Biophysical and physiological bases of fmri signals: challenges of interpretation and methodological concerns

Transcription

1 Biophysical and physiological bases of fmri signals: challenges of interpretation and methodological concerns Antonio Ferretti Institute for Advanced Biomedical Technologies, University of Chieti- Pescara Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti-Pescara IRCCS Neuromed, Pozzilli (IS)

2 Outline Blood Oxygen Level Dependent (BOLD) fmri Physiological basis of the BOLD response Interpretation of the BOLD signal The negative BOLD response Arterial Spin Labeling (ASL) fmri ASL principles ASL vs BOLD

3 Hemodynamic characterization of a gray matter MRI voxel (typical size: 3mmx3mmx3mm): Hemodynamic and metabolic variables: Cerebral Blood Volume (CBV) Cerebral Blood Flow (CBF) Cerebral Metabolic Rate of O 2 (CMRO 2 ) Oxygen Extraction Fraction (OEF) Resting values: CBV 4% CBF 60 ml/min/100g CMRO µmol/min/100g OEF 40%

4 The physiological basis of the BOLD response Blood oxygenation during rest Oxy-Hb Blood O 2 saturation = Oxy-Hb +Deoxy-Hb Arterial blood O 2 saturation 95% Venous blood O 2 saturation 60%

5 The physiological basis of the BOLD response The neurovascular unit : a close functional and structural integration of neurons, astrocytes and blood vessels.

6 The physiological basis of the BOLD response REST CBF ACTIVATION CBV CMRO 2 OEF

7 The physiological basis of the BOLD response REST O 2 saturation 95% O 2 saturation 60% ACTIVATION O 2 saturation 95% O 2 saturation 75%

8 The effect of field homogeneity on the MRI signal Physically, what we measure in a fmri experiment is the signal difference ΔS between rest and activity conditions. Since this signal difference is determined by T2* variations, the most widely used sequence for BOLD fmri is a T2* weighted gradient echo (GE) echo-planar image (EPI). S 0 S = S 0 e -t/t2* ΔS activity: less Deoxy-Hb rest: more Deoxy-Hb TE

9 fmri paradigms activity rest activity rest Optimal duration?

10 The dynamics of the BOLD response The timecourse of a typical BOLD response Activity ( 25 s) BOLD % change Overshoot Sustained response Initial dip Post stimulus undershoot s

11 Spatial and temporal resolution of neuroimaging techniques Spatial resolution (mm) Temporal resolution (seconds)

12 Interpretation of the BOLD response The BOLD response stems from a complex chain of physiological processes. As such it is only an indirect and non quantitative measure of neuronal activity

13 Interpretation of the BOLD response So, given the two results below, it would be incorrect to conclude that the motor area showed less neuronal activity in subject 2 than subject 1. Subject 1 Subject 2

14 Interpretation of the BOLD response BOLD signal transients Activity ( 25 s) BOLD % change Overshoot Sustained response Initial dip Post stimulus undershoot s

15 The negative BOLD response Visual stimulation:

16 The negative BOLD response Median nerve stimulation:

17 The negative BOLD response

18 fmri paradigms: methodological concerns Low frequency noise in fmri time series Long block paradigms are not optimal!! activity rest minutes or more minutes or more

19 fmri paradigms: methodological concerns BOLD fmri not optimal for the study of ongoing or background pain, as this behavior cannot be broken up into blocks or interrupted by rest periods PET does not suffer this limitation but is more invasive and expensive Another MRI-based technique, arterial spin labeling (ASL), provides noninvasive, quantitative indices of CBF with the sensitivity to detect tonic states over the course of minutes, thus ideally suitable for examining persistent or on-going pain

20 Arterial Spin Labeling (ASL) fmri B 0 A bolus of labeled (magne0cally inverted) blood water is created in the main arteries using a 180 RF pulse Non labeled blood water spins Labeled blood water spins Non labeled 0ssue water spins

21 Arterial Spin Labeling (ASL) fmri B 0 TI Non labeled blood water spins Labeled blood water spins Non labeled 0ssue water spins

22 Magnetizzazione Acquisizione TAG image TI Magnetizzazione Acquisizione CONTROL image TI

23 Delta M is sensi0ve to CBF CBF f = 8 >< >: ΔM 2αM 0B T 1B exp PLD exp PLD + τ T 1B T 1B ΔM 2αM 0B TI 1 exp TI 2 T 1B exp TE for PCASL T 2B exp TE for PASL T 2B ð3þ

24 The calibrated BOLD method ΔBOLD BOLD 0 = M 1 CBF CBF 0 α: Grubb constant (0.38) α β CMRO β 2 CMRO 20 β: oxygenation and field strength dependence of the BOLD effect (1.5) M: calibration constant (maximum BOLD change for complete removal of deoxyhemoglobin in the voxel) ΔBOLD HO BOLD 0 = M 1 CBF α HO ½dHbŠ HO + CBF 0 1 CBF 0 ½dHbŠ 0 CBF HO β Fig. 2. The hyperoxia paradigm. Hyperoxia paradigm

25 Contents lists available at ScienceDirect NeuroImage 2011 journal homepage: com/locate/yni mg Calibrated fmri during a cognitive Stroop task reveals reduced metabolic response with increasing age Rafat S. Mohtasib a,c, Guy Lumley c, Jonathan A. Goodwin a,e, Hedley C.A. Emsley b, Vanessa Sluming a,c, Laura M. Parkes a,d, a 58 healthy participants (18 71 years old) Stroop task

26 Calibrated BOLD results The BOLD response increased with increasing age but the CBF response did not alter, such that the BOLD increase is attributed to a significant reduction in the oxygen metabolism response with increasing age. Hence, in this study, the BOLD increase with age should be interpreted as a reduction in neural activity.