The objective of this work is to identify an imaging modality which can best locate heterogeneous tissue volumes when designer contrast agents are used. We used a multi- pixel, homodyne, frequency-domain photon migration detection system to acquire images of 830 nm fluorescent heterogeneities immersed within a tissue-simulating phantom that contained 0.5 percent Intralipid solution. An expanded beam of 25 mW, 778 nm light modulated at 100 MHz illuminated the phantom surface. Specifically, we monitor fluorescence average intensity, modulation amplitude, phase, and modulation ratio resulting from micromolar concentrations of indocyanine green and DTTCI embedded within tissue- mimicking, highly scattering media. The results indicate that under conditions of perfect uptake, only phase and modulation distinguish dye solutions that possess equivalent fluorescence yield but unequal lifetime when both heterogeneities are located 0.5 cm from the illumination surface. Enhanced phase contrast was observed for fluorescent solutions with short lifetimes located within a surrounding of longer lived fluorophore and visa versa. These results have important implications for the development of contrast agents whose lifetimes depend on the local biochemical environment.
In this paper we demonstrate the ability to detect the frequency-domain fluorescent signal from the contrast agent indocyanine green within the mammary chain of dogs with spontaneous mammary tumors. We use a gain-modulated image intensifier to rapidly capture multi-pixel images of the fluorescent modulation amplitude, modulation phase, and average intensity signals. Excitation is provided by a 100 MHz amplitude-modulated, 780 nm laser diode. Time series images of the uptake and clearance of the contrast agent in the diseased tissue are also presented.
In order for photon migration imaging to be clinically feasible, data acquisition must be fast and efficient. Rapid data acquisition minimizes error due to patient movement and improves patient acceptance. Multi-pixel imaging techniques offer the fastest method of data acquisition, however difficulties may exist in coupling the data with inversion algorithms. Single pixel measurements, while easier to couple to an inversion algorithm, require longer data acquisition times. Herein a heterodyne procedure for speeding the data acquisition time using single pixel techniques is presented. This simple extension of the heterodyne method enables the use of multiple sources simultaneously with the signal from various source-detector pairs discriminated by FFT analysis.
In order to reconstruct images of heterogeneities embedded deep within tissues, multiple-pixel measurements of frequency domain photon migration are necessary. Typically, these measurements are performed at multiple locations on the periphery of the sample using individual fiber optics. However, measurements using multiple fiber optics are both tedious and time consuming, especially as one increases spatial measurement resolution. In our research, we acquire multi-pixel measurements by employing a gain-modulated image intensified CCD camera and near infrared milliwatt laser diodes to monitor the propagation characteristics of sinusoidally modulated light as it passes through tissue-like phantoms containing 0.5% intralipid solutions. Our results show that images of millimeter sized absorbing objects located greater than 1 cm inside an ideal tissue phantom an be successfully obtained. In addition, we have been able to generate fluorescent images locating portions of micromolar concentrations of indocyanine green embedded within an intralipid solution contained within a glass cylindrical vessel (10 mm by 4 mm diameter).
A gain-modulated image intensifier with a CCD array was developed and used to simultaneously acquire multi-pixel modulation amplitude and phase images of the interference pattern within 0.5% intralipid solution and resulting from two 5 mW near infrared sources modulated 180 degrees out-of-phase at frequencies between 10 and 120 MHz. Gain modulation was achieved by modulating the voltage between the image intensifier's photocathode and multichannel plate input. Homodyning the gain modulation and source signals enabled images of the interference pattern to be obtained with total exposure times on the order of 3 seconds or less. A strongly absorbing, embedded heterogeneity could be localized in two dimensions by its deflection of the interference plane between two out-of-phase sources.
Both theory and experimental results show the capacity to locate the presence of a fluorescent volume incurred within a scattering medium from frequency-domain measurements of photon migration. Frequency-domain measurements consisted of monitoring the phase-shift and amplitude demodulation of fluorescent and excitation light reemitted from a tissue phantom in response to a sinusoidally modulated excitation source located 2.8 cm away from a detecting fiber positioned on the phantom periphery. Measurements of modulation phase- shift and amplitude were conducted as a 9 mm diameter cylindrical heterogeneity containing micromolar concentrations of IR-125 and DTTCI in 0.5%. Intralipid was moved within a 20 cm diameter vessel filled with 0.5 Intralipid. These measurements were investigated to evaluate the contrast offered by lifetime, fluorescent yield, and the fluorophore concentration difference between the heterogeneity and its surroundings. Our results show that the degree of contrast offered by fluorescence is always superior to that afforded by light absorption, enabling better detection of a diseased tissue with preferential fluorescent dye uptake. Contrast is also enhanced by the lifetime of the fluorescent dye, its uptake into simulated diseased volume, and the volume into which preferential uptake occurs relative to the surrounding tissues.
We introduce a low cost apparatus utilizing a PIN photodiode receiver and a LED transmitter for frequency domain optical diffusion imaging. We present sample data to demonstrate the system performance and discuss the performance of LED sources and solid state detectors.
A micro-Raman apparatus was used to detect an object embedded within a scattering medium. The Raman vibrational frequency of diamond in an intralipid scattering medium was detected at different radial distances from the diamond. Scanned images of a single diamond, two diamonds, and a diamond through an aperture are presented. This experiment shows that Raman spectroscopy can be a useful tool in locating and characterizing heterogeneities contained within a scattering medium.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.