Rationale and Objectives
Development of imaging biomarkers often relies on their correlation with histopathology. Our aim was to compare two approaches for correlating pathology to multiparametric magnetic resonance (MR) imaging (mpMRI) for localization and quantitative assessment of prostate cancer (PCa) index tumor using whole mount (WM) pathology (WMP) as the reference.
Materials and Methods
Patients ( N = 30) underwent mpMRI that included diffusion-weighted imaging and dynamic contrast-enhanced (DCE) MRI at 3 T before radical prostatectomy (RP). RP specimens were processed using WM technique (WMP) and findings summarized in a standard surgical pathology report (SPR). Histology index tumor volumes (HTVs) were compared to MR tumor volumes (MRTVs) using two approaches for index lesion identification on mpMRI using annotated WMP slides as the reference (WMP) and using routine SPR as the reference. Consistency of index tumor localization, tumor volume, and mean values of the derived quantitative parameters (mean apparent diffusion coefficient [ADC], K trans , and v e ) were compared.
Results
Index lesions from 16 of 30 patients met the selection criteria. There was WMP/SRP agreement in index tumor in 13 of 16 patients. ADC-based MRTVs were larger ( P < .05) than DCE-based MRTVs. ADC MRTVs were smaller than HTV ( P < .005). There was a strong correlation between HTV and MRTV (Pearson ρ > 0.8; P < .05). No significant differences were observed in the mean values of K trans and ADC between the WMP and SPR.
Conclusions
WMP correlation is superior to SPR for accurate localization of all index lesions. The use of WMP is however not required to distinguish significant differences of mean values of quantitative MRI parameters within tumor volume.
Magnetic resonance (MR) imaging (MRI) of the prostate has become an essential modality for staging and characterizing prostate cancer (PCa) . Current imaging protocols use multiparametric MRI (mpMRI) with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI in addition to conventional T2- and T1-weighted imaging for a comprehensive assessment of PCa. The current recommendations for the clinical use of MRI rely on the qualitative assessment of the MR parameters , but much work is currently being done to refine mpMRI acquisitions, analyses, and validations to establish the clinical utility of quantitative prostate imaging. Each individual imaging sequence can provide unique and complementary quantitative measurements of the underlying physiology and pathophysiology of the prostate tissue, leading to improved detection of PCa . However, exactly what pathophysiology these quantitative measurements represent is not well established.
Development and validation of quantitative imaging tools requires correlation with established markers of the disease. A pathology-derived Gleason score remains the cornerstone for decision making with regard to therapy selection and disease prognosis . As such, numerous studies have been conducted to correlate quantitative mpMRI parameters with histology for the purposes of localizing the lesion and assessing its aggressiveness . Likewise, correlation with histology is also a necessary component in the validation of mpMRI as a means of response to therapy. However, the methods used for pathologic correlation vary widely, ranging from in-depth whole mount (WM) processing of the specimen followed by delineation of tumor foci by a pathologist directly on the glass sides and comparison to MRI data, to simply correlating MR images to the standard clinical pathology report. These two correlative pathology approaches are very different in terms of resources, expertise, and time involvement. WM pathology (WMP) correlation requires a technologist with expertise in WM fixation, embedding and sectioning, extensive pathologist involvement and is considered the “gold standard” for an imaging correlative approach. In contrast to standard pathologic processing used routinely, where individual cross-sections of the prostate are further cut into four quadrants or more, WMP allows for increased accuracy of the spatial mapping between pathology specimen and images, as axial sections of the prostate specimen are processed using large WM slides, which are marked to facilitate volumetric reconstruction of the specimen. The tumor areas are next contoured on each slide, thus simplifying spatial localization of the matching lesions in the imaging data. This in-depth correlative approach has been used by many . In contrast, a more common routine processing protocol provides pathology information necessary for clinical decision making, and including overall Gleason score and whether or not there is an extracapsular extension of tumor, it may include one- or two-dimensional measurement of the tumor area(s). As such, routine processing does not allow for volumetric reconstruction of the specimen, and so, three-dimensional volumes cannot be easily estimated. The surgical pathology report (SPR) is therefore not focused on providing detailed information for validating imaging studies. However, given the ubiquitous availability of SPR data, and the relatively low cost of implementing imaging correlative studies that rely on SPR, the practical question is whether SPR alone is sufficient for accurate localization of PCa. If the index lesion is correctly localized, it is unknown whether the assumed improvement in the accuracy of tumor delineation using WMP leads to significant differences in the tumor volume outlined, or differences in the quantitative MR parameters obtained.
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Materials and methods
Patients
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MR Imaging
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Image Processing
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Histopathology Acquisition and Analysis
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Lesion Localization
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Comparison Analysis
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Results
Study Population
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Comparative Analysis between Pathologic Approaches
Index Lesion Localization
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Tumor Volume Assessment
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Table 1
Tumor Volume Estimates From the Individual MRI Sequences Using SPR and WMP Correlative Approaches (MRTV SPR and MRTV WMP , Respectively) and Their Differences Versus HTV
mpMRI Parameter Mean (SD) MRTV SPR , mm 3 Mean (SD) Difference between HTV and MRTV SPR , mm 3 Mean (SD) MRTV WMP , mm 3 Mean (SD) Difference between HTV and MRTV WMP , mm 3 T2WI 1073 (1022)* 919 (745) 1376 (1176) 626 (1229) DCE 1314 (974) 678 (1021) 1711 (1303) 280 (940) ADC 790 (950)* 1202 (794) 931 (1036)* 1061 (730)
ADC, apparent diffusion coefficient; DCE, dynamic contrast enhanced; HTV, histology index tumor volume; mpMRI, multiparametric magnetic resonance imaging; MRI, magnetic resonance imaging; MRTV, magnetic resonance tumor volumes; SD, standard deviation; SPR, surgical pathology report; T2WI, T2-weighted imaging; WMP, whole mount pathology.
MRI-based measurements that were significantly smaller ( P < .005) than HTV based on three-way pairwise comparison between the SPR, WMP, and HTV measurements are marked with asterisk.
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Comparison of Quantitative Multiparametric Parameters between Tumor and Nontumor ROIs
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Table 2
Mean Quantitative Parameters Extracted From the Tumor and Normal ROI Delineated Using WMP and SPR Approaches
mpMRI Parameter SPR, Tumor SPR, Normal WMP, Tumor WMP, Normal K trans , min −1 0.4 (0.17) 0.19 (0.1) 0.37 (0.13) 0.18 (0.09) v e 0.26 (0.07) 0.2 (0.1) 0.26 (0.08) 0.2 (0.05) ADC b500, × 10 −6 mm 2 /s 978 (200) 1714 (237) 1018 (181) 1542 (160)
ADC, apparent diffusion coefficient; mpMRI, multiparametric magnetic resonance imaging; ROI, region of interest; SPR, surgical pathology report; WMP, whole mount pathology.
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Discussion
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Table 3
Summary of the Advantages and Disadvantages between the WMP and SPR-based Pathology to Imaging Correlation Methods
Imaging to Pathology Correlation Approach Advantages Disadvantages Whole mount processing (WMP)
Surgical pathology report (SPR)
SPR, surgical pathology report; WMP, whole mount pathology.
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Acknowledgments
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