Spectroscopy of reperfused tissue after stroke reveals heightened metabolism in patients with good clinical outcomes

Abstract

The aim of acute stroke treatment is to reperfuse the penumbra. However, not all posttreatment reperfusion is associated with a good outcome. Recent arterial spin labeling (ASL) studies suggest that patients with hyperperfusion after treatment have a better clinical recovery. This study aimed to determine whether there was a distinctive magnetic resonance spectroscopy (MRS) metabolite profile in hyperperfused tissue after stroke reperfusion therapy. We studied 77 ischemic stroke patients 24 hours after treatment using MRS (single voxel spectroscopy, point resolved spectroscopy, echo time 30 ms), ASL, and diffusion-weighted imaging (DWI). Magnetic resonance spectroscopy voxels were placed in cortical tissue that was penumbral on baseline perfusion imaging but had reperfused at 24 hours (and did not progress to infarction). Additionally, 20 healthy age matched controls underwent MRS. In all, 24 patients had hyperperfusion; 36 had reperfused penumbra without hyperperfusion, and 17 were excluded due to no reperfusion. Hyperperfusion was significantly related to better 3-month clinical outcome compared with patients without hyperperfusion (P=0.007). Patients with hyperperfusion showed increased glutamate (P<0.001), increased N-Acetylaspartate (NAA) (P=0.038), and increased lactate (P<0.002) in reperfused tissue compared with contralateral tissue and healthy controls. Hyperperfused tissue has a characteristic metabolite signature, suggesting that it is more metabolically active and perhaps more capable of later neuroplasticity.

Figure 1

Placement of magentic resonance (MR) spectroscopy (MRS) voxels using acute computed tomography (CT) perfusion (CTP) imaging as a reference. Identification of hyperperfused tissue required acute CTP imaging (Top row, first map). Next, 24 hours magnetic resonance imaging (MRI) using arterial spin labeling (ASL-CBF, bottom row, first image) and diffusion-weighted imaging (DWI, bottom row second imaging) was performed to measure reperfusion and penumbral salvage. MRS voxels were placed in the reperfused region on ASL that did not show infarct on DWI (bottom row second imaging, yellow box) to measure metabolic concentrations. CBF, cerebral blood flow.

Figure 2

The appearance of hyperperfusion after acute ischemic stroke treatment was independent of the acute clinical and imaging criteria, however, hyperperfusion predicted good outcome (modified Rankin score (mRS) 0 to 2). Columns are divided by post processed imaging maps, the first being an acute computed tomography perfusion (CTP) looking at the penumbra (green) and infarct core (red) volumes and acute CTP cerebral blood flow (CTP-CBF). The last three columns are from 24-hour magnetic resonance imaging (MRI) including arterial spin labeling (ASL-CBF), diffusion-weighted imaging (DWI) and 24-hour bolus tracking perfusion-weighted imaging cerebral blood flow (PWI-CBF). The second and fourth patients show hyperperfusion on follow-up ASL imaging (white arrows) while the first, third, and fifth patients do not show hyperperfusion on 24-hour ASL-CBF. Note that hyperperfusion observed on ASL-CBF is not apparent on the 24-hour PWI-CBF maps obtained concurrently. Also, the bottom patient did not show reperfusion and had persistent hypoperfusion on ASL-CBF, and was not included in the magnetic resonance spectroscopy (MRS) studies. Units are in mmol/L.

Figure 3

Study results for the variation of Glutamate (GLU), Lactate (Lac), N-Acetylaspartate (NAA), and Creatine (Cr) between regions of hyperperfusion, nonhyperperfusion, contralateral tissue, and controls. This shows that GLU is significantly higher in hyperperfused tissue compared with controls. Additionally, the nonhyperperfused GLU concentration is less than in ‘healthy' controls. There was also less NAA loss in hyperperfused patients compared with controls. Patients without hyperperfusion slowed lower NAA compared with hyperperfused patients but not when compared with contralateral tissue suggesting that these patients may have a lower baseline NAA concentration. Lac and Cr were also significantly higher in the hyperperfused area compared with patients without hyperperfusion. Error bars for standard deviation. Units are in mmol/L. *P<0.001 ^P<0.05, >0.001.

Figure 4

Peri-infarct Glutamate (GLU) predicts 3-month modified Rankin score (mRS). There was a strong relationship between the peri-infarct GLU and the resulting 3-month disability of patients after successful reperfusion. Error bars for standard deviation. Units are in mmol/L.