Renal perfusion measurement with Ultrasound Contrast Agents. Emilio Quaia. Department of Radiology University of Trieste

Transcription

1 Renal perfusion measurement with Ultrasound Contrast Agents Emilio Quaia Department of Radiology University of Trieste

2 Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment

3 1. US contrast agents - Chemicals Gas-filled microbubbles with an acoustic impedance different from the blood and relatively permeable shell 2 7 µm

4 1. US contrast agents - Chemicals Optical Micrograph Microbubbles red blood cells

5 1. US contrast agents - Chemicals Strategies to increase persistence Capsule stabilization (phospholipid- or albumin - coated microbubbles) PFCs Modified from: Blomley MJK BMJ 2001

6 1. US contrast agents - Chemicals Licensed in Europe: Definity *, Optison *, SonoVue, Levovist * Cardiac use only (LVO and EBD) Liver Imaging in Canada

7 1. US contrast agents - Chemicals

8 Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment

9 2. US contrast agents - Physics Microbubble Insonation volume pulsation gas bubble transducer ultrasound wave

10 2. US contrast agents - Physics Microbubble Insonation volume pulsation Scattered ultrasound wave

11 2. US contrast agents - Physics Microbubble Insonation Mechanical Index (MI) Resonance frequency (f 0 ) Scattering Cross Section (σ)

12 2. US contrast agents - Physics MI determines the type of signal produced by microbubbles MI Destruction Wideband emission Resonance Scattering Harmonics MI = P - f

13 2. US contrast agents - Physics Low MI: Symetric behaviour; Higher MI: Non-linear behaviour;

14 2. US contrast agents - Physics Linear response: Mean diameter vs time is smaller; Lower σ; Non-Linear response: Mean diameter vs time is larger; Higher σ;

15 2. US contrast agents - Physics

16 2. US contrast agents - Physics Contrast specific imaging techniques are necessary for a correct management of the harmonic signal Signal saturation Artifacts: Blooming Jail bar artifact

17 Blooming Jail bar

18 Contrast-specific Techniques 1. Pseudo - Doppler 2. Harmonic Imaging Aims: 1. Detect echo from bubbles 2. Suppress echo from tissues 3. Phase Modulation 4. Amplitude Modulation 5. Phase and Amplitude modulation

19 Contrast-specific Techniques 3. Phase Modulation Pulse Inversion Mode (2 impulsi) Power Pulse Inversion (3 impulsi) Coherent Contrast Imaging Vascular Recognition Imaging Color Flow Contrast Coded Harmonic Angio

20 Pulse Inversion

21 Burns et al Pulse Inversion

22 Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment

23 3. Pharmacokinetics SF 6 SF6 SF 6 SF 6 Microbubbles Structure SF 6 SF 6 Intravascular agents: Rapid transit through the lungs, cardiac chambers; Phospholipids Hydrophobic chain SF 6 SF 6 Hydrophilic pole

24 3. Pharmacokinetics Mean terminal half-life life 12 min (range 2 33 min); Half-life life elimination less than 1min; 98% of SF6 exhaled within 2 minutes; Pharmacokinetic properties typical of the different microbubbles;

25 Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment

26 4. Renal perfusion assessment

27 Frames grabbing Video-intensity analysis MPEG-encoder and Frames-grabber software Digital cine-clips registered directly by the US-equipment (DICOM, AVI, or propietary formats) A/D Output video Digital cine-clips

28 Linear correlation between microbubble concentration and video-intensity

29 Echo-signal quantification Software working on cine-clips - Log-compressed data for video presentation Video-intensity = 10 * log 10 (I / I ref ) = Raw data before log-compression

30 4. Renal perfusion assessment For perfusion quantification it is mandatory slow infusion by a dedicated injector bolus infusion steady state

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33 Negative exponential: y = A(1-e ) Parenchyma = Replenishment The exponential behaviour is a consequence of diffusion

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35 Real time low MI imaging Tempo Destructive pulse I 5 4 Blood volume (A) 3 I = A (1 e (-βt) ) Blood velocity (β) t

36 Quantification Parameters Plateau phase (A) ~ Relative (fractional) blood volume Slope of the curve (b) ~ Blood B flow speed A x b ~ Perfusion AUC ~ Microbubble concentration ~ Perfusion Time to peak (secs) ~ Blood B flow speed Peak enhancement ~ Relative blood volume Washin and washout rate ~ Blood B flow speed

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38 Mathematical Algorithms ~ Arterial Input Function 1. Gamma variate (peripheral vessels) 2. Negative Exponential (parenchyma) 3. Other algorithms

39 Negative exponential: A = A 0 (1-e -βt ) A A = A 0 [1 e βt ] Wei K et al. Circulation 97: , 1998

40 Beam width = v

41 Renal artery stenosis vs Normal kidney

42 Negative exponential Limitations: 1. The percentage of destroyed microbubbles entering the ROI is not null; 2. Assumption of a constant concentration of microbubble entering the ROI; 3. Neglects the different direction of vessels entering in the ROI;

43 Sigmoid A approximations Lucidarme O et al. Radiology 228: , 2003

44 Beam width = v

45 Piecewise Linear Function Microbubble void is dragged by the liquid and is filled by microbubble diffusion

46 Beam width = v

47 The transit times are the times that separate the linear tracts; The slopes are directly related to the flows; The signal intensities at the transit times are related to the compartment volumes. Quaia E et al. Ultrasound Medicine Biology 2009

48 MSE 0.25 vs 0.15

49 Piecewise Linear Function 25 vs 70 years old volunteer

50 Piecewise Linear Function 25 vs 70 years old volunteer

51 Renal perfusion defects

52 Quaia E et al. Eur Radiol 2006

53 Results - Conspicuity

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60 Conclusions Contrast-enhanced US allows: 1. Quantitation of renal perfusion - Problems related to slice thickness and mathematical model 2. Detection of renal perfusion defects - Problems related to the limited spatial resolution 3. Functional studies and neoangiogenesis

61 MCQ 1. The most accurate quantitation of the echo-signal intensity is based on: a. Lineary scale; b. Logarithmic scale; c. Digitation of video-intensity; d. None of the previous;

62 MCQ 2. How quantitation of renal perfusion by contrast-enhanced ultrasound can be defined? a. quantitative; b. semiquantitative; c. qualitative; d. none of the previous;