Korean J Radiol.  2012 Feb;13(1):82-89. 10.3348/kjr.2012.13.1.82.

Diffusion-Weighted Imaging of a Prostate Cancer Xenograft Model Seen on a 7 Tesla Animal MR Scanner: Comparison of ADC Values and Pathologic Findings

• Jung DC
• Lee HJ
• Seo JW
• Park SY
• Lee SJ
• Lee JH
• Kim IH

• KMID: 1058797
• DOI: http://doi.org/10.3348/kjr.2012.13.1.82

Abstract

OBJECTIVE
To assess the relationship between apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance (MR) imaging and pathologic measures of a tumor using a prostate cancer xenograft model.
MATERIALS AND METHODS
Eighteen athymic nude mice with 36 PC-3-induced tumors were sacrificed to obtain specimens immediately after MR imaging in order to compare the findings on MR images with those seen on pathological specimens. Using a high-field small-animal MR scanner, T1- and T2-weighted imaging and DW MR imaging was performed. Tumors were then processed for Hematoxylin and Eosin staining to evaluate tumor cellularity, intratumoral necrosis and immunostaining using antibodies directed against CD31 and vascular endothelial growth factor (VEGF) to determine the levels of microvessel density (MVD). Mean ADC values that were measured on the solid portion within each tumor were compared with tumor volume, cellularity, degree of necrosis, VEGF expression, and MVD in the corresponding section of the pathological specimen.
RESULTS
Mean ADC values of the solid portion within the PC-3-induced high-grade tumors were significantly correlated with the degree of intratumoral necrosis (r = 0.63, p < 0.0001) and MVD (r = -0.44, p = 0.008) on pathologic slides. The ADC values were not significantly correlated with tumor cellularity, VEGF expression, or tumor volume in high-grade prostate cancer tissues.
CONCLUSION
In the xenografted prostate cancer model, the ADC values of the solid portion of the tumors are significantly correlated with tumor necrosis and MVD of the pathologic specimens. The ADC values may be utilized as surrogate markers for the noninvasive assessment of tumor necrosis and MVD in high-grade prostate cancer.

Keyword

PC3; Prostate; Diffusion weighted imaging; MR; Necrosis; MVD

MeSH Terms

Animals
Diffusion Magnetic Resonance Imaging/instrumentation/*methods
Male
Mice
Mice, Nude
Prostatic Neoplasms/*pathology
Transplantation, Heterologous
Vascular Endothelial Growth Factor A/metabolism

Figure

• 

  Fig. 1 Human prostate cancer cell (PC-3) induced bilateral subcutaneous tumors on flank of athymic mouse. A. T2-weighted MR images (Bruker RARE sequence; field of view = 3 × 2.5 cm, matrix = 256 × 256, spatial resolution = 117 × 98 µm/pixel, slice thickness = 1.0 mm, repetition time = 2500 ms, TEeff = 36.0 ms) of axial planes show homogeneous high signal intensity mass in injected area of both backs (arrows). B. Rectangular region of interest was placed within left tumor on axial plane of heavily T2 weighted MR image. Console program shows process of calculating apparent diffusion coefficient value of pixel area in region of interest. Apparent diffusion coefficient values for region of interest as well as apparent diffusion coefficient map could be calculated from following equation: Y = A + I * exp (-b * D). These parameters are defined as follows: Y: image intensity, A: absolute bias, I: multiplication constant, b: diffusion b-value and D: diffusion constant. This function (supplied by BRUKER®) uses b-value list calculated to generate x-axis. Fit is based on magnitude images of reconstructed data set using least squares mono exponential fitting. C. Photography of entire section (× 10) in pathological specimen stained with Hematoxylin and Eosin staining. Analysis program developed with visual C++ automatically performed calculation of percentage (%) of necrosis within tumor. D. Photomicrograph of immunohistochemical staining shows CD31 expression; microvessels stained with CD-31 were counted in four adjacent fields at × 200.

• 

  Fig. 2 Scatter plots of with regression line of apparent diffusion coefficient (ADC) value (mm2/s) of high-grade prostate cancer xenograft. A. Scatter plot with regression line between tumor necrosis (%) and mean apparent diffusion coefficient value. Linear relationship was found between mean apparent diffusion coefficient value and tumor necrosis (R2 = 0.402, F-ratio = 22.89, p < 0.001). B. Scatter plot with regression line between microvessel density (MVD) and mean apparent diffusion coefficient value. There was linear relationship between mean apparent diffusion coefficient value and microvessel density (R2 = 0.19, F-ratio = 7.96, p = 0.008).

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