We developed an endorectal time-resolved optical probe aiming at an early detection of prostate tumors targeted by
fluorescent markers. Optical fibers are embedded inside a clinical available ultrasound endorectal probe. Excitation light
is driven sequentially from a femtosecond laser (775 nm) into 6 source fibers. 4 detection fibers collect the medium
responses at the excitation and fluorescence wavelength (850 nm) by the mean of 4 photomultipliers associated with a 4
channel time-correlated single photon counting card.
We also developed the method to process the experimental data. This involves the numerical computation of the
forward model, the creation of robust features which are automatically correctly from numerous experimental possible
biases and the reconstruction of the inclusion by using the intensity and mean time of these features.
To evaluate our system performance, we acquired measurements of a 40 μL ICG inclusion (10 μmol.L-1) at
various lateral and depth locations in a phantom. Analysis of results showed we correctly reconstructed the
fluorophore for the lateral positions (16 mm range) and for a distance to the probe going up to 1.5 cm. Precision of
localization was found to be around 1 mm which complies well with precision specifications needed for the clinical
application.
The protocol for prostate cancer diagnosis, currently based on ultrasound guided biopsy, is limited by a lack of
relevance. To improve this protocol, a new approach was proposed combining optical and ultrasound measurements to
guide biopsy specifically to the tumors. Adding an optical measurement modality into an already existing ultrasound
probe is challenging as the overall size of the system should not exceed a given dimension so as to fit the operative
environment. Moreover, examination should not take more than 15 min to avoid any complication.
A combined ultrasound and optical endorectal probe was designed to comply with the constraints of the
sterilization protocols, the examination duration and required compactness. Therefore a totally innovative pulsed laser
source has been designed to meet compactness requirements while providing accurate time-resolved measurements. A
dedicated multi-channel photon counting system was optimized to decrease the examination duration. A fast
reconstruction method based on the analysis of the intensity and time of flight of the detected photons has been
associated to provide 3D localization of fluorescent dots almost immediately after acquisition.
The bi-modal probe was capable of withstanding the sterilization procedures. The performance of the compact
laser source has been shown at the same level as that of a standard laboratory Titane:Sapphire laser. The dedicated
photon counting solution was capable of acquiring optical data in less than one minute. To evaluate the overall
performance of the system in dealing with a realistic background signal, measurements and reconstructions were
conducted on prostate mimicking phantom and in vivo.
Finding a way to combine ultrasound and fluorescence optical imaging on an endorectal probe may improve early
detection of prostate cancer. A trans-rectal probe adapted to fluorescence diffuse optical tomography measurements was
developed by our team. This probe is based on a pulsed NIR laser source, an optical fiber network and a time-resolved
detection system. A reconstruction algorithm was used to help locate and quantify fluorescent prostate tumors.
In this study, two different kinds of time-resolved detectors are compared: High Rate Imaging system (HRI) and a
photon counting system. The HRI is based on an intensified multichannel plate and a CCD Camera. The temporal
resolution is obtained through a gating of the HRI. Despite a low temporal resolution (300ps), this system allows a
simultaneous acquisition of the signal from a large number of detection fibers. In the photon counting setup, 4
photomultipliers are connected to a Time Correlated Single Photon Counting (TCSPC) board, providing a better
temporal resolution (0.1 ps) at the expense of a limited number of detection fibers (4).
At last, we show that the limited number of detection fibers of the photon counting setup is enough for a good
localization and dramatically improves the overall acquisition time. The photon counting approach is then validated
through the localization of fluorescent inclusions in a prostate-mimicking phantom.
To increase prostate cancer diagnosis sensibility, we propose to add an optical modality to an US biopsy tool to localize
fluorophore marked tumors. Optical signals are acquired on a time-resolved acquisition chain composed by a 770 nm
femtosecond laser source and a four channels TCSPC device. The fluorescence concentration is reconstructed by using
intensity and mean time of flight acquired from each time-resolved source-detector signal. Validation experiments are
performed on a phantom mimicking prostate both on its optical and ultrasound properties with 10 μmol/L ICG 1 cm deep double fluorescent inclusions to simulate marked tumors. An exhaustive search algorithm succeeded in reconstructing the two distinct fluorescence dots with correct locations.
Optical imaging of fluorescent probes is an essential tool for investigation of molecular events in small animals for drug developments. In order to get localization and quantification information of fluorescent labels, CEA-LETI has developed efficient approaches in classical reflectance imaging as well as in diffuse optical tomographic imaging with continuous and temporal signals. This paper presents an overview of the different approaches investigated and their performances. High quality fluorescence reflectance imaging is obtained thanks to the development of an original "multiple wavelengths" system. The uniformity of the excitation light surface area is better than 15%. Combined with the use of adapted fluorescent probes, this system enables an accurate detection of pathological tissues, such as nodules, beneath the animal's observed area. Performances for the detection of ovarian nodules on a nude mouse are shown. In order to investigate deeper inside animals and get 3D localization, diffuse optical tomography systems are being developed for both slab and cylindrical geometries. For these two geometries, our reconstruction algorithms are based on analytical expression of light diffusion. Thanks to an accurate introduction of light/matter interaction process in the algorithms, high quality reconstructions of tumors in mice have been obtained. Reconstruction of lung tumors on mice are presented.
By the use of temporal diffuse optical imaging, localization and quantification performances can be improved at the price of a more sophisticated acquisition system and more elaborate information processing methods. Such a system based on a pulsed laser diode and a time correlated single photon counting system has been set up. Performances of this system for localization and quantification of fluorescent probes are presented.
Among the different existing techniques in optical molecular imaging, time-domain approaches can supply information on the probe concentration or localization, in case of specific fluorescent labelling. We present an experimental validation of an analytical solution to the time-domain fluorescence diffusion equation in an infinite medium. A fitting method issued from frequency domain calculations is also presented. The instrumentation employs a pulsed laser diode as light source, optical fibres, and a photomultiplier as the detector in a time correlated single photon counting (TCSPC) system. Measurements were performed on tissue simulating phantoms containing a small fluorescent inclusion, with the fibres either imbedded deep within the volume or placed at the surface, above the inclusion. Good adequacy was found between the simulations and the within medium measurements. We also demonstrate good performances of the method to recover the fluorophore localization.
The determination of optical properties of a semi-infinite medium such as biological tissue has been widely investigated by many authors. Reflectance formulas can be derived from the diffusion equation for different boundary conditions at the medium-air interface. This quantity can be measured at the medium surface.
For realistic objects, such as a mouse, tissue optical properties can only be determined at the object surface. However, near the surface, the diffusion approximation is weak and boundary models have to be considered. In order to investigate the validity of the time resolved reflectance approach at the object boundary, we have estimated optical properties of a liquid semi-infinite medium by this method for different boundary conditions and different positions of the fibers beneath the surface.The time-correlated single photon counting (TCSPC) technique is used to measure the reflectance curve. Our liquid phantoms are made of water, white paint and Ink. Laser light is delivered by a pulsed laser diode. Measurements are then fitted to theoretical solutions expressed as a function of source and detector’s depths and distance.By taking as reference the optical properties obtained from the infinite model for fibers deeply immersed, the influence of the different boundary conditions and bias induced are established for different fibers' depths and a variety of solutions. This influence is analyzed by comparing evolution of the reflectance models, as well as estimations of absorption and reduced scattering coefficients.
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