Dual-energy contrast-enhanced digital mammography: initial clinical results of a multireader, multicase study.

INTRODUCTION: The purpose of this study was to compare the diagnostic accuracy of dual-energy contrast-enhanced digital mammography (CEDM) as an adjunct to mammography (MX) ± ultrasonography (US) with the diagnostic accuracy of MX ± US alone. METHODS: One hundred ten consenting women with 148 breast lesions (84 malignant, 64 benign) underwent two-view dual-energy CEDM in addition to MX and US using a specially modified digital mammography system (Senographe DS, GE Healthcare). Reference standard was histology for 138 lesions and follow-up for 12 lesions. Six radiologists from 4 institutions interpreted the images using high-resolution softcopy workstations. Confidence of presence (5-point scale), probability of cancer (7-point scale), and BI-RADS scores were evaluated for each finding. Sensitivity, specificity and ROC curve areas were estimated for each reader and overall. Visibility of findings on MX ± CEDM and MX ± US was evaluated with a Likert scale. RESULTS: The average per-lesion sensitivity across all readers was significantly higher for MX ± US ± CEDM than for MX ± US (0.78 vs. 0.71 using BIRADS, p = 0.006). All readers improved their clinical performance and the average area under the ROC curve was significantly superior for MX ± US ± CEDM than for MX ± US ((0.87 vs 0.83, p = 0.045). Finding visibility was similar or better on MX ± CEDM than MX ± US in 80% of cases. CONCLUSIONS: Dual-energy contrast-enhanced digital mammography as an adjunct to MX ± US improves diagnostic accuracy compared to MX ± US alone. Addition of iodinated contrast agent to MX facilitates the visualization of breast lesions.

Cancer cases from ACRIN digital mammographic imaging screening trial: radiologist analysis with use of a logistic regression model.

PURPOSE: To determine which factors contributed to the Digital Mammographic Imaging Screening Trial (DMIST) cancer detection results. MATERIALS AND METHODS: This project was HIPAA compliant and institutional review board approved. Seven radiologist readers reviewed the film hard-copy (screen-film) and digital mammograms in DMIST cancer cases and assessed the factors that contributed to lesion visibility on both types of images. Two multinomial logistic regression models were used to analyze the combined and condensed visibility ratings assigned by the readers to the paired digital and screen-film images. RESULTS: Readers most frequently attributed differences in DMIST cancer visibility to variations in image contrast--not differences in positioning or compression--between digital and screen-film mammography. The odds of a cancer being more visible on a digital mammogram--rather than being equally visible on digital and screen-film mammograms--were significantly greater for women with dense breasts than for women with nondense breasts, even with the data adjusted for patient age, lesion type, and mammography system (odds ratio, 2.28; P < .0001). The odds of a cancer being more visible at digital mammography--rather than being equally visible at digital and screen-film mammography--were significantly greater for lesions imaged with the General Electric digital mammography system than for lesions imaged with the Fischer (P = .0070) and Fuji (P = .0070) devices. CONCLUSION: The significantly better diagnostic accuracy of digital mammography, as compared with screen-film mammography, in women with dense breasts demonstrated in the DMIST was most likely attributable to differences in image contrast, which were most likely due to the inherent system performance improvements that are available with digital mammography. The authors conclude that the DMIST results were attributable primarily to differences in the display and acquisition characteristics of the mammography devices rather than to reader variability.

Comparison of calcification specificity in digital mammography using soft-copy display versus screen-film mammography.

OBJECTIVE: The purpose of this study was to compare specificity in the interpretation of calcifications in soft-copy reviewing of digital mammograms versus hard-copy reviewing of screen-film mammograms. MATERIALS AND METHODS: A total of 130 consecutive cases with calcifications (44 malignant and 86 benign) that had been evaluated with needle or surgical biopsy were collected. Both screen-film mammography and soft-copy digital mammography were obtained in the same patients under existing research protocols using Fischer Imaging's SenoScan (n = 71), Lorad's digital mammography system (n = 35), and GE Healthcare's Senographe 2000D (n = 24). Eight trained radiologists scored all lesions--cropped or masked to display just the region of interest--both on screen-film and soft-copy digital mammography with a month between reviews to reduce the effects of learning and memory. A 5-point malignancy scale was used, with 1 as definitely not, 2 as probably not, 3 as possibly, 4 as probably, and 5 as definitely. Reviewers were randomly assigned condition order, and images within each condition were randomly ordered. Repeated measures analysis of variance was used to test for differences between conditions in specificity computed via nonparametric receiver operating characteristic (ROC) study separately for each reviewer and condition. RESULTS: Across all reviewers, the mean specificity for 1 or 2 versus 3, 4, or 5 was 0.803 for screen-film mammography (range, 0.413-0.938; SD +/- 0.166) and 0.833 for soft-copy image (range, 0.375-0.951; SD +/- 0.187). Although not statistically significant (Student's t test p values from 0.19 to 0.99 across all cut points), numeric values of specificity were consistently higher for soft-copy versus screen-film mammography. No statistical significance in specificity was seen using all possible cut points in the 5-point scale, although the primary analysis used the cutpoint for differentiation between benign and malignant cases as 1 or 2 versus 3, 4, or 5. CONCLUSION: No statistically significant difference was shown in specificity achievable using soft-copy digital versus screen-film mammography in this study.

Consensus review: A method of assessment of calcifications that appropriately undergo a six-month follow-up.

RATIONALE AND OBJECTIVES: Breast calcifications seen on mammography may be associated with benign conditions or malignancies. Accurate characterization of these calcifications is crucial to providing optimal care that may spare women unnecessary biopsies and appropriately allow interval mammography. The purpose of this study is to determine if consensus characterization of calcifications by two breast imaging experts using standardized criteria can establish that follow-up is a safe option. MATERIALS AND METHODS: For this retrospective study, our breast imaging database was reviewed and the cases imaged between the years 1999 and 2001 were used to identify patients with calcifications who were recommended for a six-month follow-up or biopsy. All cases had been prospectively assessed by at least two expert breast imagers using standardized features to assess the findings before a recommendation for follow-up or a biopsy was made. A retrospective chart review examining the radiology reports was done to determine the percentage of women from each of the two groups who developed malignancies. RESULTS: Of 744 patients who had mammographically identified clusters of calcifications, 490 clusters (409 single and 81 multiple) were diagnosed as probably-benign, and a short-interval 6-month follow-up was recommended. Of these calcifications followed for three years, only two (0.5%) of the single clusters proved to be malignant, and malignancy was diagnosed at the 12-month follow-up examination. In both cases, the women were diagnosed with ductal carcinoma in situ (DCIS). Of 254 clusters recommended for biopsy, 242 (215 single and 27 multiple) underwent biopsy. A total of 70 cancers were diagnosed: 54 (77.1%) were DCIS and 16 (22.9%) were primary invasive mammary carcinoma (10 cases of invasive ductal carcinoma, 3 cases of invasive lobular carcinoma, 2 cases of invasive ductal carcinoma with DCIS, and one case of invasive mucinous carcinoma with DCIS). Twenty-nine percent of women who had a biopsy performed had calcifications associated with malignancy. In contrast, in the women whose calcifications were followed by mammography, only 0.5% went on to develop malignancies. CONCLUSION: Consensus review of calcifications by two breast imagers using standardized criteria is a safe follow-up option.

Correlation of HER-2/neu overexpression with mammography and age distribution in primary breast carcinomas.

RATIONALE AND OBJECTIVES: HER-2/neu is a valuable prognostic and therapeutic marker in primary breast carcinoma. The objective of this study was to determine the mammographic and patient characteristics (age) that correlate with HER-2/neu overexpression in primary breast carcinoma. MATERIALS AND METHODS: HER-2/neu characteristics and preoperative mammograms were available in 498 patients with 543 primary breast carcinomas (526 invasive carcinomas and 17 ductal carcinoma in situ). HER-2/neu status was determined by immunohistochemistry and fluorescence in situ hybridization. For evaluation of patient age distribution, age was divided into 5 groups. For mammography, breast composition and abnormal findings were categorized. Abnormal findings were divided into mass, calcification, architectural distortion, asymmetric density, or none. RESULTS: For age distribution, women under than 50 years had more frequent HER-2/neu overexpression than women aged 60-69 years (P < .05). On mammography, there was no significant correlation between breast composition and HER-2/neu status (P > .05). Calcifications were more significantly frequent in carcinomas with HER-2/neu overexpression (56%) than in those without HER-2/neu overexpression (40%) (P = .001). Of the 242 carcinomas with calcifications on mammography, fine linear morphology was more significantly frequent in carcinomas with HER-2/neu overexpression (20%) when compared with those without HER-2/neu overexpression (10%) (P = .023). Diffuse distribution of calcifications was more common in carcinomas with HER-2/neu overexpression (11%) compared with carcinomas without HER-2/neu overexpression (5%) (P = .051). CONCLUSION: HER-2/neu overexpression in primary breast carcinoma is correlated with patients' age (under age 50) and calcifications at mammography.

The positive predictive value for diagnosis of breast cancer full-field digital mammography versus film-screen mammography in the diagnostic mammographic population.

RATIONALE AND OBJECTIVES: Diagnostic mammography is performed on women with clinical symptoms that suggest breast cancer or women for whom further mammographic evaluation has been requested because of an abnormal screening mammography. We assessed whether the use of full-field digital mammography would improve the positive predictive value (PPV) for the diagnosis of breast cancer in a diagnostic population compared with film-screen mammography. MATERIALS AND METHODS: From January 2002 to December 2003, 11,621 patients underwent diagnostic mammography at the University of North Carolina Hospital, Chapel Hill. Among these 11,621 patients, 1400 lesions in 1121 patients underwent biopsy. We included the biopsy-performed lesions, so PPV3 was used for comparison of PPVs between film-screen mammography and full-field digital mammography. Six breast radiologists interpreted the images using the Breast Imaging Reporting and Data System of the American College of Radiology. PPV3s were compared between film-screen and full-field digital mammography in the entire study cohort and in specified subgroups according to different radiologists, breast density, and lesion type on mammography. The chi(2) and Fisher's exact tests were used for comparison of PPV3s between two modalities of mammography with the Bonferroni procedure for subgroup analysis. RESULTS: In the entire study cohort, PPV3s of full-field digital mammography and film-screen mammography were similar (difference in PPV3,-0.007; 95% confidence interval, -0.081 to 0.068; P = .8602). In predefined subgroups, there was no difference in PPV3 by the radiologist, breast density, or lesion type between two modalities of mammography (P > .005). CONCLUSION: There is no improvement in PPV for the diagnosis of breast cancer with full-field digital mammography compared with film-screen mammography in a large diagnostic population.

A comparative study of mobile electronic data entry systems for clinical trials data collection.

PURPOSE: To determine the speed, accuracy, ease of use, and user satisfaction of various electronic data entry platforms for use in the collection of mammography clinical trials data. METHOD AND MATERIALS: Four electronic data entry platforms were tested: standalone personal digital assistant (PDA), Tablet PC, digitizer Tablet/PDA Hybrid (DTP Hybrid), and digital pen (d-pen). Standard paper data entry was used as control. Each of five radiologist readers was assigned to enter interpretations for 20 screening mammograms using three out of the five data entry methods. Assistants recorded both start and stop data entry times of the radiologists and the number of help requests made. Data were checked for handwriting recognition accuracy for the d-pen platform using handwriting verification software. A user satisfaction survey was administered at the end of each platform reading session. RESULTS: Tablet PC and d-pen were statistically equivalent to conventional pen and paper in initial data entry speed. Average verification time for d-pen was significantly less than secondary electronic data entry of paper forms (p-value <0.001). The number of errors in handwriting recognition for d-pen was less than secondary electronic data entry of the paper forms data. Users were most satisfied with Tablet PC, d-pen, and conventional pen and paper for data entry. CONCLUSIONS: Tablet PC and d-pen are equally fast and easy-to-use data entry methods that are well tolerated by radiologist users. Handwriting recognition review and correction for the d-pen is significantly faster and more accurate than secondary manual keyboard and mouse data entry.

Comparison of full-field digital mammography to screen-film mammography with respect to contrast and spatial resolution in tissue equivalent breast phantoms.

To determine if the improved contrast resolution of full-field digital mammography (FFDM) with reduced spatial resolution allows for superior or equal phantom object detection compared with screen-film mammography (SFM). Tissue equivalent breast phantoms simulating an adipose to glandular ratio of 50/50,30/70, and 20/80 were imaged according to each manufacturers' recommendation with four full-field digital mammography units (Fuji, Sectra, Fischer, and General Electric) and a screen-film mammography unit (MammoMatII 2000, Siemens, Munich, Germany). A total of 20 images were obtained in both hard- and soft-copy formats. For the purpose of soft-copy display, the screen-film hard-copy images were digitized with a 50 microm micron scanner. Six radiologists, experts in breast imaging, and three physicists, experts in scoring mammography phantoms, participated in a reader study where each reader scored each phantom for visibility of line-pairs and for 24 objects (fibers, clusters of specks, and masses). The data were recorded, entered into a database, and analyzed by a mixed-effect model. The limiting spatial resolution in line-pairs per millimeter visible with the digital units was less, regardless of display modality used, than that provided by the screen-film unit. The difference was statistically significant for the General Electric (p < 0.01) and Fuji digital mammography units (p = 0.03). With respect to the number of visible objects, a statistically significant higher number could be detected with the screen-film unit as compared to the Fischer (p < 0.01) and Sectra (p < 0.01) digital mammography units, but there was no significant difference between the other digital units and screen film. Overall, there was significantly better performance on the 50/50 phantom than with the 30/70 and 20/80 phantoms (p = 0.01, p < 0.01) for object visibility. For the digital mammography units, soft-copy display performed better than hard-copy display for the Fischer and Sectra images, but worse for Fuji and General Electric. In addition, soft-copy display of digitized screen-film images was significantly better than hard-copy display (p =0.02) of the original screen films for object visibility, but worse for spatial resolution. The higher contrast resolution of the FFDM units tested did not result in improved detection of line-pair resolution or objects in the phantoms tested versus screen-film mammography. The phantom performance of a digital mammography unit seems to be influenced by the type of detection task (line-pair resolution versus object visibility), the display modality (soft-copy versus hard-copy) chosen to score the phantoms, and the parenchymal pattern composition of the phantom.

The effects of gray scale image processing on digital mammography interpretation performance.

RATIONALE AND OBJECTIVES: To determine the effects of three image-processing algorithms on diagnostic accuracy of digital mammography in comparison with conventional screen-film mammography. MATERIALS AND METHODS: A total of 201 cases consisting of nonprocessed soft copy versions of the digital mammograms acquired from GE, Fischer, and Trex digital mammography systems (1997-1999) and conventional screen-film mammograms of the same patients were interpreted by nine radiologists. The raw digital data were processed with each of three different image-processing algorithms creating three presentations-manufacturer's default (applied and laser printed to film by each of the manufacturers), MUSICA, and PLAHE-were presented in soft copy display. There were three radiologists per presentation. RESULTS: Area under the receiver operating characteristic curve for GE digital mass cases was worse than screen-film for all digital presentations. The area under the receiver operating characteristic for Trex digital mass cases was better, but only with images processed with the manufacturer's default algorithm. Sensitivity for GE digital mass cases was worse than screen film for all digital presentations. Specificity for Fischer digital calcifications cases was worse than screen film for images processed in default and PLAHE algorithms. Specificity for Trex digital calcifications cases was worse than screen film for images processed with MUSICA. CONCLUSION: Specific image-processing algorithms may be necessary for optimal presentation for interpretation based on machine and lesion type.

The role of magnetic resonance imaging in diagnosis and management of breast cancer.

A review of the literature on the current applications of breast magnetic resonance imaging (MRI) indications, their rationale and their place in diagnosis and management of breast cancer was given. Contrast-enhanced breast MRI is developing as a valuable adjunct to mammography and sonography. Its high sensitivity for invasive breast cancer establishes its superiority in evaluation of multifocality/multicentricity, tumor response to neoadjuvant chemotherapy, detection of recurrence, and staging. Emerging applications include spectroscopy, usage of new contrast agents, and MRI-guided interventions, including noninvasive treatment of breast cancer. Its potential benefit in screening high-risk women has yet to be established with prospective studies, particularly with regard to false positive results.

Factors affecting increasing radiation dose for mammography in North Carolina from 1997 through 2001: an analysis of Food and Drug Administration annual surveys.

RATIONALE AND OBJECTIVES: To determine which factors affected the increase in average glandular dose recorded at the annual US Food and Drug Administration Mammography Quality Standards Act inspections of mammography equipment in North Carolina from 1997 to 2001. MATERIALS AND METHODS: Average glandular dose, HVL, kVp, ambient light, luminance, equipment age, processing speed, and system speed for every mammography unit at all facilities in the state were collected by state inspectors. A mixed-effect model was used to assess the average changes of glandular dose over time and to identify the factors associated with these changes. RESULTS: There was a statistically significant increase in the average glandular dose in North Carolina in 1999, 2000, and 2001 when compared with the baseline year of 1997. Factors that were statistically significantly linked to this effect were changes in kVp, processing speed, and system speed. CONCLUSION: Average glandular dose for mammography has recently increased in North Carolina. This change is likely caused by changes in screen-film products and processing techniques.

Comparison of image acquisition and radiologist interpretation times in a diagnostic mammography center.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the acquisition and interpretation times of screen-film mammography and soft-copy digital mammography in a diagnostic mammography center. MATERIALS AND METHODS: The study was conducted in three phases for patients presenting for clinical diagnostic workup to a mammography clinic. In the first phase, technologist acquisition and processing times and radiologist interpretation time were measured for patients imaged with a screen-film mammographic system. During the second phase of the study, times were measured for patients imaged with a direct radiographic digital mammographic system, with interpretation performed on a soft-copy display system. During the third phase, 3 months after installation of the soft-copy display system, times were measured again for patients imaged on the same direct radiographic digital mammographic system, with interpretation with the same soft-copy system. The same four experienced breast imaging radiologists and seven technologists participated in all phases of the study. All data were entered into a database, and statistical analysis was conducted using weighted linear models and logarithmic transformation. RESULTS: Times were obtained for 295 patients. There were 100 patients each for phases 1 and 2 and 95 patients for phase 3. Diagnostic mammographic acquisition times with processing were 13.02 min/case for screen film (phase 1), 8.16 min/case for digital (phase 2), and 10.66 min/case for digital (phase 3) (P < .001 and P < .0001, respectively). In addition, the radiologist interpretation time for digital mammography in both phases was not significantly different from that for film mammography (P = .2853 and P = .2893, respectively). There was no significant difference between phases 2 and 3 (P = 1.0000). The mean interpretation times were 3.75 min/case for screen film, 2.14 min/case for digital (phase 2), and 2.26 min/case for digital (phase 3). CONCLUSIONS: Digital mammography significantly shortened the acquisition time for diagnostic mammography. There was no significant difference in interpretation time compared to screen-film mammography in a diagnostic mammography setting.

Effect of breast compression on lesion characteristic visibility with diffraction-enhanced imaging.

RATIONALE AND OBJECTIVES: Conventional mammography can not distinguish between transmitted, scattered, or refracted x-rays, thus requiring breast compression to decrease tissue depth and separate overlapping structures. Diffraction-enhanced imaging (DEI) uses monochromatic x-rays and perfect crystal diffraction to generate images with contrast based on absorption, refraction, or scatter. Because DEI possesses inherently superior contrast mechanisms, the current study assesses the effect of breast compression on lesion characteristic visibility with DEI imaging of breast specimens. MATERIALS AND METHODS: Eleven breast tissue specimens, containing a total of 21 regions of interest, were imaged by DEI uncompressed, half-compressed, or fully compressed. A fully compressed DEI image was displayed on a soft-copy mammography review workstation, next to a DEI image acquired with reduced compression, maintaining all other imaging parameters. Five breast imaging radiologists scored image quality metrics considering known lesion pathology, ranking their findings on a 7-point Likert scale. RESULTS: When fully compressed DEI images were compared to those acquired with approximately a 25% difference in tissue thickness, there was no difference in scoring of lesion feature visibility. For fully compressed DEI images compared to those acquired with approximately a 50% difference in tissue thickness, across the five readers, there was a difference in scoring of lesion feature visibility. The scores for this difference in tissue thickness were significantly different at one rocking curve position and for benign lesion characterizations. These results should be verified in a larger study because when evaluating the radiologist scores overall, we detected a significant difference between the scores reported by the five radiologists. CONCLUSIONS: Reducing the need for breast compression might increase patient comfort during mammography. Our results suggest that DEI may allow a reduction in compression without substantially compromising clinical image quality.

Radiologist evaluation of an X-ray tube-based diffraction-enhanced imaging prototype using full-thickness breast specimens.

RATIONALE AND OBJECTIVES: Conventional mammographic image contrast is derived from x-ray absorption, resulting in breast structure visualization due to density gradients that attenuate radiation without distinction between transmitted, scattered, or refracted x-rays. Diffraction-enhanced imaging (DEI) allows for increased contrast with decreased radiation dose compared to conventional mammographic imaging because of monochromatic x-rays, its unique refraction-based contrast mechanism, and excellent scatter rejection. However, a lingering drawback to the clinical translation of DEI has been the requirement for synchrotron radiation. MATERIALS AND METHODS: The authors' laboratory developed a DEI prototype (DEI-PR) using a readily available tungsten x-ray tube source and traditional DEI crystal optics, providing soft tissue images at 60 keV. Images of full-thickness human breast tissue specimens were acquired on synchrotron-based DEI (DEI-SR), DEI-PR, and digital mammographic systems. A panel of expert radiologists evaluated lesion feature visibility and correlation with pathology after receiving training on the interpretation of refraction contrast mammographic images. RESULTS: For mammographic features (mass, calcification), no significant differences were detected between the DEI-SR and DEI-PR systems. Benign lesions were perceived as better seen by radiologists using the DEI-SR system than the DEI-PR system at the [111] reflectivity, with generalizations limited by small sample size. No significant differences between DEI-SR and DEI-PR were detected for any other lesion type (atypical, cancer) at either crystal reflectivity. CONCLUSIONS: Thus, except for benign lesion characterizations, the DEI-PR system's performance was roughly equivalent to that of the traditional DEI system, demonstrating a significant step toward clinical translation of this modality for breast cancer applications.

Ultrasound in the management of breast disease.

Since its introduction in the 1960s, ultrasound (US) has never been more important in breast disease management as it is today. Its historical role as an adjunct modality to mammography in differentiating cystic from solid lesions has been widely expanded. US-guided sampling procedures represent widely accepted modalities in lesion evaluation. Preoperative localization under US guidance is one of the methods of choice for nonpalpable solid lesions. Screening breast US is currently being investigated and might prove useful for high-risk women and women with dense breasts. Continuous technologic advances, such as high-frequency transducers, new Doppler-based techniques, microbubble contrast agents, harmonic and compound imaging, three-dimensional US, elasticity imaging, US detection of microcalcifications, perfusion US imaging, and computer-aided diagnosis all carry promise of further increases in US utility in the diagnosis and detection of breast disease.