Abstract
Ultrasound is a common and established imaging method for the initial characterization of renal lesions. The widespread used Bosniak classification (I–IV) classifies renal lesions in five individual groups using contrast-enhanced computer tomography (CE-CT), magnetic resonance imaging (MRI) and/or contrast-enhanced ultrasound (CEUS) imaging criteria. For complex pathologies, CEUS/MRI image fusion is a novel imaging technique for the differentiation of benign and malignant renal lesions. Compared to CE-CT and MRI alone, ultrasound image fusion offers the additional possibility of being a real-time imaging technique that can be used together with other cross-sectional imaging techniques.
This article describes the newest possibilities of image fusion with CEUS and MRI in detection and characterization of unclear renal lesions.
Introduction
Renal pathologies can be incidentally found in approx. 13–27% of all patients using cross-sectional imaging techniques [19], whereas the age of the patients positively correlates with the incidence of focal renal lesions. Renal lesions can be observed in about 20% of patients reaching their 5th life decade and in 50% of all performed post-mortem autopsies. Additionally, renal pathologies are more commonly associated with male patients with a ratio of 2:1 in favour of female patients [40, 43]. The most commonly used initial imaging modality for the classification of renal lesions is conventional B-mode ultrasound, which can sufficiently discriminate between solid and cystic renal lesions. B-mode ultrasound is the method of choice for the diagnosis of simple cysts (Bosniak I) and slightly complicated cysts (Bosniak II). Bosniak II F to IV cysts are usually characterized using contrast-enhanced computer tomography (CE-CT) or magnetic resonance imaging (MRI) [34]. The key challenge in imaging renal lesions is to distinguish between simple and complicated cystic renal lesions and cystic and solid renal tumors. Approximately 6% of all renal lesions not showing any clinical symptoms are cystic renal cell carcinomas (RCC) [37, 48]. RCCs are the most common primary malign neoplasms of the kidneys and are regularly coincidentally detected in patients with other primary diseases receiving diagnostic imaging for their initial diseases [2, 43]. Depending on localization and size of the tumor, therapy options include full or partial nephrectomy [6]. For the characterization of difficult pathologies, MRI/contrast-enhanced ultrasound (CEUS) image fusion offers the combination of real time examinations with intravenously injected ultrasound contrast agents and MRI image data sets for better diagnostic insights and clinical decision making. Image fusion and CEUS are options for the further workup of unclear MR renal pathologies, especially in young patients and patients with impaired renal function or other contraindications for MRI or CE-CT like contrast agent allergies [13–14, 36]. Additionally, image fusion and CEUS capabilities are more and more integrated into clinical High-End ultrasound systems, making them more available to clinical experts.
Native B-mode sonography and contrast enhanced ultrasound and image fusion
All images depicted in this article were evaluated with a Philips EPIQ 7 (Philips Medical Systems, Bothell, WA) High-End ultrasound system and a 9 MHz curved array multi-frequency transducer. The authors followed the ethical guidelines for publication in Clinical Hemorheology and Microcirculation [1].
All ultrasound scans were initially accomplished using conventional B-mode ultrasound. Conventional B-mode sonography is commonly acknowledged as the standard workup in the evaluation of renal pathologies [17]. After an initial conventional B-mode ultrasound, oral and written informed consent was obtained from all patients and an additional CEUS was performed. CEUS was performed using a phase inversion mode of the Philips EPIQ system. Phase inversion is a technique that eliminates linear signals echoed from the body tissue and highlights non-linear signals echoed from oscillating microbubbles of the contrast agent, which normally oscillate between 3 and 5 MHz, to better visualize and observe enhancement patterns [23]. To minimize the destruction of the oscillating microbubbles a low mechanical index is usually used for longer diagnostic views [24]. The Philips system uses a high performance processor for the documentation and storing of dynamic image sequences in cine mode. After being intravenously injected, the microbubbles oscillate on the same wave length responding to the ultrasound echoes emitted by the transducer and return a thousand times increased echo with an increased signal intensity of up to 30 dB [2, 29]. Contemporary ultrasound contrast agents of the 2nd generation (for example SonoVue®, Bracco, Milan, Italy) are encapsulated microbubbles containing for example sulphurhexa-fluoride gas (SF-6) that are stabilized by a shell of phospholipids [23]. After intravenous injection the contrast agent dissolves within several minutes. The lipid-shell is endogenously metabolized, primarily via the liver, and the SF-6 gas is exhaled through the lungs within 4 to 8 minutes. Additionally, the ultrasound contrast agent is independent from renal or thyroid function and can be used in patients with reduced renal function or hyperthyroidism. With a size marginally smaller than a single erythrocyte, the microbubbles (2–10 μm) purely act as an intravascular blood-pool contrast agent showing only vascularized tissue, which is different to CT and MRI contrast agents that diffuse into the interstitial room [23–24]. Thereby, CEUS can visualize vessels down to a size of 40 μm [11]. Intravenous hand bolus injection of 1.0 to 1.5 mL ultrasound contrast agent followed by a bolus of 5 to 10 mL saline solution (0.9 & NaCL) is usually performed for diagnostic kidney imaging [25, 40]. An advantage of ultrasound contrast agent is the rare occurrence of serious side effects that must be considered in daily clinical routine. An anaphylactic reaction is the most critical side effect of ultrasound contrast agents that occurs in about 1 of 10.000 cases [38, 49].
For complex renal lesions, real time MRI/CEUS image fusion can be carried out with the help of High-End ultrasound systems. This is particularly beneficial for young patients and patients with contraindications for MRI and CE-CT scans, minimizing the radiation exposure as well as the use of nephrotoxic MRI and CE-CT contrast agents [8, 35].
A modern High-End ultrasound system uses a magnetic field generator combined with a position sensor for the ultrasound transducer to generate diagnostic images with image fusion. The position sensor allows the detection of the position of the transducer in the three-dimensional space. Image fusion is supported in combination with all other imaging techniques including CE-CT and MRI. It Is possible to coregister DICOM (“digital imaging and communication in medicine”) data sets of CE-CT and MRI scans and real-time ultrasound scans using a special system software of the High-end ultrasound systems. The DICOM data sets and the real-time ultrasounds scans can be viewed either in a side-by-side mode or in an overlay mode [16]. While being in image fusion software mode, the ultrasound system can still offer all available additional imaging options like color Doppler or CEUS. The ability to use all different image techniques in a real time examination setting allows extensive possibilities to image and characterize the vascularization of renal pathologies [9, 41].
Bosniak classification of renal cysts
Initially published in 1986 and modified in 1993, Bosniak described the nowadays mostly used classification for the differentiation of renal cysts in CE-CT that offers an orientation for the risk stratification of potentially malignat renal lesions [3–7, 22]. Several studies showed a good inter-rater reliability of the Bosniak classification for different raters [18, 44]. The Bosniak classification can also be used to interpret renal lesions in other imaging modalities, including MRI and CEUS. Thereby, CEUS/MRI image fusion can add additional information for the detection and classification of renal pathologies.
The possible malignancy rates of renal cystic lesions are stratified upon morphological imaging features into five different groups (Bosniak category I–IV) that are organized in rising probability of malignancy.
Bosniak category I cysts show an anechoic lumen, a posterior acoustic ultrasound enhancement, no wall thickening, no enhancement in CEUS and no intraluminal septa [6]. A deviation from these imaging features results in a categorization of the examined cyst in one of the other four categories (Bosniak category II, II F, III and IV) [6, 42] (Figs. 1–8).
Category I
Category I cysts are 100% benign cysts without visible wall thickening and without septa, contrast enhancement or calcifications [31, 39].
Category II
Category II cysts are 100% benign cysts that can show a few fine septa thinner than 1 mm, with or without fine septal calcifications and they also might show temporary observable contrast enhancement but no continuous contrast enhancement [27, 39]. Cysts smaller than 3 cm with visible protein or hemorrhage inside the lumen do also fit into this category.
Category II F
Category II F cysts are cysts with a possible malignancy rate of about 6%. They can show multiple fine and thin septa that might additionally show a continuous contrast enhancement. Furthermore, thickened walls or septa with nodular calcifications might be observed and are characteristical for this category [13, 31].
Category III
Category III cysts are cysts with a possible malignancy rate of about 50%. They can show irregular walls and/or septa that are measurably thickened and a continuous and extended contrast enhancement. They also might additionally show multiple nodular and/or irregular calcifications. Enhancing soft tissue components cannot be observed. All cysts in this category must be further evaluated [13, 45].
Category IV
Category IV cysts are cysts with a malignancy rate of about 100%. They show all imaging features of a category III cyst but do additionally feature soft tissue components independent of the walls or septa that also show a continuous and extended contrast enhancement [13, 48].
Conclusion
MRI/CEUS image fusion is a viable option for the classification of unclear and difficult renal lesions. The combination of CEUS and MRI image information allows a detailed characterization of the vascularization of walls and septa and additional soft tissue components. The integration of image fusion into modern High-end ultrasound systems and the broader availability of the necessary hardware and software promote image fusion as a beneficial addition to the diagnostic tools available for the workup of renal pathologies.