Erini Makariou

Real-time imaging and characterization of human breast tissue by reflectance confocal microscopy

Real-time technologies can increase the efficiency of obtaining informative biopsies and accelerate interpretation of biopsy pathological review. Cellular aberrations inherent to cancer cells, including nuclear size, can currently be detected, but few technologies are available to evaluate adequacy of specimens in real time. The aims of this study are: 1. to determine if near-infrared reflectance confocal microscopy (RCM) can be used to assess epithelial/stromal content of core needle breast biopsy samples in real time, 2. to determine if epithelial cell nuclear size can be measured on RCM images, and 3. to test if RCM images can be accurately read for presence/absence of histologically relevant features of malignancy. Breast biopsies are obtained following a medically indicated breast core needle diagnostic biopsy for RCM examination. Acetic acid is used as a contrast agent to visualize structures within breast tissue. Structures are identified and optically serially sectioned, and digital images are cataloged. Relative amounts of epithelial, fatty, and collagenous tissue are determined. RCM biopsies are formalin-fixed and stained for hematoxylin and eosin (H and E) comparison with RCM images. RCM data are comparable to data from H and E sections. Epithelial cell nuclear size is measured on stored digital RCM images. We compare RCM and H and E images from 16 patients and 25 core needle biopsy samples.

Growth Rate Characteristics of Acoustic Neuromas Associated With Neurofibromatosis Type 2

Neurofibromatosis type 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral acoustic neuromas (ANs) and other central nervous system tumors. Magnetic resonance images and audiologic data on 22 patients with NF2 who underwent multiple studies at the National Institutes of Health between 1983 and 1993 were reviewed to determine the growth characteristics of ANs in these patients.

Phase contrast digital mammography using molybdenum x-ray: clinical implications in detectability improvement

We have applied phase imaging on digital mammography to investigate adequate contrast of printed images for digital phase contrast mammography using a practical molybdenum X-ray tube. Phase contrast mammography procedures were performed with defined air gap (e.g., 0.6 m) configuration using customized mammography equipment and a computed radiography (CR) system. Magnified (x2) phase contrast images acquired with 0.0875mm per pixel were mapped onto the laser imager resolution at 0.04375mm per pixel for printing life-size object on wet processing silver halide recording film. For contact mammography of screen-film system, we used MinR2000 system as a baseline method. ACR 156 phantom printed images with contrasts of 2.8, 3.7, 4.9, 5.7 and 6.7 were evaluated by five radiologists. The ACR scores for the life-size image based on the 2 times magnified phase contrast image acquired by the computed radiography were higher than the scores of MinR2000 image, when the contrast of printed images for both methods was 3.7. The ACR scores were lower in the low contrast images (i.e., 2.8) than its higher contrast counterparts (i.e., >= 3.7) for all techniques used. The detectability improvement should be due to higher spatial resolution and lower noise in the phase contrast images.

Mammographic Breast Density as a Risk Factor for Breast Cancer: Awareness in a Recently Screened Clinical Sample

BACKGROUND Breast density is an established, independent risk factor for breast cancer. Despite this, density has not been included in standard risk models or routinely disclosed to patients. However, this is changing in the face of legal mandates and advocacy efforts. Little information exists regarding womens awareness of density as a risk factor, their personal risk, and risk management options. METHODS We assessed awareness of density as a risk factor and whether sociodemographic variables, breast cancer risk factors. and perceived breast cancer risk were associated with awareness in 344 women with a recent screening mammogram at a tertiary care center. FINDINGS Overall, 62% of women had heard about density as a risk factor and 33% had spoken to a provider about breast density. Of the sample, 18% reported that their provider indicated that they had high breast density. Awareness of density as a risk factor was greater among White women and those with other breast cancer risk factors. CONCLUSION Our results suggest that although a growing number of women are aware of breast density as a risk factor, this awareness varies. Growing mandates for disclosure suggest the need for patient education interventions for women at increased risk for the disease and to ensure all women are equally aware of their risks.

Stereotactic Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Rationale, Feasibility, and Early Experience Using the CyberKnife Radiosurgery Delivery Platform

Purpose The efficacy of accelerated partial breast irradiation (APBI) utilizing brachytherapy or conventional external beam radiation has been studied in early-stage breast cancer treated with breast-conserving surgery. Data regarding stereotactic treatment approaches are emerging. The CyberKnife linear accelerator enables excellent dose conformality to target structures while adjusting for target and patient motion. We report our institutional experience on the technical feasibility and rationale for stereotactic accelerated partial breast irradiation (SAPBI) delivery using the CyberKnife radiosurgery system. Methods Ten patients completed CyberKnife SAPBI (CK-SAPBI) in 2013 at Georgetown University Hospital. Four gold fiducials were implanted around the lumpectomy cavity prior to treatment under ultrasound guidance. The synchrony system tracked intrafraction motion of the fiducials. The clinical target volume was defined on contrast enhanced CT scans using surgical clips and post-operative changes. A 5 mm expansion was added to create the planning treatment volume (PTV). A total dose of 30 Gy was delivered to the PTV in five consecutive fractions. Target and critical structure doses were assessed as per the National Surgical Adjuvant Breast and Bowel Project B-39 study. Results At least three fiducials were tracked in 100% of cases. The Mean treated PTV was 70 cm3 and the mean prescription isodose line was 80%. Mean dose to target volumes and constraints are as follows: 100% of the PTV received the prescription dose (PTV30). The volume of the ipsilateral breast receiving 30 Gy (V30) and above 15 Gy (V > 15) was 14 and 31%, respectively. The ipsilateral lung volume receiving 9 Gy (V9) was 3%, and the contralateral lung volume receiving 1.5 Gy (V1.5) was 8%. For left-sided breast cancers, the volume of heart receiving 1.5 Gy (V1.5) was 31%. Maximum skin dose was 36 Gy. At a median follow-up of 1.3 years, all patients have experienced excellent/good breast cosmesis outcomes, and no breast events have been recorded. Conclusion CyberKnife stereotactic accelerated partial breast irradiation is an appealing technique for partial breast irradiation offering improvements over existing APBI techniques. Our early findings indicate that CK-SAPBI delivered in five daily fractions is feasible, well tolerated, and is a reliable platform for delivering APBI.

A Pivotal Study of Optoacoustic Imaging to Diagnose Benign and Malignant Breast Masses: A New Evaluation Tool for Radiologists

Purpose To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses. Materials and Methods This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared. Results Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone. Online supplemental material is available for this article.

Silicone Granuloma Mimicking Breast Cancer Recurrence on PET CT

The patient is a 67-year-old female with a history of bilateral breast augmentation and implant rupture. Her imaging history was complicated by the development of new parenchymal densities on mammogram, proven to be silicone granulomas by core needle biopsy. The pathologically proven silicone granuloma in the left breast had been stable in mammographic appearance for years (Fig. 1). The ruptured implants were eventually surgically removed and the residual silicone granulomas remained unchanged. She subsequently developed suspicious microcalcifications in her left breast in region of the dense silicone granulomas (Fig. 2). The microcalcifications were pathologically proven infiltrating ductal carcinoma by core needle biopsy. The patient was found to have positive supraclavicular and left axillary lymph nodes. She underwent a left mastectomy and radiation therapy. During the course of her surveillance for breast cancer recurrence, an abdominal CT detected hypervascular liver lesions which prompted further investigation for metastases with PET CT. The PET scan showed no

Automatic Categorization of Mammographic Masses Using BI-RADS as a Guidance

In this study, we present a clinically guided technical method for content-based categorization of mammographic masses. Our work is motivated by the continuing effort in content-based image annotation and retrieval to extract and model the semantic content of images. Specifically, we classified the shape and margin of mammographic mass into different categories, which are designated by radiologists according to descriptors from Breast Imaging Reporting and Data System Atlas (BI-RADS). Experiments were conducted within subsets selected from datasets consisting of 346 masses. In the experiments that categorize lesion shape, we obtained a precision of 70% with three classes and 87.4% with two classes. In the experiments that categorize margin, we obtained precisions of 69.4% and 74.7% for the use of four and three classes, respectively. In this study, we intend to demonstrate that this classification based method is applicable in extracting the semantic characteristics of mass appearances, and thus has the potential to be used for automatic categorization and retrieval tasks in clinical applications.

Effectiveness of a Rapid Lumbar Spine MRI Protocol Using 3D T2-Weighted SPACE Imaging Versus a Standard Protocol for Evaluation of Degenerative Changes of the Lumbar Spine.

OBJECTIVE Reducing lumbar spine MRI scanning time while retaining diagnostic accuracy can benefit patients and reduce health care costs. This study compares the effectiveness of a rapid lumbar MRI protocol using 3D T2-weighted sampling perfection with application-optimized contrast with different flip-angle evolutions (SPACE) sequences with a standard MRI protocol for evaluation of lumbar spondylosis. MATERIALS AND METHODS Two hundred fifty consecutive unenhanced lumbar MRI examinations performed at 1.5 T were retrospectively reviewed. Full, rapid, and complete versions of each examination were interpreted for spondylotic changes at each lumbar level, including herniations and neural compromise. The full examination consisted of sagittal T1-weighted, T2-weighted turbo spin-echo (TSE), and STIR sequences; and axial T1- and T2-weighted TSE sequences (time, 18 minutes 40 seconds). The rapid examination consisted of sagittal T1- and T2-weighted SPACE sequences, with axial SPACE reformations (time, 8 minutes 46 seconds). The complete examination consisted of the full examination plus the T2-weighted SPACE sequence. Sensitivities and specificities of the full and rapid examinations were calculated using the complete study as the reference standard. RESULTS The rapid and full studies had sensitivities of 76.0% and 69.3%, with specificities of 97.2% and 97.9%, respectively, for all degenerative processes. Rapid and full sensitivities were 68.7% and 66.3% for disk herniation, 85.2% and 81.5% for canal compromise, 82.9% and 69.1% for lateral recess compromise, and 76.9% and 69.7% for foraminal compromise, respectively. CONCLUSION Isotropic SPACE T2-weighted imaging provides high-quality imaging of lumbar spondylosis, with multiplanar reformatting capability. Our SPACE-based rapid protocol had sensitivities and specificities for herniations and neural compromise comparable to those of the protocol without SPACE. This protocol fits within a 15-minute slot, potentially reducing costs and discomfort for a large subgroup of patients.

Mass segmentation of dense breasts on digitized mammograms: analysis of a probability-based function

In this study, a segmentation algorithm based on the steepest changes of a probabilistic cost function was tested on non-processed and pre-processed dense breast images in an attempt to determine the efficacy of pre-processing for dense breast masses. Also, the inter-observer variability between expert radiologists was studied. Background trend correction was used as the pre-processing method. The algorithm, based on searching the steepest changes on a probabilistic cost function, was tested on 107 cancerous masses and 98 benign masses with density ratings of 3 or 4 according to the American College of Radiologys density rating scale. The computer-segmented results were validated using the following statistics: overlap, accuracy, sensitivity, specificity, Dice similarity index, and kappa. The mean accuracy statistic value ranged from 0.71 to 0.84 for cancer cases and 0.81 to 0.86 for benign cases. For nearly all statistics there were statistically significant differences between the expert radiologists.