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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.


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Real-time quantitative structural imaging of nanosphere aggregates using SESF. (a) Illustration of the nanosphere aggregate configuration. At the image plane of the SESF system, (b) bright-field and (c) SESF images of nanosphere aggregates with four different sizes: 125 nm, 147 nm, 203 nm and 240 nm. (d) The average axial spatial period for the dominant structure of each sample. (e) Distribution of axial spatial period on the backscattering angle for each sample.
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Figure 5: Real-time quantitative structural imaging of nanosphere aggregates using SESF. (a) Illustration of the nanosphere aggregate configuration. At the image plane of the SESF system, (b) bright-field and (c) SESF images of nanosphere aggregates with four different sizes: 125 nm, 147 nm, 203 nm and 240 nm. (d) The average axial spatial period for the dominant structure of each sample. (e) Distribution of axial spatial period on the backscattering angle for each sample.

Mentions: The ability of SESF system for real-time quantitative structural imaging of a complex 3D object and nanoscale sensitivity was demonstrated using nanosphere aggregates of known sizes: 125 ± 3 nm; 147 ± 3 nm; 203 ± 5 nm; 240 ± 5 nm, as illustrated in Figure 5a [21]. The nanosphere aggregate is formed by a self-assembling process [21,28,29]. The optical thickness of the nanosphere aggregate was ~30 μm, suggesting a multi-layer structure. Figures 5B-C show the bright-field and corresponding real-time SESF images of nanospheres captured with a colored CCD camera. The nanosphere size is well beyond the lateral resolution limit of our optical system, indistinguishable in conventional bright-field images, but the axial structural information can pass through the optical system using SESF. The nanoscale size differences are clearly presented as distinct colors in the SESF images. The dominant color in each SESF image is directly correlated with the dominant spatial frequency of the axial structure, which depends on nanosphere size. It should be noted that what we measure with SESF is the axial spatial period, which is not always equivalent to the size of the nanosphere aggregate. As size increases, the axial spatial period increases and the SESF image shows progressively red-shifted color as predicted by Eq. (11). The average dominant wavelengths (Figure 5d) also show a progressive increase. Even a 22 nm difference can be distinguished by spectral color shift, suggesting a nanoscale sensitivity in detecting structural changes.


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)

Real-time quantitative structural imaging of nanosphere aggregates using SESF. (a) Illustration of the nanosphere aggregate configuration. At the image plane of the SESF system, (b) bright-field and (c) SESF images of nanosphere aggregates with four different sizes: 125 nm, 147 nm, 203 nm and 240 nm. (d) The average axial spatial period for the dominant structure of each sample. (e) Distribution of axial spatial period on the backscattering angle for each sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Real-time quantitative structural imaging of nanosphere aggregates using SESF. (a) Illustration of the nanosphere aggregate configuration. At the image plane of the SESF system, (b) bright-field and (c) SESF images of nanosphere aggregates with four different sizes: 125 nm, 147 nm, 203 nm and 240 nm. (d) The average axial spatial period for the dominant structure of each sample. (e) Distribution of axial spatial period on the backscattering angle for each sample.
Mentions: The ability of SESF system for real-time quantitative structural imaging of a complex 3D object and nanoscale sensitivity was demonstrated using nanosphere aggregates of known sizes: 125 ± 3 nm; 147 ± 3 nm; 203 ± 5 nm; 240 ± 5 nm, as illustrated in Figure 5a [21]. The nanosphere aggregate is formed by a self-assembling process [21,28,29]. The optical thickness of the nanosphere aggregate was ~30 μm, suggesting a multi-layer structure. Figures 5B-C show the bright-field and corresponding real-time SESF images of nanospheres captured with a colored CCD camera. The nanosphere size is well beyond the lateral resolution limit of our optical system, indistinguishable in conventional bright-field images, but the axial structural information can pass through the optical system using SESF. The nanoscale size differences are clearly presented as distinct colors in the SESF images. The dominant color in each SESF image is directly correlated with the dominant spatial frequency of the axial structure, which depends on nanosphere size. It should be noted that what we measure with SESF is the axial spatial period, which is not always equivalent to the size of the nanosphere aggregate. As size increases, the axial spatial period increases and the SESF image shows progressively red-shifted color as predicted by Eq. (11). The average dominant wavelengths (Figure 5d) also show a progressive increase. Even a 22 nm difference can be distinguished by spectral color shift, suggesting a nanoscale sensitivity in detecting structural changes.

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