High‐resolution dynamic oxygen‐17 MR imaging of mouse brain with golden‐ratio–based radial sampling and k‐space–weighted image reconstruction

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Regulation of cerebral fluids plays a vital role in brain function 1. Investigation of cerebral fluid dynamics, such as blood flow, diffusion, and water movement across the blood‐brain barrier (BBB), is of great value in assessing brain physiology and function under normal and diseased conditions. While MRI with arterial spin labeling uses magnetically labeled endogenous water as a tracer to measure cerebral blood flow (CBF) 2, other imaging methods have used isotope‐labeled exogenous water tracers to quantify both CBF and water transport across the BBB 3. Using water labeled with oxygen isotopes, oxygen‐15 (15O) positron emission tomography (PET) and oxygen‐17 (17O) MRI are the only available methods capable of tracing water movement in vivo. However, 15O‐PET requires an on‐site cyclotron to generate the short‐lived 15O isotope (∼2 minute half‐life), limiting its clinical use. Alternatively, 17O is a stable MR‐detectable isotope with a natural abundance of 0.037% only. 17O‐labeled water ( JOURNAL/mrim/04.02/01445475-201801000-00025/math_25MM1/v/2017-12-21T175206Z/r/image-png ) can thus serve as a tracer for in vivo evaluation of water movement by MRI. However, use of 17O‐labeled water in vivo is challenging due to the limited signal‐to‐noise ratio (SNR) caused by the low natural abundance and MR sensitivity of 17O. Even on high‐field scanners, images are typically acquired with a large voxel size to achieve adequate SNR. In addition, using a short echo time to minimize signal loss in 17O‐MRI is critical due to the short transverse relaxation time of 17O 5.
17O‐MRI has been used extensively to evaluate cerebral metabolic activity in rats 6, healthy cats 7, and mice 8. Quantification of the cerebral metabolic rate of oxygen consumption (CMRO2) was accomplished by calculating the rate of JOURNAL/mrim/04.02/01445475-201801000-00025/math_25MM2/v/2017-12-21T175206Z/r/image-png generation from inhaled 17O‐labeled oxygen gas (17O2). Water dynamics and CBF can also be assessed with 17O‐MRI by observing the kinetics of JOURNAL/mrim/04.02/01445475-201801000-00025/math_25MM3/v/2017-12-21T175206Z/r/image-png signal either from a bolus injection of 17O‐labeled water or from metabolically produced JOURNAL/mrim/04.02/01445475-201801000-00025/math_25MM4/v/2017-12-21T175206Z/r/image-png from inhaled 17O28. Most of these studies used spectroscopic imaging methods with Cartesian encoding 10, but alternative 17O‐MRI methods have used ultra‐short echo time sequences with non‐Cartesian encoding 12, including the density‐adapted three‐dimensional (3D) radial pulse sequence 12 and the flexible twisted projection imaging acquisition 14. These methods have achieved a spatial resolution of 8 to 8.5 mm and a temporal resolution of 40 to 50 s in humans at high field. However, such spatial and temporal resolution is not sufficient for imaging small rodents.
The aim of this study was to develop a 3D dynamic 17O‐MRI method to delineate the kinetics of 17O water uptake and washout in the mouse brain. A stack‐of‐stars radial sampling method was implemented based on the golden‐angle acquisition scheme 15. A k‐space–weighted image contrast (KWIC) reconstruction was applied to the acquired data to improve the temporal rate with preserved spatial resolution 16. Simulation studies were performed to validate the method. Using this method, the kinetics of JOURNAL/mrim/04.02/01445475-201801000-00025/math_25MM5/v/2017-12-21T175206Z/r/image-png uptake and washout in the brains of mice with glioblastoma (GBM) were delineated after an intravenous bolus injection of JOURNAL/mrim/04.02/01445475-201801000-00025/math_25MM6/v/2017-12-21T175206Z/r/image-png . A temporal resolution of 7.56 s with a nominal voxel size of 5.625 μL was achieved in this study.

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