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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

Statistical analysis of (a) dominant wavelengths and (b) the corresponding dominant axial spatial period in the nuclei of normal squamous epithelial cells (NILM) and high-grade squamous intraepithelial (HSIL) cells. The error bar is standard error. The p-value of the two-sided p-value of student t-test assuming unequal variance.
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Figure 15: Statistical analysis of (a) dominant wavelengths and (b) the corresponding dominant axial spatial period in the nuclei of normal squamous epithelial cells (NILM) and high-grade squamous intraepithelial (HSIL) cells. The error bar is standard error. The p-value of the two-sided p-value of student t-test assuming unequal variance.

Mentions: As the cell-to-cell variation is often significant, to confirm that such color shift in the cell nuclei of pre-cancerous cells is also statistically significant, we evaluated ~20 cells per patient and then took the average value of the dominant wavelengths and their corresponding average dominant axial spatial periods as a representative value for the patient. As shown in Figure 15, both the average dominant wavelength and the corresponding axial spatial period show statistically significant differences between NILM and HSIL (p-value = 0.006). This result suggests that the internal structures of the high-grade pre-cancerous cell nuclei exhibit an increased axial spatial period compared with those in normal cells from the NILM patients [21]. This proof-of-concept study shows the potential of SESF to detect structural changes in pre-cancerous cells not detectable with conventional light microscopy.


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)

Statistical analysis of (a) dominant wavelengths and (b) the corresponding dominant axial spatial period in the nuclei of normal squamous epithelial cells (NILM) and high-grade squamous intraepithelial (HSIL) cells. The error bar is standard error. The p-value of the two-sided p-value of student t-test assuming unequal variance.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 15: Statistical analysis of (a) dominant wavelengths and (b) the corresponding dominant axial spatial period in the nuclei of normal squamous epithelial cells (NILM) and high-grade squamous intraepithelial (HSIL) cells. The error bar is standard error. The p-value of the two-sided p-value of student t-test assuming unequal variance.
Mentions: As the cell-to-cell variation is often significant, to confirm that such color shift in the cell nuclei of pre-cancerous cells is also statistically significant, we evaluated ~20 cells per patient and then took the average value of the dominant wavelengths and their corresponding average dominant axial spatial periods as a representative value for the patient. As shown in Figure 15, both the average dominant wavelength and the corresponding axial spatial period show statistically significant differences between NILM and HSIL (p-value = 0.006). This result suggests that the internal structures of the high-grade pre-cancerous cell nuclei exhibit an increased axial spatial period compared with those in normal cells from the NILM patients [21]. This proof-of-concept study shows the potential of SESF to detect structural changes in pre-cancerous cells not detectable with conventional light microscopy.

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