MR Microstructural Imaging for Prostate Cancer Diagnosis

Development of MR Microstructural Imaging Markers for Prostate Cancer Diagnosis and Investigation of the Associated Molecular Mechanisms

The goal of this multi-center clinical study is to evaluate whether time-dependent diffusion MRI (TDDMRI) can provide reliable microstructural imaging markers for the diagnosis of prostate cancer. The main questions this study aims to answer are:

• Do TDDMRI-derived microstructural parameters (such as cell size and density) improve diagnostic accuracy for prostate cancer compared with conventional MRI?
• How well do the microstructural parameters correlate with whole-slide pathology findings?
• Can the investigators determine diagnostic models combining multiple features for presurgical diagnosis across multiple centers?

Participants with suspected prostate cancer will undergo 3T MRI including TDDMRI. Microstructural parameters will be quantified and compared with standard multiparametric MRI. All participants will also receive prostate biopsy or prostatectomy, and imaging findings will be validated against histopathology.

This study will:

• Collect TDDMRI and conventional MRI data from six hospitals.
• Derive and validate imaging markers of prostate cancer based on microstructural parameters.
• Compare diagnostic performance across centers and against pathology as the reference standard.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Diffusion MRI
• Intervention / Treatment: Diagnostic test: MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy)

Detailed Description

Prostate cancer is one of the most common malignancies among men worldwide, and accurate diagnosis is crucial for treatment planning and outcome prediction. Conventional multiparametric MRI (mpMRI) has become an important tool in prostate cancer (PCa) diagnosis; however, its diagnostic performance remains suboptimal, e.g., for differentiating clinically significant from insignificant disease. Time-dependent diffusion MRI (TDDMRI) is an advanced technique that probes water diffusion over different diffusion times, thereby providing sensitivity to tissue microstructural features such as cell size, cellularity, and transmembrane water exchange. These parameters may serve as novel imaging biomarkers for PCa and could improve diagnostic accuracy beyond what is currently achievable with standard MRI techniques.

This is a multi-center diagnostic cohort study with prospective enrollment of suspected PCa participants, along with pathology data. The study is designed to evaluate the clinical utility of TDDMRI for PCa detection, with a focus on developing and validating MR microstructural imaging markers and establish a robust diagnostic model that is generalizable to most clinical settings.

Study Procedures Participants with clinical suspicion of prostate cancer will undergo standardized MRI examinations that include both conventional mpMRI and TDDMRI sequences. Imaging protocols will be harmonized across participating centers to ensure reproducibility of microstructural parameter estimation. Quantitative markers such as cellularity, cell size, and diffusivity metrics will be derived from TDDMRI data.

Histopathological confirmation through prostate biopsy or prostatectomy will be obtained in a subset of participants who provide informed consent. For these cases, imaging-derived microstructural parameters will be directly compared with histological measures. For participants without available pathology, imaging data will still be retained and analyzed for exploratory purposes and for cross-center reproducibility assessments.

Quality Assurance and Data Management

To guarantee data integrity and cross-site consistency, a centralized data management platform will be implemented. Key measures include:

• Predefined imaging protocols and on-site training to minimize variability across centers.
• Automated and manual data validation checks for completeness, range, and logical consistency.
• Periodic source data verification against original imaging files and pathology reports.
• Maintenance of a data dictionary with standardized definitions for all imaging and clinical variables.
• Regular quality control audits and feedback loops to ensure adherence to protocol.

Statistical and Analytical Plan The primary analysis will assess the diagnostic performance of TDDMRI-derived microstructural parameters, with histopathology as the gold standard. Diagnostic metrics including sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) will be calculated and directly compared with routine mpMRI metrics and PI-RADS scores.

Secondary analyses will evaluate:

• The correlation between TDDMRI biomarkers and Gleason score or tumor cellularity.
• Cross-center reproducibility and robustness of derived biomarkers.
• Subgroup analyses by tumor location, stage, and patient characteristics.
• Exploratory development of diagnostic thresholds or decision rules based on microstructural parameters.

Sample Size and Missing Data The study is planned as a six-center collaborative effort, with an expected 2000 participants. This target sample size accounts for inter-center variability and allows for ~10-15% attrition or unusable imaging. The final dataset is anticipated to include approximately 40% participants with prostate cancer and 60% without, enabling precise estimation of sensitivity and specificity with narrow confidence intervals.

Missing data will be handled according to predefined rules. Incomplete or degraded imaging datasets will be documented and, where possible, analyzed using available sequences.

Overall Aim The overall aim of this study is to validate TDDMRI as a clinically applicable imaging tool and to establish reproducible microstructural imaging markers that can inform prostate cancer diagnosis across diverse clinical settings. By integrating multi-center imaging data with large-scale histopathological validation, this study seeks to advance precision imaging in prostate cancer and provide evidence for the adoption of TDDMRI in routine clinical practice.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Dan Wu, PhD; Phone Number: +86 571 87951385; Email: danwu.bme@zju.edu.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Hospital
      • Contact: Chunmei Li; Phone Number: 86-15811011208; Email: bee9020@126.com
  • Henan
    • Zhengzhou, Henan, China
      • Completed
      • Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital)
      • Contact: Yudong Zhang, PhD; Phone Number: +86 25 83714511
  • Liaoning
    • Dalian, Liaoning, China
      • Recruiting
      • The First Affiliated Hospital of Dalian Medical University
      • Contact: Ailian Liu, PhD; Phone Number: +86 411 83635963; Email: cjr.liuailian@vip.163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Xiangyi Zheng, PhD; Phone Number: +86 571 87236832; Email: zheng_xy@zju.edu.cn
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Hospital
      • Contact: Jianjun Zhang; Phone Number: 86+13735882084; Email: jzhang20@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Men with clinical suspicion of prostate cancer will be recruited from six participating hospitals. Clinical suspicion may be based on elevated prostate-specific antigen (PSA) levels, abnormal digital rectal examination, or other clinical findings. All participants will undergo prostate MRI including TDDMRI. Histopathological confirmation through biopsy or prostatectomy will be obtained in a subset of participants who consent to tissue sampling. The study population will therefore include both histopathology-positive and -negative cases, enabling evaluation of diagnostic performance and development of imaging-based diagnostic criteria.

Description

Inclusion Criteria:

• Clinical suspicion of prostate cancer (elevated PSA, abnormal digital rectal examination, or other clinical indication).
• Undergoing prostate MRI including TDDMRI as part of diagnostic evaluation. Able and willing to provide written informed consent.

Exclusion Criteria:

• Contraindications to MRI (e.g., pacemaker, ferromagnetic implants, severe claustrophobia).
• Prior treatment for prostate cancer (surgery, radiation, hormonal therapy, chemotherapy).
• Severe comorbid conditions precluding MRI or biopsy.
• Inability to provide informed consent.
• Poor image quality due to motion or technical artifacts (assessed at imaging QC).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Prostate Cancer Suspected Cohort; Men with clinical suspicion of prostate cancer who undergo standardized MRI including time-dependent diffusion MRI (TDDMRI). Histopathological confirmation (biopsy or prostatectomy) will be obtained in a subset of participants who provide consent. Diagnostic accuracy of TDDMRI-derived microstructural markers will be evaluated against pathology when available. Participants without pathology will still contribute imaging data for exploratory analyses.

Diagnostic test: MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy); The investigators will compare the diagnostic power of the proposed time-dependent diffusion MRI technique with conventional multiparameter MRI for prostate diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Accuracy of TDDMRI for Clinically Significant Prostate Cancer (csPCa)	Area under the receiver operating characteristic curve (AUC, range 0-1; higher values indicate better diagnostic performance) for TDDMRI-derived microstructural parameters to detect csPCa (reference standard: histopathology; Gleason score ≥7).	Within 3 months after MRI and pathology confirmation.
Development of Imaging-Based Diagnostic Criteria	Establishment of threshold values or decision rules for TDDMRI-derived microstructural parameters (e.g., cellularity, cell size index, diffusivity) to differentiate malignant from benign prostate tissue. Diagnostic cutoffs will be derived by ROC analyses and validated against histopathology.	Within 3 months (at completion of enrollment and pathology confirmation).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cross-Center Reproducibility	Agreement of TDDMRI-derived parameters across participating centers, assessed by intraclass correlation coefficient (ICC; range 0-1, higher indicates better reproducibility).	After completion of enrollment across all centers (up to 24 months).
Sensitivity and Specificity of TDDMRI	Sensitivity and specificity (0-100%; higher indicates better diagnostic performance) of TDDMRI-derived microstructural parameters in identifying clinically significant prostate cancer.	Within 3 months after MRI and pathology confirmation.
Comparison with Conventional mpMRI	Difference in diagnostic performance (AUC, sensitivity, specificity) between TDDMRI parameters and conventional mpMRI measures : apparent diffusion coefficient (ADC) and Prostate Imaging-Reporting and Data System, version 2.1 (PI-RADS v2.1; score 1-5, higher indicates a higher likelihood of csPCa).	Within 3 months after MRI and pathology confirmation.
Correlation with Gleason Score	Correlation between TDDMRI microstructural parameters (e.g., cellularity, cell size index) and Gleason score from pathology, using Spearman's ρ (range -1 to 1; larger magnitude indicates stronger monotonic association), with 95% confidence intervals.	Within 3 months after MRI scan

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Henan Cancer Hospital; Beijing Hospital; Zhejiang University; The First Affiliated Hospital of Dalian Medical University; Jiangsu Provincial People's Hospital; Zhejiang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: September 1, 2025
• First Submitted That Met QC Criteria: November 22, 2025
• First Posted (Actual): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 22, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Prostate Cancer; Diagnostic Accuracy; Time-dependent Diffusion MRI (TDDMRI); Multi-center Study
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Image Interpretation, Computer-Assisted; Image Enhancement; Photography; Tomography, Emission-Computed; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Magnetic Resonance Imaging; Positron-Emission Tomography
• Other Study ID Numbers: [2025B] IIT.No. 0321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The investigators will share the study protocol after its publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No