Synopsis
Streamlined-qBOLD is applied to an exploratory
cohort of acute stroke patients in a serial imaging study to map brain oxygen
metabolism. Quantitative brain oxygenation parameters are demonstrated to vary
between regions with different tissue outcomes and this imaging approach is
shown to have the potential to refine the identification of the ischemic
penumbra.Purpose
Streamlined-qBOLD
1 is a recently proposed refinement of the qBOLD
methodology
2
that provides a simplified approach to mapping baseline brain oxygen metabolism. We demonstrate its potential
to observe the evolution of oxygen metabolism in the ischaemic penumbra in serially
imaged patients with acute stroke.
Background
The original concept of the
ischaemic penumbra suggested that concurrent imaging of regional cerebral blood
flow (CBF) and metabolism would be required to identify tissue at risk that may
benefit from intervention
3. qBOLD is a non-invasive MR technique that describes the transverse MR
signal decay in the presence of a blood vessel network by exploiting the
sensitivity of the reversible-transverse-relaxation-rate (R
2′) to Oxygen Extraction Fraction (OEF) and Deoxygenated
Blood Volume (DBV)
2.
Streamlined-qBOLD uses a novel acquisition protocol to minimise
confounding effects (CSF contamination, magnetic field inhomogeneities and R
2-weighting) from the measurement of R
2′ and improve the robustness of the resultant
parametric maps. Streamlined-qBOLD
provides an approach to mapping baseline brain oxygenation with good brain coverage in a
clinically feasible acquisition time and a non-invasive, patient friendly
manner. As such, this technique is ideally suited to
clinical studies requiring repeated imaging sessions to track the progression
of baseline brain oxygenation and metabolism.
Methods
Patients with acute
ischaemic stroke were recruited and scanned at 3T under a National Ethic Committee
approved protocol, which included possible repeat scanning at 2 hours, 24
hours, 1 week and 1 month after initial scan. Nine patients were scanned on presentation with a minimum of one
follow-up scan.
Imaging sequences
included streamlined-qBOLD (FOV=220mm
2, 96x96 matrix, nine 5mm
slabs, 1mm gap, TR/TE=3s/74ms, BW=2004Hz/px, TI
FLAIR=1210ms, ASE-sampling
scheme 𝜏
start:Δ𝜏:𝜏
finish=-16:8:64ms,
scan duration 4.5mins), alongside
T
1-, T
2- and diffusion (DWI) weighted imaging with apparent
diffusion coefficient (ADC) calculation. R
2′ was calculated
using a log-linear fit to the mono-exponential regime (𝜏>15ms)
4 of the ASE data. The intercept of this fit and the
spin-echo signal (𝜏=0ms)
were subtracted to measure DBV. OEF was then calculated using, $$OEF=\frac{R_2^\prime}{DBV\;\gamma\frac{4}{3}\pi\;\Delta\chi_0\;Hct\;B_0}\tag{1}$$ where parameters are known or assumed constants (Δ𝜒0=0.264x10
-6, Hct=0.34)
2.
Results
Figures 1-3 show T
1-weighted,
T
2-weighted, DWI (b-1000 and ADC) and baseline brain oxygen weighted
(Spin Echo, R
2′, OEF and DBV) maps over
multiple imaging time-points from example patients chosen to demonstrate the
potential and limitations of streamlined-qBOLD. Patient characteristics are reported in figure
captions, including National Institutes of Health Stroke Scores (NIHSS). It
should also be noted that OEF and DBV are physiological measurements,
whereas R
2′ is sensitive to the product of these parameters.
Discussion
Streamlined-qBOLD imaging of acute stroke
patients in this exploratory cohort appears to deliver similar information on the
evolution of oxygen metabolism in the ischaemic penumbra to previous studies
using Positron Emission Tomography (PET) imaging
5. In Figure 1 there is a region of elevated R
2′ on presentation, not within
the presenting DWI lesion. This region is later recruited to the 24 hour DWI lesion.
This supports the potential of using brain oxygenation imaging to identify tissue at risk of infarction. Figure 2 shows an area of elevated R
2′ which corresponds with the lesion as identified on DWI. This appears to repeat the PET observation
of ongoing metabolism within a DWI lesion
6. Motion artefact can also be seen in the R
2′ image at
presentation where CSF suppression was not effective (high signal in the
ventricles). Despite this artefact the area of ischemia is still visible in the
presenting R
2′ map.
Figure 3 shows a lesion in deep grey matter. The R
2′-map demonstrates elevated R
2′ bilaterally due to the high iron content of these structures. Despite
this the OEF maps discriminate ischemic from normal tissue and are elevated on
the affected side. Further work involving the use of imaging based regional definitions of
ischaemia
7 could help clarify the role of R
2′ and OEF in defining regions
of metabolic stress and the relevance of these regions to final infarct
outcome.
Future methodological developments will concentrate on improving
robustness to subject motion (a particular problem in this patient cohort) and
improving the quantification of OEF and DBV.
Conclusion
Streamlined-qBOLD offers metabolic information in
an acute patient population which is complimentary to the current methodologies.
Resting brain oxygenation characteristics are demonstrated to vary between
regions with different tissue outcomes. This imaging approach has the potential
to refine the identification of the ischemic penumbra.
Acknowledgements
This study was funded by the Engineering and
Physical Sciences Research Council under grant number EP/K025716/1, the
National Institute for Health Research Oxford Biomedical Research Centre
Programme, the National Institute for Health Research Clinical Research
Network, the Dunhill Medical Trust [grant number: OSRP1/1006] and the Centre of
Excellence for Personalized Healthcare funded by the Wellcome Trust and
Engineering and Physical Sciences Research Council under grant number
WT088877/Z/09/Z.References
[1] Stone AJ & Blockley NP. A
streamlined approach to mapping the oxygen extraction fraction (OEF) and
deoxygenated blood volume (DBV) using the quantitative BOLD technique. Proc.
Intl. Soc. Mag. Reson. Med. 23, 2015;
Abstract #0219;
[2] He X,
Yablonskiy DA. Quantitative BOLD: mapping of human cerebral deoxygenated blood
volume and oxygen extraction fraction: default state. Magn. Reson. Med. 2007;
57(1): 115–126.
[3] Astrup J,
Siesjo BK, Symon L. Thresholds in cerebral ischemia - the ischemic penumbra. Stroke
1981; 12: 723–5.
[4] Yablonskiy DA,
Haacke EM. Theory of NMR signal behavior in magnetically inhomogeneous tissues:
the static dephasing regime. Magn Reson Med 1994;32:749–763.
[5] Guadagno, J. V., Donnan, G., Markus, R., Gillard, J. H., &
Baron, J.-C. (2004). Imaging the ischaemic penumbra. Current Opinion in
Neurology, 17(1), 61–67.
[6] Guadagno, J. V., Warburton, E. A., Jones, P. S., Fryer, T. D., Day,
D. J., Gillard, J. H., et al. (2005). The diffusion-weighted lesion in acute
stroke: heterogeneous patterns of flow/metabolism uncoupling as assessed by
quantitative positron emission tomography. Cerebrovascular Diseases 19(4),
239–246.
[7] Harston, G. W., Tee, Y. K., Blockley, N., Okell, T. W., Thandeswaran, S., Shaya, G., et al. (2015). Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging. Brain 138, 36–42.