An observational study in Solitary Pulmonary Nodule, Multiple Pulmonary Nodules and Lung Neoplasms, sponsored by University of Florida. Not yet recruiting at 1 site in United States. Open to participants aged 50 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by University of Florida · Observational
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.
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.
93 studies on the registry are indexed under Solitary Pulmonary Nodule; 20 are open to participants now.
This study's planned enrollment of 30 is below the median of 401 across 45 observational studies indexed under Solitary Pulmonary Nodule.
Browse Solitary Pulmonary Nodule studies →University of Florida is the lead sponsor of 1,287 studies on the registry; 199 are open to participants now.
Of its 180 completed or terminated interventional studies of FDA-regulated products, 143 (79%) have results posted.
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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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Sensitivity and specificity of multiparametric chest MRI for malignancy in Lung-RADS 4 lesions
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.
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 diffusion-weighted imaging alone
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).
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.
Diagnostic performance of chest MRI compared with PET/CT
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.
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.
Apparent diffusion coefficient (ADC) threshold for malignancy
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.
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.
Lesion-to-spinal-cord signal intensity ratio (LSR) threshold for malignancy
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.
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.
Native T1 and T2 thresholds for malignancy
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.
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.
Interobserver agreement between the two readers
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.
Time frame: 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
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.
Time frame: At completion of image interpretation, after both reading rounds are finished for all enrolled participants. Up to 48 months from study start.
Diagnostic performance of a short (<10 minute) acquisition protocol
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.
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.
Feasibility: prevalence of eligible patients and conversion of eligible patients to enrolled participant
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.
Time frame: Through the enrollment period, up to 24 months from study start.
Plan to share: Undecided
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Start is estimated for Jan 2027; primary completion for Jan 2031, 48 months later.
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