Recent advances in arterial spin labeling perfusion MRI in patients with vascular cognitive impairment

Abstract

Cognitive impairment (CI) is a major health concern in aging populations. It impairs patients' independent life and may progress to dementia. Vascular cognitive impairment (VCI) encompasses all cerebrovascular pathologies that contribute to cognitive impairment (CI). Moreover, the majority of CI subtypes involve various aspects of vascular dysfunction. Recent research highlights the critical role of reduced cerebral blood flow (CBF) in the progress of VCI, and the detection of altered CBF may help to detect or even predict the onset of VCI. Arterial spin labeling (ASL) is a non-invasive, non-ionizing perfusion MRI technique for assessing CBF qualitatively and quantitatively. Recent methodological advances enabling improved signal-to-noise ratio (SNR) and data acquisition have led to an increase in the use of ASL to assess CBF in VCI patients. Combined with other imaging modalities and biomarkers, ASL has great potential for identifying early VCI and guiding prediction and prevention strategies. This review focuses on recent advances in ASL-based perfusion MRI for identifying patients at high risk of VCI.

Keywords: Vascular cognitive impairment; arterial spin labeling; cerebral blood flow; neuroimaging; neurovascular unit; perfusion MRI; vascular dementia.

Figure 1.

Classification of VCI according to the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) guideline. VCI is divided into mild VCI (VCI-no dementia, VCIND) and major VCI (vascular dementia, VaD). VaD can be further classified into 4 subtypes: post-stroke dementia (PSD), subcortical ischemic VaD, multi-infarct (cortical) dementia, and mixed dementia with nonvascular pathologies.

Figure 2.

Schematic diagram and detailed functions of the cellular components of the neurovascular unit (NVU). The NVU is the functional unit helping CBF regulation. Detailed functions (in black) of normal pericytes, vascular smooth muscle cells (SMCs) and endothelial cells, three components of the NVU, are depicted. Dysfunction of any cellular component of the NVU (in red) can contribute to vascular cognitive impairment (VCI). SMCs can directly control the vessel diameter and have autoregulatory effects on brain tissue perfusion. SMCs degeneration disturbs steady cerebral perfusion and is associated with vascular injury, microbleed development and blood-brain barrier (BBB) disruption. Endothelial cells mediate neurovascular coupling, microvascular responses, endothelial nitric oxide synthase (eNOS) production. Dysfunction of endothelium causes increased toxic factors and reduced production of NO, which can promote the development of VCI. Pericytes are crucial in CBF controlling, BBB permeability maintaining, and angiogenesis promotion. The loss of pericytes in VCI leads to BBB damage, CBF reduction, and neuronal loss.

Figure 3.

Schematic diagram displaying the main differences between pulsed arterial spin labeling (pASL), continuous ASL (cASL), and pseudo-continuous ASL (pcASL), in labeling zone and duration. pASL refers to a single short pulse to label inflowing arterial blood, while cASL/pcASL involves a continuous pulse or over 1000 shaped pulses with high frequency at a thin slice, through the neck over a period of time. Arterial transit time (ATT) refers to the time between labeling and screening, which can lead to cerebral blood flow (CBF) underestimation in ASL due to relaxation of labeled spins. The post-labeling delay (PLD, or inversion time in pASL) is artificially preset to be longer than the longest ATT to delay the screening time and minimize the inaccuracy caused by ATT. However, single-PLD ASL can cause errors due to the mismatch between the single PLD and ATT, especially in vessel stenosis and occlusion, which is common in VCI patients. This challenge can be overcomed by multi-PLD ASL or the use of spatial coefficient of variation (CoV).