contrast agents for enhanced ultrasound imaging and for ... · a pulse of ultrasound is applied (c)...
Post on 15-Mar-2020
5 Views
Preview:
TRANSCRIPT
UNIVERSITETET I OSLO
Contrast Agents for gEnhanced Ultrasound Imaging and for
Drug DeliveryDrug DeliverySverre Holm
INSTITUTT FOR INFORMATIKK SH, 1
UNIVERSITETET I OSLO
Mi b bbl ( hit )Microbubbles (white) –red blood cells (black)( )
• 2-6 m diameter• Shell of biocompatible
material• Filled with gas
• Quaia 2007
INSTITUTT FOR INFORMATIKK SH, 2
UNIVERSITETET I OSLO
Contrast agents classified according to the filling gas (Quaia 2007)to the filling gas (Quaia 2007)
INSTITUTT FOR INFORMATIKK SH, 3
UNIVERSITETET I OSLO
ApplicationsApplications• Enhanced Imaging• Gene and Drug Delivery
INSTITUTT FOR INFORMATIKK SH, 4
UNIVERSITETET I OSLO
Linear and non-linear responseLinear and non linear response
• Microbubbles show a non-linear response if the• Microbubbles show a linear physical • Microbubbles show a non-linear response if the acoustic power of insonation is progressively increased at the resonance frequency (b) and the degree of microbubble expansion is greater than its compression. This nonlinear response to the
• Microbubbles show a linear physical behavior at very low acoustic power since the microbubble radius presents a degree of compression during the positive phase that is equal to the degree of expansion
INSTITUTT FOR INFORMATIKK SH, 5
insonation determines the production of harmonic frequencies,
• Quaia 2007
during the negative phase (a).
UNIVERSITETET I OSLO
Contrast-specific ultrasound techniquesContrast specific ultrasound techniques• Pulse Inversion• Cadence Contrast Pulse Sequencing
INSTITUTT FOR INFORMATIKK SH, 6
UNIVERSITETET I OSLO
Pulse InversionPulse Inversion• Principle of Pulse Inversion. Two
sequential US waves that aresequential US waves that are inverted replicas of each other are transmitted into tissue (a), and the resulting echoes are summed.
• For a linear medium (b) the echoes from the two waves are inverted copies of each other, and the
lti iresulting sum is zero. • For non-linear media (c) such as
microbubbles, the echoes will not be inverted copies and the sum isbe inverted copies, and the sum is not zero
• Quaia 2007
INSTITUTT FOR INFORMATIKK SH, 7
UNIVERSITETET I OSLO Pulse InversionPulse Inversion
(Ferrara et al, 2007)
INSTITUTT FOR INFORMATIKK SH, 8
UNIVERSITETET I OSLO
Cadence Contrast Pulse SequencingCadence Contrast Pulse Sequencing• Principle of Cadence Contrast Pulse
Sequencing. Three pulses are Seque c g ee pu ses a etransmitted along each line (a), and the first and the third are half in the amplitude in comparison with the second pulse, presenting ansecond pulse, presenting an opposed phase with respect to the others, and the returning echoes are summed. F li di (b) th lti• For a linear medium (b) the resulting sum is zero,
• while for a non-linear medium such as microbubbles the sum is not zero both for the non-linear fundamental (c) and non-linear harmonic frequencies (d)
INSTITUTT FOR INFORMATIKK SH, 9
UNIVERSITETET I OSLO
Liver – hepatocellular carcinoma (Quaia 2007)
INSTITUTT FOR INFORMATIKK SH, 10
UNIVERSITETET I OSLO Liver – metastatis (Quaia 2007)Liver metastatis (Quaia 2007)
INSTITUTT FOR INFORMATIKK SH, 11
UNIVERSITETET I OSLO
Spleen nodularlymphomalymphomaQuaia 2007• Lymfekreft
INSTITUTT FOR INFORMATIKK SH, 12
UNIVERSITETET I OSLO Kidney carcinomaKidney - carcinoma
Contrast enhancement after 30 secLoss of intensity after 90 sec
INSTITUTT FOR INFORMATIKK SH, 13
UNIVERSITETET I OSLO Kidney, power Dopplery, p pp
• (a) B-mode ultrasound image of the left kidney of a 9-week-old mouse (bar=0 5 cm) (b) The same kidney as in (a) isold mouse (bar=0.5 cm). (b) The same kidney as in (a) is shown following intravenous administration of ultrasound contrast and application of power Doppler. Notice that the kidney vasculature is visualized to the level of the
INSTITUTT FOR INFORMATIKK SH, 14
kidney vasculature is visualized to the level of the interlobular vessels (arrows). A=aorta. Ferrara et al, 2007
UNIVERSITETET I OSLO
Destruction-l i h treplenishment
Ult d t t t i• Ultrasound contrast agent is freely circulating in the vasculature.
• In a destruction replenishment• In a destruction-replenishment scheme, a strong ultrasound pulse destroys the agent in the imaging plane. g g p
• Low-pressure pulses are then used to observe the contrast agent returning to the imaging plane.
INSTITUTT FOR INFORMATIKK SH, 15
UNIVERSITETET I OSLO
Kidney: Destruction - replenishmentKidney: Destruction replenishment• (a) A destructive pulse destroys
all contrast agents in this rat a co as age s s akidney.
• (b) Contrast cadence pulse sequencing (CPS) visualizes contrast replenishment into thecontrast replenishment into the kidney at 2 s while negating most signal from regional tissue.
• (c) Contrast is refilling the kidney ( ) g yvasculature at 12 s and
• (d ) 30 s after the destructive pulse. Ti i t it b• Time-intensity curves can be generated from any part of the kidney.
INSTITUTT FOR INFORMATIKK SH, 16
UNIVERSITETET I OSLO Abdominal aorta (Quaia 2007)Abdominal aorta (Quaia, 2007)
Imaging of contrast leakage in aortic aneurysm rupture
d d l kand endoleaks (Fig. 11) after endovascularendovascular abdominal aorta repairrepair
INSTITUTT FOR INFORMATIKK SH, 17
UNIVERSITETET I OSLO Local drug delivery
(a) Ultrasound contrast agents are freely circulating in small vessels along with drug particles (blue). Once a sufficiently strong ultrasound
(b) Drug-laden ultrasound contrastagents are freely circulating throughout the vasculature. A pulse of ultrasound is applied
(c) Drug-laden ultrasound contrast agents baring surface ligands targeted to specific endothelial receptors are freely circulating. The ligand preferentially binds the ultrasoundsufficiently strong ultrasound
pulse is applied to the area, the contrast agent expands rupturing the endothelial lining. Drug is then able to extravasate.
and ruptures the contrast agent, thereby liberating the drug payload. Because ultrasound is only applied in the region of interest drug is preferentially
The ligand preferentially binds the ultrasound contrast agent in the target region, increasing local agent accumulation. An ultrasound pulse is then applied liberating the drug payload.
F t l 2007
INSTITUTT FOR INFORMATIKK SH, 18
interest, drug is preferentially delivered locally.
Ferrara et al 2007
UNIVERSITETET I OSLO
ReferencesReferences• Emilio Quaia, "Microbubble ultrasound contrast agents: an
update " European radiology 17 8 (2007): 1995 2008update. European radiology 17.8 (2007): 1995-2008.• Katherine Ferrara, Rachel Pollard, and Mark Borden.
"Ultrasound microbubble contrast agents: fundamentals and li ti t d d d li " A R Bi dapplication to gene and drug delivery." Annu. Rev. Biomed.
Eng. 9 (2007): 415-447. • Shengping Qin, Charles F. Caskey, and Katherine W.
Ferrara. "Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering." Physics in medicine and biology 54.6 (2009): R27.
INSTITUTT FOR INFORMATIKK SH, 20
top related