Restingstate f MRI Algorithms and Applications to Brain
Resting-state f. MRI: Algorithms and Applications to Brain Disorders ZANG Yu-Feng 臧玉峰 M. D. zangyf@gmail. com YAN Chao-Gan 严超赣 Ph. D. ycg. yan@gmail. com State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China 1
Outline • What is resting-state f. MRI? • Computational methodology • Applications to brain disorders 2
Functional MRI? Generally • Blood oxygenation level dependent (BOLD) • Perfusion • Diffusion • Magnetic resonance spectroscopy (MRS) • …… 3
Functional MRI? More Specifically • BOLD-f. MRI • Perfusion Most Specifically • BOLD-f. MRI 4
Functional MRI? 5
Task-state f. MRI? Contrast within a scanning session is necessary! Design T C T C Expected signal 6
Task-state f. MRI What is activation? activated delta baseline or control 7
Task-state f. MRI What is abnormal activation for patients? Abnormal activated level? Abnormal delta Abnormal baseline? So, baseline is important! 8
What is resting-state f. MRI? • Eyes closed or open with no task • Continuously • Quite a few minutes or more • Not to fall asleep • Not to think of anything in particular • Low frequency fluctuation (LFF, 0. 01 – 0. 08 Hz) 9
The nature of task BOLD “the haemodynamic response seems to be better correlated with the LFPs, implying that activation in an area is often likely to reflect the incoming input and the local processing in a given area rather than the spiking activity. ” (Logothetis et al. , 2001, Nature) BOLD ≈ LFP 10
The nature of spontaneous BOLD “It was found that the impulse response function computed from LFP and BOLD under conditions of no stimulation can predict the response under stimulation conditions. ” (Logothetis et al. , 2001, Nature) Spontaneous BOLD ≈ spontaneous LFP 11
Resting-state BOLD-f. MRI signal reflects: However, also physiological noise (respiration, cardiovascular pulsation, etc) (Cordes et al. , 2001; Birn et al. , 2006) 12
Outline • What is resting-state f. MRI? • Computational methodology • Applications to AD studies 13
Task-state f. MRI • Functional segregation (activation detection) • Functional integration (inter-regional relationship or connectivity) 1 >> 2 14
Most of resting-state f. MRI studies: integration (connectivity) v Correlation: (Biswal et al. , 1995; ……) v ICA: (Kiviniemi et al. , 2003; van de Ven et al. , 2004; Greicius et al. , 2004) v Hierarchical Clustering: (Cordes et al. , 2000; Salvador et al. , 2005) v Self Organization Map: (Peltier et al. , 2003) v. . 15
The first Resting-state f. MRI study (Biswal et al. , 1995) Bilateral finger tapping (task vs. rest) Resting-state correlation of low frequency fluctuation (LFF, 0. 01 – 0. 08 Hz) (Courtesy of Dr. WENG Xu-Chu) 16
Linear Correlation Spontaneous LFF was highly synchronous among: v Bilateral motor cortices (Biswal et al. , 1995) v Bilateral visual cortices (Lowe et al. , 1998; Kiviniemi et al. , 2004) v Bilateral auditory cortices (Cordes et al. , 2001) v Bilateral amygdala (Lowe et al. , 1998) v Bilateral thalamus (Stein et al. , 2000) v Language cortices (Hampson et al. , 2002) v Default mode network (Greicius et al. , 2003; Fox et al. , 2005. . ) 17
A default mode of brain function (Raichle et al. , 2001) PCC, MPFC, IPL etc. , 1) Consistently show task-independent deactivation (TID) during a wide range of tasks with cognitive demand 2) Highest metabolic rate in the brain during resting state 1) 2) 18
Functions of the default mode network Intrinsic activities (Fransson, 2005): • Self-reflection, self-referential processing, self awareness • Task-unrelated thought (TUT) • Mind wandering or daydreaming • Streams of consciousness • Memory retrieval of autobiographic events • …… 19
Most of resting-state f. MRI studies: integration (connectivity) v Correlation: (Biswal et al. , 1995; ……) v ICA: (Kiviniemi et al. , 2003; van de Ven et al. , 2004; Greicius et al. , 2004) v Hierarchical Cluster: (Cordes et al. , 2000; Salvador et al. , 2005) v Self Organization Map: (Peltier et al. , 2003) v. . 20
Independent Component Analysis (ICA) Spatial ICA for f. MRI data: separate a mixture of a 4 D data into a set of spatially independent components (Mc. Kowen et al. , 1998) 21
Spatial ICA for resting-state f. MRI Vascular component Visual component (Kiviniemi et al. , 2000) 22
“Integrative” is really good, but: Decreased functional connectivity Question: Is A, B, C, or……abnormal? 23
Only A few resting-state f. MRI studies: Segregation v rms, power spectrum, ALFF: (Biswal et al. , 1995; Li et al. , 2000; Kiviniemi et al. , 2000; Zang et al. , 2007) v TCA: (Liu et al. , 2000; Morgan et al. , 2004) v Regional Homogeneity: (Zang et al. , 2004) v Multiple Regressors: (Fransson, 2005) v Autoregressive Noise Model: (Cordes et al. , 2005) v Fractional Gaussian Noise: (Maxim et al. , 2005) 24
rms, power, ALFF For a given frequency: root mean square (rms) standard deviation amplitude Square root of the power rms: white matter vs. gray matter = 0. 6 : 1 (Biswal et al. , 1995; Li et al. , 2000) 25
rms, power, ALFF v. Power spectrum: Higher power at 0. 033 Hz in visual area (Kiviniemi et al. , 2000) 26
Amplitude of Low Frequency Fluctuation (ALFF) (Zang et al. , 2007; Yang et al. , 2007) TR 400 ms 0. 01 -0. 08 Hz 1. 25 Hz Steps: square root, average of 0. 01 -0. 08 Hz, standardization by global mean 27
ALFF PET (Raichle et al. , 2001) ALFF (Zang et al. , 2007) noise 28
Abnormal ALFF ADHD vs. controls (n=13) (n=12) (Zang et al. , 2007) Early AD vs. controls (He Y et al. , 2007) (Please see below for details) 29
Improvement: fractional ALFF Suprasellar cistern PCC 30
Improvement: fractional ALFF (Zou et al. , 2008) 31
Regional Homogeneity (Re. Ho) Similarity or coherence of the time courses within a functional cluster (Zang et al. , 2004) 32
Re. Ho: motor task state vs. pure resting state (Zang et al. , 2004) Rest > Motor > Rest a) Higher Re. Ho in bilateral primary motor cortices during motor task b) Higher Re. Ho in default mode network (PCC, MPFC, IPL) during rest (Raichle et al. , 2001; Greicius et al. , 2003) 33
Re. Ho applications to brain disorders v ADHD: Zhu et al. , 2005, 2007; Cao et al. , 2006 v AD/MCI: He et al. , 2007; Bai et al. , 2008 v Schizophrenia: Liu et al. , 2006, Shi et al. , 2007 v Aging: Wu et al. , 2007 v PD: Wu et al. , 2008 v Depression: Yuan et al. , 2008 34
Outline • What is resting-state f. MRI? • Computational methodology • Applications to brain disorders 35
RESTing-state f. MRI data analysis toolkit (REST) By Song et al. , http: //www. restfmri. net 36
Data Processing Assistant for Resting-State f. MRI (DPARSF) Yan CG* and Zang YF* (2010) DPARSF: a MATLAB toolbox for "pipeline" data analysis of resting-state f. MRI. Frontiers in Systems Neuroscience. 4(13) http: //www. restfmri. net 37
Outline • What is resting-state f. MRI? • Computational methodology • Applications to brain disorders 38
Some issues about resting-state f. MRI • Definition and instruction? • Sampling rates (TR) • Length • Standard method for data analysis? 39
Definition and Instruction? • Eyes closed or open with no cognitive task • Continuously • Not to fall asleep • Not to think of anything particular ill defined! 40
Different resting conditions? The functional connectivity patterns of the default mode network was minimally disturbed during different resting conditions with limited cognitive demand (Greicius et al. , 2003; Fransson, 2005; Fox et al. , 2005) Fox et al. , 2005 41
Different resting conditions? Functional connectivity maps Significantly different between different resting conditions with limited cognitive demand Yan et al. , PLo. S ONE 2009 42
Different resting conditions? Regional activity (ALFF) Significantly different between different resting conditions with limited cognitive demand Yan et al. , PLo. S ONE 2009 43
Different resting conditions? Suggestion: eyes closed for patients studies 44
Is the resting block a resting-state? In block design Long resting No study has compared directly between them yet 45
Is the resting block a restingstate? Stimulus Peak: 4 -8 s 20 - 30 s BOLD Post undershoot: > 15 s 46
Some issues about resting-state f. MRI • Definition and instruction? • Sampling rates (TR) • Length • Standard method for data analysis? 47
Some issues about resting-state f. MRI Sampling rates (TR) Nyquist sampling theorem: Shorter TR (<400 ms, >2. 5 Hz) for heart beating (around 1. 3 Hz) 48
Sampling rate and physiological noise But for respiration (around 0. 3 Hz)? Is TR <1. 5 s fast enough? Courtesy of SONG Xiao. Wei Simultaneous recording of respiration and heart beat to remove physiological noise (Hu et al. , 1995, MRM) 49
Some issues about resting-state f. MRI • Definition and instruction? • Sampling rates (TR) • Length • Standard data analysis? 50
Some issues about resting-state f. MRI Length? LFF: 0. 01 -0. 08 Hz Peak around 0. 033 Hz (Kiviniemi et al. , 2000, MRM) ≈2/min 8 min, we used 51
Some issues about resting-state f. MRI • Definition and instruction? • Sampling rates (TR) • Length • Standard data analysis? Not yet 52
Applications to brain disorders • Functional connectivity (integration) Linear correlation Independent component analysis • Regional activity (functional segregation) Regional Homogeneity (Re. Ho) Amplitude of low frequency fluctuation (ALFF) 53
Functional connectivity, linear correlation analysis Multiple Sclerosis: Low-Frequency Temporal Blood Oxygen Level–Dependent Fluctuations Indicate Reduced Functional Connectivity Initial Results (Lowe et al. , 2002) 54
Functional connectivity, linear correlation analysis v Data analysis and results MT: the middle part of corpus callosum (connecting bilateral M 1), lower in MS patients (Lowe et al. , 2002) 55
Functional connectivity, linear correlation analysis Decreased functional connectivity between bilateral sensorimotor cortex (Lowe et al. , 2002) 56
Functional connectivity, linear correlation analysis Changes in hippocampal connectivity in the early stages of Alzheimer's disease: evidence from resting state f. MRI • Pure resting state • Subject-specific Seed ROIs in bilateral hippocampus • Correlation analysis (Wang L et al. , 2006) 57
(Wang L et al. , 2006) AD: decreased connectivity with the right hippocampus 58
Applications to brain disorders • Functional connectivity (integration) Linear correlation Independent component analysis • Regional activity (functional segregation) Regional Homogeneity (Re. Ho) Amplitude of low frequency fluctuation (ALFF) 59
Functional connectivity, Independent component analysis (ICA) Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI (Greicius et al. , 2004) 60
Methods v. Data: sensorimotor task in event-related design v. Independent component analysis (ICA) v. Define the default mode network component by “goodness-of-fit” with a PCC-template v. Between-group comparison on the Z maps v. Between-group comparison on the “goodness-of-fit” (Greicius et al. , 2004) 61
“Goodness-of-fit” Increased functional connectivity in normal elderly (Greicius et al. , 2004) 62
Applications to brain disorders • Functional connectivity (integration) Linear correlation Independent component analysis • Regional activity (functional segregation) Regional Homogeneity (Re. Ho) Amplitude of low frequency fluctuation (ALFF) 63
Regional coherence changes in the early stages of Alzheimer's disease: a combined structural and resting-state functional MRI study (He Y et al. , 2007) • Pure resting state • Regional homogeneity (Re. Ho) • Amplitude of low frequency fluctuation (ALFF) 64
MCI: decreased Re. Ho and ALFF in PCC, while increased in visual cortex (p < 0. 001, corrected) (He Y et al. , 2007) 65
Correlated with MMSE (He Y et al. , 2007) Consistent with PET studies (Reiman et al. , 1996; Minoshima et al. , 1994) 66
Summary on the resting-state f. MRI v Mechanism: needs further studies v Application to clinical studies: easy, cheap v Combine with other MRI: structure, perfusion (ASL), DTI 67
Multiple MRI modalities Computational Neuroanatomy MRS f. MRI: Task, Rest Others DTI 68
Multiple Disciplines v. Neurology and Psychiatry v. Neuroradiology v. Computer Science v. Cognitive Neuroscience v…… 69
Thanks to 拼音顺序: 贺永 贾建平 金真 蒋田仔 李坤成 Kiviniemi, Vesa 杨一鸿 王玉凤 翁旭初 谢晟 张岱 朱朝喆 …… All the group members! NSFC 30470575 30625024 30728017 30621130074 70
Thanks for your attention! 71
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