Ultrasonic spectrum analysis for in vivo characterization of tumor microstructural changes in the evaluation of tumor response to chemotherapy using diagnostic ultrasound

Jian-Wei Wang,Long-Hui Cao,An-Hua Li,Chun-Yi Lin,Wei Zheng,Zi-Zhen Feng,Jian-Hua Zhou,Yao Chen

doi:10.1186/1471-2407-13-302

Abstract

BackgroundThere is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy. The purpose of this study was to determine the feasibility of ultrasonic spectral analysis for the in vivo characterization of changes in tumor microstructure in the evaluation of tumor response to chemotherapy using diagnostic ultrasound.MethodsExperiments were approved by the regional animal care committee. Twenty-four MCF-7 breast cancer bearing nude mice were treated with adriamycin or sterile saline administered by intraperitoneal injection. Ultrasonic radio-frequency (RF) data was collected using a clinically available ultrasound scanner (6-MHz linear transducer). Linear regression parameters (spectral slope and midband-fit) regarding the calibrated power spectra from the RF signals were tested to monitor tumor response to treatment. The section equivalent to the ultrasound imaging plane was stained with hematoxylin and eosin to allow for assessment of the density of tumor cell nuclei.ResultsTreatment with adriamycin significantly reduced tumor growth in comparison with the control group (p = 0.003). Significant changes were observed in the ultrasonic parameters of the treated relative to the untreated tumors (p < 0.05). The spectral slope increased by 48.5%, from −10.66 ± 2.96 to −5.49 ± 2.69; the midband-fit increased by 12.8%, from −57.10 ± 7.68 to −49.81 ± 5.40. Treated tumors were associated with a significant decrease in the density of tumor cell nuclei as compared with control tumors (p < 0.001).ConclusionsUltrasonic spectral analysis can detect changes in tumor microstructure after chemotherapy, and this will be helpful in the early evaluation tumor response to chemotherapy.

Highlights

There is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy
Spectrum analysis of frequency-dependent backscattered radiofrequency data showed the difference in spectral parameters between the treated and control tumors
Seven days treatment with adriamycin (4 mg/kg once daily) significantly increased spectral slope in comparison to the control group (p < 0.001)

Summary

Introduction

There is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy. The use of such imaging modalities to monitor tumor responses to chemotherapy can be limited either by their cost or exposure of the patient to radiation. The aim of cancer therapy is to kill tumors by inducing cell death that can be used as an indicator of tumor response to therapy [4]. Increased tumor cell death early during the course of treatment, in preclinical and clinical studies, has been shown to be a good prognostic indicator of outcome [5,6]. Standard methods for detecting cell death are invasive and require tissue biopsy for histologic analysis. Assessment of tumor response to chemotherapy requires repeated examinations and the cost of MRI limits its clinical use

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