The capabilities of ultrasound optical tomography (UOT) is investigated through Monte Carlo simulations on realistic breast tissue phantoms constructed using the OpenVCT platform. This work indicates that UOT is a method capable of distinguishing malignant tumor tissue from benign glandular tissue deep inside the breast, despite the natural variations of adipose and glandular compartments within a breast or between breasts with different volume breast densities.
Each year, about 30% of all newly diagnosed cancer cases in women worldwide are breast cancers [1]. One of the most common techniques for breast cancer diagnosis is mammography. However, this technique provides limited functional information regarding breast tissue morphology. In cases of suspected malignancy invasive techniques such as biopsy are implemented.
In this work an optical deep tissue imaging technique called ultrasound optical tomography (UOT) which combines laser light and ultrasound is implemented for a non-invasive lesion (tumour) characterization in breast tissue.
The experiments were performed using 794 nm laser wavelength, 6 MHz ultrasound frequency and a narrowband spectral filter material, Tm3+:LiNbO3. The measurements were carried out in 5 cm thick agar phantoms using a range of tumor mimicking inclusions of 3 different sizes.
This work is the first deep tissue imaging demonstration using UOT at tissue relevant wavelengths. Current results indicate that the UOT technique can become an important and valuable tool for lesion characterization in breast tissue.
Ultrasound Optical Tomography (UOT) combines the high-resolution imaging capability of ultrasound with measurements of light absorption and scattering properties of human tissue. This non-invasive technique could distinguish between cancerous and non-cancerous lesions inside the breast tissue, follow tumor shrinkage during pre-operative treatment, or provide information on blood oxygenation levels. Recent measurements of phantoms mimicking the optical properties of breast tissue with various lesions indicated that the technique can probe 50 mm deep through the tissue. This work concentrates on developing the UOT setup in transmission mode and discusses its advantages, limitations, and possible improvements.
We propose a novel analytical time-domain model for migration of Raman scattered photons in inhomogeneous two-layer diffusive media. Based on this model, the methods for reconstruction of the Raman spectra of the two layers are developed, tested in simulations and validated on phantom measurements data.
Significance: Despite remarkable advances in the core modalities used in combating cancer, malignant diseases remain the second largest cause of death globally. Interstitial photodynamic therapy (IPDT) has emerged as an alternative approach for the treatment of solid tumors.
Aim: The aim of our study is to outline the advancements in IPDT in recent years and provide our vision for the inclusion of IPDT in standard-of-care (SoC) treatment guidelines of specific malignant diseases.
Approach: First, the SoC treatment for solid tumors is described, and the attractive properties of IPDT are presented. Second, the application of IPDT for selected types of tumors is discussed. Finally, future opportunities are considered.
Results: Strong research efforts in academic, clinical, and industrial settings have led to significant improvements in the current implementation of IPDT, and these studies have demonstrated the unique advantages of this modality for the treatment of solid tumors. It is envisioned that further randomized prospective clinical trials and treatment optimization will enable a wide acceptance of IPDT in the clinical community and inclusion in SoC guidelines for well-defined clinical indications.
Conclusions: The minimally invasive nature of this treatment modality combined with the relatively mild side effects makes IPDT a compelling alternative option for treatment in a number of clinical applications. The adaptability of this technique provides many opportunities to both optimize and personalize the treatment.
Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose–response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.
The first results from a clinical study for Temoporfin-mediated photodynamic therapy (PDT) of low-grade (T1c) primary prostate cancer using online dosimetry are presented. Dosimetric feedback in real time was applied, for the first time to our knowledge, in interstitial photodynamic therapy. The dosimetry software IDOSE provided dose plans, including optical fiber positions and light doses based on 3-D tissue models generated from ultrasound images. Tissue optical property measurements were obtained using the same fibers used for light delivery. Measurements were taken before, during, and after the treatment session. On the basis of these real-time measured optical properties, the light-dose plan was recalculated. The aim of the treatment was to ablate the entire prostate while minimizing exposure to surrounding organs. The results indicate that online dosimetry based on real-time tissue optical property measurements enabled the light dose to be adapted and optimized. However, histopathological analysis of tissue biopsies taken six months post-PDT treatment showed there were still residual viable cancer cells present in the prostate tissue sections. The authors propose that the incomplete treatment of the prostate tissue could be due to a too low light threshold dose, which was set to 5 J/cm2.
Photodynamic therapy (PDT) for the treatment of prostate cancer has been demonstrated to be a safe treatment
option capable of inducing tissue necrosis and decrease in prostate specific antigen (PSA). Research groups report
on large variations in treatment response, possibly due to biological variations in tissue composition and short-term
response to the therapeutic irradiation. Within our group, an instrument for interstitial PDT on prostate
tissue that incorporates realtime treatment feedback is being developed. The treatment protocol consists of
two parts. The first part incorporates the pre-treatment plan with ultrasound investigations, providing the
geometry for the prostate gland and surrounding risk organs, an iterative random-search algorithm to determine
near-optimal fiber positions within the reconstructed geometry and a Block-Cimmino optimization algorithm for
predicting individual fiber irradiation times. During the second part, the therapeutic light delivery is combined
with measurements of the light transmission signals between the optical fibers, thus monitoring the tissue effective
attenuation coefficient by means of spatially resolved spectroscopy. These data are then used as input for repeated
runs of the Block-Cimmino optimization algorithm. Thus, the irradiation times for individual fibers are updated
throughout the treatment in order to compensate for the influence of changes in tissue composition on the light
distribution at the therapeutic wavelength.
We demonstrate the feasibility of white-light time-resolved optical mammography. The instrumentation is based on supercontinuum light generated in photonic crystal fiber and 32-channel parallel time-correlated single-photon-counting detection. Total measurement time is of the order of 10 min for typical clinical applications. Preliminary measurements performed on volunteers show the ability of the system to determine tissue constituent concentrations and structure over the entire breast area. Furthermore, measurements on a tissue-like sample demonstrate detection and characterization of inclusions.
The concept of optical coherence tomography (OCT) for high-resolution imaging of tissues in vivo is introduced. Analytical and numerical models for describing and understanding the light propagation in samples imaged by OCT systems are presented. An analytical model for calculating the OCT signal based on the extended Huygens-Fresnel principle and valid both for single and multiple scattering regimes is outlined. From this model, an algorithm for extracting tissue optical properties for multi-layered tissues is derived. The algorithm is first verified for various optical properties and geometries using solid phantoms and numerical simulations. The applicability of the algorithm for extraction of tissue optical properties is then demonstrated for vascular tissue samples ex vivo. With the use of data from numerical phantoms, the validity of the OCT extraction algorithm for a two-layer geometry is further supported. It is concluded that by using optical properties extracted from OCT images of human tissues, the clinical utility of OCT imaging can be substantially increased.
We report on an instrument for time-resolved spectroscopy (TRS) based on white-light generation in a highly non-linear crystal fiber. TRS in the visible and near-infrared region at picosecond-to-nanosecond time scales has attracted increased interest in recent years owing to the possibility of spectroscopic analysis of turbid media, such as biological tissues. A self-mode-locked Ti:Sapphire oscillator pumped by an Ar:ion laser provides pulses 50 - 100 fs long, at 85 MHz repetition rate. The light is focused into a crystal fiber, which consists of a core surrounded by a mesh of air-filled holes. White light is generated by a combination of several non-linear effects in the fiber. We optimize the spectrum for measurements in the region 600 - 1000 nm. For detection, we use an imaging spectrometer coupled to a 16-channel photomultiplier tube, enabling simultaneous detection in 16 wavelength bands. We use time-correlated single-photon counting to record the signal, with a temporal resolution of ~160 ps. To demonstrate the system, we have performed measurements of the diffuse time-resolved reflectance of tissue phantoms made of epoxy resin with added scattering and absorbing materials. The data was evaluated using a light propagation model based on diffusion theory, to extract the scattering and absorption coefficients of the medium. The results corresponded very well with previous measurements on the phantoms performed using other TRS instruments.
We present a novel method for estimating the depth of a fluorescent lesion in tissue based on measurements of the fluorescence signal in different wavelength bands. The measured fluorescence spectrum following irradiation by excitation light at the surface is a function of several parameters, because the fluorescence light has to pass through tissue with characteristic scattering and absorption properties. Thus, the intrinsic fluorescence spectrum will be altered, in a way determined by the tissue optical properties, the depth of the fluorophore, and also by the geometry of the light irradiation and the detection system. By analyzing the ratio between the signals at two wavelengths we show that it is possible to estimate the depth of the lesion. We have performed Monte Carlo simulations and measurements on an Intralipid phantom in the wavelength range 850 - 1000 nm. By taking the ratio between the signals at the wavelengths 875 and 930 nm the depth of a fluorescing layer could be determined with 0.8 mm accuracy down at least a depth of 10 mm. Monte Carlo simulations were also performed for different tissue types with various composition. The results indicate that depth estimation of a lesion is possible with no assumptions made about the optical properties for a wide range of tissues.
The first, to our knowledge, in-vivo broadband spectroscopic characterization of breast tissue using different interfiber distances as well as transmittance measurements is presented. Absorption and scattering properties are measured on six healthy subjects, using time-resolved diffuse spectroscopy and an inverse model based on the diffusion equation. Wavelength-tunable picosecond-pulse lasers and time-correlated single-photon counting detection are employed, enabling fully spectroscopic measurements in the range 610 to 1040 nm. Characterization of the absorption and reduced scattering coefficients of breast tissue is made with the aim of investigating individual variations, as well as variations due to different measurement geometries. Diffuse reflectance measurements at different interfiber distances (2, 3, and 4 cm) are performed, as well as measurements in transmittance mode, meaning that different sampling volumes are involved. The results show a large variation in the absorption and scattering properties depending on the subject, correlating mainly with the water versus lipid content of the breast. Intrasubject variations, due to different interfiber distances or transmittance modes, correlate with the known structures of the breast, but these variations are small compared to the subject-to-subject variation. The intrasubject variations are larger for the scattering data than the absorption data; this is consistent with different spatial localization of the measurements of these parameters, which is explained by the photon migration theory.
Two systems for measurements of absorption and scattering properties, based on picosecond-pulse lasers and singlephoton counting detection, were characterized using a detailed protocol. The first system utilizes diode lasers at 660, 785, 910 and 974 nm as light sources. The second employs a Ti:sapphire and a mode-locked dye laser to produce tunable pulses in the range 610 - 1000 nm. Using solid tissue phantoms, the systems were rigorously characterized and compared in terms of absolute accuracy of the measured scattering and absorption coefficients, the linearity over the parameter range, the precision with respect to injected light energy, the stability over time, and the reproducibility of the results. The phantoms were made of epoxy resin with TiO as scatterer and black toner powder as absorber.
Two systems for time-resolved diffuse spectroscopy were used for the optical characterization of the female breast in 4 volunteers. A first system was a compact laser diode instrument operated at 660 and 785 nm, while the second one was a broadband laboratory set-up based on mode-locked lasers tunable in the 610-1000 nm range. Measurements were obtained both in transmittance and in reflectance geometry at 5 inter-fiber distances ranging from 1 to 4 cm at different locations on the breast. Distinct spectral features both in absorption and in scattering were observed among the 4 volunteers, and for each subject between reflectance and transmittance measurements. These differences are correlated with the abundance of the glandular tissue and blood absorption. Upon increasing the inter-fiber distance in reflectance,
deeper tissue structures were investigated, generally resulting in higher water contribution.
Time-efficient Monte Carlo models for fluorescence from layered tissue were developed. The computation time is reduced significantly by recognizing symmetry properties of the problem, and by reversing computation of the photon paths for the fluorescence light. Further reduction is obtained by using a white Monte Carlo approach, which enables scaling of the results to the desired optical properties after the simulation. The methods reduce computation time more than two orders of magnitude compared with conventional Monte Carlo code.
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.