Showing papers in "Journal of Biomedical Optics in 2013"

Laser speckle contrast imaging: theoretical and practical limitations

Abstract: When laser light illuminates a diffuse object, it produces a random interference effect known as a speckle pattern. If there is movement in the object, the speckles fluctuate in intensity. These fluctuations can provide infor- mation about the movement. A simple way of accessing this information is to image the speckle pattern with an exposure time longer than the shortest speckle fluctuation time scale—the fluctuations cause a blurring of the speckle, leading to a reduction in the local speckle contrast. Thus, velocity distributions are coded as speckle con- trast variations. The same information can be obtained by using the Doppler effect, but producing a two-dimen- sional Doppler map requires either scanning of the laser beam or imaging with a high-speed camera: laser speckle contrast imaging (LSCI) avoids the need to scan and can be performed with a normal CCD- or CMOS-camera. LSCI is used primarily to map flow systems, especially blood flow. The development of LSCI is reviewed and its lim- itations and problems are investigated. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

Review of spectral imaging technology in biomedical engineering: achievements and challenges

Abstract: Spectral imaging is a technology that integrates conventional imaging and spectroscopy to get both spatial and spectral information from an object. Although this technology was originally developed for remote sensing, it has been extended to the biomedical engineering field as a powerful analytical tool for biological and biomedical research. This review introduces the basics of spectral imaging, imaging methods, current equipment, and recent advances in biomedical applications. The performance and analytical capabilities of spectral imaging systems for biological and biomedical imaging are discussed. In particular, the current achievements and limitations of this technology in biomedical engineering are presented. The benefits and development trends of biomedical spectral imaging are highlighted to provide the reader with an insight into the current technological advances and its potential for biomedical research.

Review of Monte Carlo modeling of light transport in tissues

Abstract: A general survey is provided on the capability of Monte Carlo (MC) modeling in tissue optics while paying special attention to the recent progress in the development of methods for speeding up MC simulations. The principles of MC modeling for the simulation of light transport in tissues, which includes the general procedure of tracking an individual photon packet, common light-tissue interactions that can be simulated, frequently used tissue models, common contact/noncontact illumination and detection setups, and the treatment of time-resolved and fre- quency-domain optical measurements, are briefly described to help interested readers achieve a quick start. Following that, a variety of methods for speeding up MC simulations, which includes scaling methods, perturbation methods, hybrid methods, variance reduction techniques, parallel computation, and special methods for fluorescence simulations, as well as their respective advantages and disadvantages are discussed. Then the applications of MC methods in tissue optics, laser Doppler flowmetry, photodynamic therapy, optical coherence tomography, and diffuse opticaltomography are briefly surveyed. Finally, the potential directionsfor the future development of the MC method in tissue optics are discussed. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. (DOI: 10.1117/1.JBO.18.5.050902)

High-resolution three-dimensional imaging of red blood cells parasitized by Plasmodium falciparum and in situ hemozoin crystals using optical diffraction tomography

Abstract: We present high-resolution optical tomographic images of human red blood cells (RBC) parasitized by malaria-inducing Plasmodium falciparum (Pf)-RBCs. Three-dimensional (3-D) refractive index (RI) tomograms are reconstructed by recourse to a diffraction algorithm from multiple two-dimensional holograms with various angles of illumination. These 3-D RI tomograms of Pf-RBCs show cellular and subcellular structures of host RBCs and invaded parasites in fine detail. Full asexual intraerythrocytic stages of parasite maturation (ring to trophozoite to schizont stages) are then systematically investigated using optical diffraction tomography algorithms. These analyses provide quantitative information on the structural and chemical characteristics of individual host Pf-RBCs, parasitophorous vacuole, and cytoplasm. The in situ structural evolution and chemical characteristics of subcellular hemozoin crystals are also elucidated.

General equation for the differential pathlength factor of the frontal human head depending on wavelength and age

Abstract: Continuous-wave near-infrared spectroscopy and near-infrared imaging enable the measurement of relative concentration changes in oxy- and deoxyhemoglobin and thus hemodynamics and oxygenation. The accuracy of determined changes depends mainly on the modeling of the light transport through the probed tissue. Due to the highly scattering nature of tissue, the light path is longer than the source-detector separation (d). This is incorporated in modeling by multiplying d by a differential pathlength factor (DPF) which depends on several factors such as wavelength, age of the subject, and type of tissue. In the present work, we derive a general DPF equation for the frontal human head, incorporating dependency on wavelength and age, based on published data. We validated the equation using different data sets of experimentally determined DPFs from six independent studies.

Optical coherence tomography in dermatology

Abstract: Optical coherence tomography (OCT) is a noninvasive diagnostic method that offers a view into the superficial layers of the skin in vivo in real-time. An infrared broadband light source allows the investigation of skin architecture and changes up to a depth of 1 to 2 mm with a resolution between 15 and 3 μm, depending on the system used. Thus OCT enables evaluation of skin lesions, especially nonmelanoma skin cancers and inflammatory diseases, quantification of skin changes, visualization of parasitic infestations, and examination of other indications such as the investigation of nails. OCT provides a quick and useful diagnostic imaging technique for a number of clinical questions and is a valuable addition or complement to other noninvasive imaging tools such as dermoscopy, high-frequency ultrasound, and confocal laser scan microscopy.

Review of speckle and phase variance optical coherence tomography to visualize microvascular networks.

Abstract: High-resolution mapping of microvasculature has been applied to diverse body systems, including the retinal and choroidal vasculature, cardiac vasculature, the central nervous system, and various tumor models. Many imaging techniques have been developed to address specific research questions, and each has its own merits and drawbacks. Understanding, optimization, and proper implementation of these imaging techniques can significantly improve the data obtained along the spectrum of unique research projects to obtain diagnostic clinical information. We describe the recently developed algorithms and applications of two general classes of microvascular imaging techniques: speckle-variance and phase-variance optical coherence tomography (OCT). We compare and contrast their performance with Doppler OCT and optical microangiography. In addition, we highlight ongoing work in the development of variance-based techniques to further refine the characterization of microvascular networks.

Review of fiber-optic pressure sensors for biomedical and biomechanical applications.

Abstract: As optical fibers revolutionize the way data is carried in telecommunications, the same is happening in the world of sensing. Fiber-optic sensors (FOS) rely on the principle of changing the properties of light that propagate in the fiber due to the effect of a specific physical or chemical parameter. We demonstrate the potentialities of this sensing concept to assess pressure in biomedical and biomechanical applications. FOSs are introduced after an overview of conventional sensors that are being used in the field. Pointing out their limitations, particularly as minimally invasive sensors, is also the starting point to argue FOSs are an alternative or a substitution technology. Even so, this technology will be more or less effective depending on the efforts to present more affordable turnkey solutions and peer-reviewed papers reporting in vivo experiments and clinical trials.

Fast segmentation and high-quality three-dimensional volume mesh creation from medical images for diffuse optical tomography.

Abstract: Multimodal approaches that combine near-infrared (NIR) and conventional imaging modalities have been shown to improve optical parameter estimation dramatically and thus represent a prevailing trend in NIR imaging. These approaches typically involve applying anatomical templates from magnetic resonance imaging/computed tomography/ultrasound images to guide the recovery of optical parameters. However, merging these data sets using current technology requires multiple software packages, substantial expertise, significant time-commitment, and often results in unacceptably poor mesh quality for optical image reconstruction, a reality that represents a significant roadblock for translational research of multimodal NIR imaging. This work addresses these challenges directly by introducing automated digital imaging and communications in medicine image stack segmentation and a new one-click three-dimensional mesh generator optimized for multimodal NIR imaging, and combining these capabilities into a single software package (available for free download) with a streamlined workflow. Image processing time and mesh quality benchmarks were examined for four common multimodal NIR use-cases (breast, brain, pancreas, and small animal) and were compared to a commercial image processing package. Applying these tools resulted in a fivefold decrease in image processing time and 62% improvement in minimum mesh quality, in the absence of extra mesh postprocessing. These capabilities represent a significant step toward enabling translational multimodal NIR research for both expert and nonexpert users in an open-source platform.

Multispectral Mueller polarimetric imaging detecting residual cancer and cancer regression after neoadjuvant treatment for colorectal carcinomas.

Abstract: This work is devoted to a first exploration of Mueller polarimetric imaging for the detection of residual cancer after neoadjuvant treatment for the rectum. Three samples of colorectal carcinomas treated by radiochemotherapy together with one untreated sample are analyzed ex vivo before fixation in formalin by using a multispectral Mueller polarimetric imaging system operated from 500 to 700 nm. The Mueller images, analyzed using the Lu-Chipmann decomposition, show negligible diattenuation and retardation. The nonirradiated rectum exhibits a variation of depolarization with cancer evolution stage. At all wavelengths on irradiated samples, the contrast between the footprint of the initial tumor and surrounding healthy tissue is found to be much smaller for complete tumor regression than when a residual tumor is present, even at volume fractions of the order of 5%. This high sensitivity is attributed to the modification of stromal collagen induced by the cancer. The depolarization contrast between treated cancer and healthy tissue is found to increase monotonously with the volume fraction of residual cancer in the red part of the spectrum. Polarimetric imaging is a promising technique for detecting short-time small residual cancers, which is valuable information for pathological diagnosis and patient management by clinicians.

First human Cerenkography.

Abstract: 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.

Graphics processing unit accelerated optical coherence tomography processing at megahertz axial scan rate and high resolution video rate volumetric rendering

Abstract: In this report, we describe how to highly optimize a computer unified device architecture based platform to perform real-time processing of optical coherence tomography interferometric data and three-dimensional (3-D) volumetric rendering using a commercially available, cost-effective, graphics processing unit (GPU). The maximum complete attainable axial scan processing rate, including memory transfer and displaying B-scan frame, was 2.24 MHz for 16 bits pixel depth and 2048 fast Fourier transform size; the maximum 3-D volumetric rendering rate, including B-scan, en face view display, and 3-D rendering, was ~23 volumes/second (volume size: 1024×256×200). To the best of our knowledge, this is the fastest processing rate reported to date with a single-chip GPU and the first implementation of real-time video-rate volumetric optical coherence tomography (OCT) processing and rendering that is capable of matching the acquisition rates of ultrahigh-speed OCT.

Tracking mechanical wave propagation within tissue using phase-sensitive optical coherence tomography: motion artifact and its compensation

Abstract: We describe theoretical and experimental investigations of motion artifacts that can arise in the detection of shear wave propagating within tissue with phase-sensitive optical coherence tomography. We find that the motion artifact is a combined product of sample surface motion and refractive index difference between sample and air, which cannot be neglected when estimating the tissue motion within tissue. A method of compensating the motion artifact is demonstrated, the results of which emphasize the need for surface motion compensation when measuring the mechanical response for elastography or other biomedical applications.

Spatial frequency domain imaging of burn wounds in a preclinical model of graded burn severity.

Abstract: Frequent monitoring of early-stage burns is necessary for deciding optimal treatment and management. Both superficial and full thickness burns are relatively easy to diagnose based on clinical observation. In between these two extremes are superficial-partial thickness and deep-partial thickness burns. These burns, while visually similar, differ dramatically in terms of clinical treatment and are known to progress in severity over time. The objective of this study was to determine the potential of spatial frequency domain imaging (SFDI) for noninvasively mapping quantitative changes in chromophore and optical properties that may be an indicative of burn wound severity. A controlled protocol of graded burn severity was developed and applied to 17 rats. SFDI data was acquired at multiple near-infrared wavelengths over a course of 3 h. Burn severity was verified using hematoxylin and eosin histology. From this study, we found that changes in water concentration (edema), deoxygenated hemoglobin concentration, and optical scattering (tissue denaturation) to be statistically significant at differentiating superficial partial-thickness burns from deep-partial thickness burns.

Noise-equivalent sensitivity of photoacoustics

Abstract: The fundamental limitations of photoacoustic microscopy for detecting optically absorbing molecules are investigated both theoretically and experimentally. We experimentally demonstrate noise-equivalent detection sensitivities of 160,000 methylene blue molecules (270 zeptomol or 2.7×10^(−19) mol) and 86,000 oxygenated hemoglobin molecules (140 zeptomol) using narrowband continuous-wave photoacoustics. The ultimate sensitivity of photoacoustics is fundamentally limited by thermal noise, which can present in the acoustic detection system as well as in the medium itself. Under the optimized conditions described herein and using commercially available detectors, photoacoustic microscopy can detect as few as 100s of oxygenated hemoglobin molecules. Realizable improvements to the detector may enable single molecule detection of select molecules.

New method for detection of gastric cancer by hyperspectral imaging: a pilot study

Abstract: We developed a new, easy, and objective method to detect gastric cancer using hyperspectral imaging (HSI) technology combining spectroscopy and imaging A total of 16 gastroduodenal tumors removed by endoscopic resection or surgery from 14 patients at Yamaguchi University Hospital, Japan, were recorded using a hyperspectral camera (HSC) equipped with HSI technology Corrected spectral reflectance was obtained from 10 samples of normal mucosa and 10 samples of tumors for each case The 16 cases were divided into eight training cases (160 training samples) and eight test cases (160 test samples) We established a diagnostic algorithm with training samples and evaluated it with test samples Diagnostic capability of the algorithm for each tumor was validated, and enhancement of tumors by image processing using the HSC was evaluated The diagnostic algorithm used the 726-nm wavelength, with a cutoff point established from training samples The sensitivity, specificity, and accuracy rates of the algorithm's diagnostic capability in the test samples were 78.8% (63/80), 92.5% (74/80), and 85.6% (137/160), respectively Tumors in HSC images of 13 (81.3%) cases were well enhanced by image processing Differences in spectral reflectance between tumors and normal mucosa suggested that tumors can be clearly distinguished from background mucosa with HSI technology.

Fiber Bragg grating-based sensor for monitoring respiration and heart activity during magnetic resonance imaging examinations

Abstract: We present a fiber-optic sensor for monitoring respiration and heart activity designed to operate in the magnetic resonance imaging (MRI) environment. The sensor employs a Plexiglas springboard, which converts movements of the patient's body lying on the board (i.e., lung- and heart-induced vibrations) to strain, where a fiber Bragg grating attached to the board is used to measure this strain. Experimental studies are carried out during thoracic spine MRI examinations. The presence of the metal-free sensor construction in the MRI environment does not pose a threat to the patient and has no influence over the quality of imaging, and the signal is identical to that obtained without any electromagnetic interference. The results show that the sensor is able to accurately reflect the ballistocardiographic signal, enabling determinations of the respiration rate (RR) and heart rate (HR). The data delivered by the sensor are normally distributed on the Bland-Altman plot for the characteristic point determination and exhibit clear dependence on the RR and HR values for the RR and HR determinations, respectively. Measurement accuracies are better than 7% of the average values, and thus, with further development, the sensor will be implemented in routine MRI examinations.

Detection of colon cancer by continuous-wave terahertz polarization imaging technique

Abstract: We demonstrate a reflective, continuous-wave terahertz (THz) imaging system to acquire ex vivo images of fresh human colonic excisions. Reflection measurements of 5-mm-thick sections of colorectal tissues were obtained using a polarization-specific detection technique. Two- dimensional THz reflection images of both normal and can- cerous colon tissues with a spatial resolution of 0.6 mm were acquired using an optically pumped far-infrared molecular gas laser. Good contrast has been observed between normal and tumorous tissues at 584 GHz frequency. The resulting THz reflection images compared with the tissue histology showed a correlation between cancerous region and increased reflection. We hypothesize that the imaging sys- tem and polarization techniques are capable of registering reflectance differences between cancerous and normal colon. However, further investigations are necessary to completely understand the source mechanism behind the contrast and confirm the hypothesis; if true, it likely repre- sents the first continuous-wave THz reflection imaging tech- nique to show sufficient contrast to identify colon tumor margins. Also, it may represent a significant step forward in clinical endoscopic application of THz technology to aid in in vivo colorectal cancer screening. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. (DOI: 10.1117/1 .JBO.18.9.090504)

Monte Carlo lookup table-based inverse model for extracting optical properties from tissue-simulating phantoms using diffuse reflectance spectroscopy

Abstract: We present a Monte Carlo lookup table (MCLUT)-based inverse model for extracting optical properties from tissue-simulating phantoms. This model is valid for close source-detector separation and highly absorbing tissues. The MCLUT is based entirely on Monte Carlo simulation, which was implemented using a graphics processing unit. We used tissue-simulating phantoms to determine the accuracy of the MCLUT inverse model. Our results show strong agreement between extracted and expected optical properties, with errors rate of 1.74% for extracted reduced scattering values, 0.74% for extracted absorption values, and 2.42% for extracted hemoglobin concentration values.

Label-free photoacoustic microscopy of cytochromes.

Abstract: Photoacoustic microscopy (PAM) has achieved submicron lateral resolution in showing subcellular structures; however, relatively few endogenous subcellular contrasts have so far been imaged. Given that the hemeprotein, mostly cytochromes in general cells, is optically absorbing around the Soret peak (∼420 nm), we implemented label-free PAM of cytochromes in cytoplasm for the first time. By measuring the photoacoustic spectra of the oxidized and reduced states of fibroblast lysate and fitting the difference spectrum with three types of cytochromes, we found that the three cytochromes account for more than half the optical absorption in the cell lysate at 420 nm wavelength. Fixed fibroblasts on slides were imaged by PAM at 422 and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard staining histology. PAM was also applied to label-free histology of mouse ear sections by showing cytoplasms and nuclei of various cells. PAM of cytochromes in cytoplasm is expected to be a high-throughput, label-free technique for studying live cell functions, which cannot be accomplished by conventional histology.

Shear modulus imaging by direct visualization of propagating shear waves with phase-sensitive optical coherence tomography.

Abstract: We propose an integrated method combining low-frequency mechanics with optical imaging to map the shear modulus within the biological tissue. Induced shear wave propagating in tissue is tracked in space and time using phase-sensitive optical coherence tomography (PhS-OCT). Local estimates of the shear-wave speed obtained from tracking results can image the local shear modulus. A PhS-OCT system remotely records depth-resolved, dynamic mechanical waves at an equivalent frame rate of ∼47 kHz with the high spatial resolution. The proposed method was validated by examining tissue-mimicking phantoms made of agar and light scattering material. Results demonstrate that the shear wave imaging can accurately map the elastic moduli of these phantoms.

Fluorescence Microscopy: From Principles to Biological Applications

Abstract: Microscopes are tools invented by humans to study specimens at spatial and temporal resolution that exceed the human eye. Today the researcher has a wide range of microscopes to employ in order to answer carefully poised experimental questions. The key is to match the research questions with the appropriate microscope. In order to optimize the success it is necessary to understand the physical principles of the microscope, how to properly align the instrument, and how to correctly use the instrument. The object of the investigation or measurement is also a major consideration as well as the preparation of the specimen, the interaction of the specimen, and the radiation from the microscope. Often the words “quantitative microscopy” appear in publications; but all measurements contain errors, and the critical investigator must be able to understand the sources of error in a measurement and, if possible, mitigate the magnitude of the errors. Validation of microscopic measurements across disparate types of microscopes is a useful approach. The critical elements in optical microscopy include: optical aberrations, sampling errors, nonphysiological specimen preparation, such as over expression of genetic fluorescent proteins, the deleterious effects of the light source on biological specimens, nonlinear effects in the detector and amplifiers, and artifacts of image analysis and image interpretation.

Optical methods for noninvasive determination of carotenoids in human and animal skin.

Abstract: Carotenoids are important substances for human skin due to their powerful antioxidant properties in reaction of neutralization of free radicals and especially reactive oxygen species, including singlet oxygen. Concentration of carotenoids in the skin could mirror the current redox status of the skin and should be investigated in vivo. Optical methods are ideally suited for determination of carotenoids in mammalian skin in vivo as they are both noninvasive and quick. Four different optical methods could be used for in vivo measurement of carotenoids in the human or animal skin: (1) resonance Raman spectroscopy; (2) Raman microscopy; (3) reflection spectroscopy; (4) skin color measurements. The advantages, shortcomings, and limitations of the above-mentioned optical methods are discussed.

Reduction of trial-to-trial variability in functional near-infrared spectroscopy signals by accounting for resting-state functional connectivity

Abstract: The reduction of trial-to-trial variability (TTV) in task-evoked functional near-infrared spectroscopy signals by considering the correlated low-frequency spontaneous fluctuations that account for the resting-state functional connectivity in the brain is investigated. A resting-state session followed by a task-state session of a right hand finger-tapping task has been performed on five subjects. Significant ipsilateral and bilateral resting-state functional connectivity has been detected at the subjects' motor cortex using the seed correlation method. The correlation coefficients obtained during the resting-state are used to reduce the TTV in the signals measured during the task sessions. The results suggest that correlated spontaneous low-frequency fluctuations contribute significantly to the TTV in the task evoked fNIRS signals.

Photoacoustic lifetime contrast between methylene blue monomers and self-quenched dimers as a model for dual-labeled activatable probes.

Abstract: Activatable photoacoustic probes efficiently combine the high spatial resolution and penetration depth of ultrasound with the high optical contrast and versatility of molecular imaging agents. Our approach is based on photoacoustic probing of the excited-state lifetime of methylene blue (MB), a fluorophore widely used in clinical therapeutic and diagnostic applications. Upon aggregation, static quenching between the bound molecules dramatically shortens their lifetime by three orders of magnitude. We present preliminary results demonstrating the ability of photoacoustic imaging to probe the lifetime contrast between monomers and dimers with high sensitivity in cylindrical phantoms. Gradual dimerization enhancement, driven by the addition of increasing concentrations of sodium sulfate to a MB solution, showed that lifetime-based photoacoustic probing decreases linearly with monomer concentration. Similarly, the addition of 4 mM sodium dodecyl sulfate, a concentration that amplifies MB aggregation and reduces the monomer concentration by more than 20-fold, led to a signal decrease of more than 20 dB compared to a solution free of surfactant. These results suggest that photoacoustic imaging can be used to selectively detect the presence of monomers. We conclude by discussing the implementation of the monomer-dimer contrast mechanism for the development of an enzyme-specific activatable probe.

Photoacoustic needle: minimally invasive guidance to biopsy

Abstract: We introduce a needle probe based on photoacoustics (PA) to extend the scope of optical needle methods in guiding biopsies. Pulsed light is coupled to an optical fiber in a needle to be inserted in tissue, and PA signals are detected using an ultrasound imager used for needle guidance. This PA needle samples large volumes and possesses an imaging component so that sites forward and off-axis of the fiber are surveyed. This allows navigation of those regions for optical characterization and direct biopsy in a subsequent step. The concept is explored on simple phantoms and biological specimens.

Needle optical coherence elastography for the measurement of microscale mechanical contrast deep within human breast tissues

Abstract: Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mmof tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements 4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.

Acoustic attenuation compensation in photoacoustic tomography using time-variant filtering

Abstract: Most reconstruction algorithms used in photoacoustic tomography do not account for the effects of acoustic attenuation on the recorded signals. For experimental measurements made in biological tissue, the frequency dependent acoustic attenuation causes high frequency components of the propagating photoacoustic waves to be significantly reduced. This signal loss manifests as a depth dependent magnitude error and blurring of features within the reconstructed image. Here, a general method for compensating for this attenuation using time-variant filtering is presented. The time-variant filter is constructed to correct for acoustic attenuation and dispersion following a frequency power law under the assumption the distribution of attenuation parameters is homogeneous. The filter is then applied directly to the recorded time-domain signals using a form of nonstationary convolution. Regularization is achieved using a time-variant window where the cutoff frequency is based on the local time-frequency distribution of the recorded signals. The approach is computationally efficient and can be used in combination with any detector geometry or reconstruction algorithm. Numerical and experimental examples are presented to illustrate the utility of the technique. Clear improvements in the magnitude and resolution of reconstructed photoacoustic images are seen when acoustic attenuation compensation is applied.

Monitoring remineralization of enamel subsurface lesions by optical coherence tomography.

Abstract: Optical coherence tomography (OCT) is a potential clinical tool for enamel lesion monitoring. Swept-source OCT findings were compared with cross-sectional nanohardness findings of enamel. Subsurface bovine enamel lesions in three groups were subjected to (1) deionized water (control), (2) phosphoryl oligosaccharide of calcium (POs-Ca) or (3) POs-Ca with 1 ppm fluoride for 14 days. B-scans images were obtained at 1310-nm center wavelength on sound, demineralized and remineralized areas after 4, 7, and 14 days. The specimens were processed for cross-sectional nanoindentation. Reflectivity from enamel that had increased with demineralization decreased with remineralization. An OCT attenuation coefficient parameter (μt), derived based on the Beer-Lambert law as a function of backscatter signal slope, showed a strong linear regression with integrated nanohardness of all regions (p<0.001, r=-0.97). Sound enamel showed the smallest, while demineralized enamel showed the highest μt. In group three, μt was significantly lower at four days than baseline, but remained constant afterwards. In group two, the changes were rather gradual. There was no significant difference between groups two and three at 14 days in nanohardness or μt POs-Ca with fluoride-enhanced nanohardness of the superficial zone. OCT signal attenuation demonstrated a capability for monitoring changes of enamel lesions during remineralization.

Feasibility study of the optical imaging of a breast cancer lesion labeled with upconversion nanoparticle biocomplexes

Abstract: Innovative luminescent nanomaterials, termed upconversion nanoparticles (UCNPs), have demonstrated considerable promise as molecular probes for high-contrast optical imaging in cells and small animals. The fea- sibility study of optical diagnostics in humans is reported here based on experimental and theoretical modeling of optical imaging of an UCNP-labeled breast cancer lesion. UCNPs synthesized in-house were surface-capped with an amphiphilic polymer to achieve good colloidal stability in aqueous buffer solutions. The scFv4D5 mini-anti- bodies were grafted onto the UCNPs via a high-affinity molecular linker barstar:barnase (Bs:Bn) to allow their spe- cific binding to the human epidermal growth factor receptor HER2/neu, which is overexpressed in human breast adenocarcinoma cells SK-BR-3. UCNP-Bs:Bn-scFv4D5 biocomplexes exhibited high-specific immobilization on the SK-BR-3 cells with the optical contrast as high as 10∶1 benchmarked against a negative control cell line. Breast cancer optical diagnostics was experimentally modeled by means of epi-luminescence imaging of a mono- layer of the UCNP-labeled SK-BR-3 cells buried under a breast tissue mimicking optical phantom. The experimental results were analyzed theoretically and projected to in vivo detection of early-stage breast cancer. The model pre- dicts that the UCNP-assisted cancer detection is feasible up to 4 mm in tissue depth, showing considerable potential for diagnostic and image-guided surgery applications. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. (DOI: 10 .1117/1.JBO.18.7.076004)