Genitourinary Imaging Original Research

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1 Genitourinary Imaging Original Research Woodfield et al. DWI of Prostate Cancer Genitourinary Imaging Original Research Courtney A. Woodfield 1,2 Glenn A. Tung 1,2 David J. Grand 1,2 John A. Pezzullo 1,2 Jason T. Machan 3 Joseph F. Renzulli II 2,4 Woodfield CA, Tung GA, Grand DJ, Pezzullo JA, Machan JT, Renzulli JF II Keywords: diffusion-weighted imaging, Gleason score, MRI, prostate cancer, tumor volume DOI: /AJR Received February 24, 2009; accepted after revision October 9, Department of Diagnostic Imaging, Rhode Island Hospital, 593 Eddy St., Providence, RI Address correspondence to C. A. Woodfield (courtneywoodfield@ yahoo.com). 2 The Warren Alpert Medical School of Brown University, Providence, RI. 3 Department of Biostatistics, Rhode Island Hospital, Providence, RI. 4 Division of Urology, Rhode Island Hospital, Providence, RI. WEB This is a Web exclusive article. AJR 2010; 194:W316 W X/10/1944 W316 American Roentgen Ray Society Diffusion-Weighted MRI of Peripheral Zone Prostate Cancer: Comparison of Tumor Apparent Diffusion Coefficient With Gleason Score and Percentage of Tumor on Core Biopsy OBJECTIVE. The objective of our study was to determine the relationship between the apparent diffusion coefficient (ADC) value on diffusion-weighted imaging (DWI) and Gleason score of prostate cancer and percentage of tumor involvement on prostate core biopsy. MATERIALS AND METHODS. We performed a retrospective study of 57 patients with biopsy-proven prostate cancer who underwent endorectal MRI with DWI between July 2007 and March Regions of interest (ROIs) were drawn on ADC maps at sites of visible tumor on DW images and ADC maps. A hierarchic mixed linear model was used to compare the ADC value of prostate cancer with the Gleason score and the percentage of tumor on core biopsy. RESULTS. Eighty-one sites of biopsy-proven prostate cancer were visible on DW images and ADC maps. The least-squares mean ADC for disease with a Gleason score of 6 was mm 2 /s (standard error of the mean [SEM], 0.036); Gleason score of 7, mm 2 /s (SEM, 0.030); Gleason score of 8, mm 2 /s (SEM, 0.057); and Gleason score of 9, mm 2 /s (SEM, 0.067). Differences between the mean ADC values for a prostate tumor with a Gleason score of 6 and one with a Gleason score of 7 (p = ) and for a prostate tumor with a Gleason score of 6 and one with a Gleason score of 8 (p = ) were significant. Comparison between the ADC and percentage of tumor on core biopsy showed a mean ADC decrease of (range, mm 2 /s) for every 1% increase in tumor in the core biopsy specimen. CONCLUSION. DWI may help differentiate between low-risk (Gleason score, 6) and intermediate-risk (Gleason score, 7) prostate cancer and between low-risk (Gleason score, 6) and high-risk (Gleason score > 7) prostate cancer. There is an inverse relationship between the ADC and the percentage of tumor involvement on prostate core biopsies. M RI of prostate cancer with conventional T2-weighted imaging is predominantly limited to staging for the presence of extracapsular extension and seminal vesicle invasion. However, the more recent application of functional MRI techniques, including diffusion-weighted imaging (DWI), has the potential to expand the role of MRI to noninvasive characterization of prostate cancer by providing more specific information regarding tumor location, size, and aggressiveness [1 6]. Several recent studies have shown that DWI can help differentiate between malignant and benign prostatic tissue on the basis of lower apparent diffusion coefficient (ADC) values of prostate carcinoma compared with normal prostate tissue [2 4, 7 12]. Decreased diffusion in prostate carcinoma is believed to be caused, at least partly, by the more highly cellular environment of neoplastic tissue, which restricts water molecule movement in the ex- tracellular space. The reported ADC values of prostate cancer in the peripheral zone range between 0.93 and mm 2 /s [2 4, 8 13]. This variability in ADC values may be related, at least in part, to the heterogeneous tissue composition of prostate cancer [14]. The histopathologic reference standard for measuring and reporting prostate cancer aggressiveness is the Gleason grading system. Gleason grades 1 5 correspond to progressively more poorly differentiated prostate cancer. A given tumor is assigned both a primary (most prevalent) and a secondary (second most prevalent) Gleason grade, and the sum of these grades yields the Gleason score. Gleason scores are also used to describe tumors as low grade (Gleason score, 6), intermediate grade (Gleason score, 7), or high grade (Gleason score, > 7) with respect to tumor aggressiveness. More aggressive tumors are associated with an increased likelihood of prostate cancer recurrence [15]. A larger tumor volume is also W316 AJR:194, April 2010

2 DWI of Prostate Cancer associated with an increased risk of tumor recurrence [16]. The purpose of this study was to investigate the relationship between the ADC value of prostate cancer on MRI and the Gleason score and tumor volume of prostate cancer on transrectal ultrasound guided prostate core biopsy. Further understanding of the restricted diffusion characteristics of prostate cancer may allow improved assessment of tumor aggressiveness with MRI. Materials and Methods Patients This retrospective study was approved by our institutional review board (IRB) and was compliant with HIPAA. The IRB waived the requirement for informed patient consent. Between July 2007 and March 2008, 90 men underwent endorectal prostate MRI at our institution. Thirty-three of these men were excluded from this study because one or more of the following inclusion criteria were not met: MRI examination included DWI; transrectal ultrasound guided biopsy results were available for review; MRI was performed 3 weeks to less than 6 months after prostate biopsy; and no treatment of prostate cancer had been received before MRI. In all subjects, a tissue diagnosis of prostate cancer was determined from analysis of transrectal ultrasound guided biopsy specimens. Patient age, serum prostate-specific antigen (PSA) level, biopsy results for Gleason score, and percentage of tumor involvement of the biopsy core were recorded from review of the medical records. MRI Technique All prostate MRI examinations were performed on a 1.5-T system (Signa Excite, GE Healthcare) with a gradient strength of 120 mt/m and using both a pelvic phased-array coil and balloon-covered expandable endorectal coil. Glucagon, 1 mg, was administered subcutaneously immediately before the start of the examination. All patients were imaged in the supine position. After the acquisition of localizing images, sagittal T2-weighted singleshot fast spin-echo imaging through the pelvis was performed to confirm the position of the endorectal coil. Axial, coronal, and sagittal thin-section, high-spatial-resolution T2-weighted fast spin-echo (FSE) images through the prostate and seminal vesicles were obtained using the following parameters: TR range, 3,000 4,000 milliseconds; TE, 120 milliseconds; echo-train length, 16; field of view (FOV), 12 cm; section thickness, 3 mm; intersection gap, 0 mm; matrix, ; and number of excitations (NEX), 4. Transverse axial T1-weighted spoiled gradient-echo images with a TR/TE of 325/4.2 and all other parameters matched to the axial high-resolution T2-weighted FSE sequence were obtained. Transverse axial T1-weighted spoiled gradient-echo images were also obtained from the aortic bifurcation to the symphysis pubis using the following parameters: 100/4.2; FOV, 38 cm; section thickness, 5 mm; intersection gap, 1 mm; matrix, ; and NEX, 1. DWI was performed using a single-shot echoplanar imaging technique with a TR of 3,000 milliseconds and a minimum TE; FOV, 18 cm; section thickness, 3 mm; intersection gap, 0 mm; matrix, ; NEX, 6; and b values, 0 and 1,000 s/ mm 2. Before this study, we established that a b value of 1,000 s/mm 2 provided the highest image contrast between normal and malignant prostate tissue on our 1.5-T system. In addition, a larger FOV (18 cm) was used for the DWI sequences than for the T1- and T2-weighted sequences (FOV, 12 cm) to optimize the signal-to-noise ratio on the DWI images. In other studies, the highest b values used for DWI of prostate cancer range between 500 and 1,000 s/mm 2 [1 12]. The use of b values higher than 1,000 s/mm 2 has not been shown to further improve differentiation between normal and malignant prostate tissues [17]. ADC values were obtained from the DWI sequences performed with b values of 0 and 1,000 s/mm 2, and the ADC maps were generated by calculating the ADC value in each pixel of each slice. MR Image Analysis MRI was analyzed by a radiologist blinded to Gleason score and tumor volume but with knowledge of the location of prostate cancer from transrectal ultrasound guided prostate biopsy results. The transverse, longitudinal, and lateral locations of the prostate biopsy were described by the urologist who performed the biopsy as right or left side of gland; base of gland, mid gland, or apex of gland; and medial, central, or lateral, respectively, to help determine the biopsy locations on MR images. All of the biopsied tumors were located in the prostatic peripheral zone. None of the patients had central gland biopsies. All sequences of the MR examination were reviewed for each patient by a radiologist with 5 years of experience interpreting prostate MR examinations and 2 years of experience interpreting DWI of the prostate. The criteria for tumor visibility were focal hyperintensity on DW images and corresponding hypointensity on ADC maps relative to the rest of the prostate gland and at a site of biopsy-proven carcinoma. Focal hypointensity at a site of biopsyproven carcinoma on both T1- and T2-weighted images was not a criterion for tumor visibility. The T1- and T2-weighted sequences were reviewed only to confirm findings on other sequences and to ensure that any measured areas of restricted diffusion were not due to the presence of blood products. If an area of decreased signal intensity was detected on a T1- and T2-weighted image at a site of biopsy-proven carcinoma, it still did not meet criteria for tumor visibility if there was no corresponding restricted diffusion. The FOVs were different for the T2- weighted and DWI sequences. Therefore, a region of interest (ROI) placed in the center of the tumor on T2-weighted imaging could not be precisely crossreferenced to the corresponding DW image. Similarly, biopsy-proven sites of carcinoma that were not visible on T2-weighted imaging or DWI were not analyzed because we believe that estimated ROI measurements based on biopsy site description alone would not be accurate. The criterion for benign prostate tissue was the absence of hyperintensity on the DWI sequence and absence of hypointensity on T2-weighted images in the peripheral zone at a site of biopsy-proven benign tissue. ROIs were drawn manually by the reviewing radiologist on ADC maps in the center of each visible tumor and at sites of biopsy-proven benign tissue. The ROIs were drawn to encompass the largest area of prostate cancer or benign tissue without including the tumor margins, the prostate capsule, or the urethra (Figs. 1 and 2). The areas of ROIs ranged from 3 to 20 mm 2. The wide range of areas was due to the wide range in the sizes of prostate glands and prostate carcinomas. The size and location of all biopsyproven tumor foci visible on DW images and ADC maps were also recorded. Tumor size was measured on ADC maps. Mean signal intensity values and SDs in the ROI were automatically determined by the PACS (Synpase, Fuji Medical Systems). Biopsyrelated hemorrhage in the prostate gland was also scored on a 4-point scale: 0, no blood; 1, blood in less than 25% of the peripheral zone; 2, blood in 25 50% of the peripheral zone; and 3, blood in more than 50% of the peripheral zone. Statistical Analysis A generalized estimating equation was used first to determine whether there was a relationship between tumor visibility on DW images and ADC maps and pathologic Gleason score. An unstructured variance covariance structure was used. To further evaluate the relationship between ADC values of visible tumor and pathologic Gleason score and between ADC values of visible tumor and the percentage of tumor on core biopsy, a hierarchic mixed linear model was used to predict ADC, in which Gleason score was a categoric fixed and random effect and percentage of tumor involvement on core biopsy as a continuous fixed and random effect. This model was chosen to account for the clustered nature of multiple samples from the same patient. In addition, a Bonferroni adjustment was used to adjust p values on the basis of the number of follow-up comparisons performed if necessary. An AJR:194, April 2010 W317

3 Woodfield et al. unstructured variance covariance structure was also used. A linear trend was tested for increases in ADC as a function of increasing Gleason score. A chi-square test was used to assess the effect of biopsy-related hemorrhage on tumor visibility, where only one observation was made per patient. A hierarchic model was also used to compare the percentage of tumor involvement on core biopsy for DWI and ADC value for tumors visible on DW images and ADC maps and tumors not visible on DW images and ADC maps. Results In this study, 57 men (mean age, 66 years; SD, 10.9; range, years) had a total of 342 transrectal ultrasound guided core prostate biopsies and 185 (54%) of these sextant biopsies yielded prostate cancer. Forty-four A Fig year-old man with prostate cancer with Gleason score of 6 in peripheral zone of right mid gland involving 50% of core biopsy. A, Axial diffusion-weighted image (b = 1,000 s/mm 2 ) shows area of slightly rounded hyperintensity (arrow) at site of biopsy-proven carcinoma. Note similar increased signal intensity at contralateral base due to coil artifact. B, Isotropic axial apparent diffusion coefficient (ADC) map shows area of hypointensity (arrow) corresponding to that shown in A. C, Isotropic axial ADC map with region of interest (circle) placed in center of hypointense signal yields ADC of mm 2 /s. A Fig year-old man with prostate cancer with Gleason score of 8 in peripheral zone of right mid gland involving 53% of prostate core biopsy. A, Axial diffusion-weighted image (b = 1,000 s/mm 2 ) shows area of increased signal intensity (arrow) at site of biopsy-proven carcinoma. B, Isotropic axial apparent diffusion coefficient (ADC) map shows area of hypointensity (arrow) corresponding to that shown in A. C, Isotropic axial ADC map with region of interest (circle) placed in center of hypointense signal yields measured ADC of mm 2 /s. subjects (77%) had more than one site of tumor on sextant biopsy: seven subjects had two sites; 15, three sites; six, four sites; seven, five sites; and nine, six sites. All transrectal ultrasound guided biopsies and sites of tumor were in the peripheral zone of the prostate gland. None of the patients who met inclusion criteria for this study had biopsy of TABLE 1: Probability of Prostate Tumor Being Visible on Diffusion-Weighted Imaging (DWI) by Gleason Score Gleason Score No. (%) of Tumors Odds That Tumor Is Visible on DWI a 95% CI Visible on DWI Not Visible on DWI Mean Lower Limit Upper Limit 6 25 (37) 43 (63) (44) 48 (56) (43) 13 (57) (100) 0 (0) Note Increase in odds was 8.44 (linear trend) with a 95% CI of (p = ). a Generalized estimating equation with biopsy location nested within patient. B B C C W318 AJR:194, April 2010

4 DWI of Prostate Cancer the central or transitional zone. The mean PSA level was 10.3 ng/ml (SD, 7.2; range, ng/ml). Diffusion-Weighted MRI The mean number of days between transrectal ultrasound guided prostate biopsy and MRI was 44 days (SD, 15; range, days). Most of the biopsy-proven sites of prostate cancer were not visible on DWI. Eightyone biopsy-proven sites of prostate carcinoma (44%) were detected on DWI. The remaining 104 biopsy-proven sites of cancer (56%) were not visible on DWI. Five of these 104 sites of cancer were visible as focal hypointensity on T2-weighted images, but the remaining 99 tumors were not visible on DWI or T2-weighted imaging. The Gleason scores for the 81 tumors visible on DWI and ADC maps and the 104 nonvisible tumors are outlined in Table 1. In 62 of the prostate cancers that were visible A D Fig year-old man with biopsy-proven prostate cancer with Gleason score of 7 in peripheral zone of left base (60% of core) and peripheral zone of right mid gland (20% of core). A, Axial T2-weighted image illustrates focal low-signal-intensity nodule (arrow) in peripheral zone of left base at site of biopsy-proven carcinoma. B and C, Restricted diffusion (arrow) is shown on axial diffusion-weighted image (B) (b = 1,000 s/mm 2 ) and isotropic axial ADC map (C). D, Axial T2-weighted image through mid gland shows heterogeneous signal intensity (arrows) in peripheral zone bilaterally, but no discrete right midgland tumor nodule. E and F, There is no evidence of restricted diffusion in mid gland on corresponding axial diffusion-weighted image (E) (b = 1,000 s/mm 2 ) and isotropic axial ADC map (F). on DWI (77%) and 91 of those that were not visible (88%), disease was characterized as a Gleason score of 6 or 7 on prostate biopsy. The odds of tumor being visible on DWI increased with increasing Gleason score (linear trend, p = ). There was also a statistically significant difference (p ) between the percentage of tumor involvement on core biopsy between the tumors not visible on DWI and those that were visible on DWI (Fig. 3). The mean percentage of tumor on core biopsy for tumors not visible on DWI was 19% (SD, 25.2; range, 1 95%) versus 52% (SD, 19.9; range, 1 100%) for those visible on DWI. For the 81 tumors that were visible on DWI, the amount of blood in the peripheral zone was a score of 0 for four tumors (5%), a score of 1 for 26 (32%), a score of 2 for 24 (30%), and a score of 3 for 27 (33%). For the 104 tumors not visible on DWI, the amount of blood in the peripheral zone was a score B E of 0 for three tumors (3%), a score of 1 for 36 (35%), a score of 2 for 15 (14%), and a score of 3 for 50 (48%). There was no statistically significant difference in the amount of hem- Fig. 4 Venn diagram illustrates number of biopsyproven prostate carcinomas visible on only diffusionweighted images and ADC maps (blue); on only T2- weighted images (yellow); and on diffusion-weighted images, ADC maps, and T2-weighted images (green). C F AJR:194, April 2010 W319

5 Woodfield et al. TABLE 2: Apparent Diffusion Coefficient (ADC) Values for Tumors Visible on Diffusion-Weighted Imaging According to Gleason Score Gleason Score ADC ( 10 3 mm 2 /s) No. of Tumors ADC ( 10 3 mm 2 /s) Least-Squares Mean Standard Error of Mean Range Gleason Score Fig. 5 Scatterplot shows relationship between apparent diffusion coefficient (ADC) values in diffusion-weighted image and ADC visible tumors and tumor Gleason score. Data shown are multiple observations from same patients accounted for in analysis estimating mean ADC values. Differences between mean ADC values of tumors with Gleason score of 6 and those with Gleason score of 7 and of tumors with Gleason score of 6 and those with Gleason score of > 7 are significant. orrhage in the peripheral zone for the tumors that were visible and those that were not visible on DW images. Twenty-three tumors were visible on DWI only, five on T2-weighted imaging only, and 58 tumors were visible on both (Fig. 4). There was no significant difference in the estimated odds of tumor visibility on T2-weighted images compared with DW images. The odds ratio for visualizing tumor on T2-weighted imaging was (95% CI, ), which overlaps with the CIs for the odds ratio of visualizing tumor on DWI, (95% CI, ). One-hundred forty-eight of the 157 sites of biopsy-proven benign prostate tissue met visibility criteria. Nine biopsy-proven sites of benign peripheral zone tissue had focal hyperintensity in the peripheral zone on DWI with corresponding hypointensity on the ADC map, but there was no corresponding low signal intensity on T1- and T2-weighted images for these cases. None of the biopsyproven sites of benign peripheral zone tissue had DWI hyperintensity with corresponding ADC map hypointensity and corresponding T1- and T2-weighted hypointensity. Eleven sites of restricted diffusion with corresponding low signal intensity on T1- and T2- weighted images were detected in the central gland of nine patients; these sites are suspicious for central gland tumor, but to date none of these patients has undergone additional biopsy or surgery for confirmation. For the 81 tumors visible on DWI, the mean tumor volume was 1.4 cm 3 (SD, 1.2; range, cm 3 ). All were identified in the peripheral zone of the prostate gland, with 31 (38%) in the base of the gland, 19 (23%) in the mid gland, and 31 (38%) in the apex of the gland. The mean ADC (± SD) for 148 measurements of biopsy-proven benign peripheral zone tissue was ± mm 2 /s (range, mm 2 /s), and the mean ADC for the 81 visible sites of biopsy- ADC ( 10 3 mm 2 /s) proven tumor was ± mm 2 /s (range, mm 2 /s). The ADC values and the mean ADC values for visible tumor with disease characterized as a Gleason score of 6 9 are indicated in Table 2 and Figure 5. Differences between the mean ADC values of tumors with a Gleason score of 6 and those with a Gleason score of 7 (p = ) and tumors with a Gleason score of 6 and those with a Gleason score of 8 (p = ) were statistically significant. The difference between the mean ADC value of tumor with a Gleason score of 6 and that of tumor with a Gleason score of 9 was also initially statistically significant (p = ); however, after the Bonferroni adjustment was used to adjust for multiple comparisons, this difference was not significant (p = ). The differences between the mean ADC values of tumors with a Gleason score of 7, 8, and 9 were not significantly different with or without adjustment. A mean ADC decrease of mm 2 /s (range, mm 2 /s) was detected for every 1% increase in tumor in the core biopsy specimen (Fig. 6). Discussion A significant reduction in the diffusion properties of water protons in prostate cancer and the resulting reduction in the measured ADC value of prostate cancer relative to normal prostatic tissue have been well documented [3, 4, 7 9, 11, 12] and are supported by our Percentage of Tumor at Core Biopsy Fig. 6 Scatterplot shows relationship between apparent diffusion coefficient (ADC) values in diffusion-weighted image and ADC visible tumors and percentage of tumor involvement of core biopsy. Figure contains multiple observations from same patients which were accounted for in analysis which estimated plotted linear function. There is correlation between increasing percent core involvement and decreasing ADC value. W320 AJR:194, April 2010

6 DWI of Prostate Cancer investigation. The diffusion characteristics of any biologic tissue are based on the relative combination of water proton movement in the extracellular environment, across cell membranes, and within the cells of that tissue [18, 19]. Any change in the architecture of a tissue such as an increase in the proportion of intracellular to extracellular water protons, which occurs with the replacement of less cellular normal prostate tissue with more highly cellular neoplastic tissue, results in more restricted movement of water protons. This more restricted movement is due to a combination of decreased extracellular space and a more viscous and complex intracellular environment [20 22]. Although the more restricted movement of water protons and resulting lower ADC values in prostate cancer have been well described, only a few prior studies to date have investigated the relationship between prostate cancer ADC values and tumor aggressiveness [1 4, 6]. In our investigation of the relationship between the diffusion characteristics and aggressiveness of prostate cancer, we found that lower ADC values were associated with higher Gleason scores and that ADC values may help to differentiate between low-risk (Gleason score, 6) and intermediate-risk (Gleason score, 7) prostate cancer and between lowrisk (Gleason score, 6) and high-risk (Gleason score, > 7) prostate cancer if the tumor is visible on DW images and ADC maps. However, because of the retrospective nature of this study and overlap in the ADC values of tumors with different Gleason scores, we did not find that ADC values alone can always differentiate between tumors with low Gleason scores and those with high Gleason scores. The overlap of ADC values for tumors with Gleason scores of 7, 8, and 9 in our study may have been partly related to tumor heterogeneity, similarity in the cellular density of prostate cancers with a Gleason score of 7 or greater, or both. Investigators have reported that prostate cancer may be heterogeneous at histopathology, with one tumor composed of more than one Gleason grade and score [23]. The lower mean ADC values in the more aggressive tumors in our study may be due to higher cellular density in poorly differentiated tumors, resulting in more restricted movement of water protons. Zelhof et al. [24] recently reported that ADC values of prostate cancer correlate with cellular density and described a significant correlation between decreasing ADC values and increasing cellular density of prostate cancer. For the tumors visible on DWI, we also found a relationship between decreasing ADC values and increasing percentage of tumor involvement on prostate core biopsies, another measure of tumor aggressiveness. This tendency for ADC to decrease as tumor volume increases is likely due, at least partly, to better visibility of denser tumors on DW images and ADC maps compared with less dense tumors. This greater visibility facilitates larger and more accurate ROI placement on ADC maps. In contrast, in earlier studies of patients with prostate cancer imaged on a 3-T magnet without an endorectal coil and using maximal b values of 500 s/mm 2 [3, 4] and 1,000 s/mm 2 [2], Gibbs et al. [3], Pickles et al. [4], and Kim et al. [2] found no correlation between ADC values and Gleason scores. A more recent study by Yoshimitsu et al. [1] of 37 patients imaged on a 1.5-T magnet without the use of an endorectal coil and using b values of 0, 500, and 1,000 s/mm 2 found an inverse correlation between ADC values and Gleason scores, which is similar to the results of our study. Also similar to our study is that this difference was significant only between well-differentiated carcinomas (mean ADC, 1.19 ± mm 2 /s) and poorly differentiated carcinomas (mean ADC, 0.93 ± mm 2 /s) [1]. Tamada et al. [6] also recently reported a correlation between decreasing ADC values of peripheral zone prostate cancer and increasing Gleason score on prostate biopsy. In their series of patients with prostate cancer, imaging was performed on a 1.5-T magnet without the use of an endorectal coil and using 800 s/mm 2 as the highest b value. No other previous studies, to our knowledge, have compared the ADC values of prostate cancer with the percentage of tumor involvement on core biopsy or tumor volume at histopathology. The reported sensitivity and specificity of DWI with ADC maps for detecting prostate cancer range from 54% to 94% and from 61% to 100%, respectively [1 3]. These variable detection rates and the low detection rate in our study may be attributed in part to the use of biopsy and pathology results that include even small foci of tumor as gold standards. Langer et al. [14] recently reported that sparse tumors (i.e., those with > 50% of cross-sectional tumor area composed of normal peripheral zone) have ADC and T2 values similar to normal peripheral zone tissue. We found a similar trend in that the smaller the percentage of tumor involvement in a core biopsy, the less likely was the tumor to be visible on DW images and ADC maps. In addition, tumors with a low Gleason score (Gleason score, 6) comprised 72% of the tumors in our study, and we also found that these tumors were less likely to be visible on DW images and ADC maps. DW images and ADC maps also did not significantly improved tumor visibility compared with T2-weighted images alone. One of the limitations of this study is that step-section histopathology was not used as the gold standard for comparing ADC values with Gleason scores. Gleason scores are known to be prone to sampling error, and the final Gleason score at histopathology may differ from that determined by transrectal ultrasound guided biopsy. In general, there may be a 20 30% upstaging of Gleason score from core biopsy to surgical pathology. Similarly, the volume of disease may have been underestimated on core biopsy, which might also account for the high mean PSA value of 10.3 ng/ml in our study. However, because of the retrospective nature of this study, we included all patients scheduled for prostate MRI regardless of ultimate treatment and only eight of the 57 study patients had undergone radical prostatectomy at the time of study completion. An additional limitation of the study is the relatively small number of high-risk tumors with Gleason scores of 8 or 9, which reduces confidence in findings both within these groups and between these scores and other scores. All of the patients had also undergone prostate biopsy before the MRI examination. In a recent study, Tamada et al. [25] found that the degree of hemorrhage in the prostate gland did not correlate significantly with the time between biopsy and MRI. Although we did not find a significant difference between the amount of blood products in the peripheral zone of tumors not visible on DW images and ADC maps compared with visible tumors, blood products may still have affected measured ADC values. In conclusion, we found that the ADC values of prostate carcinoma on MRI performed at 1.5 T and using an endorectal coil and b values of 0 and 1,000 s/mm 2 may help differentiate between low-risk (Gleason score, 6) and intermediate-risk (Gleason score, 7) disease and between low-risk and high-risk (Gleason score > 7) disease. In addition, we found an inverse relationship between the ADC value and the percentage of tumor involvement on prostate core biopsies. The finding that lower ADC values are associat- AJR:194, April 2010 W321

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