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. 2021 Mar 18;18(1):12.
doi: 10.1186/s12987-021-00246-3.

In vitro evaluation of cerebrospinal fluid velocity measurement in type I Chiari malformation: repeatability, reproducibility, and agreement using 2D phase contrast and 4D flow MRI

Gwendolyn Williams  1 , Suraj Thyagaraj  2 , Audrey Fu  3 , John Oshinski  4 , Daniel Giese  5 , Alexander C Bunck  5 , Eleonora Fornari  6 , Francesco Santini  7   8 , Mark Luciano  9 , Francis Loth  2 , Bryn A Martin  10   11
Affiliations
Free PMC article

In vitro evaluation of cerebrospinal fluid velocity measurement in type I Chiari malformation: repeatability, reproducibility, and agreement using 2D phase contrast and 4D flow MRI

Gwendolyn Williams et al. Fluids Barriers CNS. .
Free PMC article

Abstract

Background: Phase contrast magnetic resonance imaging, PC MRI, is a valuable tool allowing for non-invasive quantification of CSF dynamics, but has lacked adoption in clinical practice for Chiari malformation diagnostics. To improve these diagnostic practices, a better understanding of PC MRI based measurement agreement, repeatability, and reproducibility of CSF dynamics is needed.

Methods: An anatomically realistic in vitro subject specific model of a Chiari malformation patient was scanned three times at five different scanning centers using 2D PC MRI and 4D Flow techniques to quantify intra-scanner repeatability, inter-scanner reproducibility, and agreement between imaging modalities. Peak systolic CSF velocities were measured at nine axial planes using 2D PC MRI, which were then compared to 4D Flow peak systolic velocity measurements extracted at those exact axial positions along the model.

Results: Comparison of measurement results showed good overall agreement of CSF velocity detection between 2D PC MRI and 4D Flow (p = 0.86), fair intra-scanner repeatability (confidence intervals ± 1.5 cm/s), and poor inter-scanner reproducibility. On average, 4D Flow measurements had a larger variability than 2D PC MRI measurements (standard deviations 1.83 and 1.04 cm/s, respectively).

Conclusion: Agreement, repeatability, and reproducibility of 2D PC MRI and 4D Flow detection of peak CSF velocities was quantified using a patient-specific in vitro model of Chiari malformation. In combination, the greatest factor leading to measurement inconsistency was determined to be a lack of reproducibility between different MRI centers. Overall, these findings may help lead to better understanding for application of 2D PC MRI and 4D Flow techniques as diagnostic tools for CSF dynamics quantification in Chiari malformation and related diseases.

Keywords: Cerebrospinal fluid; Chiari malformation; Magnetic resonance imaging; Phase contrast; Spinal cord.

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Conflict of interest statement

BAM is a full-time employee at Alcyone Therapeutics and has received grant support from Genentech, Minnetronix Neuro, Biogen, Voyager Therapeutics, and Alcyone Therapeutics. BAM is scientific advisory board member for Anuncia Inc., Alcyone Therapeutics Inc., International Society for Hydrocephalus and CSF Disorders, and the Chiari and Syringomyelia Foundation and has served as a consultant to Roche, InviCRO, Praxis Medicines, SwanBio Therapeutics, Cerebral Therapeutics, Minnetronix Medical, Genentech and CereVasc. DG is a full-time employee of Siemens Healthcare since December 2018. All of the work related to the current study was performed prior and / or outside of his duties at Siemens.

Figures

Fig. 1
Fig. 1
Summary of the average peak CSF velocities reported in 2D PC MRI (a) and 4D PC MRI (b) literature for healthy subjects and Chiari malformation patients pre-decompression surgery. Average values in figure are weighted by number of subjects within each study. Error bars represent pooled reported standard deviation for studies included in each group. The total number of healthy and Chiari malformation patient studies included is 91 and 166, respectively (see Table 1 for individual values). FM = foramen magnum
Fig. 2
Fig. 2
a Development of in vitro models based on subject specific scans. First, subjects were scanned to produce a T2 anatomical MRI and a 4D Flow MRI. The anatomical MRI was then used as a basis for the 3D model. The 4D Flow MRI allows the determination of the cerebrospinal fluid (CSF) flow waveform which informs a computer-controlled pump. The model is then connected to the pump and scanned at each MRI center. b Cross section of the completed model. A = anterior, P = posterior, S = superior, I = inferior
Fig. 3
Fig. 3
Axial positions of 2D PC MRI and 4D Flow MRI velocity measurements with flow inlets and outlets indicated. Distance between imaging planes can be found in Table 4. A = anterior, P = posterior, S = superior, I = inferior
Fig. 4
Fig. 4
Bland–Altman plot showing agreement between 2D PC MRI and 4D Flow measurements; the trendline of the data is indicated by the black line, the mean of the differences is shown in blue, and the mean ± 2STD is indicated by the red lines
Fig. 5
Fig. 5
Box plot showing the difference between average velocity measurement at each axial location and each individual axial velocity measurements at each center. Top and bottom of boxes indicate 25th and 75th percentile of values with horizontal lines indicating the median of each value set and outliers represented as red cross marks
Fig. 6
Fig. 6
a Peak systolic 2D PC MRI CSF velocity at each axial position for each center. b Peak systolic 4D Flow CSF velocity at each axial position for each center. Error bars shown represent standard deviation
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