Shear wave elastography can stratify rectal cancer response to short-course radiation therapy.

Rectal cancer is a deadly disease typically treated using neoadjuvant chemoradiotherapy followed by total mesorectal excision surgery. To reduce the occurrence of mesorectal excision surgery for patients whose tumors regress from the neoadjuvant therapy alone, conventional imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI), is used to assess tumor response to neoadjuvant therapy before surgery. In this work, we hypothesize that shear wave elastography offers valuable insights into tumor response to short-course radiation therapy (SCRT)-information that could help distinguish radiation-responsive from radiation-non-responsive tumors and shed light on changes in the tumor microenvironment that may affect radiation response. To test this hypothesis, we performed elastographic imaging on murine rectal tumors (n = 32) on days 6, 10, 12, 16, 18, 20, 23, and 25 post-tumor cell injection. The study revealed that radiation-responsive and non-radiation-responsive tumors had different mechanical properties. Specifically, radiation-non-responsive tumors showed significantly higher shear wave speed SWS (p < 0.01) than radiation-responsive tumors 11 days after SCRT. Furthermore, there was a significant difference in shear wave attenuation (SWA) (p < 0.01) in radiation-non-responsive tumors 16 days after SCRT compared to SWA measured just one day after SCRT. These results demonstrate the potential of shear wave elastography to provide valuable insights into tumor response to SCRT and aid in exploring the underlying biology that drives tumors' responses to radiation.

A Robust and Fast Method for 2-D Shear Wave Speed Calculation.

We developed a new method, called the tangent plane method (TPM), for more efficiently and accurately estimating 2-D shear wave speed (SWS) from any direction of wave propagation. In this technique, we estimate SWS by solving the Eikonal equation because this approach is more robust to noise. To further enhance the performance, we computed the tangent plane of the arrival time surface. To evaluate the approach, we performed simulations and also conducted phantom studies. Simulation studies showed that TPM was more robust to noise than the conventional methods such as 2-D cross correlation (CC) and the distance method. The contrast/CNR for an inclusion (69 kPa; manufacturer provided stiffness) of a phantom is 0.54/4.17, 0.54/1.82, and 0.46/1.22. SWS results [mean and standard deviation (SD)] were 4.41 ± 0.49, 4.62 ± 0.85, and 3.66 ± 0.99 m/s, respectively, while the manufacturer's reported value (mean and range) is 4.81 ± 0.49 m/s. This shows that TPM has the higher CNR and lower SD than other methods. To increase the computation speed, an iterative version of TPM (ITPM) was also developed, which calculated the time-of-flight iteratively. ITPM reduced the computation time to 3.6%, i.e., from 748 to 27 s. In vivo case analysis demonstrated the feasibility of using the conventional ultrasound scanner for the proposed 2-D SWS algorithms.

Shear Wave Elastography Can Differentiate between Radiation-Responsive and Non-responsive Pancreatic Tumors: An ex Vivo Study with Murine Models.

Neither contrast-enhanced computed tomography nor magnetic resonance imaging can monitor changes in the pancreatic ductal adenocarcinoma microenvironment during therapy. We hypothesized that shear wave elastography could overcome this limitation. To test this hypothesis, we measured the shear modulus of two groups of murine pancreatic tumors (KCKO, n = 30; PAN02, n = 30) treated with stereotactic body radiation therapy (SBRT). The mean shear modulus of KCKO tumors was 7.651 kPa higher than that of PAN02 tumors (p < 0.001). SBRT reduced the shear modulus in KCKO tumors by 8.914 kPa (p < 0.001). No significant difference in the shear modulus of SBRT-treated PAN02 tumors was observed. Additionally, necrotic and collagen densities were reduced only in the SBRT-treated KCKO tumors. Shear modulus was dependent on collagen distribution and histological texture parameters (i.e., entropy and fractional dimension). Shear wave elastography imaging differentiates between SBRT-responsive (KCKO) and non-responsive (PAN02) tumors.

Elastography Can Map the Local Inverse Relationship between Shear Modulus and Drug Delivery within the Pancreatic Ductal Adenocarcinoma Microenvironment.

PURPOSE: High tissue pressure prevents chemotherapeutics from reaching the core of pancreatic tumors. Therefore, targeted therapies have been developed to reduce this pressure. While point probes have shown the effectiveness of these pressure-reducing therapies via single-location estimates, ultrasound elastography is now widely available as an imaging technique to provide real-time spatial maps of shear modulus (tissue stiffness). However, the relationship between shear modulus and the underlying tumor microenvironmental causes of high tissue pressure has not been investigated. In this work, elastography was used to investigate how shear modulus influences drug delivery in situ, and how it correlates with collagen density, hyaluronic acid content, and patent vessel density-features of the tumor microenvironment known to influence tissue pressure. EXPERIMENTAL DESIGN: Intravenous injection of verteporfin, an approved human fluorescent drug, was used in two pancreatic cancer xenograft models [AsPC-1 (n = 25) and BxPC-3 (n = 25)]. RESULTS: Fluorescence intensity was higher in AsPC-1 tumors than in BxPC-3 tumors (P < 0.0001). Comparing drug uptake images and shear wave elastographic images with histologic images revealed that: (i) drug delivery and shear modulus were inversely related, (ii) shear modulus increased linearly with increasing collagen density, and (iii) shear modulus was marginally correlated with the local assessment of hyaluronic acid content. CONCLUSIONS: These results demonstrate that elastography could guide targeted therapy and/or identify patients with highly elevated tissue pressure.See related commentary by Nia et al., p. 2024.