shu-508 and Prostatic-Neoplasms

The value of ultrasound (US) in the diagnosis of prostate cancer has increased in importance in the past decade, which is mainly related due to the increasing incidence of prostate cancer, the most common malignancy in men. The value of conventional gray-scale US for prostate cancer detection has been extensively investigated. The introduction of US contrast agents has dramatically changed the role of US for prostate cancer detection. Advances in US techniques were introduced to further increase the role of US contrast agents. Although most of these advances in US techniques, which use the interaction of the contrast agent with the transmitted US waves are very sensitive for the detection of microbubbles, are mostly unexplored, in particular for prostate applications. First reports of contrast-enhanced US investigations of blood flow of the prostate have shown that contrast-enhanced US adds important information to the conventional US technique. We present a critical evaluation of the current status of transrectal US imaging for prostate cancer detection. Furthermore, we give background information on US contrast agents and imaging modalities. Early results of contrast-enhanced US suggest the feasibility of the use of US contrast agents to enhance US imaging of the prostate. The application of US contrast agents for the detection and clinical staging of prostate cancer is promising. However, future clinical trials will be needed to determine the promise of contrast-enhanced US of the prostate evolves into clinical application.

Topics: Biopsy; Clinical Trials as Topic; Contrast Media; Diagnosis, Differential; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatitis; Sensitivity and Specificity; Ultrasonography, Doppler; Ultrasonography, Doppler, Color

To determine the feasibility of contrast-enhanced three-dimensional (3D) imaging of the prostatic vasculature using power Doppler imaging and to analyze whether semiquantitative judgments of 3D images with respect to symmetry and distribution of vascular structures correlated with biopsy outcome.. 3D power Doppler images were obtained before and after intravenous administration of 2.5 g Levovist. Subsequently, random and/or directed transrectal ultrasound (TRUS)-guided biopsies were performed. Vascular images were analyzed by two experts. Prostate vasculature was judged with respect to symmetry and vessel distribution using a (scale) grading system.. Eighteen patients with a suspicion of prostate cancer either because of an elevated prostate-specific antigen (greater than 4.0 ng/mL; Tandem-R-assay) or an abnormal digital rectal examination were included in the study. Prostate cancer was detected in 13 patients. Vascular anatomy was judged abnormal in unenhanced images in 6 cases, of which 5 proved malignant. Enhanced images were considered suspicious for malignancy in 12 cases, including 1 benign and 11 malignant biopsy results. Sensitivity of enhanced images was 85% (specificity 80%) compared with 38% for unenhanced images (specificity 80%) and 77% for conventional gray-scale TRUS (specificity 60%). Of 6 patients who showed no B-mode abnormalities, vascular patterns were judged abnormal in 4 cases, of which 3 were malignant.. Contrast-enhanced 3D power Doppler angiography is feasible in patients with suspicion of prostate cancer who are scheduled for prostate biopsies. The sensitivity of power Doppler 3D imaging for the detection of prostate malignancy increased from 38% (5 of 13) to 85% (11 of 13) after administration of intravascular microbubble contrast (Levovist), and specificity was found to be 80% (4 of 5) for both imaging modalities. Thus, the use of Levovist when combined with the power Doppler display mode and 3D image reconstruction offers a promising new research area that might prove useful in prostate cancer detection in the future.

Topics: Angiography; Biopsy; Contrast Media; Humans; Male; Polysaccharides; Prostatic Neoplasms; Sensitivity and Specificity; Ultrasonography, Doppler, Color

To evaluate whether the adjunct of an ultrasound contrast medium improves the detection rate of prostate cancer.. In 34 patients, scheduled to undergo a trans-perineal extended prostate biopsy, we carried out a color-Doppler ultrasound (CDU) of the prostate before and after i.v. injection of Levovist, an ultrasound contrast medium. Further bioptic samples were taken in the areas where a marked increase in vascularization was noticed.. The overall diagnostic sensitivity, specificity and efficiency were respectively 72.7, 56.2 and 62.9% for transrectal ultrasound (TRUS); 80, 56.2 and 65.3% for CDU and 88.8, 54.5 and 68% for CDU after Levovist injection; 66.5, 72.6 and 65.1% for digito-rectal examination (DRE); 100, 51.4 and 65.4% for total PSA; and 100, 88.8 and 94.3% for PSA free/total. In the 16 patients with prostate carcinoma, the sensitivity of CDU after Levovist was 92.3, 66% for both DRE and TRUS, and 80% for DRE plus TRUS.. Considering the cost and the results obtained (high sensitivity and low specificity), a routine use of Levovist does not seem indicated in patients undergoing prostatic biopsy. An exception may be represented by patients with both negative DRE and TRUS.

Topics: Aged; Biopsy; Contrast Media; Health Care Costs; Humans; Male; Middle Aged; Polysaccharides; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Rectum; Sensitivity and Specificity; Ultrasonography, Doppler, Color

We quantified changes in prostate carcinoma vascularity treated with anti-androgens using color Doppler and power transrectal ultrasound in combination with microbubble contrast agent Levovist.. Thirty-six men with prostate carcinoma were studied at baseline and at intervals during treatment. At each attendance, Levovist((R)) (10 ml, 300 mg/ml) was given as an iv bolus. Using quantitative analysis, we calculated the pre-enhancement scores, arrival time, time to peak, peak value, and area under the time-enhancement curve (AUC). These were compared to pre-treatment values and serial PSA measurements.. The pre-enhancement, peak value, and AUC each showed a marked response with reductions within one week. The average AUC declined to 68% +/- 9% (mean +/- standard error) by week 1, 56% +/- 9% by week 3, and 20% +/- 4% by week 6. A strong correlation with changes in the mean PSA (r = 0.95, P < 0.001) was also measured. In four patients, Doppler indices did not fall with PSA: two patients with the most marked discrepancy relapsed at 6 months.. The vascular enhancement declined with therapy, similar to PSA. Microbubble enhanced ultrasound can show early response to treatment.

Topics: Androgen Antagonists; Carcinoma; Contrast Media; Humans; Male; Middle Aged; Neoplasm Staging; Polysaccharides; Prostate-Specific Antigen; Prostatic Neoplasms; Rectum; Sensitivity and Specificity; Treatment Outcome; Ultrasonography, Doppler, Color

To determine the feasibility of contrast-enhanced three-dimensional (3D) imaging of the prostatic vasculature using power Doppler imaging and to analyze whether semiquantitative judgments of 3D images with respect to symmetry and distribution of vascular structures correlated with biopsy outcome.. 3D power Doppler images were obtained before and after intravenous administration of 2.5 g Levovist. Subsequently, random and/or directed transrectal ultrasound (TRUS)-guided biopsies were performed. Vascular images were analyzed by two experts. Prostate vasculature was judged with respect to symmetry and vessel distribution using a (scale) grading system.. Eighteen patients with a suspicion of prostate cancer either because of an elevated prostate-specific antigen (greater than 4.0 ng/mL; Tandem-R-assay) or an abnormal digital rectal examination were included in the study. Prostate cancer was detected in 13 patients. Vascular anatomy was judged abnormal in unenhanced images in 6 cases, of which 5 proved malignant. Enhanced images were considered suspicious for malignancy in 12 cases, including 1 benign and 11 malignant biopsy results. Sensitivity of enhanced images was 85% (specificity 80%) compared with 38% for unenhanced images (specificity 80%) and 77% for conventional gray-scale TRUS (specificity 60%). Of 6 patients who showed no B-mode abnormalities, vascular patterns were judged abnormal in 4 cases, of which 3 were malignant.. Contrast-enhanced 3D power Doppler angiography is feasible in patients with suspicion of prostate cancer who are scheduled for prostate biopsies. The sensitivity of power Doppler 3D imaging for the detection of prostate malignancy increased from 38% (5 of 13) to 85% (11 of 13) after administration of intravascular microbubble contrast (Levovist), and specificity was found to be 80% (4 of 5) for both imaging modalities. Thus, the use of Levovist when combined with the power Doppler display mode and 3D image reconstruction offers a promising new research area that might prove useful in prostate cancer detection in the future.

Topics: Angiography; Biopsy; Contrast Media; Humans; Male; Polysaccharides; Prostatic Neoplasms; Sensitivity and Specificity; Ultrasonography, Doppler, Color

We compared the enhancement effects of three different echo contrast agents (ECAs); Levovist, YM454, and MRX-815H as artificial microbubbles on ultrasound mediated gene transfection (USMGT) with 1MHz ultrasound at 0.2MPa using a luciferase expression vector in PC3 cells and elucidated the mechanisms of differences of USMGT facilitation by these ECAs. At a concentration of each ECA that induced iso-survival, ECAs with lipid shell (YM454 and MRX-815H) facilitated USMGT higher than those without shell (Levovist), and the order of the ECAs facilitating free radical formation by sonication was; YM454>MRX-815H>Levovist. These results suggested that the lipid shell type ECAs facilitated gene transfer higher than that by the non-shell type ECA.

Topics: Cell Line, Tumor; Contrast Media; Genes, Reporter; Humans; Luciferases; Male; Microbubbles; Polysaccharides; Prostatic Neoplasms; Sonication; Transfection

To characterize the hypoechoic prostate nodules in the peripheral zone by means of power Doppler ultrasonography (PDUS) and contrast enhanced PDUS (CE-PDUS).. Thirty-two patients with dijital rectal examination findings suspicious for malignancy and/or a serum PSA level higher than 4 ng/dl, and who had hypoechoic nodules on transrectal ultrasonography were enrolled in this prospective study. Power Doppler ultrasonography (PDUS) images before and after sonocontrast (Levovist) injection were photographed for further evaluation. All patients were also evaluated by a systematic and nodule targeted biopsy approach. The photographs were re-evaluated by two radiologists for the presence and type of vascularity. The type of vascularity was categorized as peripheral, central, mixed and penetrating. The latter two were accepted as representatives of malignancy. The results of PDUS and CE-PDUS were compared to each other and to the pathological results.. There was a high level of interobserver agreement (Kappa: 0.80-0.95). Nineteen patients, but only 14 nodules were malignant on pathological examination. Sensitivity, specificity positive and negative predictive values for PDUS were 57, 50, 47, and 60%, respectively. On CE-PDUS, the sensitivity increased (93%) in expense of specifity (17%). The positive and negative predictive values were 46 and 75%, respectively. There was no significant difference between PDUS and CE-PDUS.. This study revealed that both benign and malignant nodules might be hypervascular and show malignant type of vascularity on PDUS. Contrary to some recent reports, we can conclude that the CE-PDUS does not provide a considerable aid to the diagnosis of prostate carcinoma on morphological basis due to its very low specificity despite its relatively higher sensitivity.

Topics: Aged; Aged, 80 and over; Contrast Media; Diagnosis, Differential; Humans; Male; Middle Aged; Polysaccharides; Predictive Value of Tests; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Rectum; Sensitivity and Specificity; Ultrasonography, Doppler

The objective of this study is to define enhancement characteristics that correlate to the presence of prostate cancer (PCa) and to evaluate the value of these characteristics in the localization of prostate cancer.. 29 patients with proven prostate malignancy, scheduled for radical prostatectomy, underwent an ultrasound examination prior to surgery. A bolus injection of contrast agent was administered intravenously. The distribution of the contrast enhanced blood to the prostate was monitored using Transrectal Contrast Enhanced Power Doppler Ultrasound. Fixed protocols and settings were used for all patients. The percentage of a selected area that showed enhancement was observed in time. The resulting enhancement curves were described using the parameters time to start, time to the maximum of the enhancement, the maximum value of the enhancement, and the rise time of the enhancement. Three evaluation-protocols divided the prostate into a number of areas of interest: into two areas using the Left-Right (LR) and Dorsal-Ventral (DV) protocols and into four areas using the Quadrant-protocol (Q). The enhancement parameters of the areas of interest were compared to identify the most affected area. The results were compared to the histopathological findings.. For the LR-protocol, the minimal time to peak proved to be the most predictive parameter for selecting the major malignant area. 78% of the patients were diagnosed correctly (N=23). Accurate localization of the major malignancy in either the ventral or dorsal side of the prostate was not feasible using the current protocol.. Malignancies can be accurately localized in either the left or the right side of the prostate based on the time to the maximum of the enhancement. An accurate discrimination between malignancies in either the dorsal or ventral side of the prostate cannot be performed. This is most likely due to anatomical differences between the dorsal and ventral area.

Topics: Contrast Media; Humans; Image Processing, Computer-Assisted; Injections, Intravenous; Male; Polysaccharides; Predictive Value of Tests; Prostatic Neoplasms; Sensitivity and Specificity; Ultrasonography, Doppler

We present an experimental, statistical approach to estimate the size required for small vessels to become detectable with color Doppler sonography.. A murine experimental tumor was examined with color Doppler sonography after injection of 1.5 ml of the contrast medium Levovist. Histologically, we measured vessel diameters inside the tumor as well as other, clearly identifiable locations.. With color Doppler at a transmit frequency of 7 MHz, vessels were only detected in the tumor's environment, but not inside. From the 95% quantiles of the vessel diameter distribution found histologically, we estimate that vessels 80-140 microns in diameter or above may be detectable with color Doppler sonography, while vessels 40 microns in diameter or smaller are indetectable.. Although a direct sonographic--histologic correlation is impossible for small vessels, a systematic assessment of the size distribution in clearly identifiable regions permits to estimate the sensitivity of color Doppler to detect blood flow in small vessels. According to our results, capillary blood flow is indetectable, and precapillary vessels may be detected only under optimal conditions.

Topics: Animals; Contrast Media; Image Processing, Computer-Assisted; Male; Microcirculation; Neoplasm Transplantation; Polysaccharides; Prostatic Neoplasms; Rats; Sensitivity and Specificity; Ultrasonography, Doppler, Color

The diagnosis of prostate cancer is currently limited by the low sensitivity and specificity of systematic conventional grey-scale ultrasonography. We assessed contrast-enhanced colour Doppler ultrasonography by means of a microbubble ultrasound contrast agent to detect tumour vascularity and improve the diagnosis of prostate cancer. The use of a microbubble ultrasound contrast agent for transrectal colour Doppler targeted biopsy significantly improved the detection of prostate cancer compared with systematic biopsy following conventional grey-scale ultrasonography (p<0.001). Contrast-agent enhanced colour Doppler imaging may allow for limited targeted biopsies (five or less), which reduces costs and morbidity.

Topics: Adult; Aged; Biopsy, Needle; Contrast Media; Endosonography; Humans; Image Enhancement; Male; Middle Aged; Polysaccharides; Predictive Value of Tests; Prostate; Prostatic Neoplasms; Ultrasonography, Doppler, Color

To investigate if the use of a contrast agent (Levovist) improves the specificity of US in the diagnosis of prostate carcinoma, having the results of prostate biopsy as the gold standard.. Thirty patients with physical findings suspicious for prostate carcinoma and PSA ranging 5 ng/mL to 15 ng/mL were examined with transrectal US (TRUS) integrated with the color Doppler mode and contrast agent administration (4 g injected at 4 mL/min: 300 mL concentration).. Based on bioptic and surgical results, 14 prostate carcinomas were found, all of them < 1.2 cm. Conventional US recognized the suspected nodule in 11 cases, with 78% sensitivity and 93% specificity. Color Doppler showed color signals in 8/14 cases, which were peripheral to the lesion or intranodular, but did not add any important finding to those of gray-scale US. In contrast, contrast enhanced studies showed 13/14 carcinomas, which improved sensitivity significantly (92%). Particularly, 11/14 lesions had a typical avascular pattern within the strongly enhanced peripheral gland, while 2 small lesions only exhibited intranodular vessels.. We compared our results with the Microscopic Angiogenesis Grading System (MAGS) index and found it exceeded 30 in the 11 avascular lesions value indicates microneoangiogenesis. In the other two cases a value < 30 was correlated with a different type of tumor vascularization typical of macroangiogenesis.

Topics: Aged; Aged, 80 and over; Biopsy; Carcinoma; Contrast Media; Humans; Male; Middle Aged; Neovascularization, Pathologic; Polysaccharides; Prostate; Prostatic Neoplasms; Ultrasonography, Doppler, Color; Ultrasonography, Interventional

The purpose of this study was to estimate the size required for small vessels to become detectable with color Doppler sonography. A murine experimental tumor was examined with color Doppler sonography after injection of 1.5 mL of the contrast medium Levovist. Histologically, we measured vessel diameters inside the tumor, as well as in its direct neighborhood. With color Doppler at a transmit frequency of 7 MHz, vessels were only detected in the tumor's environment, but not inside. By histology, the 95% quantile of the vessel diameter distribution was found to be 21 microm inside the tumor, 37 microm in the underlying muscle, and 73 microm in the directly adjacent connective tissue. Vessels in the upper range of the size distribution in the muscle and connective tissue are probably detectable. Using the 95% quantile as an estimate, and correcting the values for possible shrinkage, using a factor of 1.91 reported in the literature, vessels in the 74-134 microm range may be detected under the given conditions, whereas vessels measuring 38 microm or less are inaccessible to color Doppler.

Topics: Animals; Contrast Media; Disease Models, Animal; Male; Neoplasm Transplantation; Polysaccharides; Prostatic Neoplasms; Rats; Sensitivity and Specificity; Thigh; Ultrasonography, Doppler, Color