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CVRPresentation2016
- 1. A Resting-State BOLDStudy of Cerebrovascular Reactivity in Stroke Daniel Worstell, Hanzhang Lu, Argye Hillis, and Peiying Liu Department of Radiology
- 2. Stroke Diagnosis andAssessment • Neuroimaging in stroke aims to characterize ischemia (location, size, risk of enlargement) and asses scope of penumbra (neural tissue around stroke that is not irreversibly damaged) • Perfusion imaging is used to identify penumbra by perfusion/diffusion mismatch • DSC perfusion, CT perfusion, etc. • But, could be shadowed by autoregulation • Therefore, cerebrovascular reserve (reactivity) may be a more sensitive indicator of perfusion deficit in stroke Neumann-Haefelin et al., Stroke 1999 Brunser et al., Stroke 2013 Jordan and Powers, Am J Hypertens 2012
- 3. Cerebrovascular reactivity • CVRis a specific measure of the dilatory function of brain vasculature • May be used as an indicator of vascular health, can assist with diagnosis and treatment evaluation • CVR mapping typically done using hypercapnic gas inhalation • May be practically difficult to obtain in acute patients using conventional methods Mandell et al., Stroke 2008 Donahue et al., JMRI 2013 Yezhuvath et al., NMR in Biomed 2009 Ogasawara et al., Stroke 2002
- 4. How to measureCVR without using gas challenge
- 5. Resting state CVR(rsCVR) • Highly reproducible – similar results across multiple scans • Shown to have similar physiological origin to CO2-inhalation-derived CVR Scan 1 Scan 2 Scan 3 Scan 4 Scan 5 Scan 6 Scan 7 RestingStateCO2CVR Liu et al., ISMRM 2015 DWI
- 6. TOF MRA FLAIR CBF RS CVR CVRin Moya Moya Disease CBV 0 0.02 %/mmHgO2 -3 3 relativeunit 0 150 ml/100g/min
- 7. Hypothesis CVR can beused as a perfusion index to define vascular deficit in stroke patients
- 8. Methods •Subjects (n =16) • Clearly visible lesions, >= 400 voxels •Times of scans • Scans took place from 0 to 11 weeks post-stroke •Imaging parameters • Resting state BOLD scans, 432 seconds each -Single shot gradient echo EPI, voxel size 3.0 X 3.0 X 4.0 mm3 , 35 axial slices, TR/TE = 2000/30 ms
- 9.
- 10. Results CVR mapDWI CVRmapDWI CVR mapDWI -0.5% 1.5% 3.5% ΔBOLD Subject 1 Subject 2 Subject 3
- 11. ROI generation andanalysis DWI Lesion + Control P=0.009 Paired T-Test
- 12. Identification of deficitregion in rsCVR -0.5% 1.5% 3.5% ΔBOLD CVR mapDWI CVR mapDWI CVR mapDWI Subject 1 Subject 2 Subject 3
- 13. Summary • A newmethod to map cerebrovascular function without gas inhalation – Generate reproducible resting CVR maps – Of similar physiological origin to CO2-inhalation-derived CVR – Uses data that is readily available from rs-BOLD scans, and usually discarded • This method may be a potential surrogate for detecting deficits in vascular reserve when CVR mapping with gas inhalation is not feasible, such as in stroke patients
- 14.
Editor's Notes
- #3 Neuroimaging, in stroke, focuses on the characterization of stroke and of the penumbra – neural tissue around the stroke that is not irreversibly damaged. Currently, perfusion imaging is used to identify the penumbra. A higher perfusion/diffusion mismatch provides evidence that tissue is “at risk,” and that a lesion may expand into it. DSC perfusion, CT perfusion and other perfusion imaging methods are used for this purpose. However, autoregulation of blood flow in the brain, when the brain compensates for reduced CBF to stroke regions by increasing flow directly, may reduce the effect of stroke in reducing perfusion detected by these methods. We have suggested, then, that cerebrovascular reactivity may be a better indicator of perfusion deficit in stroke.
- #4 Cerebrovascular reactivity (CVR) is a specific measure of cerebral blood vessels’ ability to dilate. It is an important marker of the brain’s vascular health. During the past few years, CVR mapping has been shown to provide valuable information for the diagnosis and treatment evaluation of patients with cerebrovascular diseases, including stroke patients. CVR mapping is typically done by taking BOLD images of subjects after hypercapnic gas inhalation, which acts as a vasoactive challenge. However, gas inhalation and the required setup may present difficulties for routine CVR mapping, especially for patients with stroke or other acute problems. Therefore, we sought to develop an alternative method to generate a reliable CVR map, which may be useful when profiling vascular function in acute patients. Here shown is a setup for generating CVR using hypercapnia. The subject breathes gas which has a high CO2 concentration. BOLD images are taken over time, and a timecourse of the BOLD signal and ETCO2 are generated. These timecourses can then be averaged and used to make a CVR map. You can see in the diagram of the hypercapnia apparatus that this setup is not feasible for acutely ill subjects — such subjects need a minimally involved imaging method in order to generate CVR, both to avoid image distortion due to motion and to avoid worsening their conditions.
- #5 Spontaneous fluctuation in the resting-state BOLD MRI signal is well known in the functional connectivity MRI (fcMRI) literature. It is thought to have many origins. And, it is commonly considered to be a nuisance signal in fcMRI, so it is usually discarded in pre-processing. However, the information regarding the spontaneous fluctuation of CO2 in the signal can be used to generate a CVR map after filtering out other portions of the signal based on frequency, selecting frequencies that best correspond with the fluctuation of CO2.
- #6 We have previously shown that the CVR map generated from fluctuations in the BOLD signal is reproducible in healthy subjects. Here shown are results from a previous study in a healthy subject, across 7 scans, evidencing this reproducibility. Also shown is that the resting state CVR map has a physiological origin that is similar to a CO2-inhalation-derived CVR map. Large veins, gray matter and white matter have similar image contrast in each. This scatterplot from the prior experiment shows a high degree of correlation between resting state and CO2-inhalation-derived CVR.
- #7 We have also previously demonstrated the capacity for rsCVR to provide information about perfusion in patients with Moya Moya - a cerebral stenotic disease. Here is shown an rsCVR map of a patient with MMD as compared with an angiogram, anatomical images, a CBV and a CBF map. The CBF information is retained within the CVR map — dark regions, indicating low CVR, correspond to dark regions of low CBF. This CBF information is useful in predicting the risk of future lesion development. Specifically, reduced CBF is an indication of a higher risk for lesion development.
- #8 In light of the CBF information contained within the CVR map, in this study, our focus was on testing whether CVR can be used as a perfusion index to define vascular deficit in stroke patients.
- #9 We performed a retrospective study, in which data from previously scanned subjects was used. 16 subjects with relatively large lesions and who moved minimally during imaging were chosen for analysis. Diffusion and rsBOLD images were taken from 0 to 11 weeks post-stroke.
- #10 Resting-state BOLD images from each subject were passed through an image processing pipeline in order to generate a CVR map. BOLD images were motion corrected, smoothed, detrended, and filtered. The original BOLD images were also used to generate a whole-brain reference mask. Next, using this mask, the whole-brain-averaged gray matter BOLD time course in a scan was used as the independent variable and each individual voxel’s time course was used as the dependent variable in a linear regression analysis. This analysis yielded a resting-state CVR map in units of %BOLD signal change. Resting CVR maps were obtained for each subject.
- #11 These are representative subjects showing that rsCVR mapping may provide valuable information when evaluating strokes. Here you can see hyperintensity in the DW images indicating stroke regions. In the corresponding regions of the CVR maps, as indicated by the green arrows, is it apparent that CVR is reduced. A contrast between grey matter and white matter is also visible in the images, but this does not account for the specific, unilateral effect of the lesions on the CVR maps.
- #12 A region of interest was drawn around the lesion of each selected subject on the DWIs. Afterward, the lesion ROI was flipped across the midline to generate a contralateral control brain region. The average CVR within the lesion and control regions, across the 16 subjects, is given as the figure at the right. It was found that the control regions had a significantly higher average CVR than did the lesion regions, as determined by a paired t test taken between the two populations of ROIs. The error bars show standard error.
- #13 We also performed a second, exploratory analysis following ROI analysis. We observed how the deficit region as identified by the CVR map compares with the stroke region identified by the DWIs. The deficit region is shown here as a green overlay. It is apparent that the darker area of the rsCVR map, indicating a lower rsCVR value at those voxels, includes more voxels than were delineated in diffusion images. The larger deficit region indicates that the brain area affected by stroke may be larger than diffusion images would imply.
- #14 In summary, we have proposed a new method to map cerebrovascular function without gas inhalation that uses information which is routinely gathered in fcMRI. Our results showed that CVR generated by this method is reproducible, and is of a similar physiological origin to CO2-inhalation-derived CVR. We hope that our results may prove useful in future studies, or in generating disease models to assist clinicians with monitoring disease and evaluating treatments, especially with models of acute cerebrovascular disease such as stroke.