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Declaration of Conflict of Interest or Relationship

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Presentation on theme: "Declaration of Conflict of Interest or Relationship"— 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 Thomas Liu University of California, San Diego May 4, 2008

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 HbO2 Release of O2 to tissue results in deoxyhemoglobin dHBO2 B0 Field Maps More dHB Less dHB

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

8 BOLD Signal Equation Cerebral Blood Volume Large vessels Linear =1
Ogawa et al, 1993 Large vessels Linear =1 Cerebral Blood Volume Diffusion around small vessels Quadratic =2 Simulations suggest  1.5 is a reasonable value Ogawa et al, 1993; Boxerman et al 1995, Hoge et al. 1999

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 (CMRO2) is the rate of oxygen consumption (units of mol/(g-min)) CBF [O2]arterial Oxygen extraction fraction (E) CMRO2 CMRO2= E CBF [O2]arterial

10 Deoxyhemoglobin O2 [dHB]venous  E [O2]arterial / 4 = CMRO2 / 4CBF

11 fMRI: Spatial Temporal Dynamics
arteriole capillary bed venule CBF oxyHb deoxyHb Neural activity CMRO2 CMRO2 CBV CBF dHb Positive BOLD Post-stimulus Response Initial dip CMRO2 CBV CBF dHb CMRO2 CBV CBF dHb

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

13 Davis Model Hoge et al. 1999

14 BOLD Signal Path Cerebral Blood Volume deoxyHb Neural Activity
Blood Flow Metabolism (CMRO2) 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 Carbon Dioxide Lower CBF Higher CBF Cohen et al 2002

21 Caffeine Lower CBF Liu et al 2004

22 Interpreting BOLD Ianetti and Wise, MRI, 2007

23 ASL measures of regional baseline CBF
Response to Breathhold or CO2; Resting-state Fluctuations Cerebral Blood Volume deoxyHb Neural Activity Cerebral Blood Flow Metabolism (CMRO2) BOLD Signal Trust MRI Measures of whole brain venous oxygenation

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. Yv [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 CBF0 M BOLD dHb BOLD ? CBF 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

30 Breathhold Calibration
Breathhold Signal Thomason et al, 2007

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 ASL Signal Cerebral Blood Volume deoxyHb Neural Activity Cerebral Blood Flow Metabolism (CMRO2) BOLD Signal

38 Calibrated fMRI (Davis et al 1998)

39 Experimental Protocol
2x Block design visual stimulus 20s 60s 2x 5% CO2 Scans 2min air 3min CO2 %∆CBF %∆BOLD M %∆CMRO2

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
Young Old Normalized CMRO2 Young Old %CMRO2 Restom et al, NIMG 2007

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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