MRI evaluation of cerebrovascular reactivity in obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is characterized by intermittent obstruction of the airways during sleep. Cerebrovascular reactivity (CVR) is an index of cerebral vessels' ability to respond to a vasoactive stimulus, such as increased CO₂. We hypothesized that OSA alters CVR, expressed as a breath-hold index (BHI) defined as the rate of change in CBF or BOLD signal during a controlled breath-hold stimulus mimicking spontaneous apneas by being both hypercapnic and hypoxic. In 37 OSA and 23 matched non sleep apnea (NSA) subjects, we obtained high temporal resolution CBF and BOLD MRI data before, during, and between five consecutive BH stimuli of 24 s, each averaged to yield a single BHI value. Greater BHI was observed in OSA relative to NSA as derived from whole-brain CBF (78.6 ± 29.6 vs. 60.0 ± 20.0 mL/min²/100 g, P = 0.010) as well as from flow velocity in the superior sagittal sinus (0.48 ± 0.18 vs. 0.36 ± 0.10 cm/s², P = 0.014). Similarly, BOLD-based BHI was greater in OSA in whole brain (0.19 ± 0.08 vs. 0.15 ± 0.03%/s, P = 0.009), gray matter (0.22 ± 0.09 vs. 0.17 ± 0.03%/s, P = 0.011), and white matter (0.14 ± 0.06 vs. 0.10 ± 0.02%/s, P = 0.010). The greater CVR is not currently understood but may represent a compensatory mechanism of the brain to maintain oxygen supply during intermittent apneas.

Keywords: BOLD; breath-hold index; cerebrovascular reactivity; obstructive sleep apnea; radial phase-contrast MRI.

Figure 1.

Volitional apneic paradigm and MR protocol. (a) The apnea paradigm consisted of five BH periods and 66 s of normal breathing. Blue boxes indicate 24-s instructed breath-holds. (b) Time of flight MR projection angiogram, T₁-weighted MPRAGE and interleaved PC-MRI were acquired for slice prescription, brain segmentation and calibration ratio, respectively. Reconstructed radial PC-MRI to generate time-course of SSS velocity, and BOLD images for evaluation of response to volitional apnea. Two 24-s practice apneas were included in the protocol prior to 10 min of continuous scanning.

Figure 2.

Whole-brain data: (a) BHI expressed as temporal change in tCBF (left) and SSS flow velocity (right), based on phase-contrast flow velocity measurements. Subjects with OSA (red) had a significantly greater BHI derived from tCBF (79 vs. 60 mL/min²/100 g, P = 0.010) and from flow velocity (0.48 vs. 0.36 cm/s², P = 0.014). (b) Neither the flow upscaling calibration factor nor the brain mass were significantly different between groups.

Figure 3.

Temporal response to intermittent 24-s BH challenges in a patient with OSA (AHI = 28) and BOLD-derived BH indices. (a) BOLD signal (%) averaged across the whole brain, gray matter and white matter; (c) tCBF (mL/min/100 g brain) and SSS flow velocity (cm/s). (b, d) Temporal averages of time-course data in (a, c), with dashed lines representing calculated slopes yielding BHI. Shaded area represents apneic period. (e) BHI maps derived from BOLD for three imaging slices from the same OSA patient and a representative NSA subject. (f) BHI for OSA subjects (red) and NSA reference subjects (green) pertaining to whole brain, GM, and WM. Greater BH indices in OSA were significant in all three brain regions.

Figure 4.

Spontaneous apneas in a patient with severe apnea (AHI=80.5 events/h). The patient was unable to stay awake and adhere to the breath-hold instructions, showing quasi-periodic fluctuations: (a) computed for total CBF and SSS velocity; (b) regional BOLD response.