Serial Quantification of Brain Oxygenation using Streamlined-qBOLD in Acute Stroke Patients
Alan J Stone1, George WJ Harston2, Davide Carone2, Mmua Ngwako2, Radim Licenik2, James Kennedy 2, and Nicholas P Blockley1

1FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, 2Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom

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-qBOLD1 is a recently proposed refinement of the qBOLD methodology2 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 intervention3. 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 (R2′) 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 R2-weighting) from the measurement of R2′ 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=220mm2, 96x96 matrix, nine 5mm slabs, 1mm gap, TR/TE=3s/74ms, BW=2004Hz/px, TIFLAIR=1210ms, ASE-sampling scheme 𝜏start:Δ𝜏:𝜏finish=-16:8:64ms, scan duration 4.5mins), alongside T1-, T2- and diffusion (DWI) weighted imaging with apparent diffusion coefficient (ADC) calculation. R2′ 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 T1-weighted, T2-weighted, DWI (b-1000 and ADC) and baseline brain oxygen weighted (Spin Echo, R2′, 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 R2′ 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) imaging5. In Figure 1 there is a region of elevated R2′ 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 R2′ which corresponds with the lesion as identified on DWI. This appears to repeat the PET observation of ongoing metabolism within a DWI lesion6. Motion artefact can also be seen in the R2′ 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 R2′ map. Figure 3 shows a lesion in deep grey matter. The R2′-map demonstrates elevated R2′ 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 ischaemia7 could help clarify the role of R2′ 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.

Figures

Figure 1: On presentation, the DWI lesion (green arrow) is surrounded by areas of elevated R2′ and OEF (red arrow). These regions are later recruited to the 24 hour DWI lesion. (Male, 79yo, NIHSS=14, IV thrombolysis at 1hr24mins post onset, presentation MRI at 2hrs20mins post onset)

Figure 2: The presentation R2′ and OEF maps both show a heterogeneous pattern within the DWI lesion (green arrow). Note: in this patient the second time point was acquired at 38 hours after the initial scan. (Male, 78yo, NIHSS=4, no IV thrombolysis, presentation MRI at 28hrs20mins post onset)

Figure 3: Elevated R2′ matches the DWI lesion in the basal ganglia (white arrow), though partly obscured by the bilateral elevation of R2′. OEF maps delineate the DWI lesion more clearly from the normal contralateral hemisphere. (Male, 87yo, IV thromobolysis at 3hr28mins post onset, presentation MRI at 13hrs49mins post onset)



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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