Roberta A. Jong

A hybrid breast biopsy system combining ultrasound and MRI

System design and initial phantom accuracy results for a novel biopsy system integrating both magnetic resonance (MR) and ultrasound (US) imaging modalities are presented. A phantom experiment was performed to investigate the efficacy of this hybrid guidance biopsy technique in a breast tissue mimicking phantom. A comparison between MR-guided core biopsy verses MR/US-guided core biopsy of phantom targets was realized using a scoring system based on the consistency of the acquired core samples (14 gauge). It was determined that the addition of US to guide needle placement improved the accuracy from an average score of 7.4 out of 10 (MRI guidance alone), to 9.6 (MRI/US guidance) over 21 trials. The average amount of needle tip correction resulting from the additional US information was determined to be 3.7 mm. This correction value is substantial, equal to approximately one radius of the intended targets. Hybrid US/MRI guided biopsy appears to offer a simple means to ensure accurate breast tissue sampling without the need for repeat MRI scans for verification or the need for real-time imaging in open MRI geometries.

Improvement in DCIS Detection Rates by MRI Over Time in a High‐Risk Breast Screening Study

Abstract:  Although magnetic resonance imaging (MRI) is much more sensitive than mammography for detecting early invasive breast cancer, in many high‐risk screening studies MRI was less sensitive than mammography for detecting ductal carcinoma in situ (DCIS). We reviewed our experience detecting DCIS in our single center study of annual MRI, mammography, ultrasound and clinical breast examination (CBE) for screening very high‐risk women. All cases of DCIS ± microinvasion and invasive cancer were compared in two time frames: before (period A) and after (period B) July 2001—when we acquired expertise in the detection of DCIS with MRI—with respect to patient demographics, method of detection, and rates of detection of invasive cancer and DCIS. In period A there were 15 cases (3.1% of 486 screens) in 223 women, of which 2 (13%) were DCIS—one with microinvasion—neither detected by MRI. In period B there were 29 cases (3.3% of 877 screens) in 391 women, of which 10 (34%) were DCIS ± microinvasion (p = 0.04), all 10 detected by MRI but only one by mammography. No DCIS cases were detected by ultrasound or CBE. Specificity was lower in period B than in period A but acceptable. The ability to detect DCIS with screening MRI improves significantly with experience. MRI‐guided biopsy capability is essential for a high‐risk screening program. In experienced centers the increased sensitivity of MRI relative to mammography is at least as high for DCIS as it is for invasive breast cancer.

Quantifying masking in clinical mammograms via local detectability of simulated lesions

PURPOSE High mammographic density is known to be associated with decreased sensitivity of mammography. Recent changes in the BI-RADS density assessment address the effect of masking by densities, but the BI-RADS assessment remains qualitative and achieves only moderate agreement between radiologists. An automated, quantitative algorithm that estimates the likelihood of masking of simulated masses in a mammogram by dense tissue has been developed. The algorithm considers both the effects of loss of contrast due to density and the distracting texture or appearance of dense tissue. METHODS A local detectability (dL) map is created by tessellating the mammograms into overlapping regions of interest (ROIs), for which the detectability by a non-prewhitening observer is computed using local estimates of the noise power spectrum and volumetric breast density (VBD). The dL calculation was validated in a 4-alternative forced-choice observer study on the ROIs of 150 craniocaudal digital mammograms. The dL metric was compared against the inverse threshold contrast, (ΔμT)(-1) from the observer study, the anatomic noise parameter β, the radiologists BI-RADS density category, and a validated measure of VBD (Cumulus). RESULTS The mean dL had a high correlation of r = 0.915 and r = 0.699 with (ΔμT)(-1) in the computerized and human observer study, respectively. In comparison, the local VBD estimate had a low correlation of 0.538 with (ΔμT)(-1). The mean dL had a correlation of 0.663, 0.835, and 0.696 with BI-RADS density, β, and Cumulus VBD, respectively. CONCLUSIONS The proposed dL metric may be useful in characterizing the potential for lesion masking by dense tissue. Because it uses information about the anatomic noise or tissue appearance, it is more closely linked to lesion detectability than VBD metrics.

Design and validation of a mathematical breast phantom for contrast-enhanced digital mammography

In contrast-enhanced digital mammography (CEDM) an iodinated contrast agent is employed to increase lesion contrast and to provide tissue functional information. Here, we present the details of a software phantom that can be used as a tool for the simulation of CEDM images, and compare the degree of anatomic noise present in images simulated using the phantom to that associated with breast parenchyma in clinical CEDM images. Such a phantom could be useful for multiparametric investigations including characterization of CEDM imaging performance and system optimization. The phantom has a realistic mammographic appearance based on a clustered lumpy background and models contrast agent uptake according to breast tissue physiology. Fifty unique phantoms were generated and used to simulate regions of interest (ROI) of pre-contrast images and logarithmically subtracted CEDM images using monoenergetic ray tracing. Power law exponents, β, were used as a measure of anatomic noise and were determined using a linear least-squares fit to log-log plots of the square of the modulus of radially averaged image power spectra versus spatial frequency. The power spectra for ROI selected from regions of normal parenchyma in 10 pairs of clinical CEDM pre-contrast and subtracted images were also measured for comparison with the simulated images. There was good agreement between the measured β in the simulated CEDM images and the clinical images. The values of β were consistently lower for the logarithmically subtracted CEDM images compared to the pre-contrast images, indicating that the subtraction process reduced anatomical noise.

A Prospective Study of Breast Cancer Incidence and Stage Distribution in Women with a BRCA1 or BRCA2 Mutation under Surveillance with and without Magnetic Resonance Imaging.

Introduction: The sensitivity of MRI for the detection of pre-clinical breast cancer exceeds that of mammography and of other screening tests. If MRI screening leads to reduced mortality in women with a BRCA1 or BRCA2 mutation, then it is expected that the incidence of advanced stage breast cancers should be reduced in a cohort of women undergoing regular MRI screening, compared to conventional screening. Methods: We followed 1275 women with a BRCA1 or BRCA2 mutation for a mean of 3.2 years for incident breast cancers. 445 women were enrolled in an MRI screening trial in Toronto and 830 controls, from elsewhere in Canada and the United States, underwent conventional screening. The cumulative incidences of DCIS, of early-stage and of late-stage breast cancer were estimated at six years in the two cohorts. Results: There were 41 cases of breast cancer diagnosed in the MRI-screened cohort and 76 cases of breast cancer diagnosed in the control cohort. The cumulative incidence of DCIS or stage I breast cancer at six years was 12.7% in the MRI-screened cohort and was 9.5% in the control group (p = 0.02; log rank test). The cumulative incidence of stage II – IV breast cancers at six years was 2.0% in the MRI-screened cohort and was 7.1% in the control group (p = 0.02; log rank test). The adjusted hazard ratio for the development of stage II – IV breast cancer associated with membership in the MRI-screened cohort was 0.30 (95% CI: 0.12 to 0.72; p = 0.008). Conclusion: Annual surveillance with MRI is associated with a significant reduction in the incidence of advanced stage breast cancer in BRCA1 and BRCA2 carriers.Funding for this study is generously provided by the Canadian Breast Cancer Research Alliance. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 26.

Effect of age and temporal patterns over 5 years in a Magnetic Resonance Imaging (MRI)-based breast surveillance study for BRCA mutation carriers

9500 Background: With mammography (M) -based screening for BRCA mutation carriers, interval cancer rates are 44-56% and node +ve rates are 23-56%. (Brekelmans JCO 2001, Scheuer JCO 2002). Breast MRI is more sensitive than M but less specific (Robson ASCO 2002), and a reduction in breast cancer mortality is yet unproven. METHODS Since 11/97 BRCA mutation carriers ages 25 to 65 have been enrolled in a 5 year surveillance study of annual M, ultrasound (US), MRI, and semi-annual clinical breast examination (CBE). RESULTS 279 women (57% BRCA1, 39% previously affected) have had at least 1 round of screening, with 30 screen-detected cancers in 29 women and only 1 interval cancer (3%). Overall sensitivity of MRI was 84%, M 32% (p=0.005), US 40%, CBE 7%. These differences in sensitivity were almost identical for the 14 women ≥ age 50 vs. 17 women < age 50 at diagnosis, and for the 10 in-situ (DCIS) vs. 21 invasive cancers, and did not vary significantly over the 5 years. (See table below.) Conclusions: 1. MRI is significantly more sensitive than mammography independent of age. 2. MRI specificity improves more than ultrasound over time and is acceptable after the 1st year. 3. The extremely low interval cancer rate and tumour stage compared to historical controls, and the decrease in cancer detection rate and tumour stage after the first screen, all predict that MRI-based surveillance will likely lower cancer mortality rates in BRCA mutation carriers. [Figure: see text] [Table: see text].

Is Ductal Carcinoma In Situ With “Possible Invasion” More Predictive of Invasive Carcinoma Than Pure Ductal Carcinoma In Situ?

Objectives To compare the underestimation of ductal carcinoma in situ (DCIS) vs DCIS with “possible invasion” at breast biopsy and to determine if any factors related to clinical indication, imaging abnormality, biopsy, or DCIS-grade affected the likelihood of underestimation. Methods Of 3836 consecutive lesions that were biopsied by using a 14-gauge needle, 117 lesions revealed DCIS. Surgical pathology results of invasive carcinoma were compared with needle biopsy results of DCIS or DCIS with possible invasion. Clinical indication, imaging abnormality, biopsy guidance modality, sample number, and histologic grade were recorded. Yates corrected χ2 and Fisher exact tests were used to determine differences between groups. Results A total of 101 lesions were DCIS and 16 were DCIS with possible invasion at biopsy. Thirty-six of 117 lesions (31%) revealed invasive carcinoma at resection pathology. Invasive carcinoma was present more often when DCIS with possible invasion was diagnosed compared with pure DCIS (7/16 [44%] vs 29/101 [29%], P = .36). No factor, including clinical indication, imaging abnormality, biopsy guidance method, sample number, or grade, was found to significantly affect the likelihood of underestimation for lesions diagnosed as DCIS vs DCIS with “possible invasion.” The likelihood of pure DCIS underestimation significantly increased when lesions were high grade compared with either intermediate or low grade (18/44 [41%] vs 9/44 [21%] vs 2/10 [20%], P = .03). Conclusion For lesions biopsied by using a 14-gauge needle, there is a trend towards underestimation of the presence of invasive carcinoma when pathology reveals DCIS with possible invasion compared with pure DCIS. High-grade DCIS was significantly more likely to be underestimated.

Women with Locally Advanced Breast Cancer are Not at Higher Risk for Contralateral Synchronous Breast Cancer

Abstract:  Breast magnetic resonance imaging (MRI) may provide a more accurate assessment of synchronous contralateral breast cancer in select cohorts of patients. The utility of this imaging technique for detecting synchronous contralateral breast cancers in patients with locally advanced breast cancer (LABC) has not previously been described. We report our experience in assessing contralateral disease in a cohort of women with LABC who had clinical assessment, mammography, ultrasound, and MRI prior to neo‐adjuvant therapy. Patients, who presented with LABC, stage IIB (T3N0), stage III A/B, were identified from a prospectively kept data base at a single tertiary care centre between November 2001 and August 2005. Charts were retrospectively reviewed and demographic, imaging and pathologic variables were abstracted. One hundred and one female patients with LABC were identified (median age 49). One hundred of 101 patients presented with a clinically obvious LABC. Three patients had LABC that was not visualized mammographically but was detected on ultrasound and MRI. Seventeen of 101 patients (17%) had contralateral imaging findings that required biopsy for diagnosis. Of the contralateral biopsies, 41% (7/17) were malignant. These malignant lesions were identified clinically in 4/7 patients, on 7/7 ultrasounds, 7/7 mammograms, and 5/5 MRI. Overall, 7% (7/101) patients had malignant synchronous contralateral disease. In our LABC patient cohort, 7% of patients presented with malignant contralateral disease. The incidence of contralateral disease in women with LABC is comparable with patients who present with early stage breast cancer. No single screening technique, ultrasound, mammogram or MRI, appeared to be superior for identifying contralateral synchronous malignancy.

Rapid MRI of the breast in evaluating lesions discovered on screening

In Canada, breast MRI has traditionally been reserved for evaluation of disease extent in patients with known breast malignancy. More recently, MRI has been emerging as an instrument for breast screening. However, its utilization is limited by increased relative cost and increased reader time. In this study, we evaluate a rapid MRI protocol for breast cancer screening within a breast screening population.

Local Detectability Maps as a Tool for Predicting Masking Probability and Mammographic Performance

High mammographic density is associated with reduced sensitivity of mammography. Recent changes in the BI-RADS density assessment address the potential for dense tissue to mask lesions, but the assessment remains qualitative and achieves only moderate agreement between radiologists. We have developed an automated, quantitative algorithm that generates a local detectability dL map, which estimates the likelihood that a simulated lesion would be missed if present. The dL map is computed by tessellating the mammogram into overlapping regions of interest, for which the detectability of a simulated lesion by a non-prewhitening model observer is calculated using local estimates of the noise power spectrum and volumetric breast density. The algorithm considers both the effects of loss of contrast due to density and the distracting appearance of density on lesion conspicuity. In previous work, it has been shown that the mean dL from the maps are strongly correlated to detection performance by computerized and human readers in a controlled reader study. Here, we investigate how various statistical features of the dL maps gray-level histogram and co-occurrence features are related to the diagnostic performance of mammography in a set of images comprised of 8 cancer cases that were mammographically occult and 40 cancer that were detected in screening mammography.