Tissue harmonic imaging and contrast enhanced ultrasound are advanced ultrasound techniques that provide higher quality images. Tissue harmonic imaging uses harmonic frequencies to reduce artifacts and improve resolution of small lesions compared to conventional ultrasound. Contrast enhanced ultrasound uses microbubble contrast agents and specialized imaging modes to visualize microvascular blood flow and perfusion. It has applications in evaluating lesions in the liver, pancreas, and kidneys by analyzing enhancement patterns in arterial, portal, and late phases. These techniques increase the diagnostic accuracy and confidence for characterizing benign and malignant lesions compared to conventional ultrasound alone.

1. ADVANCES IN ULTRASOUND
THI,CEUS and TRUS
PRESENTOR-DR.SANGEETA JHA
MODERATOR-DR GAURAV SHRIVASTAVA

2. TISSUE HARMONIC IMAGING
• Is a grayscale ultrasound mode that provides images of higher
quality than conventional sonography
Based on the phenomenon of nonlinear distortion of acoustic
signal as it travels through the body.
Imaging begins with insonation of tissue with ultrasound waves
of a specific transmitted frequency.
Harmonics are produced by tissue vibration and are usually
integral multiples of the transmitted frequency
In comparison ,conventional ultrasound waves are generated at
the surface of the transducer and progressively decrease in
intensity as they traverse the body
Harmonic wave frequencies are higher integer multiples of the
transmitted frequency, Current technology uses only the second
harmonic(twice the transmitted frequency) for imaging.
The processed image is formed with use of the harmonic-
frequency bandwidth in the received signal after the transmitted
frequency spectrum is filtered out

3. Time sequence illustrates the generation of harmonic frequencies. Time step 1 contains a
wave of single frequency. As the wave travels into the tissue (time step 2), it becomes
distorted. Additional frequency components are created that are integer multiples of the initial
frequency. These components are called “harmonic frequencies.” As the wave continues to travel, it
becomes highly distorted (time step 3) and very rich in harmonic frequencies. Harmonic frequencies
are created and accumulate as the wave travels through the tissue. Amplitudes of the higher
harmonics are extremely small. Therefore, current technology uses only the second harmonic (2f),
which is twice the nominal transmitted frequency.

4. Frequency spectrum of the transmitted and received waves.
The fundamental wave (f) is generated at the transducer surface and attenuates linearly as it is
transmitted through the body.
The harmonic wave (2f) is generated as the fundamental wave travels through the body. The
harmonic wave increases exponentially in intensity before attenuating within the deeper tissues.
Harmonic imaging uses only the second harmonic frequency in the echo signal received by
filtering out the transmitted frequency spectrum in the signal

5. Schematic depicts the relative intensities and frequency changes of
harmonic ultrasound beams
and fundamental transmitted waves with increasing depth in tissues.

6. ADVANTAGE OF THI
1) Improved axial resolution -due to shorter wavelength
2) better lateral resolution -due to improved focusing
with higher frequencies,
3) less artifact than with conventional US- Reduced
artifact in harmonic imaging is due to the relatively
small amplitude of the harmonic waves, which reduces
detection of echoes from multiple scattering events.
4) less side lobes artifacts.
5) Better imaging option for obese patients- harmonic
beams are produced beyond the body wall, thereby
reducing the defocusing effect of the body wall.

7. Harmonic imaging increases diagnostic confidence in
differentiating cystic from solid hepatic lesions,
Improves detection of gallbladder and biliary calculi,
Improves pancreatic definition
Allows distinction of simple from complex renal cysts.

8. Comparison of conventional gray scale imaging (A) with tissue
harmonic imaging (B)
THI clearly demonstrates target lesions in a metastatic liver disease.
additional lesions are also detected at THI

9. Tissue harmonic imaging (A) demonstrates much better
delineation of both cystic and solid lesions in this patient of Renal
angiomyolipomas, when compared to conventional grayscale
imaging (B)

10. THI better demonstrate fine septations and mural nodule in complex renal
cyst as compared to conventional ultrasound

11. Choledocholithiasis with liver metastases.
Both the harmonic (a) and conventional (b) US images show a dilated
common duct and multiple liver metastases.
The obstructing stone in the common duct was detected on only a,

12. Gallbladder polyp.
Small polyp on the anterior surface of the gallbladder is seen on the harmonic image (a) with marked
reduction of noise in the gallbladder lumen compared with that on the conventional US image (b).

13. Renal carcinoma in an obese patient.
Exophytic solid mass in the lower pole of the left kidney is seen on the harmonic
image (a) but not on the conventional US image (b),
which demonstrates the benefits of harmonic imaging in obese patients.

14. In conventional US, optimal resolution was
achieved by using a higher frequency. This, at
times, compromised adequate penetration,
which necessitated use of a lower frequency.
Harmonic imaging provides better resolution
by using a higher frequency for imaging
without compromising depth penetration.

15. CONTRAST ENHANCED ULTRASOUND
It has twin components-
-ultrasound contrast agent (UCA)
- contrast specific imaging modes.
It can detect the hemodynamics of the targeted organ and
provide detailed information of the microvascularity and
microperfusion observed by real time scanning .

16. Although Doppler imaging may provide valuable
directional blood flow information but is is most
effective for evaluating large blood vessels with fast
flowing blood such as the carotid arteries,leg
veins,and major visceral vessels of the abdomen,
including the portal veins and hepatic arteries.
The ability of Doppler imaging to detect blood flow
at the tissue perfusion level is limited.

17. The remedy for this problem is to add microbubble contrast agents and
specialized ultrasound imaging techniques.
The former enhances the Doppler signal from blood, whereas the latter
serves to suppress the signals from the background tissue while
enhancing the sensitivity to the Doppler signals from the microbubbles
within the blood pool.
These additions allow ultrasound imaging of blood flow at the tissue
perfusion level, thus enabling ultrasound to play a competitive role
relative to CT and MRI in the evaluation of the solid and hollow organs
of the abdomen and pelvis.

18. CONTRAST AGENTS
microbubbles composed of tiny bubbles of an injectable
gas in a supporting shell.
They are blood pool agents and remain confined to the
intravascular space after intravenous injection.
Small microbubbles (1-10 um) can pass through the
lung capillaries and remain in circulation for a short time
and eventually get dissolved.
The gas gets exhaled while the shell gets metabolized in
the liver.
The UCAs, while in circulation, strongly increase the
ultrasound backscatter and produce enhancement of
echogenicity for the assessment of blood flow

20. FIRST GENERATION US CONTRAST AGENTS
Tendency to dissolve into the solution very quickly, resulting in
short imaging window.
ECHOVIST
 was the first commercially available UCA introduced in 1991,
 Made of air bubbles coated with galactose
 Had a very short life in the blood with minimal transpulmonary
circulation limiting its clinical utility.
 It was predominantly used for the evaluation of the cardiac shunt
and the female genital tract.

21. ALBUNEX
 was the first FDA approved contrast agent in 1994.
 Composed of air filled albumin microspheres suspended in 5
percent w/v human albumin solution.
 In vivo half life < 5 minutes.
 It was used predominantly for the evaluation of cardiac
shunts and valvular regurgitation with limited extra-cardiac
applications
 It is no longer manufactured.

22. LEVOVIST
 Came up In 1996, it was a relatively longer lasting UCA
 It contained air bubbles with a galactose/ palmitic acid surfactant
coating .
 Main indications for use were cardiac, intracranial and abdominal.
 However, the Levovist bubbles easily collapsed under ultrasound
emission owing to its fragile properties, therefore real time
images could not be obtained for a longer period

23. SECOND GENERATION US CONTRAST AGENTS
 The second generation UCAs are pure blood pool agents as they
are unable to destroy the vascular endothelium and thus remain
exclusively intravascular resulting in prolonged enhancement of
the vascular system. No extravasation into the interstitial fluid
occurs.
 Contain insoluble gases like sulphur hexafluoride (SF6) or
perfluorocarbons and have a surface shell made of different
substances like phospholipids, albumin or polymers providing
better stabilization.
 Their smaller size enables a successful transpulmonary passage to
reach the various target organs.
 After intravenous injection, due to their low solubility in water,
better stabilization and strong harmonic response-- prolonged
visualization of dynamic enhancement of the organ can be
observed on real-time ultrasound scanning

25. OPTISON AND LUMINITY
 Made of octafluoropropane coated with albumin and lipid
shell respectively.
 The octafluoropropane gas has low water solubility and is
more stable providing longer imaging period.
 However, their sole indication for use has been cardiac.
SONOVUE
 contains sulphur hexafluoride stabilized by phospholipid
shell.
 It is an ideal ultrasound contrast agent for vascular phase
imaging of different target organs and is being used widely
with promising results.
 It is the only contrast agent available in India.

26. SONAZOID
 Most recent second generation UCA
 Contains perflubutane and has a hard shell.
 exhibits the longest window period for imaging, the extended
late phase.
 It has been successfully used in the evaluation of liver tumors.
 This UCA can depict the hemodynamics of the liver in the
vascular and the post vascular phase also called the ‘Kupffer
phase’. This is because, the Kupffer cells of the liver phagocytose
Sonazoid microbubbles and thus persist in the liver for long.
 it is available only in Japan.

27. IMAGING TECHCHNIQUE
• A good US machine equipped with low MI contrast imaging
mode is required.
• For intravenous use-recommended dose of SonoVue is 2.4
ml.
• A higher dose is used for endoscopic contrast enhanced
ultrasound (CE-EUS) and when using high frequency
transducers.
• For renal and pancreatic evaluation a low dose of 1.0 ml is
used.
• For extravascular use, a few drops of SonoVue in 10 to 100
ml of saline may be sufficient.

28. For intravenous use of UCAs-
• Antecubital access using 20 gauge venflon with a three way
connector is obtained.
• The contrast material in the vial, e.g. (SonoVue) is prepared
in the soluble form 5 minutes prior and shaken well to be
properly dissolved for use.
• The target organ is visualized on the B mode US and then
keeping the lesion in focus the contrast-specific imaging
mode is turned on.
• A simultaneous display of the tissue and contrast signals
can be seen on the monitor as a dual window which ensures
the target lesion remains in the field of view throughout the
study.

29. • The freshly prepared Sonovue is administered as an
intravenous bolus followed by flushing with 10 ml of
0.9 percent normal saline.
• The enhancement characteristics of the target organ
is observed on real time by continuously scanning till
the three vascular phases post injection.
• The observation is recorded on the cine mode.
• Post procedure, the patient is observed for about an
hour for any adverse reaction if any due to the UCA

30. SAFETY OF UCAs
UCAs are well tolerated and safe with few non-specific side
effects.
Clearance of UCA is very fast and 80 to 90 percent of it gets
eliminated through the lungs in 11 minutes.
Life threatening anaphylactoid complications are very rare
(0.001%).
Unlike other contrast agents used for CT or MRI, the UCAs
are not nephrotoxic as they have no renal excretion.
Hence, CEUS can be safely done in patients with
compromised renal function.

31. CONTRAINDICATIONS TO THE USE OF UCAS
• cardio-pulmonary disease
• pregnancy and breast-feeding
• severe coronary artery disease.
• Cautious use is recommended in neonates
• use prior to extra-corporeal shock wave therapy

32. ADVANTAGES OF CEUS
cost-effective
 can provide accurate diagnostic information
comparable to CT and MRI
can be performed at the bedside
no ionizing radiation
has no nephrotoxicity-do not require lab evaluation
and can be used repeatedly in renal failure
patients.

33. DIAGNOSTIC APPLICATIONS OF UCAs
Applications in Hepatic Imaging
liver has a dual blood supply -hepatic artery and the
portal vein which allows evaluation of the liver by
real time scanning in three vascular phases
Enhancement pattern of the liver nodule is observed
-arterial phase (AP) upto 30 secs
-portal venous phase (PP) from 31 to 120 secs and
-delayed phase (DP) from 120 to 180 secs.
Intermittent scanning is done where contrast is seen
persisting in the late phase upto 5 minutes or so.
If another mass needs to be studied in the same
patient, then the same procedure is repeated with a
fresh bolus of UCA after 10 minutes.

34. Enhancement patterns of benign focal liver lesions
Focal liver lesion Arterial phase Portal venous phase Late phase
Hemangioma Peripheral nodular
enhancement
Partial/complete
centripetal fill in
Complete
enhancement
Focal nodular
hyperplasia
Hyperenhancing
from the center,
early Spoke wheel
arteries, feeding
artery
Hyperenhancing Iso/hyperenhancing
Unenhanced central
scar
Hepatocellular
adenoma
Hyperenhancing,
complete
Isoenhancing Isoenhancing
Focal fatty
infiltration/sparing
Isoenhancing Isoenhancing Isoenhancing
Simple cyst Nonenhancing Nonenhancing Nonenhancing

35. Hemangioma – Typical pattern.
showing peripheral nodular enhancement (arrow heads) in the AP at 23 secs post-
contrast injection (A)
with progressive centripetal enhancement (B)
becoming isoenhancing (arrow) in the LP at 240 secs (C)

36. FOCAL NODULAR HYPERPLASIA
Arterial phase contrast-enhanced ultrasound
(CEUS) images obtained with maximum-
intensity projection technique show superb
vessel delineation.
Arterial phase -show stellate vascularity, centrifugal
filling
portal phase-homogeneous hypervascularity
late phase at 3 minutes -shows sustained contrast
enhancement and central nonenhancing scar

37. • Enhancement patterns of malignant focal liver
lesions
FLL Arterial phase Portal venous phase Late Phase
Metastasis Rim-enhancement Hypoenhancing Hypo/non enhancing
HCC(non-cirrhotic )
HCC(cirrhotic)
Hyperenhancing
Inhomogenous
hyperenhancing
Isoenhancing
Isoenhancing
Hypo/non enhancing
Iso/hypoenhancing
Cholangiocarcinoma Rim-like
hyperenhancement,
central
hypoenhancement /
Inhomogenous
hyperenhancement
Hypoenhancing Non enhancing

38. HCC-Typical pattern.
AP image -at 26 secs showing hyperenhancement (arrow) (A)
hypoenhancement (arrow) in the VP at 45 secs

39. HCC- Atypical pattern.
AP image showing inhomogeneous hyperenhancement (arrow) at 30 secs (A)
with retained contrast appearing isoenhancing (arrows) in the VP and LP at 110
and 240 secs respectively (B and C). Histopathology suggested well differentiated
HCC

40. Hepatic metastasis from colon cancer- arterial phase showing marked
rimenhancement .
in late phases shows hypoenhancecement.

41. Applications in Pancreatic Imaging
Detection of Focal Pancreatic Lesions
If the lesion is less than 2 cms-CEUS is superior to US alone,
comparable efficacy with that of EUS,more diagnostic accuracy than
CT
Four patterns of enhancement of focal pancreatic lesions are seen-
no enhancement-type I
vascularity less than adjacent pancreatic parenchyma-type II
vascularity equal to adjacent pancreatic parenchyma-type III
more than the adjacent pancreatic parenchyma-type IV.
Pancreatic adenocarcinoma usually demonstrate type I and II
patterns.
Pancreatic neuroendocrine tumors can depict significant
enhancement in the arterial phase of CEUS(type IV) even when it
may not show significant increased vascularity on Doppler imaging

42. Ductal adenocarcinoma (between arrows) of the pancreas
showing poor enhancement in the arterial phase.It will show poor
enhancement in venous phase also

43. Neuroendocrine tumour (arrow) shows a rapid intense enhancement
in the early arterial phase of contrast-enhanced ultrasound examination

44. Differentiation of Cystic Pancreatic Tumors from
Pancreatic Pseudocyst
CEUS can differentiate a cystic pancreatic neoplasm
from a pseudocyst by demonstrating the
enhancement of septae, nodules and solid
components in a tumor.
On the contrary; pancreatic pseudocysts are devoid
of any contrast enhancement, even though the
internal contents may appear echogenic on US
Detection of Pancreatic Necrosis in Acute Pancreatitis

45. Applications in Renal Imaging
Characterization of Renal Masses -Since CEUS is
more sensitive to detection of blood flow than CECT,
it can differentiate a solid mass lesion from a cystic
one with greater accuracy. It also scores over CECT in
characterization of complex cystic renal masses as it
can detect the septa and solid components in
Bosniak grade 2 to 4 cysts with better sensitivity than
CECT.
Differentiation of Renal Tumors from Pseudotumors-
Enhancement of pseudotumors is similar to the
normal renal parenchyma on all phases of
enhancement.
Enhancement pattern of solid renal tumors differs
from that of the normal renal parenchyma in at least
one phase of enhancement.

46. Renal Vascular Lesions-
Differentiate renal infarcts from ischemic areas-
The infarcted area shows no enhancement whereas
hypoperfused area retains its blood flow, although
reduced
Differentiate renal infarct from cortical necrosis-
shows preserved hilar vascularity in contrast to
infarct.

47. Application in Abdominal Trauma
CEUS can detect intra-abdominal solid organ injuries
(including liver, splenic, renal lesions) with higher
sensitivity and specificity than US
A contusion is seen as a hypoechoic area within the
enhancing parenchyma with ill defined borders
A laceration is a more well defined linear non-
enhancing area
In hypovolemic shock all the abdominal solid organs
show reduced enhancement

48. US-B-mode (b) and CEUS (c) in a 40 year- male patient with blunt abdominal
trauma.
parenchymal lacerative area not recognizable by US B-Mode examination
CEUS demonstrate splenic hypoechoic lesion

49. US-B-mode (b) and CEUS (c) in a patient with blunt abdominal
trauma. intra-parenchymal traumatic area in liver (a) not recocognizable by US B-
Mode examination
(b)CEUS demonstrate hepatic hypoechoic lesion.

50. Applications in Breast Imaging
Benign masses (like fibroadenoma) show smooth
vessels at the periphery and less avid enhancement
whereas the malignant masses appear spiculated
have more tortuous vessels with irregular course,
and have inter-vascular shunts

51. Benign breast mass (Fibroadenoma).
B-mode US image shows a well defined smoothly marginated hypoechoic mass
lesion (A).
CEUS image reveals minimal enhancement and peripheral branching vessels
(arrow

52. Invasive ductal carcinoma of breast.
B-mode US image (A) reveals an illdefined hypoechoic mass lesion (block arrow)
which is taller than wide.
CEUS (B) demonstrates the spiculated margins of the mass and avid peripheral
enhancement with central nonenhancing area. The ductal extension of tumor also
shows avid enhancement (arrow)

53. TRUS-TRANSRECTAL ULTRASOUND

54. TECHNIQUE
Left lateral position
DRE
Introduce rectal ultrasound probe
No anaesthesia is required
Mild sedation is required if we have to do some
drainage,aspiration or biopsy

60. INDICATIONS OF TRUS
1. Prostatic cancer- diagnosis, staging and TRUS
guided biopsy
2. Benign prostatic hyperplasia
3. Evaluation of male infertility-vas diference
obstruction-dilated seminal vesicle>1.6cm in
transverse plane
Dilated ejaculatory duct>2.5mm in transverse plane.