Quantitative basal CBF and CBF fMRI of rhesus monkeys using three-coil continuous arterial spin labeling

Abstract

A three-coil continuous arterial-spin-labeling technique with a separate neck labeling coil was implemented on a Siemens 3T Trio for quantitative cerebral blood flow (CBF) and CBF fMRI measurements in non-human primates (rhesus monkeys). The optimal labeling power was 2 W, labeling efficiency was 92 ± 2%, and optimal post-labeling delay was 0.8 s. Gray matter (GM) and white matter (WM) were segmented based on T₁ maps. Quantitative CBF were obtained in 3 min with 1.5-mm isotropic resolution. Whole-brain average ΔS/S was 1.0–1.5%. GM CBF was 104 ± 3 ml/100 g/min (n = 6, SD) and WM CBF was 45 ± 6 ml/100 g/min in isoflurane-anesthetized rhesus monkeys, with the CBF GM/WM ratio of 2.3 ± 0.2. Combined CBF and BOLD (blood-oxygenation-level-dependent) fMRI associated with hypercapnia and hyperoxia were made with 8-s temporal resolution. CBF fMRI responses to 5% CO₂ were 59 ± 10% (GM) and 37 ± 4% (WM); BOLD fMRI responses were 2.0 ± 0.4% (GM) and 1.2 ± 0.4% (WM). CBF fMRI responses to 100% O₂ were − 9.4 ± 2% (GM) and − 3.9 ± 2.6% (WM); BOLD responses were 2.4 ± 0.7% (GM) and 0.8 ± 0.2% (WM). The use of a separate neck coil for spin labeling significantly increased CBF signal-to-noise ratio and the use of small receive-only surface coil significantly increased signal-to-noise ratio and spatial resolution. This study sets the stage for quantitative perfusion imaging and CBF fMRI for neurological diseases in anesthetized and awake monkeys.

Introduction

Non-invasive cerebral blood flow (CBF) measurement using MRI is widely used to study normal physiology and pathophysiology. Quantitative CBF can be obtained at high temporal and spatial resolution. Functional MRI based on CBF change is spatially more specific to the site of increased neural activity, capable of resolving cortical columns (Duong et al., 2001), is easier to interpret than the blood-oxygenation-level-dependent (BOLD) fMRI signals, has less susceptibility to pathologic perturbations, and less inter-subject and cross-day variability (Barbier et al., 2001). Combined cerebral blood flow and BOLD fMRI measurements offer the means to estimate the stimulus-evoked changes in cerebral metabolic rate of oxygen in a totally non-invasive manner (Kim and Ugurbil, 1997, Davis et al., 1998, Hoge et al., 1999). The main drawbacks of quantitative CBF and CBF fMRI measurements are relatively low temporal resolution, low signal-to-noise ratio (SNR) per unit time, and greater susceptibility to motion artifacts (Calamante et al., 1999, Barbier et al., 2001).

CBF can be measured by using an exogenous intravascular contrast agent or by magnetically labeling the endogenous water in blood (Calamante et al., 1999, Barbier et al., 2001). The former is efficient but it is incompatible with dynamic CBF fMRI because the long half life of the contrast agent allows only one CBF measurement per bolus injection. Arterial spin labeling (ASL) techniques, on the other hand, are totally non-invasive, and the labeled water has a short half-life (∼ blood T₁) making it possible to perform repeated measurements which can be used to augment spatial resolution and/or signal-to-noise ratio. ASL is compatible with dynamic CBF fMRI studies.

ASL can be performed using pulsed labeling (Detre et al., 1994, Wong et al., 1998, Wang et al., 2005) or continuous labeling (Silva et al., 1995, Zaharchuk et al., 1999, Talagala et al., 2004); both are capable of multislice and whole-brain imaging. Continuous ASL (cASL) can be achieved with the same radiofrequency (RF) coil used for imaging or a separate neck coil. cASL with a separate neck coil is generally more sensitive relative to the single-coil technique (Kim, 1995, Wong et al., 1998, Wang et al., 2005), particularly in small animals such as rodents which have short arterial transit time (Silva et al., 1999, Duong et al., 2000b). With the separate neck coil, magnetization-transfer effect is eliminated if the coils are properly decoupled, resulting in a larger signal difference between labeled and non-labeled images, and thus improved CBF SNR. RF power deposition is localized to the neck area and unlabeled images can be acquired without labeling RF, reducing specific absorption rate (SAR) (Zhang et al., 1995). While cASL technique for measuring quantitative basal CBF and CBF-based MRI is more readily available on animal scanners for rodent imaging (Silva et al., 1999, Duong et al., 2000b), similar studies on humans and large non-human primates are sparse because clinical scanners generally lack the necessary hardware and software. cASL using a separate neck coil has been reported on General Electric scanners for human studies (Zaharchuk et al., 1999, Talagala et al., 2004), although its advantage over the single-coil arterial spin labeling technique remains to be demonstrated because of the long arterial transit time in humans. The typical spatial resolution of basal ASL CBF measurements on human scanners was ~ 70 mm³ (Zaharchuk et al., 1999, Talagala et al., 2004). CBF-based fMRI using cASL with a separate neck coil on human scanners remains to be demonstrated.

The goal of this study was to implement a three-coil arterial spin-labeling technique on a Siemens 3T Trio clinical scanner for non-human primate (rhesus monkey) studies. Due to the difficulty and safety concerns in re-configuring the Siemens hardware, we instead constructed a stand-alone hardware unit for cASL using a separate neck coil. Hardware components which included an external RF amplifier, control electronics, optical–electrical relays, active decoupling circuits and radiofrequency probes were built, interfaced and tested on a Siemens 3T Trio. This approach was demonstrated by obtaining: (i) high-resolution (1.5-mm isotropic resolution or 3.3 mm³ resolution) quantitative basal CBF in 3 min, and (ii) high-resolution combined CBF and BOLD fMRI with 8-s temporal resolution associated with hypercapnic and hyperoxic challenges. Technical issues associated with performing CBF measurements on rhesus monkeys are detailed.