Comparison of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in the evaluation of unclear solid renal lesions

1 Introduction

With the almost ubiquitous use of ultrasound across all clinical disciplines incidentally found unclear renal lesions are more commonly seen nowadays and preoperative clinical management and characterisation of these lesions is important for patient care [4, 32]. Mainly, incidentally found renal lesions are benign simple renal cysts and malignancy can be safely ruled out using different imaging methods [3, 24]. The main differential diagnosis for solid or cystic renal lesions is the renal cell carcinoma that shows an incidence rate of 3% of all malign neoplasms and is one of the most common tumours of the urinary tract [16]. In the up-to-date 2014 European guidelines for renal cell carcinoma, contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) are the initial imaging modalities of choice for the characterization and diagnosis of renal cell carcinomas. In patients with chronic renal failure or a known allergy to contrast media containing iodine or gadolinium, contrast-enhanced ultrasound (CEUS) can be used as a complementary option (10). Different to CE-CT and MRI, ultrasound contrast agents are purely intravascular and do not diffuse into the interstitial room [12–14]. Additionally, they can be used independently from thyroid and renal function and show a low incidence of adverse events like an anaphylactic reaction that only occurs in 1 of 10.000 cases [21, 30]. Nowadays, CEUS is already used in clinical daily routine as a fast, low-risk and cost effective modality for the local diagnosis and staging of renal cell carcinomas [6, 25]. Using CEUS, malignant renal lesions show a different enhancement pattern as the surrounding healthy renal parenchyma making it possible to differentiate between benign and malignant renal lesions. Unfortunately, some benign renal lesions like oncocytomas are hardly to differentiate from malignant lesions like renal cell carcinomas because of similar enhancement patterns in CEUS, CE-CT and MRI [2, 17]. This retrospective analysis study was performed to compare the sensitivity and specificity of CEUS and MRI in the evaluation of unclear renal lesions to the histopathological outcome as a gold standard.

2 Materials and methods

Between 2005 and 2015 a total of 36 patients with a single unclear solid renal lesion were examined at our department using CEUS prior to biopsy or operation. All patients had additional MRI imaging studies from our department. The local ethics committee approved this study. All study data were collected in compliance with the principles of the Helsinki/Edinburgh Declaration of 2002 and the ethical guidelines for publication in Clinical Hemorheology and Microcirculation [1]. Oral and written informed consent of all patients was obtained prior to each CEUS, CT and MRI examination.

The additional imaging studies could consist of contrast enhanced MRI scans or unenhanced MRI scans performed on the basis of imaging protocols and with scanners used at the time the scans were conducted.

The CEUS examinations were conducted with high-end ultrasound systems with up-to-date CEUS specific examination protocols available at the time of the examination (Siemens Acuson Sequoia and Siemens S2000, EPIQ 7, Philips Ultrasound). Used ultrasound probes included the C4-1 and C6-1 HD for the Siemens ultrasound system and C9-2 probe for the Philips system. All CEUS examinations were performed and interpreted by a single radiologist with more than 15 years of experience in CEUS. A low mechanical index (always < 0.4) was used for examination to avoid unintentional destructions of microbubbles.

A second-generation blood pool contrast agent media (SonoVue^®, Bracco, Milan, Italy) was used in all examinations and was administered through a peripheral 20–22 G needle as a bolus injection followed by a flush of 5 to 10 ml of 0.9% saline solution (0.9% NaCl). 1.4 to 2.0 ml of contrast agent was administered in most cases and with a maximum of 4.8 ml and minimum of 1.0 ml. In most cases a single dose of contrast agent was given. After the injection of the contrast agent cine loops were acquired and stored in the picture archiving and communication system. Mean examination time was 3–5 minutes for the whole examination. If additional imaging was necessary a total of up to three injections of contrast agent was given.

From the patients record files we retrospectively obtained the results of the initial CEUS examinations and the additional MRI examinations in cases they were available. All findings of the CEUS and MRI examinations were reported at the time of the examination without knowing the histopathological results. Lesions were classified as malignant or benign depending on their enhancement behaviour in the CEUS examination.

Out of the 36 renal lesions a total of 28 lesions were malignant (77.8%) and 8 were found to be benign (22.2%) in the final histopathological report. Histological material could be gathered after surgical removal of the lesion, after biopsy or after fine needle aspiration.

For statistical analysis diagnostic accuracy of CEUS and MRI was tested using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). If in the initial MRI report the results were unclear and no clear statement regarding malignancy could be made, the value for MRI was set to the value of the corresponding CEUS examination regarding malignancy.

3 Results

CEUS showed a sensitivity of 96.4%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 88,9%.

MRI showed a sensitivity of 96.4%, a specificity of 75.0%, a PPV of 93.1% and a NPV of 85.7%.

Out of the 28 malignant lesions a total of 18 clear cell renal carcinomas, 6 papillary renal cell carcinomas and 4 other malignant lesions, e.g. metastases, were diagnosed. Out of the 8 benign lesions a total 3 angiomyolipomas, 2 oncocytomas, 1 benign renal cyst and 2 other benign lesions, e.g. renal adenomas were diagnosed. Using CEUS, 1 lesion was falsely identified as benign. Using MRI, 2 lesions were falsely identified as benign and 1 lesion was falsely identified as malignant.

1 clear cell renal carcinoma was misdiagnosed using CEUS as benign. 1 clear cell renal carcinoma was misdiagnosed as benign using MRI and 2 benign lesions (1 angiomyolipoma (Figs. 1–3) and 1 adenoma) were falsely diagnosed as malignant.

4 Discussion

Incidentally found solid renal lesions are a challenge to sufficiently characterize but critical for patient management. Although most malignant lesions can preoperatively be diagnosed with adequate certainty some histopathological benign lesions are biopsied or surgically removed because of uncertain imaging results. CEUS can be used to evaluate unclear renal lesions with a high PPV and NPV. The additional use of CEUS for these lesions can aid diagnosis and reduce the number of biopsies and surgical removal or can validate malignancy in lesions that otherwise only would be follow-upped. In this retrospective study we demonstrated that CEUS shows an excellent PPV (100.0%), an excellent specificity (100.0%) and an high sensitivity (96.4%) for the prediction of a renal tumour comparable to other imaging modalities like MRI. These findings are in line with several previous studies conducted about this topic [1, 26]. In our study angiomyolipomas and adenomas were misdiagnosed using cross-sectional imaging techniques, which is concordant to other studies that reported similar difficulties in the differentiation of these entities from malignant tumours because of similar imaging features of these lesions to malignant lesions [9, 27–29].

For patients suffering from chronic renal failure with impaired renal function, suffering from hyperthyroidism, metal implants that are not suitable for MRI or known history of allergic reaction to iodine or gadolinium CEUS is a viable alternative for the accurate characterization of unclear renal lesions. Additionally, using CEUS adds the benefit of using a non-ionizing radiation approach compared to CT and is much more cost-effective than using MRI. Furthermore, CEUS is a dynamic examination technique with the ability to repeat contrast agent administration multiple times because of the characteristic features of the used contrast agents that do not interfere with renal, thyroid or hepatic function. The high PPV and NPV of CEUS could reduce the number of necessary CT examinations and the associated use of radiation and contrast agents with renal toxicity and of MRI and the associated economic burden for the health system.

This study was limited by several factors. First of all this was a retrospectively conducted mono-center study with only one radiologists evaluating the lesions at CEUS. Different equipment was used and contrast agent doses varied on patients depending on the CEUS techniques existing at the time of the examination. The MRI protocols and imaging series varied among the patients also depending on the protocols and scanner existing and available at the time of the examination. In this study only a relatively small percentage of all unclear lesions were found to benign (22.2%) in histopathological workup, which is much lower compared to the expected 45% from national statistics [23]. If in the initial MRI report the results were unclear and no clear statement regarding malignancy could be made, the value for MRI was set to the value of the corresponding CEUS examination regarding malignancy, which was necessary for statistics but is not totally correct.

5 Conclusion

CEUS is an useful method which can be additionally used to differentiate often between malignant and benign solid renal lesions and especially for complex or haemorrhage cystic lesions. CEUS shows a comparable sensitivity, specificity, PPV and NPV to MRI and can help reduce the number of biopsies and unnecessary surgical removals. In daily clinical routine, patients with contraindications for other imaging modalities can particularly benefit using this method.