Tissue-simulating Phantoms Research Articles

Multimodal optical imaging of the oculofacial region using a solid tissue-simulating facial phantom.

Spatial frequency domain imaging (SFDI) applies patterned near-infrared illumination to quantify the optical properties of subsurface tissue. The periocular region is unique due to its complex ocular adnexal anatomy. Although SFDI has been successfully applied to relatively flat in vivo tissues, regions that have significant height variations and curvature may result in optical property inaccuracies. We characterize the geometric impact of the periocular region on SFDI imaging reliability. SFDI was employed to measure the reduced scattering coefficient ( ) and absorption coefficient ( ) of the periocular region in a cast facial tissue-simulating phantom by capturing images along regions of interest (ROIs): inferior temporal quadrant (ITQ), inferior nasal quadrant (INQ), superior temporal quadrant (STQ), central eyelid margin (CEM), rostral lateral nasal bridge (RLNB), and forehead (FH). The phantom was placed on a chin rest and imaged nine times from an "en face" or "side profile" position, and the flat back of the phantom was measured 15 times. The measured and of a cast facial phantom are accurate when comparing the ITQ, INQ, STQ, and FH to its flat posterior surface. Paired tests of ITQ, INQ, STQ, and FH and concluded that there is not enough evidence to suggest that imaging orientation impacted the measurement accuracy. Regions of extreme topographical variation, i.e., CEM and RLNB, did exhibit differences in measured optical properties. We are the first to evaluate the geometric implications of wide-field imaging along the periocular region using a solid tissue-simulating facial phantom. Results suggest that the ITQ, INQ, STQ, and FH of a generalized face have minimal impact on the SFDI measurement accuracy. Areas with heightened topographic variation exhibit measurement variability. Device and facial positioning do not appear to bias measurements. These findings confirm the need to carefully select ROIs when measuring optical properties along the periocular region.

Noninvasive Temperature Measurements in Tissue-Simulating Phantoms Using a Solid-State Near-Infrared Sensor.

The monitoring of body temperature is a recent addition to the plethora of parameters provided by wellness and fitness wearable devices. Current wearable temperature measurements are made at the skin surface, a measurement that is impacted by the ambient environment of the individual. The use of near-infrared spectroscopy provides the potential for a measurement below the epidermal layer of skin, thereby having the potential advantage of being more reflective of physiological conditions. The feasibility of noninvasive temperature measurements is demonstrated by using an in vitro model designed to mimic the near-infrared spectra of skin. A miniaturizable solid-state laser-diode-based near-infrared spectrometer was used to collect diffuse reflectance spectra for a set of seven tissue phantoms composed of different amounts of water, gelatin, and Intralipid. Temperatures were varied between 20-24 °C while collecting these spectra. Two types of partial least squares (PLS) calibration models were developed to evaluate the analytical utility of this approach. In both cases, the collected spectra were used without pre-processing and the number of latent variables was the only optimized parameter. The first approach involved splitting the whole dataset into separate calibration and prediction subsets for which a single optimized PLS model was developed. For this first case, the coefficient of determination (R2) is 0.95 and the standard error of prediction (SEP) is 0.22 °C for temperature predictions. The second strategy used a leave-one-phantom-out methodology that resulted in seven PLS models, each predicting the temperatures for all spectra in the held-out phantom. For this set of phantom-specific predicted temperatures, R2 and SEP values range from 0.67-0.99 and 0.19-0.65 °C, respectively. The stability and reproducibility of the sample-to-spectrometer interface are identified as major sources of spectral variance within and between phantoms. Overall, results from this in vitro study justify the development of future in vivo measurement technologies for applications as wearables for continuous, real-time monitoring of body temperature for both healthy and ill individuals.

An essentially radiation-transparent body coil integrated with a patient rotation system for MR-guided particle therapy.

The pursuit of adaptive radiotherapy using MR imaging for better precision in patient positioning puts stringent demands on the hardware components of the MR scanner. Particularly in particle therapy, the dose distribution and thus the efficacy of the treatment is susceptible to beam attenuation from interfering materials in the irradiation path. This severely limits the usefulness of conventional imaging coils, which contain highly attenuating parts such as capacitors and preamplifiers in an unknown position, and requires development of a dedicated radiofrequency (RF) coil with close consideration of the materials and components used. In MR-guided radiation therapy in the human torso, imaging coils with a large FOV and homogeneous B1 field distribution are required for reliable tissue classification. In this work, an imaging coil for MR-guided particle therapy was developed with minimal ion attenuation while maintaining flexibility in treatment. A birdcage coil consisting of nearly radiation-transparent materials was designed and constructed for a closed-bore 1.5 T MR system. Additionally, the coil was mounted on a rotatable patient capsule for flexible positioning of the patient relative to the beam. The ion attenuation of the RF coil was investigated in theory and via measurements of the Bragg peak position. To characterize the imaging quality of the RF coil, transmit and receive field distributions were simulated and measured inside a homogeneous tissue-simulating phantom for various rotation angles of the patient capsule ranging from 0° to 345° in steps of 15°. Furthermore, simulations with a heterogeneous human voxel model were performed to better estimate the effect of real patient loading, and the RF coil was compared to the internal body coil in terms of SNR for a full rotation of the patient capsule. The RF coil (total water equivalent thickness (WET) ≈ 420µm, WET of conductor ≈ 210µm) can be considered to be radiation-transparent, and a measured transmit power efficiency (B1 +/ ) between 0.17 µT/ and 0.26 µT/ could be achieved in a volume (Δz=216mm, complete x and y range) for the 24 investigated rotation angles of the patient capsule. Furthermore, homogeneous transmit and receive field distributions were measured and simulated in the transverse, coronal and sagittal planes in a homogeneous phantom and a human voxel model. In addition, the SNR of the radiation-transparent RF coil varied between 103 and 150, in the volume (Δz=216mm) of a homogeneous phantom and surpasses the SNR of the internal body coil for all rotation angles of the patient capsule. A radiation-transparent RF coil was developed and built that enables flexible patient to beam positioning via full rotation capability of the RF coil and patient relative to the beam, with results providing promising potential for adaptive MR-guided particle therapy.

Comparing fluorescent contrast agents for fluorescence guided surgery using 3-D cryo-imaging.

Fluorescence cryo-imaging is a high-resolution optical imaging technique that produces 3-D whole-body biodistributions of fluorescent molecules within an animal specimen. To accomplish this, animal specimens are administered a fluorescent molecule or reporter and are frozen to be autonomously sectioned and imaged at a temperature of -20°C or below. Thus, to apply this technique effectively, administered fluorescent molecules should be relatively invariant to low temperature conditions for cryo-imaging and ideally the fluorescence intensity should be stable and consistent in both physiological and cryo-imaging conditions. Herein, we assessed the mean fluorescence intensity of 11 fluorescent contrast agents as they are frozen in a tissue-simulating phantom experiment and show an example of a tested fluorescent contrast agent in a cryo-imaged whole pig brain. Most fluorescent contrast agents were stable within ~25% except for FITC and PEGylated FITC derivatives, which showed a dramatic decrease in fluorescence intensity when frozen.

Gold nanoparticle-mediated photothermal therapy guidance with multi-wavelength photomagnetic imaging

Difficulty in heating tumors with high spatial selectivity while protecting surrounding healthy tissues from thermal harm is a challenge for cancer photothermal treatment (PTT). To mitigate this problem, PTT mediated by photothermal agents (PTAs) has been established as a potential therapeutic technique to boost selectivity and reduce damage to surrounding healthy tissues. Various gold nanoparticles (AuNP) have been effectively utilized as PTAs, mainly using strategies to target cancerous tissue and increase selective thermal damage. Meanwhile, imaging can be used in tandem to monitor the AuNP distribution and guide the PTT. Mainly, the parameters impacting the induced temperature can be determined using simulation tools before treatment for effective PTT. However, accurate simulations can only be performed if the amount of AuNPs accumulated in the tumor is known. This study introduces Photo-Magnetic Imaging (PMI), which can appropriately recover the AuNP concentration to guide the PTT. Using multi-wavelength measurements, PMI can provide AuNP concentration based on their distinct absorption spectra. Tissue-simulating phantom studies are conducted to demonstrate the potential of PMI in recovering AuNP concentration for PTT planning. The recovered AuNP concentration is used to model the temperature increase accurately in a small inclusion representing tumor using a multiphysics solver that takes into account the light propagation and heat diffusion in turbid media.

Short-wave infrared fluorescence imaging of near-infrared dyes with robust end-tail emission using a small-animal imaging device.

Commercially available near-infrared (NIR) dyes, including indocyanine green (ICG), display an end-tail of the fluorescence emission spectrum detectable in the short-wave infrared (SWIR) window. Imaging methods based on the second NIR spectral region (1,000-1,700 nm) are gaining interest within the biomedical imaging community due to minimal autofluorescence and scattering, allowing higher spatial resolution and depth sensitivity. Using a SWIR fluorescence imaging device, the properties of ICG vs. heptamethine cyanine dyes with emission >800 nm were evaluated using tissue-simulating phantoms and animal experiments. In this study, we tested the hypothesis that an increased rigidity of the heptamethine chain may increase the SWIR imaging performance due to the bathochromic shift of the emission spectrum. Fluorescence SWIR imaging of capillary plastic tubes filled with dyes was followed by experiments on healthy animals in which a time series of fluorescence hindlimb images were analyzed. Our findings suggest that higher spatial resolution can be achieved even at greater depths (>5 mm) or longer wavelengths (>1,100 nm), in both tissue phantoms and animals, opening the possibility to translate the SWIR prototype toward clinical application.

A birefringent spectral demultiplexer enables fast hyper-spectral imaging of protoporphyrin IX during neurosurgery

Hyperspectral imaging and spectral analysis quantifies fluorophore concentration during fluorescence-guided surgery1–6. However, acquisition of the multiple wavelengths required to implement these methods can be time-consuming and hinder surgical workflow. To this end, a snapshot hyperspectral imaging system capable of acquiring 64 channels of spectral data simultaneously was developed for rapid hyperspectral imaging during neurosurgery. The system uses a birefringent spectral demultiplexer to split incoming light and redirect wavelengths to different sections of a large format microscope sensor. Its configuration achieves high optical throughput, accepts unpolarized input light and exceeds channel count of prior image-replicating imaging spectrometers by 4-fold. Tissue-simulating phantoms consisting of serial dilutions of the fluorescent agent characterize system linearity and sensitivity, and comparisons to performance of a liquid crystal tunable filter based hyperspectral imaging device are favorable. The new instrument showed comparable, if not improved, sensitivity at low fluorophore concentrations; yet, acquired wide-field images at more than 70-fold increase in frame rate. Image data acquired in the operating room during human brain tumor resection confirm these findings. The new device is an important advance in achieving real-time quantitative imaging of fluorophore concentration for guiding surgery.

A real-time IR navigation system for pleural photodynamic therapy with a 3D surface acquisition system.

Photodynamic therapy (PDT) has been used intraoperatively to treat patients with malignant pleural mesothelioma. For the efficiency of PDT, it is crucial to deliver light doses uniformly. The current procedure utilizes eight light detectors placed inside the pleural cavity to monitor the light. An updated navigation system, combined with a novel scanning system, is developed to provide real-time guidance for physicians during pleural PDT to improve light delivery. The scanning system consists of two handheld three-dimensional (3D) scanners to capture the pleural cavity's surface topographies quickly and precisely before PDT so that the target surface can be identified for real-time light fluence distribution calculation during PDT. An algorithm is developed to further process the scanned volume to denoise for accurate light fluence calculation and rotate the local coordinate system into any desired direction for a clear visualization during the real-time guidance. The navigation coordinate system is registered to the patient coordinate system utilizing at least three markers to track the light source point position within the pleural cavity throughout the treatment. During PDT, the light source position, the scanned pleural cavity, and the light fluence distribution for the cavity's surface will be displayed in 3D and 2D, respectively. For validation, this novel system is tested using phantom studies with a large chest phantom and 3D-printed lung phantoms of different volumes based on a personal CT scan, immersed in a liquid tissue-simulating phantom with different optical properties, and treated with eight isotropic detectors and the navigation system.

Detection and differentiation of semi-transparent materials simulating biological structures using optical coherence tomography: a phantom study.

.SignificanceLymphatic and peripheral nervous system imaging is of prime importance for monitoring various important pathologic processes including cancer development and metastasis, and response to therapy.AimOptical coherence tomography (OCT) is a promising approach for this imaging task but is challenged by the near-transparent nature of these structures. Our aim is to detect and differentiate semi-transparent materials using OCT texture analysis, toward label-free neurography and lymphography.ApproachWe have recently demonstrated an innovative OCT texture analysis-based approach that used speckle statistics to image lymphatics and nerves in-vivo that does not rely on negative contrast. However, these two near-transparent structures could not be easily differentiated from each other in the texture analysis parameter space. Here, we perform a rigorous follow-up study to improve upon this differentiation in controlled phantoms mimicking the optical properties of these tissues.ResultsThe results of the three-parameter Rayleigh distribution fit to the OCT images of six types of tissue-mimicking materials varying in transparency and biophysical properties demonstrate clear differences between them, suggesting routes for improved lymphatics-nerves differentiation.ConclusionsWe demonstrate a novel OCT texture analysis-based lymphatics-nerves differentiation methodology in tissue-simulating phantoms. Future work will focus on longitudinal in-vivo lymphangiography and neurography in response to cancer therapeutics toward adaptive personalized medicine.

Shortwave infrared spatial frequency domain imaging for non-invasive measurement of tissue and blood optical properties.

.SignificanceThe shortwave infrared (SWIR) optical window (∼900 to 2000 nm) has attracted interest for deep tissue imaging due to the lower scattering of light. SWIR spatial frequency domain imaging (SWIR SFDI) provides wide-field tissue optical property measurements in this wavelength band. Key design and performance characteristics, such as portability, wavelength selection, measurement resolution, and the effect of skin have not yet been addressed for SWIR SFDI.AimTo fabricate and characterize a SWIR SFDI system for clinical use.ApproachThe optimal choice of wavelengths was identified based on optical property uncertainty estimates and imaging depth. A compact light-emitting diode-based dual wavelength SWIR SFDI system was fabricated. A two-layer inverse model was developed to account for the layered structure of skin. Performance was validated using tissue-simulating phantoms and in-vivo measurements from three healthy subjects.ResultsThe SWIR SFDI system had a resolution of at least at 880 nm and at 1100 nm. The two-layer inverse model reduced the error in deeper layer extractions by at least 24% in the phantom study. The two-layer model also increased the contrast between superficial vessels and the surrounding tissue for in-vivo measurements.ConclusionThe clinic-ready SWIR SFDI device is sensitive to small optical property alterations in diffuse media, provides enhanced accuracy in quantifying optical properties in the deeper layers in phantoms, and provided enhanced contrast of subcutaneous blood vessels.

Autofluorescence detection and co-axial projection for intraoperative localization of parathyroid gland

BackgroundNear-infrared (NIR) autofluorescence detection is an effective method for identifying parathyroid glands (PGs) in thyroidectomy or parathyroidectomy. Fiber optical probes provide quantitative autofluorescence measurements for PG detection owing to its high sensitivity and high excitation light cut-off efficiency at a fixed detection distance. However, an optical fiber probe lacks the imaging capability and cannot map the autofluorescence distribution on top of normal tissue background. Therefore, there is a need for intraoperative mapping of PGs with high sensitivity and imaging resolution.MethodsWe have developed a fluorescence scanning and projection (FSP) system that combines a scanning probe and a co-axial projector for intraoperative localization and in situ display of PGs. Some of the key performance characteristics, including spatial resolution and sensitivity for detection, spatial resolution for imaging, dynamic time latency, and PG localization capability, are characterized and verified by benchtop experiments. Clinical utility of the system is simulated by a fluorescence-guided PG localization surgery on a tissue-simulating phantom and validated in an ex vivo experiment.ResultsThe system is able to detect indocyanine green (ICG) solution of 5 pM at a high signal-to-noise ratio (SNR). Additionally, it has a maximal projection error of 0.92 mm, an averaged projection error of 0.5 ± 0.23 mm, and an imaging resolution of 748 μm at a working distance ranging from 35 to 55 cm. The dynamic testing yields a short latency of 153 ± 54 ms, allowing for intraoperative scanning on target tissue during a surgical intervention. The simulated fluorescence-guided PG localization surgery has validated the system’s capability to locate PG phantom with operating room ambient light interference. The simulation experiment on the PG phantom yields a position detection bias of 0.36 ± 0.17 mm, and an area intersection over unit (IoU) of 76.6% ± 6.4%. Fluorescence intensity attenuates exponentially with the thickness of covered tissue over the PG phantom, indicating the need to remove surrounding tissue in order to reveal the weak autofluorescence signal from PGs. The ex vivo experiment demonstrates the technical feasibility of the FSP system for intraoperative PG localization with accuracy.ConclusionWe have developed a novel probe-based imaging and navigation system with high sensitivity for fluorescence detection, capability for fluorescence image reconstruction, multimodal image fusion and in situ PG display function. Our studies have demonstrated its clinical potential for intraoperative localization and in situ display of PGs in thyroidectomy or parathyroidectomy.

3D-printed tissue-simulating phantoms for near-infrared fluorescence imaging of rheumatoid diseases.

.SignificanceFluorescence imaging of rheumatoid diseases with indocyanine green (ICG) is an emerging technique with unique potential for diagnosis and therapy. Device characterization, monitoring of the performance, and further developments of the technique require tissue-equivalent fluorescent phantoms of high stability with appropriate anatomical shapes.AimOur investigations aim at the development of a three-dimensional (3D) printing technique to fabricate hand and finger models with appropriate optical properties in the near-infrared spectral range. These phantoms should have fluorescence properties similar to ICG, and excellent photostability and durability over years.ApproachWe modified a 3D printing methacrylate photopolymer by adding the fluorescent dye Lumogen IR 765 to the raw material. Reduced scattering and absorption coefficients were adjusted to values representative of the human hand by incorporating titanium dioxide powder and black ink. The properties of printed phantoms of various compositions were characterized using UV/Vis and fluorescence spectroscopy, and time-resolved measurements. Photostability and bleaching were investigated with a hand imager. For comparison, several phantoms with ICG as fluorescent dye were printed and characterized as well.ResultsThe spectral properties of Lumogen IR 765 are very similar to those of ICG. By optimizing the concentrations of Lumogen, titanium dioxide, and ink, anatomically shaped hand and vessel models with properties equivalent to in vivo investigations with a fluorescence hand imager could be printed. Phantoms with Lumogen IR 765 had an excellent photostability over up to 4 years. In contrast, phantoms printed with ICG showed significant bleaching and degradation of fluorescence over time.Conclusions3D printing of phantoms with Lumogen IR 765 is a promising method for fabricating anatomically shaped fluorescent tissue models of excellent stability with spectral properties similar to ICG. The phantoms are well-suited to monitor the performance of hand imagers. Concepts can easily be transferred to other fluorescence imaging applications of ICG.

Characterization of pasteurized milk in the near infrared range for construction of tissue-mimicking optical phantoms

Optical phantoms have been indispensable tools for validating the performance of biomedical optical devices. Low-cost and readily available materials are gaining great interest for the construction of biomedical optical phantoms. The main objective of this work is to investigate the feasibility of using commercial pasteurized milk as a scattering component of optical phantoms. To that end, milk samples with varying concentrations were prepared. Transmittance and diffuse reflectance spectroscopy at 690 and 830 nm were measured for milk samples. Then, the optical properties of pasteurized milk were determined. The results demonstrate the suitability of using pasteurized milk as a potential scattering element for building tissue-simulating optical phantoms in the NIR range of wavelength. Low fat pasteurized milk samples outperformed full-fat milk samples resulting in lower uncertainty levels in estimating scattering coefficient at 690 and 830 nm. The effect of batch-to-batch variation on scattering coefficient evaluation is investigated and discussed. The preliminary findings of this work provide a base for the rapid preparation of scattering-dependent optical phantoms needed for the validation and calibration of biomedical optical instrumentation.

Evaluation of the robustness of cerebral oximetry to variations in skin pigmentation using a tissue-simulating phantom.

Clinical studies have demonstrated that epidermal pigmentation level can affect cerebral oximetry measurements. To evaluate the robustness of these devices, we have developed a phantom-based test method that includes an epidermis-simulating layer with several melanin concentrations and a 3D-printed cerebrovascular module. Measurements were performed with neonatal, pediatric and adult sensors from two commercial oximeters, where neonatal probes had shorter source-detector separation distances. Referenced blood oxygenation levels ranged from 30 to 90%. Cerebral oximeter outputs exhibited a consistent decrease in saturation level with simulated melanin content; this effect was greatest at low saturation levels, producing a change of up to 15%. Dependence on pigmentation was strongest in a neonatal sensor, possibly due to its high reflectivity. Overall, our findings indicate that a modular channel-array phantom approach can provide a practical tool for assessing the impact of skin pigmentation on cerebral oximeter performance and that modifications to algorithms and/or instrumentation may be needed to mitigate pigmentation bias.

Validation of multispectral singlet oxygen luminescence dosimetry (MSOLD) for photofrin-mediated photodynamic therapy.

Accurate dosimetry is crucial for the ongoing development and clinical study of photodynamic therapy (PDT). Current dosimetry standards range from less accurate methods involving measurement of only light fluence and photosensitizer concentration during treatment, to significantly improved methods such as singlet oxygen explicit dosimetry (SOED), a macroscopic model that includes an additional important parameter in its dosimetric calculations: ground-state oxygen concentration ([3O2]). However, neither of these models is a method of direct dosimetry. Multispectral singlet oxygen luminescence dosimetry (MSOLD) shows promise in this regard but requires significant improvement in signal quality and remains to be validated in a clinical setting. In this study, we validate a linearly increasing MSOLD signal with an InGaAs photodiode detector for increasing concentration (0 mg/kg to 200 mg/kg) in tissue-simulating phantoms containing photofrin, calculating a calibration curve based on 1270 nm peak-intensity signal and area under the curve for background-subtracted singlet oxygen emission. Additionally, we validate MSOLD against the current clinical dosimetry standard, SOED, through simultaneous measurement of SOED parameters and MSOLD signal for varying concentrations (50 μM - 300 μM). Finally, we investigate the effects of using very high gain amplification on InGaAs photodiode detectors to amplify the MSOLD signal for use in clinical models. We show that a calibration curve relating photosensitizer concentration (PS) and MSOLD signal can be established. Additionally, we demonstrate good correlation between MSOLD signal and SOED-calculated [1O2]rx. However, we show that when using high amplification on InGaAs photodiodes for long illumination times, the inherent instability in these detectors becomes apparent.

Real-time PDT Dose Dosimetry for Pleural Photodynamic Therapy.

PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), an eight-channel PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously from eight different sites in the pleural cavity during PDT. An isotropic detector with bifurcated fibers was used for each channel to ensure detected light was split equally to the photodiode and spectrometer. The light fluence rate distribution is monitored using an IR navigation system. The navigation system allows 2D light fluence mapping throughout the whole pleural cavity rather than just the selected points. The fluorescence signal is normalized by the light fluence measured at treatment wavelength. We have shown that the absolute photosensitizer concentration can be obtained by applying optical properties correction and linear spectral fitting to the measured fluorescence data. The detection limit and the optical property correction factor of each channel were determined and validated using tissue-simulating phantoms with known varying concentration of Photofrin. Tissue optical properties are determined using an absorption spectroscopy probe immediately before PDT at the same sites. The combination of 8-channel PDT dosimeter system and IR navigation system, which can calculate light fluence rate in the pleural cavity in real-time, providing a mean to determine the distribution of PDT dose on the entire pleural cavity to investigate the heterogeneity of PDT dose on the pleural cavity.

Preclinical evaluation of a clinical prototype transrectal diffuse optical tomography system for monitoring photothermal therapy of focal prostate cancer.

.Significance: Our work demonstrates in preclinical models that continuous-wave transrectal diffuse optical tomography (TRDOT) can be used to accurately monitor photothermal therapy (PTT) and, in particular, the progression of the photocoagulation boundary toward the rectum. When used in patients, this should prevent rectal damage during PTT, thereby achieving maximum treatment efficacy while ensuring safety, using a technology platform suitable for wide dissemination.Aim: We aim to validate that TRDOT measurements analyzed using a shape-based image-reconstruction algorithm (SBDOT) allow localization of the photocoagulation boundary during PTT within toward the rectum in the transverse plane.Approach: TRDOT measurements were performed in tissue-simulating phantoms, ex vivo tissues, and an in vivo canine prostate model. The accuracy and sensitivity of reconstructing the size and location of the coagulation zone were determined, based on changes in the tissue absorption and reduced scattering coefficients upon photocoagulation. The reconstruction also yields the native and coagulated tissue optical properties.Results: The TRDOT measurements and SBDOT reconstruction algorithm were confirmed to perform sufficiently well for clinical translation in PTT monitoring, recovering the location of the coagulation boundary within compared to the true value as determined by direct visualization postexcision and/or MRI.Conclusions: Implementing previously described TRDOT instrumentation and SBDOT image reconstruction in different tissue models confirms the potential for clinincal translation, including required refinements of the system and reconstruction algorithm.

Imaging Radiotherapy-Induced Cherenkov Emission in Color

<h3>Purpose/Objective(s)</h3> In the last decade, Cherenkov imaging has been demonstrated as a useful clinical technique both for real-time surface dose visualization during patient treatment and for various high-resolution QA measurements. However there remains much work to be done in the development of Cherenkov-based in vivo dosimetry. In this work, the concept of in vivo color Cherenkov imaging is introduced. It is hypothesized that Cherenkov images with sensitivity to the spectral quality of Cherenkov emission induced inside tissue can provide increased information about tissue composition as opposed to monochromatic, red-weighted images used in prior work. <h3>Materials/Methods</h3> A custom Color Cherenkov camera was created from three time-gated intensified CMOS cameras, each with varying spectral sensitivity of the photocathode, and sharing one imaging lens. A dichroic mirror assembly allowed for incoming Cherenkov light signals to be redirected according to wavelength to the appropriate camera resulting in three raw image stacks for each acquisition. These images were then reconstructed into three-channel color images via color calibration, summed, and background subtracted. In vivo color Cherenkov images of three right-sided breast patients were acquired for one treatment fraction each as part of an IRB-approved clinical trial. These images were interpreted alongside images of liquid tissue-simulating phantoms that matched tissue optical properties. Variations in oxygenation and blood volume were mimicked in this way, and the data was used to interpret the clinical images. Impacts on Cherenkov emission spectra from tissue under these various conditions were also estimated. <h3>Results</h3> The presence of oxygenated vs deoxygenated blood in tissue has a visible impact on the color of Cherenkov emission, leading to a redder hue due to decreased attenuation of red wavelengths by oxyhemoglobin, similar to erythema or blush of tissue. This was verified in the tissue phantoms. Variations in blood concentration produce a strong blue-red trend in color space (R² = 0.96), as verified by detailed analysis. Color Cherenkov images of right breast radiotherapy treatments displayed pink regions across the breast coincident with the treated area for all three patients, and the variations in color were interpreted relative to the phantom data. <h3>Conclusion</h3> This first investigation of color Cherenkov imaging uncovered the natural relationship between tissue composition and the spectral quality of emitted Cherenkov light. The correlation between blood content and color will be translated in future work to in vivo sensing of variations in fat and fibroglandular content in irradiated tissues. These findings will allow for the correction of Cherenkov images to produce accurate in vivo surface dose maps during patient treatments.

Fast diffuse correlation spectroscopy with a low-cost, fiber-less embedded diode laser.

Diffuse correlation spectroscopy (DCS), a popular optical technique for fast noninvasive measurement of blood flow, is commonly implemented using expensive fiber-coupled long coherence length laser systems. Here, we report the development of a portable and fiber-less approach that can be used as a low-cost alternative to illuminate tissue in DCS instruments. We validate the accuracy and noise characteristics of the fiber-less DCS laser source, by comparisons against traditional DCS light sources, with experiments on controlled tissue-simulating phantoms and in humans.

Extraction of tissue optical property and blood flow from speckle contrast diffuse correlation tomography (scDCT) measurements.

Measurement of blood flow in tissue provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. A noncontact, camera-based, near-infrared speckle contrast diffuse correlation tomography (scDCT) technique has been recently developed for 3D imaging of blood flow index (αDB) distributions in deep tissues up to a centimeter. A limitation with the continuous-wave scDCT measurement of blood flow is the assumption of constant and homogenous tissue absorption coefficient (μ a ). The present study took the advantage of rapid, high-density, noncontact scDCT measurements of both light intensities and diffuse speckle contrast at multiple source-detector distances and developed two-step fitting algorithms for extracting both μ a and αDB. The new algorithms were tested in tissue-simulating phantoms with known optical properties and human forearms. Measurement results were compared against established near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) techniques. The accuracies of our new fitting algorithms with scDCT measurements in phantoms (up to 16% errors) and forearms (up to 23% errors) are comparable to relevant study results (up to 25% errors). Knowledge of μ a not only improved the accuracy in calculating αDB but also provided the potential for quantifying tissue blood oxygenation via spectral measurements. A multiple-wavelength scDCT system with new algorithms is currently developing to fit multi-wavelength and multi-distance data for 3D imaging of both blood flow and oxygenation distributions in deep tissues.