7T BOLD fMRI charactersiation of depth dependent hemodynamics in developing human cortex.
Poster No:
1284
Submission Type:
Abstract Submission
Authors:
Jucha Willers Moore1, Elisabeth Pickles1, Philippa Bridgen2, Pierluigi Di Cio2, Alena Uus1, Ines Tomazinho1, Beya Bonse1, Maria Deprez1, Sharon Giles2, A. Edwards1, Joseph Hajnal1, Shaihan Malik1, Tomoki Arichi1, Jonathan Polimeni3
Institutions:
1King's College London, London, United Kingdom, 2London Collaborative Ultra high field System (LoCUS), London, United Kingdom, 3Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA
First Author:
Co-Author(s):
Jonathan Polimeni
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
Charlestown, MA
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
Charlestown, MA
Introduction:
Neuronal activity, neurovascular coupling and vascular dynamics undergo rapid maturation in the perinatal period [1-3]. The amplitude and temporal features of the neonatal hemodynamic response to neuronal activity therefore differs markedly from that typically seen in adults [4]. It is thus unclear if cerebral cortical depth-dependent hemodynamic responses features related to differences in hemodynamics across different levels of the intracortical vascular hierarchy [5] can be generalised to the developing newborn brain [1,2]. To address this, we developed a platform for high-resolution 7T fMRI studies in newborn infants and performed a cortical-depth analysis of task-driven BOLD responses in primary motor cortex (M1).
Methods:
NHS research ethics committee approval and written parental consent was provided for data collection.
Data were acquired from 10 healthy infants at term equivalent age (median: 39.7 weeks postmenstrual age at scan (range: 37.4–42.9), 5 female) during natural sleep using a Siemens 7T system (MAGNETOM Terra, Siemens Healthineers, Erlangen, DE) and a 1TX-32RX Nova Medical head coil (Wilmington, MA, USA) with locally imposed safety restrictions [6]. A GRE-EPI sequence was used to acquired BOLD fMRI data over 6 m 51 s with parameters: resolution=0.8 mm isotropic (full Fourier), TR/TE=2660/48 ms, 25 slices, 1.06 ms nominal echo spacing, and R=2 acceleration with Dual-Polarity GRAPPA reconstruction [7]. Sensorimotor stimulation (on/off blocks of 26.6 s) was elicited with a custom robotic device [8] (Fig. 1A). After pre-processing using tools implemented in FSL, ROIs spanning the full cortical thickness were manually defined within significant clusters of activation (Z>2) in M1; data were up-sampled; 3 equi-volume layers were defined using LAYNII [9]; and layer-specific BOLD timeseries were extracted, from which normalized trial responses of percent signal change were calculated and then averaged across infants (Fig. 1B-D).
Data were acquired from 10 healthy infants at term equivalent age (median: 39.7 weeks postmenstrual age at scan (range: 37.4–42.9), 5 female) during natural sleep using a Siemens 7T system (MAGNETOM Terra, Siemens Healthineers, Erlangen, DE) and a 1TX-32RX Nova Medical head coil (Wilmington, MA, USA) with locally imposed safety restrictions [6]. A GRE-EPI sequence was used to acquired BOLD fMRI data over 6 m 51 s with parameters: resolution=0.8 mm isotropic (full Fourier), TR/TE=2660/48 ms, 25 slices, 1.06 ms nominal echo spacing, and R=2 acceleration with Dual-Polarity GRAPPA reconstruction [7]. Sensorimotor stimulation (on/off blocks of 26.6 s) was elicited with a custom robotic device [8] (Fig. 1A). After pre-processing using tools implemented in FSL, ROIs spanning the full cortical thickness were manually defined within significant clusters of activation (Z>2) in M1; data were up-sampled; 3 equi-volume layers were defined using LAYNII [9]; and layer-specific BOLD timeseries were extracted, from which normalized trial responses of percent signal change were calculated and then averaged across infants (Fig. 1B-D).
Results:
fMRI data were successfully acquired in 7/10 infants with significant activation identified in the contralateral hand area of M1 in response to sensorimotor stimulation (Fig. 1B).
Trial-averaged responses showed a rise in BOLD signal around 8 s after stimulus onset in the superficial cortical depths (Fig. 1E, F) with a median positive peak of 5.54 % BOLD signal change (Fig. 2B). Conversely, at deeper cortical depths, a subtle initial dip was seen followed by a trend for a delayed rise in BOLD signal and a significantly lower median peak amplitude of 3.08 % signal change (p=0.004) and 1.79 % signal change (p=0.002) in the middle and deep cortical depths respectively (Fig. 2A, B). A trend emerged for a more pronounced post-stimulus undershoot in the BOLD response at superficial cortical depths, but it did not reach significance.
Trial-averaged responses showed a rise in BOLD signal around 8 s after stimulus onset in the superficial cortical depths (Fig. 1E, F) with a median positive peak of 5.54 % BOLD signal change (Fig. 2B). Conversely, at deeper cortical depths, a subtle initial dip was seen followed by a trend for a delayed rise in BOLD signal and a significantly lower median peak amplitude of 3.08 % signal change (p=0.004) and 1.79 % signal change (p=0.002) in the middle and deep cortical depths respectively (Fig. 2A, B). A trend emerged for a more pronounced post-stimulus undershoot in the BOLD response at superficial cortical depths, but it did not reach significance.
Conclusions:
We present the first evidence of differing hemodynamic responses across cortical depths in the neonatal brain, which differ markedly than those typically seen in adults.
This may reflect differences in the vasculature, such as the endothelium of the diving arterioles which dilate first in the deeper cortical depths in adults, propagating vasodilation upstream to the pial surface [5]. As the arteriolar endothelium develops postnatally, propagation likely differs in neonates [1] resulting in a delayed BOLD response in the deeper cortical layers.
The increased functional contrast-to-noise ratio at 7T [10] provides a unique opportunity for detailed in vivo studies of neurovascular coupling and hemodynamics during the critically important perinatal period. This offers new insight into the early development of cortical hemodynamics and a means to explore generalisability of our mechanistic understanding of adult cortical hemodynamics. Future work can investigate how hemodynamics evolve during early development, whether the sleeping state during our task affects hemodynamics, and whether alterations are seen in pathology.
This may reflect differences in the vasculature, such as the endothelium of the diving arterioles which dilate first in the deeper cortical depths in adults, propagating vasodilation upstream to the pial surface [5]. As the arteriolar endothelium develops postnatally, propagation likely differs in neonates [1] resulting in a delayed BOLD response in the deeper cortical layers.
The increased functional contrast-to-noise ratio at 7T [10] provides a unique opportunity for detailed in vivo studies of neurovascular coupling and hemodynamics during the critically important perinatal period. This offers new insight into the early development of cortical hemodynamics and a means to explore generalisability of our mechanistic understanding of adult cortical hemodynamics. Future work can investigate how hemodynamics evolve during early development, whether the sleeping state during our task affects hemodynamics, and whether alterations are seen in pathology.
Lifespan Development:
Normal Brain Development: Fetus to Adolescence 1
Novel Imaging Acquisition Methods:
BOLD fMRI
Physiology, Metabolism and Neurotransmission :
Cerebral Metabolism and Hemodynamics 2
Keywords:
Cortical Layers
Development
FUNCTIONAL MRI
HIGH FIELD MR
Other - Hemodynamics; Neonates
1|2Indicates the priority used for review
Provide references using author date format
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