A model based upon pseudo regular spacing of cells combined with the randomisation of the nuclei can explain the significant changes in high-frequency ultrasound signals during apoptosis

Hunt, J.W.; Worthington, A. E.; Xuan, Andrew; Kolios, Michael C.; Czarnota, Gregory J.; Sherar, Michael D.

doi:10.1016/s0301-5629(01)00494-x

Cited by 69 publications

(42 citation statements)

References 23 publications

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“…Whereas, there may be a cellular redistribution of water as measured by MRI (24) and would likely not account on its own in the absence of nuclear morphologic changes for the consistent spectral and ultrasound backscatter changes associated with cell death. In addition, the ultrasound changes detected here are not treatment modality or melanoma tumorspecific and are similar to those detected with chemotherapy in preclinical mouse tumor lymphoma models and radiation therapy in a number of preclinical xenograft tumor models (25,26).…”

Section: Discussionmentioning

confidence: 56%

Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects

Banihashemi

Vlad²,

Debeljevic³

et al. 2008

Cancer Research

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137

157

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High-frequency ultrasound is a novel method to detect apoptotic cell death based on changes in cell morphology that cause alterations in the viscoelastic and, consequently, the acoustic properties of cell ensembles and tissues. In this study, we evaluated the first preclinical tumor-based use of highfrequency ultrasound spectroscopy to noninvasively monitor tumor treatment by following xenograft malignant melanoma tumor responses to photodynamic therapy (PDT) in vivo. We observed a time-dependant increase in ultrasound backscatter variables after treatment. The observed increases in spectroscopic variables correlated with morphologic findings, indicating increases in apoptotic cell death, which peaked at 24 hours after PDT. We analyzed the changes in spectral slope and backscatter in relation to apoptosis and histologic variations in cell nuclear size. Changes in spectral slope strongly correlated with the changes in mean nuclear size over time, associated with apoptosis, after PDT (P < 0.05). At 48 hours, a decrease in ultrasound backscatter was observed, which could be explained by an increase in cell nuclear degradation. In summary, we show that high-frequency ultrasound spectroscopic variables can be used noninvasively to monitor response after treatment in a preclinical tumor cancer model. These findings provide a foundation for future investigations regarding the use of ultrasound to monitor and aid the customization of treatments noninvasively based on responses to specific interventions. [Cancer Res 2008;68(20):8590-6]

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Section: Discussionmentioning

confidence: 56%

Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects

Banihashemi

Vlad²,

Debeljevic³

et al. 2008

Cancer Research

Self Cite

137

157

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“…In the present study, we also investigated the variance of cell sizes (the squared standard deviation), because it can considerably influence cell and nuclei spatial organization in a sample (24,25). The UIB measured from all cell samples correlated well with the variance of cell sizes, with a Pearson correlation coefficient of r = 0.80 and statistical significance of p < 0.01 (Fig.…”

Section: Resultsmentioning

confidence: 81%

Quantitative Ultrasound Characterization of Cancer Radiotherapy Effects In Vitro

Vlad

Alajez

Giles

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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“…Speckle patterns still forming at these low frequencies also suggest that several subresolution scatterers contribute to the detected signals. Another factor which can also influence ultrasound backscatter characteristics is the spatial organization of cellular-based scatterers (32) which can be altered with cell death. Banihashmei and colleagues showed that these subresolution scatterers can affect ultrasound at low-frequency with cell death (13) and evidence for the role of cell death-related nuclear changes is summarized there.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Ultrasound Evaluation of Tumor Cell Death Response in Locally Advanced Breast Cancer Patients Receiving Chemotherapy

Sadeghi‐Naini

Papanicolau

Falou

et al. 2013

Clinical Cancer Research

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115

114

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Purpose: Quantitative ultrasound techniques have been recently shown to be capable of detecting cell death through studies conducted on in vitro and in vivo models. This study investigates for the first time the potential of early detection of tumor cell death in response to clinical cancer therapy administration in patients using quantitative ultrasound spectroscopic methods.Experimental Design: Patients (n ¼ 24) with locally advanced breast cancer received neoadjuvant chemotherapy treatments. Ultrasound data were collected before treatment onset and at 4 times during treatment (weeks 1, 4, and 8, and preoperatively). Quantitative ultrasound parameters were evaluated for clinically responsive and nonresponding patients.Results: Results indicated that quantitative ultrasound parameters showed significant changes for patients who responded to treatment, and no similar alteration was observed in treatment-refractory patients. Such differences between clinically and pathologically determined responding and nonresponding patients were statistically significant (P < 0.05) after 4 weeks of chemotherapy. Responding patients showed changes in parameters related to cell death with, on average, an increase in mid-band fit and 0-MHz intercept of 9.1 AE 1.2 dBr and 8.9 AE 1.9 dBr , respectively, whereas spectral slope was invariant. Linear discriminant analysis revealed a sensitivity of 100% and a specificity of 83.3% for distinguishing nonresponding patients by the fourth week into a course of chemotherapy lasting several months.Conclusion: This study reports for the first time that quantitative ultrasound spectroscopic methods can be applied clinically to evaluate cancer treatment responses noninvasively. The results form a basis for monitoring chemotherapy effects and facilitating the personalization of cancer treatment.

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A model based upon pseudo regular spacing of cells combined with the randomisation of the nuclei can explain the significant changes in high-frequency ultrasound signals during apoptosis

Cited by 69 publications

References 23 publications

Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects

Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects

Quantitative Ultrasound Characterization of Cancer Radiotherapy Effects In Vitro

Quantitative Ultrasound Evaluation of Tumor Cell Death Response in Locally Advanced Breast Cancer Patients Receiving Chemotherapy

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