Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy

Yu, Chung; Lau, Condon; Tunnell, James W.; Hunter, Martin; Kalashnikov, Maxim; Fang-Yen, Christopher; Fulghum, Stephen F.; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.

doi:10.1364/ol.31.003119

Cited by 19 publications

(18 citation statements)

References 9 publications

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“…Most importantly, it is obvious that azimuthally asymmetric backscattering is indicative of dysplastic progression; increased asymmetry for severely dysplastic or CIS nuclei is manifested in significantly lower correlation values and can be traced back to a more heterogeneous nuclear texture depicted in Table 2. This finding agrees well with prior observations on azimuth-resolved backscattering measurements [13].…”

Section: Discussionsupporting

confidence: 93%

“…If the entire range of polar angles is considered and the integrand is properly normalized, the computed metric gives the scattering cross section that characterizes the overall scattering strength of the nuclei. As these intricate structures are not perfectly spherical and contain refractive index heterogeneities at different length scales, however, their scattering response will exhibit complex azimuthal asymmetry [12][13][14][15][16]. It may thus prove worthwhile to carry out a comprehensive two-dimensional investigation that will enable a comparative assessment of azimuthal dependence in nuclear scattering profiles.…”

Section: Introductionmentioning

confidence: 99%

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Numerical investigation of two-dimensional light scattering patterns of cervical cell nuclei to map dysplastic changes at different epithelial depths

Arifler

MacAulay²,

Follen

et al. 2014

Biomed. Opt. Express

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Abstract:We use an extensive set of quantitative histopathology data to construct realistic three-dimensional models of normal and dysplastic cervical cell nuclei at different epithelial depths. We then employ the finitedifference time-domain method to numerically simulate the light scattering response of these representative models as a function of the polar and azimuthal scattering angles. The results indicate that intensity and shape metrics computed from two-dimensional scattering patterns can be used to distinguish between different diagnostic categories. Our numerical study also suggests that different epithelial layers and angular ranges need to be considered separately to fully exploit the diagnostic potential of twodimensional light scattering measurements.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Numerical investigation of two-dimensional light scattering patterns of cervical cell nuclei to map dysplastic changes at different epithelial depths

Arifler

MacAulay²,

Follen

et al. 2014

Biomed. Opt. Express

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“…An improved method for detecting the light scattered from the nucleus has been reported recently and will be further explored in the future. 43 Nevertheless, sensitivity of light scattering to the longitudinal and not to the cross-sectional nuclear diameter was also reported in another light scattering study that investigated nuclear morphology of T84 epithelial cells with Fourier domain low coherence interferometry. 44 Interestingly, we find through LSS and confocal microscopy that the longitudinal diameter of HPVimmortalized cells is significantly smaller than that of normal keratinocytes.…”

Section: Discussionmentioning

confidence: 79%

Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells

Mujat

Greiner

Baldwin

et al. 2007

Intl Journal of Cancer

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Cellular transformation is associated with a number of phenotypic, cell biological, biochemical and metabolic alterations. The detection and classification of morphological cellular abnormalities represents the foundation of classical histopathology and remains an important mainstay in the clinic. More recently, significant effort is being expended towards the development of noninvasive modalities for the detection of cancer at an early stage, when therapeutic interventions are highly successful. Methods that rely on the detection of optical signatures represent one class of such approaches that have yielded promising results. In our study, we have applied two spectroscopic imaging approaches to systematically identify in a quantitative manner the fluorescence and light scattering signatures of subcellular abnormalities that are associated with cellular transformation. Notably, we find that tryptophan images reveal not only intensity but also localization differences between normal and human papillomavirus immortalized cells, possibly originating from changes in the expression, 3D packing and organization of proteins and protein-rich subcellular organelles. Additionally, we detect alterations in cellular metabolism through quantitative evaluation of the NADH, FAD fluorescence and the corresponding redox ratio. Finally, we use light scattering spectroscopy to identify differences in nuclear morphology and subcellular organization that occur from the nanometer to the micrometer scale. Thus, these optical approaches provide complementary biomarkers based on endogenous fluorescence and scattering cellular changes that occur at the molecular, biochemical and morphological level. Since they obviate the need for staining and tissue removal and can be easily combined, they provide desirable options for further clinical development and assessment. ' 2007 Wiley-Liss, Inc.Key words: cancer biomarkers; noninvasive imaging; cancer diagnosis; spectroscopy; fluorescence; light scattering; HPV; cervical cancer Clinical cancer detection has relied heavily on the use of simple stains to visualize and classify morphological cellular abnormalities. The development of more sophisticated probes to evaluate specific oncogenic events continues to revolutionize early detection of various cancers. Nevertheless, a simple morphological evaluation of exfoliated cervical epithelial cells, the Papanicolaou (''Pap'') smear has been exceedingly useful for detection of precancerous cervical lesions and may have saved more lives than any other commonly used cancer screening procedure. Many of the more sophisticated diagnostic tests involve physical removal of suspect tissue or other invasive or physically unpleasant procedures. Hence, the development of rapid, noninvasive methods is of paramount importance for successful early detection. Relatively simple spectroscopic procedures are available to measure alterations in a number of cellular parameters and may be well suited for this purpose.Indeed, optical spectroscopy and imaging techniques exhib...

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“…Georgakoudi et al 55 found a sensitivity of 100% and specificity of 91% for HGD versus LGD+ BE using this technique. A significant advance in LSS was reported recently by Yu et al at MIT,60 in which the backscatter spectra were measured at the tissue surface for both large and small values of the azimuthal angle between the incident light polarization and the scattering plane. This further isolated the contribution of nuclear scattering from that of other smaller organelles in the epithelial cells, as demonstrated by in vivo measurements in the colon in a small number of patients.…”

Section: Point Spectroscopiesmentioning

confidence: 97%

Detection and treatment of dysplasia in Barrett’s esophagus: a pivotal challenge in translating biophotonics from bench to bedside

Wilson

2007

J. Biomed. Opt.

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Barrett's esophagus (BE) is a condition that poses high risk of developing dysplasia leading to cancer. Detection of dysplasia is a critical element in determining therapy but is extremely challenging, so that standard white-light endoscopy is used only as a means to guide biopsy. Many novel optical techniques have been aimed at this problem, including various forms of improved wide-field white-light (chromoendscopy/magnification and narrow-band) and fluorescence imaging, and "optical biopsy" techniques (diffuse reflectance, elastic light scattering, fluorescence and Raman spectroscopies, confocal microendoscopy, and optical coherence tomography). While promising, either as stand-alone modalities or in combination, to date none has solved this pivotal challenge to the point of clinical adoption. Likewise, minimally invasive treatment of BE patients with dysplasia remains suboptimal, despite recent approval of photodynamic therapy for this indication. This work presents a critique and summary of each of these biophotonic technologies, and discusses the fundamental advantages and limitations of each. The future directions for this field are considered, particularly from the perspective of relying on intrinsic (endogenous) optical signatures compared with the use of exogenous contrast agents.

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Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy

Cited by 19 publications

References 9 publications

Numerical investigation of two-dimensional light scattering patterns of cervical cell nuclei to map dysplastic changes at different epithelial depths

Numerical investigation of two-dimensional light scattering patterns of cervical cell nuclei to map dysplastic changes at different epithelial depths

Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells

Detection and treatment of dysplasia in Barrett’s esophagus: a pivotal challenge in translating biophotonics from bench to bedside

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