Development of ¹⁷ O NMR approach for fast imaging of cerebral metabolic rate of oxygen in rat brain at high field

Abstract

A comprehensive technique was developed for using threedimensional 17 O magnetic resonance spectroscopic imaging at 9.4T for rapidly imaging the cerebral metabolic rate of oxygen consumption (CMRO2) in the rat brain during a two-min inhalation of 17 O2. The CMRO2 value (2.19 ؎ 0.14 mol͞g͞min, n ‫؍‬ 7) was determined in the rat anesthetized with ␣-chloralose by independent and concurrent 17 O NMR measurements of cerebral H2 17 O content, arterial input function, and cerebral perfusion. CMRO2 values obtained were consistent with the literature results for similar conditions. Our results reveal that, because of its superior sensitivity at ultra-high fields, the 17 O magnetic resonance spectroscopic imaging approach is capable of detecting small dynamic changes of metabolic H2 17 O during a short inhalation of 17 O2 gas, and ultimately, for imaging CMRO2 in the small rat brain. This study provides a crucial step toward the goal of developing a robust and noninvasive 17 O NMR approach for imaging CMRO2 in animal and human brains that can be used for studying the central role of oxidative metabolism in brain function under normal and diseased conditions, as well as for understanding the mechanisms underlying functional MRI.

In vivo17O NMR approaches for brain study at high field

“…In vivo 17 O approaches can be potentially applied to measuring and imaging two important physiological parameters, namely CMRO 2 and CBF. 6,8,14,16,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] The 17 O NMR approaches for in vivo determinations of CMRO 2 and CBF involve the measurement of (i) the amount of 17 O-labeled water metabolically generated from the inhaled 17 O 2 gas through the oxidative pathway, and (ii) the washout rate of the 17 O-labeled water tracer introduced by a bolus injection, respectively. In terms of methodology, there is a close similarity between the in vivo 17 O approaches and PET approaches, especially for CBF measurements.…”

“…46 This complete model requires multiple in vivo measurements to determine four variables of CBF, A, n and C b (t) in order to calculate CMRO 2 . Fig.…”

“…Two unit conversion factors, f 1 ¼ 1.266 and f 2 ¼ 1.05, are used to achieve consistency of units among all parameters used in eqn (6). 43,46,48 If water in the brain tissue is in equilibrium with water in the venous blood, then…”

“…The quantification approach based on eqn (10) is a complete model accounting for all required parameters for precisely determining CMRO 2 . 46,48 CBF quantification using in vivo 17 O approach…”

“…6,9 The sensitivity gain at high/ultrahigh fields is essential for further development and improvement of the direct in vivo 17 O approaches for quantifying and imaging CMRO 2 robustly and reliably. 46,48 …”