1. Basics of Perfusion Imaging With Dynamic Contrast MRI Larry Panych, PhD Brigham and Women’s Hospital

2. Contents What is perfusion and why do we care about it? How can it be measured and what are the parameters? What MR approaches are used in perfusion studies? How is dynamic contrast data processed?

3. Perfusion is the steady state delivery of blood to the tissue

4. Elastic Arteries Large arteries close to the heart Expand and recoil with changes in blood volume Relatively inactive in vasoconstriction Can be viewed as simple elastic tubes Muscular Arteries Medium and smaller arteries Less elastic, more smooth muscle more active in vasoconstriction distribute blood to specific organs Arterioles Lumen diameter less than.5mm Coils of smooth muscle Constriction/dilation controls flow of blood to capillary bed Capillaries Blood cells flow in single file Average length is 1mm and diameter.01mm Provide access to all cells in the body Exchange materials between blood and interstitial fluid

5. Much of pathology begins at the cellular and tissue level and is not accompanied by changes in macroscopic blood flow

6. Some methods to image perfusion PET SPECT CT MRI

7. MRI Perfusion Methods Bolus Tracking (T1 and T2) Steady State Techniques Arterial Spin Labeling

8. Perfusion Parameters Blood Flow (ml of blood/gm of tissue/sec) Blood Volume (ml of blood/gm of tissue) Mean Transit Time (MTT) (sec) V = F MTT

9. Bolus injection of paramagnetic agent (Gd) Contrast agent injected into vein Lung Heart Arm

10. Blood Vessel Contrast Agent Particles Susceptibility Gradient Intra-voxel Incoherent motion (  T2) Intra-voxel static dephasing (  T2*) Figure from Cerebral MR Perfusion. Sorensen and Reimer

11. Intra-voxel Spin Motion Random or very Intelligently Designed??

12. Signal loss depends on vessel size and type of scan Spin-echo sequences are more selective for small vessels because diffusion effects dominate for smaller vessels. Voxel close to large vessel sees little field variation voxel close to small vessel sees large field variation Figure from Cerebral MR Perfusion. Sorensen and Reimer

13. A.Pre-injection baseline B.Contrast arrival C.Peak signal change D.Recirculation E.Post-injection baseline A.Arrival time B.Maximum contrast concentration C.Full-width at half maximum Change in MRI signal due to passage of contrast agent Figure from Cerebral MR Perfusion. Sorensen and Reimer

14. Conversion of signal-vs-time to concentration-vs-time C(t) = -k/T E ln(s(t)/s o ) Figure from Cerebral MR Perfusion. Sorensen and Reimer

15. Assume a known amount of tracer is injected in a volume and flow is constant. The flow can be measured by monitoring the concentration, C(t), at the output of the volume. Flow = A / C(t) dt where A is total amount of agent injected. Indicator Dilution Theory Tracer in Tracer out Figure from Cerebral MR Perfusion. Sorensen and Reimer

16. Indicator Dilution Theory C(t) tt A = C(  t) F  t + C(2  t) F  t + …. C(n  t) F  t + … A = F C(t) dt or F = A / C(t) dt Units: A, mmol C(t), mmol/ml F, ml/sec

17. Differences in Dynamic Contrast MRI don’t know how much goes into each voxel the injection is not instantaneous don’t monitor concentration at output flow may not be uniform in voxel

18. Indicator Dilution Theory Applied to DC-MRI tt C V (  t) = C A (  t) R 1 F  t C V (2  t) = C A (2  t) R 1 F  t + C A (  t) R 2 F  t … C V (n  t) = C A (n  t) R 1 F  t + … C A (  t) R n F  t Units: C V, mmol/gm C A (t), mmol/ml F, ml/gm/sec R n, Fraction of contrast agent remaining in the tissue VOI where R 1 = 1. C A (t), Arterial Input Function

19. C V (  t) C V (2  t) C V (3  t) … C V (n  t) C A (  t) C A (2  t) C A (  t) C A (3  t) C A (2  t) C A (  t) C A (4  t) C A (3  t) C A ( 2  t) … C A (n  t) C A ((n-1)  t) … C A (  t) = R1R2R3…Rn R1R2R3…Rn F C V = F C A R Solve for FR. F = max of FR. V = F  R Indicator Dilution Theory Applied to DC-MRI 0

20. C V = F C A R. How to solve for FR? One method: Get pseudo-inverse of C A. SVD truncation threshold can be set arbitrarily or by optimizing ‘goodness’ parameters.

21. A B C A: SVD Threshold = 0.015C: SVD Threshold = 0.200 B: SVD Threshold = 0.050

22. Getting an Arterial Input Function MCA Pre-injection scanPost-injection – at peak signal change

23. Very difficult to get a curve that truly represents the concentration of the contrast agent in the vessel. This is a major factor in limiting the ability to absolute perfusion measures. Getting an Arterial Input Function

24. Other Issues for Quantitative Perfusion Even if a good concentration curve can be obtained, the arterial input function measured at the large artery does not represent the true arterial input to the voxel. There is possibly delay and dispersion of the AIF. Obtaining absolute quantitative perfusion measures requires knowledge of a number of physiological parameters that can not be determined with great accuracy.