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Multicenter Study
. 2025 Oct;35(10):6171-6182.
doi: 10.1007/s00330-025-11547-8. Epub 2025 Apr 7.

Diffusion levels for quantitative assessment of the apparent diffusion coefficient value in prostate MRI: a proof-of-concept bicentric study

Rossano Girometti  1   2 , Valeria Peruzzi  3 , Paola Clauser  4 , Nina Pötsch  4 , Maria De Martino  5 , Miriam Isola  5 , Gianluca Giannarini  6 , Alessandro Crestani  6   7 , Chiara Zuiani  3   8 , Lorenzo Cereser  3   8 , Pascal At Baltzer  4
Affiliations
Multicenter Study

Diffusion levels for quantitative assessment of the apparent diffusion coefficient value in prostate MRI: a proof-of-concept bicentric study

Rossano Girometti et al. Eur Radiol. 2025 Oct.

Abstract

Objectives: To investigate the performance of Diffusion levels (DLs) in diagnosing clinically significant prostate cancer (csPCa) when combined with the PI-RADS version 2.1.

Materials and methods: This retrospective, bicentric study included 261 men who underwent 3.0-T prostate MRI between March 2020 and April 2023, receiving systematic and target prostate biopsy on PI-RADS ≥ 3 lesions. Two readers measured the Apparent diffusion coefficient (ADC) of PI-RADS 1-5 findings in the peripheral zone. By plotting the cumulative frequency of csPCa versus ADCs and using ROC analysis, we derived four DLs expressing levels of restricted diffusion, i.e., very low DL (VL-DL), low DL (L-DL), intermediate DL (I-DL), and high DL (H-DL). We compared the per-lesion diagnostic performance in assessing csPCa (grading group ≥ 2 cancer) assuming to biopsy PI-RADS ≥ 3 lesions (strategy 1), PI-RADS ≥ 3 lesions adjusted with ADC values (strategy 2-4), and PI-RADS ≥ 3 lesions adjusted with DLs (strategy 5-7). Net benefit was assessed with decision curve analysis.

Results: csPCa was found in 79/261 men (30.3%) and 152/528 lesions (28.8%). There was a negative correlation (p < 0.0001) between ADC versus malignancy rate (tau -0.970) and DLs versus csPCa grading group (tau -0.614). csPCa prevalence was highest in VL-DL (72.2%) and L-DL (54.4%). Most DLs-based strategies increased specificity, positive predictive value (PPV), and net benefit compared to ADC-based strategies or PI-RADS alone. The best strategy showed 94.7% sensitivity, 82.9% specificity, 69.2% PPV, and 97.5% negative predictive value.

Conclusion: While larger-scale validation is needed, DLs have the potential to improve PI-RADS-based biopsy decisions for detecting csPCa in the peripheral zone.

Key points: Question It is still unclear how to incorporate quantitative information from diffusion-weighted imaging (DWI) into prostate MRI. Findings Combining DWI-derived diffusion levels (DLs) with the PI-RADS version 2.1 categorization reduced false positives while preserving high sensitivity for clinically significant prostate cancer. Clinical relevance DLs permit to easily account for ADC values of prostate lesions and, in turn, refine biopsy decisions.

Keywords: Biopsy; Diffusion magnetic resonance imaging; Magnetic resonance imaging; Prostatic neoplasms.

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Conflict of interest statement

Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Rossano Girometti. Conflict of interest: R.G. is a Deputy Editor of European Radiology, and P.C. is a member of the Scientific Editorial Board of this journal. They have not participated in the selection nor review processes for this article. The remaining authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: Two of the authors (Maria De Martino and Miriam Isola) are biostatisticians. Informed consent: Written informed consent was waived by the Institutional Review Board because of the retrospective design. Ethical approval: The study has been approved by the Institutional Review Board (IRB) of the Department of Medicine (DMED) of the University of Udine, with the approval number RIF. Prot. IRB: 263/2023. Study subjects or cohorts overlap: The study population partially overlaps with previous publications without a focus on Diffusion-weighted imaging: (1) Girometti et al [32]. That study included biopsy-naïve patients only and focused on different PSA-density levels to predict true positivity of prostate target biopsy. (2) Girometti et al [19]. In this study, we assessed which clinical and imaging variables predict the risk of false positivity of target biopsy. (3) Girometti et al [33]. In this study, we aimed to assess the impact on biopsy decisions of the Likert score in selectively refining the PI-RADS version 2.1 categorization. Methodology: Retrospective Cross-sectional observational study Performed at two different institutions

Figures

Fig. 1
Fig. 1
Study flowchart. No men were excluded because of the absence of measurable findings in Center 2. BPH benign prostatic hyperplasia, bpMRI biparametric magnetic resonance imaging, mpMRI multiparametric magnetic resonance imaging, PZ peripheral zone, TURP Transurethral resection of the prostate
Fig. 2
Fig. 2
Biopsy decisions based on PI-RADS version 2.1 alone (strategy 1), PI-RADS version 2.1 adjusted with an absolute apparent diffusion coefficient (ADC) cutoff of 1.0 × 10−3 mm2/s (strategy 2 to 4), and PI-RADS version 2.1 adjusted with the Diffusion Levels (DLs)
Fig. 3
Fig. 3
Cumulative malignancy rates (y-axis) plotted against apparent diffusion coefficient (ADC) values (x-axis). Dots on the curve represent each single prostate lesion. The malignancy rate values corresponding to each diffusion level were ≤ 2.4% for the high level, 2.8–13.6% for the intermediate level, 13.6–22.9% for the low level, and 23.1–57.4% for the very low level
Fig. 4
Fig. 4
Results of the decision curve analysis plotting the net benefit of performing prostate biopsy against the probability of having clinically significant prostate cancer according to seven different biopsy strategies (see Fig. 2 for details)
Fig. 5
Fig. 5
A 56-year-old man showing a prostate-specific antigen level of 21.2 ng/mL and a PI-RADS 5 lesion in the right postero-lateral zone of the mid-gland, corresponding to a grading group 3 cancer. The lesion showed marked hyperintensity on b = 2000 s/mm2 b-value image (a), marked hypointensity on the ADC map (b), hypointensity on T2-weighted imaging (c), and intense early focal contrast enhancement (d). In accordance with the criteria explained in the “Materials and methods,” the region of interest was placed on the darkest region of the lesion on the ADC map (zoom of the lesion in e), measuring an apparent diffusion coefficient value of 0.65 × 10−3 mm2/s, corresponding to a very low diffusion level
Fig. 6
Fig. 6
A 60-year-old man showing a PSA level of 4.45 ng/mL. PI-RADS 3 upgraded to 4 category was attributed to a lesion in the right mid-gland posterior-lateral peripheral zone showing marked hyperintensity on the high b-value image (arrow in a), mild hypointensity on the ADC map (b), mild hypointensity on T2-weighted imaging (c) and focal early contrast enhancement (arrow in d). Target biopsy cores included high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation, and chronic inflammation. Biopsy strategy 7 would have avoided biopsy as the lesion showed an ADC value of 1.11 × 10−3 mm2/s, corresponding to a high diffusion level (H-DL)
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References

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