Evaluating hormone therapy-associated increases in breast density comparison between reported and simultaneous assignment of BI-RADS categories, visual assessment, and quantitative analysis

RATIONALE AND OBJECTIVES: Changes in breast density, which are commonly associated with hormone replacement therapy (HRT) use, may imply changes in breast cancer risk. This study explores the ability of different methods to detect hormone replacement therapy (HRT)-associated increases in breast density. MATERIALS AND METHODS: Between 1997 and 2001, 51 postmenopausal women were reported to have HRT-associated increases in breast density at our institution. Twenty postmenopausal women not reported to have an increase in density during the same period were selected as controls. Mammograms from date of report and earlier comparison were used. Breast Imaging Reporting and Data System (BI-RADS) density categories from both dates were obtained from the mammography report. Mammograms were reviewed at separate time points and density changes evaluated by assigning BI-RADS density categories, visual assessment, and computer-assisted quantitative analysis. RESULTS: Mammogram reports were not available for two patients. The remaining 49 women with reported HRT increases in density were included. Reported BI-RADS categories resulted in detection of 57%, simultaneous BI-RADS assignment in 61%, visual assessment in 100%, and quantitative assessment in 94% of women with HRT-associated increases in density. Reported BI-RADS category change was the only method that resulted in false-positive increases in density for control patients. Minimal HRT associated increases in density were the most difficult to detect, with 90% of these 21 cases not detected by simultaneous BI-RADS category assignment and 3 cases not detected by quantitative methods when defined as an increase of at least 5%. CONCLUSION: Visual and quantitative assessment best identified women with HRT-associated increases in density, including those with minimal increases. Simultaneous assignment of BI-RADS categories was considerably better than use of reported BI-RADS categories. This information may be helpful in guiding research design of studies evaluating changes in density from the HRT use.     

Inter- and intraradiologist variability in the BI-RADS assessment and breast density categories for screening mammograms

Objective

The aim of this study was to evaluate reader variability in screening mammograms according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) assessment and breast density categories.

Methods

A stratified random sample of 100 mammograms was selected from a population-based breast cancer screening programme in Barcelona, Spain: 13 histopathologically confirmed breast cancers and 51 with true-negative and 36 with false-positive results. 21 expert radiologists from radiological units of breast cancer screening programmes in Catalonia, Spain, reviewed the mammography images twice within a 6-month interval. The readers described each mammography using BI-RADS assessment and breast density categories. Inter- and intraradiologist agreement was assessed using percentage of concordance and the kappa (κ) statistic.

Results

Fair interobserver agreement was observed for the BI-RADS assessment [κ=0.37, 95% confidence interval (CI) 0.36–0.38]. When the categories were collapsed in terms of whether additional evaluation was required (Categories III, 0, IV, V) or not (I and II), moderate agreement was found (κ=0.53, 95% CI 0.52–0.54). Intra-observer agreement for BI-RADS assessment was moderate using all categories (κ=0.53, 95% CI 0.50–0.55) and substantial on recall (κ=0.66, 95% CI 0.63–0.70). Regarding breast density, inter- and intraradiologist agreement was substantial (κ=0.73, 95% CI 0.72–0.74 and κ=0.69, 95% CI 0.68–0.70, respectively).

Conclusion

We observed a substantial intra-observer agreement in the BI-RADS assessment but only moderate interobserver agreement. Both inter- and intra-observer agreement in mammographic interpretation of breast density was substantial.

Advances in knowledge

Educational efforts should be made to decrease radiologists'' variability in BI-RADS assessment interpretation in population-based breast screening programmes.Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide, accounting for 23% of the total new cancer cases and 14% of the total cancer-related deaths in 2008 [1]. In Spain, more than 20 000 cases are diagnosed and approximately 6000 females die each year because of this tumour [2].Breast cancer screening by mammography is the only evidence-based screening procedure currently available to reduce breast cancer mortality. Accuracy of screening mammography depends on various factors, such as the protocols for mammogram reading, the characteristics of the female and of the breast, and the experience of radiologists [3-5]. Great efforts have been made to improve its accuracy. One of these is the implementation of double reading as it increases the cancer detection rate and reduces the further assessment rate [6]. Furthermore, the American College of Radiology developed the Breast Imaging Reporting and Data System (BI-RADS) in order to reduce discordance in the interpretation of mammographic findings, to standardise mammographic reporting and to facilitate follow-up [7,8].A limited number of studies have analysed observer variability in mammography interpretation using BI-RADS assessment as well as breast density categories [9-13]. Thus, the aim of this study was to assess the inter- and intra-observer agreement regarding the assessment and breast density in a breast cancer screening programme in the city of Barcelona, Spain. Furthermore, we wanted to investigate the association between female characteristics and BI-RADS discordance.     

Estimation of percentage breast tissue density: comparison between digital mammography (2D full field digital mammography) and digital breast tomosynthesis according to different BI-RADS categories

Objective:

To compare breast density estimated from two-dimensional full-field digital mammography (2D FFDM) and from digital breast tomosynthesis (DBT) according to different Breast Imaging–Reporting and Data System (BI-RADS) categories, using automated software.

Methods:

Institutional review board approval and written informed patient consent were obtained. DBT and 2D FFDM were performed in the same patients to allow within-patient comparison. A total of 160 consecutive patients (mean age: 50±14 years; mean body mass index: 22±3) were included to create paired data sets of 40 patients for each BI-RADS category. Automatic software (MedDensity^©, developed by Giulio Tagliafico) was used to compare the percentage breast density between DBT and 2D FFDM. The estimated breast percentage density obtained using DBT and 2D FFDM was examined for correlation with the radiologists'' visual BI-RADS density classification.

Results:

The 2D FFDM differed from DBT by 16.0% in BI-RADS Category 1, by 11.9% in Category 2, by 3.5% in Category 3 and by 18.1% in Category 4. These differences were highly significant (p<0.0001). There was a good correlation between the BI-RADS categories and the density evaluated using 2D FFDM and DBT (r=0.56, p<0.01 and r=0.48, p<0.01, respectively).

Conclusion:

Using DBT, breast density values were lower than those obtained using 2D FFDM, with a non-linear relationship across the BI-RADS categories. These data are relevant for clinical practice and research studies using density in determining the risk.

Advances in knowledge:

On DBT, breast density values were lower than with 2D FFDM, with a non-linear relationship across the classical BI-RADS categories.To tailor screening and diagnosis protocols, it is important to identify females with an increased risk of breast cancer [1–3]. It has been estimated that females with dense breasts (breast densities of >75%) have 4–6 times higher risk of breast cancer than females with low breast densities [4] and that breast density is increasingly recognised as an independent determinant of breast cancer risk and possibly in prognosis [5]. Assessment of breast density is becoming crucial in epidemiological studies, including the estimation of breast cancer risk and assessing breast density-related risk over time, radiation dose monitoring and monitoring drug-related response [6,7].Different methods and classifications have been reported to assess breast density: the Tabar classification [8], Wolfe''s parenchymal patterns [9], and both semi-quantitative and quantitative computer-aided techniques [10–16]. The Breast Imaging–Reporting and Data System (BI-RADS) classification, considered as the additional quantitative scheme, is routinely used in the USA and was introduced to standardise reporting. Initially, it was based on four qualitative categories but an additional quantitative scheme was added in 2003, based on the extent of fibroglandular tissue [17]. Mammographic breast density estimation may be limited by the two-dimensional (2D) nature of the imaging technique, whereas a three-dimensional (3D) imaging modality, such as digital breast tomosynthesis (DBT), reduces the appearance of the overlapping parenchymal tissue and may therefore influence or alter density assessments [13,14]. In DBT, high-spatial-resolution tomographic images of the breast are reconstructed from multiple low-dose projection images acquired within a limited range of X-ray tube angles [15]. It has been demonstrated in a few studies that the automated estimation of breast density eliminates subjectivity between comparisons of full-field digital mammography (2D FFDM) and DBT and is more reproducible than a quantitative BI-RADS evaluation [14,16]. However, previous research mainly considered patients with relatively high breast density, with the possibility of the results not being applicable across all density categories and showing whether published percentage breast density differences between 2D FFDM and DBT apply to less dense or non-dense breasts. The purpose of our study was to compare the breast tissue density estimated using 2D FFDM and DBT among patients in a balanced data set of the four BI-RADS categories, using fully automated software.     

Improvement in radiologists' characterization of malignant and benign breast masses on serial mammograms with computer-aided diagnosis: an ROC study

PURPOSE: To evaluate the effects of computer-aided diagnosis (CAD) on radiologists' characterization of masses on serial mammograms. MATERIALS AND METHODS: Two hundred fifty-three temporal image pairs (138 malignant and 115 benign) obtained from 96 patients who had masses on serial mammograms were evaluated. The temporal pairs were formed by matching masses of the same view from two different examinations. Eight radiologists and two breast imaging fellows assessed the temporal pairs with and without computer aid. The classification of accuracy was quantified by using the area under receiver operating characteristic curve (A(z)). The statistical significance of the difference in A(z) between the different reading conditions was estimated with the Dorfman-Berbaum-Metz method for analysis of multireader multicase data and with the Student paired t test for analysis of observer-specific paired data. RESULTS: The average A(z) for radiologists' estimates of the likelihood of malignancy was 0.79 without CAD and improved to 0.84 with CAD. The improvement was statistically significant (P =.005). The corresponding average partial area index was 0.25 without CAD and improved to 0.37 with CAD. The improvement was also statistically significant (P =.005). On the basis of Breast Imaging Reporting and Data System assessments, it was estimated that with CAD, each radiologist, on average, reduced 0.7% (0.8 of 115) of unnecessary biopsies and correctly recommended 5.7% (7.8 of 138) of additional biopsies. CONCLUSION: CAD based on analysis of interval changes can significantly increase radiologists' accuracy in classification of masses and thereby may be useful in improving correct biopsy recommendations.     

Mammographic density estimation: one-to-one comparison of digital mammography and digital breast tomosynthesis using fully automated software

Objective

To compare breast density on digital mammography and digital breast tomosynthesis using fully automated software.

Methods

Following institutional approval and written informed consent from all participating women, both digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) were obtained. Breast percentage density was calculated with software on DBT and FFDM.

Results

Fifty consecutive patients (mean age, 51?years; range, 35–83?years) underwent both FFDM and DBT. Using a method based on the integral curve, breast density showed higher results on FFDM (68.1?±?12.1 for FFDM and 51.9?±?6.5 for DBT). FFDM overestimated breast density in 16.2% (P?P?r?=?0.54, P?r?=?0.44, P?Conclusion Breast density appeared to be significantly underestimated on digital breast tomosynthesis.

Key Points

• Breast density is considered to be an independent risk factor for cancer
• Density can be assessed on full-field digital mammography and digital breast tomosynthesis
• Objective automated estimation of breast density eliminates subjectivity
• Automated estimation is more accurate than BI-RADS quantitative evaluation
• Breast density may be significantly underestimated on digital breast tomosynthesis

     

Absolute choline concentration measured by quantitative proton MR spectroscopy correlates with cell density in meningioma

Introduction  This study was aimed to investigate the relationship between quantitative proton magnetic resonance spectroscopy (1H-MRS) and pathological changes in meningioma. Materials and methods  Twenty-two meningioma cases underwent single voxel 1H-MRS (point-resolved spectroscopy sequence, repetition time/echo time = 2,000 ms/68, 136, 272 ms). Absolute choline (Cho) concentration was calculated using tissue water as the internal reference and corrected according to intra-voxel cystic/necrotic parts. Pathological specimens were stained with MIB-1 antibody to measure cell density and proliferation index. Correlation analysis was performed between absolute Cho concentration and cell density and MIB-1 labeled proliferation index. Results  Average Cho concentration of all meningiomas before correction was 2.95 ± 0.86 mmol/kg wet weight. It was increased to 3.23 ± 1.15 mmol/kg wet weight after correction. Average cell density of all meningiomas was 333 ± 119 cells/HPF, and average proliferation index was 2.93 ± 5.72%. A linear, positive correlation between cell density and Cho concentration was observed (r = 0.650, P = 0.001). After correction of Cho concentration, the correlation became more significant (r = 0.737, P < 0.001). However, no significant correlation between Cho concentration and proliferation index was found. There seemed to be a positive correlation trend after correction of Cho concentration but did not reach significant level. Conclusion  Absolute Cho concentration, especially Cho concentration corrected according to intra-voxel cystic/necrotic parts, reflects cell density of meningioma. Grant: This study was supported by the Japan-China Sasakawa Medical Fellowship (Nippon Foundation, Japan)     

Comparison of measured and perceived time values for radiologists' work: impact on relative value scales

The authors compared the actual time required by radiologists to perform and/or interpret common diagnostic radiologic examinations with the times the same radiologists perceived were necessary (as determined with a survey) to perform and/or interpret those same examinations. Average measured times ranged from 1.7 minutes for radiologic examinations of extremities to 113.2 minutes for interventional procedures. Average survey times ranged from 3.2 minutes for examinations of extremities to 84.4 minutes for cerebral angiography. The mean difference between measured and survey times for all examinations was 48.6%. Relative value scales were developed based on measured and survey times, with the upper gastrointestinal examination assigned the base unit of 100. The difference between the measured-time and survey-time relative value scales was 98% on average for the 16 examinations compared. The study suggests that there is a need for actual measurement of at least the time component of physician work if resource-based relative value scales are to be used as the basis for physician compensation.     

Spinal bone mineral density measured with quantitative CT: effect of region of interest, vertebral level, and technique

This study documents the relationship between different vertebral bone compartments with quantitative computed tomography (CT). Four distinct patient groups were investigated: healthy pre- and early postmenopausal women as well as healthy and osteoporotic late postmenopausal women. Three different regions of interest (ROIs) were employed: the elliptical ROI located in the anterior trabecular portion of the vertebral body, the peeled ROI of irregular shape that circumscribes most of the trabecular bone, and the integral ROI including all bone except for the transverse processes. Both single- and dual-energy quantitative CT techniques were employed at T-12 through L-3. Correlation between measurements in the elliptical and peeled ROIs was high (r = .985). The authors concluded that either ROI is acceptable for clinical use. The decrements in bone mineral density (BMD) for the integral ROI were smaller than those for the elliptical ROI. Dual-energy measurements were consistently higher than single-energy measurements. BMD as a function of vertebral level decreased systematically from T-12 to L-3. However, the average density of T-12 through L-3 can be accurately predicted by the average density of L-1 and L-2 (r = .997). Precision did not deteriorate significantly when BMD was expressed as the average of L-1 and L-2 (1.5%) instead of T-12 through L-3 (1.4%). In this study the data suggest a modified quantitative CT protocol for clinical applications in which BMD of only L-1 and L-2 are measured at a fixed gantry tilt.     

Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study

The classification of breast parenchymal patterns (N1, P1, P2, DY) and the percentage of the breast containing radiographic densities are two highly correlated radiographic measures proposed as predictors of the risk of breast cancer. In this case-control study, 160 cases of breast cancer and 160 matched controls from a mammography referral practice were compared to determine the risk of breast cancer associated with each of these two radiographic measures. The mammographic densities were quantified on caudal projections by means of a compensating polar planimeter. A relative risk estimate of 3.3 (p less than .05) was associated with the P2 + DY patterns compared with the N1 + P1 patterns. Significantly elevated risks of 4.3 to 5.5 also were observed among women whose breasts contained at least 25% mammographic densities, compared with women with less than 25% involvement. These radiographic measures tended to be more predictive of the risk of breast cancer in black women than in white women. Although the precise clinical roles of breast parenchymal patterns and densities have not been defined fully, the results of this study suggest that they are useful in the recognition of women at high risk of breast cancer. We make no claims that the findings of this study are sufficiently developed to be used as a basis for screening strategies.     

Mammographic characteristics of 115 missed cancers later detected with screening mammography and the potential utility of computer-aided detection

PURPOSE: To retrospectively determine the mammographic characteristics of cancers missed at screening mammography and assess the ability of computer-aided detection (CAD) to mark the missed cancers. MATERIALS AND METHODS: A multicenter retrospective study accrued 1,083 consecutive cases of breast cancer detected at screening mammography. Prior mammograms were available in 427 cases. Of these, 286 had lesions visible in retrospect. The 286 cases underwent blinded review by panels of radiologists; a majority recommended recall for 112 cases. Two experienced radiologists compared prior mammograms in 110 of these cases with the subsequent screening mammograms (when cancer was detected), noting mammographic characteristics of breast density, lesion type, size, morphology, and subjective reasons for possible miss. The prior mammograms were then analyzed with a CAD program. RESULTS: There were 110 patients with 115 cancers. On the prior mammograms with missed cancers, 35 (30%) of the 115 lesions were calcifications, with 17 of 35 (49%) clustered or pleomorphic. Eighty of the 115 (70%) were mass lesions, with 32 of 80 (40%) spiculated or irregular. For calcifications and masses, the most frequently suggested reasons for possible miss were dense breasts (12 of 35; 34%) and distracting lesions (35 of 80; 44%), respectively. CAD marked 30 (86%) of 35 missed calcifications and 58 (73%) of 80 missed masses. CONCLUSION: Detection errors affected cases with calcifications and masses. CAD marked most (77%; 88 of 115) cancers missed at screening mammography that radiologists retrospectively judged to merit recall.     

Fractional quantitative computed tomography for bone mineral density evaluation: accuracy, precision, and comparison to quantitative computed tomography

OBJECTIVE: To evaluate bone mineral density considering its distribution, fractional quantitative computed tomography (fQCT) was designed and verified. METHODS: Quantitative computed tomography (QCT) was performed at 64 areas in 10 swine long bones. Fractional quantitative computed tomography was measured at the identical areas as the proportion of pixels showing a bone density higher than 130 mg/mL equivalent. All target areas were extracted and incinerated to measure apparent ash bone density. Based on standard references, the accuracy and precision of fQCT were evaluated and the results were compared with conventional QCT results. RESULTS: The correlation coefficient between fQCT and apparent ash bone density was 0.843 (P < 0.0001). The fQCT showed good correlation with volume fraction (r = 0.88, P < 0.0001). The coefficient of variation of fQCT was 0.42%. The fQCT revealed higher accuracy and precision than the results of QCT. CONCLUSION: Fractional quantitative computed tomography was designed and verified as a reliable method to measure bone mineral density.     

Mandibular bone mineral density measured using dual-energy X-ray absorptiometry: relationship to hip bone mineral density and quantitative ultrasound at calcaneus and hand phalanges

The main aim of this cross-sectional study was the estimation of relationships between mandibular bone mineral density (m-BMD), hip bone mineral densities (BMDs) and quantitative ultrasound at calcaneus and hand phalanges. Correlations between m-BMD and age, years since menopause (YSM) and body size were also evaluated. 42 edentulous persons (36 females and 6 males aged 60.5 +/- 6.9 years) were evaluated. In the group studied no factors affecting bone metabolism (either medical conditions or medications) were noted. Bone status was assessed by dual-energy X-ray absorptiometry (mandible, hip--Lunar DPX-L), and quantitative ultrasound (calcaneus--Lunar Achilles which measures speed of sound (SOS, m s-1) and broadband ultrasound attenuation (BUA, dB MHz-1); and phalanges of the hand--DBM Sonic 1200 which measures amplitude-dependent speed of sound (AD-SOS, m s-1)). CV% for mandibular measurements was 2.06%. m-BMD correlated significantly with the following measurements: femoral neck r = 0.39, p < 0.01; Ward's r = 0.39, p < 0.01; calcaneal BUA r = 0.39, p < 0.01; and phalangeal AD-SOS r = 0.4, p < 0.01. Negative correlation consistent with a significant decrease with age was observed in m-BMD (r = -0.36, p < 0.05) and AD-SOS (r = -0.4, p < 0.01). BMD in the mandible also decreased with YSM (r = -0.47, p < 0.01). m-BMD was correlated with age, YSM, height and weight in stepwise, multiple, linear regression analysis. The following equation was obtained: m-BMD = -2.21 + 0.018 x height (cm) -0.02 x YSM (years) + 0.13 x age (years). It may be concluded that mandibular BMD may be an appropriate measurement site for the evaluation of skeletal status in osteoporosis.     

Effect of Paget's disease of bone on areal lumbar spine bone mineral density measured by DXA, and density of cortical and trabecular bone measured by quantitative CT

Although bone density may be increased in bone that is affected by Paget's disease, density changes in cortical and trabecular bone and the effect on bone that is apparently unaffected by Paget's disease are relatively unexplored. We have investigated 81 vertebrae (28 affected, 53 unaffected) in 27 patients with Paget's disease, by dual X-ray absorptiometry (DXA) and by quantitative CT (QCT) bone density measurements of trabecular and cortical bone. DXA bone density was high (mean z-score = 1.62, p < 0.001) in vertebrae affected by Paget's disease, but not significantly different from normal in unaffected vertebrae (mean z-score = 0.07, ns). Mean QCT z-score in Paget's vertebrae was 2.07 (p = 0.009) for cortical bone and 1.37 (p = 0.008) for trabecular bone. DXA correlated with QCT cortical values in affected and unaffected bone (r = 0.8 and 0.56, respectively), and with QCT trabecular values (r = 0.72 and 0.48, respectively). There was no significant difference in the slopes for the correlations in affected or unaffected bone. Cortical QCT values are underestimated in Paget's disease compared with physical measurements of density, owing to the computer algorithm used. High DXA values may alert to the possibility of Paget's disease, especially if the value deviates from the expected normal sequence in lumbar vertebrae. Osteoporotic vertebrae may be overlooked if the average value of bone mineral density is taken in the lumbar spine without reviewing each vertebra.     

Comparison of Eustachian tube function measured by the microflow method and a new quantitative impedance method

Eustachian tube function in 25 applicants for flight training was tested during simulated flights using two methods alternately; the integrating microflow method with a stationary pressure chamber, and a new quantitative impedance method in combination with a new mobile pressure chamber. All ears were tested by both methods. The results of the various tests did not differ significantly between methods. The reliability of the measurements was good and almost equal in both methods. Several practical advantages with the new impedance method in combination with the mobile pressure chamber make it preferable.