Breast Cyst Fluid Analysis Correlations with Speed of Sound Using Transmission Ultrasound.

RATIONALE AND OBJECTIVES The purpose of this work is to determine if the speed of sound value of a breast cyst can aid in the clinical management of breast masses. Breast macrocysts are defined as fluid-filled tissue masses >1 cm in diameter and are thought to be aberrations of normal development and involution, often associated with apocrine metaplasia. The benign natural history of breast cysts is well known, and it is important to obtain high specificity in breast imaging to avoid unnecessary biopsies in women who have benign diseases, particularly those with dense breast tissue. Transmission ultrasound is a tomographic imaging modality that generates high-resolution, 3D speed of sound maps that could be used to identify breast tissue types and act as a biomarker to differentiate lesions. We performed this study to investigate the microanatomy of macrocysts observed using transmission ultrasound, as well as assess the relationship of speed of sound to the physical and biochemical parameters of cyst fluids. MATERIALS AND METHODS Cyst fluid samples were obtained from 37 patients as part of a case-collection study for ultrasound imaging of the breast. The speed of sound of each sample was measured using a quantitative transmission ultrasound scanner in vivo. Electrolytes, protein, cholesterol, viscosity, and specific gravity were also measured (in the aspirated cyst fluid) to assess their relationship to the speed of sound values obtained during breast imaging. RESULTS We found positive correlations between viscosity and cholesterol (r = 0.71) and viscosity and total protein × cholesterol (r = 0.78). Additionally, we performed direct cell counts on cyst fluids and confirmed a positive correlation of number of cells with speed of sound (r = 0.74). The speed of sound of breast macrocysts, as observed using transmission ultrasound, correlated with the cytological features of intracystic cell clumps. CONCLUSION On the basis of our work with speed as a classifier, we propose a spectrum of breast macrocysts from fluid-filled to highly cellular. Our results suggest high-speed cysts are mature macrocysts with high cell counts and many cellular clumps that correlate with cyst microanatomy as seen by transmission ultrasound. Further studies are needed to confirm our findings and to assess the clinical value of speed of sound measurements in breast imaging using transmission ultrasound.

[1]  Linda K. Olson,et al.  Quantitative volumetric breast imaging with 3D inverse scatter computed tomography , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[2]  George N. Papanicolaou Herbert F. Traut,et al.  Diagnosis of uterine cancer by the vaginal smear , 1943 .

[3]  Michael P. Andre,et al.  Clinical Results with Ultrasound Computed Tomography of the Breast , 2013 .

[4]  R. Millis,et al.  Problems in Breast Pathology , 2006, Virchows Archiv.

[5]  J. S. Tsung,et al.  Cytological and biochemical studies of breast cyst fluid. , 2005, Breast.

[6]  Jennifer Bullen,et al.  Accuracy of Cyst Versus Solid Diagnosis in the Breast Using Quantitative Transmission (QT) Ultrasound , 2017, Academic radiology.

[7]  G H Glover,et al.  Computerized time-of flight ultrasonic tomography for breast examination. , 1977, Ultrasound in medicine & biology.

[8]  F. Moinfar Essentials of Diagnostic Breast Pathology: A Practical Approach , 2007 .

[9]  J. Greenleaf,et al.  Clinical Imaging with Transmissive Ultrasonic Computerized Tomography , 1981, IEEE Transactions on Biomedical Engineering.

[10]  M. Fleisher,et al.  Cation levels in human breast cyst fluid. , 1981, Clinical oncology.

[11]  W. Miller,et al.  The morphological basis of human breast cyst populations , 1983, The British journal of surgery.

[12]  S. Bandyopadhyay,et al.  Etiologic factors related to unsatisfactory ThinPrep® cervical cytology: Evaluation and potential solutions to improve , 2015, CytoJournal.

[13]  J. Stuart,et al.  Automated measurement of plasma viscosity by capillary viscometer. , 1988, Journal of clinical pathology.

[14]  A. Chakravorty,et al.  Management of breast cysts revisited , 2007, International journal of clinical practice.

[15]  John B. Davis,et al.  Cystic disease of the breast: Relationship to carcinoma , 1964, Cancer.

[16]  C. López-Otín,et al.  Cholesterol and apolipoprotein D in gross cystic disease of the breast. , 1992, Clinical chemistry.

[17]  R. Mansel,et al.  ABERRATIONS OF NORMAL DEVELOPMENT AND INVOLUTION (ANDI): A NEW PERSPECTIVE ON PATHOGENESIS AND NOMENCLATURE OF BENIGN BREAST DISORDERS , 1987, The Lancet.

[18]  K. Mandl,et al.  National expenditure for false-positive mammograms and breast cancer overdiagnoses estimated at $4 billion a year. , 2015, Health affairs.

[19]  W. Miller,et al.  An immunohistochemical study of the tissue distribution of the breast cyst fluid protein, zinc alpha2 glycoprotein , 1987, Histopathology.

[20]  Michael P. Andre,et al.  Three-dimensional nonlinear inverse scattering: Quantitative transmission algorithms, refraction corrected reflection, scanner design and clinical results , 2013 .

[21]  Nancy A. Obuchowski,et al.  Anatomy-Correlated Breast Imaging and Visual Grading Analysis Using Quantitative Transmission Ultrasound™ , 2016, Int. J. Biomed. Imaging.

[22]  L. Dogliotti,et al.  Cations and dehydroepiandrosterone-sulfate in cyst fluid of pre- and menopausal patients with gross cystic disease of the breast. Evidence for the existence of subpopulations of cysts. , 1986, European journal of cancer & clinical oncology.

[23]  Akira Ishimaru,et al.  Wave propagation and scattering in random media , 1997 .

[24]  O. Sartorius The biochemistry of breast cyst fluids and duct secretions , 1995, Breast Cancer Research and Treatment.

[25]  Bilal H. Malik,et al.  Objective breast tissue image classification using Quantitative Transmission ultrasound tomography , 2016, Scientific Reports.

[26]  Jonathan Ophir,et al.  A Ternary Solution for Independent Acoustic Impedance and Speed of Sound Matching to Biological Tissues , 1982 .

[27]  W D Dupont,et al.  Risk factors for breast cancer in women with proliferative breast disease. , 1985, The New England journal of medicine.

[28]  D. Borup,et al.  Non-linear inverse scattering: high resolution quantitative breast tissue tomography. , 2012, The Journal of the Acoustical Society of America.

[29]  Matthew A. Lewis,et al.  Imaging Performance of Quantitative Transmission Ultrasound , 2015, Int. J. Biomed. Imaging.