Long-term outcomes of intraoperatively-placed applicator brachytherapy for rapid completion of breast conserving treatment: An analysis of a prospective registry data.

Background and purpose: To evaluate the long-term outcome of accelerated partial breast irradiation utilizing intraoperatively placed applicator-based brachytherapy (ABB) in early-stage breast cancer. Materials and methods: From our prospective registry, 223 patients with pTis-T2, pN0/pN1mic breast cancer were treated with ABB. The median treatment duration including surgery and ABB was 7 days. The prescribed doses were 32 Gy/8 fx BID (n = 25), 34 Gy/10 fx BID (n = 99), and 21 Gy/3 fx QD (n = 99). Endocrine therapy (ET) adherence was defined as completion of planned ET or ≥ 80% of the follow-up (FU) period. Cumulative incidence of ipsilateral breast tumor recurrence (IBTR) was estimated and influencing factors for IBTR-free survival rate (IBTRFS) were analyzed. Results: 218/223 patients had hormone receptor-positive tumors, including 38 (17.0%) with Tis and 185 (83.0%) with invasive cancer. After a median FU of 63 months, 19 (8.5%) patients had recurrence [17 (7.6%) with an IBTR]. Rates of 5-year IBTRFS and DFS were 92.2% and 91.1%, respectively. The 5-year IBTRFS rates were significantly higher for post-menopausal women (93.6% vs. 66.4%, p = 0.04), BMI < 30 kg/m2 (97.4% vs. 88.1%, p = 0.02), and ET-adherence (97.5% vs. 88.6%, p = 0.02). IBTRFS did not differ with dose regimens. Conclusions: Postmenopausal status, BMI < 30 kg/m2, and ET- adherence predicted favorable IBTRFS. Our results highlight the importance of careful patient selection for ABB and encouragement of ET compliance.

PPV of the Molecular Breast Imaging Lexicon.

BACKGROUND. Molecular breast imaging (MBI) is used for various breast imaging indications. An MBI lexicon has been developed, although the likelihood of malignancy of the lexicon descriptors has not been assessed to our knowledge. OBJECTIVE. The purpose of this article was to evaluate the PPV for malignancy of the MBI lexicon imaging descriptors. METHODS. This retrospective study included MBI examinations performed from August 1, 2005, through August 31, 2017, that were positive (BI-RADS analogous categories 0, 3, 4, 5, or 6) according to the clinical report and had an available reference standard. Examinations were performed using dual-detector cadmium zinc telluride MBI systems after injection of 99mTc sestamibi. Category 3 lesions had pathologic correlation, at least 2 years of imaging follow-up, or final resolution on follow-up imaging as category 1 or 2; category 4 and 5 lesions had pathologic correlation. MBI examinations were reviewed by one of two radiologists to assess lesions on the basis of the published MBI lexicon for type (mass vs nonmass uptake), distribution (if nonmass uptake), uptake intensity, and number of MBI views on which the lesion was seen. PPV for malignancy was summarized. RESULTS. The analysis included 643 lesions (479 benign, 164 malignant; 83 mass, 560 nonmass uptake) in 509 patients (median age, 56 years). PPV was 73.5% (61/83) for masses and 18.4% (103/560) for nonmass uptake. Among the nonmass uptake lesions, PPV was 36.2% (17/47) for segmental, 20.1% (77/384) for focal, 30.8% (4/13) for diffuse, and 4.3% (5/116) for regional or multiple regional distribution. PPV was 5.3% (5/94) for one view, 15.2% (32/210) for two views, 14.6% (13/89) for three views, and 45.4% (113/249) for four views showing the lesion. PPV was 14.0% (43/307) for mild, 22.4% (51/228) for moderate, and 64.8% (70/108) for marked uptake intensity. CONCLUSION. The MBI lexicon lesion descriptors are associated with likelihood of malignancy. PPV was higher for masses, lesions seen on multiple MBI views, and lesions with marked uptake intensity. Among nonmass uptake lesions, PPV was highest for those with segmental distribution. CLINICAL IMPACT. Insight into the likelihood of malignancy associated with the MBI lexicon descriptors can inform radiologists' interpretations and guide potential future incorporation of the MBI lexicon into the ACR BI-RADS Atlas.

Comparison of breast density assessments between synthesized C-View™ & intelligent 2D™ mammography.

OBJECTIVE: To compare breast density assessments between C-View™ and Intelligent 2D™, different generations of synthesized mammography (SM) from Hologic. METHODS: In this retrospective study, we identified a subset of females between March 2017 and December 2019 who underwent screening digital breast tomosynthesis (DBT) with C-View followed by DBT with Intelligent 2D. Clinical Breast Imaging Reporting and Database System breast density was obtained along with volumetric breast density measures (including density grade, breast volume, percentage volumetric density, dense volume) using VolparaTM. Differences in density measures by type of synthesized image were calculated using the pairwise t-test or McNemar's test, as appropriate. RESULTS: 67 patients (avg age 62.7; range 40-84) were included with an average of 13.3 months between the two exams. No difference was found in Breast Imaging Reporting and Database System density between the SM reconstructions (p = 0.74). Similarly, there was no difference in VolparaTM mean density grade (p = 0.71), mean breast volume (p = 0.48), mean dense volume (p = 0.43) or mean percent volumetric density (p = 0.12) between the exams. CONCLUSION: We found no significant differences in clinical and automated breast density assessments between these two versions of SM. ADVANCES IN KNOWLEDGE: Lack of differences in density estimates between the two SM reconstructions is important as density assignment impacts risk stratification and adjunct screening recommendations.

Leveling the Workload for Radiologists in Diagnostic Mammography: Application of Lean Principles and Heijunka.

To facilitate the delivery of accurate and timely care to patients in complex environments, process improvement methodologies such as Lean can be very effective. Lean is a quality improvement methodology that seeks to add value for patients and employees by continuously improving processes and eliminating waste. At our institution, Lean principles were applied to improve efficiency and minimize waste in the diagnostic breast imaging reading room. This paper describes how we applied Lean principles, including plan-do-study-act testing, level-loading (heijunka), and visual management, to level the workload of the diagnostic radiologists in our practice. Implementation of these principles to improve the diagnostic workflow in breast imaging is described along with examples from our practice, including challenges and future opportunities.

Preparing for the next pandemic: It is more than just about numbers.

The COVID-19 pandemic has brought enormous hardships to our country and healthcare system. We present our experience navigating through this pandemic with emphasis on reactivating our practice while keeping patients and staff safe. It is hoped that the methods and thought processes provided in this manuscript will help those who are in various stages of managing their practice or provide lessons learned as our country eventually moves beyond this pandemic. Lastly, we aspire to provide a guide for those who are in a position to prepare for the next pandemic.

Mitigating the Transmission of COVID-19 with the Appropriate Usage of Personal Protective Protocols and Equipment in Breast Imaging and Intervention.

The integration of personal protective equipment (PPE) and procedures into breast imaging and intervention practices will mitigate the risk of transmission of COVID-19 during the pandemic. Although supply chain shortages have improved, understanding the proper use of PPE and protocols to mitigate overconsumption are important to ensure efficacious utilization of PPE. Protocols and best practices are reviewed, and guidelines and resource materials are referenced in order to support breast imaging healthcare professionals.

Dose Reduction in Molecular Breast Imaging With a New Image-Processing Algorithm.

OBJECTIVE. The purpose of this study was to determine whether application of a proprietary image-processing algorithm would allow a reduction in the necessary administered activity for molecular breast imaging (MBI) examinations. MATERIALS AND METHODS. Images from standard-dose MBI examinations (300 MBq 99mTc-sestamibi) of 50 subjects were analyzed. The images were acquired in dynamic mode and showed at least one breast lesion. Half-dose MBI examinations were simulated by summing one-half of the dynamic frames and were processed with the algorithm under study in both a default and a preferred filter mode. Two breast radiologists independently completed a set of two-alternative forced-choice tasks to compare lesion conspicuity on standard-dose images, half-dose images, and the algorithm-processed half-dose images in both modes. RESULTS. Relative to the standard-dose images, the half-dose images were preferred in 4, the default-filtered half-dose images in 50, and preferred-filtered half-dose images in 76 of 100 readings. Compared with standard-dose images, in terms of lesion conspicuity, the half-dose images were rated better in 2, equivalent in 6, and poorer in 92 of 100 readings. The default-filtered half-dose images were rated better, equivalent, or poorer in 13, 73, and 14 of 100 readings. The preferred-filtered half-dose images were rated as better, equivalent, or poorer in 55, 34, and 11 of 100 readings. CONCLUSION. Compared with that on standard-dose images, lesion conspicuity on images obtained with the algorithm and acquired at one-half the standard dose was equivalent or better without compromise of image quality. The algorithm can also be used to decrease imaging time with a resulting increase in patient comfort and throughput.

Ability of Intraoperative Pathologic Analysis of Ductal Carcinoma In Situ to Guide Selective Use of Sentinel Lymph Node Surgery.

For patients with ductal carcinoma In Situ (DCIS), sentinel lymph node (SLN) surgery is generally reserved for patients at high risk of being upstaged to invasive disease. The use of frozen section (FS) pathologic analysis of the primary tumor may allow for selective surgical nodal staging within one procedure. We sought to define the reliability of FS for detection of upstaging. Eight hundred and twenty-seven patients were identified with DCIS on core needle biopsy that underwent 834 operations at our institution between January 2004 and October 2014. We calculated the rate of upstage from DCIS to invasive cancer on both intraoperative FS and final pathology to determine the performance of FS. Upstage rate on final pathology was 118/834 (14.1%) 95 per cent confidence interval 11.8 to 16.7 per cent. FS identified 88/118 (74.6%) of the upstages. Specificity was 99.3 per cent (711/716). Overall accuracy was 95.8 per cent (799/834) and the positive predictive value was 96.0 per cent (711/741 patients). Mean size of invasive cancers identified on FS was 5.6 mm, versus 3.5 mm for those identified only on permanent section, P = 0.11. Intraoperative FS analysis of DCIS is useful for identification of upstage to invasive disease. This may facilitate a selective approach to SLN surgery that both decreases unnecessary SLN surgery and the need for a second operation.

BEST PRACTICES IN MOLECULAR BREAST IMAGING: A GUIDE FOR TECHNOLOGISTS.

Molecular breast imaging (MBI) technologists are required to possess a combination of nuclear medicine skills and mammographic positioning techniques. Currently, no formal programs offer this type of hybrid technologist training. The purpose of this perspective is to provide a best practices guide for technologists performing MBI. Familiarity with best practices may aid in obtaining high-quality MBI examinations by decreasing the likelihood of image artifacts, positioning problems and other factors that contribute to false negative or false positive findings.

Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study.

BACKGROUND: Patient-derived xenografts (PDXs) are increasingly used in cancer research as a tool to inform cancer biology and drug response. Most available breast cancer PDXs have been generated in the metastatic setting. However, in the setting of operable breast cancer, PDX models both sensitive and resistant to chemotherapy are needed for drug development and prospective data are lacking regarding the clinical and molecular characteristics associated with PDX take rate in this setting. METHODS: The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant chemotherapy (NAC) trial of stage I-III breast cancer patients treated with neoadjuvant weekly taxane+/-trastuzumab followed by anthracycline-based chemotherapy. Using percutaneous tumor biopsies (PTB), we established and characterized PDXs from both primary (untreated) and residual (treated) tumors. Tumor take rate was defined as percent of patients with the development of at least one stably transplantable (passed at least for four generations) xenograft that was pathologically confirmed as breast cancer. RESULTS: Baseline PTB samples from 113 women were implanted with an overall take rate of 27.4% (31/113). By clinical subtype, the take rate was 51.3% (20/39) in triple negative (TN) breast cancer, 26.5% (9/34) in HER2+, 5.0% (2/40) in luminal B and 0% (0/3) in luminal A. The take rate for those with pCR did not differ from those with residual disease in TN (p = 0.999) and HER2+ (p = 0.2401) tumors. The xenografts from 28 of these 31 patients were such that at least one of the xenografts generated had the same molecular subtype as the patient. Among the 35 patients with residual tumor after NAC adequate for implantation, the take rate was 17.1%. PDX response to paclitaxel mirrored the patients' clinical response in all eight PDX tested. CONCLUSIONS: The generation of PDX models both sensitive and resistant to standard NAC is feasible and these models exhibit similar biological and drug response characteristics as the patients' primary tumors. Taken together, these models may be useful for biomarker discovery and future drug development.

A Validated Nomogram to Predict Upstaging of Ductal Carcinoma in Situ to Invasive Disease.

BACKGROUND: Approximately 8-56% of patients with a core needle biopsy (CNB) diagnosis of ductal carcinoma in situ (DCIS) will be upstaged to invasive disease at the time of excision. Patients with invasive disease are recommended to undergo axillary nodal staging, most often requiring a second operation. We developed and validated a nomogram to preoperatively predict percentage of risk for upstaging to invasive cancer. METHODS: We reviewed 834 cases of DCIS on CNB between January 2004 and October 2014. Multivariable analysis was used to evaluate CNB and imaging factors to develop a nomogram to predict the risk of upstaging from DCIS to invasive cancer. This nomogram was validated with an external dataset of 579 similar patients between November 1998 and September 2016. An area under the receiver operating characteristic curve was constructed to evaluate nomogram discrimination. RESULTS: The rate of upstaging to invasive disease was 118/834 (14.1%). On multivariable analysis, grade on CNB and imaging factors, including mass lesion, multicentric disease, and largest linear dimension, were associated with upstage to invasive disease, and was used to develop a nomogram (c-statistic 0.71). In the external validation dataset, 62/579 (10.7%) patients were upstaged to invasive disease. Our nomogram was validated in this dataset with a c-statistic of 0.71. CONCLUSION: For patients with a CNB diagnosis of DCIS, our validated nomogram using DCIS grade on biopsy, and imaging factors of mass lesion, multicentric disease, and largest linear dimension, may be used for preoperative assessment of risk of upstaging to invasive disease, allowing patient counseling regarding axillary staging at the time of definitive surgery.

Identifying a subset of patients with DCIS who have a low likelihood of residual disease at surgical excision following a core needle biopsy.

BACKGROUND AND OBJECTIVES: Current randomized controlled trials are investigating the outcomes of non-surgical treatment for patients with ductal carcinoma in situ (DCIS). We sought to evaluate pre-operative factors associated with no residual disease at definitive resection following a core needle biopsy (CNB) diagnosis of DCIS. METHODS: Eight hundred and thirty-four operations for DCIS were performed at our institution between January 2004 and October 2014. We evaluated patient and biopsy tumor characteristics to determine pre-operative factors associated with no residual disease at surgical resection using uni- and multivariable analyses. RESULTS: Sixty-nine patients (8%) had no residual disease on final pathology. On multivariable analysis, low- or intermediate-grade lesions, <1 cm in size on mammography, and lesions where ≥90% of calcifications were removed correlated with finding no residual disease on final pathology, c-statistic 0.84. Of the 14 patients with all three low-risk factors, 36% had no residual disease on final pathology. CONCLUSIONS: Although our multivariable analysis performed well, its clinical utility would be limited as we were unable to identify a subset of patients with DCIS in whom the probability of finding no residual disease is low enough to consider routine use of non-surgical management.

Technical Note: Development of a combined molecular breast imaging/ultrasound system for diagnostic evaluation of MBI-detected lesions.

PURPOSE: The purpose of this study was to perform a pilot evaluation of an integrated molecular breast imaging/ultrasound (MBI/US) system designed to enable, in real-time, the registration of US to MBI and diagnostic evaluation of breast lesions detected on MBI. METHODS: The MBI/US system was constructed by modifying an existing dual-head cadmium zinc telluride (CZT)-based MBI gamma camera. The upper MBI detector head was replaced with a mesh panel, which allowed an ultrasound probe to access the breast. An optical tracking system was used to monitor the location of the ultrasound transducer, referenced to the MBI detector. The lesion depth at which ultrasound was targeted was estimated from analysis of previously acquired dual-head MBI datasets. A software tool was developed to project the US field of view onto the current MBI image. Correlation of lesion location between both modalities with real-time MBI/US scanning was confirmed in a breast phantom model and assessed in 12 patients with a breast lesion detected on MBI. RESULTS: Combined MBI/US scanning allowed for registration of lesions detected on US and MBI as validated in phantom experiments. In patient studies, successful registration was achieved in 8 of 12 (67%) patients, with complete registration achieved in seven and partial registration achieved in one patient. In 4 of 12 (37%) patients, lesion registration was not achieved, partially attributed to uncertainty in lesion depth estimates from MBI. CONCLUSION: The MBI/US system enabled successful registration of US to MBI in over half of patients studied in this pilot evaluation. Future studies are needed to determine if real-time, registered US imaging of MBI-detected lesions may obviate the need to proceed to more expensive procedures such as contrast-enhanced breast MRI for diagnostic workup or biopsy of MBI findings.

Performance characteristics of dedicated molecular breast imaging systems at low doses.

PURPOSE: The purpose of this study was to compare the system performance characteristics and lesion detection capability of two molecular breast imaging (MBI) systems: a multicrystal sodium iodide (NaI)-based single-head system and a cadmium zinc telluride (CZT)-based dual-head system at low administered doses (150-300 MBq) of Tc-99m sestamibi. METHODS: System performance characteristics including count sensitivity, uniformity, energy resolution, and spatial resolution were measured using standard NEMA methods, or a modified version thereof in cases where the standard NEMA protocol could not be applied. A contrast-detail phantom with 48 lesions at varying depths from the collimator surface was used to assess lesion contrast-to-noise-ratio (CNR) using background count densities comparable to those observed in patient studies performed with administered doses of 150 MBq Tc-99m sestamibi. Lesions with CNR >3 were deemed to be detectable. Thirty patients undergoing MBI examinations with administered doses of 150-300 MBq were scanned for an additional view on the pixelated NaI system. CNR was calculated for lesions observed on patient images. Background count densities of patient images were measured and compared between the two systems. RESULTS: Over the central field of view, integral and differential uniformity were 6.1% and 4.2%, respectively, for the pixelated NaI system, and 3.8% and 2.7%, respectively, for the CZT system. Count sensitivity was 10.8 kcts/min/MBq for the NaI system and 32.9 kcts/min/MBq for the CZT system. Energy resolution was 13.5% on the pixelated NaI system and 4.5% on the CZT system. Spatial resolution (full-width at half-maximum) for the pixelated NaI detector was 4.2 mm at a distance of 1.2 cm from the collimator and 5.2 mm at 3.1 cm. Spatial resolution of a single CZT detector was 2.9 mm at a distance of 1.2 cm from the collimator and 4.7 mm at 3.1 cm. Effective spatial resolution obtained with dual-head CZT was below 4.7 mm throughout a simulated breast thickness of 6 cm. From contrast-detail phantom images of lesions at distances of 1.5-4.5 cm from the collimator face, the CZT system detected 124 of 144 (86%) of lesions compared to 97 of 144 (67%) with the NaI system. In patient studies, from comparison of the same view with both systems, a total of 7 breast lesions were identified on CZT system in seven patients, and 4 of 7 (57%) were detected on NaI system. Patient image background count densities on the CZT system were on average 3.4 times higher than those on the NaI system. CONCLUSIONS: The CZT system demonstrated better uniformity, count sensitivity, spatial resolution, energy resolution, and lesion detection in phantom and patient studies compared to the NaI system. At administered doses of 150-300 MBq Tc-99m sestamibi, patient results obtained with CZT systems may not be directly translatable to NaI systems.

Radial scar/complex sclerosing lesions: a clinicopathologic correlation study from a single institution.

Radial scars (RSs) or complex sclerosing lesions (CSLs) of the breast are benign radiologic and histologic entities. With the introduction of population-based screening programs, their incidence has increased to 0.03% to 0.09% of all core needle biopsies (CNBs). They can pose diagnostic difficulty because their radiologic and histologic appearances mimic carcinoma. We retrospectively searched for and reviewed all cases of RS/CSL diagnosed on image-guided CNB from January 1, 1994, to August 31, 2013, at a single institution. We also assessed the pathologic reports from excisional biopsies to identify cases upstaged to atypia or neoplasm. After exclusions, 100 CNBs were identified from 97 women, which showed RS/CSL without concomitant atypia. Mean age of the women was 52.9 years. Thirty-five women (38/100 CNBs, 38%) had follow-up excision. The median size of the excised RS/CSLs was 1.2 cm; 69% were larger than 1.0 cm. Almost all excised cases (92%) showed radiologic and pathologic concordance, and 79% were designated as suspicious for malignancy (Breast Imaging Reporting and Data System level 4). The most common findings of 38 follow-up excisional biopsies were residual RS (22 [58%]), atypical lobular hyperplasia (5 [13%]), and no residual lesion (5 [13%]). Eleven excisional biopsies (29%) were upstaged to invasive or in situ carcinoma or to atypical hyperplasia. Follow-up excisional biopsy is warranted for RS/CSLs, specifically those larger than 1.0 cm with worrisome radiographic findings or with radiologic and pathologic discordance. Approximately 29% of cases were upstaged to in situ or invasive carcinomas or other high-risk lesions in our study.

Collimator design for a dedicated molecular breast imaging-guided biopsy system: proof-of-concept.

PURPOSE: Molecular breast imaging (MBI) is a dedicated nuclear medicine breast imaging modality that employs dual-head cadmium zinc telluride (CZT) gamma cameras to functionally detect breast cancer. MBI has been shown to detect breast cancers otherwise occult on mammography and ultrasound. Currently, a MBI-guided biopsy system does not exist to biopsy such lesions. Our objective was to consider the utility of a novel conical slant-hole (CSH) collimator for rapid (<1 min) and accurate monitoring of lesion position to serve as part of a MBI-guided biopsy system. METHODS: An initial CSH collimator design was derived from the dimensions of a parallel-hole collimator optimized for MBI performed with dual-head CZT gamma cameras. The parameters of the CSH collimator included the collimator height, cone slant angle, thickness of septa and cones of the collimator, and the annular areas exposed at the base of the cones. These parameters were varied within the geometric constraints of the MBI system to create several potential CSH collimator designs. The CSH collimator designs were evaluated using Monte Carlo simulations. The model included a breast compressed to a thickness of 6 cm with a 1-cm diameter lesion located 3 cm from the collimator face. The number of particles simulated was chosen to represent the count density of a low-dose, screening MBI study acquired with the parallel-hole collimator for 10 min after a ∼150 MBq (4 mCi) injection of Tc-99m sestamibi. The same number of particles was used for the CSH collimator simulations. In the resulting simulated images, the count sensitivity, spatial resolution, and accuracy of the lesion depth determined from the lesion profile width were evaluated. RESULTS: The CSH collimator design with default parameters derived from the optimal parallel-hole collimator provided 1-min images with error in the lesion depth estimation of 1.1 ± 0.7 mm and over 21 times the lesion count sensitivity relative to 1-min images acquired with the current parallel-hole collimator. Sensitivity was increased via more vertical cone slant angles, larger annular areas, thinner cone walls, shorter cone heights, and thinner radiating septa. Full width at half maximum trended in the opposite direction as sensitivity for all parameters. There was less error in the depth estimates for less vertical slant angles, smaller annular areas, thinner cone walls, cone heights near 1 cm, and generally thinner radiating septa. CONCLUSIONS: A Monte Carlo model was used to demonstrate the feasibility of a CSH collimator design for rapid biopsy application in molecular breast imaging. Specifically, lesion depth of a 1-cm diameter lesion positioned in the center of a typical breast can be estimated with error of less than 2 mm using circumferential count profiles of images acquired in 1 min.

Proof of concept for low-dose molecular breast imaging with a dual-head CZT gamma camera. Part II. Evaluation in patients.

PURPOSE: Molecular breast imaging (MBI) has shown promise as an adjunct screening technique to mammography for women with dense breasts. The demonstration of reliable lesion detection with MBI performed at low administered doses of Tc-99 m sestamibi, comparable in effective radiation dose to screening mammography, is essential to adoption of MBI for screening. The concept of performing low-dose MBI with dual-head cadmium zinc telluride (CZT) gamma cameras has been investigated in phantoms in Part I. In this work, the objectives were to evaluate the impact of the count sensitivity improvement methods on image quality in patient MBI exams and to determine if adequate lesion detection could be achieved at reduced doses. METHODS: Following the implementation of two count sensitivity improvement methods, registered collimation optimized for near-field imaging and energy acceptance window optimized for CZT, MBI exams were performed in the course of clinical care. Clinical image count density (counts/cm(2)) was compared between standard MBI [740 MBq (20 mCi) Tc-99 m sestamibi, standard collimation, standard energy window] and low-dose MBI [296 MBq (8 mCi) Tc-99 m sestamibi, optimized collimation, wide energy window] in a cohort of 50 patients who had both types of MBI exams performed. Lesion detection at low doses was evaluated in a separate cohort of 32 patients, in which low-dose MBI was performed following 296 MBq injection and acquired in dynamic mode, allowing the generation of images acquired for 2.5, 5, 7.5, and 10 min/breast view with proportionately reduced count densities. Diagnostic accuracy at each count density level was compared and kappa statistic was used to assess intrareader agreement between 10 min acquisitions and those at shorter acquisition durations. RESULTS: In patient studies, low-dose MBI performed with 296 MBq Tc-99 m sestamibi and new optimal collimation/wide energy window resulted in an average relative gain in count density of 4.2 ± 1.3 compared to standard MBI performed with 740 MBq. Interpretation of low-dose 296 MBq images with count densities corresponding to acquisitions of 2.5, 5, 7.5, and 10 min/view and median lesion size of 1.4 cm resulted in similar diagnostic accuracy across count densities and substantial to near-perfect intrareader agreement between full 10 min-views and lower count density views. CONCLUSIONS: Review of patient studies showed that registered optimized collimation and wide energy window resulted in a substantial gain in count sensitivity as previously indicated by phantom results. This proof of concept work indicates that MBI performed at administered doses of 296 MBq Tc-99 m sestamibi with the applied count sensitivity improvements permits the detection of small breast lesions in patients. Findings suggest that further reductions in acquisition duration or administered dose may be achievable.