PET Quantification of Cerebral Oxygen Metabolism in Small Animals

Abstract

Understanding cerebral oxygen metabolism is of great importance in both clinical diagnosis and animal experiments because oxygen is a fundamental source of brain energy and supports brain functional activities. Since small animals such as rats are widely used to study various diseases including cerebral ischemia, cerebrovascular diseases, and neurodegenerative diseases, the development of a noninvasive in vivo measurement method of cerebral oxygen metabolic parameters such as oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) as well as cerebral blood flow (CBF) and cerebral blood volume (CBV) has been a priority. Although positron emission tomography (PET) with 15O labeled gas tracers has been recognized as a powerful way to evaluate cerebral oxygen metabolism in humans, this method could not be applied to rats due to technical problems and there were no reports of PET measurement of cerebral oxygen metabolism in rats until an 15O-O2 injection method was developed a decade ago. Herein, we introduce an intravenous administration method using two types of injectable 15O-O2 and an 15O-O2 gas inhalation method through an airway placed in the trachea, which enables oxygen metabolism measurements in rats.

Sequential PET estimation of cerebral oxygen metabolism with spontaneous respiration of 15O-gas in mice with bilateral common carotid artery stenosis

“…Since oxygen is a fundamental energy source for brain activity, use of Positron emission tomography (PET) for in vivo quantitative measurements of parameters related to cerebral oxygen metabolism such as cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ) in the presence of 15 O labeled gases ( 15 O-O 2 , 15 O-CO 2 , and 15 O-CO) is of great importance both in clinical [1][2][3][4] and basic settings. [5][6][7] Given the importance of small animal models such as mice and rats to many research fields, the development of noninvasive measurement methods to assess oxygen metabolism in small animals is needed.…”

“…In vivo measurements of cerebral oxygen metabolism by living rats can be achieved using PET and injectable 15 O-O 2 [8][9][10][11][12] or 15 O-O 2 gas inhaled through a tracheotomy catheter. 13,14 Both techniques are applicable to O-15 tracers other than O 2 .…”

“…13,14 Both techniques are applicable to O-15 tracers other than O 2 . Although both techniques are valuable for evaluating cerebral oxygen metabolism in ischemic brains of normal and hypertensive rats, 15 to date there are no reports of methods that can be applied to monitor cerebral oxygen metabolism in live mouse brains. Both techniques described above could be adapted to mice, but they have several limitations, including inadequate specific activity of injectable 15 O-O 2 , animal sacrifice for probe preparation, and invasiveness of the tracheotomy.…”

“…17 However, this study included no information related to oxygen metabolism. Thus, in this study, we first developed a noninvasive PET method to evaluate cerebral oxygen metabolism in mice with spontaneous respiration of 15 O-gas, and evaluated the usefulness of this method for sequential evaluation of the cerebral oxygen metabolism in BCAS mice during the first 28 days after the operation.…”

High-speed quantitative optical imaging of absolute metabolism in the rat cortex

“…Measurement of CMRO 2 requires medical imaging techniques such as Positron Emission Tomography (PET) or functional Magnetic Resonance Imaging (fMRI). PET [1][2][3][4][5] can measure absolute CMRO 2 , but it is expensive, nonportable, and uses exogenous contrast agents containing radioactive tracers. fMRI measures CMRO 2 changes via the blood oxygen level dependent (BOLD) signal, but it struggles to provide absolute CMRO 2 without extensive calibration because it uses the BOLD signal as a surrogate for cerebral blood flow and hemoglobin content as opposed to directly measuring these quantities.…”