Quantitative near-infrared spectroscopy of cervical dysplasia in vivo

Hornung, René; Pham, Tuan H.; Keefe, Kristen A.; Berns, Michael W.; Tadir, Yona; Tromberg, Bruce J.

doi:10.1093/humrep/14.11.2908

Cited by 90 publications

(60 citation statements)

References 41 publications

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“…For example, it has been estimated that the dispersion, ⌬n, of the rat tail tendon for ex ϭ 1,064 nm is 0.026 (14). Assuming that the sin 2 function describing the experimentally observed spectral dependence of the SHG intensity is equal to the interference factor sin 2 (2 ⌬nl scat ͞ ex ), we can estimate the RAFT scattering length as l scat ϭ ( ex ͞2 ⌬n)(2 ex ͞c ϩ d), which for ex ϭ 1,064 nm, ⌬n ϭ 0.026, c ϭ 453.7, and d ϭ 6.28 yields l scat Ϸ 137 m. This value is in good agreement with previous nearinfrared spectroscopic measurements of l scat Ϸ 100-150 m in nonkeratinized epithelial tissue (31).…”

Section: Resultssupporting

confidence: 89%

Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence

Zoumi

Yeh²,

Tromberg³

2002

Proc. Natl. Acad. Sci. U.S.A.

809

725

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Multiphoton microscopy relies on nonlinear light-matter interactions to provide contrast and optical sectioning capability for high-resolution imaging. Most multiphoton microscopy studies in biological systems have relied on two-photon excited fluorescence (TPEF) to produce images. With increasing applications of multiphoton microscopy to thick-tissue ''intravital'' imaging, second-harmonic generation (SHG) from structural proteins has emerged as a potentially important new contrast mechanism. However, SHG is typically detected in transmission mode, thus limiting TPEF͞SHG coregistration and its practical utility for in vivo thick-tissue applications. In this study, we use a broad range of excitation wavelengths (730 -880 nm) to demonstrate that TPEF͞SHG coregistration can easily be achieved in unstained tissues by using a simple backscattering geometry. The combined TPEF͞SHG technique was applied to imaging a threedimensional organotypic tissue model (RAFT). The structural and molecular origin of the image-forming signal from the various tissue constituents was determined by simultaneous spectroscopic measurements and confirming immunofluorescence staining. Our results show that at shorter excitation wavelengths (<800 nm), the signal emitted from the extracellular matrix (ECM) is a combination of SHG and TPEF from collagen, whereas at longer excitation wavelengths the ECM signal is exclusively due to SHG. Endogenous cellular signals are consistent with TPEF spectra of cofactors NAD(P)H and FAD at all excitation wavelengths. The reflected SHG intensity follows a quadratic dependence on the excitation power, decays exponentially with depth, and exhibits a spectral dependence in accordance with previous theoretical studies. The use of SHG and TPEF in combination provides complementary information that allows noninvasive, spatially localized in vivo characterization of cell-ECM interactions in unstained thick tissues. S ince its introduction by Denk et al.(1), two-photon excited fluorescence (TPEF) has been widely used for imaging structure and dynamic interactions in biological tissues (2-5). Although second-harmonic generation (SHG) in biological tissues was first demonstrated two decades ago (6-8), SHG has only recently been used for biological imaging applications (9-12). Because TPEF and SHG involve different contrast mechanisms, they can be used in tandem to provide complementary information regarding tissue structure and function. Specifically, SHG signals depend on the orientation, polarization, and local symmetry properties of chiral molecules, whereas TPEF results from the nonlinear excitation of molecular fluorescence.The primary tissue constituent responsible for SHG is collagen (9,13,14), which is also a well documented source of tissue autofluorescence (4,15). This fact has created uncertainty over whether the image-forming signal from two-photon excitation of collagen in biological tissues is TPEF or SHG and prompts further investigation into the precise origin of signal in the nonlinear microscopy of...

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Section: Resultssupporting

confidence: 89%

Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence

Zoumi

Yeh²,

Tromberg³

2002

Proc. Natl. Acad. Sci. U.S.A.

809

725

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“…1), similar to the previously described [8], specifically designed for measurements of the human uterine cervix. The vaginal probe was slightly bent allowing good visualization during placement on the cervix.…”

Section: Methodsmentioning

confidence: 99%

Frequency domain near‐infrared spectroscopy of the uterine cervix during cervical ripening

Baños

Wolf²,

Grawe

et al. 2007

Lasers Surg Med

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Objective: Preterm labor is a common obstetric complication. Clinical evaluation of cervical ripening to predict preterm labor has a substantial inter-and intraobserver variability. We used frequency domain near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of the optical properties (i.e., absorption and scattering of light) in the uterine cervix during druginduced cervical ripening. Methods: Ten volunteers scheduled for abortion were examined. Optical properties of the uterine cervix were measured and physiological parameters were calculated prior to and after induction of cervical ripening using topical misoprostol. Mean relative changes, standard error of the mean as well as statistical significance using the t-test were calculated for oxy-and deoxyhemoglobin, total hemoglobin, oxygen-saturation, and water. The wavelength-dependent decrease of scattering (scatter power) was calculated by an exponential fit and tested with the Wilcoxon test. Results: Misoprostol induced a decrease in total hemoglobin of 21+/-6% (P<0.05), a decrease in oxyhemoglobin of 22+/-6% (P<0.05), a decrease in deoxyhemoglobin of 16+/-11% and an increase of 368% (P<0.005) in water content. The scatter power was significantly lower (P<0.05) after cervical ripening. Conclusion: Our results show that FD-NIRS is a promising diagnostic tool to detect changes in cervical concentrations of hemoglobin and water. A severe tissue edema, probably due to a hormone-induced inflammatory process, seems to be important for cervical ripening. The reduction in total hemoglobin is likely to be a consequence of the increased water content of the tissue resulting in a dramatic increase of the distance between vessels. We propose this technology to assess the cervical ripening and eventually to predict preterm labor. Lasers Surg. Med. 39:641-646, 2007 Objective: Preterm labor is a common obstetric complication. Clinical evaluation of cervical ripening to predict preterm labor has a substantial inter-and intraobserver variability. We used frequency domain near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of the optical properties (i.e., absorption and scattering of light) in the uterine cervix during druginduced cervical ripening. Methods: Ten volunteers scheduled for abortion were examined. Optical properties of the uterine cervix were measured and physiological parameters were calculated prior to and after induction of cervical ripening using topical misoprostol. Mean relative changes, AE standard error of the mean as well as statistical significance using the t-test were calculated for oxy-and deoxyhemoglobin, total hemoglobin, oxygen-saturation, and water. The wavelength-dependent decrease of scattering (scatter power) was calculated by an exponential fit and tested with the Wilcoxon test.Results: Misoprostol induced a decrease in total hemoglobin of 21 AE 6% (P < 0.05), a decrease in oxyhemoglobin of 22 AE 6% (P < 0.05), a decrease in deoxyhemoglobin of 16 AE 11% and an increase of 36 AE 8%...

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“…[12][13][14][15][16] Substantial progress has been made during the past decade in our ability to quantify tissue optical and physiologic properties, largely due to the emergence of time and frequency-domain photon migration techniques. 11,17 Frequency-domain photon migration ͑FDPM͒ uses high frequency ͑MHz-GHz͒ intensity modulated near-infrared light to noninvasively quantify light absorption ( a ) and reduced scattering ( s Ј) parameters in tissue. a and s Ј are sensitive to biologically important light-absorbing and -scattering molecules and structures.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive monitoring of hemodynamic stress using quantitative near-infrared frequency-domain photon migration spectroscopy

Pham

Hornung

et al. 2002

J. Biomed. Opt.

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Abstract. Hemorrhagic hypovolemia and inotropic agent administration were used to manipulate cardiac output (CO) and oxygen delivery in rabbits to investigate the correlation between noninvasive frequency domain photon migration (FDPM) spectroscopy and invasive hemodynamic monitoring parameters. Frequency-domain photon migration provides quantitative measurements of light absorption and reduced scattering ( a and s Ј , respectively) in tissue. Wavelength dependent a values were used to calculate in vivo tissue concentration of deoxyhemoglobin [Hb], oxyhemoglobin ͓HbO 2 ͔, total hemoglobin [TotHb], and water ͓H 2 O͔ as well as mixed arterial-venous oxygen saturation (S t O 2 ) in tissue. FDPM-derived physiologic properties were correlated with invasive measurements of CO and mean pulmonary artery pressure (mPAP), FDPM-derived [TotHb] and S t O 2 correlated significantly with hemorrhaged volume (HV), mPAP, and CO. Correlation coefficients for [TotHb] vs HV, mPAP, and CO were −0.77, 0.86, and 0.70, respectively. Correlation coefficients of S t O 2 vs HV, mPAP, and CO were −0.71, 0.55, and 0.61, respectively. Dobutamine induced changes resulted in correlation coefficients between FDPM-derived and invasively measured physiologic parameters that are comparable to those induced by hypovolemia. FDPM spectroscopy is sensitive to changes in mPAP and CO of as little as 15%. These results suggest that FDPM spectroscopy may be used in clinical settings to noninvasively monitor central hemodynamic parameters and to directly assess oxygenation of tissues.

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Quantitative near-infrared spectroscopy of cervical dysplasia in vivo

Cited by 90 publications

References 41 publications

Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence

Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence

Frequency domain near‐infrared spectroscopy of the uterine cervix during cervical ripening

Noninvasive monitoring of hemodynamic stress using quantitative near-infrared frequency-domain photon migration spectroscopy

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