K. M. Sorensen Utah State University, Logan, Utah
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1 K. M. Sorensen Utah State University, Logan, Utah T. E. Doyle, B. D. Borget, M. Cervantes, J. A. Chappell, B. J. Curtis, M. A. Grover, J. E. Roring, J. E. Stiles, and L. A. Thompson Utah Valley University, Orem, Utah 164 th Meeting of the Acoustical Society of America, Kansas City, MO, October 2012
2 Previous findings Objective High-frequency (HF) ultrasound can differentiate between a range of breast pathologies in surgical specimens Two parameters are sensitive to histopathology Direction Determine the mechanism linking HF ultrasound to histology Approach Review breast specimen results Test range of bovine tissue from heart, kidney, and liver Hypothesis Ultrasound sensitivity is a function of the microscopic heterogeneity and therefore histology of the tissue
3 Measurements
4 Waveform Analysis Through-Transmission Pulse Echo First-Order Spectra Second-Order Spectra
5 Surgical Specimens Benign Malignant Lymph nodes Normal breast Atypical: Benign with calcifications Atypical ductal hyperplasia Fibrocystic change Papilloma FN-FA-TA: Fat necrosis Fibroadenoma Tubular adenoma Ductal Carcinomas (DC): Ductal carcinoma in situ (DCIS) DCIS, solid & cribriform Invasive ductal carcinoma (IDC) DCIS + IDC Lobular Carcinomas (LC): Lobular carcinoma in situ (LCIS) Invasive lobular carcinoma (ILC) Total measurement positions = 29 Total measurement positions = 26
6 Breast Histology Correlations Benign fibroadenoma (WebPathology.com) Normal breast tissue (U. Mich.) c Tissue heterogeneity increases from fibroadenoma (mostly stroma) to LCIS (tumor proliferation in lobules) Heterogeneity correlates with peak density, inversely with slope
7 Surgical Margin Results Peak density (number of peaks and valleys) from first-order spectra Normalized Slope from second-order spectra
8 Multivariate Analysis Attenuation vs. peak density Rotated and translated plot
9 Statistical Significance t-test results: Differentiation from normal tissue Pathology Peak density Slope Lobular carcinomas p < 0.02 p > 0.20 Ductal carcinomas p < 0.05 p < 0.20 FN-FA-TA p < 0.05 p < 0.01 Benign pathologies p < 0.10 p < 0.01 One-way ANOVA test: 5% significance level for peak density, close to 1%
10 Heart Histology Correlations Cardiac muscle (Yale Medical Histology) Muscular artery (Yale Medical Histology) Cardiac tissue displays uniform structure Vascular structure is more complex with 3 layers (tunica intima, tunica media, and tunica adventitia), smooth muscle, collagen, etc.
11 Bovine Heart Results Vascular tissue (aorta, vena cava, etc.) shows significantly higher peak densities No significant variations observed for normalized slope
12 Kidney Histology Correlations Cortex (Yale Medical Histology) Medullary collecting ducts (Yale Medical Histology) Ureter (Yale Medical Histology) Tissue uniformity decreases from cortex to ureter Medulla has uniaxial collecting ducts similar to normal breast glands Size of heterogeneities increase from cortex to ureter
13 Bovine Kidney Results Ureter and surrounding fat tissue show significantly higher peak densities Renal medulla shows significantly lower normalized slope values
14 Discussion Repeatable correlations shown between tissue heterogeneity and peak density of 1 st -order spectra Human breast: Ductal and lobular carcinomas Bovine heart: Vascular tissue Bovine kidney: Ureter and surrounding stroma Correlations less repeatable for slope of 2 nd -order spectra Slopes are lowest for normal ductal structures Normal breast tissue and medullary collecting ducts No correlations seen for liver tissue or between organs Tissue uniformity (liver) Averaging effects (between organs)
15 Conclusions Tissues with greater peak densities in 1 st -order spectra exhibit: More complex, less uniform histology Larger or more widespread heterogeneities Tissues with lower slopes in 2 nd -order spectra exhibit: Normal microscopic ductal structures Examples: Normal breast glands and renal medulla Results support hypothesis that HF ultrasound is sensitive to microscopic heterogeneity and thus histology in tissues Applications Intraoperative evaluation of margins during breast cancer surgery Real-time pathology for other cancers and procedures
16 Acknowledgments Funding support: NIH Grant R21CA Utah Valley University Grant for Engaged Learning Huntsman Cancer Institute: Leigh Neumayer Rachel Factor Utah Valley University: Melissa Monk Ken Slater Circle V Meats for donation of bovine organs
17
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