Federico Lanzi1, Carmen Zumpano 2, Francesco Mazzei 2, Nicola Tosi 1, Palmira Grisolia 2, Federica Scipioni 1, Gerardo Pizzirusso 1, Filippo Gentile 1, Filippo Cecconi 1, Aude Canale 1, Giovanni De Rubertis 1, Gabriele Barbanti 1, Maria Antonietta Centra 2
  • 1 AOU Senese - U.O.C. di Urologia (Siena)
  • 2 AOU Senese - U.O.C. Diagnostica per Immagini (Siena)


According to scientific literature and EAU guidelines the most accurate diagnostic exam for detection and follow up of vescical lesion is cystoscopy. In daily practice, ultrasonography is often adopted as a non invasive examination which is proposed to avoid iterate invasive procedures. The most important limitation of ultrasonography large application is the low detection rate of small and sessile tumors and the inability to identify the aggressiveness of bladder tumors. The aim of the study is to evaluate the efficacy of time/intensity curves (T/IS) for quantitative analysis of contrast kinetics during contrast-enhanced ultrasound (CEUS) in evaluation of detrusor muscle invasion in bladder carcinomas

Methods and results

We prospectively evaluated with CEUS 82 patients with cystoscopically-detected bladder tumors. Lesions were first scanned with a gray-scale ultrasonography and color Doppler US to obtain their location and size and the best imaging plane to observe the lesions and the normal adjacent bladder wall. Thereafter, contrast enhanced agent (SonoVue, Bracco®, Milan, Italy) was injected intravenously as a bolus (average 2.5 ml/sec ) 4.8 ml dose followed by 10 ml of normal saline flush. Each exam lasted about 3 min following bolus injection. One post-contrast cine clip was acquired lasting approximately 150 sec. If necessary, the injection was repeated 15 min later. A quantitative analysis of enhancement was performed using a dedicated software (QONTRAST, manufactured by Esaote for Bracco Group) which elaborates colorimetric maps and process Time/Intensity (T/IS) curves on region of interest (ROI). If detrusor muscle invasion was suspected the patient was addressed to a contrast-enhanced CT (CECT). All patients underwent transurethral resection (TURBT) according to EAU Guidelines recommendations. The bladder wall with the detrusor muscle underlying the lesion was sent separately to histopatologic evaluation.
Overall, conventional gray-scale ultrasonography and CEUS identified 110 of the 134 bladder lesions discovered during cystoscopy. At histopathological evaluation all tumors resulted transitional cell bladder carcinomas; of these, 36 (32.8%) were Ta low-grade (LG), 8/110 (7.2%) Ta high-grade (HG), 60/110 (54.5%) were T1 HG and 6/110 (5.5%) T2. CEUS demonstrated a matching diagnosis with histopathological evaluation in identifying the depth of bladder wall invasion in 6/8 (75%) of Ta LG, 13/36 (36.1%) of Ta HG, 37/60 (61.7%) of Ta HG and in 5/6 T2 cases (83.4%) It was found a significant correlation between CEUS and histopatology in the evaluation of the depth of bladder wall invasion in Ta LG Vs T2 cases (p=0.00297) meanwhile it resulted non significant in characterizing Ta HG from T1 HG tumors (p=0.216). With the obvious limitation of the small series and the variability of interpretation CEUS seemed to be more accurate than CECT in evaluating cT2a tumors. T/IS shapes of exophytic part of tumor resulted comparable to the underlying invaded bladder wall while it was observed a slight increasing of signal intensity (SI) enhancement in endophytic Vs exophytic parts of the evaluated carcinoma (p=non-evaluable). With regards to the small series, the T/IS curves showed a sensibility of 100% and a specificity of 83.4% in identifying cT2 tumors. None of the patients has suffered adverse reactions to CEUS contrast agent, and no renal function worsening was suspected.


In our experience contrast enhanced ultrasound demonstrated to be a safe, fast and low cost procedure. It doesn't require a long learning curve and the hard disk storage of every exam allows to perform time/intensity curves in post processing phase. CEUS can be useful to better define bladder carcinomas: time/intensity shapes and the quantitative analysis of contrast kinetics may help in distinguish biologically aggressive urothelial tumors to low-grade lesions. Moreover CEUS may be represent a highly-sensitive exam to evaluate detrusor muscle invasion in bladder carcinomas. Wider series may conduce to a more accurate predictivity of T/IS curves and to develop a tailored preoperative planning and timing; moreover CEUS may be useful in postoperative follow-up of patients with Ta-T1 tumors non suitable to the recommended repeated cystoscopic schedule