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Table S1. Specifics of DCE-MRI Techniques Used; Table S2. Pathogenic mutations identified in study participants; Table S3. Patients' reasons of withdrawls from the study within 5 years

Purpose:To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer.Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene.Results:Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively.Conclusions:Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693

Figure S1. Study protocol design; Figure S2. MRI compliance during the first 5 years of study; Figure S3. Recall and biopsy rates by imaging modality

To identify the optimal threshold insup18/supF-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pOsub2/subEPRI) as ground truth for hypoxia, defined by pOsub2/sub[Formula: see text] 10 mmHg.Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue. Dynamic contrast enhanced (DCE) MRI parametric images of Ksuptrans/supand vsube/subwere generated to model tumor vascular properties. Images from PET/EPR/MRI were co-registered and resampled to isotropic 0.5 mm voxel resolution for analysis. PET images were converted to standardized uptake value (SUV) and tumor-to-muscle ratio (TMR) units. FMISO uptake thresholds were evaluated using receiver operating characteristic (ROC) curve analysis to find the optimal FMISO threshold and unit with maximum overall hypoxia similarity (OHS) with pOsub2/subEPRI, where OHS = 1 shows perfect overlap and OHS = 0 shows no overlap. The means of dice similarity coefficient, normalized Hausdorff distance, and accuracy were used to define the OHS. Monotonic relationships between EPRI/PET/DCE-MRI were evaluated with the Spearman correlation coefficient ([Formula: see text]) to quantify association of vasculature on hypoxia imaged with both FMISO PET and pOsub2/subEPRI.FMISO PET thresholds to define hypoxia with maximum OHS (both OHS = 0.728 [Formula: see text] 0.2) were SUV [Formula: see text] 1.4 [Formula: see text] SUVsubmean/suband SUV [Formula: see text] 0.6 [Formula: see text] SUVsubmax/sub. Weak-to-moderate correlations (|[Formula: see text]|lt; 0.70) were observed between PET/EPRI hypoxia images with vascular permeability (Ksuptrans/sup) or fractional extracellular-extravascular space (vsube/sub) from DCE-MRI.This is the first in vivo comparison of FMISO uptake with pOsub2/subEPRI to identify the optimal FMISO threshold to define tumor hypoxia, which may successfully direct hypoxic tumor boosts in patients, thereby enhancing tumor control.

Breast cancer is the most diagnosed cancer among Latina women and is the leading cause of cancer-related death among Latinas (16.6%). While The Latino population is one of the fastest-growing populations in the US, they are severely underrepresented in clinical trials. Latinos make up 17% of the population but only 1% of clinical trial participants. Of clinical trials published covering 2001-2010, Latinos’ enrollment constituted only 2.2% of accrued participants. The percentage of Latino participants narrows down when we separate by gender. The goal of this study is to examine the prevalence of breast cancer-related barriers among Latinas and to determine the extent to which these barriers might influence Latinas enrolling in breast cancer clinical trials. If language and religion are the reason Latinas enroll less in breast cancer clinical trials, then increasing the availability of translated materials and a priest of a Catholic Church advertising the breast cancer studies will increase the enrollment rate of Latinas. Semi-constructed interviews were conducted with two Latino organizations to understand current barriers Latina’s face within the medical field. Based on these findings, I conducted an intervention at Our Lady of Tepeyac Church consisting of an information booth, making an announcement regarding Research Study 9127, and having bilingual Latinas available to give out more information while helping them enroll in Research Study 9127. At the end of the church intervention, 33 Latinas were enrolled in Research Study 9127, seeing a 550% increase in Latinas participating in Research Study 9127. Latinx women remain severely underrepresented in breast cancer clinical trials, thus limiting the generalizability of cancer clinical research, but interventions across churches would lead to improvements in general cancer knowledge, breast cancer screening practices, and intentions to enroll in clinical trials. This study can inform efforts to increase clinical trial participation in Latinas by highlighting important motivators to participation specific to Latinas and informing future interventions aimed at encouraging participation in clinical trials in a culturally sensitive and effective way. Citation Format: Monica J. Padilla, Gregory Karczmar. Barriers and effective interventions to engage Latinas' participation in breast cancer clinical trials [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 1941.

Breast cancer is the most common malignancy affecting women worldwide. Existing models being used to study breast cancer include the Patient-Derived Tumor Organoid (PDTO) Model and the Patient-Derived Tumor Xenograft (PDTX) Model. Both models involve the surgical removal of a tumor from a patient which then undergoes processing to grow an organoid or injected into mice to test different therapies outside the body. However, these models not only take a considerable amount of time to develop properly, but in many cases aren’t representative of the most aggressive tumor cells present within a heterogeneous tissue sample in order to draw the most clinically accurate conclusions of a tumor's response to therapy. In order to advance clinical research, more efficient culture systems that are faster growing and more representative of biological characteristics in-vivo are needed. Previous work from the Karczmar Lab discovered that high-resolution magnetic resonance imaging (MRI) can detect regions of aggressive cancer in biopsy specimens from mouse models, and give additional information on characteristics including cell density, tissue composition, and cancer stage. With this recent discovery, it is hypothesized that ex-vivo imaging could be used to identify aggressive tumor cells in human heterogeneous breast cancer tissue samples to produce higher quality and faster-growing models for testing new therapies and guiding individual patient therapy for breast cancer. The primary aim for this study was to specifically identify image-based markers for regions of aggressive cancer by comparing ex-vivo high-resolution MRI with histology and immunohistochemistry in 3D. Distant normal (DN) and tumor (Tu) tissue samples from breast cancer patients were obtained and imaged using T2-weighted 3D Rapid Imaging with Refocused Echoes (RARE) and stained using hematoxylin and eosin (H&E), commonly used by pathologists to diagnose cancers. Then, the ex-vivo T2-weighted 3D RARE images were correlated to the histopathological H&E staining and confirmed by breast radiologists and pathologists. Preliminary results revealed that high-resolution MR imaging detects mammary glands, ducts, and white adipose tissue in DN tissue samples and regions of invasive cancer, including ductal carcinoma in-situ (DCIS) and necrosis, in Tu tissue. Based on these results, aggressive cancer regions were proven to be identified using image-based guidance and potentially be extracted using core-needle biopsy to improve PDTO and PDTX models for studying breast cancer and advancing individual patient therapy. Citation Format: Corazon Avila, Gregory Karczmar, Devkumar Mustafi. Applications of multimodality ex-vivo tissue imaging to improve breast cancer diagnosis and treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2485.

PURPOSE: To enhance the spatial accuracy of fluorine 18 ((18)F) misonidazole (MISO) PET imaging of hypoxia by using dynamic contrast-enhanced (DCE) MR images as a basis for modifying PET images and by using electron paramagnetic resonance (EPR) partial oxygen pressure (pO(2)) as the reference standard. MATERIALS AND METHODS: Mice (n = 10) with leg-borne MCa4 mammary carcinomas underwent EPR imaging, T2-weighted and DCE MRI, and (18)F-MISO PET/CT. Images were registered to the same space for analysis. The thresholds of hypoxia for PET and EPR images were tumor-to-muscle ratios greater than or equal to 2.2 mm Hg and less than or equal to 14 mm Hg, respectively. The Dice similarity coefficient (DSC) and Hausdorff distance (d(H)) were used to quantify the three-dimensional overlap of hypoxia between pO(2) EPR and (18)F-MISO PET images. A training subset (n = 6) was used to calculate optimal DCE MRI weighting coefficients to relate EPR to the PET signal; the group average weights were then applied to all tumors (from six training mice and four test mice). The DSC and d(H) were calculated before and after DCE MRI–corrected PET images were obtained to quantify the improvement in overlap with EPR pO(2) images for measuring tumor hypoxia. RESULTS: The means and standard deviations of the DSC and d(H) between hypoxic regions in original PET and EPR images were 0.35 mm ± 0.23 and 5.70 mm ± 1.7, respectively, for images of all 10 mice. After implementing a preliminary DCE MRI correction to PET data, the DSC increased to 0.86 mm ± 0.18 and the d(H) decreased to 2.29 mm ± 0.70, showing significant improvement (P < .001) for images of all 10 mice. Specifically, for images of the four independent test mice, the DSC improved with correction from 0.19 ± 0.28 to 0.80 ± 0.29 (P = .02), and the d(H) improved from 6.40 mm ± 2.5 to 1.95 mm ± 0.63 (P = .01). CONCLUSION: Using EPR information as a reference standard, DCE MRI information can be used to correct (18)F-MISO PET information to more accurately reflect areas of hypoxia. Keywords: Animal Studies, Molecular Imaging, Molecular Imaging-Cancer, PET/CT, MR-Dynamic Contrast Enhanced, MR-Imaging, PET/MR, Breast, Oncology, Tumor Mircoenvironment, Electron Paramagnetic Resonance Supplemental material is available for this article. © RSNA, 2021

Focal laser ablation (FLA) is a minimally invasive thermal ablation, guided by MRI through an optical fiber, to induce coagulative necrosis in cancer.To evaluate the feasibility of high spectral and spatial resolution imaging using multiecho gradient echo (MEGE) MRI for identification of ablation zones, after FLA of prostate cancers.Prospective.Fourteen patients with biopsy-confirmed localized prostate cancers.FLA was performed under monitored conscious sedation with a 1.5T MRI scanner. Axial MEGE images were acquired before and after the last FLA. Pre- and postcontrast enhanced TTheNonparametric Kruskal-Wallis tests were performed to determine whether there was significant difference in calculated ablation areas and volumes betweenAverage2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:1374-1380.