Contrast and Acquisition Functional MRI: Image Contrast and Acquisition Karla L. Miller FMRIB Centre, Oxford University

Functional MRI Acquisition Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acqusition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure? Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acquisition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure?

The BOLD Effect BOLD: Blood Oxygenation Level Dependent Deoxyhemoglobin (dHb) has different resonance frequency than water dHb acts as endogenous contrast agent dHb in blood vessel creates frequency offset in surrounding tissue (approx as dipole pattern)

The BOLD Effect Frequency spread causes signal loss over time BOLD contrast: Amount of signal loss reflects [dHb] Contrast increases with delay (TE = echo time)

Vascular Response to Activation neuron capillary HbO2 HbO2 dHb HbO2 HbO2 dHb dHb = deoxyhemoglobin HbO2 = oxyhemoglobin [dHb] O2 metabolism blood flow blood volume

Sources of BOLD Signal Neuronal activity Metabolism Blood flow Blood volume [dHb] BOLD signal Very indirect measure of activity (via hemodynamic response to neural activity)! Complicated dynamics lead to reduction in [dHb] during activation (active research area)

S(TE) = S0 e–TE R2* S(TE)  TE R2* BOLD Contrast vs. TE 1–5% change BOLD effect is approximately an exponential decay: S(TE) = S0 e–TE R2* S(TE)  TE R2* R2* encapsulates all sources of signal dephasing, including sources of artifact (also increase with TE) Gradient echo (GE=GRE=FE) with moderate TE

Functional MRI Acquisition Basics of FMRI FMRI Contrast: The BOLD Effect Standard FMRI Acquisition Confounds and Limitations Beyond the Basics New Frontiers in FMRI What Else Can We Measure?

The Canonical FMRI Experiment Stimulus pattern on off Predicted BOLD signal time Subject is given sensory stimulation or task, interleaved with control or rest condition Acquire timeseries of BOLD-sensitive images during stimulation Analyse image timeseries to determine where signal changed in response to stimulation

What is required of the scanner? image 1 2 3 … Must resolve temporal dynamics of stimulus (typically, stimulus lasts 1-30 s) Requires rapid imaging: one image every few seconds (typically, 2–4 s) Anatomical images take minutes to acquire! Acquire images in single shot (or a small number of shots)

Review: Image Formation Fourier transform ky kx k-space image space Data gathered in k-space (Fourier domain of image) Gradients change position in k-space during data acquisition (location in k-space is integral of gradients) Image is Fourier transform of acquired data

BOLD Signal Dropout BOLD Non-BOLD Dephasing near air-tissue boundaries (e.g., sinuses) BOLD contrast coupled to signal loss (“black holes”)

DTI Basics – Water Diffusion (DTI – Diffusion Tensor Imaging) Einstein on Brownian Motion 1905 five important papers

Why USE DTI MRI : Detection of Acute Stroke “Diffusion Weighted Imaging (DWI) has proven to be the most effective means of detecting early strokes” Lehigh Magnetic Imaging Center Conventional T2 WI DW-EPI Sodium ion pumps fail - water goes in cells and can not diffuse – DW image gets bright (note – much later cells burst and stroke area gets very dark)

Why USE DTI MRI Tumor T2 (bright water) T2 (bright water) DWI (x direction) (T2 (bright water)+(diffusion)) Contrast (T1 + Gadolinium)

Why DTI MRI (more recently): Fiber Tracking

1st level of complexity Diffusion Weighted Image X direction Higher diffusion in X direction  lower signal Artifact or Abnormality David Porter - November 2000

T2 + diffusion T2 Sequence RF Gx Gy Gz Time T2 Image - Time T2 Image Measure diffusion Regular T2 image Excite (gradient strength)

2nd Level of complexity Measuring Diffusion in other directions DWI : 3 Direction Measuring Diffusion in other directions (examples) single-shot EPI diffusion-weighted (DW) images with b = 1000s/mm2 and diffusion gradients applied along three orthogonal directions Higher diffusion  lower signal Dzz Dxx Dyy  courtesy of Dr Sorensen, MGH, Boston David Porter - November 2000

3rd level of complexity Diffusion Tensor Imaging Basics How can we track white matter fibers using DTI Measures water diffusion in at least 6 directions Echo-planar imaging (fast acquisition) Collecting small voxels (1.8 x 1.8 x 3mm), scanning takes about 10 minutes

Higher diffusion  lower signal water Diffusion ellipsoid Diffusion ellipsoid White matter fibers Useful for following white matter tracts in healthy brain

Higher diffusion  lower signal White matter fibers Displacement of 4 particles starting at same origin Similar molecular displacements in all directions Greater molecular displacement along cylinders than across Isotropic Anisotropic Adapted from: Beaulieu (2002). NMR in Biomed; 15:435-455

DTI ellipsoid measure 6 directions to describe z no diffusion y x Ellipsoid represents magnitude of diffusion in all directions by distance from center of ellipsoid to its surface.

Information available through DTI Ellipsoid Image Information available through DTI Tract Monkey brain, in-vivo Pixel by pixel map of the diffusion ellipsoids in the ROI shown in the image. The Diffusion ellipsoids summarize all the information that we can obtain with DTI. This presentation is focused on the scalar ones, but we can clearly see the direction of the fibers in the corpus callosum. Pierpaoli and Basser, Toward a Quantitative Assessment of Diffusion Anisotropy, Magn. Reson. Med, 36, 893-906 (1996)

Tractography Superior view color fiber maps Lateral view color fiber maps Zhang & Laidlaw: http://csdl.computer.org/comp/proceedings/vis/2004/8788/00/87880028p.pdf.

axial cor sag Diffusion Tensor Imaging data for cortical spinal tract on right side blue = superior – inferior fibers green = anterior – posterior fibers red = right – left fibers Note tumor is darker mass on left side of axial slice MRISC

FA + color (largest diffusion direction) red = right – left green = anterior – posterior blue = superior - inferior

MRS – Magnetic Resonance Spectroscopy Proton spectroscopy (also can do C, O, Ph,.. Nuclei) Looking at protons in other molecules ( not water) (ie NAA, Choline, Creatine, …….) Need > mmol/l of substances high gyromagnetic ratio ( ) Just like spectroscopy used by chemist but includes spatial localization

Just looking at Proton Spectroscopy Just excite small volume Do water suppression so giant peak disappears Compare remaining peaks precession Frequency Frequency

MRS – Magnetic Resonance Spectroscopy NAA = N-acetyl aspartate, Cr = Creatine, Cho = Choline amplitude NAA Cr Cho Frequency of precession

Multi – Voxel Spectroscopy (aka Chemical Shift Imaging – CSI) Do many voxels at once Can be some disadvantages with signal to noise (S/N) and “voxel bleeding”

Evaluate Health of Neurons (NAA level) Normalize with Creatine (fairly constant in brain) Red means High NAA/CR levels

Epilepsy Seizures (effects metabolite levels) find location determine onset time

Other Nuclei of interest for Spectroscopy

23Na in Rat Brain (low resolution images are sodium 23 images) (high resolution images are hydrogen images)

Common Metabolites used in Proton Spectroscopy

Important Concepts What energies are used in each modality? How does the energy interact with the tissue? How is the image produced? What is represented in the image? What are important advantages and disadvantages of the major imaging modalities? What are the fundamental differences between the Xray technologies (2D vs 3D, Radiography vs CT vs Fluoroscopy)? What are the two major types of MRI images (T1, T2), and how are they different? How are Angiograms produced (both Xray and MRI)? Why are the advantages of combining imaging modalities?

Important Concepts What does DTI, diffusion tensor imaging, measure? What structures that we are interested in effect DTI images? What does the DTI ellipsoid represent? How might DTI be useful for clinical application or research? What are we looking at with proton spectroscopy? What are the three major metabolites we typically measure? What do we “need” to be able to do proton spectroscopy? What might proton spectroscopy be used for?