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Introduction: BI-RADS category 4 is associated with a wide variability in probability of malignancy, ranging from 2 to 95% while biopsy-derived positive predictive value (PPV3) for this category’s lesions remains low at 21.1% in the US. A major fallout of these facts is that we have way very high false positive rate leading to too many unnecessary biopsies and their associated costs and emotional burden. We improved our in-house intelligent-augmented Breast cancer RISK calculator (iBRISK), an integrated deep learning (DL) based decision support app and assessed its performance in a multicenter IRB-approved study. Methods: We improved iBRISK by retraining the DL model with an expanded dataset of 9,700 patient records of clinical risk-factors and mammographic descriptors from Houston Methodist Hospital (HMH) and validated using another 1,078 patient records. These patients were all seen between March 2006 and December 2016. We assessed the model using blinded, independent retrospective BI-RADS 4 patients who had biopsies subsequently after mammography and seen January 2015 - June 2019 at three major healthcare institutions in Texas, USA: MD Anderson Cancer Center, the University of Texas Health Sciences Center at San Antonio, and HMH. We dichotomized and trichotomized the data to evaluate precision of risk stratification and probability of malignancy (POM) estimation translated into biopsy decision augmentation. The iBRISK score as a continuous predictor of malignancy and possible cost savings was also analyzed. Results: The multicenter validation dataset had 4,209 women, median age (interquartile) was 56 (45, 65) years. The use of iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97. Among “low” and “moderate” POM patients, only two out of 1,228 patients (0.16%) and 118 out of 1788 (6.6%) were malignant respectively. This translates to an even better precision when compared to newly introduced BI-RADS 4 subcategories 4A and 4B, with associated PPV3s of 7.6% and 22%, respectively. The “high” POM group had a malignancy rate of 85.9% (1,025/1,193). Estimated potential cost savings in the US was over $260 million. Conclusion: The iBRISK app demonstrated high sensitivity in malignancy prediction and can potentially be used to safely obviate biopsies in up to 50% of patients in low/moderate POM-groups. This would result in significant healthcare quality improvement, cost savings, and help reduce patient anxiety. Citation Format: Chika F. Ezeana, Tiancheng He, Tejal A. Patel, Virginia Kaklamani, Maryam Elmi, Erica Ibarra, Pamela M. Otto, Kenneth A. Kist, Heather Speck, Lin Wang, Joe Ensor, Ya-Chen T. Shih, Bumyang Kim, I-Wen Pan, David Spak, Wei T. Yang, Jenny C. Chang, Stephen T. Wong. A multicenter study validated an integrated deep learning model for precision malignancy risk assessment and reducing unnecessary biopsies in BI-RADS 4 cases. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5698.

The histologic distinction between papillary breast lesions remains challenging, especially with core biopsy (CB) specimens. A retrospective review of the clinical, imaging, and histologic findings was performed for patients with papillary breast lesions on CB from 2013 to 2017. The interpretation accuracy was expressed as upgrade rate relative to the excision diagnosis. Diagnostic reproducibility with and without immunohistochemistry was analyzed as interobserver variability among 3 board-certified pathologists. Among 57 papillary lesions with biopsies and excisions available for review, the upgrade rates were 0% for benign papilloma, 30% for papilloma with atypical ductal hyperplasia, and 25% for papilloma with ductal carcinoma in situ, resulting in an overall upgrade rate of 11.1%. There were no statistical differences between patients in an upgrade group and others, when comparing the patient age, clinical presentation, BI-RADS (Breast Imaging Reporting and Database System) category, location, and histologic grade. The overall interobserver variability of the 60 consecutive core biopsies of papillary breast lesions by morphology alone was in the “substantial” agreement range (κ = 0.79, 86% agreement), with an excellent κ score of 0.88 for papilloma (92% agreement). “Substantial” and “fair” κ values were seen for papilloma with atypical ductal hyperplasia/ductal carcinoma in situ (0.74, 84% agreement) and invasive carcinoma (0.40, 60% agreement). Use of immunohistochemical stains improved the κ values into “excellent” range (0.92, 94% agreement). Our study favors a conservative approach in the management of benign papillomas, at least in cases of good radiologic-pathologic concordance. Papillary breast lesions with atypia/malignancy show lower diagnostic reproducibility on CB, and utility of immunohistochemistry is recommended in challenging cases.

Optoacoustic ultrasound breast imaging is a fused anatomic and functional modality that shows morphologic features, as well as hemoglobin amount and relative oxygenation within and around breast masses. The purpose of this study is to investigate the positive predictive value (PPV) of optoacoustic ultrasound features in benign and malignant masses.In this study, 92 masses assessed as BI-RADS category 3, 4, or 5 in 94 subjects were imaged with optoacoustic ultrasound. Each mass was scored by seven blinded independent readers according to three internal features in the tumor interior and two external features in its boundary zone and periphery. Mean and median optoacoustic ultrasound scores were compared with histologic findings for biopsied masses and nonbiopsied BI-RADS category 3 masses, which were considered benign if they were stable at 12-month follow-up. Statistical significance was analyzed using a two-sided Wilcoxon rank sum test with a 0.05 significance level.Mean and median optoacoustic ultrasound scores for all individual internal and external features, as well as summed scores, were higher for malignant masses than for benign masses (p0.0001). High external scores, indicating increased hemoglobin and deoxygenation and abnormal vessel morphologic features in the tumor boundary zone and periphery, better distinguished benign from malignant masses than did high internal scores reflecting increased hemoglobin and deoxygenation within the tumor interior.High optoacoustic ultrasound scores, particularly those based on external features in the boundary zone and periphery of breast masses, have high PPVs for malignancy and, conversely, low optoacoustic ultrasound scores have low PPV for malignancy. The functional component of optoacoustic ultrasound may help to overcome some of the limitations of morphologic overlap in the distinction of benign and malignant masses.

False-positive findings remain challenging in breast imaging. This study investigates the incremental value of optoacoustic imaging in improving BI-RADS categorization of breast masses at ultrasound.The study device is an optoacoustic breast imaging device with a handheld duplex laser and internal gray-scale ultrasound probe, fusing functional and morphologic information (optoacoustic ultrasound). In this prospective multisite study, breast masses assessed as BI-RADS category 3, 4A, 4B, 4C, or 5 by site radiologists underwent both gray-scale ultrasound and optoacoustic imaging with the study device. Independent reader radiologists assessed internal gray-scale ultrasound and optoacoustic ultrasound features for each mass and assigned a BI-RADS category. The percentage of mass reads for which optoacoustic ultrasound resulted in a downgrade or upgrade of BI-RADS category relative to internal gray-scale ultrasound was determined.Of 94 total masses, 39 were biopsy-proven malignant, 44 were biopsy-proven benign, and 11 BI-RADS category 3 masses were stable at 12-month follow-up. The sensitivity of both optoacoustic ultrasound and internal gray-scale ultrasound was 97.1%. The specificity was 44.3% for optoacoustic ultrasound and 36.4% for internal gray-scale ultrasound. Using optoacoustic ultrasound, 41.7% of benign masses or BI-RADS category 3 masses that were stable at 12-month follow-up were downgraded to BI-RADS category 2 by independent readers; 36.6% of masses assigned BI-RADS category 4A were downgraded to BI-RADS category 3 or 2, and 10.1% assigned BI-RADS category 4B were downgraded to BI-RADS category 3 or 2. Using optoacoustic ultrasound, independent readers upgraded 75.0% of the malignant masses classified as category 4A, 4B, 4C, or 5, and 49.4% of the malignant masses were classified as category 4B, 4C, or 5.Optoacoustic ultrasound resulted in BI-RADS category downgrading of benign masses and upgrading of malignant masses compared with gray-scale ultrasound.

Purpose To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses. Materials and Methods This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared. Results Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone. Online supplemental material is available for this article. © RSNA, 2017.

Ultrasound-guided breast interventions (core biopsies, needle-wire localizations, and fine-needle cyst aspirations) are common procedures performed by radiologists. Residents must gain competency in these interventions during training. Phantoms and simulations have been advocated for teaching interventions, and various systems are available for standard breast interventions. However, simulations for difficult/high-risk interventions are not readily available. We describe an inexpensive method for simulating difficult ultrasound-guided breast procedures, including masses over breast implants, deep masses along the chest wall, and lymph nodes adjacent to axillary vessels.

Functional opto-acoustic (OA) imaging was fused with gray-scale ultrasound acquired using a specialized duplex handheld probe. Feasibility Study findings indicated the potential to more accurately characterize breast masses for cancer than conventional diagnostic ultrasound (CDU). The Feasibility Study included OA imagery of 74 breast masses that were collected using the investigational Imagio® breast imaging system. Superior specificity and equal sensitivity to CDU was demonstrated, suggesting that OA fusion imaging may potentially obviate the need for negative biopsies without missing cancers in a certain percentage of breast masses. Preliminary results from a 100 subject Pilot Study are also discussed. A larger Pivotal Study (n=2,097 subjects) is underway to confirm the Feasibility Study and Pilot Study findings.

e14619 Background: Obesity is associated with poor breast cancer outcomes. Our prior data suggested a positive feedback loop whereby circulating factors associated with obesity induce the COX-2 enzyme, resulting in increased pro-inflammatory cytokine prostaglandin E2 (PGE2), which can then increase aromatase levels. In order to establish a better understanding of baseline PGE2 levels, as well as select the proper COX2 inhibitor for prospective study, we performed a randomized study of aspirin (ASA), fish oil (DHA/EPA), and the combination in postmenopausal women of varying body habitus and assessed changes in cytokines. Methods: Women were recruited and randomly assigned into 3 interventions: ASA 81mg, docosahexaenoic acid (DHA, 1500mg) with eicosapentaenoic acid (EPA, 2500mg), or combination ASA and DHA/EPA (DUAL). Blood was collected before and after 28 days of supplementation, and 27 cytokines were assessed by Luminex array (Millipore); PGE2 was measured by ELISA. Investigators were blinded until analysis was complete. Statistical analyses were performed in R. Results: 110 patients were included: 90% participants white; of which 50% Hispanic; average BMI 31.5±0.67; and age: 60.1±0.58. Cytokines were not correlated with demographic variables. At baseline inflammatory cytokines IL-6 and Eotaxin were correlated with BMI ((p > 0.029 and p > 0.017, respectively). After 28 days of DHA/EPA BMI was correlated with Eotaxin, Il-2, IL-7 and GM-CSF (p < 0.05), in ASA group correlation was significant only with IL-2 (cor.coef= 0.58). Two sample t-test showed significant difference between DUAL and ASA or DHA/EPA for IL-6 (p = 0.008 and p = 0.034, respectively), and for IL-2 only between DUAL and ASA (p = 0.039). Furthermore, impact on PGE2 was observed with ASA with 81% obtaining a decrease from baseline (median change -28%); by comparison 55.1% (-1%) and 65.6% (-22%) of subjects showed decrease in the DUAL and DHA/EPA groups respectively. Level of macrophage inflammatory proteins (MIP-1b) were lower in the DUAL group compare to ASA (p < 0.014). Conclusions: Chronic inflammatory cytokines are correlated with obesity, and may be modified by use of ASA and DHE/EPA. This strategy may be useful in the secondary prevention setting. Clinical trial information: NCT02062255.

We present results from a recent study involving the Imagio TM breast imaging system, which produces fused real-time two-dimensional color-coded opto-acoustic (OA) images that are co-registered and temporally inter- leaved with real-time gray scale ultrasound using a specialized duplex handheld probe. The use of dual optical wavelengths provides functional blood map images of breast tissue and tumors displayed with high contrast based on total hemoglobin and oxygen saturation of the blood. This provides functional diagnostic information pertaining to tumor metabolism. OA also shows morphologic information about tumor neo-vascularity that is complementary to the morphological information obtained with conventional gray scale ultrasound. This fusion technology conveniently enables real-time analysis of the functional opto-acoustic features of lesions detected by readers familiar with anatomical gray scale ultrasound. We demonstrate co-registered opto-acoustic and ultrasonic images of malignant and benign tumors from a recent clinical study that provide new insight into the function of tumors in-vivo. Results from the Feasibility Study show preliminary evidence that the technology may have the capability to improve characterization of benign and malignant breast masses over conventional diagnostic breast ultrasound alone and to improve overall accuracy of breast mass diagnosis. In particular, OA improved speci city over that of conventional diagnostic ultrasound, which could potentially reduce the number of negative biopsies performed without missing cancers.

Two-dimensional optoacoustic imaging with a hand-held probe operated in backward mode is being developed for diagnostic imaging of breast cancer to evaluate the feasibility of a dual-modality optoacoustic plus ultrasonic system that maps functional information of anatomical tissue structures with ultrasonic resolution. Tissue is illuminated at 757nm and 1064nm for optical contrast between hypoxic blood of breast carcinomas and normally oxygenated blood in benign masses. The system is optimized and calibrated in phantoms for a pilot clinical study of patients with breast masses suspected for malignancy. Capability of the non-invasive system to improve detection and diagnosis of breast tumors is discussed.

Purpose: To compare the signal void artifact size caused by metallic tissue marking clips at 1.5T and 3T and to test the impact of different readout bandwidth and TE on the artifact size. Methods and Materials: The signal void size of three commercially available metallic tissue marking clips were assessed at both 1.5T and 3T scanners. The clips studied were immersed in a gel phantom with enough distance (>25mm) to avoid field interference between them. An RF‐spoiled T1‐weighted gradient echo (SPGR) sequence commonly used in DCE breast imaging was used on both scanners with TR/TE/FA=32/4.6/25°, FOV=160mm, spatial resolution of 1×1×4mm3, and water fat shift of 1.534 pixels (i.e., readout bandwidth = 22.6 kHz for 1.5T, and 45.3 kHz for 3T). Same sequence was repeated with higher readout bandwidth of 139 kHz (1.5T) and 198 kHz (3T). In addition, TE=1.16ms was also tested with partial Fourier readout and high readout bandwidth to study change of TE on the effect of signal void artifact size on both scanners.Results: At TE=4.6ms, both scanners showed signal void artifacts 2∼8 times larger than the clips themselves. Importantly, the signal void size was 15%∼30% larger at 3T compared to that of 1.5T. Increasing readout bandwidth had little impact on signal void artifact size on both scanners. However, decreasing TE from 4.6 ms to 1.16 ms reduced the average artifact size at both 1.5T (27%) and 3T (31%). Conclusion: Signal void artifact size is larger at 3T for all three metallic tissue marking clips studied at the current experimental settings. This could be a disadvantage of 3T scanners when used to detect and follow‐up breast cancer adjacent to metallic tissue marking clips after biopsy. Short TE can be used to effectively reduce signal void artifacts at both 1.5T and 3T.