Theranostics 2020; 10(10):4614-4626. doi:10.7150/thno.37965

Research Paper

Noninvasive Young's modulus visualization of fibrosis progression and delineation of pancreatic ductal adenocarcinoma (PDAC) tumors using Harmonic Motion Elastography (HME) in vivo

Alireza Nabavizadeh1, Thomas Payen1, Alina C. Iuga5, Irina R. Sagalovskiy3, Deborah Desrouilleres5, Niloufar Saharkhiz1, Carmine F. Palermo3,4, Stephen A. Sastra3,4, Paul E. Oberstein7, Vilma Rosario2, Michael D. Kluger3,6, Beth A. Schrope3,6, John A. Chabot3,6, Kenneth P. Olive3,4*, Elisa E. Konofagou1,3,*,✉

1. Department of Biomedical Engineering, Columbia University Irving Medical Center, New York, NY 10032.
2. Division of Hematology & Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032.
3. Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032.
4. Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032.
5. Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY 10032.
6. Division of GI/Endocrine Surgery, Department of Surgery, Columbia University Irving Medical Center, New York, NY 10032.
7. Laura and Isaac Perlmutter Cancer Center, New York University, New York, NY.
* Co last authors.

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Citation:
Nabavizadeh A, Payen T, Iuga AC, Sagalovskiy IR, Desrouilleres D, Saharkhiz N, Palermo CF, Sastra SA, Oberstein PE, Rosario V, Kluger MD, Schrope BA, Chabot JA, Olive KP, Konofagou EE. Noninvasive Young's modulus visualization of fibrosis progression and delineation of pancreatic ductal adenocarcinoma (PDAC) tumors using Harmonic Motion Elastography (HME) in vivo. Theranostics 2020; 10(10):4614-4626. doi:10.7150/thno.37965. Available from http://www.thno.org/v10p4614.htm

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Abstract

Background and aims: Poor specificity and predictive values of current cross-sectional radiological imaging methods in evaluation of pancreatic adenocarcinoma (PDAC) limit the clinical capability to accurately stage the tumor pre-operatively and provide optimal surgical treatment and improve patient outcomes.

Methods: In this study, we applied Harmonic Motion Elastography (HME), a quantitative ultrasound-based imaging method to calculate Young's modulus (YM) in PDAC mouse models (n = 30) and human pancreatic resection specimens of PDAC (n=32). We compared the YM to the collagen assessment by Picrosirius red (PSR) stain on corresponding histologic sections.

Results: HME is capable of differentiating between different levels of fibrosis in transgenic mice. In mice without pancreatic fibrosis, the measured YM was 4.2 ± 1.3 kPa, in fibrotic murine pancreata, YM was 5.5 ± 2.0 kPa and in murine PDAC tumors, YM was 11.3 ± 1.7 kPa. The corresponding PSR values were 2.0 ± 0.8 %, 9.8 ± 3.4 %, and 13.2 ± 1.2%, respectively. In addition, three regions within each human surgical PDAC specimen were assessed: tumor, which had both the highest Young's modulus (YM > 40 kPa) and collagen density (PSR > 40 %); non-neoplastic adjacent pancreas, which had the lowest Young's modulus (YM < 15 kPa) and collagen density (PSR < 10%) and a transitional peri-lesional region between the tumor and non-neoplastic pancreas with an intermediate value of measured Young's modulus (15 kPa < YM < 40 kPa) and collagen density (15% < PSR < 35 %).

Conclusion: In conclusion, a non-invasive, quantitative imaging tool for detecting, staging and delineating PDAC tumor margins based on the change in collagen density was developed.

Keywords: PDAC: Pancreatic Ductal Adenocarcinoma, HMI: Harmonic Motion Imaging, HME: Harmonic Motion Elastography, PSR: Picrosirius Red, YM: Young's Modulus.