Brain perfusion imaging in neonates

Abstract

Abnormal variations of the neonatal brain perfusion can result in long-term neurodevelopmental consequences and cerebral perfusion imaging can play an important role in diagnostic and therapeutic decision-making. To identify at-risk situations, perfusion imaging of the neonatal brain must accurately evaluate both regional and global perfusion. To date, neonatal cerebral perfusion assessment remains challenging. The available modalities such as magnetic resonance imaging (MRI), ultrasound imaging, computed tomography (CT), near-infrared spectroscopy or nuclear imaging have multiple compromises and limitations. Several promising methods are being developed to achieve better diagnostic accuracy and higher robustness, in particular using advanced MRI and ultrasound techniques. The objective of this state-of-the-art review is to analyze the methodology and challenges of neonatal brain perfusion imaging, to describe the currently available modalities, and to outline future perspectives.

Keywords: Brain; MRI; Pediatrics; Perfusion; Ultrasound.

Graphical abstract

Fig. 1

Dynamic susceptibility contrast MRI Perfusion. Panels A and B show perfusion maps with CBF on the left and CBV on the right of each panel, at two different levels to illustrate marked hyperperfusion in the occipital lobes (A), basal ganglia (B) and motor cortex (A and B) reflective of basal ganglia injury pattern. Adapted and with permission from Wintermark et al. (Wintermark et al., 2008a).

Fig. 2

Phase Contrast MRI. Sagittal 2D phase contrast image (A) to illustrate the positioning of the axial 2D phase contrast image showing in plane flow signal intensity within the internal carotid arteries (B: 1 and 2) and the basilary artery (B: 3). Adapted and with permission from Benders et al. (Benders et al., 2011).

Fig. 3

Arterial Spin Labeling (ASL) MRI. A: Magnetization of arterial blood water spins within the pre-cerebral arteries is inverted by applying a radiofrequency pulse (left, dotted box), followed by a short delay during which the spins reach the brain circulation where a “labelled” image is obtained. Prior background magnetization is captured within the same field of view (left dashed box). Subtraction of the two images generates a perfusion-weighted image (PWI). Quantification of CBF (in units of mL/100 g of brain tissue/min) with ASL is based on mathematical models using time-averaged signal intensities in the background magnetization and arterial spin labeled images. B: ASL perfusion images representing CBF in three infants born at 25 weeks gestational age (top row), 31 weeks gestational age (middle row) and scanned 40 weeks gestational age (bottom row). Perfusion increases within the central sulcus with gestational age (middle row) and is more homogeneously spread in a term newborn (bottom row). Adapted and with permission from De Vis et al. (De Vis et al., 2013).

Fig. 4

Intravoxel Incoherent Motion (IVIM) MRI Perfusion. IVIM parameters f_IVIM (A), D* (B) and D*.f_IVIM (C) reflect hyperperfusion in both frontal lobes, predominately on the right. Signal intensity decay as function of b with corresponding biexponential fit are represented for a region of interest within the hyperperfused right frontal lobe (D) and within a left parietal control region (E). Adapted and with permission from Federau et al. (Federau et al., 2014).

Fig. 5

Conventional Doppler Ultrasound. Power Doppler flow mapping overlayed on a b-mode coronal view of the basal ganglia and anterior horns of the lateral ventricles including the middle cerebral arteries. Regional vascularity is measured during post-processing by counting the number and strength of colour pixels in a preselected region. Adapted and with permission from Heck et al. (Heck et al., 2012).

Fig. 6

Dynamic tissue perfusion measurement. A region of interest is selected within the basal ganglia on a color Doppler ultrasound clip acquired during at least one cardiac cycle to quantify mean perfusion intensity (in cm/s) shown on the intensity curve at the bottom in a 1-day-old patient diagnosed with hypoxic-ischemic encephalopathy. Adapted and with permission from Faingold et al. (Faingold et al., 2016).

Fig. 7

Contrast-enhanced Ultrasound (CEUS). A: Mid-coronal b-mode image showing bilateral frontal lobes (black arrows), frontal horns of the lateral ventricles (black chevrons), basal ganglia (white arrows), and temporal lobes (white chevrons). B-G: Static images of a dynamic microbubble wash-in on mid-coronal views of a healthy neonate. H: Posterior parietooccipital view in a neonate with hypoxic-ischemic injury showing diffuse hypoperfusion with multiple areas of paucity of microbubbles (white arrows), reflecting perfusion abnormalities. I: Coronal view through the basal ganglia in a neonate with diffuse hypoxic-ischemic injury, in the immediate post-injury period, showing diffuse hyperperfusion. J: Coronal view through the basal ganglia in an infant following prolonged cardiac arrest, showing diffuse hypoperfusion. Adapted and with permission from Hwang (Hwang, 2019).

Fig. 8

Ultrafast Ultrasound Imaging (UUI). Transfontanellar Ultrafast Doppler images of a neonate’s brain in different views. A: From left to right, coronal, tilted parasagittal and parasagittal views. The color scale maps the CBV using the ultrasound Power Doppler feature. B: From left to right, sagittal, parasagittal, and trans-temporal axial views. The Power-Doppler images include directional information (red: flow toward the probe, blue: flow away from the probe). Visible structures include pericallosal artery, veins below the cerebral ventricles, cortical penetrating arterioles and venules, and the circle of Willis. C: Vascular RI mapped in sagittal, axial, and parasagittal views. (A, B & C) Adapted and with permission from Demene et al. (Demene et al., 2019). D: Sectorial Ultrafast Doppler image obtained in coronal view. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 9

Computed Tomography (CT) Perfusion. Placement of regions of interest (ROI) for regional cerebral blood volume and flow analysis within the grey (black ROIs) and white (white ROIs) matter. Adapted and with permission from Wintermark et al. (Wintermark et al., 2004b).

Fig. 10

A - Near-Infrared Spectroscopy principles (NIRS). An optode transmits infrared light through the scalp and skull, tissue who have limited absorption at these wavelengths. A receiving optode collects the scattered light. Adapted and with permission from Mohammadi-Nejad et al (Mohammadi-Nejad et al., 2018). B - The dynamic variations of absorption can be linked to the concentration of oxy- and deoxy-hemoglobin [HbO] and [HbR], having different absorbance properties, from which cerebral blood volume variation and oximetry is then derived. [HbT] is the total concentration of hemoglobin. Adapted and with permission from Mesquita et al. (Mesquita et al., 2010).

Fig. 11

Positron Emission Tomography (PET). Cerebral metabolic rate of glucose is measured in the subacute period (10 –11 days) after perinatal asphyxia in three infants (one per column) with different degrees of hypoxic-ischemic encephalopathy and shown at the level of the cerebellum (top row), thalamus (middle row), and sensorimotor cortex (bottom row). The neonate to the right has developed cerebral palsy with complicated seizures. The neonate to the left was healthy at the two-year follow-up. Adapted and with permission from Thorngren-Jerneck et al. (Thorngren-Jerneck et al., 2001).