Rapid T2- and susceptometry-based CMRO2 quantification with interleaved TRUST (iTRUST)

Abstract

Susceptometry-based oximetry (SBO) and T2-relaxation-under-spin-tagging (TRUST) are two promising methods for quantifying the cerebral metabolic rate of oxygen (CMRO2), a critical parameter of brain function. We present a combined method, interleaved TRUST (iTRUST), which achieves rapid, simultaneous quantification of both susceptometry- and T2-based CMRO2 via insertion of a flow-encoded, dual-echo gradient-recalled echo (OxFlow) module within the T1 recovery portion of the TRUST sequence. In addition to allowing direct comparison between SBO- and TRUST-derived venous oxygen saturation (Yv) values, iTRUST substantially improves TRUST temporal resolution for CMRO2 quantification and obviates the need for a separate blood flow measurement following TRUST acquisition. iTRUST was compared directly to TRUST and OxFlow alone in three resting subjects at baseline, exhibiting close agreement with the separate techniques and comparable precision. These baseline data as well as simulation results support the use of two instead of the traditional four T2 preparation times for T2 fitting, allowing simultaneous quantification of susceptometry- and T2-based Yv (and CMRO2) with three- and six-second temporal resolution, respectively. In 10 young healthy subjects, iTRUST was applied during a 5% CO2 gas mixture-breathing paradigm. T2-based Yv values were lower at baseline relative to susceptometry (62.3 ± 3.1 vs. 66.7 ± 5.1 %HbO2, P < 0.05), but increased more in response to hypercapnia. As a result, T2-based CMRO2 decreased from 140.4 ± 9.7 to 120.0 ± 9.5 μMol/100 g/min, a significant − 14.6 ± 3.6% response (P < 0.0001), whereas susceptometry-based CMRO2 changed insignificantly from 123.4 ± 18.7 to 127.9 ± 25.7, a 3.3 ± 9.7% response (P = 0.31). These differing results are in accord with previous studies applying the parent OxFlow or TRUST sequences individually, thus supporting the reliability of iTRUST but also strongly suggesting that a systematic bias exists between the susceptometry- and T2-based Yv quantification techniques.

In vivo validation of T2‐ and susceptibility‐based SvO2 measurements with jugular vein catheterization under hypoxia and hypercapnia

“…The proportional bias between TRUST and SBO has been suggested by several prior studies, but we demonstrated it in the broad oxygenation range produced. Compared to SBO, TRUST presented significantly lower S v O 2 values under room air and hypoxia conditions but comparable S v O 2 values under hypercapnia.…”

“…Barhoum et al compared TRUST and SBO at resting condition and reported slightly lower S v O 2 values provided by TRUST. Rodgers et al performed interleaved TRUST and SBO acquisition in one sequence and observed higher S v O 2 response to hypercapnia indicated by TRUST than SBO. To our knowledge, there has been no comparison of these two methods under low saturation levels such as hypoxia.…”

Searching for a truly “iso-metabolic” gas challenge in physiological MRI

“…It has been suggested previously that hypercapnia reduced metabolic activity in the brain 1,18 while hypoxia increased metabolic activity.…”

“…These values are with the typical range of the literature reports. 1,2,12,18,[35][36][37][38][39][40][41][42] But the effect of gas modulation on neural or metabolic activity is not fully understood and is in fact still controversial. This is primarily due to a lack of tools to examine these questions, because one can no longer use vascular surrogate marker (for which plenty of tools are available) and must use direct assessment of neural activity or metabolic rate.…”

“…[13][14][15] When conducting measurements in conscious human subjects, several studies also suggested that CO 2 inhalation may suppress neural activity 16,17 and brain metabolic rate. 1,18 These potential effects of CO 2 on neurometabolism may complicate the interpretation of calibrated fMRI and CVR signals. Therefore, the central goal of the present study is to test whether we can identify a gas challenge that is truly ''iso-metabolic'' while still producing a clear vascular response.…”