3.1 T 127 MHz 3.0 T 123 MHz 2.9 T 119 MHz excite Like a swing. Got one of the 3 orthogonal spatial dimensions when we excite. z

3.1 T 127 MHz 3.0 T 123 MHz 2.9 T 119 MHz phase encode (after we excite before we listen) Got second of the 3 orthogonal spatial dimensions when we listen. fast slow regular y

3.1 T 127 MHz 3.0 T 123 MHz 2.9 T 119 MHz LISTEN Got second of the 3 orthogonal spatial dimensions when we listen. fast slow regular Model of Head Coil x signal we “hear”

Repeat 256 times for a 256x256 pixel image Different phase each time scan = 4 minutes

180 Degree RF Pulse correcting gradients Excite Z Y X Listen SPIN ECHO SEQUENCE TE – echo time TR – repeat time

Contrast T1 weighted – (MPRAGE-anatomical) T2 weighted – (fmri)

Spin Relaxation Spins do not continue to precess forever Longitudinal magnetization returns to equilibrium due to spin-lattice interactions – T 1 decay Transverse magnetization is reduced due to both spin-lattice energy loss and local, random, spin dephasing – T 2 decay Additional dephasing is introduced by magnetic field inhomogeneities within a voxel – T 2 ' decay. This can be reversible, unlike T 2 decay

T1 decay – “spins back down” Collective Magnetic Moment of Protons end start B0B0 signal we “hear” V Time T1 Recovery Longitudinal Magnetization Time 2.0s

T2 decay – separation (dephasing) of “collective magnetic moment” sometime after RF excitation Immediately after RF excitation = collective magnectic moment individual spins separation (dephasing) a little time later T2 Decay Transverse Magnetization Time 0.2s

T2 Decay Trans. Mag. T1 Recovery Long. Mag. 50 ms 1 s Image type: Proton Density Contrast TE – echo time TR – repeat time

Proton Density Weighted Image

T2 Decay Trans. Mag. T1 Recovery Long. Mag. 50 ms 1 s T1 Contrast time TE – echo time TR – repeat time

T1 Weighted Image

T2 Decay Trans. Mag. T1 Recovery Long. Mag. 50 ms 1 s T2* and T2 Contrast TE – echo time TR – repeat time

T2 Weighted IMage

ProtonDensityWeightedImageT1WeightedImageT2WeightedImage

Properties of Body Tissues MRI has high contrast for different tissue types!

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

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? 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? Functional MRI Acquisition

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)

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

HbO 2 Vascular Response to Activation dHb O 2 metabolism dHb HbO 2 dHb HbO 2 dHb HbO 2 blood flow HbO 2 [dHb] dHb = deoxyhemoglobin HbO 2 = oxyhemoglobin capillary blood volume HbO 2 neuron

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)

BOLD Contrast vs. T E BOLD effect is approximately an exponential decay: S(T E ) = S 0 e –T E R 2 *  S(T E )  T E R 2 * R 2 * encapsulates all sources of signal dephasing, including sources of artifact (also increase with T E ) Gradient echo (GE=GRE=FE) with moderate T E 1–5% change

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? Functional MRI Acquisition

The Canonical FMRI Experiment 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 Predicted BOLD signal time Stimulus pattern on off on off on off on off

What is required of the scanner? 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) 123 …image

Review: Image Formation 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 k-space image space Fourier transform kyky kxkx

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

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

Conventional T 2 WI DW-EPI 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 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 Why USE DTI MRI Tumor T2 (bright water) DWI (x direction) (T2 (bright water)+(diffusion)) Contrast (T1 + Gadolinium) T2 (bright water)

Why DTI MRI (more recently): Fiber Tracking

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

RF Gx Gy Gz - Time (gradient strength) T2T2 + diffusion T2 Image Sequence Excite Measure diffusion Regular T2 image

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

3rd level of complexity Diffusion Tensor Imaging Basics 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 How can we track white matter fibers using DTI

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

IsotropicAnisotropic Adapted from: Beaulieu (2002). NMR in Biomed; 15:  Higher diffusion  lower signal White matter fibers

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

Pierpaoli and Basser, Toward a Quantitative Assessment of Diffusion Anisotropy, Magn. Reson. Med, 36, (1996) Ellipsoid Image Tract Information available through DTI

Tractography Zhang & Laidlaw: Superior view color fiber mapsLateral view color fiber maps

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 axial sag cor MRISC

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

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 MRS – Magnetic Resonance Spectroscopy

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

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

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?