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Assessment of cerebral perfusion autoregulation impairment – An experimental setup to quantify regional cerebral blood flow (CBF) in normal and head down tilt position1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States, 2Health Sciences Fabrication Shop, Department of Medicine,Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States, 3MRI Clinical and Translational Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States, 4Department of Psychiatry,Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States, 5Department of Orthopedics,Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States
Synopsis
Previous studies using Transcranial Doppler have shown that cerebral ischemia, head trauma, and cerebral perfusion pressure are associated with an impairment of the cerebral autoregulation (CA) and alteration of perfusion. However, simulating perfusion changes and quantifying them with higher specificity repetitively has been a challenge in clinics. We propose a clinical experimental setup for an MRI-based head down tilt protocol to study the CA by quantifying perfusion. We demonstrate local perfusion change results in healthy controls and a patient.
Purpose:
Cerebral autoregulation (CA) ensures the constancy of the cerebral blood flow (CBF). Using Transcranial Doppler (TCD), previous studies have shown that cerebral ischemia, head trauma, and cerebral perfusion pressure are associated with an impairment of the CA and alteration of local CBF1-5. These studies motivate the use of CA and CBF measurements as clinical biomarkers for these pathologies. Although TCD is highly sensitive, it lacks specificity and is highly operator-dependent6,7.
Here, we present a clinically applicable experimental setup for MRI-based head-down tilt (HDT) measurements of CA. The HDT experiment assesses the CA by quantifying perfusion at different body positions in one patient with a sub-acute concussion and two healthy controls (HCs).
Method:
Experimental setup: A primary design objective for the HDT setup was that the experiment could be performed by the MRI technologist. A schematic illustration of the setup is shown in Figure-1, which consisted a special patient table that was placed on vendor’s original patient bed and could be inclined at the foot-end during an MRI session while the patient was inside the magnet. High-density polyethylene (HDPE) sheets (19mm thickness) provided sufficient stability at a minimal added vertical height of the bed at the head-end to use a vendor-provided head coil with limited cable length. An inflatable 42L polyvinylchloride airbag was placed between two HDPE-sheets, which was connected via thermoplastic rubber pipes and a custom pressure valve system (HDPE tee-valves) to a compressed air cylinder in the control room. Opening the valve raised the wedge within 1-2 minutes to 6˚, an angle that was chosen based on physiological studies on CA in HCs17-19,24,23.
Experiment: The setup was tested in 2 HCs (29 and 38 years; male) and 1 patient (15 years; female) with a post-acute concussion (IRB approved) at 3T (Toshiba Vantage Titan) using a 32 channel brain coil in supine(0˚)-incline(6˚)-supine(0˚) positions. CBF was measured using the ASTAR pulsed ASL (pASL) sequence14,15,16 with a 3D Swirl-SSFP readout (QUIPPSII16;BW=977Hz/px, TE/TR/TI/TTEC=2/2800/2000/800ms, Nsaturation=3, Navg=4, FOV=26x26x10.4cm3, matrix=64X64x13, 15cm tag thickness with 2cm gap, 10cm TEC thickness, TScan=5:22min:sec) and a PDw sequence (TScan=41sec). First, we studied the reproducibility by applying three times ASL (PDw once) in 0° (Figure-2a). To study the temporal dynamics of CBF at 6˚ (Fig.-2b), the airbag was inflated (opening V1 in Figure-1) and immediately the ASL were acquired four times (PDw once). Finally, we emptied the airbag (opening V2; Fig.-2a), and measured CBF recovery dynamics with four ASL at 0°. A high-resolution T1-weighted anatomical scan (TE/TR/TI=3.2/6.2/900ms, FOV=25.6x25.6x19.2cm3, matrix=256x256x192, TScan=5.59min) was acquired before the first ASL sequence for a region-based analysis of CBF maps and localized shimming was applied in each positions.
Data Analysis: ASL and PDw images were reconstructed in absorption-mode from k-space using coil sensitivity maps and registered22 to the T1w images. Voxel-wise division of ASL tag-control images by the PD and application of appropriate scaling factors (T1blood=1650ms26, λ=0.9ml/g27, 98% labeling efficiency16; T1-correction with T1GM=1300ms) yielded the CBF 16. A probabilistic MNI atlas21,28 was applied to determine average CBF values in gray matter (GM), whole brain, white matter, insular GM, parietal lobe GM, occipital lobe GM, and brain stem.
Results:
Mean CBF values were significantly different between the three positions (p<0.001) in HCs, with reduced CBF in the 6° position compared to 0° (Fig. 3a). The patient showed an overall increased average CBF compared to controls (Fig.3a,b),and a sharply increasing CBF was noticed immediately following the inclination (scan 4; Fig. 3b; blue), whereas CBF declined in HC1 and remained stable in HC2 (Fig. 3b; yellow/red). The initial CBF increase in the inclined patient was followed by a rapid decline to the baseline in the following three ASL measurements. Upon return to the normal supine position, another sharp increase was observed in the patient.Discussion:
We presented an experimental setup that allows performing HDT experiments in an MRI scanner without repositioning of the subject, as it was required in previous HDT experiments25. While CBF was relatively static in HCs (or decreased at 6°) due to an intact CA, CBF increased in the patient after every position change, followed by a rapid decline (over 15 minutes) to the baseline, in line with a less efficient CA compared to controls. While these findings need to be systematically confirmed in a larger group, the rapid change of CBF in the patient after position changes may allow clinical measurements of the CA with only one ASL scan in each position, limiting scan time and patient discomfort.Conclusion:
The presented HDT-setup sets the foundation for clinically feasible measurements of the CA.Acknowledgements
Research reported in this publication was funded by Toshiba Medical Systems Corporation, the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001412, and the National Institute of Neurological Disorders & Stroke under Award Number R01NS094444. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.References
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