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Fluorescence tomography (FT) has become a powerful preclinical imaging modality with a great potential for several clinical applications. Although it has superior sensitivity and utilizes low-cost instrumentation, the highly scattering nature of bio-tissue makes FT in thick samples challenging, resulting in poor resolution and low quantitative accuracy. To overcome the limitations of FT, we previously introduced a novel method, termed temperature modulated fluorescence tomography (TMFT), which is based on two key elements: (1) temperature-sensitive fluorescent agents (ThermoDots) and (2) high-intensity focused ultrasound (HIFU). The fluorescence emission of ThermoDots increases up to hundredfold with only several degree temperature elevation. The exceptional and reversible response of these ThermoDots enables their modulation, which effectively allows their localization using the HIFU. Their localization is then used as functional a priori during the FT image reconstruction process to resolve their distribution with higher spatial resolution. The last version of the TMFT system was based on a cooled CCD camera utilizing a step-and-shoot mode, which necessitated long total imaging time only for a small selected region of interest (ROI). In this paper, we present the latest version of our TMFT technology, which uses a much faster continuous HIFU scanning mode based on an intensified CCD (ICCD) camera. This new, to the best of our knowledge, version can capture the whole field-of-view (FOV) of 50×30mm2 at once and reduces the total imaging time down to 30 min, while preserving the same high resolution (∼1.3mm) and superior quantitative accuracy (<7% error) as the previous versions. Therefore, this new method is an important step toward utilization of TMFT for preclinical imaging.
Fluorescence tomography (FT) has become a powerful preclinical imaging modality with a great potential for several clinical applications. Although it has superior sensitivity and utilizes low-cost instrumentation, the highly scattering nature of bio-tissue makes FT in thick samples challenging, resulting in poor resolution and low quantitative accuracy. To overcome the limitations of FT, we previously introduced a novel method, termed temperature modulated fluorescence tomography (TMFT), which is based on two key elements: (1) temperature-sensitive fluorescent agents (ThermoDots) and (2) high-intensity focused ultrasound (HIFU). The fluorescence emission of ThermoDots increases up to hundredfold with only several degree temperature elevation. The exceptional and reversible response of these ThermoDots enables their modulation, which effectively allows their localization using the HIFU. Their localization is then used as functional a priori during the FT image reconstruction process to resolve their distribution with higher spatial resolution. The last version of the TMFT system was based on a cooled CCD camera utilizing a step-and-shoot mode, which necessitated long total imaging time only for a small selected region of interest (ROI). In this paper, we present the latest version of our TMFT technology, which uses a much faster continuous HIFU scanning mode based on an intensified CCD (ICCD) camera. This new, to the best of our knowledge, version can capture the whole field-of-view (FOV) of 50×30mm2 at once and reduces the total imaging time down to 30 min, while preserving the same high resolution (∼1.3mm) and superior quantitative accuracy (<7% error) as the previous versions. Therefore, this new method is an important step toward utilization of TMFT for preclinical imaging.
We propose the proof-of-concept of a novel method for wide-field spectrally resolved near-infrared fluorescence (NIRF) imaging using a wavelength-swept laser. The performance of our method is evaluated on a biotissue-like phantom bearing two inclusions, one filled with indocyanine green (ICG) dissolved in distilled water and the second one in dimethyl sulfoxide (DMSO). A near-infrared wavelength-swept laser covering wavelengths around the peak absorption of ICG was used. The difference in the absorption spectra of these two ICG solutions gives rise to an additional spectral contrast. The distinction between the emitted fluorescence light from the two different solutions is performed using a principal component analysis (PCA)-based method. Results show that the two different ICG solutions were successfully resolved using this approach. This technique can be a powerful method to simultaneously spatio-spectrally image multiple near-infrared fluorescence agents.
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