A DISSERTATION ON“DIAGNOSTIC ACCURACY OF CONTRAST ENHANCED- ULTRASONOGRAPHY IN CONTRAST ENHANCED COMPUTED TOMOGRAPHY
DETECTED FOCAL LIVER LESIONS.”
Submitted to
THE TAMIL NADU DR.M.G.R.MEDICAL UNIVERISTY CHENNAI
In Partial Fulfillment of the Regulations
For the Award of the degree
M.D. DEGREE BRANCH VIII RADIODIAGNOSIS
STANLEY MEDICAL COLLEGE, CHENNAI.
MAY -2020
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CERTIFICATE
This is to certify that the dissertation titled “
DIAGNOSTIC ACCURACY OF CONTRAST ENHANCED- ULTRASONOGRAPHY IN CONTRAST ENHANCED COMPUTED TOMOGRAPHY DETECTED FOCAL LIVER LESIONS
” submitted by Dr.KARTHIKRAJAN R , appearing for M.D.RADIODIAGNOSIS degree examination in April 2020, is a bonafide record of work done by him under my guidance and supervision in partial fulfillment of requirements of The Tamilnadu Dr. M.G.R Medical University, Chennai. I forward this to The Tamilnadu Dr.M.G.R Medical University, Chennai.
PROF.R.SHANTHI MALAR, M.D.,D.A., THE DEAN,
Stanley Medical College, Chennai – 600 001.
CERTIFICATE
This is to certify that the dissertation titled “
DIAGNOSTIC ACCURACY OF CONTRAST ENHANCED-ULTRASONOGRAPHY IN CONTRAST ENHANCED COMPUTED TOMOGRAPHY DETECTED FOCAL LIVER LESIONS
” submitted by Dr.KARTHIKRAJAN R , appearing for M.D.RADIODIAGNOSIS degree examination in April 2020, is a bonafide record of work done by him under my guidance and supervision in partial fulfillment of requirements of The Tamilnadu Dr. M.G.R Medical University, Chennai. I forward this to The Tamilnadu Dr.M.G.R Medical University, Chennai.
PROF.C.AMARNATH,MDRD,FRCR., Professor,
Head of the Department,
Department of Radio Diagnosis, Stanley Medical College,
Chennai – 600 001.
.
CERTIFICATE
This is to certify that the dissertation titled “
DIAGNOSTIC ACCURACY OF CONTRAST ENHANCED- ULTRASONOGRAPHY IN CONTRAST ENHANCED COMPUTED TOMOGRAPHY DETECTED FOCAL LIVER LESIONS
” submitted by Dr.KARTHIKRAJAN R , appearing for M.D.RADIODIAGNOSIS degree examination in April 2020, is a bonafide record of work done by him under my guidance and supervision in partial fulfillment of requirements of The Tamilnadu Dr. M.G.R Medical University, Chennai. I forward this to The Tamilnadu Dr.M.G.R Medical University, Chennai.
PROF DR.G.SATHYAN,MDRD., Guide,
Professor,
Department of Radio Diagnosis, Stanley Medical College,
Chennai – 600 001.
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DECLARATION
I, Dr.KARTHIKRAJAN.R, Registration number 201718203 certainly declare that this dissertation titled, “
DIAGNOSTIC ACCURACY OF CONTRAST ENHANCED-ULTRASONOGRAPHY IN CONTRAST ENHANCED COMPUTED TOMOGRAPHY DETECTED FOCAL LIVER LESIONS
”, represent a genuine work of mine done at the Department of Radio Diagnosis, Stanley Medical College, under the supervision of the PROF.G.SATHYAN, MDRD, Professor, Department of Radio Diagnosis, Stanley Medical College, Chennai – 600 001.I, also affirm that this bonafide work or part of this work was not submitted by me or any others for any award, degree or diploma to any other university board, neither in India or abroad. This is submitted to The Tamil Nadu Dr.MGR Medical University, Chennai in partial fulfilment of the rules and regulation for the award of Master of Radiodiagnosis Branch VIII.
Dr.KARTHIKRAJAN.R Date :
Place: Chennai
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ACKNOWLEDGEMENT
I would like to express my deep sense of gratitude to the Dean, PROF.SHANTHI MALAR, M.D., Stanley Medical College, Chennai, and PROF.C.AMARNATH,MDRD, Professor, Head of the Department, Department of Radio Diagnosis, Stanley Medical College, Chennai, for allowing me to undertake this study on “
DIAGNOSTIC ACCURACY OF CONTRAST ENHANCED- ULTRASONOGRAPHY IN CONTRAST ENHANCED COMPUTED TOMOGRAPHY DETECTED FOCAL LIVER LESIONS
”.I was able to carry out my study to my fullest satisfaction, thanks to guidance, encouragement, motivation and constant supervisionextended to me, by my beloved Head of the Department PROF.C.AMARNATH, MDRD, Hence my profuse thanks are due for him.
I would like to express my deep gratitude and respect to my guide PROF.G.SATHYAN, MDRD, whose advice and insight was invaluable to me.
This work would not have been possible without the guidance, support and encouragement.
I am also extremely indepted to Professor.DR.SUHASINI.B, MDRD., our former Associate Professor for her valuable suggestions, personal attention and guidance especially at the inception of the study.
My sincere thanks to Professor Dr.C.NELLAIYAPPAN, MDRD for his practical comments and constructive cricticism during my study and I also wish to thank Prof.Dr.CHIRTRARASAN, MDRD for his valuable support through out the study.
I am bound by ties of gratitude to my respected Associate Professors, Dr.Chezhian.J , Dr.Sudhakar , and Assistant Professors , Dr.Balaji.A, Dr.Komalavalli, Dr.Sivakumar.K, Dr.Priya.M , Dr.Sakthivel Raja.G, in general, for placing and guiding me on the right track from the very beginning of my career in Radiodiagnosis till this day.
I also thank my past and present fellow postgraduates who helped me in carrying out my work and preparing this dissertation. I thank all the
Radiology technicians , Staff Nurses and all the Paramedical staff members in my Department, for their fullest co-operation. I thank my statistician who rendered his valuable timely help in completing this study.
I thank my parents and my brother and sister for their constant and persistent support for my studies and in all my endeavours. My heartfelt thanks to my wife, for her endless support, continued and unfailing love, which helped me to overcome the difficulties encountered in the pursuit of this degree.
I would be failing in my duty if I don’t place on record my sincere thanks to those patients and their relatives who inspite of their sufferings extended their fullest co-operation to the study.
Dr.KARTHIKRAJAN R
TABLE OF CONTENTS
SL.NO CONTENTS PAGE
1 INTRODUCTION 1
2 AIM AND OBJECTIVES OF THE STUDY 37
3 REVIEW OF LITERATURE 39
4 MATERIALS AND METHODS 43
5 STATISTICAL ANALYSIS 51
6 OBSERVATON AND RESULTS 58
7 DISCUSSION 60
8 LIMITATIONS OF THE STUDY 71
9 CASES 72
10 CONCLUSION 84
11 BIBLIOGRAPHY 86
12 ABBREVIATIONS 90
13 ANNEXURE
I Patient proforma 91
II Patient information sheet 92
III Patient consent form 94
IV Master chart 96
V Ethical committee approval 97 VI Digital receipt of plagiarism 98
VII Plagiarism Certificate 99
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1
INTRODUCTION
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INTRODUCTION
Contrast enhanced ultra-sound is the application of ultrasound contrast medium to the tradional medical sonography.Prevalence of focal liver lesions in general population is 15.25%.
Contrast media are gas filled micro bubbles that are administered intra venously followed by dynamic real time imaging by ultrasound using a contrast specific software.It is difficult to characterize a focal liver lesion by conventional B mode and doppler ultrasound because the character of a malignant lesion may be similar to a benign lesion.
CEUS has improved the detection and characterization of focal liver lesions, offering comparable results to those with contrast CT when ultra-sound exploration is technically satisfactory.The vascular property of the lesion in arterial, portal and delayed phases by enhancement and washout is used in this technique.
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PHYSICS OF ULTRASOUND:
All diagnostic ultrasound applications are based on the detection and display of acoustic energy reflected from interfaces within the body. These interactions provide the information needed to generate high-resolution, gray-scale images of the body, as well as display information related to blood flow. Its unique imaging attributes have made ultrasound an important and versatile medical imaging tool. However, expensive state of the art instrumentation does not guarantee the production of high quality studies of diagnostic value. Gaining maximum benefit from this complex technology requires a combination of skills, including knowledge of the physical principles that empower ultrasound with its unique diagnostic capabilities. The user must understand the fundamentals of the interactions of acoustic energy with tissue and the methods and instruments used to produce and optimize the ultrasound display. With this knowledge the user can collect the maximum information from each examination, avoiding pitfalls and errors in diagnosis that may result from the omission of information or the misinterpretation of artifacts.
Ultrasound imaging and Doppler ultrasound are based on the scattering of sound energy by interfaces of materials with different properties through interactions governed by acoustic physics. The amplitude of reflected energy is used to generate ultrasound images, and frequency shifts in the backscattered ultrasound provide information relating to moving targets such as blood. To produce, detect, and process ultrasound data, users must manage numerous variables, many under their direct control. To do this, operators must understand the methods used to generate
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ultrasound data and the theory and operation of the instruments that detect, display, and store the acoustic information generated in clinical examinations.
BASIC ACOUSTICS WAVELENGTH AND FREQUENCY:
Sound is the result of mechanical energy traveling through matter as a wave producing alternating compression and rarefaction. Pressure waves are propagated by limited physical displacement of the material through which the sound is being transmitted. A plot of these changes in pressure is a sinusoidal waveform , in which the Y axis indicates the pressure at a given point and the X axis indicates time .Changes in pressure with time define the basic units of measurement for sound.
The distance between corresponding points on the time pressure curve is defined as the wavelength (λ), and the time (T) to complete a single cycle is called the period. The number of complete cycles in a unit of time is the frequency (f ) of the sound.
Frequency and period are inversely related. If the period (T) is expressed in seconds, f
= 1/T, or f = T × sec–1. The unit of acoustic frequency the hertz (Hz); 1 Hz = 1 cycle per second. High frequencies are expressed in kilohertz (kHz; 1 kHz =1000 Hz) or megahertz (MHz; 1 MHz = 1,000,000 Hz).
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In nature, acoustic frequencies span a range from less than 1 Hz to more than 100,000 Hz (100 kHz). Human hearing is limited to the lower part of this range, extending from 20 to 20,000 Hz. Ultrasound differs from audible sound only in its frequency, and it is 500 to 1000 times higher than the sound we normally hear. Sound frequencies used for diagnostic applications typically range from 2 to 15 MHz, although frequencies as high as 50 to 60 MHz are under investigation for certain specialized imaging applications. In general, the frequencies used for ultrasound imaging are higher than those used for Doppler. Regardless of the frequency, the same basic principles of acoustics apply.
PROPAGATION OF SOUND:
In most clinical applications of ultrasound, brief bursts or pulses of energy are transmitted into the body and propagated through tissue. Acoustic pressure waves can travel in a direction perpendicular to the direction of the particles being displaced (transverse waves), but in tissue and fluids, sound propagation is along the direction of particle movement (longitudinal waves). The speed at which the pressure wave moves through tissue varies greatly and is affected by the physical properties of the tissue.
Propagation velocity is largely determined by the resistance of the medium to compression, which in turn is influenced by the density of the medium and its stiffness or elasticity. Propagation velocity is increased by increasing stiffness and reduced by decreasing density. In the body, propagation velocity may be regarded as constant for a given tissue and is not affected by the frequency or wavelength of the sound.
In the body the propagation velocity of sound is assumed to be 1540 meters per second (m/sec). This value is the average of measurements obtained from normal tissues.
Although this value represents most soft tissues, such tissues as aerated lung and fat
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have propagation velocities significantly less than 1540 m/sec, whereas tissues such as bone have greater velocities. Because a few normal tissues have propagation values significantly different from the average value assumed by the ultrasound scanner, the display of such tissues may be subject to measurement artifacts or errors. The propagation velocity of sound (c) is related to frequency and wavelength by the following simple equation: c=f_1, thus a frequency of 5 MHz can be shown to have a wavelength of 0.308 mm in tissue: λ = c/f = 1540 m/sec × 5,000,000 sec–1 = 0.000308 m = 0.308 mm.
PROPAGATION VELOCITY ARTIFACT:
When sound passes through a lesion containing fat, echo return is delayed because fat has a propagation velocity of 1450 m/sec, which is less than the liver. Because the ultrasound scanner assumes that sound is being propagated at the average velocity of 1540 m/sec, the delay in echo return is interpreted as indicating a deeper target.
Therefore the final image shows a mis-registration artifact in which the diaphragm and other structures deep to the fatty lesion are shown in a deeper position than expected (simulated image).
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ACOUSTIC IMPEDANCE:
Current diagnostic ultrasound scanners rely on the detection and display of reflected sound or echoes. Imaging based on transmission of ultrasound is also possible, but this is not used clinically at present. To produce an echo, a reflecting interface must be present. Sound passing through a totally homogeneous medium encounters no interfaces to reflect sound, and the medium appears anechoic or cystic. At the junction of tissues or materials with different physical properties, acoustic interfaces are present. These interfaces are responsible for the reflection of variable amounts of the incident sound energy. Thus, when ultrasound passes from one tissue to another or encounters a vessel wall or circulating blood cells, some of the incident sound energy is reflected. The amount of reflection or backscatter is determined by the difference in the acoustic impedances of the materials forming the interface. Acoustic impedance (Z) is determined by product of the density (ρ) of the medium propagating the sound and the propagation velocity (c) of sound in that medium (Z= ρc). Interfaces with large acoustic impedance differences, such as interfaces of tissue with air or bone, reflect almost all the incident energy. Interfaces composed of substances with smaller differences in acoustic impedance, such as a muscle and fat interface, reflect only part of the incident energy, permitting the remainder to continue onward. As with propagation velocity, acoustic impedance is determined by the properties of the tissues involved and is independent of frequency.
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REFLECTION:
The way ultrasound is reflected when it strikes an acoustic interface is determined by the size and surface features of the interface. If large and relatively smooth, the interface reflects sound much as a mirror reflects light. Such interfaces are called specular reflectors because they behave as “mirrors for sound.” The amount of energy reflected by an acoustic interface can be expressed as a fraction of the incident energy; this is termed the reflection coefficient (R). If a specular reflector is perpendicular to the incident sound beam, the amount of energy reflected is determined by the following relationship:
R = (Z2-Z1)2/(Z2+Z1)2
Because ultrasound scanners only detect reflections that return to the transducer, display of specular interfaces is highly dependent on the angle of insonation (exposure to ultrasound waves). Specular reflectors will return echoes to the transducer only if the sound beam is perpendicular to the interface. If the interface is not at a 90-degree angle to the sound beam, it will be reflected away from the transducer, and the echo will not be detected Most echoes in the body do not arise from specular reflectors but rather from much smaller interfaces within solid organs.
In this case the acoustic interfaces involve structures with individual dimensions much smaller than the wavelength of the incident sound. The echoes from these interfaces are scattered in all directions. Such reflectors are called diffuse reflectors and account for the echoes that form the characteristic echo patterns seen in solid organs and tissues. The constructive and destructive interference of sound scattered by diffuse reflectors results in the production of ultrasound speckle, a feature of
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tissue texture of sonograms of solid organs for some diagnostic applications, the nature of the reflecting structures creates important conflicts. For example, most vessel walls behave as specular reflectors that require insonation at a 90-degree angle for best imaging, whereas Doppler imaging requires an angle of less than 90 degrees between the sound beam and the vessel.
EXAMPLES OF SPECULAR REFLECTORS:
• Diaphragm
• Wall of urine-filled bladder
• Endometrial stripe
A)Specular Reflector B) Diffuse Reflector- Small interfaces in liver parenchyma
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REFRACTION:
Another event that can occur when sound passes from a tissue with one acoustic propagation velocity to a tissue with a higher or lower sound velocity is a change in the direction of the sound wave. This change in direction of propagation is called refraction and is governed by Snell’s law: sin θ 1 /sin θ 2 = c1/ c2
where θ1 is the angle of incidence of the sound approaching the interface, θ2 is the angle of refraction, and c1 and c2 are the propagation velocities of sound in the media forming the interface .Refraction is important because it is one cause of mis- registration of a structure in an ultrasound image . When an ultrasound scanner detects an echo, it assumes that the source of the echo is along a fixed line of sight from the transducer. If the sound has been refracted, the echo detected may be coming from a different depth or location than the image shown in the display. If this is suspected, increasing the scan angle so that it is perpendicular to the interface minimizes the artefact.
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Refraction artifact. Axial transabdominal image of the uterus shows a small gestational sac (A) and what appears to be a second sac (B). In this case, the artifact B is caused by refraction at the edge of the rectus abdominis muscle. The bending of the path of the sound results in the creation of a duplicate of the image of the sac in an unexpected and misleading location (simulated image).
INSTRUMENTATION:
Ultrasound scanners are complex and sophisticated imaging devices, but all consist of the following basic components to perform key functions:
• Transmitter or pulser to energize the transducer
• Ultrasound transducer itself.
• Receiver and processor to detect and amplify the backscattered energy and manipulate the reflected signals for display
• Display that presents the ultrasound image or data in a form suitable for analysis and interpretation
• Method to record or store the ultrasound image
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TRANSMITTER:
Most clinical applications use pulsed ultrasound, in which brief bursts of acoustic energy are transmitted into the body. The source of these pulses, the ultrasound transducer, is energized by application of precisely timed, High amplitude voltage.
The maximum voltage that may be applied to the transducer is limited by federal regulations that restrict the acoustic output of diagnostic scanners. The transmitter also controls the rate of pulses emitted by the transducer, or the pulse repetition frequency (PRF). The PRF determines the time interval between ultrasound pulses and is important in determining the depth from which unambiguous data can be obtained both in imaging and Doppler modes. The ultrasound pulses must be spaced with enough time between the pulses to permit the sound to travel to the depth of interest and return before the next pulse is sent. For imaging, PRFs from 1 to 10 kHz are used, resulting in an interval of 0.1 to 1ms between pulses. Thus, a PRF of 5 kHz permits an echo to travel and return from a depth of 15.4 cm before the next pulse is sent.
TRANSDUCER:
A transducer is any device that converts one form of energy to another. In ultrasound the transducer converts electric energy to mechanical energy, and vice versa. In diagnostic ultrasound systems the transducer serves two functions:
(1) Converting the electric energy provided by the transmitter to the acoustic pulses directed into the patient and
(2) Serving as the receiver of reflected echoes, converting weak pressure changes into electric signals for processing.
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Ultrasound transducers use piezoelectricity, a principle discovered by Pierre and Jacques Curie in 1880.Piezoelectric materials have the unique ability to respond to the action of an electric field by changing shape. They also have the property of generating electric potentials when compressed. Changing the polarity of a voltage applied to the transducer changes the thickness of the transducer, which expands and contracts as the polarity changes.
This results in the generation of mechanical pressure waves that can be transmitted into the body. The piezoelectric effect also results in the generation of small potentials across the transducer when the transducer is struck by returning echoes.
Positive pressures cause a small polarity to develop across the transducer; negative pressure during the rarefaction portion of the acoustic wave produces the opposite polarity across the transducer. These tiny polarity changes and the associated voltages are the source of all the information processed to generate an ultrasound image or Doppler display.
Only reflections of pulses that return to the transducer are capable of stimulating transducer with small pressure changes, which are converted into the voltage changes that are detected, amplified, and processed to build an image based on the echo information.
IMAGE DISPLAY:
Ultrasound signals may be displayed in several ways.Over the years, imaging has evolved from simple A-mode and bistable display to high-resolution, real-time, grayscale imaging. The earliest A-mode devices displayed the voltage produced across the transducer by the backscattered echo as a vertical deflection on the face of
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an oscilloscope. The horizontal sweep of the oscilloscope was calibrated to indicate the distance from the transducer to the reflecting surface. In this form of display, the strength or amplitude of the reflected sound is indicated by the height of the vertical deflection displayed on the oscilloscope. With A-mode ultrasound, only the position and strength of a reflecting structure are recorded.
Another simple form of imaging, M-mode ultrasound, displays echo amplitude and shows the position of moving reflectors. M-mode imaging uses the brightness of the display to indicate the intensity of the reflected signal. The time base of the display can be adjusted to allow for varying degrees of temporal resolution, as dictated by clinical application. M-mode ultrasound is interpreted by assessing motion patterns of specific reflectors and determining anatomic relationship from characteristic patterns of motion.
Currently, the major application of M-mode display is evaluation of the rapid motion of cardiac valves and of cardiac chamber and vessel walls. M-mode imaging may play a future role in measurement of subtle changes in vessel wall elasticity accompanying atherogenesis.
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B-mode imaging; A 2-D, real-time image is built by ultrasound pulses sent down a series of successive scan lines.Each scan line adds to the image, building a 2-D representation of echoes from the object being scanned. In real-time imaging, an entire image is created 15 to 60 times per second.
The mainstay of imaging with ultrasound is provided by real-time, gray- scale, B-mode display, in which variations in display intensity or brightness are used to indicate reflected signals of differing amplitude. To generate a two-dimensional (2-D) image, multiple ultrasound pulses are sent down a series of successive scan lines, building a 2-D representation of echoes arising from the object being scanned.
When an ultrasound image is displayed on a black background, signals of greatest intensity appear as white; absence of signal is shown as black; and signals of intermediate intensity appear as shades of gray. If the ultrasound beam is moved with respect to the object being examined and the position of the reflected signal is stored, the brightest portion of the resulting 2-D image indicate structures reflecting more of the transmitted sound energy back to the transducer.
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Real-time ultrasound produces the impression of motion by generating a series of individual 2-D images at rates of 15 to 60 frames per second. Real-time, 2-D, B-mode ultrasound is now the major method for ultrasound imaging throughout the body and is the most common form of B-mode display. Real-time ultrasound permits assessment of both anatomy and motion. When images are acquired and displayed at rates of several times per second, the effect is dynamic, and because the image reflects the state and motion of the organ at the time it is examined, the information is regarded as being shown in real time. In cardiac applications the terms “2-D echocardiography”
and “2-D echo” are used to describe real-time, B-mode imaging; in most other applications the term “real-time ultrasound” is used.
TRANSDUCER SELECTION:
Practical considerations in the selection of the optimal transducer for a given application include not only the requirements for spatial resolution, but also the distance of the target object from the transducer because penetration of ultrasound diminishes as frequency increases. In general, the highest ultrasound frequency permitting penetration to the depth of interest should be selected. For superficial vessels and organs, such as the thyroid, breast, or testicle, lying within 1 to 3 cm of the surface, imaging frequencies of 7.5 to 15 MHz are typically used.For evaluation of deeper structures in the abdomen or pelvis more than 12 to 15 cm from the surface, frequencies as low as 2.25 to 3.5 MHz may be required. When maximal resolution is needed, a high frequency transducer with excellent lateral and elevation resolution at the depth of interest is required.
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IMAGE DISPLAY AND STORAGE:
With real-time ultrasound, user feedback is immediate and is provided by video display. The brightness and contrast of the image on this display are determined by the, the brightness and contrast settings of the video monitor, the system gain setting, and the TGC adjustment. The factor most affecting image quality is probably improper adjustments of the video display, with a lack of appreciation of the relationship between the video display settings. Because of the importance of the real-time video display in providing feedback to the user, it is essential that the display and the lighting conditions under which it is viewed are standardized and matched to the display used for interpretation. Interpretation of images and archival storage of images may be in the form of transparencies printed on film by optical or laser cameras and printers, videotape, or digital picture archiving and communications system (PACS). Increasingly, digital storage is being used for archiving of ultrasound images.
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CONTRAST AGENTS FOR ULTRASOUND
These agents contain micro bubbles (MB) of air, nitrogen or fluorocarbon gas coated with a thin shell of material such as albumin, galactose or lipid. Shell maintains micro bubble integrity; determines time in circulation and elasticity, bubbles determine echogenicity. Micro bubbles size 1 to 4 microns; should not cross vascular endothelium, nano bubbles 400 – 800nm size; enter pulmonary circulation will be in powder form with suspension medium (galactose) used as IV contrast. Administered within 15 minutes of preparation.
MECHANISM OF ACTION:
Many small interfaces causing backscattering of sound waves and bubble resonance Micro bubble is cleared through gas exchange through expiration by lungs. Residual shell and intact bubbles through phagocytosis gets accumulated in liver (Kupfer cells) and spleen (macrophages).
Mechanical index:
It is the measure of acoustic power output of ultrasound imaging ,increase in the MI increases image quality but leads to bubble burst. Microbubble Softshell /Microbubble thin and flexible at low MI they split into smaller bubbles.
Hardshell Microbubble produces higher echogenicity and at high MI it ruptures .
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TYPES:
• Non- targeted and targeted.
• Targeted – bind to specific molecules and then targeted at tissues expressing the substance.
Uses of targeted US Contrast Media:
Inflammatory diseases like , 1.Crohns
2.Thrombus detection ex; MI
3.Carcinoma binding to VEGF receptor 4.Drug delivery
5.Gene delivery
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Tissue specific contrast agent
Microbubble contrast agent
Vascular Enhancement agents
Targeted contrast agents
LEVOVIST SONOVIST SONOZOID
Encapsulated air bubbles 5- 10 micrometer.Eg- Albunex
& infosan.
Differential uptake
First generation USCA
Second generation USCA Third generation USCA
Non-transpulmonary vascular
Limited to the venous system and the right heart cavities after IV
injection.
Transpulmonary vascular, with short half-life (less than 5 min);
Sufficiently small and stable to pass into the systemic circulation.
Enhance the Doppler signal in various arteries after IV.
Transpulmonary vascular, with longer half-life (greater than 5 min).
Echogenic & stable
Enhance the echogenicity of parenchyma on B-mode images.
Shows perfusion, even in difficult region as the myocardium
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ADVANTAGES OF US CONTRAST MEDIA:
• No radiation
• Real time evaluation
• Cost effective
• Low dose needed
DISADVANTAGE:
• Doesn’t last long in circulation
• Produces increase heat as frequency increases
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BACKGROUND OF CEUS
Under a low MI ultrasound beam, microbubbles will have an asymmetric oscillation This oscillation produces a continuous specific signal that can be distinguished from the signal produced by tissue, because
• Tissue reacts to ultrasound in a linear way.
• Microbubbles react in a non linear way.
GAS BUBBLES IN THE BODY:
• Gas bubbles back-scatter ultrasound signal (accidental discovery)
• Gas micro-bubbles were introduced into the vessels, in an effort to increase blood signal.
• Gas micro-bubbles stay in the blood pool (i.e. do not extravasate), but still there are persistency issues.
GAS BUBBLES PROPERTIES:
At a given frequency, the backscatter index of air micro-bubbles is maximum
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MICRO-BUBBLES RESONANCE:
• Gas bubbles in an ultrasound beam may oscillate
• The oscillation is maximum at a specific beam frequency (called the frequency of resonance)
• Depending on the ultrasound beam power (also called the Mechanical Index, or MI) oscillation can result in rupture of the bubble
BUBBLE DESTRUCTION :
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THE FORTUNATE COINCIDENCE:
At given frequencies, micro-bubbles resonate and generate a strong echo signal
VERY LOW INSONATION POWER (MI):
• small oscillation
• linear behavior
MODERATELY LOW INSONATION POWER (MI):
• large oscillation
• non-linear behavior
HIGH INSONATION POWER (MI):
• micro-bubble rupture
• saturation of signal (flash) for a short time
• need to wait for more micro-bubbles to replenish the tissue.
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GENARATION OF HARMONICS:
MICRO-BUBBLE HARMONICS:
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CONTRAST SPECIFIC IMAGING TECHNIQUES:
The purpose of CSI techniques is to discriminate microbubble response from tissue signal:
• The tissue signal is linear
• The microbubble signal is non linear
CONTRAST SPECIFIC IMAGING TECHNIQUES there are 4 main techniques:
1. harmonic detection: to filter the low frequency tissue response
2. pulse inversion: the tissue signal is cancelled by the emission of two or more successive pulses of opposite phase (e.g. toshiba aplio ps)
3. amplitude modulation: the dependence of the mb amplitude and shape on transmission is directly utilised (e.g. philips sonos 5500)
4. phase modulation + amplitude modulation:
combination of the 2 techniques allows to use the non linear fundamental and harmonic microbubble signal (e.g. siemens sequoia cps)
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IMAGING METHODS:
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THE MECHANICAL INDEX (MI) :
ADVANTAGES OF LOW MI TECHNIQUE:
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THE IDEAL QUALITIES OF AN ULTRASOUND CONTRAST AGENT:
• High echogenicity;
• low attenuation;
• Low blood solubility
• Low diffusivity
• Ability to pass through the pulmonary capillary bed
• Lack of biological effects with repeated doses.
THE QUALITY OF ENHANCEMENT DEPENDS ON:
• the concentration of the contrast agent;
• the type of injection, flow rate;
• the patient characteristics
• the microbubble quality and properties of the filling gas and the shell.
MICROBUBBLES:
Microbubbles filled with air or inert gases are used as contrast agents in ultrasound imaging. Compression and rarefaction created by an ultrasound wave insonating a gas-filled microbubble along with the mechanical index of the ultrasonic beam lead to volume pulsations of the bubbles, and it is this change that results in the signal enhancement.
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AIR FILLED MICROBUBBLE:
They are not stable and rapidly dissolve in blood. Two micrometer diameter air bubble disappears in 20milli seconds. Hence, there is no chance of an US examination. One way to increase the lifetime of Microbubble is to substitute air with high molecular weight gas such as Perfluorocarbons resulting in stabilised gas filled Microbubble.
To pass through the lung capillaries and enter into the systemic circulation, microspheres should be less than 10 µm in diameter. Air bubbles in that size range persist in solution for only a short time; too short for systemic vascular use.
Microbubbles have diameters from 1 µm to 10 µ m and a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. These micro-bubbles can cross the pulmonary capillaries and have a serum half-life of a few minutes. Microbubbles in the 1-10 µm range have their resonance at the frequencies used in diagnostic ultrasound (1–15MHz).Smaller bubbles resonate at higher frequencies caused by this coincidence, they are such effective reflectors.
The intrinsic compressibility of microbubbles is approximately 17,000 times more than water, and they are very strong scatterers of ultrasound. Under acoustic pressure the vibrating bubble radius may have a conventional linear response or a harmonic non-linear response. Microbubbles usually increase the Doppler signal amplitude by up to 30 dB.
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MICROBUBBLES SHELL:
A micro bubble shell, designed to reduce diffusion into the blood, can be stiff (e.g., denatured albumin) or more flexible (phospholipid), varying in thickness from 10–200 nm.
The shell stabilizes against dissolution and coalescence with additional materials at the gas-liquid interface. This material can be an elastic solid shell that enhances stability by supporting a strain to counter the effect of surface tension. Also a surfactant, or a combination of two or more, improves the stability by a high reduction of the surface tension at the interface. Current ultrasound contrast agents are micron-sized bubbles with a stabilizing shell.
CORE GAS IN MICROBUBBLE:
The gas in microbubbles is highly compressible and, when subjected to the alternating compression and rarefaction pressures that constitute an ultrasound pulse, microbubbles oscillate at their natural frequency at which they resonate most strongly.
This is determined by their size but is also influenced by the composition of the filling gas.
Air, sulfur hexafluoride, nitrogen, and perfluoro chemicals are used as filling gases.
Most newer ultrasound contrast agents use perfluoro chemicals because of their low solubility in blood and high vapor pressure. By substituting different types of perfluorocarbon gases for air, the stability and plasma longevity of the agents have been markedly improved, usually lasting more than five minutes.
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Resonating microbubbles emit harmonic signals at double their resonance frequency. If a scanner is modified to select only these harmonic signals, this non-linear mode produces a clear image or trace. The effect depends on the fact that it is easier to expand a bubble than to compress it so that it responds asymmetrically to a symmetrical ultrasound wave.
A special array design allows to perform third or fourth harmonic imaging. This probe type is called a dual frequency phased array transducer.
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DEVELOPMENT OF GENERATIONS:
• First generation USCA = Non-transpulmonary vascular
• Second generation USCA = transpulmonary vascular, o with short half life (less than 5 min)
• Third generation USCA = transpulmonary vascular, o with longer half life (greater than 5 min).
The third generation ultrasound contrast agents (UCA/USCA) are more echogenic and stable, and are able to enhance the echogenicity of parenchyma on B-mode images.
These microbubbles may thus show perfusion, even in such a difficult region as the myocardium. In the 1990s newer developed agents with fluorocarbon gases and albumin, surfactant, lipid, or polymer shells have an increased persistence of the microspheres. This smaller, more stable microbubble agents, and improvements in ultrasound technology, have resulted in a wider range of application including myocardial perfusion.
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NEED FOR CEUS STUDY:
• Many lesions are isoechoic to background parenchyma and very often lesions are not detected at native ultrasound.Even when detected, lesions can very hardly be characterized with Ultrasound .
• For Real time detection & characterization of lesions and Enhancement pattern of the lesion.
• Immediately establish the diagnosis, especially for benign liver lesions, such as hemangiomas, avoiding further and more expensive examinations.
• There also reduced risk of radiation exposure when Compared to CT.
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AIMS AND OBJECTIVE
38
AIMS AND OBJECTIVE
• The aim of the study is to interpret the use of contrast-enhanced ultra-sound (CEUS) in characterising the focal liver lesions.
• Comparing the diagnostic accuracy of the contrast-enhanced ultra-sound with contrast enhanced CT.
OBJECTIVE:
• To explain the pattern enhancement and washout of malignancy in a focal liver lesion at CEUS.
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REVIEW OF LITERATURE
40
REVIEW OF LITERATURE
A threshold size of 1-cm for characterization of lesions with CEUS is valuable and accepted by the Liver Imaging Reporting and Data System (LI-RADS) working group (4), but in our experience, the lesions that can be seen well at gray-scale US can be accurately and confidently evaluated, especially to exclude malignancy.
In Bhayana et al non hepato cellular malignancies (ie, metastases, cholangio carcinoma, and lymphoma) shows early washout, typically before 1 minute; and HCC generally begins washing out later (after 1 minute).
The Mechanical index for CEUS is calculated from the amplitude of the ultrasound pulse, which is proportional to the peak negative pressure of the ultrasound beam(5).
The Algorithm for Enhancement pattern for Liver lesions presented in this thesis has been developed from many years of experience of the radiologists at five separate Canadian academic centers: University of Calgary, University of Toronto, University of Vancouver, Université de Montréal, and the University of Western Ontario. The schematic diagram in my discussion is based on the previous work of Wilson and Burns (9) published in 2006.
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With CEUS and other contrast-enhanced imaging modalities, washout is a feature of malignancy. Though , Bhayana et al (6) has shown that washout occurred in 97% of malignant lesions and 37% of benign lesions evaluated by CEUS. Of the benign lesions that showed washout in the study by Bhayana et al (6), many exhibited characteristic arterial phase enhancement patterns that defined them as benign lesions. In addition, washout in these benign lesions often occurs late in the examination and is often vague compared with that in malignant lesions, in which washout is more pronounced.
The DEGUM study the reference standard diagnosis was made by means of liver biopsy in 75% of cases and by contrast-enhanced CT in the other cases. The accuracy of CEUS for the diagnosis of focal liver lesions was 90.3%.
According to the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines , CEUS is indicated for lesion characterization when a lesion or suspected lesion is detected with ultrasound in patients with a known history of malignancy, as an alternative to CT or MRI, or when CT and MRI are contraindicated or inconclusive. (26)
Claudon M, Dietrich CF, Choi BI, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver update 2012—a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB,
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AIUM, ASUM, FLAUS and ICUS.
Krix M. Contrast-enhanced ultrasound for the characterization of incidental liver lesions: an economical evaluation in comparison with multiphase computed tomography [in German].
The presence of multiple enhancement phases at hepatic imaging stems from the dual hepatic blood supply. In a normal liver, 20%–25% of hepatic blood is from the hepatic artery, which correlates with the arterial phase of imaging, typically lasting up to 40 seconds. The portal vein is responsible for the remaining 75%–
80% of hepatic blood, and the portal venous phase of imaging lasts from approximately 40 seconds to 2 minutes. The late phase occurs beyond 2 minutes and represents a relative state of equilibrium (7).
Although the microbubbles are robust and provide exceptional image detail, continuous scanning from injection to 5 minutes would essentially destroy all of the microbubbles in the field of view. Our strategy of continuous scanning in the arterial phase with intermittent scanning up to 5 minutes allows for good microbubble preservation (8,9).
The US contrast agent approved in April 2016 by the U.S. Food and Drug Administration is sulfur hexafluoride lipid–type A microspheres, marketed as as SonoVue (Bracco Diagnostics, Milan, Italy). The standard dose for SonoVue ( is a 1.8–2.4-mL intravenous bolus, followed by a saline flush. In my study we used this contrast agent.(4,6,7).
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MATERIALS AND METHODS
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MATERIALS AND METHODS
STUDY DESIGN: Self control experimental study
STUDY POPULATION:
Patients with focal liver lesions detected by USG/CECT coming to Department of Radio diagnosis in Government Stanley Hospital.
STUDY DURATION:
One and a half years from January 2018 to July 2019.
SAMPLE SIZE:
Total of 51 patients detected by CECT /USG as focal liver lesions registered in Govt. Stanley Medical College hospital between January 2018 to July 2019.
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PATIENT SELECTION
INCLUSION CRITERIA:
All patients diagnosed as focal liver lesions by USG and CECT in the Department of Radio diagnosis who has registered in Govt.Stanley hospital.
EXCLUSION CRITERIA:
• Previous history of allergy to sulpha containing agents.
• Patients with pulmonary hypertension.
• Patient with acute respiratory distress syndrome.
• Patient with uncontrolled systemic hypertension.
• Multifocal liver lesions.
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METHODOLOGY:
• Ultrasound machine with contrast specific software with low mechanical index dual mode both B-mode and contrast specific mode is used.Before CEUS, a thorough conventional ultrasound the assessment of the liver lesion on B-mode imaging and by means of color Doppler ultra- sound examination of the entire liver was performed.
• All 51 patients under plain ultrasound ,Contrast Enhanced ultrasound ,Contrast enhanced CT and also underwent histopathological analysis.
• In CEUS, 1.5-2 mL of micro bubble contrast agent sulphur hexafluride is rapidly injected via an antecubital vein followed by a 10-mL saline flush.
TECHNIQUE
PREPARATION:
In our study we advised patients to preferably come morning with over night fasting also instructed not to consume alcohol or caffeine.Anti allergy drugs and emergency drugs should be kept ready (eg.Adrenaline).Bleeding and clotting profile should be normal.
POSITIONING:
Supine position with arms raised above the head level and resting state breathing.
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MACHINE REQUIREMENTS:
Contrast software enabled USG machine is used, In my study Mind Ray M6 model USG machine which supports Contrast specific software was used and dual mode display for gray scale and contrast specific imaging is required.
BASIC REQUIREMENTS DURING SONOVUE DEMO:
• IV Canula 20G – Pink.
• Preferably Two way stopper so as to enable injection of the Sonovue contrast from the centre and saline from the side. This way the microbubbles are
preserved. Do not use any tubing to inject Sonovue contrast as the microbubbles may get destroyed.
• The syringes required are 2ml syringe for Sonovue and 10ml syringe for saline chase and for subsequent patients same syringes were not used.
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STEPS OF SONOVUE KIT RECONSTITUTION:
Rod to be Plunged is fixed to a syringe containing saline and rotated.
Then mini spike is opened
Blue cap of Sonovue vial is Removed
Sonovue vial inside the spike is pushed till we hear a click sound that ensures the vial is fixed to the spike.
The seal is removed of the syringe containing saline and the syringe is fixed to the spike by removing lid of the spike
The saline is pushed into the Sonovue Vial.
The vial is shaked manually shaked to prepare the microbubbles and solution appears milky white.
The required amount of Sonovue is taken in the syringe and it is unlocked from the spike and kept ready for injection.
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PROCEDURE OF DOING A CONTRAST ENHANCED ULTRASOUND STUDY:
A baseline Ultrasound is performed to localize the lesion. Still images and in the form of clip are stored, the baseline US study for comparison later, after pressing the contrast button on the machine is switched to contrast mode. In this mode the tissue signal which appeared bright is suppressed and the entire screen looks black. Then after that the reconsiuted Sonovue is injected followed by 10ml saline chase, most important switch on the timer and start acquiring and storing it in clip form.
The dual mode one depicting the B-mode and other depicting the contrast mode will be ideal. We ensured that the clip storing is adjusted to at least 3-5min so as to enable to capture all the three phases viz. arterial, venous and equilibrium or delayed phase to check in for wash in & wash out.
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STATISTICAL ANALYSIS
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STATISTICAL ANALYSIS:
The collected data were analysed with IBM.SPSS statistics software 23.0 Version to describe about the data descriptive statistics frequency analysis, percentage analysis were used for categorical variables and the mean & S.D were used for continuous variables. To find the efficacy of the tools on comparison with HPE the Sensitivity,specificity, Ppv & Npv were used.
Crosstabs:
USG with DOPPLER VS HISTOPATHOLOGY Cross tabulation:
COUNT
HISTOPATHOLOGY
Total Positive Negative
USG and DOPPLER Positive
20 8 28
Negative
21 2 23
Total
41 10 51
%
Sensitivity 48.78 Specificity 20.00
PPV 71.43
NPV 8.70
Accuracy 34.39
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CONTRAST ENHANCED USG VS HISTOPATHOLOGY CROSS TABULATION COUNT
HISTOPATHOLOGY
Total Positive Negative
CONTRAST
ENHANCED CT Positive
34 3 37
Negative 7 7 14
Total 41 10 51
%
Sensitivity 82.93 Specificity 70.00
PPV 91.89
NPV 50.00
Accuracy 76.46
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CONTRAST ENHANCED CT VS HISTOPATHOLOGY CROSSTABULATION
COUNT
HISTOPATHOLOGY
Total Positive Negative
CONTRAST
ENHANCED CT Positive
36 2 38
Negative
5 8 13
Total 41 10 51
%
Sensitivity 87.80 Specificity 80.00 PPV 94.74 NPV 61.54 Accuracy 83.90
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DESCRIPTIVE STATISTICS:
GENDER:
Frequency Percent
Female 22 43.1
Male 29 56.9
Total 51 100.0
Gender distribution
Female Male
N Minimum Maximum Mean Std
Deviation
AGE 51 36.0 75.0 57.392 9.0556
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AGE:
Frequency Percent
Upto 40 yrs 3 5.9
41-50 yrs 9 17.6
51-60 yrs 15 29.4
61-70 yrs 21 51.2
>70 yrs 3 5.9
Total 51 100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0
Upto 40 yrs 41 - 50 yrs 51 - 60 yrs 61 - 70 yrs > 70 yrs
Percentage
Age distribution
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ROC CURVE:
Specificity
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OBSERVATION AND RESULTS
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OBSERVATION AND RESULTS
Out of 51 patient with focal liver lesions detected by conventional USG out of which 34 cases are detected as true positives out of 41 positive cases diagnosed positive in HPE and 36 patients are detected as true positives detected by CECT out of these 41 cases. Histopathological diagnostic results showed 41 cases to be positive for both benign and malignant lesions.
Negatively proven cases in Histopathology are 10 out of which True negatives in CECT is 8 and True negatives in CEUS is 7. Specificity and Sensitivity of the CECT is slightly higher than that of CEUS. Negative predictive value of the CECT is also higher than of the CEUS.
Diagnostic Accuracy for CEUS is 76.46 % and CECT is 83.9%. Sensitivity ,specificity ,PPV ,NPV and Diagnostic accuracy of the CEUS is almost near equal or comparable with that of CECT.
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DISCUSSION
61 DISCUSSION
Out of 51 cases in my Study 9 cases were diagnosed to be Hemangioma, 13 cases were diagnosed to be Hepato cellular carcinoma and 16 cases were found to be Focal liver Metastasis , 5 cases were diagnosed to be intra hepatic cholangio carcinoma, 6 cases were Focal nodular hyperplasia and 2 cases were benign Hepatic adenoma.
In total cases in my study most commonly diagnosed focal liver lesions was focal liver metastasis, hemangioma and HCC. Least diagnosed focal liver lesion in my study is benign hepatic adenoma .
Cavernous hemangiomas are the most common benign liver tumor, with an incidence of approximately 2%–20%, with a slight female predominance (14). Many gray-scale US imaging features of hemangiomas have been described, and hemangiomas are often categorized as typical or atypical on the basis of these features. In asymptomatic patients without risk factors for malignancy, many hemangiomas appear as a uniformly hyper echoic mass and can be diagnosed by using the combination of conventional gray- scale and Doppler US alone (15). Large hemangiomas or hemangiomas with an unusual appearance on gray-scale US images often require further evaluation. Similarly, in a patient at risk for malignancy, a lesion with gray-scale US imaging features suggestive of hemangioma cannot be dismissed as such, because hemangiomas can be similar in appearance to HCC, and further assessment is required to exclude the possibility of malignancy (16).
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In our study in CEUS, most of the Hemangioma shows progressive peripheral nodular enhancement with centripetal progression, occurring rapidly or slowly.This pattern is characterized by discontinuous pooling of hyperenhancing contrast agent around the periphery of the lesion in a nodular fashion. This pattern correlates nicely with the well- described enhancement pattern of hemangiomas on CT images (9). Both small and large hemangiomas demonstrate this characteristic pattern of enhancement. At any time, contrast enhancement progresses centrally, filling the lesion either completely or partially.
In our study Two cases showed a pattern of flash filling type of hemangioma which is a common variation of hemangioma .Flash-filling hemangiomas account for approximately 16% of all hemangiomas and are most common with smaller lesions;
42% of hemangiomas measuring less than 1 cm are flash-filling lesions (14). CEUS is an excellent modality for the evaluation of flash-filling hemangiomas owing to the unique real-time arterial phase imaging capabilities of CEUS. Classic peripheral nodular enhancement is also observed in the early arterial.
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HEPATOCELLULAR CARCINOMA:
HCC is the most common primary malignant neoplasm of the liver and occurs usually in patients with a background of chronic liver disease (2,8). Ultrasound is the most common screening modality for HCC in at-risk patients. Unfortunately, the gray-scale US appearance of HCC is nonspecific, and further evaluation is required.
Two arterial phase enhancement characteristics of HCC are arterial phase hyper enhancement and dysmorphic vessels . In arterial phase hyper enhancement is one of the essential components for the noninvasive diagnosis of HCC, along with nodule size of more than 10 mm and late weak washout .The dysmorphic vessels and arterial phase hyperenhancement often coexist within the same lesion, especially if the tumor is large. Disorganized arterial phase enhancement of tubular vascular structures within a lesion is suggestive of malignant neovascularity and is a well-described early arterial phase feature of HCC (2,9,11). This pattern is observed in our study.
The fill-in pattern does not always follow a strictly centrifugal or centripetal pattern and proceeds in an indifferent disorganized fashion with somewhat tortuous vessels. A basket-weave pattern of disorganized centripetal neovasculature has been described in HCC and, when present, is a specific sign of HCC (12).
This observation is demonstrated in our study. Rarely, well-differentiated HCC will show isoenhancement in the arterial phase. These lesions may continue to demonstrate
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dysmorphic vascular enhancement with portal venous or late phase washout. In addition, CEUS can be used to assess the hepatic and portal venous structures for the presence of tumor thrombus and vascular invasion. Tumor thrombus is highly suggestive of HCC; however, tumor thrombus has been increasingly recognized as a less-common feature of nonhepatocellular malignancies such as cholangiocarcinoma.
NON HEPATO CELLULAR MALIGNANCY:
The common forms of non-hepatocellular malignancy in the liver are metastases, cholangiocarcinoma, and lymphoma. In our study metastasis occurred commonly,each of these lesions is difficult to diagnose on the basis of gray-scale US alone, and the arterial phase enhancement patterns are nonspecific. Three arterial phase enhancement patterns are described for these lesions,diffuse hyperenhancement is the most commonly encountered arterial phase appearance of nonhepatocellular malignancy (9,13).
An arterial phase enhancement variation that is more suggestive of non-hepatocellular malignancy is a hyperenhancing rim with central non-enhancement or hypo- enhancement (8,9). Finally, some non-hepatocellular malignancies will demonstrate enhancement less than that of the adjacent liver in the arterial phase (2). These three arterial phase enhancement patterns (hyperenhancement, rim enhancement, and hypoenhancement) are not suggestive of a specific type of nonhepatocellular malignancy.
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In our study most of the cases in Metastatic liver lesion showed hyperenhancement in early arterial phase and rapid wash out .Then two cases showed non enhancement in all three phases and diagnosed to be cystic metastasis from colonic adeno carcinoma.
FOCAL NODULAR HYPERPLASIA:
Focal nodular hyperplasia is a hepatocellular-based lesion and it represents the second most common benign hepatic tumor (2). Focal nodular hyperplasia is a hyperplastic mass thought to be secondary to an underlying vascular abnormality (17). Focal nodular hyperplasia is typically an asymptomatic lesion seen most commonly in women between the ages of 30 and 50 years (2). Pathologically, a typical lesion of focal nodular hyperplasia is composed of a central scar with radiating fibrous septae containing arterial structures. This pathologic appearance correlates well with the enhancement characteristics (17). Because focal nodular hyperplasia is thought to relate to an arterial vascular abnormality, focal nodular hyperplasia is a hyperenhancing lesion in the arterial phase at CEUS. Real-time assessment of focal nodular hyperplasia demonstrates a spoke-wheel pattern of enhancement with an inside-to-outside, or centrifugal, filling pattern. The spoke-wheel pattern reflects the presence of arterial structures within the radiating fibrous septae. The centrifugal progression of enhancement at CEUS makes focal nodular hyperplasia appear to grow during the arterial phase. Bubble-tracking techniques optimally show the spoke-wheel pattern of vascularity in focal nodular hyperplasia.
In our study in a case of FNH there is no central enhancement of the scar in all three phases in both CECT and CEUS, there is concordance between the CECT and CEUS
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in imging findings in this case but the classical pattern of FNH is not demonstrated in this study.
CEUS COMPARED WITH CECT:
In many well-documented CT with Contrast imaging enhancement patterns are reproduced with CEUS. Classic arterial phase hyperenhancement and washout in HCC and discontinuous peripheral nodular enhancement in a hemangioma are examples of concordant imaging features across the two contrast-enhanced modalities which is explained in our study.
The dominant difference between CEUS and CECT is the method of image acquisition. CEUS is a dynamic real-time imaging technique that can demonstrate enhancement regardless of the timing or duration of enhancement. This feature is well demonstrated in the example of a flash-filling hemangioma, in which early arterial phase imaging shows classic peripheral nodular enhancement and later arterial phase imaging shows diffuse enhancement. The ability of CEUS to image the arterial phase in real time allows accurate diagnosis of hemangioma, which may have been more difficult on the contrast-enhanced portions of CT imaging examinations (25).
The second unique feature of CEUS is the entirely intravascular nature of the microbubbles (10). Iodine- and gadolinium-based contrast agents diffuse into the interstitium, resulting in some sustained lesion enhancement that is not directly related to the vascularity of the lesion, which may reduce the conspicuity of washout (6,10).
In comparison, the individual CEUS microbubbles are too large to diffuse into the interstitium; and, therefore, CEUS enhancement reflects only the vascular properties of the lesion being assessed. This property leads to a situation in which CEUS may
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show washout of a malignant lesion, and CT imaging may show increasing enhancement. This discordant appearance is best described for tumors such a cholangiocarcinoma with a permeable endothelium and a fibrous stroma.
In addition, the good sensitivity of Ultrasound to a microbubble contrast agent allows depiction of smaller differences in contrast agent concentration in a lesion, compared with that of the background liver parenchyma. These two features make CEUS extremely sensitive in the assessment of washout.
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From various referances and the outcome of results in our study we tabulated the pattern of enhancement in the focal liver lesions,
