Molecular Breast Imaging Research Articles

The Utility of Second-Look US to Evaluate Abnormal Molecular Breast Imaging Findings: A Retrospective Study.

The purpose of this study was to evaluate the utility of US for identifying and characterizing lesions detected on molecular breast imaging (MBI). A retrospective single-institution review was performed of patients with MBI studies with subsequent US for abnormal MBI findings between January 1, 2015, and September 30, 2021. Medical records, imaging, and histopathology were reviewed. The reference standard was histopathology and/or imaging follow-up. Associations among MBI findings, the presence of an US correlate, and histopathology were evaluated by Fisher exact tests. The 32 lesions detected on MBI in 25 patients were evaluated by US, and 19 lesions had an US correlate (19/32, 59%). Mass uptake was more likely to have an US correlate (11/13, 85%; P = .02) than nonmass uptake (7/19, 37%), and mass uptake was more likely to be malignant (5/13, 38%; P = .01). Of the 13 lesions without an US correlate, 5 were evaluated and subsequently biopsied by MRI (2 high-risk lesions and 3 benign lesions). Follow-up MBIs demonstrated stability/resolution for 5 lesions in 4 patients at 6 months or longer. Three patients had no further imaging. Mass lesions identified on MBI were more likely to have an US correlate and were more likely to be malignant than nonmass lesions.

Maximizing Breast Cancer Detection Through Screening: A Comparative Analysis of Imaging-Based Approaches

Introduction/BackgroundThis study estimates the percentage of detectable breast cancers in the screening population that could be found with primary and supplemental screening, and provides cost estimates for population wide supplemental screening in the U.S. Materials and MethodsPublished estimates on cancer detection rates of 2D mammography, tomosynthesis (DBT), whole breast ultrasound (US), molecular breast imaging (MBI), contrast-enhanced mammography (CEM), and MRI, the number of mammograms conducted in the United States in 2023, and the proportion of dense breast tissue, were utilized. The maximum number of detectable cancers was projected from incremental cancer detection rates of the most sensitive supplemental screening method. The proportion of cancers detectable for each modality was calculated. In 2023, Medicare reimbursement rates were used to estimate supplemental screening costs. ResultsOut of 469,437 detectable cancers, 2D mammography could detect 190,531 (41%), leaving 278,906 undetected. Adding supplemental screening could detect a combined 220,165 cancers (47%) with DBT, 237,596 (51%) with US, 331,727 (71%) with MBI, 377,049 (80%) with CEM and 469,437 (100%) with MRI. The imaging cost in US dollars to provide supplemental screening to all individuals with dense breasts in 2023 was $933M for tomosynthesis, $1.84B for US, $3.87B for CEM, $4.16B for MBI, and $6.36B for MRI. ConclusionThe study highlights potential benefits from supplemental breast cancer screening, suggesting the combination of mammography and breast MRI offers the most effective detection method though at the highest imaging cost. These findings provide valuable insights to guide future research and inform decision-making in supplemental breast cancer screening strategies.

Molecular Breast Imaging Biopsy with a Dual-Detector System.

Purpose To develop a molecular breast imaging (MBI)-guided biopsy system using dual-detector MBI and to perform initial testing in participants. Materials and Methods The Stereo Navigator MBI Accessory biopsy system comprises a lower detector, upper fenestrated compression paddle, and upper detector. The upper detector retracts, allowing craniocaudal, oblique, or medial or lateral biopsy approaches. The compression paddle allows insertion of a needle guide and needle. Lesion depth is calculated by triangulation of lesion location on the upper detector at 0° and 15° and relative lesion activity on upper and lower detectors. In a prospective study (July 2022-June 2023), participants with Breast Imaging Reporting and Data System category 2, 3, 4, or 5 breast lesions underwent MBI-guided biopsy. After injection of 740 MBq technetium 99m sestamibi, craniocaudal and mediolateral oblique MBI (2-minute acquisition per view) confirmed lesion visualization. A region of interest over the lesion permitted depth calculation in the system software. Upper detector retraction allowed biopsy device placement. Specimen images were obtained on the retracted upper detector, confirming sampling of the target. Results Of 21 participants enrolled (mean age, 50.6 years ± 10.1 [SD]; 21 [100%] women), 17 underwent MBI-guided biopsy with concordant pathology. No lesion was observed at the time of biopsy in four participants. Average lesion size was 17 mm (range, 6-38 mm). Average procedure time, including preprocedure imaging, was 55 minutes ± 13 (range, 38-90 minutes). Pathology results included invasive ductal carcinoma (n = 1), fibroadenoma (n = 4), pseudoangiomatous stromal hyperplasia (n = 6), and fibrocystic changes (n = 6). Conclusion MBI-guided biopsy using a dual-head system with retractable upper detector head was feasible, well tolerated, and efficient. Keywords: Breast Biopsy, Molecular Breast Imaging, Image-guided Biopsy, Molecular Breast Imaging-guided Biopsy, Breast Cancer Clinical trial registration no. NCT06058650 © RSNA, 2024.

Abstract PO4-19-02: Genetic risk estimation in breast cancer and assessing health disparities

Abstract Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-02.

Abstract PO1-07-10: Blood Based Early Cancer Detection Assay

Abstract Background: Breast cancer screening programs utilizing mammography have been shown to be highly effective in identifying breast cancer in women over the age of 40. High breast density is an independent risk factor for breast cancer and makes mammograms more difficult to interpret, decreasing their sensitivity. In the spring of 2023, the FDA, who certifies all mammography facilities under the Mammography Quality Standards Act, updated its regulations to require that breast density status be reported to all individuals receiving a mammogram. The new guidelines now require individuals with dense breast tissue be notified of this status. The guidelines also recommend these women discuss additional screening options with their healthcare providers1. These additional screening options may include breast tomosynthesis, breast MRI, breast ultrasound, and/or molecular breast imaging. Many of these options require additional exposure to radiation, are expensive, and are not equitably available across the country. In addition, they all require a follow-up appointment. Compliance can be challenging given the top barriers to mammography cited include the need for transportation, child-care, and the ability to take time off from work2. Genece Health is developing a simpler and less expensive screening solution that identifies the presence of early to late-stage breast cancer using cfDNA from a single blood draw. The Genece Health assay utilizes an algorithm that leverages Artificial Intelligence and Machine Learning to analyze fragment size and end motif patterns in cfDNA as well as regional mutational density to detect presence of ctDNA originating from breast cancer. This algorithm provides highly sensitive and specific results in a preliminary data set. Methods: The preliminary data set, presented herein, is a cohort of over 50 retrospective breast cancer plasma samples and over 100 presumed normal samples. The breast cancer samples were collected at all stages of progression, from stage 0, or ductal carcinoma in situ (DCIS), through stage IV. The majority ( >50%) were from stage I breast cancer. 400 µL of double spun plasma, collected in Streck BCT devices, was processed to purify and isolate cfDNA. cfDNA was used to create WGS libraries that were sequenced on a NovaSeq 6000. Sequence data were analyzed using a bioinformatics pipeline that yields an ensemble probability that correlates to the presence or absence of ctDNA from breast cancer. Results: The Genece Health assay and algorithm performed with a specificity greater than 85%. With this specificity, the assay had a sensitivity greater than 85% in samples from stages II to IV and a slightly lower sensitivity in stage 0 and I samples. Follow-up analyses were conducted to stratify performance based on breast cancer type (e.g. invasive ductal carcinoma vs invasive lobular carcinoma) and HR, PR, and HER2 status (e.g. HER2-negatives vs HER2-positives). Conclusions: The presented preliminary data indicate that the Genece Health technology can be leveraged as a complement to mammography in indications, such as dense breast tissue, where there is an unmet need for an easy and cost-effective way to monitor for breast cancer. The ability to have a blood-based test to complement mammography could reduce the access barriers most cited by females in the United States. Follow-up studies with greater numbers of samples and additional training and optimizations of the algorithm will yield performance improvements that allow the assay to detect all types and stages of breast cancer.

Abstract PO5-18-01: Cancer Detection Rate Meta-Analysis Comparison of Contemporary Dense-Breast Supplemental Screening Modalities

Abstract We performed a meta-analysis of the cancer detection rates from 24 published reports in dense breasts for all contemporary and FDA-approved imaging modalities (DM, DBT, U/S, CEM, MBI, MRI) available for supplemental breast cancer screening. This information is critical to the 40% of women with BIRADS categorized dense breasts (C,D) receiving breast cancer screening. In the paper an analysis of the net lives saved using a benefit-to-risk comparison of the ionizing imaging modalities (DM, DBT and MBI) is also presented and the safety of each technique is described. Note that it is well accepted that carcinogenic risk associated with ionizing radiation doses of < 100 mSv are considered too small to be detected or altogether non-existant. Recently, with FDA's federal MQSA requirements changing to mandate notification of womens' dense-breast status (C,D), awareness has grown substantially about the dismal cancer detection performances of DM, DBT and U/S which degrades substantially with increasing breast density. Additionally, this May 2023, federal legislation was introduced in congress. The Find It Early Act (HR3086), should it become law in 2024, will require that healthcare payors cover costs for supplemental screening of women with dense breasts. Knowing and understanding the arsenal of the highest performing imaging modalities (based on cancer detection rates (CDR), Sensitivity, Specificity, NPV) is critically important for all patients and physicians caring for them. The volume of women qualifying for supplemental breast screening is expected to be managed by existing and growing numbers of all the best performing available technologies and approaches. Since the analysis is based on numerous others’ clinical trials of CDRs evaluating the various modalities in millions of women, this comprehensive analysis presents a level playing field for comparison. The top-three high performing imaging modalities (CEM, MBI, MRI) should be used to increase the number of early-stage cancers found in order to substantially decrease mortality, decrease patient trauma, decrease procedures, and decrease costs per cancer detected, all at overall benefit to the patients, the hospitals, the payors and provide long-term benefits to society. Table. Summary of Relative Cancer Detection Rates (per 1,000 women) in Dense-Breast Supplemental Screening Results of multiple pairwise meta-analyses comparing various modalities (Digital Breast Tomosynthesis; Ultrasound; Contrast Enhanced Mammography; Molecular Breast Imaging; Magnetic Resonance Imaging) to Digital Mammography. “X” represents the second supplemental screening modality compared to DM. “+X” means the combination of DM+X. Two normalizations are compared: “CDR Ratio model” and “Incremental CDR model.” Table. Net Lives Saved by Ionizing Radiation Imaging Modalities per Age Decade Citation Format: Martin Tornai, James Hugg, Bradley Patt, Chin-Tu Chen, Eduardo Santos, Alaattin Erkanli, Samantha Morrison, Matthew Covington. Cancer Detection Rate Meta-Analysis Comparison of Contemporary Dense-Breast Supplemental Screening Modalities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-01.

Breast Radiologists' Perceptions on the Detection and Management of Invasive Lobular Carcinoma: Most Agree Imaging Beyond Mammography Is Warranted.

To determine breast radiologists' confidence in detecting invasive lobular carcinoma (ILC) on mammography and the perceived need for additional imaging in screening and preoperative settings. A 16-item anonymized survey was developed, and IRB exemption obtained, by the Society of Breast Imaging (SBI) Patient Care and Delivery Committee and the Lobular Breast Cancer Alliance. The survey was emailed to 2946 radiologist SBI members on February 15, 2023. The survey recorded demographics, perceived modality-specific sensitivity for ILC to the nearest decile, and opinions on diagnosing ILC in screening and staging imaging. Five-point Likert scales were used (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree). Response rate was 12.4% (366/2946). Perceived median (interquartile range) modality-specific sensitivities for ILC were MRI 90% (80-90), contrast-enhanced mammography 80% (70-90), molecular breast imaging 80% (60-90), digital breast tomosynthesis 70% (60-80), US 60% (50-80), and 2D mammography 50% (30-60). Only 25% (85/340) respondents were confident in detecting ILC on screening mammography in dense breasts, while 67% (229/343) were confident if breasts were nondense. Most agreed that supplemental screening is needed to detect ILC in women with dense breasts (272/344, 79%) or a personal history of ILC (248/341, 73%), with 34% (118/334) indicating that supplemental screening would also benefit women with nondense breasts. Most agreed that additional imaging is needed to evaluate extent of disease in women with newly diagnosed ILC, regardless of breast density (dense 320/329, 97%; nondense 263/329, 80%). Most breast radiologists felt that additional imaging beyond mammography is needed to more confidently screen for and stage ILC.

A Survey of Patient Experience During Molecular Breast Imaging.

Molecular breast imaging (MBI) is one of several options available to patients seeking supplemental screening due to mammographically dense breasts. Patient experience during MBI may influence willingness to undergo the test but has yet to be formally assessed. We aimed to assess patient comfort level during MBI, to compare MBI comfort with mammography comfort, to identify factors associated with MBI discomfort, and to evaluate patients' willingness to return for future MBI. Methods: A 10-question survey was sent by e-mail to patients undergoing MBI between August and December 2022 to obtain quantitative assessments and qualitative opinions about MBI. Results: Of 561 invited patients, 209 (37%) completed the survey and provided study consent. Their average age was 60.1 y (range, 40-81 y). Of the 209 responders, 202 (97%) were presenting for screening MBI, 195 (94%) had dense breasts, and 46 (22%) had a personal history of breast cancer. The average rating of MBI comfort was 2.9 (SD, 1.5; median, 3.0) on a 7-point scale (1 indicating extremely comfortable and 7 indicating extremely uncomfortable). The rating distribution was as follows: 140 (67%) comfortable (rating, 1-3); 24 (12%) neither comfortable nor uncomfortable (rating, 4); and 45 (22%) uncomfortable (rating, 5 or 6). No responders gave a 7 rating. The most frequently mentioned sources of discomfort included breast compression (n = 16), back or neck discomfort (n = 14), and maintaining position during the examination (n = 14). MBI comfort was associated with responder age (74% ≥55 y old were comfortable, versus 53% <55 y old [P = 0.003]) and history of MBI (71% with prior MBI were comfortable, versus 61% having a first MBI [P = 0.006]). Of 208 responders with a prior mammogram, 148 (71%) said MBI is more comfortable than mammography (a significant majority [P < 0.001]). Of 202 responders to the question of whether they were willing to return for a future MBI, 196 (97%) were willing. A notable factor in positive patient experience was interaction with the MBI nuclear medicine technologist. Conclusion: Most responders thought MBI to be a comfortable examination and more comfortable than mammography. Patient experience during MBI may be improved by ensuring back support and soliciting patient feedback at the time of positioning and throughout the examination. Methods under study to reduce imaging time may be most important for improving patient experience.

Impact of Imaging Biomarkers and AI on Breast Cancer Management: A Brief Review.

Breast cancer stands out as the most frequently identified malignancy, ranking as the fifth leading cause of global cancer-related deaths. The American College of Radiology (ACR) introduced the Breast Imaging Reporting and Data System (BI-RADS) as a standard terminology facilitating communication between radiologists and clinicians; however, an update is now imperative to encompass the latest imaging modalities developed subsequent to the 5th edition of BI-RADS. Within this review article, we provide a concise history of BI-RADS, delve into advanced mammography techniques, ultrasonography (US), magnetic resonance imaging (MRI), PET/CT images, and microwave breast imaging, and subsequently furnish comprehensive, updated insights into Molecular Breast Imaging (MBI), diagnostic imaging biomarkers, and the assessment of treatment responses. This endeavor aims to enhance radiologists' proficiency in catering to the personalized needs of breast cancer patients. Lastly, we explore the augmented benefits of artificial intelligence (AI), machine learning (ML), and deep learning (DL) applications in segmenting, detecting, and diagnosing breast cancer, as well as the early prediction of the response of tumors to neoadjuvant chemotherapy (NAC). By assimilating state-of-the-art computer algorithms capable of deciphering intricate imaging data and aiding radiologists in rendering precise and effective diagnoses, AI has profoundly revolutionized the landscape of breast cancer radiology. Its vast potential holds the promise of bolstering radiologists' capabilities and ameliorating patient outcomes in the realm of breast cancer management.

Breast Imaging Fellowship Training in the United States: A National Survey of Fellowship Program Directors.

To provide an updated characterization of breast imaging fellowship programs in the United States to identify opportunities for improvement and standardization. An anonymous survey was e-mailed to program directors of breast imaging fellowship programs listed on the Society of Breast Imaging website. The survey was open from April 23, 2021, through May 27, 2021. The survey was deemed exempt by the IRB. Forty-seven of 80 (59%) program directors responded, of which 36/47 (77%) represented programs dedicated 100% to breast imaging, and 11/47 (23%) represented programs dedicated 50%-75% to breast imaging. Common elements to most programs include tumor boards (47/47, 100%), journal clubs (39/47, 83%), case-based teaching sessions (35/47, 74%), didactic lectures (40/47, 85%), and participation in radiology-pathology conferences (29/47, 62%). Mammography Quality and Standards Act audit training (22/47, 47%), mammography quality control training (22/47, 47%), and formal communication training (19/47, 40%) were less common. Most programs provide exposure to wire (42/47, 89%) and wire-free localization procedures (45/47, 96%), but exposure to contrast-enhanced mammography (13/47, 28%) and molecular breast imaging (4/47, 9%) was limited. A small majority of programs (25/47, 53%) do not require weekday call; however, more (31/47, 66%) have weekend call responsibilities. Many programs (29/47, 62%) offer at least 3 weeks of elective time, which may be clinical or nonclinical. Breast imaging fellowship programs vary in curricula, modality exposure, and academic policies. The results of this survey can help guide further efforts to standardize and optimize fellowship training.

Early detection and Advanced Targeted Drug Therapies for HER2 positive breast cancer

HER 2 positive breast cancers are the aggressive subtype of breast cancer which can be treated completely if early detected. According to the National Cancer Institute, localized or stage 1 female breast cancer patients have a relative survival rate of 99% and they can survive for more than 5 years after diagnosis but only 63.1% cases are diagnosed at this stage. In later stages when it's diagnosed, the relative survival rate becomes 29%. The overexpression of HER2 proteins can be detected by early diagnosis and screening through advanced technologies like 3D mammography, Positron Emission Mammography, Molecular breast imaging, Contrast-enhanced mammography. The specific diagnosis can be done by Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) for confirmation of this type of breast cancer. Biomarkers such as Her2 heterogenicity, Her2 expression, Her2 mutations, Hormone receptor (ER positivity, PR positivity), PIK3CA mutation, PTEN, PD-L1, TIL, BRCA, miRNA can be used for detection of breast cancer. With successful early detection, which will be used to diagnose early and start the treatment as early as possible. Recently FDA has approved various individual and combination medications for treating the HER2 positive breast cancer and there are further research studies and clinical trials are going on to get more impactful treatment for providing complete cure of the deadly disease.

Feasibility of Tc-99 m sestamibi uptake quantification with few-projection emission tomography.

Molecular breast imaging uses Tc-99 m sestamibi to obtain functional images of the breast. Determining the Tc-99 m sestamibi uptake in volumes of interest in the breast may be useful in assessing the response to neoadjuvant chemotherapy or for the purposes of breast cancer risk assessment. To determine, using Monte Carlo simulation, if emission tomography can be used to quantify the uptake of Tc-99 m sestamibi in molecular breast imaging and if so, to determine the accuracy as a function of the number of projections used in the reconstruction process. In this study, two voxelized breast models are implemented with different ratios of fibroglandular to fatty tissue and tumoral masses of varying dimensions. Monte Carlo simulation is used to calculate sets of projections, which assumes that each tumoral mass contains a given Tc-99 m activity. Projections are also calculated for a calibration phantom in order to correlate the known activity with the image pixel value. For each case, the total number of calculated projections is 36 and the reconstruction is carried out for 36, 18, 9, 7 and 5 projections, respectively, using an open source image reconstruction toolbox. Study data show that determination of Tc-99 m sestamibi uptake with and average error of 7% can be carried out with as little as 7 projections. Molecular breast emission tomography enables to accurately determine the Tc-99 m sestamibi tumoral mass uptake with the number of projections very close to the number of images currently acquired in clinical practice.

Clinical impact of molecular breast imaging as adjunct diagnostic modality in evaluation of indeterminate breast abnormalities and unresolved diagnostic concerns.

Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy. We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99m Tc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months. Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9-7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge ( N = 42) and BI-RADS 3 lesions ( N = 113) MBI detected 7 of 8 occult malignancies. MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%.

Design of a Low-Dose, Stationary, Tomographic Molecular Breast Imaging System Using 3-D Position Sensitive CZT Detectors

Molecular breast imaging (MBI) has been shown to have high sensitivity for lesion detection, particularly in patients with dense breasts where conventional mammography is limited. However, relatively high radiation dose and long imaging time are limiting factors. Most current MBI systems are based on planar imaging. Improved performance can be achieved using tomographic techniques, which normally involve detector motion. Our goal is to develop a low-dose stationary tomographic MBI system with similar or better performance in terms of lesion detection compared to planar MBI. The proposed system utilizes two opposing cadmium zinc telluride detectors with high intrinsic resolution and depth of interaction (DOI) capability, combined with densely packed multipinhole collimators. This leads to improved efficiency and adequate angular sampling, but also to significant multiplexing (MX), which can result in artefacts. We have developed de-MX algorithms that take advantage of the DOI information. We have performed both analytic and Monte Carlo simulations to demonstrate the feasibility, optimize the design and investigate the expected performance of the proposed system. Lesion detectability was preserved with reduction of acquisition time (or radiation dose) by a factor of 2 compared to planar images at the lowest reported dose. The first prototype is under evaluation at Kromek.

Evaluation of CZT Drift Strip Detectors for Use in 3-D Molecular Breast Imaging

X-ray mammography is a widely used technique for breast cancer screening. However, the technique is imprecise when it comes to radiographically dense breast tissue, and therefore a supplemental screening technique, such as molecular breast imaging (MBI), could increase the cancer detection rate. Emerging technologies within MBI require excellent detector performance, preferably with a submillimeter intrinsic spatial resolution. A collaboration between Kromek and DTU Space aims to advance the DTU Space developed 3-D CdZnTe (CZT) drift strip technology, for application in new emerging MBI systems. This collaboration has resulted in ten compact 3-D MBI test modules with the goal of producing high-performance and high yield detectors. In this article, we present overall excellent detector performance, submillimeter position resolution at both 122 and 661.6 keV, and good energy resolution for the applied electrode deposition and contact optimization. Although the current experimental setup and results suffer from high electronic noise (using discrete NIM standard charge sensitive preamplifiers), we conclude that the measured spatial and spectral performance fulfills the expected requirements for the modules, with room for improvement, especially within limiting electronic noise. The detector test modules indicate a promising future for the 3-D CZT drift strip technology within future emerging MBI systems.

Monte Carlo-derived 99m Tc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations.

Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of 99m Tc uptake in benign and malignant breast tissues. This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue 99m Tc uptake MBI measurements using simulations of a commercial dual-headed planar MBI system under typical clinical and acquisition protocols. Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single-detector-based and two geometric-mean-based), two tumor MBI volume methodologies (diameter-based and ROI-based), and two normal tissue activity concentration methodologies (single-detector-based and geometric-mean-based). The most accurate of these techniques were then used to estimate tumor activity concentrations and tumor to normal tissue relative activity concentrations (RC). Single-detector techniques for tumor total activity quantification achieved mean (standard deviation) relative errors of 0.2% (4.3%) and 1.6% (4.4%) when using the near and far detector images, respectively and were more accurate and precise than the measured 8.1% (5.8%) errors of a previously published geometric-mean technique. Using these activity estimates and the true tumor volumes resulted in tumor activity concentration and RC errors within 10% of simulated values. The precision of tumor activity concentration and RC when using only MBI measurements were largely driven by the errors in estimating tumor MBI volume using planar images (±30% inter-quartile range). Planar MBI images were shown to accurately and reliably be used to estimate tumor total activities and normal tissue activity concentrations in this simulation study. However, volumetric tumor uptake measurements (i.e., absolute and relative concentrations) are limited by inaccuracies in MBI volume estimation using two-dimensional images, highlighting the need for either tomographic MBI acquisitions or anatomical volume estimates for accurate three-dimensional tumor uptake estimates.

Monte Carlo-derived 99m Tc uptake quantification with commercial planar MBI: Absolute tumor activity.

Molecular breast imaging (MBI) of 99m Tc-sestamibi is an emerging adjunct qualitative tool in the detection and diagnosis of breast cancer. This work outlines the development and performance evaluation of a methodology to absolutely quantify tumor 99m Tc activity uptake using a commercially available dual-headed MBI system by implementing corrections for background, scatter, attenuation, and detector characteristics. A validated Monte Carlo application of a commercial MBI system was used to simulate over 7000 unique acquisitions of spherical and ellipsoidal tumors in breast tissue. Tumor absolute activity was calculated following background, scatter, and attenuation corrections of tumor region of interest counts. The methodology was first optimized using a set of high-uptake spherical tumors, and its accuracy and precision was then assessed in a set of spherical tumors with clinical uptake conditions. Finally, the performance of the activity methodology was evaluated under various bias and uncertainty conditions to better characterize the technique under expected clinical measurement conditions. In a test set of images with clinically relevant contrast and noise conditions, the mean ± standard deviation relative error in total tumor activity was 0.5% ± 6.5% (n = 2363) under ideal measurement conditions. Allowing for variability in tumor and background contours and in estimated tumor depths, the expected accuracy of the methodology in clinical practice was 0.5% ± 11.1% (n = 2363), with minimal loss of accuracy for ellipsoidal tumors. Planar MBI photopeak images acquired with standard-of-care protocols can be used to accurately quantify absolute tumor 99m Tc activity with an accuracy and precision of 0.5% ± 11.1%. The reported precision was based on a comprehensive evaluation of random errors and systematic biases.

Radionuclide imaging of breast cancer: experience of FSBI “N.N. Petrov National Medical Research Centre of Oncology” of the Ministry of Healthcare of Russian Federation

Abstract. Breast cancer is one of the most common malignant neoplasms among women nowadays. Timely diagnosis is the basis for effective and successful treatment of this disease. The existing classical methods of X-ray examination (MG, ultrasound, MRI) play a major role in the detection of breast cancer, but in some cases, the diagnosis of breast cancer can be difficult. Therefore, diagnostic performance of scintimammography with specialized gamma camera called molecular breast imaging (MBI) is now of particular clinical interest.Materials and methods. 312 patients with a preliminary clinical diagnosis of breast cancer were examined in the department of radionuclide diagnostics of N.N. Petrov Research Center of Oncology. They underwent scintimammography (MBI) with a specialized gamma camera manufactured by GE (Discovery 750b). Images of both breasts were obtained 15 min after intravenous injection of 500 MBq activity of 99mTc-MIBI. The foci of moderate and intensive radiopharmaceutical accumulation in breast were considered as a sign of a tumor. The diagnostic performance of MBI and the sensitivity in detection of various biological subtypes of cancer were calculated by comparing with the results of morphological and immunohistochemically studies.Results. The sensitivity, specificity and accuracy of the MBI in the diagnostics of breast cancer were 88, 75 and 87%, respectively. Sensitivity of this method in detection of different biological subtypes ranged from 89% to 95% with lowest performance found in luminal A subtype.Conclusion. Scintimammography (MBI) is an informative way of breast cancer diagnostics. The revealed differences in the sensitivity of the method in patients with different biological subtypes of breast cancer confirm the need for further study of this topic.

Downstream imaging following abnormal molecular breast imaging, lessons learned and suggestions for success

ObjectivesMolecular breast imaging (MBI) is a supplemental screening modality that assists in detection of breast cancer. Objectives were to investigate how abnormal MBI findings were further evaluated on subsequent imaging studies and assess outcomes. MethodsRetrospective single-institution review included patients who underwent supplemental screening MBI between October 2018 and October 2021, utilizing 300 MBq (8 mCi) 99mTc-sestamibi as radiotracer. Patients with abnormal MBI were assessed for subsequent imaging, biopsies, or surgeries performed. Outcome metrics included recall rate, cancer detection rate, and positive predictive values for recall (PPV1) and biopsy (PPV3); 95% confidence intervals calculated via Wilson score interval. All tests were two-sided; p < 0.05 considered statistically significant. ResultsTotal of 716 MBI exams performed, 93 of which were read as abnormal with ultimate detection of 11 malignancies. Recall rate was 13.0%, cancer detection rate was 15.4/1000 (invasive: 11.2/1000), PPV1 was 11.8%, and PPV3 was 27.5%. Of 11 malignancies, 7 (63.6%) were not visible on concurrent or most recent mammogram. Initial subsequent imaging study detected a correlate for mass uptake in 20/22 (90.9%) cases compared to 42/70 (60.0%) for nonmass uptake (p < 0.007), with correlates for nonmass uptake seen on ultrasound or mammogram in only 5/19 (26.3%). MRI was utilized in 63 (8.8%) cases overall. ConclusionScreening MBI afforded a high cancer detection rate, yet lower detection of nonmass uptake on subsequent ultrasound/mammography resulted in increased usage of MRI compared to prior reports. As utilization of MBI increases, more reported experiences are needed to establish best practices and understand effects of implementation.

Invasive micropapillary breast carcinoma: A retrospective study on the clinical imaging features and pathologic findings.

PurposeTo describe the clinical imaging and pathological features of invasive micropapillary breast carcinoma (IMPC), including breast mammography, sonography, magnetic resonance imaging (MRI), and molecular imaging findings.Patients and methodsWe retrospectively reviewed our institution's surgical pathology database and identified 65 patients with pathologically proven IMBC; 63/65 patients had available imaging results. Two radiologists retrospectively reviewed all imaging evaluations according to the Breast Imaging Reporting / Data System (BI-RADS) Lexicon. Clinical and histopathologic features, receptor statuses, and clinical follow-up data were recorded.ResultsSixty-three patients were admitted with palpable abnormalities; one patient's mammogram revealed no abnormality (3.3%, 1/32), whereas 31 had abnormal mammograms (31/32, 96.8%) demonstrating 37 lesions. Twenty-four had irregular, spiculated masses, 12 had microcalcifications, and 19 had architectural distortion. Sonography detected 69 masses (54 patients), characterized by irregular shapes (61/69, 88.4%), hypoechoic structures (50/69, 72.4%), angular or spiculated margins (38/69, 55.1%; 30/69, 43.4%), echogenic halo (8/69, 11.5%), and abnormal vascularity (52/69, 75.3%). MRI detected 68 lesions (52 patients); 59/68 (86.8%) appeared as masses with angular or spiculated margins (32/68, 47.1%; 35/68, 51.4%), 58 exhibited irregular or lobulated shapes (58/68, 89.7%), 29 displayed heterogeneous internal enhancement (29/68, 42.5%), and 64 demonstrated type II or III washout kinetic curves (37/68, 55%; 27/68, 40%). Breast molecular imaging showed mild-to-moderate radiotracer uptake in 15 focal areas among 13 patients. Thirty-two, 38, and 43 patients had abnormal lymph nodes identified mammographically, by breast sonography, and by MRI, respectively. Immunohistochemistry revealed high estrogen receptor (90.5%), high progesterone receptor (71.6%), and low HER-2 (26.4%) positivity.ConclusionIMPC mammography, sonography, and MRI clinical imaging features highly suggest malignancy. Breast molecular imaging also contributed to the diagnosis. IMPC's invasiveness correlated well with regional lymph node metastasis. Radiologists and surgeons should be more attentive to these imaging findings and additional clinical and pathological IMPC features.