Federico Lanzi1, Francesco Mazzei2, Carmen Zumpano 2, Palmira Grisolia 2, Nicola Tosi 1, Filippo Gentile 1, Federica Scipioni 1, Gerardo Pizzirusso 1, Aude Canale 1, Filippo Cecconi 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 differentiating low and high-grade 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). All patients underwent transurethral resection (TURBT) according to EAU Guidelines recommendations. In case of multifocal tumors, every lesion was sent separately to histopathologic evaluation. Perfusion kinetics have been classified into 4 patterns: type I “rapid wash-in, slow wash-out”, type II “rapid wash-in and wash-out”, type III “slow wash-in and wash-out”, type IV “slow wash-in, rapid wash-out”
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, 74/110 (67.2%) were high-grade and 36 (32.8%) low-grade. It was found a significant correlation between type I and II patterns and high-grade carcinomas, while low-grade lesions usually presented type III-IV curves (p=0.0032). Mean (range) peak of signal intensity (SI) enhancement of high-grade tumors was 41(35-55)% while lower mean (range) peaks of SI enhancement such as 28(17-32)% resulted to be more representative of low-grade lesions (p=0.00681). The correlation between CEUS plus T/IS curves and pathological staging resulted statistically non significant (p=0.18). With regards to the small series, the T/IS curves showed a sensibility of 86.5% and a specificity of 91.2%. 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. 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.