Introduction
Many small things have contributed to advances in diagnostic ultrasound brought about by con- trast-enhanced ultrasound (CEUS). Among the most important are the development of contrast microbubbles that are stable enough for contin- uous scanning, at least at low mechanical index, and ultrasound machine software that enables us to produce images based on microbubble con- centration rather than tissue echogenicity. This enables us to add a vast improvement in contrast resolution to the already excellent spatial and temporal resolution of ultrasound images. The image resolution of ultrasound can then be used to its full advantage also in patients where other modalities may not be possible, such as in impaired renal function or possible allergic reac- tions. Thus, techniques have been developed mainly for detection and characterisation of focal liver lesions [1-3]. As has been pointed out in previous chapters, the liver is particularly suited to CEUS, as the microbubbles get trapped and remain in the sinusoids but are washed out from tumour tissue.
However, applications are emerging for other tissues and organs as well. In the kidney, images based on contrast concentration can improve the detection of non-perfused focal lesions like cysts, abscesses, infarctions and post-radio-fre- quency ablation necroses. Normal renal parenchyma does not, of course, contain sinu- soids, but preliminary work suggests that the perfusion differences between tissues with a normal capillary bed and the neovascularisation of tumours can be detected if the pattern of con- trast-enhancement is followed over time, subjec- tively or with the aid of analysis programs, preferably built into the ultrasound machine itself [4].
Normal Kidney
The established phases of contrast-enhancement after a bolus injection that are seen in the liver are not seen in the kidneys due to differences in blood supply and vasculature. Similarly, howev- er, different stages of renal enhancement exist and must be understood in order to avoid misdi- agnosis. First the arteries enhance followed closely by a complete fill-in of the cortex. The pyramids then gradually enhance over the next 30-40 seconds to become isoechoic or almost isoechoic with the cortex. As there is no accumu- lation of contrast in the kidneys (as in the sinu- soids of the liver), the enhancement decreases with the microbubble concentration in the gen- eral circulation. When this happens there may again appear a difference between the cortex and the pyramids, the latter becoming once more hypoechoic (Fig. 1).
Cysts
Ultrasound contrast agents are so-called blood pool agents, i.e., they do not, contrary to X-ray contrast media, leave the blood vessels. With the availability of ultrasound machine software that can detect the differences between an echo ema- nating from tissue and the signal sent out by a res- onating contrast bubble, images can be formed based virtually only on the presence of microbub- bles. As structures without perfusion will have no contrast uptake, they will have no brightness in the image, whether they are in the liver or else- where in the body, thus remaining dark with an excellent delineation against normal surrounding tissue. Simple cysts will then be dark even during the peak of a contrast bolus even if they contain
IV.1
Contrast-Enhanced Ultrasound of Focal Renal Lesions
Anders Nilsson
echoes on native ultrasound. Thus smaller cysts can be detected. This may possibly be important in the early detection of conditions like polycystic kidney disease, but the main advantage is that the spatial resolution of ultrasound can be used for characterisation of indeterminate focal lesions detected on, for example, computed tomography (Fig. 2) [5]. As the sensitivity for detection of small amounts of contrast agent is improved in the newer software programs, possibilities open up also for detecting thin but perfused septae in the cysts, possibly indicative of malignancy rather than simple cysts.
Abscesses, Infarctions and Ruptures
It is important to remember that CEUS is an integral part of a complete ultrasound examina- tion, not a separate entity. Whereas all things
without contrast uptake will have the same brightness on CEUS, their appearance on native ultrasound will, of course, vary. Abscesses, espe- cially when small, may derange normal renal anatomy but will otherwise contain an echogenicity that could make them difficult to detect. On CEUS they will, like cysts, remain dark. The sharp delineation against normal tis- sue will enable a detailed assessment of the lesions shape that may give clues to its nature;
abscesses (like cysts) are often round. Infarctions and post-traumatic ruptures will, in the same fashion, appear dark, the spatial resolution of ultrasound helping in detecting even small lesions where a fissure can be seen as a narrow line and infarctions wedge-shaped near the kid- ney surface [6]. The case history will, of course, give more information and it could be said that the most important roles of CEUS are to detect the lesion and to ascertain that it is indeed non- enhancing (Figs. 3, 4).
Fig. 1a-d.Normal renal enhancement after an iv bolus. Note the slower fill-in of the pyramids (arrows), also shown by the quantifica- tion graph, where a ROI has been placed in a segmental artery (red), cortex (yellow) and a pyramid (green)
a b
c d
IV.1 • Contrast-Enhanced Ultrasound of Focal Liver Lesions 167
Fig. 3a-d. Renal abscess with minimal findings on B-mode, but with a clearly demarcated non-enhancing area on CEUS (arrow). After a CEUS-guided catheter drainage of the abscess, contrast has been injected through the catheter, delineating the abscess, but also sho- wing the collecting system that fills up with contrast
Fig. 2a, b.Cysts (arrows) show a clear demarcation and no contrast uptake, regardless of size a
b
a b
c d
Infections
If the case history suggests a renal infection, it is important to be able to differentiate between an already formed abscess and a pyelonephritis. As described above, an abscess on CEUS will be dark, but early experiences indicate that the dif- ference in perfusion caused by the parenchymal oedema around a pyelonephritis can also be
detected, similar to contrast-enhanced comput- ed tomography and power Doppler examina- tions [7, 8], appearing as an area with decreased brightness (Fig. 5). As this decrease is based on perfusion variations in tissues with the same blood vessel architecture otherwise, the differ- ences are seen during all the phases of a CEUS examination, contrary to the differences seen with tumour vascularisation (see below).
Fig. 4a, b.B-mode scan of a patient presenting with sudden severe left flank pain shows nothing, but CEUS depicts a non-enhancing, wedge-shaped area near the surface of the kidney, consistent with a small renal infarction
Fig. 5a, b.Scans through the left flank of a patient with flank pain and high fever. The kidney just caudal to the spleen (S) shows a normally enhancing lower pole but, by comparison, very sparse contrast uptake in the upper pole (contour marked)
a b
a b
Tumours
Many hypovascular tumours have very little enhancement on CT, not enough to make a con- fident diagnosis of a renal cell carcinoma. It is of value to be able to make this distinction rather than having to choose between additional, costly tests, a long follow-up or a mere assumption of a malignancy. CEUS, when performed with con- trast-specific software, is very sensitive to microbubble presence, even in small quantities.
Thus, intratumoural vasculature can be detected, possibly with the aid of quantification software that can detect an increase in image brightness even when a subjective assessment may leave doubts. In addition, small vessels may be depict- ed in mural nodules, septae or thickened cyst walls whereas the detection of such small vessels is difficult with Doppler (Fig. 6). Thus, CEUS may
be used for the evaluation of CT/MR findings, atypical cysts or cyst-like lesions with echogenic contents, the existence of contrast within the suspected areas being equivalent to the existence of vessels, i.e. perfused viable tissue.
In the same manner, biopsies can be guided to non-necrotic areas of a suspected lesion, improv- ing the diagnostic yield of the puncture [9].
Renal tumours seem to have a contrast pat- tern similar to the normal renal parenchyma, at least in the early stages of enhancement. There may be a rim enhancement in a pseudo-capsule [11] but, as there is no real accumulation of con- trast in the kidneys, the detection rate of small tumours is unlikely to be as much improved by CEUS as is seen with focal liver lesions. However, malignant tumours do not have a proper capil- lary bed and early experiences indicate that con- trast will remain in the capillaries even as it is IV.1 • Contrast-Enhanced Ultrasound of Focal Liver Lesions 169
a b
c d
Fig. 6a-d.Patient with sudden flank pain. B-mode ultrasound shows the kidney (fat arrow) surrounded by a hematoma (a). On CEUS the hematoma is delineated (thin arrow) and a cyst is seen, possibly hemorrhagic, as it did not show up on B-mode (b). However, a careful CEUS scan also shows tiny perfused nodules within the cyst. A cystic renal cell carcinoma, probably the cause of the bleeding, was later removed (c, dd)
washed out of the tumour neovasculature, creat- ing a similar but weaker equivalent to the situa- tion in the liver, possibly helping characterisa- tion, if not detection [10]. Thus, malignant tumours tend to be slightly hypoechoic com- pared to normal parenchyma in the later phases.
This could be helpful in evaluating normal vari- ants, e.g., a prominent column of Bertin, and their differentiation from focal lesions suspected on basic ultrasound, especially under subopti- mal imaging conditions. The area to be studied must then be followed to the later stages of the contrast-enhancement, at least for 1 minute. In most instances, a clear difference can be detect- ed by analysis software at that stage and seen subjectively shortly thereafter, if not before (Figs. 7-9). A necrotic area in the tumour will, of course, remain dark, but as tumours with central
necrosis tend to be large and thus easily detected and characterised on native ultrasound, this is likely to be of limited importance, except as guidance for biopsies.
There are, as yet, no scientific data proving an ability to help in the differentiation between benign and malignant focal lesions, but with improved knowledge of contrast-enhancement patterns this may only be a matter of time.
Benign lesions like angiomyolipomas have been shown to enhance less than renal cell carcinomas in the arterial phase [12] and tend to retain the contrast better than a malignant tumour in the later phases, presumably due to vessel anatomy.
However, knowledge about how a small, highly differentiated tumour would behave is limited, and the differentiation of benign from malig- nant in the individual patient remains difficult.
a b
c d
Fig. 7a-d.Small renal cell carcinoma seen both on B-mode (a) and CEUS with a typical contrast-enhancement, i.e., almost isoechoic with the normal parenchyma in the early stages (b = 15 sec) and then progressively hypoechoic (c = 30 sec, d = 60 sec)
IV.1 • Contrast-Enhanced Ultrasound of Focal Liver Lesions 171
a b
c d
Fig. 8a-d.Larger renal cell carcinoma with the same enhancement pattern as in Fig. 7. Images at 15 sec (a), 30 sec (b), 45 sec (c) and 60 sec (d), by which time the tumour is virtually without enhancement, stressing the importance of following the enhancement patterns through all stages
Fig. 9a-d.Patient referred for a high blood cell count. No lesion is seen on B-mode (a), but a cyst-like lesion appears in the early stages of CEUS (b). After 60 sec, however, contrast has left the previously normal-looking margin of the lesion, creating a hypoechoic rim around the non-enhancing portion (c). An erythropoietin-producing tumour was later removed
a b
c
References
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Phase inversion sonography during the liver specif- ic late phase of contrast-enhancement: improved de- tection of liver metastases. AJR 176:1191-1198 4. Cosgrove D, Eckersley R, Blomley M, Harvey C (2002)
Quantification of blood flow. Ultrasound. ECR Cat- egorical Course Syllabus. Springer, Berlin Heidel- berg New York, pp 84-90
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sonography in the differentiation of hyperechoic re- nal masses. Abdom Imaging 26:654-660
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8. Dacher JN, Pfister C, Monroe M (1996) Power Doppler sonographic pattern of acute pyelonephritis in chil- dren: comparison with CT. AJR 166:1451-1455 9. Krause J, Nilsson A (2003) Targeted tumor biopsy
under contrast-enhanced ultrasound guidance. Eur Radiol 13 [Suppl 4]:L239-L240
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Conclusion
The intense enhancement of the normal kidney opens many possibilities for improved diagnosis and characterisation of renal lesions.
When CEUS is used with contrast-specific software, non-perfused areas are easily delineat- ed and, conversely, minimal vascularisation can be detected. Possible uses include the detection of small cysts, parenchymal rifts, renal infarc- tions, abscesses or rifts/haematomas.
Local or focal differences in blood flow can be noted, offering an indication of diffuse renal dis- ease or focal lesions impairing the blood flow to a portion of the kidney. Possible uses include the assessment of pyelonephritis, both in the detec- tion of the lesion itself and the distinction against an abscess formation.
Small amounts of contrast can be seen because of the high detection sensitivity. This improves the ability to visualise tiny vessels, indicating a possible malignancy rather than a simple cyst.
Possible uses include the characterisation of atyp- ical cysts and indeterminate lesions.
Knowledge of a normal renal enhancement pattern may allow the differentiation of renal parenchyma with an abnormal shape from solid focal lesions. Possible uses include the character- isation of suspected focal lesions and, in the future, possibly the differentiation of benign from malignant lesions.
The arrival of both stable contrast agents and the development of dedicated contrast-specific software are fairly recent events. Much work is still to be done before the above described appli- cations are properly explored and validated. It is important to remember that even though accu- mulated experience so far indicates that malig- nant tumours are hypoechoic in the later con- trast stages, it cannot be inferred that a lesion that retains contrast is benign. Similarly, that a focal pyelonephritis can be seen as a hypoechoic lesion does not mean that an infection can, with some degree of certainty, be excluded because of a normal CEUS scan. To reach this stage a lot of research is necessary, but it is almost certain that the resulting improvement in diagnostic accura- cy will be worth the effort.
Key Points
• CEUS of the kidneys can be used to get further information about the character of re- nal lesions.
• Renal cell carcinomas usually have a typical pattern of contrast-enhancement, but it is not yet possible to distinguish solid malignant lesions from benign ones.
