2004
Leveraging ASL Perfusion to Unravel Neural Activation in the Olfactory Bulb: A Proof of Concept1Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States, 2Siemens Medical Solutions USA Inc, Malvern, PA, United States, 3Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 4Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 5Department of Psychology, School of Arts and Science, University of Pennsylvania, Philadelphia, PA, United States
Synopsis
Keywords: Arterial Spin Labelling, fMRI
Motivation: The olfactory bulbs (OBs) play a key role in the detection and processing of olfactory information. However, research on human OB function has been limited due to their challenging location for conventional T2*-weighted BOLD fMRI.
Goal(s): To explore ASL as an alternative to BOLD for OB functional MRI.
Approach: We utilized ASL with a 16-shot Stack-of-Spirals 3D TSE readout to obtain short-TE functional imaging. We quantified blood flow and subsequently assessed neural activation in the OB using a blocked design olfactory paradigm.
Results: This study quantifies OB blood flow for the first time and demonstrates neural activation in the OB during odor delivery.
Impact: This work highlights ASL's potential for fMRI, especially in challenging areas with high susceptibility and low signal-to-noise ratio, making it a viable option for studying olfactory-related regions where BOLD fMRI faces difficulties.
Introduction
Olfactory bulbs (OBs) exhibit distinct neural activity compared to other primary olfactory regions in animal studies. However, human OB research faces limitations with conventional gradient-echo EPI (GE-EPI) BOLD fMRI due to their small size and location in a region of large static susceptibility artifacts1.Arterial Spin Labeling (ASL) offers an alternative for functional imaging allowing direct measurement of neurovascular coupling. Using background-suppressed (BS) 3D TSE-based readouts with spiral trajectories, ASL has demonstrated functional sensitivity in low signal-to-noise ratio and high susceptibility regions2–5.
In this pilot study, we evaluate ASL’s potential for studying OB function. A volumetric ASL sequence was optimized to minimize susceptibility artifacts and achieve high spatial resolution. We provide a first report of resting blood flow in the OB and measured neural activation during odor delivery.
Method
MRI AcquisitionStructural imaging was performed using a 1 mm isotropic T1-weighted MPRAGE and 0.8 mm isotropic slab-selective T2-weighted SPACE6,7.
For ASL imaging, we used a prototype sequence combining an optimized background-suppressed unbalanced PCASL preparation (labeling duration 3 s, post-labeling delay 1.2 s, Gmax/Gav = 3.5/0.5 mT/m, flip angle = 22.5°, 95% BS) with a highly interleaved slice-accelerated 3D Stack-of-Spirals (SoS) TSE readout (16 shots, TR/TE=5500/6.5ms, 60 slices, 2 mm isotropic resolution)8.
Resting perfusion was measured using 5 label/control pairs and two reference volumes for absolute blood flow quantification in 17.6 minutes.
For the activation study, 12 volumes of perfusion-weighted label-only data were acquired using the same parameters every 88 seconds for a total scan time of 20.5 minutes.
fMRI Experimental Paradigm and Stimuli
The fMRI sessions comprised four blocks (264 seconds/block), alternating between the control (mineral oil) and odorant stimulus (lemon oil extract) (Figure 1). Odor intensity ratings were collected every 12 seconds.
Subject
Three subjects, having given informed consent, were scanned at 3 T (MAGNETOM Prisma, Siemens Healthineers, Erlalngen, Germany) with the vendor's 64-channel head/neck coil.
Data Analysis
Individual OBs were manually segmented based on T2-weighted images, serving as the region of interest (ROI) for subsequent analysis.
After motion-correction, pairwise subtraction and averaging, OB blood flow was calculated using a single-compartment model with resting-state data9–11.
To examine activation during odor stimulation, ASL data were analyzed using a generalized linear model with the odor condition as the predictor. To further assess whether OB is activated during stimulation, a one-sample t-test (H0: β = 0, H1: β > 0) was conducted by extracting the estimated parameter β within the OB.
Results
Optimized ASL protocol detects perfusion signals in the OBFigure 2 shows anatomical images along with conventional GE-EPI and ASL images for the same subject. While GE-EPI does not capture any signal within OB due to the large static susceptibility, signal within OB can be seen in ASL images acquired with the 3D-SoS-TSE. When examining the ASL perfusion difference, a consistent signal could be detected in the OB.
OB blood flow can be measured with ASL
Resting blood flow was quantified within the OB for all 3 subjects (Figure 3b). While this study represents the first reported measurement of OB blood flow, the obtained values fell between gray and white matter CBF, suggesting that the OB may comprise both gray and white matter12,13.
OB activation can be detected using the optimized ASL protocol
All 3 subjects exhibit a cluster of positive β in the OB (mean β = 0.15, 1.21, 12.87) [Figure 3c]. While subject 1 (p = 0.48) and subject 2 (p = 0.27) did not reach statistical significance, subject 3 (p < 0.001) showed significant activation. Post-hoc power analysis revealed subject 1 (power = 0.05) and subject 2 (power = 0.14) were underpowered while subject 3 (power = 0.99) had adequate power due to differences in their OB volumes.
Discussion & Conclusion
In this study, we investigated OB neural activation during odor stimulation using ASL with a 3D SoS TSE readout. We optimized labeling and readout for perfusion sensitivity while minimizing susceptibility and T2-decay effects. We quantified resting OB blood flow for the first time and demonstrated the correlation between OB perfusion signal and odor stimulation.The small size of the olfactory bulb poses challenges in ROI definition from anatomical scans and resulted in underpowered statistical estimates as observed in subjects 1 and 2. Improved anatomical imaging, as well as additional ASL sequence optimizations will be performed to improve spatiotemporal resolution using 3D spiral acceleration3.
In conclusion, these results show that ASL offers a promising approach for investigating human olfactory-related regions, including the OBs and the orbitofrontal cortex, where BOLD fMRI faces challenges. Additionally, it elucidates direct neurovascular coupling and provides quantitative measurements.
Acknowledgements
This work was supported by the National Institutes of Health awards R01EB031080 [awarded to JAD] and R01DC019405 [awarded to JAG].References
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Figures
Figure 1. fMRI Experimental Paradigm. The paradigm consists of four blocks, each lasting 264 seconds. In the odor blocks, lemon oil extract diluted in mineral oil was delivered, while in the control blocks, mineral oil was delivered. Odor intensity ratings were collected every 12 seconds.
Figure 3. Measured Blood Flow at Resting-state and Estimated β for Correlation between Odor Condition and ASL signal. a) A representative coronal slice containing the ROI (OB) in T2-weighted anatomical images. OB is highlighted in red. b) Measured OB blood flow (mean ± 95% CI) and the number of voxels (n) within the OB (highlighted in green) for all three subjects. c) Estimated β for correlation between odor condition and ASL signal for all three subjects. OB is highlighted in white.