Introduction

Standard image-based markers do not reflect cerebral small vessel disease (SVD) itself, but rather macroscopic brain damage as a consequence of vessel abnormalities. We developed 7T-MRI methods to directly assess pulsatility and blood-flow velocity in the perforating arteries as hemodynamic parameters, that are potentially useful for evaluating vascular dysfunction in SVD^1,2,3. Previous studies have shown that these parameters are higher in the basal ganglia (BG) in patients with lacunar infarction than in healthy controls⁴. The ability to assess these hemodynamic parameters of the perforating arteries on standard clinical 3T MRI as well, would allow for widespread use in clinical studies regarding SVD. This would accelerate the evaluation of the value of these measurements in research and clinical care. Recent work showed the feasibility of measuring pulsatility in the perforating arteries at the level of the BG using 3T-MRI⁵. However, test-retest measurements have not been performed on 3T MRI, but are necessary for statistical power calculations in future studies.
This study assessed the reliability of 3T-MRI blood-flow velocity measurements in perforating arteries in the BG by performing test-retest scans. Scans were repeated with and without repositioning of the patient to also be able to assess the relative contribution of the planning uncertainty to the measurement errors.

Methods

We included 35 subjects in this study, in order to allow for estimating the standard deviation of the test-retest variability within 20% of its true values with 90% confidence⁶. Subjects were only included if they did not have cerebrovascular disease. The blood-flow velocity of the small perforating arteries of the BG was measured using a previously published velocity encoded 2-dimensional phase contrast (2D-PC) acquisition performed at 3T-MRI with a 32-channel head coil⁵.
The first 2D-PC MRI acquisition (Table 1) was acquired after initial subject positioning. Then, subjects were briefly taken out of the scanner and repositioned after a 5 minute break. After repositioning, a second 2D-PC scan was acquired to assess test-retest reliability with repositioning. A third 2D-PC scan was acquired without repositioning and replanning (Figure 1) for assessing test-retest reliability without repositioning. The 2D-PC images were processed and analyzed as described previously^1,5,7, to assess the number of detected perforating arteries (N_detected), mean blood-flow velocity (V_mean), and velocity pulsatility index (vPI=(V_max-V_min)/V_mean). vPI is obtained from the mean normalized velocity curve over all N_detected. ROIs were manually drawn by two trained independent researchers (RT and SP) to delineate the BG area. Inter-rater agreement was determined based on the first scans of 10 subjects. Similarity of the ROIs was determined by calculating the Dice Coefficient (DC)⁸.

Results

The average DC between the 10 ROIs drawn by RT and SP was 0.90 (range: 0.87-0.93) and the calculated N_detected, V_mean, and vPI using the ROIs of both observers are given in Table 2. The mean and standard deviations of N_detected, V_mean, vPI and heart rate for all subjects are given in Table 3.
Test-Retest reliability with repositioning:
V_mean was similar between first and second 2D-PC scan (6.5±1.0 cm/s and 6.6±1.4 cm/s respectively). vPI decreased from 0.45±0.14 to 0.40±0.17 between the first and second 2D-PC scan although this was not significant (P=0.18). N_detected was the same in both the first scan 8±3, and after repositioning 8±3. Limits of agreement (LoA) after repositioning, expressed as percentage of the mean values were 23±18%, 13±9% and 32±15% for N_detected, V_mean and vPI, respectively.
Test-Retest reliability without repositioning:
Comparing the two acquired 2D-PC images without repositioning, results were very similar between the second scan: N_detected=8±3, V_mean=6.6±1.4 cm/s and vPI=0.40±0.17 and the third scan: N_detected=9±4, V_mean=6.5±0.9 cm/s and vPI=0.41±0.16 (Figure 3). LoA without repositioning, expressed as percentage of the mean values were 24±19%, for 12±10% and 28±17% for N_detected, V_mean and vPI.

Discussion

The analysis tool enabled automatic and reproducible assessment of N_detected, V_mean and vPI in the perforating arteries of the BG, independent of slice planning. Slice planning was done by only one experienced operator (JZ) for all included subjects and did not lead to a significant bias in detection of number of perforating arteries. The found values in the first scan are in line with other 3T studies⁵ for N_detected (8±3 in our study, versus 5±3), Vmean (6.5±1.0 cm/s versus 6.0±1.3 cm/s) and vPI (0.45±0.14 versus 0.49±0.19). Our results are in the same range compared to literature using the LoA for velocity pulsatility for the lenticulostriatal arteries and middle cerebral artery (37% and 40% respectively)⁹ and the BG (38%)¹ using 7T-MRI. Our LoA not comparable with the LoAs of Doppler Ultrasound measurements of the middle cerebral artery pulsatility, which have been reported to be >60% and described as far from satisfactory¹⁰.

Conclusion

This study shows that cerebral perforating artery velocity and pulsatility measurements can be performed at 3T-MRI with reasonable reliability. This confirms that functional vascular parameters in small perforating vessels that are relevant for clinical research, e.g. in SVD, can be measured on 3T. The obtained results can be used to perform power calculations for designing such clinical studies at 3T.

Acknowledgements

We thank all the study participants for their participation.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 841865.

References

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