The development of stable and non-toxic near-infrared optical probes together with the recent advances in laser diode sources and detection technologies promise non-invasive, diagnostic tissue spectroscopy. However, studies show that determination of biochemical species from re-emitted tissue fluorescence spectra require deconvolution of tissue scattering and absorption properties for quantitative tissue spectroscopy. Since tissue optical properties can be expected to vary from person to person and with pathophysiology, it is unlikely that fluorescence intensity measurements will make full use of the emerging NIR optical probes. Signals which arise from endogenous species such as NAD(P)H, NAD(P), and FP are likewise influenced by tissue optical properties. In this application, the applicants proposed to couple established techniques of frequency-domain measurements of optical probe lifetimes together with a simple algorithm for excitation and fluorescent light propagation in tissues in order to quantitate metabolite concentrations using exogenous probes and metabolic state, using endogenous probes. Both computations and experimental measurements demonstrate the feasibility of our approach for lifetime-based tissue spectroscopy, in which the kinetics of fluorescent re-emission are decoupled from photon """"""""time-of-flights"""""""" in order to provide diagnostic measurements from endogenous and exogenous fluorescent probes. The applicants proposed to conduct measurements which validate (i) fluorescence-lifetime tissue spectroscopy in which a uniform distribution of probe lifetime exists, (ii) fluorescence-lifetime diagnostics in which an exogenous, metabolite-sensing fluorescent probe is immobilized in an implanted device, and (iii) fluorescence lifetime imaging in which a """"""""map"""""""" or image of lifetime provides a metabolic """"""""map"""""""" or image of diseased tissues from non-invasive optical measurements made at the tissue-air interface. These fundamental studies are pointed toward applications for biodiagnostic sensing and imaging.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA067176-02
Application #
2517623
Study Section
Special Emphasis Panel (ZRG7-DMG (01))
Project Start
1996-09-01
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Purdue University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Godavarty, Anuradha; Sevick-Muraca, Eva M; Eppstein, Margaret J (2005) Three-dimensional fluorescence lifetime tomography. Med Phys 32:992-1000
Godavarty, Anuradha; Eppstein, Margaret J; Zhang, Chaoyang et al. (2005) Detection of single and multiple targets in tissue phantoms with fluorescence-enhanced optical imaging: feasibility study. Radiology 235:148-54
Hwang, Kildong; Houston, Jessica P; Rasmussen, John C et al. (2005) Improved excitation light rejection enhances small-animal fluorescent optical imaging. Mol Imaging 4:194-204
Gurfinkel, Michael; Pan, Tianshu; Sevick-Muraca, Eva M (2004) Determination of optical properties in semi-infinite turbid media using imaging measurements of frequency-domain photon migration obtained with an intensified charge-coupled device. J Biomed Opt 9:1336-46
Godavarty, A; Zhang, C; Eppstein, M J et al. (2004) Fluorescence-enhanced optical imaging of large phantoms using single and simultaneous dual point illumination geometries. Med Phys 31:183-90
Gurfinkel, Michael; Ke, Shi; Wen, Xiaoxia et al. (2003) Near-infrared fluorescence optical imaging and tomography. Dis Markers 19:107-21
Thompson, Alan B; Sevick-Muraca, Eva M (2003) Near-infrared fluorescence contrast-enhanced imaging with intensified charge-coupled device homodyne detection: measurement precision and accuracy. J Biomed Opt 8:111-20
Roy, Ranadhir; Godavarty, Anuradha; Sevick-Muraca, Eva M (2003) Fluorescence-enhanced optical tomography using referenced measurements of heterogeneous media. IEEE Trans Med Imaging 22:824-36
Houston, Jessica P; Thompson, Alan B; Gurfinkel, Michael et al. (2003) Sensitivity and depth penetration of continuous wave versus frequency-domain photon migration near-infrared fluorescence contrast-enhanced imaging. Photochem Photobiol 77:420-30
Thompson, Alan B; Hawrysz, Daniel J; Sevick-Muraca, Eva M (2003) Near-infrared fluorescence contrast-enhanced imaging with area illumination and area detection: the forward imaging problem. Appl Opt 42:4125-36

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