Resting-state fmri and DTI

Transcription

1 Resting-state fmri and DTI David C. Zhu, Ph.D. Associate Professor of Radiology and Psychology Cognitive Imaging Research Center Michigan State University, East Lansing, Michigan, USA

2 Facts The rain is only aout 2% of total ody mass. But it consumes aout 20% of the ody s total energy at rest. Engaging in active tasks increases neuronal metaolism less than 5%. What is this energy at rest consumed y? The on-going spontaneous neuronal activity

3 Huettel SA, Song AW, McCarthy G. Functional Magnetic Resonance Imaging.

4 Oxygenated and deoxygenated hemogloin (H)

5 Two Main Paths of BOLD (Blood Oxygen Level-Dependent) fmri First 1-2 seconds Later seconds Stimulation Neuronal Activity CMR glucose CMR O2 Cereral Blood Flow (CBF) Blood Oxygen Level Blood Oxygen Level Deoxygenated hemogloin: paramagnetic Blood Magnetic Susceptiility Effects Oxygenated hemogloin: diamagnetic Blood Magnetic Susceptiility Effects T 2 * decay T 2 * decay fmri Image Signal Intensity fmri Image Signal Intensity

6 Resting-state fmri ased functional connectivity analyses Assumptions Strong BOLD fmri temporal correlation Strong neuronal synchronous activity Strong functional connectivity Same/intact network A B C D E

7 Two popular methods of processing for resting-state fmri 1. Correlation analysis 2. Independent component analysis (ICA)

8 Seed-ased correlation analysis seed EPI S measure =S intrinsic +S random

9 Time courses of correlated and uncorrelated regions Seed pc/rsp Left et MeFG Right MTG Left IPL

10 Resting-state tt fmri pre-processing steps 1. Slice-timing and motion correction. 2. Remove aseline, linear and quadratic system trends. 3. Spatial lurring. 4. Remove Nuisance signals of (a) Gloal mean () CSF (c) White matter 5. Band-pass filtering: Hz 0.08 Hz

11 Seed Region #1: pc/rsp (posterior cingulate/retrosplenial cortex) Group Integration (17 sujects): Whole-rain corrected P < Mean structural t normalized connectivity distriution > pc/rsp MeFC/ACC (Medial Frontal Cortex/ Anterior Cingulate Cortex) Zhu DC, Majumdar S. Integration of resting-state fmri and diffusion-weighted MRI connectivity analyses of the human rain: limitations and improvement. J Neuroimaging Mar-Apr;24(2):

12 Seed Region #2 : Right SPL (superior parietal a loule) Group Integration (17 sujects): Whole-rain corrected tdp P < Mean structural normalized connectivity distriution > Right SPL Left SPL

13 Seed Region #3: Left Cuneus Group Integration (17 sujects): Whole-rain corrected P < Mean structural normalized connectivity distriution > Left cuneus Right cuneus

14 Independent Component Analysis

15

16 ICA example results with MELODIC in FSL IC 1: Default Mode Network

17 IC 25: Visual Network

18 Medial temporal loe (MeTL) Default-Mode Network Medial prefrontal cortex (MePFC) (hippocampus, parahippocampal gyrus, (Medial frontal cortex, anterior cingulate entorhinal gyrus) cortex, superior frontal cortex) (memory processing) (facilitation) Structural connectivity (diffusion MRI fier tracking) Posterior cingulate cortex/retrosplenial cortex (PCC/RSC) (Integration) temporoparietal junction cortices (TPJC): (angular gyrus, superior/middle temporal gyrus, parietal loule, supramarginal gyrus) Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The rain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124, 1-38.

19 Alzheimer s disease and amnestic mild cognitive impairment weaken connections within the default-mode network Zhu DC, Majumdar S, Korolev IO, Berger KL, Bozoki AC. Alzheimer s disease and amnestic mild cognitive impairment weaken connections within the default-mode network: a multi-modal imaging study. J Alzheimer's Dis. 2013;34(4):

20 7 minute resting-state fmri EPI scan (relax and eyes open in dim-light condition): 38 contiguous 3-mm axial slices, 22 cm 22 cm FOV, matrix size, 27.7 ms TE, 2500 ms TR, 80 flip angle, 164 time points.

21 Seed location Normal Amnestic mild cognitive impairment Alzheimer s disease GM seed L TPJC R cingulum R MeFG (a) WM seed R TPJC R isthmus of cingulate GM seed R TPJC L cingulum L MeFG () WM seed L TPJC Li isthmus of cingulate Thresholds: whole-rain corrected p for functional connectivity and mean connectivity distriution of > 1000 for structural connectivity. Green: functional connection only. Orange: structural connection only. Red: coexistence of oth connections. GM: gray matter. WM: white matter. R = right. L = left. MeFG = medial frontal gyrus. TPJC = temporoparietal junction cortices.

22 Functional connectivity with seed region at the right isthmus of cingulate cortex (Normal > AD) PET R STG/MTG R precuneus L precuneus L AG LMTG R AG/IPL L CG (a) R TPJC () PCC/RSC (c) L TPJC (d) PET: NC > AD

23 Structural connectivity with the seed region in the associated white matter of the right isthmus of cingulate cortex NC > AD NC > amci

24 A potential iomarker in sports-related related concussion: rain functional connectivity alteration of the default-mode network measured with longitudinal resting-state state fmri over 30 days. Zhu DC, Covassin T, Nogle S, Doyle S, Russell D, Pearson RL, Zhu DC, Covassin T, Nogle S, Doyle S, Russell D, Pearson RL, Monroe J, Liszewski CM, DeMarco JK, Kaufman DI. J Neurotrauma Mar 1;32(5):

25 The DMN Network R IPL/AG L PCC R PCC L IPL/AG L SFG R SFG R ACC/MeFC L ACC/MeFC L Hippo

26 MN Con nnectivit ty (R) Ov verall D Mean default-mode network connectivity (7 concussed, 11 control) Day 1 Day 7 Day 30 Concussed Control

27 DMN after concussion (n = 7) (Node # 1 = left PCC, 2 = left ACC/MeFC, 3 = left SFG, 4 = left IPL/AG, 5 = left hippocampus, 6 = right PCC, 7 = right ACC/MeFC, 8 = right SFG, 9 = right IPL/AG, 10 = right hippocampus) Node Mean correlation R on Day 1 Node Node Mean correlation R on Day Mean correlation R on Day 30 R value Node t test of Day 1 vs. Day 7 Node t test of Day 7 vs. Day 30 Node t test of Day 1 vs. Day 30 p value

28 DMN of control sujects (n=11) (Node # 1 = left PCC, 2 = left ACC/MeFC, 3 = left SFG, 4 = left IPL/AG, 5 = left hippocampus, 6 = right PCC, 7 = right ACC/MeFC, 8 = right SFG, 9 = right IPL/AG, 10 = right hippocampus) Node Mean correlation R on Day 1 Node Node Mean correlation R on Day Mean correlation R on Day 30 R value Node t test of Day 1 vs. Day 7 Node t test of Day 7 vs. Day 30 Node t test of Day 1 vs. Day 30 p value

29 The mean functional connectivity to left isthmus of cingulate cortex (ICC) of the concussed group (correlation R > 0.25, n = 7) Day 1 () ANOVA: Day 1 vs. Day 7 (n = 8) Day 7 Day 30 (c) ANOVA: Day 1 vs. Day 30 (n = 7)

30 Case study The functional and structural connectivity to left isthmus of cingulate cortex of a concussed suject over one month (correlation R > 0.4 and connectivity distriution > 1000). Seed regions Day 1 Day 7 Day 30 structural functional Green: functional seed Orange: structural seed Red: overlap regions. The aove functional connectivity it reduction from Day 1 to Day 7 was seen in 8 of our 9 concussed cases.

31 Resting-state fmri ased functional connectivity analyses Assumptions? Strong BOLD fmri temporal correlation Vascular confound Strong neuronal synchronous activity it Why? Strong functional connectivity Same/intact network The underlying cellular and molecular ases A B C D E

32 Introduction to Diffusion Tensor Imaging (DTI)

33 Fick s Law descries particle movement Net flux (mole mm 2 /s): J = D ΔC C Δx Diffusion coefficient D is in mm 2 /sec ΔC Δx = concentration gradient in mole/mm 4 High concentration J Low concentration

34 Figure 5.20 Diffusion

35 Stejskal-Tanner Diffusion-weighted Sequence G

36 Isotropic Diffusion Signal attenuation due to diffusion coefficient D A = S S 0 = e D Where = commonly called factor, which characterizes the gradient pulses (timing, amplitude, shape) = clinical practice, 1000 s/mm 2

37 Stejskal-Tanner Diffusion-weighted Sequence G = γ G δ ( Δ δ ) δ

38 Anisotropic Case (for example, axons) D D A = e D D D yz yy yx xz xy xx = zz zy zx yz yy yx xz xy xx D D D D D D D D D D = diffusion tensor = zz zy zx zz zy zx ) ( D D D D D D ) ( yz yz xz xz xy xy zz zz yy yy xx xx D D D D D D e A =

39 Diagnolization DE = EΛ E = eigen vector (unit vector) Λ = eigen value = λ λ λ 3 z x x y Laoratory frame y λ λ 2 λ 3 z λ 1 Diffusion ellipsoid

40 Mean diffusivity = λ mean = (λ 1 + λ 2 +λ 3 )/3 The level of tissue constraint Fractional lanisotropy = FA = 2 2 3[( λ 1 λ mean) + ( λ 2 λ mean) + ( λ 3 λ ( λ + λ + λ ) mean ) 2 ] the directionality of diffusion Axon fier integrity Mean diffusivity map FA map

41 Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G. Diffusion tensor MR imaging of the human rain. Radiology Dec;201(3):

42 Fier Tracking

43 Deterministic approach: Answer Yes/no. Software: (1) DTI Studio (2) MedINRIA Proailistic approach: How proale two voxels/regions connected together Software: FSL

44 Proailistic tracking at Right Fornix

45 Data Acquisition GE 3T Signa HDx MR scanner with an 8-channel head coil. 12 minute and 6 second DTI scan (full-rain coverage): Dual spin echo EPI sequence, mm axial slices, 22 cm 22 cm FOV, , 2 NEX, 75 ms TE, 13.7 s TR, parallel imaging acceleration factor = 2, = 1000 s/mm 2, 25 directions

46 DTI Analysis with the Diffusion Toolox (FDT v2.0) in FSL software package Eddy-current distortion and motion correction. Applied Bayesian Estimation of Diffusion Parameters Otained using Sampling Techniques with the crossing fiers (n = 2) modeled d (BEDPOSTX). Applied proailistic tractography (PROBTRACKX) to each seed region to calculate the corresponding connectivity distriutions. The connectivity distriutions were then normalized y the total numer of generated tracts from the seed region. Behrens TE, Berg HJ, Jadi S, Rushworth MF, Woolrich MW. NeuroImage 2007, 34:

47 Integration Resting-state fmri allows the examination of rain function connectivity (1). Diffusion tensor imaging (DTI) fier tracking allows the evaluation of structural connection etween cortical regions (2). 1 F MD R i hl ME N t R N i Fox MD, Raichle ME. Nat Rev Neurosci. 2007; 8: Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, Chariat H. J Magn Reson Imaging. 2001;13:

48 Left PCC Left ACC Test oth functional and structural connectivity.

49 Case study The functional and structural connectivity to left isthmus of cingulate cortex of a concussed suject over one month (correlation R > 0.4 and connectivity distriution > 1000). Seed regions Day 1 Day 7 Day 30 structural functional Green: functional seed Orange: structural seed Red: overlap regions. The aove functional connectivity it reduction from Day 1 to Day 7 was seen in 8 of our 9 concussed cases.

50 Volumetric Analysis and Segmentation with FreeSurfer

51 Time point 0 Time point 1 % change Left-Putamen Left-Pallidum

52

53 Region Time 0 (cc) Time 1 (cc) % change lh_postcentral_volume lh_precentral_volume lh_p precuneus_ volume

54