Simon Lévy1,2,3,4, Pierre-Hugues Roche4,5, and Virginie Callot1,2,4
1Aix-Marseille Univ, CNRS, CRMBM, Marseille, France, 2APHM, Hopital Universitaire Timone, CEMEREM, Marseille, France, 3Aix-Marseille Univ, IFSTTAR, LBA, Marseille, France, 4iLab-Spine International Research Laboratory, Marseille-Montreal, QC, France, 5Neurosurgery Department, APHM, Hopital Nord, Marseille, France
Synopsis
The
performance of Dynamic Susceptibility Contrast imaging at 7T for spinal cord
perfusion mapping within clinical constraints was investigated. A cardiac-gated
spin-echo EPI sequence with 0.7x0.7mm2 in-plane resolution was used
in one healthy volunteer and two Cervical Spondylotic Myelopathy patients. Relative
blood volume and flow maps successfully revealed the higher perfusion of gray
matter versus white matter for the volunteer and one patient. Results were limited
for the patient with greater functional impairment and disadvantageous
acquisition conditions. Although human spinal cord perfusion has never been
mapped as precisely, several issues remain to address (image distortions, Specific-Absorption-Rate
limitations, Arterial Input Function).
Introduction
Spinal
cord (SC) compressions occurring in Cervical Spondylotic Myelopathy (CSM)
patients may result in local reduction of tissue perfusion, progressive
ischemia and potentially irreversible tissue damage. Reliable assessment of SC
perfusion would be highly valuable to neurosurgeons in the process of decision and design of decompression surgery. However, it has not been achieved within clinical
constraints yet. The main challenges to tackle are low perfusion levels (similar
as in brain)1–3, a small cross-sectional area (13x8mm2)
and large fluctuating B0 inhomogeneities and SC motion with breathing
and cerebrospinal fluid pulses. Previous work investigated the Intra-Voxel
Incoherent Motion (IVIM) technique for mapping SC perfusion in-vivo1. However, acquisition time required
for reliable individual mapping was too long to fit in clinical routine and to
deal with patient motion, more likely to occur than with healthy volunteers.
Today, the most widely used technique in clinics for brain perfusion exams
remains Dynamic Susceptibility Contrast (DSC) imaging with gadolinium bolus
injection, due to its short scan time and high sensitivity. To deal with the high
resolution needed in the human SC, 7T MRI is now an attractive clinical avenue,
given the increased susceptibility effects of gadolinium4–6 and higher signal-to-noise ratio compared to 3T. In
this work, we investigated the performance of DSC at 7T for assessing SC
perfusion of CSM patients within clinical constraints.Materials & Methods
Data acquisition. Acquisitions
were performed on a 7T whole-body system (Siemens Healthcare) using an
8-channel transceiver cervical spine coil array (Rapid Biomedical). Two-dimensional spin-echo
EPI was preferred over 2D gradient-echo EPI for its robustness to B0
inhomogeneity. The product sequence was modified to: (1) compress acquisition
at the beginning of TR (quiescent period of cervical SC and cerebrospinal fluid7,8), (2) record pulse oximeter and respiratory belt
signals with acquisition timestamps for post-processing corrections.
The protocol included anatomical imaging (sagittal
turbo spin-echo for vertebral levels localization, transversal multi-echo gradient-echo
for gray matter (GM) depiction), as well as B1+ and B0
mapping sequences. The DSC acquisition consisted of 3 transversal slices (0.7x0.7mm2
in-plane, 5-mm thick, matrix=136x136, TE=42ms, GRAPPA 2, partial-k=6/8) positioned
at mid-C2, C3 and C4 levels (Fig.1) in order to image in an area where the coil
transmit field remained homogeneous and efficient for most subjects. Temporal
resolution was defined by cardiac beat. Fifty repetitions were acquired for baseline
signal estimation and 170 during and after injection of Dotarem (Guerbet, 0.2mL/kg,
5mL/s, 30mL saline flush).
So far, the protocol was performed on one healthy
control (HC) and two CSM patients (CSM1, CSM2). Their functional status was
assessed with the modified Japanese Orthopaedic Association (mJOA) scale9.
Data
processing.
Data were denoised with nonlocal transform-domain filter10,
Gibbs artifacts were removed using sub-pixel
shifting method11,
rigid motion across time was corrected using ANTs12
and distortion correction was applied using Topup13
with an additional phase-encoding reversed acquisition. Signal was corrected for
effective TR and B1+. Given the effect of breathing on
signal (Fig.2), a band-stop filter (Butterworth), with minimum and maximum
breathing frequencies as cut-off, and a final smoothing (Savitzky-Golay filter)
were applied voxel-wise along time. Concentration curve was then fitted with a gamma-variate
function. Area under the curve was calculated to obtain relative Blood Volume (rBV)
maps.
With perspectives of
absolute quantification, potential Arterial Input Functions (AIF) were studied
in 3 regions: Anterior and Posterior
Spinal Arteries (ASA, PSA) and left vertebral artery. The selected AIF14 in ASA region was used for
deconvolution by block-circulant Singular Value Decomposition15, but since AIF was not consistent for all
subjects, blood flow maps were normalized by the mean value in GM (all
slices) for each subject to obtain relative Blood Flow (rBF) maps.Results & Discussion
Breathing
was correlated with the image displacement along the phase-encoding direction
as measured by the motion correction algorithm (Fig.2a-b), in agreement with the
breathing-induced frequency shift reported in SC16–18. However, a
relation between breathing and mean signal in SC still existed after motion
correction, suggesting an effect on frequency dispersion as well (Fig.2c-d).
Gadolinium
first pass could be observed on the 3 slices for HC and CSM1 (Fig.3). It was
less visible in CSM2, probably due to an accumulation of disadvantageous
conditions (32% of available signal used due to Specific-Absorption-Rate
limitations, large motion during acquisition, larger B0
inhomogeneity). Despite the B1+ normalization, peak
amplitude decreased with lower level.
rBV and rBF maps revealed
higher values within GM compared to white matter (WM) for all slices (Fig.4), in
agreement with normal perfusion distribution in human brain19,20 and mice SC3,21. However, comparison between HC and CSM patients
could not be carried out further because extracted AIF was not consistent (too
wide or late compared to tissue curve, Fig.5) to allow absolute quantification,
and percentage of available signal used was unequal across subjects (Fig.1).Conclusion & Perspectives
This
is, to our knowledge, the first DSC study at 7T. Perfusion maps discriminating
between SC WM and GM perfusion on single-slice and single-subject basis were successfully
obtained, included in patients with large Body Mass Index. However, this study remains
investigative. Several issues related to ultrahigh field (B1+,
image distortions, Specific-Absorption-Rate limitations) and to SC (AIF
extraction) still need to be addressed to compare perfusion maps across
subjects. More subjects will be included shortly.Acknowledgements
The authors would like to particularly thank Stanislas
Rapacchi and Tangi Roussel for useful discussions, as well as Lauriane Pini,
Claire Costes, Patrick Viout, Véronique Derderian and Christophe Vilmen for
study logistics.
This project has
received funding from the European Union’s Horizon 2020 research and innovation
program under the Marie Skłodowska-Curie grant agreement No713750. It has been
carried out with the financial support of the Regional Council of
Provence-Alpes-Côte d’Azur and of the A*MIDEX (n° ANR-11-IDEX-0001-02, 7T-AMI-ANR-11-EQPX-0001,
A*MIDEX-EI-13-07-130115-08.38-7T-AMISTART), funded by the Investissements
d'Avenir project funded by the French Government, managed by the French
National Research Agency (ANR). Finally, it was conducted within a laboratory member of FLI
network (grant ANR-11-INBS-0006).
References
1. Lévy,
S. et al. Intra-Voxel Incoherent Motion at 7T to quantify human spinal
cord microperfusion: pitfalls and promises. in Proceedings of the 27th
annual meeting of the International Society for Magnetic Resonance in Medicine
0301.
2. Helenius,
J. et al. Cerebral hemodynamics in a healthy population measured by
dynamic susceptibility contrast MR imaging. Acta Radiologica 44, 538–546
(2003).
3. Duhamel,
G., Callot, V., Cozzone, P. J. & Kober, F. Spinal cord blood flow
measurement by arterial spin labeling. Magnetic Resonance in Medicine 59,
846–854 (2008).
4. Shen,
Y. et al. T1 Relaxivities of Gadolinium-Based Magnetic Resonance
Contrast Agents in Human Whole Blood at 1.5, 3, and 7 T. Investigative
Radiology 50, 330–338 (2015).
5. Noebauer-Huhmann,
I. M. et al. Gadolinium-Based Magnetic Resonance Contrast
Agents at 7 Tesla: In Vitro T1 Relaxivities in Human Blood Plasma. Investigative
Radiology 45, 554–558 (2010).
6. Noebauer-Huhmann,
I. M. et al. MR Contrast Media at 7Tesla - Preliminary Study on
Relaxivities. in Proceedings of the 16th annual meeting of the International
Society for Magnetic Resonance in Medicine 1457 (2008).
7. Figley,
C. R. & Stroman, P. W. Investigation of human cervical and upper thoracic
spinal cord motion: Implications for imaging spinal cord structure and
function. Magnetic Resonance in Medicine 58, 185–189 (2007).
8. Figley,
C. R., Yau, D. & Stroman, P. W. Attenuation of Lower-Thoracic, Lumbar, and
Sacral Spinal Cord Motion: Implications for Imaging Human Spinal Cord Structure
and Function. American Journal of Neuroradiology 29, 1450–1454
(2008).
9. Kalsi-Ryan,
S. et al. Ancillary Outcome Measures for Assessment of Individuals With
Cervical Spondylotic Myelopathy: Spine 38, S111–S122 (2013).
10. Maggioni,
M., Katkovnik, V., Egiazarian, K. & Foi, A. Nonlocal Transform-Domain
Filter for Volumetric Data Denoising and Reconstruction. IEEE Trans. on
Image Process. 22, 119–133 (2013).
11. Kellner,
E., Dhital, B., Kiselev, V. G. & Reisert, M. Gibbs-ringing artifact removal
based on local subvoxel-shifts. Magnetic Resonance in Medicine 76,
1574–1581 (2016).
12. Avants,
B. B. et al. A reproducible evaluation of ANTs similarity metric
performance in brain image registration. NeuroImage 54, 2033–2044
(2011).
13. Andersson,
J. L. R., Skare, S. & Ashburner, J. How to correct susceptibility
distortions in spin-echo echo-planar images: application to diffusion tensor
imaging. NeuroImage 20, 870–888 (2003).
14. Peruzzo,
D., Bertoldo, A., Zanderigo, F. & Cobelli, C. Automatic selection of
arterial input function on dynamic contrast-enhanced MR images. Computer
Methods and Programs in Biomedicine 104, e148–e157 (2011).
15. Wu,
O. et al. Tracer arrival timing-insensitive technique for estimating
flow in MR perfusion-weighted imaging using singular value decomposition with a
block-circulant deconvolution matrix: Technique for Estimating CBF in PWI. Magnetic Resonance in Medicine 50, 164–174 (2003).
16. Brooks,
J. C. W. et al. Physiological noise modelling for spinal functional
magnetic resonance imaging studies. NeuroImage 39, 680–692
(2008).
17. Verma,
T. & Cohen-Adad, J. Effect of respiration on the B0 field in the human
spinal cord at 3T: Effect of Respiration on B0 Field in Human Spinal Cord. Magnetic Resonance in Medicine 72, 1629–1636 (2014).
18. Vannesjo,
S. J., Miller, K. L., Clare, S. & Tracey, I. Spatiotemporal
characterization of breathing-induced B0 field fluctuations in the cervical
spinal cord at 7T. NeuroImage 167, 191–202 (2018).
19. Schmainda, K. M. et al.
Moving Toward a Consensus DSC-MRI Protocol: Validation of a Low–Flip Angle
Single-Dose Option as a Reference Standard for Brain Tumors. American
Journal of Neuroradiology 40, 626–633 (2019).
20. Alsop,
D. C. et al. Recommended implementation of arterial spin-labeled
perfusion MRI for clinical applications: A consensus of the ISMRM perfusion
study group and the European consortium for ASL in dementia: Recommended
Implementation of ASL for Clinical Applications. Magnetic Resonance in
Medicine 73, 102–116 (2015).
21. Duhamel,
G. et al. Mouse lumbar and cervical spinal cord blood flow measurements
by arterial spin labeling: Sensitivity optimization and first application. Magnetic
Resonance in Medicine 62, 430–439 (2009).
22. Massire, A. et al.
High-resolution multi-parametric quantitative magnetic resonance imaging of the
human cervical spinal cord at 7T. NeuroImage 143, 58–69 (2016).