Renal perfusion measurement with Ultrasound Contrast Agents Emilio Quaia Department of Radiology University of Trieste
Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment
1. US contrast agents - Chemicals Gas-filled microbubbles with an acoustic impedance different from the blood and relatively permeable shell 2 7 µm
1. US contrast agents - Chemicals Optical Micrograph Microbubbles red blood cells
1. US contrast agents - Chemicals Strategies to increase persistence Capsule stabilization (phospholipid- or albumin - coated microbubbles) PFCs Modified from: Blomley MJK BMJ 2001
1. US contrast agents - Chemicals Licensed in Europe: Definity *, Optison *, SonoVue, Levovist * Cardiac use only (LVO and EBD) Liver Imaging in Canada
1. US contrast agents - Chemicals
Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment
2. US contrast agents - Physics Microbubble Insonation volume pulsation gas bubble transducer ultrasound wave
2. US contrast agents - Physics Microbubble Insonation volume pulsation Scattered ultrasound wave
2. US contrast agents - Physics Microbubble Insonation Mechanical Index (MI) Resonance frequency (f 0 ) Scattering Cross Section (σ)
2. US contrast agents - Physics MI determines the type of signal produced by microbubbles MI Destruction Wideband emission 0.3 0.01 Resonance Scattering Harmonics MI = P - f
2. US contrast agents - Physics Low MI: Symetric behaviour; Higher MI: Non-linear behaviour;
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;
2. US contrast agents - Physics
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
Blooming Jail bar
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
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
Pulse Inversion
Burns et al. 2001 Pulse Inversion
Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment
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
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;
Basics of Ultrasound Contrast Agents 1. Chemicals 2. Physics 3. Pharmacokinetics 4. Renal perfusion assessment
4. Renal perfusion assessment
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
Linear correlation between microbubble concentration and video-intensity
Echo-signal quantification Software working on cine-clips - Log-compressed data for video presentation Video-intensity = 10 * log 10 (I / I ref ) = 0-255 - Raw data before log-compression
4. Renal perfusion assessment For perfusion quantification it is mandatory slow infusion by a dedicated injector bolus infusion steady state
Negative exponential: y = A(1-e ) Parenchyma = Replenishment The exponential behaviour is a consequence of diffusion
Real time low MI imaging Tempo Destructive pulse I 5 4 Blood volume (A) 3 I = A (1 e (-βt) ) 2 1 0 1 Blood velocity (β) 2 3 4 5 6 7 8 t
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
Mathematical Algorithms ~ Arterial Input Function 1. Gamma variate (peripheral vessels) 2. Negative Exponential (parenchyma) 3. Other algorithms
Negative exponential: A = A 0 (1-e -βt ) A A = A 0 [1 e βt ] Wei K et al. Circulation 97: 473 483, 1998
Beam width = v
Renal artery stenosis vs Normal kidney
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;
Sigmoid A approximations Lucidarme O et al. Radiology 228: 473 479, 2003
Beam width = v
Piecewise Linear Function Microbubble void is dragged by the liquid and is filled by microbubble diffusion
Beam width = v
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
MSE 0.25 vs 0.15
Piecewise Linear Function 25 vs 70 years old volunteer
Piecewise Linear Function 25 vs 70 years old volunteer
Renal perfusion defects
Quaia E et al. Eur Radiol 2006
Results - Conspicuity
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
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;
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;