Diagnostic US for Reduction of Benign Breast Biopsies Using US-guided Optical Tomography

Study Overview
=================
Brief Summary
-----------------
Ultrasound-guided diffuse optical tomography (DOT) has demonstrated its potential role in differentiating malignant and benign breast abnormalities and in predicting and monitoring the neoadjuvant chemotherapy (NAC) response of breast cancer. This unique approach employs a commercial ultrasound (US) transducer and near infrared (NIR) optical imaging sensors mounted on a hand-held US probe. The co-registered US is used for lesion localization, and optical sensors are used for imaging tumor related vascularity.

Official Title
-----------------
Improving Diagnostic US for Reduction of Benign Breast Biopsies Using US-guided Optical Tomography

Conditions
-----------------
Breast Biopsy

Intervention / Treatment
-----------------
* Device: Hand-held hybrid probe


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female subjects ≥ 18 years old with ultrasound visible breast abnormalities (BI-RADS 3*, 4A, 4B, 4C, and 5) referred for ultrasound-guided core needle biopsy or fine needle aspiration *note that while a BI-RADS 3 assessment is probably benign, a subset of patients with this assessment choose to undergo biopsy rather than follow up imaging). Willing and able to provide informed consent Exclusion Criteria: Lesions located in the darkly pigmented nipple-areolar complex area Subjects with breast implants Abnormality in the mirror image location of the contralateral breast. Additional abnormalities in the same region of the breast that would be included in US-guided DOT imaging of the abnormality undergoing biopsy Previous breast irradiation of the mirror image location of the contralateral breast Lesions located at previous biopsy sites when biopsy occurred within the last six months. Small lesions of less than 1 cm located at skin or close to the skin Pregnancy Superficial abnormalities located entirely within (i.e. less than) 5mm of the overlying skin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I - Training Set<br>20 patients will be recruited to undergo US-DOT and CEM to allow for training study readers in assessing US-DOT data, intra-observer variability and to assess inter-observer variability in the assessment of US-DOT data A hand-held hybrid probe will be used for the scans | Device: Hand-held hybrid probe<br>* Consists of a commercially available US transducer located in the middle and near-infrared source and detector optical fibers distributed at the periphery<br>|
| Experimental: Phase 2: Prospective Trial<br>US-DOT (US/NIR) Imaging Exam Breast biopsy or FNA performed (standard of care) A hand-held hybrid probe will be used for the scans | Device: Hand-held hybrid probe<br>* Consists of a commercially available US transducer located in the middle and near-infrared source and detector optical fibers distributed at the periphery<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of US-guided DOT on the potential reduction of benign biopsies as measured by comparing the specificity of conventional imaging (CI = US +/- Mammography) alone versus CI & US-DOT | -BI-RADS scores without and then with optical data will be rendered by study radiologists. Radiologists will be blinded to the biopsy exam and pathology outcomes. Optical data including total Hemoglobin concentration will be provided by the bioengineering team. Specificity will be calculated as the proportion of subjects with a non- suspicious assessment, i.e. BIRADS 2 'benign' or BIRADS 3 'probably benign', divided by the denominator of subjects with no cancer demonstrated at biopsy. US-guided core biopsy results and subsequent surgical pathology (if present) will be entered by the study pathologist. | Completion of enrollment for all patients (estimated to be 87 months) | 
| Impact of US-guided DOT as an adjunct to conventional breast imaging on maintaining high sensitivity as measured by comparing the false negative rate of conventional imaging (CI=US +/- Mammography) alone versus CI & US-DOT | -BI-RADS scores without and then with optical data will be rendered by study radiologists. Radiologists will be blinded to the biopsy exam and pathology outcomes. Optical data including total Hemoglobin concentration will be provided by the bioengineering team. The False Negative Rate will be calculated as the proportion of subjects with a non-suspicious assessment i.e. BIRADS 2 'benign' or BIRADS 3 'probably benign', who have cancer (defined as Invasive cancer or Ductal Carcinoma In Situ) demonstrated at biopsy divided by the denominator of all subjects with cancer. US-guided core biopsy results and subsequent surgical pathology (if present) will be entered by the study pathologist | Completion of enrollment for all patients (estimated to be 87 months) |