1887
banner image
No data available.
Please log in to see this content.
You have no subscription access to this content.
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
Low-frequency quantitative ultrasound imaging of cell death in vivo
Rent:
Rent this article for
USD
10.1118/1.4812683
    + View Affiliations - Hide Affiliations
    Affiliations:
    1 Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada; and Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada
    2 Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada
    3 Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada; and Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada
    4 Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada
    5 Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada
    6 Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada
    7 Department of Computer Science, Ryerson University, Toronto, Ontario M5B 2K3, Canada
    8 Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3, Canada
    9 Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada
    10 Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada and Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3, Canada
    11 Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada; and Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada
    a) Author to whom correspondence should be addressed. Electronic mail: Gregory.Czarnota@sunnybrook.ca; Telephone: 416-480-6100 ext. 7073; Fax: 416-480-6002.
    Med. Phys. 40, 082901 (2013); http://dx.doi.org/10.1118/1.4812683
/content/aapm/journal/medphys/40/8/10.1118/1.4812683
http://aip.metastore.ingenta.com/content/aapm/journal/medphys/40/8/10.1118/1.4812683

Figures

Image of FIG. 1.
FIG. 1.

Representative ultrasound-based biomarker data from PC3 and MDA tumors. Shown are a PC3 tumor treated with antivascular microbubble followed by 8 Gy x-rays and a chemotherapy treated MDA tumor both evaluated 24 h after exposure. (a) and (b) Representative ∼7 MHz (first and third rows) and ∼20 MHz (second and fourth rows) ultrasound B-mode images of untreated (a) and treated (b) tumors, demonstrating increases in tissue echogenicity with treatment compared to untreated tumor. ROIs applied in the quantitative analyses have been specified by rectangles. The scale bar represents ∼3 mm. (c) Representative normalized power spectra obtained from tumors prior to treatment (blue) and afterwards (red). (d) Representative generalized gamma fitted histograms of the ultrasound signal intensity obtained from tumors prior to treatment and afterwards. (e) A schematic plot of the ultrasound normalized power spectrum demonstrating the extraction of spectroscopic biomarkers based on the linear regression analysis performed within −6 dB bandwidth. (f) A schematic plot of the generalized gamma distribution [ , where Γ is the Gamma function, is the signal intensity, is the scale parameter, and is the shape parameter], demonstrating effects of different histogram distributions of ultrasound signal intensity over two histogram-based biomarkers.

Image of FIG. 2.
FIG. 2.

Changes in the midband fit (a), spectral slope (b), and 0-MHz intercept (c) biomarkers for high and low-frequency data in the eight treatment groups of PC3 and MDA tumors. Control animals are untreated, MB indicates antivascular microbubble and ultrasound treatment animals, 8 Gy represents radiation treatments alone, MB + 8 Gy represents the combined treatment groups. 4, 12, and 24 h represent different times of evaluation after chemotherapy exposure. Dark and light bars represent low and high-frequency data, respectively. Error bars represent ± one standard error. Stars represent statistically significant differences ( < 0.05) in comparison to the control.

Image of FIG. 3.
FIG. 3.

Percentage changes in the Rayleigh parameter (a), generalized gamma shape parameter (b), and generalized gamma scale parameter (c) for high and low-frequency data in the eight treatment groups of PC3 and MDA tumors. Control animals are untreated, MB indicates antivascular microbubble and ultrasound treatment animals, 8 Gy represents radiation treatments alone, MB + 8 Gy represents the combined treatment groups. 4, 12, and 24 h represent different times of evaluation after chemotherapy exposure. Dark and light bars represent low and high-frequency data, respectively. Error bars represent ± one standard error. Stars represent statistically significant differences ( < 0.05) in comparison to the control.

Image of FIG. 4.
FIG. 4.

Low-frequency ultrasound B-mode images with ROI parametric overlays of the 0-MHz intercept biomarker for (a): PC3 tumors treated with antivascular microbubble therapy, (b): PC3 tumors treated with antivascular microbubble followed by 8 Gy x-ray treatment, and (c) MDA tumors were treated and evaluated at 4 (left), 12 (middle), and 24 (right) h after chemotherapy exposure. The topmost rows of images consist of data acquired prior to treatment, and the bottom following respective treatments. Scale bars represent ∼5 mm. The color bar represents a scale encompassing ∼100 dBr. The color bar scale were kept consistent covering the dynamic range observed in all the treatment groups before and after the treatment, in order to enable valid intergroup comparisons.

Image of FIG. 5.
FIG. 5.

(a) Representative data from untreated, anti-vascular microbubble, 8 Gy x-ray, and antivascular microbubble followed by 8 Gy x-ray treatment groups of PC3 tumors, from left to right, respectively. (b) Representative data from untreated group, as well as the treatment groups of MDA tumors evaluated at 4, 12, and 24 h after chemotherapy exposure of, from left to right, respectively. (First row) Low-magnification light microscopy images of TUNEL (PC3) and ISEL (MDA) stained tumors, demonstrating the areas of apoptotic cell death. The scale bar represents ∼2 mm. (Second row) Light microscopy images of haematoxylin and eosin stained tumor slices obtained at high magnification. The scale bar represents ∼10 (PC3) and ∼50 (MDA) m. (Third row) Distribution of cell versus nucleus size measurements representing morphology of responsive regions within the tumor.

Image of FIG. 6.
FIG. 6.

Results of linear (first row) and quadratic (second row) regression analyses performed on the percentages of histological cell death and changes in the midband fit biomarker after treatment administration, within the 95% confidence interval. Data represent the results obtained from PC3 and MDA tumors of different treatment groups. The linear analyses resulted in values of 0.71 and 0.82 ( < 0.001) for PC3 and MDA tumors, respectively. The quadratic analyses resulted in values of 0.76 and 0.84 ( < 0.001) for PC3 and MDA tumors, respectively.

Tables

Generic image for table
TABLE I.

Number of animals in each treatment group. Control animals are untreated.

Loading

Article metrics loading...

/content/aapm/journal/medphys/40/8/10.1118/1.4812683
2013-07-11
2014-04-20
Loading

Full text loading...

This is a required field
Please enter a valid email address
752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Low-frequency quantitative ultrasound imaging of cell death in vivo
http://aip.metastore.ingenta.com/content/aapm/journal/medphys/40/8/10.1118/1.4812683
10.1118/1.4812683
SEARCH_EXPAND_ITEM