Dual-modality thermoacoustic and photoacoustic imaging

Diagnosis of early breast cancer is the key to survival. The combined contrasts from thermoacoustic and photoacoustic tomography: TAT and PAT) can potentially predict early stage breast cancer. We have designed and engineered a breast imaging system integrating both thermoacoustic and photoacoustic imaging techniques to achieve dual-contrast: microwave and light absorption), non-ionizing, low-cost, high-resolution, three-dimensional breast imaging. We have also developed a novel concept of using a negative acoustic lens to increase the acceptance angle of an unfocused large-area ultrasonic transducer: detector), leading to more than twofold improvement of the tangential resolution in both TAT and PAT when the object is far from the scanning center. A contrast agent could be greatly beneficial for early cancer diagnosis using TAT/PAT, because the early stage intrinsic contrast can be low. We have developed a carbon nanotube-based contrast agent for both TAT and PAT. In comparison with deionized water, single-walled carbon nanotubes: SWNTs) exhibited more than twofold signal enhancement for TAT at 3 GHz, and in comparison with blood, they exhibited more than sixfold signal enhancement for PAT at 1064 nm wavelength. Using PAT in conjunction with an intradermal injection of SWNTs, we also showed the feasibility of noninvasive in vivo sentinel lymph node imaging in a rat model. We have also developed and demonstrated molecular photoacoustic imaging using unique soft-type colloidal gold nanobeacons: GNBs) in the near-infrared region. GNBs represent a novel class of stable, colloidal gold nanoparticles, incorporating small metallic gold nanoparticles that can clear from the body when the particles are metabolically disrupted. We have also imaged the sentinel lymph node using different sizes of GNBs, showing that size plays an important role in their in vivo behavior and uptake to the lymph nodes. In addition to providing diagnostic imaging, TAT and PAT can be used in therapy for real-time temperature monitoring with high spatial resolution and high temperature sensitivity, which are both needed for safe and efficient thermotherapy. Using a tissue phantom, these noninvasive methods have been demonstrated to have a high temperature sensitivity of 0.15 0C at 2 s temporal resolution: 20 signal averages)

Two dimensional angular domain optical imaging in biological tissues

Optical imaging is a modality that can detect optical contrast within a biological sample that is not detectable with other conventional imaging techniques. Optical trans-illumination images of tissue samples are degraded by optical scatter. Angular Domain Imaging (ADI) is an optical imaging technique that filters scattered photons based on the trajectory of the photons. Previous angular filters were limited to one dimensional arrays, greatly limiting the imaging capability of the system. We have developed a 2D Angular Filter Array (AFA) that is capable of acquiring two dimensional projection images of a sample. The AFA was constructed using rapid prototyping techniques. The contrast and the resolution of the AFA was evaluated. The results suggest that a 2D AFA can be used to acquire two dimensional projection images of a sample with a reduced acquisition time compared to a scanning 1D AFA

Advancing combined radiological and optical scanning for breast-conserving surgery margin guidance

Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to achieve a curative outcome. X-ray micro-computed tomography (CT) is emerging as a powerful ex vivo specimen imaging technology, as it provides robust three-dimensional sensing of tumor morphology rapidly. However, X-ray attenuation lacks contrast between soft tissues that are important for surgical decision making during BCS. Optical structured light imaging, including spatial frequency domain imaging and active line scan imaging, can act as adjuvant tools to complement micro-CT, providing wide field-of-view, non-contact sensing of relevant breast tissue subtypes on resection margins that cannot be differentiated by micro-CT alone. This thesis is dedicated to multimodal imaging of BCS tissues to ultimately improve intraoperative BCS margin assessment, reducing the number of positive margins after initial surgeries and thereby reducing the need for costly follow-up procedures. Volumetric sensing of micro-CT is combined with surface-weighted, sub-diffuse optical reflectance derived from high spatial frequency structured light imaging. Sub-diffuse reflectance plays the key role of providing enhanced contrast to a suite of normal, abnormal benign, and malignant breast tissue subtypes. This finding is corroborated through clinical studies imaging BCS specimen slices post-operatively and is further investigated through an observational clinical trial focused on combined, intraoperative micro-CT and optical imaging of whole, freshly resected BCS tumors. The central thesis of this work is that combining volumetric X-ray imaging and sub-diffuse optical scanning provides a synergistic multimodal imaging solution to margin assessment, one that can be readily implemented or retrofitted in X-ray specimen imaging systems and that could meaningfully improve surgical guidance during initial BCS procedures

Digital Image Processing Applications

Digital image processing can refer to a wide variety of techniques, concepts, and applications of different types of processing for different purposes. This book provides examples of digital image processing applications and presents recent research on processing concepts and techniques. Chapters cover such topics as image processing in medical physics, binarization, video processing, and more

Development Of Optical Coherence Tomography For Tissue Diagnostics

Microvasculature can be found in almost every part of the human body, including the internal organs. Importantly, abnormal changes in microvasculature are usually related to pathological development of the tissue cells. Monitoring of changes in blood flow properties in microvasculature, therefore, provides useful diagnostic information about pathological conditions in biological tissues as exemplified in glaucoma, diabetes, age related macular degeneration, port wine stains, burn-depth, and potentially skin cancer. However, the capillary network is typically only one cell in wall thickness with 5 to 10 microns in diameter and located in the dermis region of skin. Therefore, a non-invasive flow imaging technique that is capable of depth sectioning at high resolution and high speed is demanded. Optical coherence tomography (OCT), particularly after its advancement in frequency domain OCT (FD-OCT), is a promising tool for non-invasive high speed, high resolution, and high sensitivity depth-resolved imaging of biological tissues. Over the last ten years, numerous efforts have been paid to develop OCTbased flow imaging techniques. An important effort is the development of phase-resolved Doppler OCT (PR-DOCT). Phase-resolved Doppler imaging using FD-OCT is particularly of interest because of the direct access to the phase information of the depth profile signal. Furthermore, the high speed capability of FD-OCT is promising for real time flow monitoring as well as 3D flow segmentation applications. However, several challenges need to be addressed; 1) Flow in biological samples exhibits a wide dynamic range of flow velocity caused by, for example, the iv variation in the flow angles, flow diameters, and functionalities. However, the improvement in imaging speed of FD-OCT comes at the expense of a reduction in sensitivity to slow flow information and hence a reduction in detectable velocity range; 2) A structural ambiguity socalled \u27mirror image\u27 in FD-OCT prohibits the use of maximum sensitivity and imaging depth range; 3) The requirement of high lateral resolution to resolve capillary vessels requires the use of an imaging optics with high numerical aperture (NA) that leads to a reduction in depth of focus (DOF) and hence the imaging depth range (i.e. less than 100 microns) unless dynamic focusing is performed. Nevertheless, intrinsic to the mechanism of FD-OCT, dynamic focusing is not possible. In this dissertation, the implementation of PR-DOCT in a high speed swept-source based FD-OCT is investigated and optimized. An acquisition scheme as well as a processing algorithm that effectively extends the detectable velocity dynamic range of the PR-DOCT is presented. The proposed technique increased the overall detectable velocity dynamic range of PR-DOCT by about five times of that achieved by the conventional method. Furthermore, a novel technique of mirror image removal called ‘Dual-Detection FD-OCT’ (DD-FD-OCT) is presented. One of the advantages of DD-FD-OCT to Doppler imaging is that the full-range signal is achieved without manipulation of the phase relation between consecutive axial lines. Hence the full-range DD-FDOCT is fully applicable to phase-resolved Doppler detection without a reduction in detectable velocity dynamic range as normally encountered in other full-range techniques. In addition, PRDOCT can utilize the maximum SNR provided by the full-range capability. This capability is particularly useful for imaging of blood flow that locates deep below the sample surface, such as v blood flow at deep posterior human eye and blood vessels network in the dermis region of human skin. Beside high speed and functional imaging capability, another key parameter that will open path for optical diagnostics using OCT technology is high resolution imaging (i.e. in a regime of a few microns or sub-micron). Even though the lateral resolution of OCT can be independently improved by opening the NA of the imaging optics, the high lateral resolution is maintained only over a short range as limited by the depth of focus that varies inversely and quadratically with NA. Recently developed by our group, ‘Gabor-Domain Optical Coherence Microscopy’ (GD-OCM) is a novel imaging technique capable for invariant resolution of about 2-3 m over a 2 mm cubic field-of-view. This dissertation details the imaging protocol as well as the automatic data fusion method of GD-OCM developed to render an in-focus high-resolution image throughout the imaging depth of the sample in real time. For the application of absolute flow measurement as an example, the precise information about flow angle is required. GDOCM provides more precise interpretation of the tissue structures over a large field-of-view, which is necessary for accurate mapping of the flow structure and hence is promising for diagnostic applications particularly when combined with Doppler imaging. Potentially, the ability to perform high resolution OCT imaging inside the human body is useful for many diagnostic applications, such as providing an accurate map for biopsy, guiding surgical and other treatments, monitoring the functional state and/or the post-operative recovery process of internal organs, plaque detection in arteries, and early detection of cancers in the gastrointestinal tract. Endoscopic OCT utilizes a special miniature probe in the sample arm to vi access tubular organs inside the human body, such as the cardiovascular system, the lung, the gastrointestinal tract, the urinary tract, and the breast duct. We present an optical design of a dynamic focus endoscopic probe that is capable of about 4 to 6 m lateral resolution over a large working distance (i.e. up to 5 mm from the distal end of the probe). The dynamic focus capability allows integration of the endoscopic probe to GD-OCM imaging to achieve high resolution endoscopic tomograms. We envision the future of this developing technology as a solution to high resolution, minimally invasive, depth-resolved imaging of not only structure but also the microvasculature of in vivo biological tissues that will be useful for many clinical applications, such as dermatology, ophthalmology, endoscopy, and cardiology. The technology is also useful for animal study applications, such as the monitoring of an embryo’s heart for the development of animal models and monitoring of changes in blood circulation in response to external stimulus in small animal brains

Dual-Channel Red/Blue Fluorescence Dosimetry with Broadband Reflectance Spectroscopic Correction Measures Protoporphyrin IX Production during Photodynamic Therapy of Actinic Keratosis

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of \u3c0.9 . PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response

Entropy in Image Analysis II

Image analysis is a fundamental task for any application where extracting information from images is required. The analysis requires highly sophisticated numerical and analytical methods, particularly for those applications in medicine, security, and other fields where the results of the processing consist of data of vital importance. This fact is evident from all the articles composing the Special Issue "Entropy in Image Analysis II", in which the authors used widely tested methods to verify their results. In the process of reading the present volume, the reader will appreciate the richness of their methods and applications, in particular for medical imaging and image security, and a remarkable cross-fertilization among the proposed research areas

Handheld optoacoustic probe facilitating nearfield investigations through a transparent detector

Modern medicine relies strongly on measurement devices, enabling the physician to investigate the human body in ever greater detail. In addition to established techniques of optical microscopy, ultrasound, x-ray and magnetic resonance imaging, optoacoustic (OA) imaging is on its path to enter the clinics. The research field of optoacoustics already produced a variety of remarkable setups, from high resolution microscopy to deep penetrating tomography. Through the broad range of wavelengths available for this technique, it is capable of detecting the concentration of endogenous as well as exogenous contrast agents, even blood oxygenation levels can be determined in real time. Depending on the application, different OA setups can be created, customized to best address the specific task. This thesis is concerned with the development of a handheld optoacoustic setup to determine the thickness of melanoma. Penetration depth is the most important factor in staging of skin tumors. To facilitate near field measurements the detector is designed to be transparent, which allows illumination through the detector. Indium tin oxide electrodes are sputtered on a piezoelectric polymer film to create a circular detector area. Transparency was confirmed using spectrophotometric measurements in the visible and near infrared light spectrum. To characterize the capabilities of the transparent detector, far field measurements on hydrogel samples with layers containing different concentrations of melanin were performed. An OA measurement series on a mole under laboratory conditions showcased the possibility using wavelengths in the range from 432-652 nm with this detector. For logistical reasons, only 532 nm were used in the other measurements. Near field measurements on a coated glass plate are compared with simulation, confirming the validity of the data processing algorithm to remove the pyroelectric signal and deconvolve the instrument response function from the OA signal. In a small clinical study, suspicious nevi were investigated using the setup developed here. The obtained OA signals are discussed in relation with the histology of the respective nevus. Even though their thicknesses could not yet be determined reliably, the results are promising that further improvements with regards to noise reduction will allow real time measurements of the absorption depth profile