Contrast Sonography: Technique and Instrumentation - HD

Contrast Enhanced Ultrasound: Basic Techniques and Instrumentation

Hi, my name is Andrea Leeka Radiologist from Thomas Jefferson University Hospital in Philadelphia.

My topic gonna be about contrast enhanced ultrasound and I'm gonna talk about basic techniques and instrumentation and I'll show you how to do contrast enhanced ultrasound.

Review of Technique and Instrumentation

Let's review technique and instrumentation of contrast enhanced ultrasound.

Ultrasound contrast agents been around for quite some time. They've been introducing a late 1960s as hand agitated saline agents and they're still available for use in cardiology practices throughout the country. They're very easy to produce. All it takes to hand agitate the saline syringe with some air in it. It produce some microbio that can be detected with ultrasound and mainly used again in cardiology to look for shunts in the heart.

In eighties we had syndicated agents and galactose agents, but we don't have them anymore. They're very unstable and somewhat difficult to use.

Beginning 1990 gas and air mixture agents being introduced to the market and this is what we use currently. They have vari shells and we'll talk about them in the moment.

The micro bubbles are encapsulated heavy gas microspheres. They have lipid lip lipoprotein orin shell diameter of those guys are about two to 10 microns. They're approximately the size of red blood cell. They stay within the vessels and they do not enter enter the interst.

All agents are administered by intravenous injection and they dissolve in circulation in about 15 minutes. This is very beneficial because this provides you very nice window to image the patient. Almost all exams can be complete in 15 minutes, but if necessary, microbubbles can be injected in about 15 to 20 minutes and number of injections is not really limited.

Shells of the microbubbles are metabolized by liver and gas or gas and air mixture is excreted by lungs.

Available Contrast Agents in the United States

Three contrast agents are available in the United States. There's a definit optis zone and someo, you all of them are approved for cardiology applications and use of contrast agents in general imaging is considered of label.

Adverse Effects of Contrast Agents

Adverse effects of contrast agents are very, very mild. Some patients might complain or back or flank or renal pain. Allergic reactions have also been reported. Some other complications which have very rare include headache and dizziness, flushing, shortness of breath, hyper and hypertension.

But by far the most common complication or adverse effect of contrast agents is back of flank pain, which usually lasts for 10 to 15 seconds and goes away with no prolonged side effects.

Contraindications to Contrast Enhanced Ultrasound

Contra indications to contrast enhanced ultrasound is no suspected right to left or bidirectional cardiac shuns. It should be noted that we don't recommend screening of patients for cardiac shuns. Only patients with mild or suspected shuns should not receive contrast.

Patients with mild PFOS not detected before should not be excluded from this examination.

Prior hypersensitivity reactions to contrast is obvious contraindication, but fortunately very small amount of patients will have that and also ultrasound contrast agents should not be injected intra artily.

As you may know, there is a black box warning induced by FDA on all contrast agents and has been significantly decreased in the recent years. Current black box obligates you to tell the patient that there has been serious cardiopulmonary and allergic reactions reported within 30 minutes of contrast administration and also obligate you to have a trained personnel available to address potential side effects.

Preparation of Different Agents

Different agents supplied differently and should be activated differently.

Definitive one of the most commonly used contrast agent is supplied as a clear liquid in the vial containing approximately 1.5 ml of contrast agent. It's activated by vigorously shaking it on special shaker called vial mix for approximately 45 seconds producing this milky substance which is suspension of micro bubbles. And this suspension is ready to inject stable for approximately five to six hours and can be used throughout the normal workday.

So of you supply differently, it comes as a dried powder of microbubbles. It comes in the kit with prefilled five ml syringe, which is used to reconstitute some of your microbubbles through specially provide pin. The pin prevents micro bursting of the micro bubbles while transferring microbubbles from the vial back into the syringe.

Optio zone is supplied as ready suspension of micro bubbles. It's agitated by gently rotating vial for approximately three minutes and then is ready for injection. Same as other agents. It has couple hour shelf life once agitated and can be used on a different patients if needed.

Injection Methods for Ultrasound Contrast Agents

There are different ways of injecting ultrasound contrast agents, but most labs will use some kind of three-way stop c**k or dual lumen line to inject ultrasound contrast agents, all of them will require 10 to 26 C saline flush to clear the line and push microbubbles into the circulation.

We like to connect contrast syringe to the straight arm of the three-way stop c**k to prevent turbulence and save microbubbles from bursting. Your flash syringe can go to the side arm and use to flash microbubbles into the line for body applications for liver and kidney imaging.

Doses for Body Applications

Doses of ultrasound contrast variety between contrast agents definitive usually takes 0.3 to 0.4 ml to adequately image, liver or kidney. You might increase your dose if you use contrast enhance ultrasound to image organs with very slow profusion like ovaries or decrease it for something superficial or very vascular.

Some of you recommended dose is 2.4 ml. Some authors recommend going down to 1.5, but this will be depends on the patient and application of contras cancer ultrasound dose is 0.5 ml and again can be adjusted for individual patient and application.

Contrast Imaging Techniques

Different contrast imaging techniques being used to detect micro bubbles. We started with static B mode and M mode, then moved to real time BB mode and color adopter. Currently we use harmonic imaging or some combination of those producing complex imaging processing techniques that are used by different manufacturers to detect microbubbles in the circulation.

Principle of Signal Production

Let's review principle of signal production. When ultrasound wave heat microbubble microbubble will compress and expand depends on the cycle of the ultrasound wave producing the volume pulsation that can be detected by ultrasound system.

Amount of pulsation and amount of compression and expansion depends on power of ultrasound signal. At low power ultrasound bubble will contract and expand in linear fashion producing linear signal. When you increase your power, microbubble will contract and expand in non-linear fashion. It'll expand more than contracts producing non-linear signal, which is very different from signal produced by normal tissues.

When you increase your power to the breaking point, you can burst microbubbles producing very strong nonlinear back scatter for very short duration. This is very beneficial if you want to clear the field view from micro bubbles and then wash the replenishment to better quantify tissue profusion in the result.

As a result of this non-linear ation, when normal tissues hit with 2.5 megahertz frequency, they will return signal at 2.5 megahertz. There will be no other frequencies returned or at least no frequencies at high power enough to be detected by ultrasound system.

When we introduce microbubbles intonated tissues at at 2.5 megahertz, we'll return signal at two different frequencies. One is 2.5 megahertz, which is a fundamental of base frequency and in addition you're gonna detect signal at five megahertz, which is produced by a non-linear solution of micro bubbles.

If you plot those frequency and look at them with normal linear resonance, you're gonna have one peak frequency with microbubbles in the circulation you would have two. And by filtering this base or fundamental frequency out of your imaging, you can potentially produce image that will be only composed of signal from micro bubbles. This will, it looks like an ultrasound scanner.

Contrast Imaging Setup and Post-Injection Observations

Majority of the system will perform or at least allow you to perform ultra conscious enhanced ultrasound using some kind of split screen technique. On one side you're gonna see contrast mode image that without injection of microbubbles should be completely black. You're allowed to have a little bit of noise next to the face of the transducer, but you should not see much of a signal within the image itself.

Next to it you will see BMO image, which will be slightly degraded quality due to low mechanical index used to produce these images. But this is a phenomenal tool to guide the ultrasound examination to know exactly where you imaging with contrast after injection.

You will see that microbubbles will rapidly feel the entire field of profused tissue with high signal leaving non profused areas black. Comparing pre and post contrast images, you're gonna see drastic difference in contrast mode images only.

It's very difficult to detect microbubbles on B mode images, they're very, very bright. They're gonna be almost as bright as background tissues and they're almost undetectable to normal observer. But using different countries enhanced detection techniques, you can filter out your normal base frequency. You can filter out your entire volume of normal tissues and only detect microbubbles after the injection.

Quantification of Microbubble Enhancement

If you follow the microbubble source, keep scanning for a certain time, ultrasound images can be quantified. What we can do, we can select region of interest that includes perfused areas in this tumor and then computer will upload time intensity curves. After we have that, we can quantify different parameters and use them to make a diagnosis.

You can calculate time to peak, time from the injection to peak intensity, which is very useful to detect cancers and also to judge treatment response. You can look for half wash out time, which is time between peak enhancement and time when 50% of enhancement had disappeared.

You can also walk, look at the wash out which time between the peak enhancement and complete disappearance of the ultrasound contrast agent from the circulation or area under the enhancement curve. That sums up all those criteria.

Another way to do contrast enhancement ultrasound is to inject the bolus ultrasound contrast and wait until it reaches steady state. After that, you can apply high intensity ultrasound pulses to destroy all micro bubbles in your field of view and then without moving a transducer, which the replenishment of contrast in the field of view from that replenishment curve, you can get multiple values.

You can quantify intensity value, which reflects micro vessels, cross-sectional area or the amount of perfused blood vessels within the region of interest. You can also quantify rate of intensity increase, which reflects blood flow velocity in your field of view, and then multiplying intensity value by rate of increase. You can get some value that reflects profusion within the area.

Microvascular Imaging

Another helpful tool is microvascular imaging, which provides some of microbubble signals over time as they transverse the, IT is very helpful tool for lesions with very slow flow or with very low levels of vascularity like this. Benign fibroma in the ovary, very slowly profused tumor with very few vessels, but using this microvascular imaging technique, you can see microbubbles filling the entire volume of the tumor, providing your nice delineation of tumor boundaries and potential quantification of blood flow.

Conclusion

As a conclusion, they encapsulate the gas microbubbles, a very useful contrast agents for ultrasound. They increase the back scatter signal from the blood and substantially enhanced ultrasound images. They produce nonlinear resonance, which can be detected by harmonic imaging techniques, different ways of quantification available to you.

Majority of them will employ some kind of time intensity curve plotting and quantifying different parameters. Microvascular imaging is helpful for lesions with slow flow velocity or micro or low levels of vascularity.

And finally, contrast enhanced kinetics can be used to characterize micro vessel, cross-sectional area flow velocity and overall perfusion, which is useful in cancer imaging.

Thank you.