1. Fund BioImag 2013 13-1 13: Advanced MRI Contrast Mechanisms 1.How does moving blood affect the image phase ? 2.What is the effect of self-diffusion on the MR signal ? 3.Why is diffusion in vivo not isotropic ? Fiber tracking 4.How do the different imaging modalities compare ? Capabilities Limitations Choice Comparison by examples After this week you 1.Understand the influence of motion on the phase of magnetization 2.Understand how random motion leads to echo amplitude reduction 3.Are able to calculate the attenuation of the MR signal due to diffusion 4.Understand how diffusion-weighted MRI signal reflects cellular structure and how this can be exploited to track nerve fibers, among others 5.Have a firm grasp on the premises and limitations of the imaging modalities covered in this course

2. Fund BioImag 2013 13-2 Blood moving with velocity v time T2T0 13-1. How does Bulk Motion affect the Rephased Signal ? (Blood Flow) Freq. Encode (G x ) TE x(t)=x 0 +vt  (t) For transverse magnetization at point (x,y): Phase  of the magnetization: (Gradient along x)  does not depend on x  Entire echo has phase  at TE  (TE)

3. Fund BioImag 2013 13-3 13-2. How does self-Diffusion influence the MR signal ? = 20  m  = 0.1 s = 45  m  = 0.5 s = 63  m  = 1 s Einstein random walk: D: self diffusion coefficient : root mean square displacement after  seconds

4. Fund BioImag 2013 13-4 What is the effect of random motion on magnetization phase ? when applying pulsed gradient RF G 90° a b c d abcd Static magnetization: Magnetization in motion: stationary spins Displaced spins net transverse magnetization c: Particle displaces by r

5. Fund BioImag 2013 13-5 Ex. Effect of Diffusion on Magnetization Phase  of M xy Incoherent motion Absence of incoherent motion: Echo formation time T T G(t)  (t) All in-phase: max. echo formation  (t) Not all in-phase: reduced echo amplitude No diffusion With diffusion 

6. Fund BioImag 2013 13-6 gradient echo, i.e. sensitive to T 2 * How is the effect of diffusion on the MR signal described ? Mathematical description Degree of echo signal reduction 1.Strength of the diffusion process (D) 2.Delay between dephasing and rephasing gradient (  ) 3.Area of the dephasing gradient (strength G, duration  )   G Attenuation of the signal (echo amplitude) due to diffusion in the direction of G D: apparent diffusion coefficient (ADC)   G G 180 0 RF Equivalent sequence (spin echo, i.e. sensitive to T 2 )

7. Fund BioImag 2013 13-7 13-3. How is Anisotropic Water Diffusion described ? Consider structure along (myelinated) axon (or myofibril)  Anisotropic mean displacement  Anisotropic diffusion coefficient Diffusion coefficient depends on gradient orientation → Diffusion tensor D ij Motion (diffusion) of water molecules: Restricted by cell membranes Corpus callosum CSF (isotropic) GxGx GzGz GyGy 

8. Fund BioImag 2013 13-8 Diffusion tensor imaging (DTI) imaging anisotropic diffusion λ3λ3 λ1λ1 λ2λ2 Diffusion tensor symmetric: D ij = D ji 3 orthogonal Eigenvectors → Eigenvalues i For each voxel determine direction of principal eigenvector (largest ): Pseudocolor directionality Mean diffusivity (trace D ij ) Fractional Anisotropy ( 1 - 3 )

9. Fund BioImag 2013 13-9 Application: Fiber Tracking using Diffusion MRI from diffusion anisotropy to connectivity 1. Image of diffusion anisotropy 2. Directionality of water diffusion connects adjacent voxels (spaghettis) 3. Establish fiber tracks

10. Fund BioImag 2013 13-10 13-4. Bio-imaging modalities comparison I. contrast and limitations Major limitations strong e - density differences (bone) Ionizing radiation  emitters available non-uniform spatial resolution & sensitivity sensitivity time-consuming & motion-sensitive complex methodology does not penetrate hard objects (e.g. bone ) Major limitations strong e - density differences (bone) Ionizing radiation  emitters available non-uniform spatial resolution & sensitivity sensitivity time-consuming & motion-sensitive complex methodology does not penetrate hard objects (e.g. bone ) Contrast mechanisms CT e - density, Z MR (Spin concentration) Relaxation of magnetization Fat/Water (chemical shift) Diffusion (etc …) SPECT PET Tracer distribution in tissue US Boundaries of tissues with different mechanical properties

11. Fund BioImag 2013 13-11 Comparison II SNR, reconstruction, contrast agents Image reconstruction CT SPECT PET Directionality of photon →Radon transform Projection reconstruction MR precession of M  (gradient G) → Frequency analysis Fourier transform Contrast agents (contrast modifiers) Contrast agents (contrast modifiers) CT, x-ray Compounds with high Z MR Compounds shortening relaxation times (T 1, T 2, or T 2 *) Maximize SNR CT Increase radiation dose MR Increase magnetic field SPECT PET Increase tracer dose Limited by Effective radiation dose Equilibrium magnetization (Boltzmann distribution) Scatter noise Radiation dose

12. Fund BioImag 2013 13-12 Which bioimaging modality is right for you ? Rapid and least invasive assessment of tissue close to surface Contrast between air-tissue or bone- tissue Rapid scan with high spatial resolution Image receptors, glucose metabolism, transport, perfusion Biochemical information of tissue Exquisite soft tissue contrast with mm spatial resolution (rodent 100µm) Functional information US X-ray, CT SPECT, PET NMR spectroscopy MRI Immobile spins Bone Air Air- Tissue interface multiple exposures (ionizing radiation) Metallic implants & devices Moving blood (angiography) MRI (multiple means) CT (contrast agents) Doppler US

13. Fund BioImag 2013 13-13 13-5. Comparison of imaging modalities: Brain Skull gets in the way of X-ray imaging: –Bone scatters X-rays much more than soft tissue –MRI radio waves pass unimpeded through bone Images have been “skull stripped” Same patient FBPA-PET PETMRI (T 1 ) Contrast agents CT MRI prepost MRI (T 1 ) MRI (T 2 ) TE=30 msTE=80 ms FDG-PET MRI (T 1 ) MRI (T 2 ) post High grade astrocytoma High grade astrocytoma: registered MRI and PET images. Contrast-enhanced spin echo T1 MRI (upper left), registered PET FDG (upper right), and two T2-weighted MRI images (less T2- weighting Te = 30 ms, TR = 2,500 ms [lower left]; more T2-weighting [Te = 80 ms, tR = 2,500 ms] [lower right]) in a patient with a recurrent high-grade astrocytoma. Note irregular zone of contrast enhancement on contrast-enhanced T1 MRI image adjacent to posterior margin of lateral ventricle. PET FDG image was registered and aligned to correspond to the level and angle of the MRI images. Note zone of increased uptake of FDG, indicating viable tumor, best seen on anterior margin of lesion. Central zone of decreased FDG uptake and low signal on contrast- enhanced MRI within the lesion is consistent with central necrosis of the lesion. Also note diminished FDG uptake in overlying occipital cortex, corresponding in distribution to edema evident on T2 images (lower row).

14. Fund BioImag 2013 13-14 http://www.eradimaging.com/site/article.cfm?ID=327 PETMRI SPECT MRI Heart Lung Liver Whole body CT MRI US 3D CT of mouse Comparison of modalities: Body