Until recently, the use of CEUS has been limited to its clinical applications on the liver; however, due to its safety and cost-effectiveness, it has gained importance answering several clinical questions related to the kidneys. In select cases, CEUS can also negate the need for magnetic image resonance and computed tomography .
Contrast-enhanced ultrasound is particularly useful in imaging the kidneys. CEUS can differentiate solid renal tumors from pseudo-tumors and cystic lesions in the kidneys. It has also shown advantages in characterization of renal lesions and also by being able to differentiate between a non-perfused kidney lesion and normal perfused renal tissue. In addition, CEUS can help classify complex cystic renal masses according to the Bosniak classification system. Visualization of renal trauma, ischemia, and infections can also be demonstrated. CEUS has also been utilized in vascular imaging for renal artery stenosis, and appraisal of percutaneous ablation therapy for renal tumors. These indications for the use of CEUS have been set by The European Federation of Societies indications for CEUS for Ultrasound in Medicine and Biology (EFSUMB) in its 2011 updated Guidelines and Recommendations .
Intra-operative technology currently used for real-time imaging of the renal blood flow is mainly FireFly fluorescence with indocyanine green (ICG), and the drop-in ultrasound with power Doppler. Regrettably, these techniques have some limitations. Power Doppler is dependent on the movement of blood in vessels for real-time imaging of renal vasculature. Consequently, accidental movement of the probe over the surface of the kidney can give a false positive artifact by mimicking blood flow within the kidney. In practice, power Doppler may, thus, only be more useful over the renal hilum where the vessels are much larger and minor movement artifacts relatively less important. CEUS is not affected by movement artifact of the ultrasound probe and which makes CEUS a better technique in comparison to the power Doppler .
Another limitation of Firefly is that it only allows visualization of blood flow on the surface of the kidney devoid of perinephric fat or skeletonized vessels . Removal of perinephric fat in patients with sticky or toxic fat can also increase the time taken to complete a RPN procedure. Defatting a kidney to visualize the renal cortex could theoretically compromise oncological margins in a patient with microscopic pT3a disease. It is fortunate that, CEUS overcomes the limitations of the Firefly system, by enabling visualization of the renal blood flow and the location of tumor through the perinephric fat .
Firefly fluorescence imaging is used in conjunction with the da Vinci Si surgical system. At the time of writing, it has not yet been approved for use with the latest da Vinci Xi model. Although, Firefly technology enables real-time imaging of renal perfusion with identification of important anatomical detail, it requires a special camera, light source and telescope to detect the florescence, which makes this technique more expensive.
There is a growing interest to minimize costs, improve quality and optimize access to new health care technologies. Similarly, many of the new and or evolving technologies can only be effectively evaluated after widespread use in clinical practice.
RPN using either ICG or CEUS technology, essentially requires a robotic intra-operative US transducer probe e.g. ProART robotic transducer 8826 (BK Medical). The estimate cost is in the range of $ 20,000–23,000 (estimate supplied by the UK distributor).
Compared to ICG, CEUS requires an additional estimate cost (supplied by U.K distributor) in the range of $ 3,000–5,000 for the integrated CEUS software (BK Medical) and $ 70–80 per vial cost of contrast agent including cannulation e.g. SonoVue (Bracco Diagnostics).
In contrary, ICG has extra cost of $100,000 for the near infrared fluorescence imaging (NIRF) integrated robotic camera system and $100 per vial cost of ICG . Figure 6
A fact worth noting, ICG used in Firefly technique contains sodium iodide, which could potentially have a risk of anaphylactic shock. It is therefore important to check a patient’s past history of allergy prior to administering ICG. On the other spectrum, despite a minor concern that interaction between ultrasound and the microbubble contrast agents may lead to theoretical in vitro hemolysis and cell death at capillary levels. However, extensive studies ostensibly demonstrated that those concerns have not been clinically encountered. Similarly safety analysis of SonoVue in more than 20,000 patients revealed a rate of serious adverse effects of 0.0086 % [16–20].
SonoVue comprises of gas microbubbles similar in size to red blood cells. Microbubble contrast agents circulate for several minutes inside the blood vessels lumen then they dissolve. Each of these microbubbles is covered outwardly by a lipid, protein, or polymer coating shell. The lungs excrete the gas contained in the microbubbles, while the liver metabolizes the protein, lipid, or polymer shell .
SonoVue a second-generation ultrasound contrast agent used in the CEUS procedure is non-allergenic and does not interfere with renal function, as it is not excreted by the kidneys, unlike the contrast agents used in other imaging techniques. It is, therefore, not contra-indicated in patients with impaired renal function.
Studies have confirmed that the kidney and the pelvicalyceal system have no role in the accumulation and excretion or of the microbubble contrast agents. More over, recent reports have demonstrated a valuable a supportive diagnostic role of CEUS in acute and chronic rejection after renal transplantation [21, 22].
Due to of this metabolic pathway, renal impairment is not a contraindication for the use of microbubble contrast agents. Hence in conditions of reduced renal blood perfusion, ischemia, and diabetic nephropathy; the short duration of uptake of the microbubble contrast agent can safely be overcome by administering the agent as multiple injections .
When an ultrasound wave falls on the microbubbles, they expand to almost double their original size and contract simultaneously, producing an oscillatory movement. This movement further results in the transmission of return signals to the US machine transducer , resulting in successful enhancement of the renal microvasculature and accurate tumor marking. A technique, which we are still developing, is sequential occlusion angiography. In this technique we capitalize on the ability to rapidly destroy or “rupture” the SonoVue microbubbles by increasing the ultrasound scanning frequency. This effectively clears the renal parenchyma or tissue being scanned of microbubbles and allows a second or subsequent intravenous injection of SonoVue to be administered immediately. In our hands, this is the real advantage of CEUS, which undoubtedly, seems to offer a better intra-operative imaging in comparison to power Doppler and Firefly.
The combination of CEUS and microbubble contrast agents allows a definite enhancement of contrast resolution, and inhibition of signals from stationary tissues. Although, SonoVue is more widely used for CEUS in most countries except the U.S., there are a number of other alternative contrast agents available for this purpose.
In recent years, there has been a positive shift towards robotic-assisted partial nephrectomy in comparison to laparoscopic partial nephrectomy, due to its ability to reduce the WIT and learning curve during nephron-sparing surgery .
The robotic technique of partial nephrectomy was first performed, and subsequently published by Gettman and colleagues in 2004 . A prolonged WIT is potentially deleterious to the recovery of the renal functions post RPN, especially in patients with high risk factors, or underlying disorders such as hypertension, diabetes, and small vessel disease [26, 27]. Surgeons at present are encouraged to avoid global ischemia and consequently reduce the WIT. Ligating or clamping selective arteries that supply blood to the segment of the kidney containing the tumor helps achieve a lower WIT.
Intra-operative ultrasound is invaluable for this purpose, as it can demonstrate real-time imaging of the renal vasculature. CEUS is capable of further reducing the WIT by aiding the process of selective clamping, since it permits real-time scanning of the macrovasculature and microvasculature of the kidneys without the need for removing the perinephric fat.
Intra-operative imaging using a robotic ultrasound probe can significantly increase the diagnostic acumen of the surgeon, with its high-resolution real-time images, which may thus improve outcomes of RPN in patients post-surgery. Laparoscopic ultrasound probes for intra-operative scanning have limitations and may reduce surgical precision, as the assistant holds and manipulates the laparoscopic ultrasound probe. The laparoscopic ultrasound probe is also prone to slipping off the kidney surface, and requires the assistance of a robotic instrument for repositioning the probe or to prevent it slipping off the kidney . A robotic ultrasound probe gives the surgeon full autonomy in the surgical field, as the fin is placed just over the transducer array and is controlled by the surgeon. The robotic ultrasound probe also eliminates the issue of instrument clashing in the operating field . Figure 7 shows the difference between a laparoscopic US probe and a robotic US probe.
CEUS performed with a robotic ultrasound probe, thus, aids improved identification of the tumor, mapping of the renal blood vessels, and precise resection of the tumor. Tumors generally have good vascularity, a feature which can enhance the quality of the signals detected with CEUS and the robotic probe. In our experience, when combining selective occlusion angiography with CEUS using the robotic ProART probe, CEUS was more useful in assessing the regions of ischemia and perfusion, in comparison to power Doppler.
Contrast-enhanced ultrasound does have some limitations. Although they are few in number and its benefits outweigh them. The contrast agents used in the CEUS imaging are not nephrotoxic, but they are contra-indicated in patients with underlying cardiopulmonary disorders, since the lungs and liver excrete the microbubbles [27, 28]. Also, due to the limited period of tissue enhancement, which is dependent on perfusion with the microbubble contrast agents, following injection of ultrasound contrast agent, CEUS can visualize only one kidney at a time, unlike Magnetic resonance imaging and computed tomography, in which both kidneys are scanned at the same time.