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Real Time 4D flow MRI assessment of Low Frequency Oscillations in Large Intracranial Vessels at Rest and During Hypercapnia

Kathleen B Miller¹, Leonardo A Rivera-Rivera¹, Oliver Wieben¹, Kevin M Johnson¹, Sterling C Johnson¹, and Jill N Barnes¹
¹University of Wisconsin-Madison, Madison, WI, United States

Synopsis

Low frequency oscillations (LFOs) of cerebral vessels may be important indicators of aging and disease related changes to cerebral autoregulation and glymphatic clearance. Assessing LFOs during a vasodilatory stimulus, such as hypercapnia, may reveal age-associated changes not apparent at rest. This study utilized 3D radial sampling and local low-rank reconstruction of 4D flow MRI scans to achieve real time temporal resolution to assess LFOs. Preliminary results suggest that there were no hypercapnia or age-associated changes in LFOs in the large intracranial arteries; however, there were both age and hypercapnia effects on LFOs in the venous circulation.

Introduction

Analysis of oscillations in the low frequency spectrum (LFOs) in cerebral vessels may be a useful tool to assess cerebrovascular function. Impairments in LFOs have been implicated in carotid artery disease,¹ ischemic stroke, ¹ Alzheimer’s disease ²and aging ³ and may indicate reduced autoregulatory function and glymphatic clearance. ⁴ Commonly used methods to measure LFOs in the cerebral vessels include near-infrared spectroscopy (NIRS) and blood-oxygen level derived (BOLD) functional magnetic resonance imaging (fMRI). However, both techniques are limited by their indirect blood flow measurement derived from oxygenated and deoxygenated hemoglobin. Recently, 4D flow MRI has been utilized to assess LFOs in the large intracranial vessels. ²This technique applies both 3D radial sampling and a local low-rank reconstruction approach to feasibly achieve real time temporal resolution. Using this approach, LFOs have been assessed at rest; however, aging is associated with a reduction in cerebral vasodilatory capacity, ⁵ and age-related changes in LFOs may be more apparent during hypercapnia. The purpose of this study was to evaluate LFOs in both the arterial and venous cerebral vasculature at rest and, for the first time, during hypercapnia using 4D flow MRI. Our exploratory analysis evaluated the effect of primary aging on LFOs parameters.

Methods

This study included 10 healthy participants with low vascular risk (5 young adults, age=24±1, men=3, women=2; 5 middle-aged/older adults, age=62±2, men=3, women=2). Participants were fitted with an MRI compatible facemask with a one-way value to prevent re-breathing. They were instrumented with a pulse oximeter to measure heart rate and oxygen saturation (SPO₂), a nasal cannula to measure end-tidal carbon dioxide (ETCO₂), and a blood pressure cuff to measure mean arterial pressure (MAP). MR imaging was performed with a 3T clinical scanner (MR750, GE Healthcare) with a 32-channel head coil (Nova Medical Head Coil). 4D flow MRI data were acquired using a 3D radially undersampled sequence. ⁶ The scan parameters were as follows: velocity encoding (Venc) = 80 cm/s, FOV = 220 mm, acquired spatial resolution = 0.7 mm isotropic, TR = 7.8 ms, TE = 2.7 ms, flip angle = 8°, bandwidth = 83.3 kHz, 14,000 projection angles and scan time ∼7 min. The first scan was acquired while participants were breathing medical grade normoxic, normocapnic air (baseline). The second scan was acquired while participants were breathing a hypercapnic gas mixture that contained 6% CO₂, 21% O₂ and balanced nitrogen (hypercapnia). The flow encoded images from the 4D flow MRI scans were reconstructed to 100 frames using GPU accelerated iterative SENSE with a local low-rank constraint. ^7–9 Reconstructions were performed with 8x8x8 blocks and a manually tuned regularization parameter. The reconstructed spatial resolution was 1.38mm isotropic and the temporal resolution was approximately 4.3 seconds. Vessel segmentation and LFO analysis was performed offline in MATLAB (Mathworks). ¹⁰ Flow parameters were extracted from both the left and right internal carotid arteries (ICAs) (between the cervical and petrous segments) as well as the posterior, inferior portion of the superior sagittal sinus (SSS). Flow ranges, standard deviations and standard deviation normalized to brain volume were calculated for each vessel. In addition, a Fourier transform was performed on the flow time series. The power spectral density (PSD) was calculated between 0.002 and 0.10 Hz. LFO parameters were compared between baseline and hypercapnia using a 2-tailed paired t-test. The effect of aging on LFO parameters was assessed using a 2-tailed unpaired t-test, alpha <0.05.

Results

Hypercapnia increased flow in the right ICA, left ICA, and the SSS as expected (Figure 1, p<0.05 for all). In the ICAs, there were no effects of hypercapnia on LFO parameters including flow range, flow standard deviation, and low-frequency power (Figure 2, p>0.05 for all). In the SSS, hypercapnia was associated with increased flow range (p<0.01), increased flow standard deviation (p<0.001), and a trend for decreased average low-frequency power (p=0.06; Figure 3). Results were similar when flow standard deviation was normalized to brain volume. There were no age-related differences in LFO parameters in the right and left ICAs at baseline or hypercapnia (p>0.05). However, there was a trend for smaller flow range (p=0.06), smaller flow standard deviation (p=0.08), and lower low-frequency power (p=0.08) in the SSS at baseline in middle-aged/older adults compared with young adults (Figure 4). There were no age-related differences in LFO parameters of the SSS during hypercapnia (p>0.05 for all).

Discussion and Conclusions

We observed no change in LFOs from baseline to hypercapnia in the arterial system (ICAs). However, hypercapnia caused changes in LFO parameters in the venous system (SSS) including an increase in flow variations and a trend of reduced LFO power. Because flow in the SSS is sensitive to changes in MAP and respiration, our results suggest that LFO changes during hypercapnia may be related to systemic, rather than cerebral, factors. We also observed a trend for an age-related reduction in LFO parameters in the SSS at baseline. This suggests that primary aging may be associated with changes in LFOs in the venous circulation. Future work is needed to determine the mechanisms by which hypercapnia may induce changes in 4D flow based LFOs.

Acknowledgements

We acknowledge funding support from the Wisconsin Alumni Research Foundation (JNB), NIH grants HL118154 (JNB), NS117746 (JNB), and Alzheimer's Association grant AARFD-20-678095s (LARR).

References

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Figures

Figure 1 shows box plots of the flow in the right internal carotid artery (R-ICA), left internal carotid artery (L-ICA), and superior sagittal sinus (SSS) at baseline and during hypercapnia (n=10). The baseline condition is shown in white and the hypercapnic condition is shown in black. As expected, hypercapnia significantly increased flow in all three vessels.

Figure 2 shows box plots of the flow standard deviation (stdev) and the average low-frequency power measured in the right internal carotid artery (R-ICA, top) and the left internal carotid artery (L-ICA, bottom) (n=10). The baseline condition is shown in white and the hypercapnic condition is shown in black. There were no differences between baseline and hypercapnic conditions in either of the low-frequency oscillation parameters.

Figure 3 shows box plots of the flow standard deviation (stdev) and the average low-frequency power measured in the superior sagittal sinus (SSS) (n=10). The baseline condition is shown in white and the hypercapnic condition is shown in black. Hypercapnia was associated with a significant increase in flow standard deviation. There was also a trend for lower, low-frequency power in the hypercapnic condition compared with baseline.

Figure 4 shows box plots of the flow standard deviation (stdev) and the average low-frequency power measured in the superior sagittal sinus (SSS) at baseline. Young adults (n=5) are shown in white and middle-age/older adults (n=5) are shown in dashed blue lines. There was a trend for middle-age/older adults to demonstrate a smaller flow standard deviation, and lower, low-frequency power compared with young adults.

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)

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