Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy

Kaffas, Ahmed El; Sadeghi‐Naini, Ali; Falou, Omar; Tran, William T.; Zhou, Shouming; Hashim, Amr; Fernandes, Jason; Giles, Anoja; Czarnota, Gregory J.

doi:10.1118/1.4926554

Cited by 6 publications

(11 citation statements)

References 66 publications

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“…Other studies have begun to assess such factors using image-based texture analysis to account for tumor heterogeneity [44] . Other studies have demonstrated recently also the effect of tumor vascularity on QUS parameters [45] .…”

Section: Discussionmentioning

confidence: 89%

Quantification of Ultrasonic Scattering Properties of In Vivo Tumor Cell Death in Mouse Models of Breast Cancer

Tadayyon

Sannachi

Sadeghi‐Naini

et al. 2015

Translational Oncology

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INTRODUCTION: Quantitative ultrasound parameters based on form factor models were investigated as potential biomarkers of cell death in breast tumor (MDA-231) xenografts treated with chemotherapy. METHODS: Ultrasound backscatter radiofrequency data were acquired from MDA-231 breast cancer tumor–bearing mice (n = 20) before and after the administration of chemotherapy drugs at two ultrasound frequencies: 7 MHz and 20 MHz. Radiofrequency spectral analysis involved estimating the backscatter coefficient from regions of interest in the center of the tumor, to which form factor models were fitted, resulting in estimates of average scatterer diameter and average acoustic concentration (AAC). RESULTS: The ∆AAC parameter extracted from the spherical Gaussian model was found to be the most effective cell death biomarker (at the lower frequency range, r2 = 0.40). At both frequencies, AAC in the treated tumors increased significantly (P = .026 and .035 at low and high frequencies, respectively) 24 hours after treatment compared with control tumors. Furthermore, stepwise multiple linear regression analysis of the low-frequency data revealed that a multiparameter quantitative ultrasound model was strongly correlated to cell death determined histologically posttreatment (r2 = 0.74). CONCLUSION: The Gaussian form factor model–based scattering parameters can potentially be used to track the extent of cell death at clinically relevant frequencies (7 MHz). The 20-MHz results agreed with previous findings in which parameters related to the backscatter intensity (i.e., AAC) increased with cell death. The findings suggested that, in addition to the backscatter coefficient parameter ∆AAC, biological features including tumor heterogeneity and initial tumor volume were important factors in the prediction of cell death response.

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Section: Discussionmentioning

confidence: 89%

Quantification of Ultrasonic Scattering Properties of In Vivo Tumor Cell Death in Mouse Models of Breast Cancer

Tadayyon

Sannachi

Sadeghi‐Naini

et al. 2015

Translational Oncology

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“…Staining with ISEL was quantified by computing a ratio of ISEL stained areas to whole tumour cross-sectional area, resulting in a percent cell death index. This was carried-out using a custom MATLAB (The MathWorks, Natick, MA) routine, which allows the user to compute the number of brown pixels (ISEL-stained) over the total number of pixels per whole segmented tumour cross-section in a digitized histology slide 7 , 27 , 31 . Endothelial-specific CD31 staining was used to quantify micro-vascular densities (MVD) and to complement power Doppler findings.…”

Section: Methodsmentioning

confidence: 99%

“…More specifically, volumetric power Doppler ultrasound was utilized to monitor tumour vascular responses in longitudinal studies 20 - 22 . Furthermore, power Doppler, quantitative ultrasound spectroscopy (QUS) methods were used to assess acute tumour responses to prescribed therapies 23 - 27 . In addition to ultrasound, we collected tumours post-mortem to assess cell death and micro-vascular densities using standard immunohistological methods (CD31 and ISEL).…”

Section: Introductionmentioning

confidence: 99%

Tumour Vascular Shutdown and Cell Death Following Ultrasound-Microbubble Enhanced Radiation Therapy

et al. 2018

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High-dose radiotherapy effects are regulated by acute tumour endothelial cell death followed by rapid tumour cell death instead of canonical DNA break damage. Pre-treatment with ultrasound-stimulated microbubbles (USMB) has enabled higher-dose radiation effects with conventional radiation doses. This study aimed to confirm acute and longitudinal relationships between vascular shutdown and tumour cell death following radiation and USMB in a wild type murine fibrosarcoma model using in vivo imaging.Methods: Tumour xenografts were treated with single radiation doses of 2 or 8 Gy alone, or in combination with low-/high-concentration USMB. Vascular changes and tumour cell death were evaluated at 3, 24 and 72 h following therapy, using high-frequency 3D power Doppler and quantitative ultrasound spectroscopy (QUS) methods, respectively. Staining using in situ end labelling (ISEL) and cluster of differentiation 31 (CD31) of tumour sections were used to assess cell death and vascular distributions, respectively, as gold standard histological methods.Results: Results indicated a decrease in the power Doppler signal of up to 50%, and an increase of more than 5 dBr in cell-death linked QUS parameters at 24 h for tumours treated with combined USMB and radiotherapy. Power Doppler and quantitative ultrasound results were significantly correlated with CD31 and ISEL staining results (p < 0.05), respectively. Moreover, a relationship was found between ultrasound power Doppler and QUS results, as well as between micro-vascular densities (CD31) and the percentage of cell death (ISEL) (R2 0.5-0.9).Conclusions: This study demonstrated, for the first time, the link between acute vascular shutdown and acute tumour cell death using in vivo longitudinal imaging, contributing to the development of theoretical models that incorporate vascular effects in radiation therapy. Overall, this study paves the way for theranostic use of ultrasound in radiation oncology as a diagnostic modality to characterize vascular and tumour response effects simultaneously, as well as a therapeutic modality to complement radiation therapy.

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“…Structural and morphological properties impact these parameters, which are related to the scatterer size (SI, SS), the acoustics scatterer concentration (MBF, SI), or difference in acoustic impedance between the scatterer and its surrounding medium (SI). Spatial parametric images of the MBF were generated by displaying the results of a sliding window analysis on a pixel-by-pixel basis within the ROI [ 17, 19, 20 ]. Statistical analysis was done with a multivariate model analysis and a one-way ANOVA as presented in Tables 1 and 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, regions-of-interest (ROIs) were selected to encompass the MFP and exclude image artifacts and skin lines. A Fourier transform was applied to the RF data along each scan line within the ROI to obtain a power spectrum; spectra were averaged over all scan lines in the ROI and normalized to a reference phantom power spectrum [15][16][17][18][19][20]. Linear regression analysis was performed on each normalized power spectrum to generate a best-fit-line within a -6dB window to obtain MBF, SS, and SI parameters [15][16][17][18][19][20].…”

Section: Ultrasound Imaging and Qusmentioning

confidence: 99%

Non-Invasive monitoring of normal tissue radiation damage using quantitative ultrasound spectroscopy

Rafat

Kaffas

Swarnakar

et al. 2022

Preprint

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BackgroundWhile radiation therapy (RT) is an critical component of breast cancer therapy and is known to decrease overall local recurrence rates, recent studies have shown that normal tissue radiation damage may increase recurrence risk. Fibrosis is a well-known consequence of RT, but the specific sequence of molecular and mechanical changes induced by RT remains poorly understood.PurposeThere is currently a need to understand the contribution of the irradiated tissue microenvironment to recurrence to improve cancer therapy outcomes. This study seeks to evaluate the use of quantitative ultrasound spectroscopy (QUS) for real time determination of the normal tissue characteristic radiation response and to correlate these results to molecular features in irradiated tissues.MethodsMurine mammary fat pads (MFPs) were irradiated to 20 Gy, and QUS was used to analyze tissue physical properties pre-irradiation as well as at 1, 5, and 10 days post-irradiation. Tissues were processed for scanning electron microscopy imaging as well as histological and immunohistochemical staining to evaluate morphology and structure.ResultsTissue morphological and structural changes were observed non-invasively following radiation using mid-band fit (MBF), spectral slope (SS), and spectral intercept (SI) measurements obtained from QUS. Statistically significant shifts in MBF and SI indicate structural tissue changes in real time, which matched histological observations. Radiation damage was indicated by increased adipose tissue density and extracellular matrix (ECM) deposition.ConclusionsOur findings demonstrate the potential of using QUS to non-invasively evaluate normal tissue changes resulting from radiation damage. This supports further pre-clinical studies to determine how the tissue microenvironment and physical properties change in response to therapy, which may be important for improving treatment strategies.

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Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy

Cited by 6 publications

References 66 publications

Quantification of Ultrasonic Scattering Properties of In Vivo Tumor Cell Death in Mouse Models of Breast Cancer

Quantification of Ultrasonic Scattering Properties of In Vivo Tumor Cell Death in Mouse Models of Breast Cancer

Tumour Vascular Shutdown and Cell Death Following Ultrasound-Microbubble Enhanced Radiation Therapy

Non-Invasive monitoring of normal tissue radiation damage using quantitative ultrasound spectroscopy

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