Multiparametric Lung MRI With Diffusion-Weighted Imaging in Lung-RADS 4 Lesion Characterization

August 17, 2026 updated by: University of Florida

Multiparametric Lung MRI With Diffusion-Weighted Imaging in Lung-RADS 4 Lesion Characterization: A Single-Center Prospective Diagnostic Accuracy Study

This study evaluates whether multiparametric chest magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI), performed without any contrast material, can distinguish malignant from benign lung lesions that were assigned Lung-RADS category 4 on a standard-of-care lung cancer screening low-dose CT.

Participants who have a Lung-RADS 4 lesion on screening CT undergo one non-contrast research MRI of the chest at 3.0 Tesla. The MRI is added to standard care; no standard-of-care imaging, biopsy, or treatment is withheld or replaced, and the research MRI is not used for clinical decision making. Participants then continue routine clinical management, and the final nature of the lesion is established from pathology or microbiology when tissue is obtained, or otherwise from at least 24 months of clinical and imaging follow-up.

The primary measure is the sensitivity and specificity of multiparametric MRI against that final diagnosis. Secondary measures include whether DWI alone performs as well as the full MRI protocol, how MRI compares with PET/CT in participants who had PET/CT as part of their care, and quantitative MRI thresholds (apparent diffusion coefficient, lesion-to-spinal-cord signal intensity ratio, native T1 and T2).

This is an exploratory pilot and feasibility study. No formal power calculation was performed; the sample size is intended to support feasibility assessment, protocol optimization, and preliminary estimates of diagnostic performance.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

OBJECTIVES

Aim 1. Determine the sensitivity and specificity of multiparametric chest MRI with DWI in differentiating malignant from benign Lung-RADS 4 lesions.

Aim 2. Determine whether DWI alone is as effective as the full chest protocol in malignancy classification of Lung-RADS 4 lesions.

Aim 3. Compare the diagnostic performance of chest MRI to PET/CT in the characterization of Lung-RADS 4 lesions.

DESIGN

Single-center prospective observational cohort study of diagnostic accuracy at the University of Florida. Participants identified from the institutional lung cancer screening program with a Lung-RADS 4 (4A, 4B, 4X) finding on standard-of-care low-dose CT undergo one non-contrast research chest MRI. There is no randomization and no comparator group; the comparator is the reference standard (final clinical diagnosis) and, for Aim 3, the participant's standard-of-care PET/CT where performed.

INDEX TEST

All examinations are performed on a 3.0 Tesla scanner (GE Healthcare or Siemens Healthineers) with a vendor-specific surface coil; an interlocking neck coil may be added to the torso coil for apical lesions. No intravenous or other contrast material is administered. Sequences comprise axial breath-hold 2D in- and opposed-phase gradient echo T1-weighted imaging; axial breath-hold and/or respiratory-triggered DWI using multi-shot fat-suppressed echo-planar imaging with two b values; DWI sequences with restricted z-axis coverage centered on the nodule (EPI-DWI, FOCUS/ZOOMit-EPI, MUSE/RESOLVE); and axial respiratory-triggered T2-weighted imaging with fat suppression or Dixon. Ultra-short echo time imaging and T1/T2 mapping centered on the nodule may be added if time allows. Pulse-sequence parameters are optimized to the vendor platform during a pre-clinical optimization phase and after the first participants are scanned.

IMAGE ANALYSIS

Anonymized MRI examinations are read independently by two cardiothoracic radiologists with more than 5 years of MRI experience. Readers have the companion low-dose CT but are blinded to clinical data and to any additional imaging. Reading proceeds in two rounds: DWI alone in conjunction with the LDCT (Aim 2), then the full set of sequences (Aim 1). Each examination is classified as (1) negative / low suspicion for malignancy, (2) indeterminate, would benefit from short-term follow-up, or (3) positive / high suspicion for malignancy. Quantitative measures are the apparent diffusion coefficient from a circular or elliptical ROI over the lowest-signal component of the nodule, and the nodule-to-spinal-cord signal intensity ratio measured at the same level.

REFERENCE STANDARD

The final etiology of the lesion is determined by histopathological and/or microbiological data when available, or otherwise by imaging and clinical follow-up for at least 24 months. A lesion that disappears or decreases in size on follow-up is deemed benign; a lesion that remains stable for at least 24 months is deemed benign.

STATISTICAL ANALYSIS

Sensitivity and specificity of chest MRI and of DW-MRI alone are reported with 95% confidence intervals, computed both excluding and including indeterminate examinations. For participants whose standard-of-care PET/CT was performed within a 3-week interval, sensitivity and specificity of the two modalities are compared pairwise by McNemar's test. Thresholds for ADC, lesion-to-spinal-cord ratio, native T1 and T2 are explored by ROC analysis at Youden's index. Interobserver agreement is assessed by kappa for categorical variables and intraclass correlation for continuous variables. Analyses are performed in R version 4.4.1 or higher at a significance level of 0.05. No interim analysis is planned.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adults aged 50 to 80 years enrolled in the University of Florida lung cancer screening program who meet 2021 USPSTF screening eligibility (at least a 20 pack-year smoking history, currently smoking or quit within the past 15 years) and whose standard-of-care screening low-dose chest CT was assigned Lung-RADS category 4 (4A, 4B, or 4X). Participants are identified consecutively from institutional lung cancer screening CT reports and approached through a treating clinician who is a listed investigator, or through the UF Consent2Share registry.

Description

Inclusion Criteria:

  1. Age 50 to 80 years, inclusive.
  2. At least a 20 pack-year cigarette smoking history, and currently smoking or quit within the past 15 years (2021 USPSTF lung cancer screening eligibility).
  3. Underwent a standard-of-care lung cancer screening low-dose chest CT (LDCT) at the University of Florida that was assigned Lung-RADS category 4 (4A, 4B, or 4X) per ACR Lung-RADS v2022.
  4. Able to provide written informed consent independently.

Exclusion Criteria:

  1. Part-solid or cystic nodule with a solid component measuring less than 8 mm.
  2. Endobronchial nodule.
  3. MRI-incompatible or potentially MRI-incompatible implanted device.
  4. Claustrophobia that would prevent the participant from tolerating the MRI examination.
  5. Metallic device in the chest wall or spine that may interfere with adequate image acquisition in the field of view (assessed case by case).
  6. History of prior lung resection for a benign condition that may create susceptibility artifact in the field of view.
  7. Home oxygen supplementation.
  8. Active or treated lower respiratory tract infection within the prior 4 weeks.
  9. Lack of capacity to consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Lung-RADS 4 lesion on screening LDCT
Adults aged 50-80 who meet 2021 USPSTF lung cancer screening criteria and have a Lung-RADS category 4 (4A, 4B, or 4X) lesion on a standard-of-care lung cancer screening low-dose chest CT. Each participant undergoes one non-contrast multiparametric chest MRI at 3.0 T for research purposes, in addition to standard of care. No standard-of-care imaging, biopsy, or treatment is withheld or replaced, and the research MRI is not used for clinical decision making. Participants continue routine clinical management; the final nature of the lesion is established from histopathology or microbiology when tissue is obtained, or otherwise from at least 24 months of clinical and imaging follow-up.
Diagnostic test: Multiparametric chest MRI with diffusion-weighted imaging
Single non-contrast chest MRI on a 3.0 Tesla scanner (GE Healthcare or Siemens Healthineers) with a vendor-specific surface coil. Sequences: axial breath-hold 2D in- and opposed-phase gradient echo T1-weighted imaging; axial breath-hold and/or respiratory-triggered multi-shot fat-suppressed EPI DWI with two b values; reduced-FOV DWI centered on the nodule; axial respiratory-triggered T2-weighted imaging with fat suppression or Dixon. Optional UTE and T1/T2 mapping if time allows. No intravenous or other contrast material is administered.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity of multiparametric chest MRI for malignancy in Lung-RADS 4 lesions
Time Frame: From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Sensitivity and specificity, each with a 95% confidence interval, of the reader classification of multiparametric chest MRI (full protocol) for malignant versus benign lesion, against the final clinical diagnosis as the reference standard. Reported both excluding and including examinations classified as indeterminate, to determine whether indeterminate examinations are better grouped with low or with high suspicion.
From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity of diffusion-weighted imaging alone
Time Frame: From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Sensitivity and specificity with 95% confidence intervals of the reader classification based on DWI alone read in conjunction with the companion low-dose CT (round 1), against the final clinical diagnosis, for comparison with the full-protocol estimates (Aim 2).
From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Diagnostic performance of chest MRI compared with PET/CT
Time Frame: From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Sensitivity and specificity of chest MRI and of standard-of-care PET/CT compared pairwise by McNemar's test, in the subset of participants whose PET/CT was performed within a 3-week interval (Aim 3). PET/CT is standard of care and is not scheduled by the study.
From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Apparent diffusion coefficient (ADC) threshold for malignancy
Time Frame: From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Optimal ADC threshold identified by ROC analysis at Youden's index, with the sensitivity, specificity and 95% confidence intervals at that threshold. ADC is measured from a circular or elliptical region of interest placed over the lowest-signal component of the nodule, avoiding artifact, with correlation to the low-dose CT.
From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Lesion-to-spinal-cord signal intensity ratio (LSR) threshold for malignancy
Time Frame: From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Optimal LSR threshold by ROC analysis at Youden's index with sensitivity, specificity and 95% confidence intervals. LSR is calculated from the signal intensity of the nodule and of the spinal cord measured at the same level.
From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Native T1 and T2 thresholds for malignancy
Time Frame: From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Optimal native T1 and T2 thresholds by ROC analysis at Youden's index, with sensitivity, specificity and 95% confidence intervals at each threshold, in participants for whom T1 and T2 mapping centered on the nodule was acquired.
From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Diagnostic performance of a short (<10 minute) acquisition protocol
Time Frame: From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Sensitivity and specificity of the abbreviated acquisition (a single diffusion sequence with restricted z-axis coverage centered on the nodule, acquisition time under 10 minutes) compared with the full protocol, to assess whether the short protocol is non-inferior.
From the research MRI to establishment of the final diagnosis: histopathology or microbiology when tissue is obtained, otherwise at least 24 months of clinical and imaging follow-up per participant.
Feasibility: prevalence of eligible patients and conversion of eligible patients to enrolled participant
Time Frame: Through the enrollment period, up to 24 months from study start.
Number of Lung-RADS 4 examinations screened, number meeting all eligibility criteria, and number enrolled and scanned, yielding the prevalence of eligible patients in the UF lung cancer screening population and the eligible-to-enrolled conversion rate. Stated in the source protocol as an explicit goal the sample size is intended to support.
Through the enrollment period, up to 24 months from study start.
Interobserver agreement between the two readers
Time Frame: At completion of image interpretation, after both reading rounds are finished for all enrolled participants. Up to 48 months from study start.
Agreement between the two independent cardiothoracic radiologists: Cohen's kappa for the three-category suspicion classification and intraclass correlation coefficients for continuous measures (ADC, LSR, T1, T2). Interpreted as 0.01-0.20 minor, 0.21-0.40 fair, 0.41-0.60 moderate, 0.61-0.80 high, 0.81-1.00 excellent.
At completion of image interpretation, after both reading rounds are finished for all enrolled participants. Up to 48 months from study start.
Prevalence of each MRI suspicion category
Time Frame: At completion of image interpretation, after both reading rounds are finished for all enrolled participants. Up to 48 months from study start.
Proportion of examinations classified into each of the three reader categories: (1) negative / low suspicion for malignancy, (2) indeterminate, would benefit from short-term follow-up, (3) positive / high suspicion for malignancy.
At completion of image interpretation, after both reading rounds are finished for all enrolled participants. Up to 48 months from study start.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2027

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2032

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 17, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB202601035

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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