Digital Breast Tomosynthesis: Physics, Artifacts, and Quality Control Considerations.

As digital breast tomosynthesis (DBT) becomes widely used, radiologists must understand the basic principles of (a) image acquisition, (b) artifacts, and (c) quality control (QC) that are specific to DBT. Standard acquisition parameters common to both full-field digital mammography (FFDM) and DBT are combinations of x-ray tube voltage, current exposure time, and anode target and filter combinations. Image acquisition parameters specific to DBT include tube motion, sweep angle, and number of projections. Continuous tube motion or x-ray emission decreases imaging time but leads to focal spot blurring when compared with step-and-shoot techniques. The sweep angle and number of projections determines resolution. Wider sweep angles allow greater out-of-plane (z-axis) resolution, improving visualization of masses and architecture distortion. A greater number of projections increases in-plane or x-y axis resolution, improving visualization of microcalcifications. Artifacts related to DBT include blurring-ripple, truncation, and loss of skin and superficial tissue resolution. Motion artifacts are difficult to recognize because of inherent out-of-plane blurring. To maintain optimal image quality and an "as low as reasonably achievable" (ALARA) radiation dose, regular QC must be performed. DBT is considered a new imaging modality; therefore, breast imaging facilities are required to obtain a separate certification in addition to that in FFDM, and all personnel (radiologists, technologists, and medical physicists) are mandated to complete initial DBT training and maintain appropriate continuing medical education credits. ©RSNA, 2019.

Breast Cancer Tissue Markers, Genomic Profiling, and Other Prognostic Factors: A Primer for Radiologists.

An understanding of prognostic factors in breast cancer is imperative for guiding patient care. Increased tumor size and more advanced nodal status are established independent prognostic factors of poor outcomes and are incorporated into the American Joint Committee on Cancer (AJCC) TNM (primary tumor, regional lymph node, distant metastasis) staging system. However, other factors including imaging findings, histologic evaluation results, and molecular findings can have a direct effect on a patient's prognosis, including risk of recurrence and relative survival. Several microarray panels for gene profiling of tumors are approved by the U.S. Food and Drug Administration and endorsed by the American Society of Clinical Oncology. This article highlights prognostic factors currently in use for individualizing and guiding breast cancer therapy and is divided into four sections. The first section addresses patient considerations, in which modifiable and nonmodifiable prognostic factors including age, race and ethnicity, and lifestyle factors are discussed. The second part is focused on imaging considerations such as multicentric and/or multifocal disease, an extensive intraductal component, and skin or chest wall involvement and their effect on treatment and prognosis. The third section is about histopathologic findings such as the grade and presence of lymphovascular invasion. Last, tumor biomarkers and tumor biology are discussed, namely hormone receptors, proliferative markers, and categorization of tumors into four recognized molecular subtypes including luminal A, luminal B, human epidermal growth factor receptor 2-enriched, and triple-negative tumors. By understanding the clinical effect of these prognostic factors, radiologists, along with a multidisciplinary team, can use these tools to achieve individualized patient care and to improve patient outcomes. ©RSNA, 2018.

Breaking Bad News: A Survey of Radiology Residents' Experiences Communicating Results to Patients.

PURPOSE: The practice of radiology often includes routine communication of diagnostic test results directly to patients in breast imaging and interventional radiology. There is increasing interest in expanding direct communication throughout radiology. Though these conversations can substantially affect patient well-being, there is limited evidence indicating that radiology residents are specifically taught methods to effectively convey imaging results to patients. Our purpose is to evaluate resident experience communicating imaging results to patients. MATERIALS AND METHODS: An IRB-approved study with a total of 11 pilot-tested questions was used. Surveyed programs included radiology residents (PGY2-PGY5) at 2 urban residency programs. Online surveys were administered using SurveyMonkey and e-mailed to residents at both programs (starting November 20, 2015, completed March 31, 2016). Demographics were obtained with survey proportions compared using logistic regression (P < 0.05, statistically significant). RESULTS: A total of 73 residents responded (93.6% response rate) with similar response rates at each institution (P = 0.689). Most were male (71.2%) with 17.8% planning to go into breast imaging (21.9%, interventional radiology (IR)). Furthermore, 83.6% described no training in communicating radiology results to patients; 91.8% of residents communicated results with patients (87.7% diagnostic imaging tests and 57.5% biopsies). Residents most commonly communicated results in person (75.3%) followed by phone (64.4%), and 79.4% agreed or strongly agreed that additional training relaying results would be helpful. CONCLUSIONS: A large majority of radiology residents have communicated test results to patients, yet few have received training in how to communicate these results. A large majority of residents expressed interest in obtaining additional communication training. Additional research is required to determine ideal methods to educate residents on communicating test results.

Phase I study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies.

PURPOSE: A phase I dose escalation study was performed with systemically delivered lyso-thermosensitive liposomal doxorubicin (LTLD). The primary objectives were to determine the safe maximum tolerated dose (MTD), pharmacokinetic properties, and dose-limiting toxicity (DLT) of LTLD during this combination therapy. MATERIALS AND METHODS: Subjects eligible for percutaneous or surgical radiofrequency (RF) ablation with primary (n = 9) or metastatic (n = 15) tumors of the liver, with four or fewer lesions as large as 7 cm in diameter, were included. RF ablation was initiated 15 minutes after starting a 30-minute intravenous LTLD infusion. Dose levels between 20 mg/m(2) and 60 mg/m(2) were evaluated. Magnetic resonance imaging, positron emission tomography, and computed tomography were performed at predetermined intervals before and after treatment until evidence of recurrence was seen, administration of additional antitumor treatment was performed, or a total of 3 years had elapsed. RESULTS: DLT criteria were met at 60 mg/m(2), and the MTD was defined as 50 mg/m(2). RF ablation was performed during the peak of the plasma concentration-time curve in an effort to yield maximal drug deposition. LTLD produced reversible, dose-dependent neutropenia and leukopenia. CONCLUSIONS: LTLD can be safely administered systemically at the MTD (50 mg/m(2)) in combination with RF ablation, with limited and manageable toxicity. Further evaluation of this agent combined with RF ablation is warranted to determine its role in the management of liver tumors.

Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity.

PURPOSE: To evaluate the influence of subtotal radiofrequency (RF) ablation on a tumor-specific immune response in a murine tumor model and to explore the role of intratumoral dendritic cells (ITDCs) in mediating this effect. MATERIALS AND METHODS: Animal work was performed according to an approved protocol and in compliance with the National Cancer Institute Animal Care and Use Committee guidelines and regulations. A murine urothelial carcinoma (MB49) model expressing the male minor histocompatibility (HY) antigen was inoculated subcutaneously in female mice. Fourteen days later, splenic T cells were analyzed with enzyme-linked immunosorbent spot for HY immune response (n = 57). In subsequent experiments, mice were randomized into control (n = 7), RF ablation, ITDC (n = 9), and RF ablation + ITDC (n = 9) groups and monitored for tumor growth. Eleven days after treatment, tumors were harvested for histologic and immunohistochemical analysis. Animals demonstrating complete tumor regression were rechallenged in the contralateral flank. RESULTS: Animals treated with subtotal RF ablation showed significant increases in tumor-specific class I and II responses to HY antigens and tumor regression. RF ablation, ITDC, and combined groups demonstrated similar levels of antigen-presenting cell infiltration; all groups demonstrated greater levels of infiltration compared with untreated controls. ITDC injection also resulted in tumor regression. However, combination therapy did not enhance tumor regression when compared with either treatment alone. Rechallenged mice in RF ablation, ITDC, and combination groups demonstrated significant tumor growth inhibition compared with controls. CONCLUSION: Subtotal RF ablation treatment results in enhanced systemic antitumor T-cell immune responses and tumor regression that is associated with increased dendritic cell infiltration. ITDC injection mimics the RF ablation effect but does not increase immune responses when injected immediately after RF ablation.

In vitro and in vivo evaluations of increased effective beam width for heat deposition using a split focus high intensity ultrasound (HIFU) transducer.

PURPOSE: To develop a novel and efficient, in vitro method for characterizing temporal and spatial heat generation of focused ultrasound exposures, and evaluate this method to compare a split focus and conventional single focus high intensity focused ultrasound transducer. MATERIALS AND METHODS: A HIFU tissue-mimicking phantom was validated by comparing respective temperature elevations generated in the phantoms and in murine tumors in vivo. The phantom was then used in combination with IR thermography to spatially and temporally characterize differences in low-level temperature elevation (e.g. 3-5 degrees C) produced by a single focus and split focus HIFU transducer, where the latter produces four simultaneous foci. In vivo experiments with heat sensitive liposomes containing doxorubicin were then carried out to determine if the larger beam width of the split focus transducer, compared to the single focus, could increase overall deployment of the drug from the liposome. RESULTS: Temperature elevations generated in the HIFU phantom were not found to be different from those measured in vivo when compensating for disparities in attenuation coefficient and specific heat, and between the two transducers by increasing the energy deposition. Exposures with the split focus transducer provided significant increases in the area treated compared to the single focus, which then translated to significant increases in drug deposition in vivo. CONCLUSIONS: Preliminary evidence was provided indicating the potential for using this novel technique for characterizing hyperthermia produced by focused ultrasound devices. Further development will be required for its suitability for correlating in vitro and in vivo outcomes.

Pulsed-high intensity focused ultrasound and low temperature-sensitive liposomes for enhanced targeted drug delivery and antitumor effect.

PURPOSE: To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in tumors. EXPERIMENTAL DESIGN: Comparisons in vitro and in vivo were carried out between non-thermosensitive liposomes (NTSL) and low temperature-sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors. RESULTS: In vitro incubations simulating the pulsed-HIFU thermal dose (42 degrees C for 2 min) triggered release of 50% of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups. CONCLUSIONS: Combining low-temperature heat-sensitive liposomes with noninvasive and nondestructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.

Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study.

INTRODUCTION: Thrombotic disease continues to account for significant morbidity and mortality. Ultrasound energy has been investigated as a potential primary and adjunctive treatment for thrombotic disease. We have previously shown that pulsed-high intensity focused ultrasound (HIFU) enhances thrombolysis induced by tissue plasminogen activator (tPA) in vitro, including describing the non-destructive mechanism by which tPA availability and consequent activity are increased. In this study we aimed to determine if the same effects could be achieved in vivo. MATERIALS AND METHODS: In this study, pulsed-HIFU exposures combined with tPA boluses were compared to treatment with tPA alone, HIFU alone and control in a novel in vivo clot model. Clots were formed in the rabbit marginal ear vein and verified using venography and infrared imaging. The efficacy of thrombolytic treatment was monitored via high resolution ultrasonography for 5 h post-treatment. The cross-sectional area of clots at 4 points along the vein was measured and normalized to the pre-treatment size. RESULTS: At 5 h the complete recanalization of clots treated with pulsed-HIFU and tPA was significantly different from the partial recanalization seen with tPA treatment alone. tPA treatment alone showed a significant decrease in clot versus control, where HIFU was not significantly different than control. Histological analysis of the vessel walls in the treated veins showed no apparent irreversible damage to endothelial cells or extravascular tissue. CONCLUSIONS: This study demonstrates that tPA mediated thrombolysis can be significantly enhanced when combined with non-invasive pulsed-HIFU exposures.

CT fluoroscopy shielding: decreases in scattered radiation for the patient and operator.

PURPOSE: High-radiation exposure occurs during computed tomographic (CT) fluoroscopy. Patient and operator doses during thoracic and abdominal interventional procedures were studied in the present experiment, and a novel shielding device to reduce exposure to the patient and operator was evaluated. MATERIALS AND METHODS: With a 16-slice CT scanner in CT fluoroscopy mode (120 kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The shielding was composed of tungsten antimony in the form of a lightweight polymer sheet. Doses to the patient were measured with and without shielding for thoracic and abdominal procedures. Doses to the operator were recorded with and without phantom, gantry, and table shielding in place. Double-layer lead-free gloves were used by the operator during the procedures. RESULTS: Tungsten antimony shielding adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the operator's torso, gonads, and hands, respectively. The use of double-layer lead-free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS: Methods to reduce exposure during CT fluoroscopy are effective and should be searched for. Significant reduction in radiation doses to the patient and operator can be accomplished with tungsten antimony shielding.

Heavy metal pad shielding during fluoroscopic interventions.

Significant direct and scatter radiation doses to patient and physician may result from routine interventional radiology practice. A lead-free disposable tungsten antimony shielding pad was tested in phantom patients during simulated diagnostic angiography procedures. Although the exact risk of low doses of ionizing radiation is unknown, dramatic dose reductions can be seen with routine use of this simple, sterile pad made from lightweight tungsten antimony material.

Delivery of liposomal doxorubicin (Doxil) in a breast cancer tumor model: investigation of potential enhancement by pulsed-high intensity focused ultrasound exposure.

RATIONALE AND OBJECTIVES: To investigate the potential of using pulsed high-intensity focused ultrasound (HIFU) exposures to enhance the delivery, and hence therapeutic effect of liposomal doxorubicin (Doxil) in a murine breast cancer tumor model. MATERIALS AND METHODS: Tumors were grown in the bilateral flanks of mice using a mammary adenocarcinoma cell line. Experiments consisted of exposing one of two tumors to pulsed-HIFU, followed by tail vein injections of Doxil. Tumor growth rates were monitored, and assays carried out for doxorubicin concentration in these tumors as well as in a second (squamous cell carcinoma) tumor model and in muscle. Laser scanning confocal microscopy was used with fluorescent probes to observe both the uptake of polystyrene nanoparticles and dilation of exposed blood vessels. Additional experiments involving histologic analysis and real-time temperature measurements were performed to determine the safety of the exposures. RESULTS: Pulsed-HIFU exposures were shown to be safe, producing no apparent deleterious effects in the tumors. The exposures, however, were not found to enhance the delivery of Doxil, and consequently did not allow for lower doses for obtaining tumor regression. Imaging with a fluorescent dextran showed blood vessels to be dilated as a result of the exposures. Experiments with polystyrene nanoparticles of similar size to the liposomes showed a greater abundance to be present in the treated tumors. CONCLUSION: Although past studies have shown the advantages of pulsed-HIFU exposures for enhancing delivery, this was not observed with the liposomes, apparently because of their inherent ability to preferentially accumulate into tumors on their own. Potential mechanisms for enhanced uptake of non-liposomal nanoparticles are discussed.