The main goal of this work is to show that soft tissue interaction with high-intensity focused ultrasound (HIFU) or direct heating leads to a weak light emission detectable using a small animal optical imaging system. Our results show that the luminescence signal is detectable after 30 min of heating, resembling the time scale of delayed luminescence. The imaging of a soft tissue after heating it using an HIFU field shows that the luminescence pattern closely matches the shape of the cone typical of the HIFU beam. We conclude that heating a soft tissue using two different sources leads to the emission of a weak luminescence signal from the heated region with a decay half-life of a few minutes (4 to 6 min). The origin of such light emission needs to be further investigated.
There is experimental evidence for the production of non-Cerenkov radioluminescence in a variety of materials, including tissue. We constructed a Geant4 Monte Carlo simulation of the radiation from P32 and Tc99m interacting in chicken breast and used experimental imaging data to model a scintillation-like emission. The same radioluminescence spectrum is visible from both isotopes and cannot otherwise be explained through fluorescence or filter miscalibration. We conclude that chicken breast has a near-infrared scintillation-like response with a light yield three orders of magnitude smaller than BGO.
We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of Y90-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device coupled with an f/0.95 17-mm C-mount lens. We showed for the first time the possibility of obtaining CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery.
The in vitro and in vivo detection of visible photons from radioisotopes using optical techniques is a fast-growing field in molecular imaging. Tc 99m -pertechnetate is used as an alternative to I 123 in imaging of the thyroid and is generally imaged with gamma cameras or single photon emission tomography instruments. The uptake in the thyroid tissue is mediated by the sodium-iodide symporter (NIS), a glycoprotein that actively mediates iodide transport into the thyroid follicular cells and several extrathyroidal tissues. The luminescence of the gamma emitter Tc 99m -pertechnetate in order to visualize its biodistribution in healthy small living animals by using a commercial optical imaging system is investigated. Here we show that in Nu/Nu mice, the uptake of Tc 99m -pertechnetate in the thyroid gland and in salivary glands is very detectable by using radionuclide luminescence imaging. We also found light emission from the stomach in accordance with the literature. The localization of the light signals in the anatomical regions where the radiopharmaceutical is expected, confirmed by resections, shows that it is possible to image NIS-expressing tissues.
Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.
In vivo Cerenkov luminescence imaging is a rapidly growing molecular imaging research field based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues. We investigated theoretically the possibility of enhancing the number of the detected Cerenkov photons in the near infrared (NIR) region of the spectrum. The analysis is based on applying a photon propagation diffusion model to Cerenkov photons in the tissue. Results show that despite the smaller number of Cerenkov photons in the NIR region, the fraction exiting the tissues is greater than in the visible range, and thus, a charge-coupled device detector optimized for the NIR range will allow to obtain a higher signal. The comparison was performed considering Cerenkov point sources located at different depths inside the animal. We concluded that the improvement can be up to 35% and is more significant when the Cerenkov source to be imaged is located deeper inside the animal.
Clustering analysis (CA) and principal component analysis (PCA) were applied to dynamic Cerenkov luminescence images (dCLI). In order to investigate the performances of the proposed approaches, two distinct dynamic data sets obtained by injecting mice with 32P-ATP and 18F-FDG were acquired using the IVIS 200 optical imager. The k-means clustering algorithm has been applied to dCLI and was implemented using interactive data language 8.1. We show that cluster analysis allows us to obtain good agreement between the clustered and the corresponding emission regions like the bladder, the liver, and the tumor. We also show a good correspondence between the time activity curves of the different regions obtained by using CA and manual region of interest analysis on dCLIT and PCA images. We conclude that CA provides an automatic unsupervised method for the analysis of preclinical dynamic Cerenkov luminescence image data.
There has been growing interest in investigating both the in vitro and in vivo detection of optical photons from a plethora of beta emitters using optical techniques. In this paper we have investigated an alpha particle induced fluorescence signal by using a commercial CCD-based small animal optical imaging system. The light emission of a 241Am source was simulated using GEANT4 and tested in different experimental conditions including the imaging of in vivo tissue. We believe that the results presented in this work can be useful to describe a possible mechanism for the in vivo detection of alpha emitters used for therapeutic purposes.
It has been recently shown that optical imaging (OI) methods can be used to image the in vivo biodistribution of several radiopharmaceuticals labeled with beta or alpha emitters. In this work particular attention has been focused on investigating the weaker optical signal induced by an almost pure gamma emitter like Tc-99m. Visible light emission measurements of a water solution containing Tc-99m were performed using a small animal OI system. A sequence of images was acquired for 24 h in order to study the decay of the luminescence signal. The difference between the luminescence decay half life and well-known Tc-99m half life was equal to 1%. in vivo imaging was performed by injecting one control nude mice with Tc-99m-MDP. Optical images obtained with equipment designed for bioluminescence imaging showed that a visible light emission was distinguishable and correctly localized in the bladder region where a higher concentration of Tc-99m-MDP was expected. The bladder to background ratio was always greater than 1. We conclude that the experimental data presented in this paper show that it is possible to detect in vivo luminescence optical photons induced by Tc-99m. This is important especially considering the large number of Tc-99m-based radiopharmaceutical currently available.
A general approach for partial volume correction of positron emission tomography (PET) images is introduced. The method is based on the merging of functional information from PET images and anatomical information using high resolution anatomical images. In order to decompose the PET and high resolution images
the "á trous" algorithm was implemented. Results obtained with simulated and real patients images show a significant partial volume reduction and image enhancement. The relative errors in the partial volume corrected image are always less than 3,6% with respect to 16% of the original image.