Tissue Harmonic Imaging

Author: Philip W. Ralls M.D.

Objectives: Upon completion of this CME article, the reader will be able to1. Explain what tissue harmonics are and how they are generated.2. Describe how tissue harmonic imaging has advantages over

conventional pulse-echo imaging.3. Describe how tissue harmonic imaging might be used in the clinical setting.

IntroductionTissue harmonic imaging is a new grayscale imaging technique.

It creates images that are derived solely from the higher frequency, second harmonic sound produced when the ultrasound pulse passes through tissue within the body. Tissue harmonics uses various techniques to eliminate the echoes arising from the main transmitted ultrasound beam (“the fundamental frequencies”), from which conventional images are made. Once the fundamental frequencies are eliminated, only the harmonic frequencies are left for image formation. Indeed, the quality of the harmonic image is primarily dependent on the complete elimination of all echoes derived from the transmitted frequencies. Tissue harmonic imaging offers several advantages over conventional pulse-echo imaging, including improved contrast resolution, reduced noise and clutter, improved lateral resolution, reduced slice thickness, reduced artifacts (side lobes, reverberations) and, in many instances, improved signal-to-noise ratio.

What are Tissue Harmonics?

Harmonics are familiar to most of us because of their importance in music. Musical tones can generally be described by their loudness, pitch (frequency) and quality. Quality is the difference that can be heard between two notes that have the same loudness and pitch. Thus, a guitar playing a C-note produces different quality sound than a piano playing the same C-note. The difference between these two notes is a result of the presence of harmonic frequencies. It is the varying amounts of harmonics that give an instrument its characteristic sound. Harmonic frequencies are integral multiples of the fundamental frequency. Thus, a string vibrating at a fundamental frequency of 440 Hz, (C-note) may also have vibrational modes at 880, 1320, 1760 Hz corresponding to harmonics at 2X, 3X and 4X the fundamental frequency.

Ultrasound pressure waves can be described in a very similar manner. A modern 2.0 MHz transducer transmits a band of frequencies centered on the 2.0 MHz frequency. For this transducer, a typical transmitted frequency band might be from 1.2 MHz to 2.8 MHz, covering a range of 1.6 MHz, or 80% bandwidth. In conventional fundamental imaging, when tissue is evaluated with a band of frequencies centered at 2 MHz, most of the echoes that come back to the transducer will be echoes related to the same 2 MHz frequency band. Harmonics are multiples of the fundamental beam, therefore, transmitting a band of frequencies centered at 2 MHz will result in the production of harmonic frequency bands centered at 4 MHZ, 6 MHZ, 8 MHZ, etc..

Only a small part of the returning sound involves these higher frequency harmonics (4, 6, 8 MHz) because they are much lower in amplitude than the reflected fundamental beam. As a practical matter, only the lowest frequency harmonic (double the fundamental frequency) is used to form images. This doubled frequency sound is called the second harmonic. Higher order harmonics (three or more multiples of the fundamental) are not used in image formation. There are a number of reasons why this is so, which are:

the range of frequencies that current transducers can detect is insufficiently large to capture these higher frequency signals

these higher order harmonics are progressively lower in amplitude, and

the higher frequencies are more quickly lost as they pass through tissue

Generation of Tissue HarmonicsHarmonics are generated by the passage of the ultrasound

beam as it passes through tissue. The peaks and troughs of the transmit pulse cause the tissue to alternatively expand and contract, distorting its shape. Because tissue is not linearly elastic, it contracts less than it expands. During tissue contraction, tissue density increases, causing the peak of the sound wave to travel slightly faster than the trough. The result of this process, called non-linear propagation, is that the wave becomes progressively more asymmetrical. This asymmetrical distortion results in harmonics.

Although the amount of harmonics that tissue generates at any given instant is small, the harmonics build as the pulse propagates through tissue. A similar effect is seen as an ocean wave approaches a beach. At sea, the wave is smooth and symmetrical. When the wave reaches shallow water, friction causes the bottom of the wave to slow down, whereas the top of the wave continues at its original velocity. As the wave gets progressively closer to shore, it “sharpens”, or even breaks. Thus, as the ultrasound wave travels through more tissue, more harmonics are generated.

Higher intensity transmit waves generate both higher intensity harmonics and more harmonics. The production of harmonics is proportional to the square of the fundamental intensity. Thus, a 3-dB increase in the fundamental beam will result in a 6-dB increase in harmonic intensity. For this reason, harmonics are generated predominantly by the main transmit beam. The region of maximal production of harmonics is at the focal zone, because beam intensity is highest at that location. Little or no harmonics are produced by weak waves, such as side lobes, grating lobes, scattered echoes, and at the edges of the main ultrasound beam. As a result, beams formed from tissue harmonic signals have less side lobes, less noise, and improved contrast resolution.

Artifact Reduction with Tissue HarmonicsThe major benefit of tissue harmonic imaging is artifact

reduction. Tissue harmonic images often exhibit a reduction in image noise and clutter with a consequent improvement in contrast resolution (improved signal-to-noise). Artifact reduction results in less noisy images, making cysts appear clearer and improving visualization of pathologic conditions and normal structures. Tissue harmonic imaging reduces artifact in several ways, which are:

1. Decreased scatter from the body wall

2. Reduced artifacts from weak echoes such as side lobes, scatter, and grating lobes3. Less near field haze from body wall reverberations.

1. Decreased Effects of the Body WallSound does not travel in straight lines or at a constant velocity

through the body wall because tissue has a complex composition – fat, skin, muscle, and subcutaneous tissue. This causes significant distortion and scattering of the transmitted ultrasound beam. In conventional fundamental imaging, beams have to pass through the body wall twice – once with the initial transmission and second, when the echo returns. Unlike fundamental echoes, tissue harmonic signals, which are produced in the tissue from within the body, only pass through the body wall one time. Because tissue harmonics are mainly generated in the tissue beyond the body wall, the distortion and scattering is greatly reduced.

2. Reduced Artifacts from Weak Echoes

One important consequence of nonlinear wave generation is that it depends on the intensity (strength) of the incident wave. Roughly, the generation of harmonics may be thought of as an inverse quadratic relationship or square law. That means that if a weaker fundamental pulse (for example, a side lobe) is one third as strong as the echo from the main beam, the side lobe will produce only one ninth of the harmonics. Therefore, a weak wave (such as that from the edge of the ultrasound beam, or a scattered echo, or a side lobe) produces little or no harmonics, while a strong wave (such as the center of the transmit beam) produces disproportionately more harmonic energy. By detecting the harmonics only, harmonic imaging preferentially rejects echoes that come from weak parts of the beam. In this way, side lobe, reverberation, and other artifacts are reduced in harmonic images. Harmonic-related artifacts, therefore, are less prominent than artifacts associated with the fundamental frequency. This results in “cleaner” looking images, especially in cystic structures, and improved detection of parenchymal lesions.

3. Decreased Body Wall ReverberationsAnother major benefit of harmonic imaging is the virtual

elimination of reverberation artifacts from the body wall. Harmonics do not develop in the first few centimeters, but many artifacts do. In particular, multiple reverberations between the transducer and the body wall layers cast a ‘haze’ that overlies the image. Because in reality these artifacts are mis-registered echoes from the near field, they do not contain harmonics and disappear in the tissue harmonic image.

Image Formation in Tissue Harmonics

Tissue harmonic imaging operates by transmitting a fundamental beam that has a lower frequency. This fundamental pulse, as it propagates through tissue inside the body, generates the higher frequency harmonic sound. The key to understanding tissue harmonic imaging is that the image is formed only from the higher frequency harmonic sound. Echoes from the fundamental frequency are rejected and thus, are not used in making the image. Indeed, if the higher amplitude fundamental echoes are not eliminated, they degrade the image to the point that there is no benefit from tissue harmonic imaging. The stronger fundamental echoes, if not eliminated, will mask the harmonics. Obviously, sophisticated transmit beam formation and signal detection is required to produce good quality harmonic images. It is possible that the ability to produce high quality harmonic images may be an interesting test of an ultrasound system’s overall capabilities.

Several techniques are currently employed to detect harmonics and eliminate the unwanted fundamental echoes. Filtration techniques remove the echoes from the fundamental frequency and allow the harmonic frequencies to pass, so that the harmonic image can be formed. Other techniques cancel the fundamental echoes. Some of these include single line pulse inversion (PI), side-by-side phase cancellation, and transmit pulse encoding. All of these techniques require excellent transmit beamformer performance. Other pulse manipulation techniques will undoubtedly be developed in the future.

Filtration

Filtration to remove the fundamental frequency is the technique currently used most commonly to produce tissue harmonic images. Filtration uses sophisticated transmit beam formers to produce a narrower bandwidth and signal processing techniques to filter out the spectrum of frequencies that are likely to arise from the fundamental beam. The fundamental ultrasound pulse is not a single frequency, but is really a range of many frequencies that are distributed around the mean transmitting frequency (for example, a band of frequencies from 1.2 to 2.8 MHZ for a 2 MHZ transducer). Because of this, there are frequencies at which the information from both the fundamental signal and the harmonic signal overlaps.

If a system produces a broader bandwidth, then the overlap between the harmonic echoes and the fundamental signals is greater. In this setting, filtration will then result in the removal of significant harmonic information along with the unwanted fundamental echoes. However, use of a narrower bandwidth will result in less overlap. With narrow bandwidth beams, filtration can provide a much cleaner separation of the harmonic-related information from the fundamental signal (figure 1).

Single Line Pulse Inversion (PI)

Pulse inversion is a technique that adds the echoes from two opposite polarity pulses to cancel the fundamental echoes, leaving only the harmonic information. An initial pulse is sent into the body and the returning echoes are recorded. This first pulse-echo cycle results in both fundamental and harmonic frequencies returning from the tissue and the data received are stored. A second inverted pulse (opposite in polarity, or phase) is then transmitted. Fundamental and harmonic frequencies of the second cycle are received and added to the data received from the first cycle. Assuming no patient motion, adding the data will then cancel the linear, fundamental echoes. The non-linear harmonic information remains, resulting in an unfiltered harmonic signal over the entire frequency bandwidth of the transducer. This is advantageous because the images produced do not suffer degradation of axial resolution. However, the potential problem is that this method can suffer image degradation from tissue motion.

Side-by-side Phase CancellationSide-by-side phase cancellation is similar to pulse inversion.

Instead of two firings of opposite phase ultrasound beams along the same line, this method sends both signals together at the same time with opposite phases. These adjacent lines are then added. The resulting cancellation of the fundamental opposite phase lines leaves the harmonics, from which images can be made. Like pulse inversion, this technique preserves the bandwidth of the harmonic sound. This technique is a spatial cancellation technique, while pulse inversion is a temporal cancellation technique.

Pulse Encoding

Pulse encoding of the transmitted ultrasound beam is another technique to cancel the fundamental echoes and enhance harmonic detection. Transmit pulse encoding uses relatively complex waveform sequences to give each a unique, recognizable signature or code. This complex, coded pulse is sent into the body. The unique code is then recognized in the return waveform by a special decoder that is part of the equipment. Because the linear, fundamental echoes have a specific code, they can be identified and canceled. The remaining nonlinear harmonic signal is then processed to form the image. This technique has proved especially useful in the near field.

Tissue Harmonic – Image CharacteristicsDecreased Image Dynamic Range

Images produced with harmonic imaging often appear different from those generated with fundamental frequencies. The amplitude of the harmonic signals is generally one to two orders lower in magnitude than the fundamental signal. Because of this, the dynamic range of harmonic imaging is lower, as much as 18 dB lower than the fundamental beam. This much weaker signal level of the harmonic results in images with more contrast. This characteristic may, on occasion, actually improve visualization and conspicuity of subtle parenchymal lesions.

Better Lateral Resolution – Reduced Slice ThicknessThe beam profile (slice thickness) of the harmonic frequencies is

always narrower than the fundamental pulse that is used to produce it. This occurs because the acoustic intensity of the transmitted ultrasound pulse is lowest along the edges and highest in the center. Thus, the edges of any ultrasound beam produce fewer harmonics than the more intense central beam. This peripheral dropout means that the harmonic beam has smaller dimensions, both in lateral and slice thickness (elevation) directions.

ArtifactsTissue harmonic imaging reduces some artifacts, and enhances

others. Fortuitously, it is often the detrimental artifacts that are reduced, while the useful artifacts, which often reveal important information about the anatomy and pathology, are made more visible. For example, echoes resulting from side lobes are often reduced (figure 2) or eliminated.

The square law in harmonic imaging, which states that harmonic production is proportional to the square of the fundamental amplitude, results in minimizing certain artifacts. Reverberations, side lobe artifacts, and partial volume artifacts due to slice thickness are good examples of echoes that are small in amplitude and therefore produce minimal harmonics.

Some artifacts may be more prominent on tissue harmonic images. Examples include acoustic enhancement deep to a fluid collection (through transmission), acoustic shadowing (figure 3), and comet tail artifacts.

Worse Images in “Glass Body” PatientsBecause filtration decreases bandwidth, in some cases, the

resolution in harmonic images may be worse than fundamental imaging. Tissue harmonic images may be inferior to conventional high frequency fundamental images in patients who are excellent ultrasound subjects (“glass bodies”). This difference is related to the better contrast resolution of the higher frequency fundamental image.

Clinical Effects of Tissue Harmonic Imaging

While the focus of this manuscript has been to improve the understanding of the basic principles of tissue harmonic imaging, speculation regarding the clinical impact of this modality is appropriate. Harmonic imaging is not a universal solution to ultrasound imaging problems, although in certain patient populations it clearly provides more diagnostic information. Preliminary studies suggest that tissue harmonic resolution improves clinical imaging in several applications. The eventual impact of tissue harmonic imaging, however, is not yet clear. Harmonic imaging relies on weak echoes that cannot be achieved uniformly on a patient-to-patient basis. Only when tissue harmonic techniques are technologically mature and more widely distributed will we know the ultimate clinical usefulness.

Tissue harmonic imaging may display pathology and normal structures with greater clarity than fundamental imaging. Good images are often obtained with less effort. It may be easier to scan technically difficult patients. Because of these features, tissue harmonic imaging has the potential to decrease the time required to scan some patients.

The clearer images sometimes provided by harmonic imaging can lead to important clinical information. Questionable lesions may be either confidently identified or excluded on harmonic images. On occasion, harmonic images identify lesions that are invisible, or nearly invisible, even in retrospect, on the fundamental images. Common duct stones (figure 4) and focal liver lesions are examples of this. Pathology suspected on fundamental images may not be present when harmonics shows the anatomy more clearly.

Tissue harmonic imaging seems especially effective in renal imaging, probably because of the considerable distortion related to the body wall in that area. In a number of cases using tissue harmonics we have been able to confidently diagnose renal cell carcinoma and kidney stones that were undetected with fundamental imaging. Often, simple renal cysts can be definitively diagnosed on harmonic images when fundamental images are non-diagnostic (figure 5), reducing the need for follow-up CT exams.

By making it easier to obtain better quality images, tissue harmonic imaging may improve the overall quality of ultrasound diagnosis. Tissue harmonic sonography is still in its infancy. The eventual usefulness of harmonic imaging will be better understood, as it becomes increasingly available and more technically mature on sonographic systems.

Figures1 Tighter beam profile (narrower transmit bandwidth), makes it

easier to remove the fundamental echoes by filtration.2 Echoes resulting from grating lobes are often reduced or eliminated.3 The increased contrast of tissue harmonic images makes some

artifacts more prominent. Fortunately, these are usually “helpful” artifacts.

4 Tissue harmonics shows a common duct stone missed with fundamental imaging.

5 Simple renal cyst. Tissue harmonics often makes definitive diagnosis possible, obviating further imaging.

References or Suggested Reading:1. Averkiou MA, Hamilton MF. Measurements of harmonic

generation in a focused finite-amplitude sound beam. J Acoust Soc Am 1995; 98:3439-42.

2. Christopher T. Finite amplitude distortion-based inhomogeneous pulse echo ultrasonic imaging. IEEE Trans. Ultrason. Ferroelec. Freq. Contr., 1997 Jan; 44:125-139.

3. Desser TS, Jeffrey RB Jr, Lane MJ, Ralls PW. Tissue harmonic imaging: utility in abdominal and pelvic sonography. J Clin Ultrasound 1999 Mar-Apr;27(3):135-42.

4. Hann LE, Bach AM, Cramer LD, Siegel D, Yoo HH, Garcia R. Hepatic sonography: comparison of tissue harmonic and standard sonography techniques. AJR Am J Roentgenol 1999 Jul;173(1):201-6.

5. Hope Simpson D, Chin CT, Burns PN. Pulse Inversion Doppler: A new method for detecting nonlinear echoes from microbubble contrast agents. IEEE Transactions UFFC 1999; 46:372-382.

6. Li PC. Pulse compression for finite amplitude distortion based harmonic imaging using coded waveforms. Ultrason Imaging. 1999 Jan;21(1):1-16.

7. Shapiro RS, Wagreich J, Parsons RB, Stancato-Pasik A, Yeh HC, Lao R. Tissue harmonic imaging sonography: evaluation of image quality compared with conventional sonography. AJR Am J Roentgenol 1998 Nov;171(5):1203-6.

Thanks for the indispensable assistance of Peter Burns, Anne Hall, Tom Jedrzejewicz, and Jonathan Rubin

About the AuthorDr.Philip W. Ralls is a Professor of Radiology at Keck School of

Medicine, University of Southern California. He is an active Radiologist and is a Fellow of the American College of Radiology and numerous other professional organizations.

Dr. Ralls has presented numerous lectures on ultrasound topics at many different conferences around the country and is actively involved in research. In addition, he has authored several publications in peer-review medical journals.

Examination:1. Tissue harmonic imaging offers several advantages over

conventional pulse-echo imaging, including all of the following exceptA. reduced noise and clutterB. reduced slice thicknessC. increased artifacts (side lobes, reverberations)D. improved lateral resolutionE. improved signal-to-noise ratio

2. As a practical matter, only the harmonic is used to form images.

A. firstB. secondC. thirdD. fourthE. fifth

3. Higher order harmonics (three or more multiples of the fundamental) are not used in image formation, for which of the following reasons?A. the range of frequencies that current transducers can

detect is insufficiently large to capture these higher frequency signals

B. these higher order harmonics are progressively higher in amplitude

C. the higher frequencies are not lost as quickly as the lower frequencies as they pass through tissue

D. A & B aboveE. B & C above

4. Regarding the generation of tissue harmonics, which of the following statements is true?A. Because tissue is not linearly elastic, it contracts more

than it expands.B. During tissue contraction, tissue density increases,

causing the peak of the sound wave to travel slightly faster than the trough.

C. The result of the tissue’s contracting and expanding on the sound wave is called linear propagation, in that the wave becomes progressively more symmetrical.

D. Although the amount of harmonics that tissue generates at any given instant is small, the harmonics decrease as the pulse propagates through tissue.

E. As the ultrasound wave travels through more tissue, less harmonics are generated.

5. The region of maximal production of harmonics is at the _____, because beam intensity is highest at that location.A. focal zoneB. side lobesC. grating lobesD. skin surfaceE. edges of the main ultrasound beam

6. Tissue harmonic imaging reduces artifact in several ways byA. decreased scatter from the body wallB. reduced artifacts from weak echoes such as side lobes,

scatter, and grating lobesC. more near field haze from body wall reverberationsD. A & B aboveE. B & C above

7. Regarding the effects of the body wall, which of the following is a true statement?

A. Sound does not travel in straight lines but does travel at a constant velocity through the body wall.

B. Even though tissue has a complex composition, this does not cause a significant distortion of the transmitted ultrasound beam.

C. In conventional fundamental imaging, beams have to pass through the body wall twice.

D. Tissue harmonic signals, which are produced in the tissue from within the body, pass through the body wall twice.

E. Because tissue harmonics are mainly generated in the tissue beyond the body wall, the distortion and scattering is greatly increased.

8. Regarding reduced artifacts from weak echoes, all of the following are true statements exceptA. One important consequence of nonlinear wave generation

is that it depends on the intensity (strength) of the incident wave.

B. Roughly, the generation of harmonics may be thought of as an inverse quadratic relationship or square law.

C. A weak wave (such as that from the edge of the ultrasound beam) produces little or no harmonics, while a strong wave (such as the center of the transmit beam) produces disproportionately more harmonic energy.

D. By detecting the harmonics only, harmonic imaging preferentially rejects echoes that come from weak parts of the beam.

E. Harmonic-related artifacts, therefore, are more prominent than artifacts associated with the fundamental frequency.

9. Regarding decreased body wall reverberations, which of the following statements is (are) true?A. Harmonics do develop in the first few centimeters, but many artifacts do not.B. Multiple reverberations between the transducer and the

body wall layers cast a ‘haze’ that overlies the image.C. Because in reality these artifacts are mis-registered

echoes from the near field, they do not contain harmonics and disappear in the tissue harmonic image.

D. A & B above are true.E. B & C above are true.

10. Regarding image formation in tissue harmonics, all of the following are true exceptA. Tissue harmonic imaging operates by transmitting a

fundamental beam that has a lower frequency.B. This lower frequency fundamental pulse, as it propagates

through tissue inside the body, generates the higher frequency harmonic sound.

C. The key to understanding tissue harmonic imaging is that the image is formed only from the higher frequency harmonic sound.

D. Echoes from the fundamental frequency are included in order to make a sharper image.

E. Sophisticated transmit beam formation and signal detection is required to produce good quality harmonic images.

11. Several techniques are currently employed to detect harmonics and eliminate the unwanted fundamental echoes including all of the following exceptA. Filtration techniquesB. Single line pulse inversionC. Side-by-side phase cancellation

D. Transmit pulse encodingE. Reduced signal-to-noise ratio

12. Regarding filtration, which of the following statements is (are) true?

A. Filtration uses sophisticated transmit beam formers to produce a narrower bandwidth and signal processing techniques to filter out the spectrum of frequencies that are likely to arise from the fundamental beam.

B. If a system produces a broader bandwidth, then the overlap between the harmonic echoes and the fundamental signals is less.

C. With narrow bandwidth beams, filtration cannot provide a very clean separation of the harmonic-related information from the fundamental signal.

D. A & B above.E. B & C above.

13. Regarding single line pulse inversion, the potential factor that can degrade the image with this method isA. scar tissueB. a large amount of subcutaneous tissueC. obesityD. hemorrhage within the tissueE. tissue motion

14. The technique that is a spatial cancellation technique is theA. Filtration techniqueB. Single line pulse inversion techniqueC. Side-by-side phase cancellation techniqueD. Transmit pulse encoding techniqueE. Reduced signal-to-noise ratio technique

15. The technique that requires the equipment to have a special decoder is theA. Filtration techniqueB. Single line pulse inversion techniqueC. Side-by-side phase cancellation techniqueD. Transmit pulse encoding techniqueE. Reduced signal-to-noise ratio technique

16. Regarding tissue harmonic image characteristics, the amplitude of the harmonic signals is generally ______ orders lower in magnitude than the fundamental signal.A. one to twoB. two to three

C. three to fourD. four to fiveE. five to six

17. Regarding the slice thickness, which of the following statements is (are) true?A. The beam profile (slice thickness) of the harmonic

frequencies is always wider than the fundamental pulse that is used to produce it.

B. The acoustic intensity of the transmitted ultrasound pulse is highest along the edges and lowest in the center.

C. The edges of any ultrasound beam produce fewer harmonics than the more intense central beam.

D. A & B above are true.E. B & C above are true

18. An example of an artifact that may be more prominent on tissue harmonic imaging isA. a side lobe artifactB. a comet tail artifactC. a body wall reverberation artifactD. an artifact from the edge of the ultrasound beamE. a grating lobe artifact

19. In some cases, the resolution in harmonic images may be worse than fundamental imaging. Tissue harmonic images may be inferior to conventional high frequency fundamental images in patients who A. are poor ultrasound subjectsB. are ultrasound subjects with “glass bodies”C. have a large amount of subcutaneous tissueD. are obeseE. have scar tissue

20. According to the author, tissue harmonic imaging seems especially effective in _____

imagingA. musculoskeletalB. cardiacC. obstetricalD. renalE. gastrointestinal