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Declaration of Conflict of Interest or Relationship Speaker Name: Thomas Liu I have no conflicts of interest to disclose with regard to the subject matter.

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Presentation on theme: "Declaration of Conflict of Interest or Relationship Speaker Name: Thomas Liu I have no conflicts of interest to disclose with regard to the subject matter."— Presentation transcript:

1 Declaration of Conflict of Interest or Relationship Speaker Name: Thomas Liu I have no conflicts of interest to disclose with regard to the subject matter of this presentation.

2 Thomas Liu University of California, San Diego May 4, 2008 Functional MRI Signal Interpretation and Calibration

3 Topics BOLD signal model Sources of Variability and Confounds Normalization Methods Calibration Methods

4 BOLD Contrast Source: Ogawa et al., 1992

5 BOLD Signal Change Baseline Signal TE Activation Signal

6 Hemoglobin and Field Inhomogeneities Oxygen binds to the iron atoms to form oxyhemoglobin HbO 2 Release of O 2 to tissue results in deoxyhemoglobin dHBO 2 B0B0 Field Maps More dHB Less dHB

7 Signal Decay time 0TE Some dHB, Some dephasing More dHB, More dephasing, Decrease in MR signal

8 BOLD Signal Equation Ogawa et al, 1993; Boxerman et al 1995, Hoge et al Ogawa et al, 1993 Large vessels Linear  =1 Diffusion around small vessels Quadratic  =2 Simulations suggest   1.5 is a reasonable value Cerebral Blood Volume

9 Blood Flow and Oxygen Metabolism Cerebral Blood Flow (CBF) measures delivery of blood to brain tissue (units of ml/(g-min)) Cerebral Metabolic Rate of (CMRO 2 ) is the rate of oxygen consumption (units of  mol/(g-min)) CBF [O 2 ] arterial CMRO 2 Oxygen extraction fraction (E) CMRO 2 = E CBF [O 2 ] arterial

10 Deoxyhemoglobin = CMRO 2 / 4CBF CMRO 2 [dHB] venous CBF [dHB] venous O2O2 [dHB] venous  E [O 2 ] arterial / 4

11 fMRI: Spatial Temporal Dynamics arteriolevenule capillary bed CMRO 2 CBF oxyHb deoxyHb Initial dip Positive BOLD Post-stimulus Response Neural activity CMRO 2 CBV CBF dHb CMRO 2 CBV CBF dHb CMRO 2 CBV CBF dHb

12 BOLD Signal Equation (Davis Model) Maximal BOLD signal Grubb’s Relation;  0.38

13 Davis Model Hoge et al. 1999

14 BOLD Signal Path Neural Activity Metabolism (CMRO 2 ) Cerebral Blood Flow Cerebral Blood Volume deoxyHb BOLD Signal

15 Interpreting BOLD Most fMRI studies assume that the BOLD signal is is proportional to brain activity. This is a reasonable assumption for basic studies of healthy young unmedicated subjects. However, the assumption is less valid for studies where disease, medication, and age may be a factor. Boynton et al, 1996

16 Variability in BOLD amplitude Data courtesy of J. Liau

17 BOLD Signal Chain Ianetti and Wise, MRI, 2007

18 Effect of Age D’Esposito et al 2003

19 Effects of Vascular Disease D’Esposito et al 2003 Iadecola et al 2003

20 Cohen et al 2002 Carbon Dioxide Higher CBF Lower CBF

21 Caffeine Liu et al 2004 Lower CBF

22 Interpreting BOLD Ianetti and Wise, MRI, 2007

23 Neural Activity Metabolism (CMRO 2 ) Cerebral Blood Flow Cerebral Blood Volume deoxyHb BOLD Signal Trust MRI Measures of whole brain venous oxygenation Response to Breathhold or CO2; Resting-state Fluctuations ASL measures of regional baseline CBF

24 BOLD and Venous Oxygenation Inter-subject Differences in M can lead to inter-subject differences in BOLD TRUST MRI (Lu et al 2007): Measures of whole brain venous oxygenation saturation. YvYv [dHB] venous BOLD

25 Venous Oxygenation (TRUST MRI) Lu, ISMRM 2007

26 TRUST MRI Lu et al, Abstract 855, ISMRM 2008

27 BOLD and Baseline CBF ? dHb BOLD  CBF BOLD CBF 0 M BOLD

28 BOLD variability and Baseline CBF M appears to be independent of CBF -- effects of increased CBF and decreased [dHb] appear to cancel out Variability in the BOLD response across subjects appears to be driven by inter-subject differences in the CBF response. Liau et al, Abstract 854, ISMRM 2008

29 Breathold/Hypercapnic Normalization 1

30 Breathhold Calibration Thomason et al, 2007 Breathhold Signal

31 Breathhold Calibration Thomason et al, 2007

32 Hypercapnic Calibration Cohen et al, 2004

33 Scaling with Resting-State Fluctuations Wise et al 2004;

34 Scaling with Resting-State Fluctuations Birn et al 2006;

35 Scaling with Resting-State Fluctuations Kannapurti and Biswal 2008; also Abstract 750

36 Summary of Normalization Approaches Additional measures can account for BOLD variability due to variations in baseline blood flow, volume, oxygenation, field strength, etc. Measures of venous oxygenation, cerebral blood flow, and resting fluctuations have the advantage of not requiring the subject to perform additional tasks. These approaches offer some insight into the factors that can affect the BOLD response between subjects, groups, and conditions.

37 Neural Activity Metabolism (CMRO 2 ) Cerebral Blood Flow Cerebral Blood Volume deoxyHb BOLD Signal ASL Signal

38 Calibrated fMRI (Davis et al 1998) 1

39 Experimental Protocol 2x Block design visual stimulus 20s60s %∆CBF %∆BOLD 2x 5% CO 2 Scans 2min air 3min CO 2 2min air M %∆CMRO 2

40 Calibrated fMRI Ances et al, NIMG 2007

41 Calibrated fMRI of HIV Ances et al, in preparation

42 Effect of age on CBF and BOLD Restom et al, NIMG 2007 Young Old %  CMRO 2 Young Old Normalized CMRO 2

43 Calibrated fMRI Can provide insights that BOLD measures alone cannot provide. Can be difficult to apply to cognitive tasks and special populations, due to low sensitivity of ASL. The need for breathhold or hypercapnia can also be an issue. Hyperoxia-based method may be an alternative.

44 Conclusions The BOLD signal is a complex function of the baseline state and changes in blood flow, volume, and metabolism. Differences in the BOLD signal do NOT always reflect differences in neural activity. Instead they may reflect differences in the baseline vascular or metabolic state. Normalization methods can help to reduce inter-subject variability. Calibrated fMRI can provide additional insights into differences in brain activity, especially in the presence of disease, medication, and age.

45 Acknowledgements Beau Ances Yashar Behzadi Rick Buxton David Dubowitz Joy Liau Oleg Leontiev Joanna Perthen Khaled Restom Eric Wong


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