Viral transport in a sand and gravel aquifer under field pumping conditions.

Ground water supplies contaminated with microbes cause more than 50% of the water-borne disease outbreaks in the United States. Proposed regulations suggest natural disinfection as a possible mechanism to treat microbe-impacted ground water under favorable conditions. However, the usefulness of current models employed to predict viral transport and natural attenuation rates is limited by the absence of field scale calibration data. At a remote floodplain aquifer in western Montana, the bacteriophages MS2, phiX174, and PRD1; attenuated poliovirus type-1 (CHAT strain); and bromide were seeded as a slug 21.5 m from a well pumping at a steady rate of 408 L/min. Over the 47-hour duration of the test, resulting in the exchange of 12 to 13 pore volumes, 77% of the bromide, 55% of the PRD1, 17% of the MS2, 7% of the phiX174, and 0.12% of the poliovirus masses were recovered at the pumping well. Virus transport behavior was controlled by mechanical dispersion, preferential flow, time-dependent nonreversible and reversible attachment, and apparent mass transfer to immobile domains within the sand and gravel dominated aquifer. The percentage of virus recovery appears correlated with reported viral isoelectric point (pI) values. Successful modeling of viral transport in coarse-grained aquifers will require separation of viral specific properties from reported lumped viral-transport system parameters.

Optical properties of human skin in the near infrared wavelength range of 1000 to 2200 nm.

In this paper we present the absorption coefficient mu(a) and the isotropic scattering coefficient mu(s)(') for 22 human skin samples measured using a double integrating sphere apparatus in the wavelength range of 1000-2200 nm. These in vitro results show that values for mua) follow 70% of the absorption coefficient of water and values for mu(s)(') range from 3 to 16 cm(-1). From the measured optical properties, it was found that a 2% Intralipid solution provides a suitable skin tissue phantom.

Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study.

We present in vivo fluorescent, near-infrared (NIR), reflectance images of indocyanine green (ICG) and carotene-conjugated 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH-car) to discriminate spontaneous canine adenocarcinoma from normal mammary tissue. Following intravenous administration of 1.0 mg kg-1 ICG or 0.3 mg kg-1 HPPH-car into the canine, a 25 mW, 778 nm or 70 mW, 660 nm laser diode beam, expanded by a diverging lens to approximately 4 cm in diameter, illuminated the surface of the mammary tissue. Successfully propagating to the tissue surface, ICG or HPPH-car fluorescence generated from within the tissue was collected by an image-intensified, charge-coupled device camera fitted with an 830 or 710 nm bandpass interference filter. Upon collecting time-dependent fluorescence images at the tissue surface overlying both normal and diseased tissue volumes, and fitting these images to a pharmacokinetic model describing the uptake (wash-in) and release (wash-out) of fluorescent dye, the pharmacokinetics of fluorescent dye was spatially determined. Mapping the fluorescence intensity owing to ICG indicates that the dye acts as a blood pool or blood persistent agent, for the model parameters show no difference in the ICG uptake rates between normal and diseased tissue regions. The wash-out of ICG was delayed for up to 72 h after intravenous injection in tissue volumes associated with disease, because ICG fluorescence was still detected in the diseased tissue 72 h after injection. In contrast, HPPH-car pharmacokinetics illustrated active uptake into diseased tissues, perhaps owing to the overexpression of LDL receptors associated with the malignant cells. HPPH-car fluorescence was not discernable after 24 h. This work illustrates the ability to monitor the pharmacokinetic delivery of NIR fluorescent dyes within tissue volumes as great as 0.5-1 cm from the tissue surface in order to differentiate normal from diseased tissue volumes on the basis of parameters obtained from the pharmacokinetic models.

Imaging of spontaneous canine mammary tumors using fluorescent contrast agents.

We present near-infrared frequency-domain photon migration imaging for the lifetime sensitive detection and localization of exogenous fluorescent contrast agents within tissue-simulating phantoms and actual tissues. We employ intensity-modulated excitation light that is expanded and delivered to the surface of a tissue or tissue-simulating phantom. The intensity-modulated fluorescence generated from within the volume propagates to the surface and is collected using a gain-modulated image-intensified charge-coupled device camera. From the spatial values of modulation amplitude and phase of the detected fluorescent light, micromolar volumes of diethylthiatricarbocyanine iodide (tau = 1.17 ns) and indocyanine green (ICG) (tau = 0.58 ns) embedded 1.0 cm deep in a tissue phantom are localized and discriminated on the basis of their lifetime differences. To demonstrate the utility of frequency-domain fluorescent measurements for imaging disease, we image the fluorescence emitted from the surface of in vivo and ex vivo canine mammary gland tissues containing lesions with preferential uptake of ICG. Pathology confirms the ability to detect spontaneous mammary tumors and regional lymph nodes amidst normal mammary tissue and fat as deep as 1.5 cm from the tissue surface.

Biomedical optical tomography using dynamic parameterization and bayesian conditioning on photon migration measurements.

Stochastic reconstruction techniques are developed for mapping the interior optical properties of tissues from exterior frequency-domain photon migration measurements at the air-tissue interface. Parameter fields of absorption cross section, fluorescence lifetime, and quantum efficiency are accurately reconstructed from simulated noisy measurements of phase shift and amplitude modulation by use of a recursive, Bayesian, minimum-variance estimator known as the approximate extended Kalman filter. Parameter field updates are followed by data-driven zonation to improve the accuracy, stability, and computational efficiency of the method by moving the system from an underdetermined toward an overdetermined set of equations. These methods were originally developed by Eppstein and Dougherty [Water Resources Res. 32, 3321 (1996)] for applications in geohydrology. Estimates are constrained to within feasible ranges by modeling of parameters as beta-distributed random variables. No arbitrary smoothing, regularization, or interpolation is required. Results are compared with those determined by use of Newton-Raphson-based inversions. The speed and accuracy of these preliminary Bayesian reconstructions suggest the near-future application of this inversion technology to three-dimensional biomedical imaging with frequency-domain photon migration.

Fluorescence lifetime spectroscopic imaging with measurements of photon migration.

Frequency-domain measurements of photon migration are coupled with a model of fluorescence generation and propagation in order to develop a method for reconstructing maps of fluorescent properties within interior tissue volumes from exterior measurements at the air-tissue interface. Simulation results confirm the feasibility of optical imaging through the use of exogenously administered contrast agents on the basis of fluorophore decay kinetics and yield. Experimental measurements using single-pixel and multipixel devices illustrate that the contrast owing to exogenous fluorescence exceeds that owing to absorption or scattering caused by endogenous chromophores or tissue structure and owing to absorption caused by exogenous contrast agents.

Multipixel techniques for frequency-domain photon migration imaging.

The ability to map interior optical properties of a highly scattering medium from exterior measurements of light propagation is afforded by optical tomography. In this communication, we describe the problem of optical tomography, the techniques of photon migration measurements necessary to accomplish it, and the development of multipixel measurements for rapid collection of optical signals. These multipixel measurements are shown to provide detection of contrast owing to the optical properties of absorption and fluorescence associated with dye-laden heterogeneities embedded in a tissue-like scattering medium. From these rapid measurements, successful reconstruction of an interior optical property map may now be possible with clinically realistic data acquisition times. Applications for the technology arise for biomedical optical imaging for the in vivo detection of disease and the diagnosis of tissue (bio-) chemistry.

Fluorescence and absorption contrast mechanisms for biomedical optical imaging using frequency-domain techniques.

The ability to optically image or detect diseased tissue volumes located deep within tissues depends upon the degree of contrast provided by differences in local optical properties. In this report, we show that the exogenous contrast offered by fluorescent compounds is superior to that provided by nonfluorescing, light-absorbing compounds when time-dependent measurements are employed. In addition, we show that the induced contrast is not only moderated by the preferential uptake of fluorescent agents into diseased tissue volumes of interest but also by the fluorescent optical properties and the fluorescence dynamics in the specific tissue volume. Using tissue phantom studies, we demonstrated experimentally that near-infrared-absorbing and fluorescent dyes such as indocyanine green can provide detection of diseased tissue volumes from fluorescence measurements made at the periphery of tissue when there is perfect, 100-fold and 10-fold partitioning in diseased tissues over that in surrounding normal tissues. Experimental results of common laser dyes show the contrast is also mediated by the quantum yield and lifetime parameters that may be dependent upon the local tissue environment.

Role of higher-order scattering in solutions to the forward and inverse optical-imaging problems in random media.

From analytical and numerical solutions that predict the scattering of diffuse photon density waves and from experimental measurements of changes in phase shift theta and ac amplitude demodulation M caused by the presence of single and double cylindrical heterogeneities, we show that second- and higher-order perturbations can affect the prediction of the propagation characteristics of diffuse photon density waves. Our experimental results for perfect absorbers in a lossless medium suggest that the performance of fast inverse-imaging algorithms that use first-order Born or Rytov approximations might have inherent limitations compared with inverse solutions that use iterative solutions of a linear perturbation equation or numerical solutions of the diffusion equation.

Fluorescence-lifetime determination in tissues or other scattering media from measurement of excitation and emission kinetics.

Measurements of nanosecond and subnanosecond fluorescence lifetimes are restricted to dilute, nonscattering systems since excitation and emission photon times of flight significantly affect measured fluorescent decay kinetics. We provide the theoretical rationale for frequency-domain measurements of phase-shift and amplitude demodulation made at excitation and emission wavelengths for direct determination of lifetimes in tissues and other scattering media. We confirm our analytical expressions using standard laser dyes such as 3,3'-diethylthiatricarbocyanine iodide, IR- 125, and IR- 140 in polystyrene suspensions with similar scattering properties as tissues. Our results have significant implication for lifetime-based spectroscopy in tissues and other scattering media.