Lisa J. Wilmes

Magnetic resonance imaging for secondary assessment of breast density in a high-risk cohort

A quantitative measure of three-dimensional breast density derived from noncontrast magnetic resonance imaging (MRI) was investigated in 35 women at high-risk for breast cancer. A semiautomatic segmentation tool was used to quantify the total volume of the breast and to separate volumes of fibroglandular and adipose tissue in noncontrast MRI data. The MRI density measure was defined as the ratio of breast fibroglandular volume over total volume of the breast. The overall correlation between MRI and mammographic density measures was R(2)=.67. However the MRI/mammography density correlation was higher in patients with lower breast density (R(2)=.73) than in patients with higher breast density (R(2)=.26). Women with mammographic density higher than 25% exhibited very different magnetic resonance density measures spread over a broad range of values. These results suggest that MRI may provide a volumetric measure more representative of breast composition than mammography, particularly in groups of women with dense breasts. Magnetic resonance imaging density could potentially be quantified and used for a better assessment of breast cancer risk in these populations.

Quantification of breast tissue index from MR data using fuzzy clustering

The study objective was to develop a segmentation technique to quantify breast tissue and total breast volume from magnetic resonance imaging (MRI) data to obtain a breast tissue index (BTI) related to breast density. Our goal is to quantify MR breast density to improve breast cancer risk assessment for certain high-risk populations for whom mammography is of limited usefulness due to high breast density. A semi-automatic 3D segmentation technique was implemented based on a fuzzy c-means technique (FCM) to segment fibroglandular tissue from fat in the breast images. After validation on a phantom, our FCM technique was first used to test the breast tissue measures reproducibility in two consecutive MR examinations of the same patients. The technique was then applied to measure the BTI on 10 high-risk patients. Results of BTI obtained with the semi-automated FCM method were compared with BTI results for the same patients using two other techniques, manual delineation and global threshold. BTI measures correlated well with mammographic densities (Pearson coefficients r = 0.78 using MR manual delineation, and r = 0.75 using MR FCM). The breast tissue index could therefore become a common measure for future studies of using noncontrast MRI data.

Diffusion-weighted MRI: influence of intravoxel fat signal and breast density on breast tumor conspicuity and apparent diffusion coefficient measurements.

Promising recent investigations have shown that breast malignancies exhibit restricted diffusion on diffusion-weighted imaging (DWI) and may be distinguished from normal tissue and benign lesions in the breast based on differences in apparent diffusion coefficient (ADC) values. In this study, we assessed the influence of intravoxel fat signal on breast diffusion measures by comparing ADC values obtained using a diffusion-weighted single shot fast spin-echo sequence with and without fat suppression. The influence of breast density on ADC measures was also evaluated. ADC values were calculated for both tumor and normal fibroglandular tissue in a group of 21 women with diagnosed breast cancer. There were systematic underestimations of ADC for both tumor and normal breast tissue due to intravoxel contribution from fat signal on non-fat-suppressed DWI. This ADC underestimation was more pronounced for normal tissue values (mean difference=40%) than for tumors (mean difference=27%, P<.001) and was worse in women with low breast tissue density vs. those with extremely dense breasts (P<.05 for both tumor and normal tissue). Tumor conspicuity measured by contrast-to-noise ratio was significantly higher on ADC maps created with fat suppression and was not significantly associated with breast density. In summary, robust fat suppression is important for accurate breast ADC measures and optimal lesion conspicuity on DWI.

Heterogeneity in the angiogenic response of a BT474 human breast cancer to a novel vascular endothelial growth factor‐receptor tyrosine kinase inhibitor: Assessment by voxel analysis of dynamic contrast‐enhanced MRI

To investigate the heterogeneity in the angiogenic response of a human breast cancer xenograft to a novel vascular endothelial growth factor (VEGF)‐receptor tyrosine kinase inhibitor, AG‐013736, using dynamic contrast‐enhanced MR imaging (DCE‐MRI).

Kinetic Assessment of Breast Tumors Using High Spatial Resolution Signal Enhancement Ratio (SER) Imaging

The goal of this study was to investigate the relationship between an empirical contrast kinetic parameter, the signal enhancement ratio (SER), for three‐timepoint, high spatial resolution contrast‐enhanced (CE) MRI, and a commonly analyzed pharmacokinetic parameter, kep, using dynamic high temporal resolution CE‐MRI. Computer simulation was performed to investigate: 1) the relationship between the SER and the contrast agent concentration ratio (CACR) of two postcontrast timepoints (tp1 and tp2); 2) the relationship between the CACR and the redistribution rate constant (kep) based on a two‐compartment pharmacokinetic model; and 3) the sensitivity of the relationship between the SER and kep to native tissue T1 relaxation time, T10, and to errors in an assumed vascular input function. The relationship between SER and kep was verified experimentally using a mouse model of breast cancer. The results showed that a monotonic mathematical relationship between SER and kep could be established if the acquisition parameters and the two postinjection timepoints of SER, tp1, tp2, were appropriately chosen. The in vivo study demonstrated a close correlation between SER and kep on a pixel‐by‐pixel basis (Spearman rank correlation coefficient = 0.87 ± 0.03). The SER is easy to calculate and may have a unique role in breast tissue characterization. Magn Reson Med, 2007.

Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development

Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2, gelatinase A) are associated with syndromes that include abnormal facial appearance, short stature, and severe bone loss. Mmp2−/− mice have only mild aspects of these abnormalities, suggesting that MMP2 function is redundant during skeletal development in the mouse. Here, we report that Mmp2−/− mice with additional mutations that render type I collagen resistant to collagenase‐mediated cleavage to TCA and TCB fragments (Col1a1r/r mice) have severe developmental defects resembling those observed in MMP2‐null humans. Composite Mmp2−/−;Col1a1r/r mice were born in expected Mendelian ratios but were half the size of wild‐type, Mmp2−/−, and Col1a1r/r mice and failed to thrive. Furthermore, composite Mmp2−/−;Col1a1r/r animals had very abnormal craniofacial features with shorter snouts, bulging skulls, incompletely developed calvarial bones and unclosed cranial sutures. In addition, trabecular bone mass was reduced concomitant with increased numbers of bone‐resorbing osteoclasts and osteopenia. In vitro, MMP2 had a unique ability among the collagenolytic MMPs to degrade mutant collagen, offering a possible explanation for the genetic interaction between Mmp2 and Col1a1r. Thus, because mutations in the type I collagen gene alter the phenotype of mice with null mutations in Mmp2, we conclude that type I collagen is an important modifier gene for Mmp2. Developmental Dynamics 236:1683–1693, 2007.

Quantitative tissue oxygen measurement in multiple organs using 19F MRI in a rat model

Measurement of individual organ tissue oxygen levels can provide information to help evaluate and optimize medical interventions in many areas including wound healing, resuscitation strategies, and cancer therapeutics. Echo planar 19F MRI has previously focused on tumor oxygen measurement at low oxygen levels (pO2) <30 mmHg. It uses the linear relationship between spin‐lattice relaxation rate (R1) of hexafluorobenzene (HFB) and pO2. The feasibility of this technique for a wider range of pO2values and individual organ tissue pO2 measurement was investigated in a rat model. Spin‐lattice relaxation times (T1= 1/R1) of hexafluorobenzene were measured using 19F saturation recovery echo planar imaging. Initial in vitro studies validated the linear relationship between R1 and pO2 from 0 to 760 mmHg oxygen partial pressure at 25, 37, and 41°C at 7 Tesla for hexafluorobenzene. In vivo experiments measured rat tissue oxygen (ptO2) levels of brain, kidney, liver, gut, muscle, and skin during inhalation of both 30 and 100% oxygen. All organ ptO2 values significantly increased with hyperoxia (P < 0.001). This study demonstrates that 19F MRI of hexafluorobenzene offers a feasible tool to measure regional ptO2 in vivo, and that hyperoxia significantly increases ptO2 of multiple organs in a rat model. Magn Reson Med, 2011.

Demonstration of nonlinearity bias in the measurement of the apparent diffusion coefficient in multicenter trials.

Characterize system‐specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials.

High-Resolution Diffusion-Weighted Imaging for Monitoring Breast Cancer Treatment Response

RATIONALE AND OBJECTIVES The aim of this work was to compare a high-resolution diffusion-weighted imaging (HR-DWI) acquisition (voxel size = 4.8 mm(3)) to a standard diffusion-weighted imaging (STD-DWI) acquisition (voxel size = 29.3 mm(3)) for monitoring neoadjuvant therapy-induced changes in breast tumors. MATERIALS AND METHODS Nine women with locally advanced breast cancer were imaged with both HR-DWI and STD-DWI before and after 3 weeks (early treatment) of neoadjuvant taxane-based treatment. Tumor apparent diffusion coefficient (ADC) metrics (mean and histogram percentiles) from both DWI methods were calculated, and their relationship to tumor volume change after 12 weeks of treatment (posttreatment) measured by dynamic contrast enhanced magnetic resonance imaging was evaluated with a Spearmans rank correlation. RESULTS The HR-DWI pretreatment 15th percentile tumor ADC (P = .03) and early treatment 15th, 25th, and 50th percentile tumor ADCs (P = .008, .010, .04, respectively) were significantly lower than the corresponding STD-DWI percentile ADCs. The mean tumor HR-ADC was significantly lower than STD-ADC at the early treatment time point (P = .02), but not at the pretreatment time point (P = .07). A significant early treatment increase in tumor ADC was found with both methods (P < .05). Correlations between HR-DWI tumor ADC and posttreatment tumor volume change were higher than the STD-DWI correlations at both time points and the lower percentile ADCs had the strongest correlations. CONCLUSION These initial results suggest that the HR-DWI technique has potential for improving characterization of low tumor ADC values over STD-DWI and that HR-DWI may be of value in evaluating tumor change with treatment.

Quantification of background enhancement in breast magnetic resonance imaging

To present a novel technique for measuring tissue enhancement in breast fibroglandular tissue regions on contrast‐enhanced breast magnetic resonance imaging (MRI) aimed at quantifying the enhancement of breast parenchyma, also known as “background enhancement.”