Bedside optical imaging of occipital resting-state functional connectivity in neonates

Abstract

Resting-state networks derived from temporal correlations of spontaneous hemodynamic fluctuations have been extensively used to elucidate the functional organization of the brain in adults and infants. We have previously developed functional connectivity diffuse optical tomography methods in adults, and we now apply these techniques to study functional connectivity in newborn infants at the bedside. We present functional connectivity maps in the occipital cortices obtained from healthy term-born infants and premature infants, including one infant with an occipital stroke. Our results suggest that functional connectivity diffuse optical tomography has potential as a valuable clinical tool for the early detection of functional deficits and for providing prognostic information on future development.

Fig. 1

Bedside functional imaging of infants with DOT. (A) Infant head model and visual cortex imaging pad with 18 sources (red) and 16 detectors (blue), placed over the occipital cortex. (B) Photograph of the optical probe on a premature infant in an isolette. (C) Detected light level vs. source-detector separation on an infant. All first- and second-nearest neighbor pairs were detected simultaneously and were well above the noise floor (shown by the horizontal dotted line).

Fig. 2

Neonatal fcDOT using seed-based correlation analysis in the visual cortex (HbO₂). (A, B) Correlation maps using seeds placed in the left and right visual cortices of a healthy term infant. Note the strong ipsilateral and contralateral correlations. (C,D) Correlation maps in a preterm infant with relatively less complicated clinical course, which also show bilateral correlation patterns. (All correlation images are scaled from r=−1 to 1 and have a threshold at |r|>0.3. The area covered by the imaging pad is shown in cyan.).

Fig. 3

Correlation maps obtained for six infants without significant morbidities using right seeds in the visual cortex (HbO₂). (A) Individual correlation maps of three healthy term-born infants. (B) Similar correlation patterns were obtained for three preterm infants with relatively less complicated clinical courses.

Fig. 4

Neonatal fcDOT in a preterm infant with an occipital stroke (HbO₂). (A) An axial slice (neurological orientation) of a T2-weighted MRI of this infant done at approximately 36 weeks corrected gestational age, showing the stroke. (B) Correlation maps using seeds placed where the left and right visual cortices are expected to be. In both cases, we see only unilateral correlations. (All correlation images are scaled from r=−1 to 1.).

Fig. 5

Neonatal fcDOT in a preterm infant with a complicated clinical course. (HbO₂). (A) An axial slice (neurological orientation) of a T2-weighted MRI showing minimal anatomical abnormalities at term-equivalent age, just prior to discharge. However, there appears to be white matter changes in the periventricular regions. (B) Correlation maps using seeds placed in the left and right visual cortices. We see the bilateral correlation patterns of a healthy visual cortex (all correlation images are scaled from r=−1 to 1).

Fig. 6

Average interhemispheric correlation coefficients for all infant groups and all three hemodynamic contrasts. Error bars show standard deviation over subjects (except for groups with only one subject).

Fig. 7

Neonatal fcDOT using independent component analysis (HbO₂). (A) Independent component (IC) in a healthy term infant showing a bilateral pattern (similar to Figs. 2A-B). (B) IC for a preterm infant with no significant anatomical brain injury (compare to Figs. 2C-D). (C) IC for the preterm infant with a complicated clinical course (compare to Fig. 5B). (D) Unilateral IC in the infant with the unilateral occipital stroke (compare to Fig. 4B). All components are scaled to their maximum, keeping zero at the center of the color scale, and the sign convention is that the strong “correlations” are positive; since ICA is unique only up to a multiplicative constant. The color scale threshold is similar to seed-based analysis.

Fig. 8

Resting-state DOT power spectra in neonates (HbO₂ and Hb_R). (A) In the healthy term-born infant we can see a 1/f curve as well as pulse peaks in both visual hemispheres. (B) In the infant with a left occipital stroke, we can still see systemic physiology in the affected hemisphere (pulse, and some 1/f fluctuations), but low frequency power is markedly lower, an indication of the lack of brain activity.

Fig. 9

Maps of resting-state low frequency power (Hb_R). (A) Maps of low frequency power in a healthy term neonate. Note the bilateral pattern. (B, C) A similar bilateral power is seen in preterm infants with no significant anatomical injuries. (D) In the low frequency power map, power is only seen in the intact hemisphere in the infant with occipital stroke.