Advanced Diffusion Magnetic reSonance Prostate Imaging for Reducing Extraneous Biopsies (ASPIRE) - Calibration Component (Multi-centre Scanner Calibration) and Validation Component (Multi-centre Validation) (ASPIRE MS)

In 2019 the UK National Institute for Health and Care Excellence (NICE) updated its guidelines to recommend Magnetic Resonance Imaging (MRI) for all patients prior to biopsy as it permits the targeted sampling of suspicious lesions rather than blind systematic biopsy, thereby improving detection of clinically significant prostate cancer while avoiding some unnecessary biopsies.

However, there is still the major clinical problem of patients who have an 'MRI suspicious' lesion ultimately having no clinically significant cancer on biopsy. It was calculated that even by using MRI, up to 50% of prostate biopsies may be unnecessary. Prostate biopsies carry many risks and burdens for patients so reducing unnecessary biopsies is therefore a critical unmet need in prostate cancer diagnostics.

The ASPIRE study has been designed to enable the safe implementation of advanced diffusion MRI into the prostate cancer diagnostic pathway.

This study will compare 3 different advanced diffusion MRI sequences, Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours (VERDICT), fast-VERDICT or Restriction Spectrum Imaging (RSI) to discover which one is superior in identifying patients who can safely avoid a biopsy.

The study is also separated into 3 distinct components. Firstly, there is an optional component which, once these advanced diffusion sequences have been programmed onto MRI scanners, will recruit local volunteers who were already planning to have to routine MRI as a quality assurance measure.

Component 1 (Calibration) is concerned with calibrating the same participants scans over more than one site to enable direct comparison of measurements. Patients under active follow up or previously diagnosed cancer should be enrolled in this component.

Component 2 (Validation) sees a participant receiving a standard MRI scan as well as the new advanced diffusion sequences to evaluate the new tests against the reference standard without altering the standard-of-care management.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer (Diagnosis)
• Intervention / Treatment: Procedure: MRI

Detailed Description

Overview: ASPIRE constitutes three components:

• Scanner Set-up Component (optional), at all sites (except University College London Hospitals NHS Foundation Trust (UCLH)),
• Multi-centre Calibration Component and
• Multi-centre Diagnostic Accuracy Validation Component Scanner Set-up Component (optional): A multi-centre optional optimisation study conducted across multiple National Health Service (NHS) hospital sites, apart from UCLH, once the advanced MRI sequences (VERDICT, fast VERDICT, and RSI) have been installed or programmed on each scanner by a dedicated research engineering team. Sequence parameters (such as b-value distributions, diffusion times, and echo times) will be standardised as much as possible across platforms, recognising that some vendor-specific adjustments may be required. This component includes a very small, optional cohort of local volunteer patients who are already undergoing a planned, routine MRI scan. Scans in this component are planning to be used as a quality assurance measure once these advanced sequences are installed ahead of the calibration cohort.

This Optional Scanner Set Up Component is not powered to test a clinical hypothesis; instead, its endpoint is the successful implementation of protocols and generation of reliable imaging at each site. As a process measure, success will be declared if the advanced sequences are operational on all scanners with adequate image quality. Men will be referred to this component based on a clinical suspicion of prostate cancer. Patients can expect 1 standard MRI scan plus all additional study sequences. The standard MRI scan can be either a bi-parametric or multiparametric MRI scan depending on the availability of the site where the scan is being performed. Patients will complete this MRI and exit the study with no follow up planned for this component.

Multi-centre Calibration Component: A technical feasibility assessment study involving NHS hospital sites equipped with 3 Tesla MRI scanners from each major MRI vendor (Philips, Siemens, GE) with potential for additional sites to represent duplicates from vendors, covering platform variations. The participating site selection captures the vendor diversity likely to be encountered in a larger trial. At each site, the VERDICT, fast VERDICT, and RSI MRI sequences will be installed and tested. This component involves a small travelling volunteer cohort design of patients who will undergo the advanced diffusion research MRI scan on two different scanners within a short timeframe. By scanning the same individuals at different sites, within a small timeframe, we are enabling direct comparison of measurements and direct calibration of the quantitative parameters can be performed. This component seeks primarily to develop methods (proof-of-concept) and is not designed to evaluate clinical outcomes.

The primary data collected in the Calibration Component are the imaging metrics (e.g., VERDICT Fractional intracellular volume (fIC) values) from each scanner for each subject. These will be analysed to derive transformation formulas that map values from one scanner to an equivalent value on another, effectively creating a calibration curve for each scanner/vendor combination. This component will also record practical aspects such as the success rate of sequence deployment, any scanner-specific issues, and qualitative image quality assessments at each site.

The Calibration Component is not powered to test a clinical hypothesis; instead, its endpoint is the successful implementation of protocols and generation of calibration equations. As a process measure, success will be declared if the advanced sequences are operational on all scanners with adequate image quality, and if the analysis of the travelling volunteer data shows a consistent relationship (correlation) between scanners. For example, preliminary data already suggest that VERDICT fIC values on a Siemens scanner are systematically lower than on a Philips scanner, but with a linear mapping that could adjust one to the other. This component will formally validate this across more subjects and across all vendor pairs.

Men will be identified based on whether they are in current active surveillance for previously diagnosed low-risk prostate cancer or awaiting definitive treatment for clinical suspicion of prostate cancer. Patients will be informed that travel as a part of this component is mandatory and should not provide full informed consent if travel is not possible for them. Participants in this cohort will have 2 scans at 2 different major vendors, one will occur at UCLH and the other at a secondary site within 2 months of the first scan. As soon as the secondary scan is completed, their participation ceases and will resume standard of care treatment.

Multi-centre Diagnostic Accuracy Validation Component: A multi-site diagnostic accuracy study with embedded technical comparison of patients undergoing initial evaluation for suspected prostate cancer at four external NHS sites to assess and compare the diagnostic performance of VERDICT, fast VERDICT, and RSI (additional research sequences) when added to standard MRI as per normal clinical protocol) in the same session. Following SoC imaging, all patients will proceed to the normal diagnostic pathway: those with MRI findings warranting biopsy (typically Prostate Imaging - Reporting and Data System (PI-RADS) or Likert score ≥3) will undergo a targeted biopsy of the identified lesion(s) and any appropriate systematic sampling as per local standard. Patients with negative MRI (score 1-2, indicating low suspicion) generally do not undergo immediate biopsy as part of standard care; these patients will be managed according to standard local practice (which may involve clinical observation and repeat Prostate-Specific Antigen (PSA) or MRI at a later date). Importantly, the results of the advanced diffusion MRI sequences will not be used to direct patient management in the Validation Component.

For the patients who undergo a biopsy, as directed by the clinical findings of their MRI scan, while the results of the biopsy will be blinded, we will know the lesions that were identified on MRI that underwent the biopsy. Using this location information, we will draw the lesion onto the VERDICT, fast-VERDICT, RSI maps to determine the diagnostic accuracy of the MRI with the additional advanced diffusion imaging (each of the three techniques independently), allowing comparison of diagnostic accuracy within the same individuals, which is referred to as a paired within subject design. Each patients MRI will be interpreted both with and without the retrospective advanced diffusion metrics. This design allows evaluation of the new tests against the reference standard without altering the standard-of-care management. It is ethically appropriate because it avoids withholding recommended biopsies or performing unnecessary ones purely for research purposes. There is no randomisation; every participant receives all imaging tests under evaluation. The interpretation of the advanced diffusion MRI results, however, will be retrospective and not influence immediate clinical management, to avoid introducing any experimental risk.

All components are prospective in that participants are enrolled going forward with data collected in real-time. The protocol will be implemented concurrently at multiple centres, leveraging each site's clinical workflow for prostate MRI and biopsy. The Calibration Component will begin concurrently to the Validation Component, and the calibration results will inform the analysis of the validation data.

After all imaging and biopsy procedures, an independent evaluation of the MRI data will be conducted at the sites as per standard-of-care. The MRI for each patient will be interpreted in two ways: (a) using standard MRI alone (using PI-RADS v2.1 or local Likert scoring for suspicion), and (b) using MRI plus each advanced method (e.g., MRI+VERDICT). For the combined interpretation, predefined criteria will be used such as: "Consider an MRI-suspicious lesion as benign (no biopsy needed) if VERDICT fIC is below threshold X" - where X may be a site-calibrated threshold corresponding to ~90% sensitivity for cancer detection. By comparing these interpretations to the biopsy-confirmed outcomes, diagnostic performance characteristics for each approach can be calculated. The primary analysis will focus on specificity (proportion of patients without significant cancer who are correctly identified as such and spared biopsy) and sensitivity (proportion of patients with significant cancer correctly identified) of the new pathway versus standard care.

All Validation Component sites will follow a common master protocol for imaging and data collection to ensure consistency. The study is not randomized; every participant effectively serves as their own control for comparing tests. The Validation Component is designed in accordance with STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines, including clearly defined index tests and reference standards, blinded interpretation, and paired analysis.

• Study Type: Interventional
• Enrollment (Estimated): 660
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shonit Punwani, FRCR/MRCPUK/MBBS/PhD/BSc; Phone Number: 0207 679 5033; Email: s.punwani@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • University College London Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged ≥18 scheduled for a prostate mpMRI (Optional Component)
• Willing and able to provide written informed consent (Optional Component, Component 1 and Component 2)
• Patients aged ≥18 with a prior mpMRI demonstrating at least one definite lesion suspicious for prostate cancer (Likert or PI-RADS score 4 or 5) and either under active surveillance for previously diagnosed low-risk prostate cancer or awaiting definitive treatment (Component 1)
• Willing and able to undergo multiple MRI scans at different hospitals (Component 1)
• Patients aged ≥18 with clinical suspicion of prostate cancer, who are scheduled for or have just undergone a prostate mpMRI as part of initial diagnostic workup (Component 2)

Exclusion Criteria:

• Contraindications to MRI (Optional Component, Component 1 and Component 2)
• Inability to provide informed consent (Optional Component, Component 1 and Component 2)
• Prostate biopsy within the last 3 months (Component 1) OR prior prostate cancer diagnosis or treatment (Component 2)
• Inability to travel to partner hospital site (Component 1)
• Contraindication to biopsy (Component 2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Optional Scanner Set-Up Component; Local Volunteers who were already scheduled for a routine mpMRI who agree to having the advanced diffusion sequences added as a research scan to their planned MRI scan. The research scan will not be used to influence clinical decisions and just to see if the new advanced diffusion sequences are optimised	Procedure: MRI; The combination of the 3 additional sequences as a part of the research scan will distinguish this intervention from other studies.; Other Names: MRI + VERDICT, fast-VERDICT and RSI scan
Other: Component 1 (Calibration); Travelling volunteer study design of patients with confirmed prostate cancer who will agree to have one mpMRI with the added advanced diffusion sequences research scan at their home site of UCLH and then one more mpMRI with the added advanced diffusion sequences research scan at one of four external NHS hospital sites. These research scans will not be used to influence clinical decisions for the participant but will be used to calibrate the new sequences across different scanners at different sites.	Procedure: MRI; The combination of the 3 additional sequences as a part of the research scan will distinguish this intervention from other studies.; Other Names: MRI + VERDICT, fast-VERDICT and RSI scan
Active Comparator: Component 2 (Validation); A prospective cohort study at four external sites for participants with suspected prostate cancer to assess and compare the diagnostic performance of VERDICT, fast VERDICT, and RSI when added to standard mpMRI. The results of the advanced diffusion MRI sequences will not be used to direct patient management in the Validation Component. Radiologists and urologists will remain blinded to the VERDICT/RSI findings when making biopsy decisions, to ensure the study does not influence or compromise care.	Procedure: MRI; The combination of the 3 additional sequences as a part of the research scan will distinguish this intervention from other studies.; Other Names: MRI + VERDICT, fast-VERDICT and RSI scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calibration Component Analysis: The goal is to characterise differences in quantitative MRI metrics between scanners and derive calibration adjustments. For each pair of scanners (e.g., Philips vs Siemens), a scatter plot of VERDICT fIC values (or other	Calibration Component Analysis: The goal is to characterise differences in quantitative MRI metrics between scanners and derive calibration adjustments. For each pair of scanners (e.g., Philips vs Siemens), a scatter plot of VERDICT fIC values (or other metric) will be examined across all subjects who were scanned on both. We will calculate the mean difference and 95% limits of agreement (Bland-Altman analysis) to quantify bias and variability. A linear regression will be performed, and the regression equation (slope, intercept) will be used as the calibration formula. If needed, higher-order terms or non-linear fit will be considered, but simplicity is preferred. We will also assess the repeatability of measurements on the same scanner (some participants may have had repeat scans on the same machine or two Philips sites, etc.). The outcome of Calibration Component will be reported descriptively. No formal hypothesis test is applicable, but we will note if the inter-scanner difference	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Direct comparison between VERDICT, fast VERDICT, and RSI	For each patient, we will have three outcomes (for each advanced method combined with MRI). We will compare, for example, MRI+VERDICT vs MRI+RSI specificity by looking at the subset of patients who have discordant results (one test positive, the other negative, and no cancer or cancer accordingly) using McNemar's test. We will do this pairwise for all combinations (VERDICT vs RSI, VERDICT vs fast VERDICT, RSI vs fast VERDICT). Additionally, we may compare AUC (area under the ROC curve) for the continuous metrics from each technique. The ROC curves will be generated for VERDICT fIC, RSI index, etc., against the outcome, possibly stratified by site or vendor. An averaged (pooled data) ROC comparison will indicate overall performance differences	5 years
Comparison of calibrated vs uncalibrated threshold performance	This will involve looking at the sensitivity and specificity of, for example, a uniform fIC threshold of 0.41 across all sites vs using each site's calibrated equivalent threshold (e.g. 0.35 on Siemens, etc.). We will report whether calibration improved the alignment of results. A paired comparison of these two approaches in the same dataset will be conducted (each patient can be classified by both methods). We hypothesize calibration will modestly improve specificity or consistency across sites, but this needs confirmation.	5 years
Subgroup analyses	We will examine performance by site and by scanner vendor. For each site individually, we will replicate the primary analysis to see if VERDICT added benefit at that site (these are the "individually powered" validations - each site with ~150 patients should be powered ~80% to see a similar effect size). This will tell us if any site deviates significantly. We will also aggregate data by vendor (e.g., combine both Siemens sites' data) to see if, say, all Siemens scanners behave similarly vs others. If needed, statistical models like logistic regression with site or vendor as random effects could be used to formally test for heterogeneity, but with a minimum of four sites it may be simpler to descriptively report these results.	5 years
Negative MRI cohort	Although patients with a negative MRI likely won't have biopsy verification, we will track any who had follow-up MRIs or biopsies. We will calculate the observed outcome at 1 year: how many were found to have cancer later. This is not comparative, but it gives an estimate of false negatives for both standard and advanced MRI (since an advanced MRI might conceivably pick up something in an MRI-negative case; we will see if any such case occurred and what their follow-up showed).	5 years

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: University College London Hospitals; Cambridge University Hospitals NHS Foundation Trust; Royal Free Hospital NHS Foundation Trust; University Hospital Southampton NHS Foundation Trust; Imperial College Healthcare NHS Trust
• Investigators: Principal Investigator: Shonit Punwani, s.punwani@ucl.ac.uk, UCL

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: August 12, 2026
• First Submitted That Met QC Criteria: September 1, 2026
• First Posted (Actual): September 9, 2026

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: prostate cancer; diagnostic; RSI; ASPIRE; Diffusion-weighted imaging; VERDICT; fast-VERDICT; Fractional intracellular volume; Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours; no biopsy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Pathological Conditions, Signs and Symptoms; Prostatic Neoplasms; Disease; Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: 348487; MA-TIA24-006 (Other Grant/Funding Number: Prostate Cancer UK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised data will be available at request for bona fide researchers with important research questions subject to approval by the study steering committee.
• IPD Sharing Time Frame: Data will become available 1 year after publication of the main study results.
• IPD Sharing Access Criteria: A study steering committee will review all requests for access to the data and will make decisions on whether or not to grant access to bona fide researchers based on the importance of the research question being asked, ensuring analysis is non overlapping with existing analyses and planned analyses.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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