1. Global brain physiology does not impact regional BOLD activations Yufen Jennie Chen Xue Wang Todd B. Parrish 1 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20

2. Disclosure The authors have no relevant financial interest or relationship to disclose with regard to the subject matter of this presentation. 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 2

3. Purpose  Blood-oxygenation level dependent (BOLD) fMRI is a complex interplay between multiple physiological processes including cerebral blood flow, cerebral blood volume, oxygen consumption and neural activity.  Intersubject variability in baseline local CBF accounts for variability in BOLD response to tasks 1  Recently developed MRI techniques can quantitatively measure global cerebral metabolic rate of oxygen (CMRO 2 ) 2 The purpose of this study is to investigate whether global CMRO 2 will affect the amplitude of task-related BOLD response 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 3

4. Materials & Methods  Subjects  Group 1: 9 subjects (4F, 36 ± 9 years old)  Group 2: 8 subjects (4F, 29 ± 4 years old)  Tasks  Synonyms task (group 1): alternating 30s epochs of word pairs and letter strings, repeated 8 times (scan time: 8’06”)  Story comprehension (group 2): alternating 24s epochs of stories and scrambled words, repeated 8 times (scan time: 6’30”) 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 4

5. Materials & Methods  Imaging  3.0T Siemens TIM Trio & 32 channel head coil  BOLD fMRI: gradient-echo echo planar imaging (EPI)  Group 1: 1.7x1.7x3mm 3, TE=20ms, TR=2s, 35 slices  Group 2: 1.7x1.7x3mm 3, TE=20ms, TR=2.4s, 42 slices  Venous oxygenation: postsat-TRUST 3  1.4x1.4x5mm 3, TE=18ms, TR=4s, TE eff =0/40/80/160 ms, 1 slice through sagittal sinus 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 5

6. Materials & Methods  Imaging (Cont.)  Global blood flow: retro-gated phased contrast MRI (PC-MRI)  0.5x0.5x5mm 3, V enc =80cm/s, 20 phases, TE=3.81ms, TR=66.3ms, 1 slice positioned perpendicular to carotids and vertebrals based on non-contrast time-of-flight scan  Multiple scans were run to ensure perpendicular cross- section for all major arteries 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 6 Sample position planning of scan for carotids

7. Materials & Methods  BOLD analysis  Preprocessing: coregistration, motion correction, smoothing (6mm), non-linear spatial normalization to MNI152_T1 template  First-level GLM analysis for each subject  Preprocessing and first-level analysis performed via online pipeline 4  Second-level GLM analysis on the contrast images of the group  % signal change extracted from two ROIs using MarsBar 5 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 7 Location of ROIs 1 2

8. Materials & Methods  Data analysis for TRUST  Coregistration between TE eff data and motion-correction within TE eff data  pairwise subtraction between control & tag images  Extract mean signal of 6 highest signal voxels in sagittal sinus  Fit for blood T 2 and Yv 3 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 8 Example of data & fit

9. Materials & Methods  Data analysis for PC-MRI  Calculate total CBF by summation of flow in bilateral carotids and vertebral arteries, average over cardiac cycle  Estimate brain volume from tissue segmentation of high resolution anatomical T1  Calculate normalized CBF per tissue mass 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 9

10. Materials & Methods  CMRO 2 calculation  CMRO 2 = CBF * (Ya-Yv) * C a  Ya = arterial oxygenation ~ 100%  Yv = venous oxygenation (calculated from TRUST)  C a = amount of oxygen/volume of blood = 8.337  mol O 2 /ml of blood 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 10

11. Results: Correlations with physiology 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 11 Total flow is positively correlated with both venous oxygenation (Yv) and cerebral metabolic rate of oxygen (CMRO 2 )

12. Results: Correlations with %  BOLD ROI1ROI2 rprp Group 1 CBF (ml/100g/min) 0.330.380.140.71 Yv (%)0.350.360.220.57 CMRO 2 (  mol/100g/min) 0.260.500.100.79 Group 2 CBF (ml/100g/min) 0.030.940.150.72 Yv (%)0.020.970.280.51 CMRO 2 (  mol/100g/min) 0.140.74-0.370.36 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 12

13. Conclusion  Global CBF is positively correlated with venous oxygenation and oxygen consumption  None of the physiological metrics correlated with %  BOLD  Global physiology is preserved in spite of local disturbances such as functional activation  Current CMRO 2 technique is a static measure, which may not be sensitive to local dynamic changes queried by BOLD  Balance in global physiology may be disrupted with aging and disease of the neurovascular system 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 13

14. Future Work  Implement technique for local physiological metrics to better understand their effects on functional activity  Extend findings in older healthy controls and chronic stroke patients 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 14

15. References 1.Liau J., Liu TT. Inter-subject variability in hypercapnic normalization of the BOLD fMRI response. Neuroimage 45 (2009) 420–430 2.Xu F., Ge Y., Lu H. Noninvasive Quantification of Whole-Brain Cerebral Metabolic Rate of Oxygen (CMRO2) by MRI. Magn Reson Med 62 (2009) 141–148 3.Xu F., Uh J., Liu P., Lu H. On Improving the Speed and Reliability of T2-Relaxation-Under-Spin-Tagging (TRUST) MRI. Magn Reson Med 68 (2012) 198–204 4.Song X., et al. Robust web-based parallel-optimized minimal preprocessing and analysis pipeline for fMRI big data. OHBM 2015, Honolulu, Hawaii 5.Brett M., et al. Region of interest analysis using an SPM toolbox. OHBM 2002, Sendai, Japan 53rd ASNR meeting 2015, Chicago IL Poster #:EP-20 15