What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Alzheimer's disease (n=112). Intervention: Alzheimer's disease vs. Age-matched healthy controls. Primary outcome: Low frequency flow oscillations (LFOs) measured from flow variation range in the internal carotid artery (p=0.005).

What does this research mean for the field?

Patients with Alzheimer's disease exhibit significantly lower low-frequency flow oscillations in intracranial arteries compared to healthy controls, indicating altered vascular function. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 1, 2020Open Access

Intracranial vascular flow oscillations in Alzheimer’s disease from 4D flow MRI

Key Result

Alzheimer's disease was associated with significantly lower low frequency flow oscillations in the internal carotid artery compared to age-matched controls (P=0.005 for flow range).

Study Design

Type

Cross-Sectional (n=112)

Multicenter

Structured PICO

Does 4D flow MRI detect altered intracranial vascular low frequency flow oscillations in patients with Alzheimer's disease compared to healthy controls?

Population

112 participants, including 23 with Alzheimer's disease and 89 healthy controls (mean age 66 years, 68% female), underwent 4D flow MRI to assess intracranial vascular flow oscillations.

Exposure

4D flow MRI (time-resolved 3D phase contrast MRI) reconstructed using a low-rank temporal constraint to measure low frequency flow oscillations (LFOs)

Comparator

Age-matched cognitively healthy controls and other healthy cohorts (for clinical comparison); standard 2D phase contrast (PC) MRI (for phantom and volunteer validation)

Outcome

Low frequency flow oscillations (LFOs) quantified from flow range, standard deviation, demeaned temporal flow changes, and power spectral density in intracranial arteries and veinssurrogate

4D flow MRI demonstrates that Alzheimer's disease is associated with significantly reduced intracranial vascular low frequency flow oscillations, suggesting altered vascular function and potentially impaired metabolite clearance.

Main Result

p-value: p=0.005

Limitations

Material and arterial/vein compliance matching was not considered in the physical model experiments.
Spatial resolution was traded for higher temporal binning (1.38 mm isotropic), limiting analysis to relatively large arteries.
Lack of bulk motion correction methods to improve time-resolved imaging reproducibility.
Did not explore potential effects from breath-to-breath variations on 4D flow-based LFO measurements.
Cannot entirely rule out that observed deficits in LFOs are partially driven by impairment in vascular tone attributed to concomitant cerebral small vessel disease.
Temporal resolution (4.30 sec) was insufficient to distinguish delayed transit times from the internal carotid artery to the superior sagittal sinus.

Abstract

Recent modeling and experimental evidence suggests clearance of soluble metabolites from the brain can be driven by low frequency flow oscillations (LFOs) through the intramural periarterial drainage (IPAD) pathway. This study investigates the use of 4D flow MRI to derive LFOs from arterial and venous measures of blood flow. 3D radial 4D flow MRI data were acquired on a 3.0 T scanner and reconstructed using a low-rank constraint to produce time resolved measurements of blood flow. Physical phantom experiments were performed to validate the time resolved 4D flow against a standard 2D phase contrast (PC) approach. To evaluate the ability of 4D flow to distinguish physiologic flow changes from noise, healthy volunteers were scanned during a breath-hold (BH) maneuver and compared against 2D PC measures. Finally, flow measures were performed in intracranial arteries and veins of 112 participants including subjects diagnosed with Alzheimer's disease (AD) clinical syndrome (n = 23), and healthy controls (n = 89) on whom apolipoprotein ɛ4 positivity (APOE4+) and parental history of AD dementia (FH+) was known. To assess LFOs, flow range, standard deviation, demeaned temporal flow changes, and power spectral density were quantified from the time series. Group differences were assessed using ANOVA followed by Tukey-Kramer method for pairwise comparison for adjusted means (P < 0.05). Significantly lower LFOs as measured from flow variation range and standard deviations were observed in the arteries of AD subjects when compared to age-matched controls (P = 0.005, P = 0.011). Results suggest altered vascular function in AD subjects. 4D flow based spontaneous LFO measures might hold potential for longitudinal studies aimed at predicting cognitive trajectories in AD and study disease mechanisms.

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