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Published online before print August 30, 2002, 10.1148/radiol.2251011938
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(Radiology 2002;225:71-77.)
© RSNA, 2002

Genitourinary Imaging

Prostate: High-Frequency Doppler US Imaging for Cancer Detection1

Ethan J. Halpern, MD, Ferdinand Frauscher, MD, Stephen E. Strup, MD, Levon N. Nazarian, MD, Patrick O’Kane, MD and Leonard G. Gomella, MD

1 From the Departments of Radiology (E.J.H., F.F., L.N.N., P.O.) and Urology (S.E.S., L.G.G.), Jefferson Prostate Diagnostic Center, Thomas Jefferson University, 132 S 10th St, Philadelphia, PA 19107-5244. Received November 27, 2001; revision requested January 17, 2002; revision received January 29; accepted February 28. Address correspondence to E.J.H. (e-mail: ethan.halpern@mail.tju.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate cancer detection with targeted biopsy of the prostate performed on the basis of high-frequency Doppler ultrasonographic (US) imaging findings versus cancer detection with a modified sextant biopsy approach with laterally directed cores.

MATERIALS AND METHODS: Sixty-two patients were prospectively evaluated with gray-scale, color, and power Doppler transrectal US performed with patients in the lithotomy position. Gray-scale and Doppler findings within each sextant were rated on a five-point scale. Up to four targeted biopsy specimens were obtained from each patient on the basis of Doppler findings; this was followed by a modified sextant biopsy. Conditional logistic regression analysis was performed to compare the positive yields for targeted and sextant biopsy specimens. Clustered receiver operating characteristic analysis was performed to compare gray-scale, color, and power Doppler detection of cancer at sextant biopsy sites.

RESULTS: Cancer was detected in 18 (29%) of 62 patients, including 11 patients in whom cancer was detected with both sextant and targeted biopsy, six in whom cancer was detected only with sextant biopsy, and one in whom cancer was detected only with targeted biopsy. The positive biopsy rate for targeted biopsy (24 [13%] of 185 cores) was slightly higher than that for sextant biopsy (36 [9.7%] of 372 cores; P = .1). The odds ratio for cancer detection with targeted versus sextant cores was 1.8 (95% CI: 0.9, 3.7). Receiver operating characteristic analysis demonstrated that overall identification of positive sextant biopsy sites was close to random chance for gray-scale (area under the curve, 0.53), color Doppler (area under the curve, 0.50), and power Doppler (area under the curve, 0.47) imaging.

CONCLUSION: Targeted biopsy performed on the basis of high-frequency color or power Doppler findings will miss a substantial number of cancers detected with sextant biopsy.

© RSNA, 2002

Index terms: Prostate, biopsy, 844.1261 • Prostate neoplasms, 844.32 • Prostate, US, 844.12983, 844.12984


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Conventional sextant biopsy of the prostate includes systematic acquisition of six biopsy cores to sample the base, midgland, and apex on either side of the midline (1). Unfortunately, 15%–35% of cancers are missed with conventional sextant biopsy (2,3). On the basis of the known growth patterns of prostate cancer, a modified sextant biopsy approach has been proposed that includes the acquisition of laterally directed sextant cores; this approach may provide superior results with fewer biopsy cores (4). Other researchers have suggested that an optimal systematic approach requires a greater number of biopsy cores (5,6).

Because of the increased neovascularity found in pathologic specimens of prostate cancer, use of Doppler ultrasonographic (US) imaging with targeted biopsy might be expected to improve cancer detection (7,8). In fact, color and power Doppler US do improve the yield of targeted biopsy (9–17), but these techniques have yet to result in sufficient sensitivity to replace systematic biopsy (18–20). Because there is no proven technique for identifying and localizing cancer within the prostate, research on prostate biopsy strategies has focused on finding the optimal spatial distribution of biopsy cores, with an ever-increasing number of cores per patient (21–23).

Improved Doppler sensitivity to flow in small arteries may be obtained at higher frequencies of insonation (24,25). In a recent study, we noted excellent detection of flow within the prostate with a Doppler frequency of 9 MHz, with more flow visible on the dependent side of the normal prostate in volunteers imaged in the decubitus position (26). The purpose of our present study was to evaluate cancer detection with targeted biopsy of the prostate on the basis of high-frequency Doppler US imaging in comparison with detection with a modified sextant biopsy approach that included the acquisition of laterally directed cores.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
Our study protocol was approved by our institutional review board. Written informed consent was obtained from each study subject. Patients were referred for biopsy of the prostate on the basis of an elevated serum prostate-specific antigen (PSA) level (>=4.0 ng/mL) or an abnormal result at digital rectal examination. Sixty-two consecutive patients were enrolled over a 7-month period from April to October 2001. The study population included 51 white men, seven black men, and four Asian men. Patient ages ranged from 46 to 80 years, with a mean of 63.5 years. No patient was excluded on the basis of age or race. PSA levels ranged from 0.5 to 46 ng/mL, with a mean of 9.8 ng/mL and an SD of 8.9. Of the 62 patients, 36 had not previously undergone biopsy, 17 had previously undergone a single biopsy, four had previously undergone two biopsies, three had previously undergone three biopsies, and two had previously undergone four biopsies.

US Procedure and Grading of Images
Gray-scale, color, and power Doppler transrectal US were performed with each patient in the lithotomy position. All examinations were performed with the EC10C5 end-fire probe and the Sequoia 512 system (Acuson, Mountain View, Calif). The center probe frequency was 10.0 MHz for gray-scale imaging. The center probe frequency was 9.0 MHz for color and power Doppler imaging. Color and power Doppler gain were adjusted as follows: Gain was increased until clutter was observed and then was reduced just enough to remove clutter from the appearance of the prostate. Transrectal gray-scale US examination followed a standard sequence consisting of transverse images obtained from base to apex followed by sagittal images obtained from right to left. Doppler examination followed a standard sequence consisting of transverse images obtained from base to apex. Each examination began with gray-scale imaging, followed by color Doppler imaging and finally power Doppler imaging.

Gray-scale and Doppler findings were recorded prospectively for each sextant of the prostate. A separate five-point rating scale was used to classify each site for gray-scale, color Doppler, and power Doppler findings. The gray-scale score was based on the presence of an echotexture abnormality or a contour deformity. Echotexture abnormalities included the presence of a definite hypoechoic lesion or an area of heterogeneous echotexture. Contour deformity was defined as a focal bulge of the contour of the prostate. Color and power Doppler images were evaluated for the presence of increased flow within the parenchyma of the prostate. The amount of flow within each sextant was determined on the basis of visual inspection of the color pixel density. Gray-scale and Doppler abnormalities were judged primarily on the basis of transverse US images; the appearance of the contralateral half of the gland was evaluated for comparison.

Each five-point scale assessment was a prospective and subjective assessment made by one of four physicians (E.J.H., S.E.S., L.N.N., P.O.) who performed the examinations. Sites were graded according to the following scale: 5, definitely abnormal (ie, a focal hypoechoic mass was present on gray-scale images or obvious increase in flow was present on Doppler images); 4, probably abnormal (ie, a probable hypoechoic mass was present on gray-scale images or a mild increase in flow was present on Doppler images); 3, indeterminate (ie, abnormal echotexture without definite mass was present on gray-scale images or subtle increase in flow was present on Doppler images); 2, probably normal (ie, sites showed heterogeneity on gray-scale images or minimal asymmetry in flow, which might simply represent a normal variation, on Doppler images); and 1, definitely normal (ie, homogeneous appearance on gray-scale images and symmetric flow pattern on Doppler images).

Biopsy Procedure and Pathologic Results
Prostate biopsy was performed immediately after gray-scale and Doppler evaluation. A single physician performed the diagnostic examination and the biopsy procedure. A maximum of four targeted biopsy specimens were obtained from the outer gland of each patient on the basis of the gray-scale and Doppler findings.

Targeted biopsy sites were chosen to include the most abnormal areas in the prostate on the basis of the previously described subjective rating scale. Sites that received a rating of 4 or 5 were preferentially chosen for targeted biopsy. When such suspicious sites were present, up to four targeted cores were obtained, often from only one or two locations. In a patient with no sites rated as 4 or 5, sites that were rated as 2 or 3 were targeted for biopsy. Up to four targeted cores were obtained, but usually not more than one additional targeted core per location. Targeted biopsy was not performed when all sites were rated as 1 at gray-scale and Doppler imaging. Targeted biopsy was not performed in the inner portion of the gland because it is not possible to distinguish the hypervascularity of benign prostatic hyperplasia from cancer.

The choice of whether color or power Doppler US imaging should be used for positioning the biopsy needle for targeted biopsy was left to the discretion of the examining physician and was made on the basis of which technique most clearly identified an area as hypervascular. Targeted biopsy was followed by modified sextant biopsy with a protocol that included the acquisition of six laterally distributed biopsy cores (4). Sextant biopsy specimens were obtained as peripherally as possible at the base, middle, and apex of the gland without regard to gray-scale and Doppler findings.

Additional transition-zone biopsies were performed in patients with a PSA level above 10 ng/mL and a negative result after previous biopsy (27), but these inner gland specimens were not included in our analysis. An 18-gauge core biopsy needle was used to obtain all specimens. Each outer gland biopsy core was marked as having been obtained at targeted or sextant biopsy and was labeled as to location (ie, left or right and base, midgland, or apex).

Reports of pathologic examination of all sextant and targeted core biopsy samples were reviewed (E.J.H. and F.F.). Each core was classified as benign or malignant; a Gleason score was recorded for each malignant core. The positive biopsy yield was computed individually for sextant and for targeted biopsy cores.

Statistical Evaluation
To determine whether there was a trend for increased detection of cancer when a larger number of targeted cores was obtained, a {chi}2 test for trend was performed. To determine whether higher-grade cancer was detected with targeted biopsy, the Gleason scores of sextant biopsy cores and targeted biopsy cores were compared with the Wilcoxon rank sum test.

Regression analysis was performed to compare the positive biopsy yield for targeted and sextant cores. Because biopsy data were clustered by patient, conditional logistic regression analysis was used to compensate for the lack of statistical independence among multiple cores within each patient. In the regression model, the pathologic finding of malignant or benign tissue was considered the dependent variable and biopsy type (targeted vs sextant) was considered the independent variable. Regression analysis provides an odds ratio that represents the odds of finding a cancer with a single targeted core versus the odds of finding a cancer with a single sextant core.

A recent study has suggested that more extensive biopsy sampling of the prostate may be required when the gland is larger than 45 cm3 (28). To determine whether detection of cancer at Doppler US is influenced by gland volume, patients were placed into groups that were stratified by gland volume and the regression analysis was repeated. For the purposes of this analysis, gland volume was computed from three orthogonal US measurements with the formula for a prolate ellipse (29). A cutoff value of 45 cm3 was used for stratification into two groups (gland volume < 45 cm3 and gland volume >= 45 cm3).

Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic utility of gray-scale, color, and power Doppler imaging. To compensate for within-patient clustering of data from multiple cores, a nonparametric clustered ROC analysis was performed with a modified structural components method (30).

Further analysis was performed to evaluate the distribution of Doppler signals in our study population. To determine whether there was a significant change in intensity of the Doppler signal based on location within the prostate, the Kruskal-Wallis test was performed to compare the Doppler signal ratings obtained from the six sextant locations. When a significant P value was obtained with the Kruskal-Wallis test, paired comparisons were performed with the Wilcoxon signed rank test to determine the location of this effect (left base vs right base, left midgland vs right midgland, left apex vs right apex, left base vs left apex, and right base vs right apex). To compensate for multiple comparisons, an adjusted P value of .05 divided by 5 equals .01 was established as the cutoff for a statistically significant result (Bonferroni method).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
A total of 372 sextant cores and 185 targeted cores were obtained. The number of targeted cores is summarized in Table 1. There was no significant trend for a higher rate of cancer detection in patients in whom more targeted cores were obtained ({chi}2 test for trend, P = .68).


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  		TABLE 1. Distribution of the Number of Targeted Biopsy Cores among Patients with Positive and Patients with Negative Pathologic Findings

 
No positive cores were obtained from biopsy of the transition zone. Sixty positive cores were obtained in 18 of the 62 patients in our study population, for a positive biopsy rate of 29%. Gleason scores ranged from 5 to 9 (Table 2). Although Gleason scores were slightly higher among targeted biopsy cores, this trend was not statistically significant (Wilcoxon signed rank test, P = .06). Among the 18 cases of cancer, 11 were detected with both sextant and targeted cores, six were detected only with sextant cores, and one was detected only with targeted cores. In four of the six subjects in whom cancer was not detected with targeted biopsy, targeted biopsy cores had been obtained on the side of the gland opposite the site where the positive sextant core had been obtained.


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  		TABLE 2. Distribution of Gleason Scores among Positive Biopsy Cores

 
The positive biopsy rate for targeted biopsy (24 [13%] of 185 cores) was slightly higher than that for sextant biopsy (36 [9.7%] of 372 cores). On the basis of conditional logistic regression analysis, the odds ratio for cancer detection with a targeted core versus a sextant core was found to be 1.8 (95% CI: 0.9, 3.7). The detection rates for targeted and sextant biopsy cores were not significantly different (P = .1). The volume of the prostate glands in our population varied from 11.7 to 227 cm3, with a mean of 60.2 cm3 and an SD of 40.1. Among 26 prostate glands under 45 cm3 in volume, the odds ratio for cancer detection with a targeted core versus a sextant core increased to 2.2 (95% CI: 0.8, 6.7).

ROC curves for gray-scale, color, and power Doppler depiction of cancer are presented in Figure 1. The areas under the curve were 0.53 for gray scale, 0.50 for color Doppler, and 0.47 for power Doppler. There was no significant difference among the areas below these curves (comparison of gray-scale and color Doppler imaging: P = .63; comparison of gray-scale and power Doppler imaging: P = .36). Furthermore, none of these curves demonstrated a significant advantage over the area of .5 that corresponds to random chance at the correct diagnosis.



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  		Figure 1. Graph depicts ROC curves for the detection of prostate cancer at gray-scale ({blacksquare}), color Doppler ({bullet}), and power Doppler ({blacktriangleup}) imaging.

 
The mean rating scores obtained for color and power Doppler US evaluations of our 62 patients in the lithotomy position are presented in Table 3. One hundred eighty-five targeted biopsy cores were obtained in areas with increased Doppler flow. Seven of these cores in three different patients were obtained posteriorly in the midline (Fig 2). The distribution of the remaining 178 cores is shown in Table 3. Most targeted biopsies were obtained laterally at the base or midgland level (Figs 3, 4).


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  		TABLE 3. Mean Doppler Ratings by Sextant Location and Distribution of Targeted Biopsy Cores

 


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  		Figure 2a. Transverse (a) color Doppler and (b) power Doppler US images of the prostate at midgland level in a 59-year-old man. Doppler flow (arrows) is increased posteriorly in the midline on color and power Doppler images. Three of four targeted biopsy cores were positive for cancer of the prostate (Gleason score, 7) in the midline (n = 2) and the right portion of the base (n = 1). One of six sextant cores was also positive for cancer in the right portion of the base.

 


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  		Figure 2b. Transverse (a) color Doppler and (b) power Doppler US images of the prostate at midgland level in a 59-year-old man. Doppler flow (arrows) is increased posteriorly in the midline on color and power Doppler images. Three of four targeted biopsy cores were positive for cancer of the prostate (Gleason score, 7) in the midline (n = 2) and the right portion of the base (n = 1). One of six sextant cores was also positive for cancer in the right portion of the base.

 


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  		Figure 3a. Transverse (a) color Doppler and (b) power Doppler US images of the prostate at midgland level in a 71-year-old man. Doppler flow (arrows) is increased in a capsular vessel along the right portion of the midgland on color and power Doppler images. Small perforating branches from this capsular vessel enter the peripheral zone. Increased flow (arrowheads) is also demonstrated in the enlarged transition zone. Three of four targeted biopsy cores were positive for cancer (Gleason score, 6 or 7) of the prostate in the right portion of the midgland. All sextant biopsy cores were negative.

 


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  		Figure 3b. Transverse (a) color Doppler and (b) power Doppler US images of the prostate at midgland level in a 71-year-old man. Doppler flow (arrows) is increased in a capsular vessel along the right portion of the midgland on color and power Doppler images. Small perforating branches from this capsular vessel enter the peripheral zone. Increased flow (arrowheads) is also demonstrated in the enlarged transition zone. Three of four targeted biopsy cores were positive for cancer (Gleason score, 6 or 7) of the prostate in the right portion of the midgland. All sextant biopsy cores were negative.

 


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  		Figure 4a. Transverse (a) color Doppler and (b) power Doppler US images of the midgland of the prostate in a 54-year-old man. Increased Doppler flow (arrows) is identified along the left side of the prostate with both color and power Doppler imaging. All four targeted biopsy cores on the left side were negative. A positive sextant core was obtained from the right portion of the midgland.

 


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  		Figure 4b. Transverse (a) color Doppler and (b) power Doppler US images of the midgland of the prostate in a 54-year-old man. Increased Doppler flow (arrows) is identified along the left side of the prostate with both color and power Doppler imaging. All four targeted biopsy cores on the left side were negative. A positive sextant core was obtained from the right portion of the midgland.

 
The Kruskal-Wallis test demonstrated a significant effect of location on flow for both color Doppler (P = .001) and power Doppler (P = .001). Paired comparison with the Wilcoxon signed rank test demonstrated significantly more flow in the left side of the base compared with the right side of the base and in the left side of the apex compared with the right side of the apex on both color and power Doppler images (P < .01). There was a trend that greater flow was visualized in the left side of the midgland compared with the right side, but these differences did not reach statistical significance (P = .02). Significantly greater flow was visualized at the base of the gland compared with the apex on both color and power Doppler images (P = .001).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
Previously published studies of Doppler US of the prostate, including all studies cited in this article, involved the use of Doppler frequencies in the range of 5–7.5 MHz. In a recent study, we demonstrated excellent Doppler detection of flow within the prostate with a frequency of 9 MHz (26). The present study was conducted to evaluate detection of cancer with targeted biopsy performed on the basis of the results of color and power Doppler examination at 9 MHz.

Although the positive yield of targeted biopsy in our study was greater than the yield of sextant biopsy, a substantial number of cancers that were detected with sextant biopsy (six of 17) were not found with targeted biopsy. On the basis of our results, we conclude that targeted biopsy with Doppler imaging cannot replace systematic biopsy of the prostate, even when state-of-the-art high-frequency color and power Doppler imaging are used.

When we reviewed our results, we first suspected that we might have missed the hypervascular areas with our targeted biopsy approach. Our end-fire probe allows imaging in only one plane at a time. Because we performed all of our biopsies in the transverse plane, we were unable to confirm the precise location of the biopsy needle in the craniocaudal dimension. Did we simply miss the cancers in the hypervascular areas? Further analysis, however, suggests that we cannot explain our misses by poor aim alone because the targeted cores were directed to the side opposite the cancer in four of our six missed cases.

In our previous study we noted a substantial effect of positional change on Doppler flow patterns in healthy volunteers (26). In both the right and left lateral decubitus positions, Doppler flow was more pronounced on the dependent side of the prostate. To minimize the effect of patient position in the present study, Doppler examination was performed with patients in the lithotomy position. We expected that the lithotomy position would result in an even distribution of blood flow throughout the gland. Our subjective impression is that the degree of asymmetry in blood flow observed in the present study was less than that observed in our previous experience with patients in the left lateral decubitus position. Nonetheless, flow was still more pronounced on the left side. We do not have an adequate explanation for this finding.

On several occasions during Doppler US imaging the probe was rotated 180° to check for the possibility that asymmetric flow might be related to asymmetric sensitivity of the transducer, but no difference in flow patterns was demonstrated. Because the pressure of the probe can reduce blood flow in the prostate (31), it is possible that uneven pressure on the prostate from the probe resulted in asymmetric reduction of blood flow. The transducer was always held in the right hand of the examining physician, and the examining physician was always positioned on the patient’s right side, adjacent to the US system. This explanation, however, seems somewhat unlikely because all Doppler imaging was performed in a transverse orientation with the probe in the midline (Figs 2–4). Furthermore, each examiner used the minimum degree of probe pressure required to maintain adequate contact and image quality.

In addition to the presence of more flow on the left side, the amount of flow detected at Doppler imaging appears to decrease from the base toward the apex. Although this may represent a true physiologic finding, it could also be related to the use of an end-fire probe. To visualize the apex of the prostate in the transverse plane with an end-fire probe, the probe must be angled anteriorly. Angling of the probe requires a definite amount of torque that may result in increased probe pressure to the apex of the prostate, and, consequently, in reduced blood flow. It would be interesting to repeat this study with a side-fire probe that is simply withdrawn from the rectum and does not require the application of any torque for imaging the apex of the prostate.

One possible explanation for our poor results with targeted biopsy is the large size of the glands in this study. The average gland volume in our study was 60 cm3, and 36 of the 62 glands were larger than 45 cm3. Most prostatic enlargement is related to benign prostatic hyperplasia of the transition zone. The enlarged transition zone is almost always hypervascular and often protrudes into the outer portion of the gland. Hypervascular foci of benign prostatic hyperplasia may be misinterpreted as hypervascular regions in the outer gland. Furthermore, the enlarged transition zone compresses the outer gland and may asymmetrically distort the radial flow pattern that is visible in the normal young prostate. Results of our stratified conditional logistic regression analysis confirm that Doppler findings may be more useful in smaller glands, though this finding was not significant because of the small number of subjects (n = 26) in our study with a gland volume of less than 45 cm3.

In addition to cancers that were missed with the targeted biopsy approach, negative results were obtained in 161 of 185 targeted cores. Clearly, the presence of increased flow is not specific for cancer. Although some of these hypervascular areas may be explained by the presence of benign prostatic hyperplasia or prostatitis, most of these cores were interpreted by the pathologist as normal, benign prostatic tissue. We did not attempt to analyze the patterns of hypervascularity visualized in the prostate prospectively. On the basis of pathologic findings, vessels in malignant prostatic tissue lack the normal orientation around glandular elements that characterizes benign tissue and demonstrate a greater variability in vessel size (7). It is possible that irregularly oriented, tortuous vessels (Fig 2) are more likely to be associated with malignancy than are normally oriented radial vessels (Fig 4) (32).

The ultimate goal in Doppler imaging of the prostate is to enable the visualization of increased flow in microvessels that should be associated with cancer (7). Microvessel density within the prostate is associated with metastases (33), cancer stage (34–36), and disease-specific survival (37,38). A previous study demonstrated no difference in microvessel density between malignant cores from areas with increased Doppler flow and malignant cores from areas with no detectable Doppler flow (39). A more recent study demonstrated negative correlation between microvessel density count and conventional color Doppler pixel density (40). The addition of intravascular contrast agents may allow the imaging of flow within vessels that cannot be visualized with the resolution of conventional Doppler systems (41). Studies with US contrast agents have demonstrated that they improve detection of prostate cancer (42). One recent report suggests that targeted biopsy performed on the basis of results of contrast material–enhanced color Doppler US is superior to systematic biopsy (43). It is likely that images obtained with contrast-enhanced US depict flow within true neovessels (44,45). Although such microvessels are below the resolution of conventional Doppler systems, they may be visible with microbubble contrast agents.

In designing the present study, we reasoned that the improved Doppler sensitivity and imaging resolution of a state-of-the-art 9-MHz Doppler system might result in depiction of more of the smaller vessels associated with prostate cancer. Although some cancers clearly did appear hypervascular at Doppler evaluation, a substantial number of clinically important lesions were missed with Doppler-directed targeted biopsy alone. One might wonder if the high Doppler frequency of the EC10C5 probe is a potential limitation for detection of deeper cancers. Fortunately, most cancers of the prostate are situated in the outer portion of the gland, relatively close to the transducer. Furthermore, because biopsy of the transition zone and anterior gland was not performed in our study, the biopsy cores included in our analysis were obtained from the near field (within 2–3 cm), where adequate penetration was not a problem. Finally, our experience in this study suggests that overall visualization of Doppler flow with the EC10C5 probe is substantially better than that obtained with other lower-frequency probes.

A second potential limitation of our study was the fact that the same physician who performed targeted biopsies in each patient subsequently performed the sextant biopsy. The examining physician could be biased by findings noted during the Doppler examination; this might increase the detection rate of sextant biopsy. This bias might have been avoided by having two different physicians treat each patient—one physician would perform the sextant biopsy and one would perform the targeted biopsy. Nonetheless, because sextant biopsies were performed in a standard spatial distribution regardless of US findings, we believe that targeted biopsy based on results of Doppler imaging performed without the administration of contrast material cannot replace systematic biopsy of the prostate, even when state-of-the-art high-frequency color and power Doppler imaging are used.


   FOOTNOTES
 
Abbreviations: PSA = prostate-specific antigen, ROC = receiver operating characteristic

Author contributions: Guarantor of integrity of entire study, E.J.H.; study concepts and design, E.J.H., F.F.; literature research, E.J.H., F.F.; clinical studies, all authors; data acquisition, all authors; data analysis/interpretation, E.J.H., F.F.; statistical analysis, E.J.H.; manuscript preparation, E.J.H., F.F.; manuscript definition of intellectual content, editing, revision/review, and final version approval, all authors.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

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