Spectral derivative based image reconstruction provides inherent insensitivity to coupling and geometric errors

A reconstruction algorithm for multiwavelength diffuse optical tomography is presented, where instead of using data at each wavelength separately or even simultaneously, the difference in data for multiple wavelength pairs is used to reconstruct absolute concentration maps of chromophores. The results indicate a dramatic improvement in image reconstruction and the elimination of image artifacts, which are often associated with unknown measurement errors such as coupling coefficients and external boundary variations, because these errors are often less dependent on wavelength, and are effectively removed from the data set of the first derivative of intensity with respect to wavelength.     

Pre-clinical whole-body fluorescence imaging: Review of instruments,methods and applications

Fluorescence sampling of cellular function is widely used in all aspects of biology, allowing the visualization of cellular and sub-cellular biological processes with spatial resolutions in the range from nanometers up to centimeters. Imaging of fluorescence in vivo has become the most commonly used radiological tool in all pre-clinical work. In the last decade, full-body pre-clinical imaging systems have emerged with a wide range of utilities and niche application areas. The range of fluorescent probes that can be excited in the visible to near-infrared part of the electromagnetic spectrum continues to expand, with the most value for in vivo use being beyond the 630 nm wavelength, because the absorption of light sharply decreases. Whole-body in vivo fluorescence imaging has not yet reached a state of maturity that allows its routine use in the scope of large-scale pre-clinical studies. This is in part due to an incomplete understanding of what the actual fundamental capabilities and limitations of this imaging modality are. However, progress is continuously being made in research laboratories pushing the limits of the approach to consistently improve its performance in terms of spatial resolution, sensitivity and quantification. This paper reviews this imaging technology with a particular emphasis on its potential uses and limitations, the required instrumentation, and the possible imaging geometries and applications. A detailed account of the main commercially available systems is provided as well as some perspective relating to the future of the technology development. Although the vast majority of applications of in vivo small animal imaging are based on epi-illumination planar imaging, the future success of the method relies heavily on the design of novel imaging systems based on state-of-the-art optical technology used in conjunction with high spatial resolution structural modalities such as MRI, CT or ultrasound.     

Multiple-gate time domain diffuse fluorescence tomography allows more sparse tissue sampling without compromising image quality

Diffuse fluorescence tomography systems that employ highly sensitive photo-multiplier tubes for single-photon detection are pushing the sensitivity limits of the field. However, each of these detectors only offers a single data projection to be collected, implying these imaging systems either require many detectors or long scan times to collect full data sets for image reconstruction. This study presents a method of utilizing the time-resolved collection capabilities of time-correlated single-photon counting techniques to increase spatial resolution and to reduce the number of data projections to produce reliable fluorescence reconstructions. Experimental tissue phantom results demonstrate that using data at 10 time gates in the fluorescence reconstructions for only 40 data projections provided superior image accuracy when compared to reconstructions on 320 continuous-wave data projections.     

Birefringence thermal analysis of liquid crystalline monomers and their photopolymers

Birefringence analysis was used to measure thermal transitions in liquid crystal diacrylate monomers and their corresponding polymers. In this technique, linearly polarized light was used to probe the sample as the temperature increased via a linear ramp. Various phase transitions were observed in the liquid crystalline monomers. In addition, the monomers were isothermally photopolymerized in the liquid crystalline state and the resulting polymer networks retained their liquid crystalline order. Glass-to-rubber transitions as well as indications of further thermal polymerization and stress relaxation were detected. Results from birefringence experiments were compared to those of more traditional thermal analysis techniques including DSC and TMA.The authors would like to thank the National Science Foundation for sponsoring this research under NSF Grant No. DMR-9420357. We would also like to thank Mary Galaska and John Murphy, of the University of Dayton, for their help in conducting experiments, and Katy Weaver, also of the University of Dayton, for her help in sample preparation.     

Toward whole-body optical imaging of rats using single-photon counting fluorescence tomography

We used single-photon counting (SPC) detection for diffuse fluorescence tomography to image nanomolar (nM) concentrations of reporter dyes through a rat. Detailed phantom data are presented to show that every centimeter increase in tissue thickness leads to 1 order of magnitude decrease in the minimum fluorophore concentration detectable for a given detector sensitivity. Specifically, here, detection of Alexa Fluor 647 dyes is shown to be achievable for concentrations as low as 1 nM (<200 fM) through more than 5 cm in tissue phantoms, which indicates that this is feasible in larger rodent models. Because it is possible to detect sub-nM fluorescent inclusions with SPC technology in rats, it follows that it is possible to localize subpicomolar fluorophore concentrations in mice, putting the concentration sensitivity limits on the same order as nuclear medicine methods.     

Weather-informed Light–tissue Model–Based Dose Planning for Indoor Daylight Photodynamic Therapy

Daylight activation for photodynamic therapy (PDT) of skin lesions is now widely adopted in many countries as a less painful and equally effective treatment mechanism, as compared to red or blue light activation. However, seasonal daylight availability and transient weather conditions complicate light dose estimations. A method is presented for dose planning without placing a large burden on clinical staff, by limiting spectral measurements to a one-time site assessment, and then using automatically acquired weather reports to track transient conditions. The site assessment tools are used to identify appropriate treatment locations for the annual and daily variations in sunlight exposure for clinical center planning. The spectral information collected from the site assessment can then be integrated with real-time daily electronic weather data. It was shown that a directly measured light exposure has strong correlation (R²: 0.87) with both satellite cloud coverage data and UV index, suggesting that the automated weather indexes can be surrogates for daylight PDT optical dose. These updated inputs can be used in a dose-planning treatment model to estimate photodynamic dose at depth in tissue. A simple standardized method for estimating light dose during daylight-PDT could help improve intersite reproducibility while minimizing treatment times.     

Time-gated Cherenkov emission spectroscopy from linear accelerator irradiation of tissue phantoms

Radiation from a linear accelerator induces Cherenkov emission in tissue, which has recently been shown to produce biochemical spectral signatures that can be interpreted to estimate tissue hemoglobin and oxygen saturation or molecular fluorescence from reporters. The Cherenkov optical light levels are in the range of 10(-6) to 10(-9) W/cm2, which limits the practical utility of the signal in routine radiation therapy monitoring. However, due to the fact that the radiation is pulsed, gated-acquisition of the signal allows detection in the presence of ambient lighting, as is demonstrated here. This observation has the potential to significantly increase the value of Cherenkov emission spectroscopy during radiation therapy to monitor tissue molecular events.     

Dark-field scanning in situ spectroscopy platform for broadband imaging of resected tissue

A dark-field geometry spectral imaging system is presented to raster scan thick tissue samples in situ in 1.5 cm square sections, recovering full spectra from each 100 μm diameter pixel. This spot size provides adequate resolution for wide field scanning, while also facilitating scatter imaging without requiring sophisticated light-tissue transport modeling. The system is demonstrated showing accurate estimation of localized scatter parameters and the potential to recover absorption-based contrast from broadband reflectance data measured from 480 nm up to 750 nm in tissue phantoms. Results obtained from xenograft pancreas tumors show the ability to quantitatively image changes in localized scatter response in this fast-imaging geometry. The polychromatic raster scan design allows the rapid scanning necessary for use in surgical/clinical applications where timely decisions are required about tissue pathology.     

Solution thermodynamics of first row transition elements. 3. Apparent molal volumes of aqueous ZnCl2 and Zn(CIO4)2 from 15 to 55°C and an examination of solute-solute and solute-solvent interactions

The apparent molal volumes of aqueous ZnCl₂ and Zn(ClO₄)₂ solutions have been measured from 15–55°C. The dilute solution data are extrapolated to infinite dilution using the Redlich-Meyer equation. The full concentration range data are fitted with the Pitzer formalism. The data are then compared with the data on the previously measured salts of Mn²⁺, Fe²⁺, Co²⁺, Ni²⁺, and Cu²⁺. The effect of complex ion formation is easily seen in the Cu²⁺ and Zn²⁺ salt data. A new approach to single ion volumes from salt volumes is proposed. The calculated ionic volumes at infinite dilution are compared, and it is clear that crystal field effects must be considered in any quantitative theory of transition element volumes.