Non-contrast DWI for Supplemental Screening

Study Overview
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Brief Summary
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Diffusion-weighted imaging (DWI) is a short (under 5 minutes) non-contrast MRI technique that has shown promise for the detection and characterization of breast cancer. Our preliminary data has shown that DWI holds potential for detecting mammographically and clinically-occult breast cancers. However, current technical limitations reduce the sensitivity of DWI for screening applications. The identification of a screening tool to complement mammography that is more accurate than ultrasound and faster, less expensive, and safer than conventional contrast-enhanced MRI would have significant clinical impact by improving the early detection of cancer in women with dense breasts. We hypothesize that an optimized DWI approach will enable detection of mammographically occult breast cancer in women with dense breasts with high sensitivity and low false positive rate.

Detailed Description
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Hypothesis: With technical optimizations, non-contrast DWI can detect clinically and mammographically occult breast cancer in women with dense breasts with high sensitivity and low false positive rate. Aim 1: Improve the breast DWI technique to maximize spatial resolution, reduce distortion, and increase lesion contrast. Develop novel DWI acquisition to increase spatial resolution and reduce distortion (using reduced field of-view and/or multishot echo planar imaging techniques) Identify optimal diffusion sensitization (b-value) to maximize conspicuity of cancers in women with dense breasts Aim 2: Develop interpretation tools to optimize diagnostic performance for detecting cancer on DWI. Determine quantitative DWI thresholds (contrast-to-noise ratio, apparent diffusion coefficient [ADC]) that best differentiate benign and malignant lesions (i.e. maximize sensitivity and specificity) Develop computer aided assessment tools to facilitate clinical implementation and optimize reader accuracy Aim 3: Test the performance of the optimized DWI approach for detecting clinically and mammographically-occult cancer in women with dense breasts. Conduct a controlled reader study of non-contrast DWI alone for breast cancer detection Perform receiver operating characteristic (ROC) analysis and determine the sensitivity and specificity for detection of mammographically occult cancer

Official Title
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Non-contrast DWI for Supplemental Screening of Women With Dense Breasts

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: Non-contrast DWI
* Device: Non-contrast MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 or older Dense breast identified on mammogram Exclusion Criteria: Contra-indication to contrast-enhanced breast MRI (e.g. renal insufficiency with GFR<60, contrast allergy, incompatible metal) Patients who currently are undergoing chemoprevention therapy (e.g. aromatase inhibitors or selective estrogen receptor modulators) Women who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Phase 1: Pilot Study Phase<br>Optimize DWI sequences to maximize spatial resolution, reduce distortion, and increase lesion contrast. | Device: Non-contrast DWI<br>* Diffusion-weighted imaging (DWI) is a non-contrast MRI technique that typically can be acquired in under 5 minutes. DWI reflects the microscopic cellular environment and can demonstrate differences between normal and malignant breast tissue without the aid of intravenous gadolinium.<br>|
| Phase 2: Development Phase<br>Develop interpretation tools to optimize diagnostic performance for detecting cx on DWI. | Device: Non-contrast MRI<br>* Non-contrast MRI scans will include DWI along with anatomical T1-weighted and T2-weighted sequences.<br>|
| Phase 3: Reader Performance Phase<br>Test the performance of the optimized DWI approach for detecting clinically and mammographically-occult cancer in women with dense breasts. | Device: Non-contrast MRI<br>* Non-contrast MRI scans will include DWI along with anatomical T1-weighted and T2-weighted sequences.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diffusion sensitization (b value) | Identify optimal b value to maximize conspicuity of cancers in women with dense breasts | 2.5 years | 
| Reader Interpretation strategy | Identify optimal ADC thresholds to differentiate malignant from benign lesions | 3.5 years | 
| Specificity | Specificity will be assessed for non-contrast DWI | 4.5 years | 
| Sensitivity | Sensitivity will be assessed for non-contrast DWI | 4.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Supplemental Screening, Dense Breasts, Diffusion Weighted Imaging