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Investigation of nanoscale structural alterations of cell nucleus as an early sign of cancer.

Liu Y, Uttam S, Alexandrov S, Bista RK - BMC Biophys (2014)

Bottom Line: The cell and tissue structural properties assessed with a conventional bright-field light microscope play a key role in cancer diagnosis, but they sometimes have limited accuracy in detecting early-stage cancers or predicting future risk of cancer progression for individual patients (i.e., prognosis) if no frank cancer is found.The recent development in optical microscopy techniques now permit the nanoscale structural imaging and quantitative structural analysis of tissue and cells, which offers a new opportunity to investigate the structural properties of cell and tissue below 200 - 250 nm as an early sign of carcinogenesis, prior to the presence of microscale morphological abnormalities.These two techniques use the scattered light from biological cells and tissue and share a common experimental approach of assessing the Fourier space by various wavelengths to quantify the 3D structural information of the scattering object at the nanoscale sensitivity with a simple reflectance-mode light microscopy setup without the need for high-NA optics.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Optical Imaging Laboratory, Department of Medicine, Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. liuy@pitt.edu.

ABSTRACT

Background: The cell and tissue structural properties assessed with a conventional bright-field light microscope play a key role in cancer diagnosis, but they sometimes have limited accuracy in detecting early-stage cancers or predicting future risk of cancer progression for individual patients (i.e., prognosis) if no frank cancer is found. The recent development in optical microscopy techniques now permit the nanoscale structural imaging and quantitative structural analysis of tissue and cells, which offers a new opportunity to investigate the structural properties of cell and tissue below 200 - 250 nm as an early sign of carcinogenesis, prior to the presence of microscale morphological abnormalities. Identification of nanoscale structural signatures is significant for earlier and more accurate cancer detection and prognosis.

Results: Our group has recently developed two simple spectral-domain optical microscopy techniques for assessing 3D nanoscale structural alterations - spectral-encoding of spatial frequency microscopy and spatial-domain low-coherence quantitative phase microscopy. These two techniques use the scattered light from biological cells and tissue and share a common experimental approach of assessing the Fourier space by various wavelengths to quantify the 3D structural information of the scattering object at the nanoscale sensitivity with a simple reflectance-mode light microscopy setup without the need for high-NA optics. This review paper discusses the physical principles and validation of these two techniques to interrogate nanoscale structural properties, as well as the use of these methods to probe nanoscale nuclear architectural alterations during carcinogenesis in cancer cell lines and well-annotated human tissue during carcinogenesis.

Conclusions: The analysis of nanoscale structural characteristics has shown promise in detecting cancer before the microscopically visible changes become evident and proof-of-concept studies have shown its feasibility as an earlier or more sensitive marker for cancer detection or diagnosis. Further biophysical investigation of specific 3D nanoscale structural characteristics in carcinogenesis, especially with well-annotated human cells and tissue, is much needed in cancer research.

No MeSH data available.


Related in: MedlinePlus

The schematic of SESF system. S: sample; IP: image plane; FP: Fourier plane; SF: Spatial filter.
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Figure 4: The schematic of SESF system. S: sample; IP: image plane; FP: Fourier plane; SF: Spatial filter.

Mentions: The schematic of the SESF system is shown in Figure 4. This setup is built upon a commercial microscope frame (AXIO Observer, Carl Zeiss) using reflection configuration at normal illumination. A broadband white-light source (Xenon-arc lamp 150 W, Newport Inc) was collimated and the backscattered light was collected by the objective (NA = 0.5). The annular-shaped spatial filter (SF) was used on Fourier plane (FP) to collect the spectral signals for all accessible scattering and azimuthal angles simultaneously. This SF suppresses the zero-order signal and removes the contribution of non-informative zero-order broadband spectrum from each image point, to provide the required bandwidth of spatial frequencies and spectral range for spectral encoding of the axial spatial frequency. On the other hand, the annular Fourier mask also effectively uses the NA of the optical system to form a relatively high resolution image. The SESF and bright-field images were recorded using either color CCD camera (AxioCam HRc, Carl Zeiss) on the image plane. Alternatively, a spectral device such as spectrometer (Acton Research) is also used to obtain the spectroscopic data on the image plane.


Investigation of nanoscale structural alterations of cell nucleus as an early sign of cancer.

Liu Y, Uttam S, Alexandrov S, Bista RK - BMC Biophys (2014)

The schematic of SESF system. S: sample; IP: image plane; FP: Fourier plane; SF: Spatial filter.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3928095&req=5

Figure 4: The schematic of SESF system. S: sample; IP: image plane; FP: Fourier plane; SF: Spatial filter.
Mentions: The schematic of the SESF system is shown in Figure 4. This setup is built upon a commercial microscope frame (AXIO Observer, Carl Zeiss) using reflection configuration at normal illumination. A broadband white-light source (Xenon-arc lamp 150 W, Newport Inc) was collimated and the backscattered light was collected by the objective (NA = 0.5). The annular-shaped spatial filter (SF) was used on Fourier plane (FP) to collect the spectral signals for all accessible scattering and azimuthal angles simultaneously. This SF suppresses the zero-order signal and removes the contribution of non-informative zero-order broadband spectrum from each image point, to provide the required bandwidth of spatial frequencies and spectral range for spectral encoding of the axial spatial frequency. On the other hand, the annular Fourier mask also effectively uses the NA of the optical system to form a relatively high resolution image. The SESF and bright-field images were recorded using either color CCD camera (AxioCam HRc, Carl Zeiss) on the image plane. Alternatively, a spectral device such as spectrometer (Acton Research) is also used to obtain the spectroscopic data on the image plane.

Bottom Line: The cell and tissue structural properties assessed with a conventional bright-field light microscope play a key role in cancer diagnosis, but they sometimes have limited accuracy in detecting early-stage cancers or predicting future risk of cancer progression for individual patients (i.e., prognosis) if no frank cancer is found.The recent development in optical microscopy techniques now permit the nanoscale structural imaging and quantitative structural analysis of tissue and cells, which offers a new opportunity to investigate the structural properties of cell and tissue below 200 - 250 nm as an early sign of carcinogenesis, prior to the presence of microscale morphological abnormalities.These two techniques use the scattered light from biological cells and tissue and share a common experimental approach of assessing the Fourier space by various wavelengths to quantify the 3D structural information of the scattering object at the nanoscale sensitivity with a simple reflectance-mode light microscopy setup without the need for high-NA optics.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Optical Imaging Laboratory, Department of Medicine, Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. liuy@pitt.edu.

ABSTRACT

Background: The cell and tissue structural properties assessed with a conventional bright-field light microscope play a key role in cancer diagnosis, but they sometimes have limited accuracy in detecting early-stage cancers or predicting future risk of cancer progression for individual patients (i.e., prognosis) if no frank cancer is found. The recent development in optical microscopy techniques now permit the nanoscale structural imaging and quantitative structural analysis of tissue and cells, which offers a new opportunity to investigate the structural properties of cell and tissue below 200 - 250 nm as an early sign of carcinogenesis, prior to the presence of microscale morphological abnormalities. Identification of nanoscale structural signatures is significant for earlier and more accurate cancer detection and prognosis.

Results: Our group has recently developed two simple spectral-domain optical microscopy techniques for assessing 3D nanoscale structural alterations - spectral-encoding of spatial frequency microscopy and spatial-domain low-coherence quantitative phase microscopy. These two techniques use the scattered light from biological cells and tissue and share a common experimental approach of assessing the Fourier space by various wavelengths to quantify the 3D structural information of the scattering object at the nanoscale sensitivity with a simple reflectance-mode light microscopy setup without the need for high-NA optics. This review paper discusses the physical principles and validation of these two techniques to interrogate nanoscale structural properties, as well as the use of these methods to probe nanoscale nuclear architectural alterations during carcinogenesis in cancer cell lines and well-annotated human tissue during carcinogenesis.

Conclusions: The analysis of nanoscale structural characteristics has shown promise in detecting cancer before the microscopically visible changes become evident and proof-of-concept studies have shown its feasibility as an earlier or more sensitive marker for cancer detection or diagnosis. Further biophysical investigation of specific 3D nanoscale structural characteristics in carcinogenesis, especially with well-annotated human cells and tissue, is much needed in cancer research.

No MeSH data available.


Related in: MedlinePlus