to 238 Torr in thigh muscle and a smaller, but significant, increase in mean pO 2 from 17 Torr to 78 Torr in MAT-Lu tumors. Thus, PISTOL enabled mapping of tissue pO 2 at multiple locations and dynamic changes in pO 2 in response to intervention. This new method offers a potentially valuable new tool to image pO 2 in vivo for any healthy or diseased state by 1 H MRI.

O-HO PET imaging is an accurate method to measure cerebral blood flow (CBF) but it requires an arterial input function (AIF). Historically, image-derived AIF estimation suffers from low temporal resolution, spill-in, and spill-over problems. Here, we optimized tracer dose on a time-of-flight PET/MR according to the acquisition-specific noise-equivalent count rate curve. An optimized dose of 850 MBq of O-HO was determined, which allowed sufficient counts to reconstruct a short time-frame PET angiogram (PETA) during the arterial phase. This PETA enabled the measurement of the extent of spill-over, while an MR angiogram was used to measure the true arterial volume for AIF estimation. A segment of the high cervical arteries outside the brain was chosen, where the measured spill-in effects were minimal. CBF studies were performed twice with separate [15O]-HO injections in 10 healthy subjects, yielding values of 88 ± 16, 44 ± 9, and 58 ± 11 mL/min/100 g for gray matter, white matter, and whole brain, with intra-subject CBF differences of 5.0 ± 4.0%, 4.1 ± 3.3%, and 4.5 ± 3.7%, respectively. A third CBF measurement after the administration of 1 g of acetazolamide showed 35 ± 23%, 29 ± 20%, and 33 ± 22% increase in gray matter, white matter, and whole brain, respectively. Based on these findings, the proposed noninvasive AIF method provides robust CBF measurement with O-HO PET.