628 research outputs found

    A Digital X-Ray Tomosynthesis Coupled Near Infrared Spectral Tomography System for Dual-Modality Breast Imaging

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    A Near Infrared Spectral Tomography (NIRST) system has been developed and integrated into a commercial Digital Breast Tomosynthesis (DBT) scanner to allow structural and functional imaging of breast in vivo. The NIRST instrument uses an 8-wavelength continuous wave (CW) laser-based scanning source assembly and a 75-element silicon photodiode solid-state detector panel to produce dense spectral and spatial projection data from which spectrally constrained 3D tomographic images of tissue chromophores are produced. Integration of the optical imaging system into the DBT scanner allows direct co-registration of the optical and DBT images, while also facilitating the synergistic use of x-ray contrast as anatomical priors in optical image reconstruction. Currently, the total scan time for a combined NIRST-DBT exam is ~50s with data collection from 8 wavelengths in the optical scan requiring ~42s to complete. The system was tested in breast simulating phantoms constructed using intralipid and blood in an agarose matrix with a 3 cm x 2 cm cylindrical inclusion at 1 cm depth from the surface. Diffuse image reconstruction of total hemoglobin (HbT) concentration resulted in accurate recovery of the lateral size and position of the inclusion to within 6% and 8%, respectively. Use of DBT structural priors in the NIRST reconstruction process improved the quantitative accuracy of the HbT recovery, and led to linear changes in imaged versus actual contrast, underscoring the advantages of dual-modality optical imaging approaches. The quantitative accuracy of the system can be further improved with independent measurements of scattering properties through integration of frequency or time domain data

    Ultrasound-Guided Optical Tomographic Imaging of Malignant and Benign Breast Lesions: Initial Clinical Results of 19 Cases

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    AbstractThe diagnosis of solid benign and malignant tumors presents a unique challenge to all noninvasive imaging modalities. Ultrasound is used in conjunction with mammography to differentiate simple cysts from solid lesions. However, the overlapping appearances of benign and malignant lesions make ultrasound less useful in differentiating solid lesions, resulting in a large number of benign biopsies. Optical tomography using near-infrared diffused light has great potential for imaging functional parameters of 1) tumor hemoglobin concentration, 2) oxygen saturation, 3) metabolism, as well as other tumor distinguishing characteristics. These parameters can differentiate benign from malignant lesions. However, optical tomography, when used alone, suffers from low spatial resolution and target localization uncertainty due to intensive light scattering. Our aim is to combine diffused light imaging with ultrasound in a novel way for the detection and diagnosis of solid lesions. Initial findings of two earlystage invasive carcinomas, one combined fibroadenoma and fibrocystic change with scattered foci of lobular neoplasia/lobular carcinoma in situ, 16 benign lesions are reported in this paper. The invasive cancer cases reveal about two-fold greater total hemoglobin concentration (mean 119 μmol) than benign cases (mean 67 μmol), suggest that the discrimination of benign and malignant breast lesions might be enhanced by this type of achievable optical quantification with ultrasound localization. Furthermore, the small invasive cancers are well localized and have wavelength-dependent appearance in optical absorption maps, whereas the benign lesions appear diffused and relatively wavelength-independent

    Calibration and Optimization of 3D Digital Breast Tomosynthesis Guided Near Infrared Spectral Tomography

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    Calibration of a three-dimensional multimodal digital breast tomosynthesis (DBT) x-ray and non-fiber based near infrared spectral tomography (NIRST) system is challenging but essential for clinical studies. Phantom imaging results yielded linear contrast recovery of total hemoglobin (HbT) concentration for cylindrical inclusions of 15 mm, 10 mm and 7 mm with a 3.5% decrease in the HbT estimate for each 1 cm increase in inclusion depth. A clinical exam of a patient\u27s breast containing both benign and malignant lesions was successfully imaged, with greater HbT was found in the malignancy relative to the benign abnormality and fibroglandular regions (11 μM vs. 9.5 μM). Tools developed improved imaging system characterization and optimization of signal quality, which will ultimately improve patient selection and subsequent clinical trial results

    Review of optical breast imaging and spectroscopy

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    Diffuse optical imaging and spectroscopy of the female breast is an area of active research. We review the present status of this field and discuss the broad range of methodologies and applications. Starting with a brief overview on breast physiology, the remodeling of vasculature and extracellular matrix caused by solid tumors is highlighted that is relevant for contrast in optical imaging. Then, the various instrumental techniques and the related methods of data analysis and image generation are described and compared including multimodality instrumentation, fluorescence mammography, broadband spectroscopy, and diffuse correlation spectroscopy. We review the clinical results on functional properties of malignant and benign breast lesions compared to host tissue and discuss the various methods to improve contrast between healthy and diseased tissue, such as enhanced spectroscopic information, dynamic variations of functional properties, pharmacokinetics of extrinsic contrast agents, including the enhanced permeability and retention effect. We discuss research on monitoring neoadjuvant chemotherapy and on breast cancer risk assessment as potential clinical applications of optical breast imaging and spectroscopy. Moreover, we consider new experimental approaches, such as photoacoustic imaging and long-wavelength tissue spectroscopy

    Fluorescence molecular tomography: Principles and potential for pharmaceutical research

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    Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue’s optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development

    Dual-modality thermoacoustic and photoacoustic imaging

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    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)

    Ultrasound-guided Optical Techniques for Cancer Diagnosis: System and Algorithm Development

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    Worldwide, breast cancer is the most common cancer among women. In the United States alone, the American cancer society has estimated there will be 271,270 new breast cancer cases in 2019, and 42,260 lives will be lost to the disease. Ultrasound (US), mammography, and magnetic resonance imaging (MRI) are regularly used for breast cancer diagnosis and therapy monitoring. However, they sometimes fail to diagnose breast cancer effectively. These shortcomings have motivated researchers to explore new modalities. One of these modalities, diffuse optical tomography (DOT), utilizes near-infrared (NIR) light to reveal the optical properties of tissue. NIR-based DOT images the contrast between a suspected lesion’s location and the background tissue, caused by the higher NIR absorption of the hemoglobin which characterizes tumors. The limitation of high light scattering inside tissue is minimized by using ultrasound image to find the tumor location. This thesis focuses on developing a compact, low-cost ultrasound guided diffuse optical tomography imaging system and on improving optical image reconstruction by extracting the tumor’s location and size from co-registered ultrasound images. Several electronic components have been redesigned and optimized to save space and cost and to improve the user experience. In terms of software and algorithm development, manual extraction of tumor information from ultrasound images has been replaced by using a semi-automated ultrasound image segmentation algorithm that reduces the optical image reconstruction time and operator dependency. This system and algorithm have been validated with phantom and clinical data and have demonstrated their efficacy. An ongoing clinical trial will continue to gather more patient data to improve the robustness of the imaging algorithm. Another part of this research focuses on ovarian cancer diagnosis. Ovarian cancer is the most deadly of all gynecological cancers, with a less than 50% five-year survival rate. This cancer can evolve without any noticeable symptom, which makes it difficult to diagnose in an early stage. Although ultrasound-guided photoacoustic tomography (PAT) has demonstrated potential for early detection of ovarian cancer, clinical studies have been very limited due to the lack of robust PAT systems. In this research, we have customized a commercial ultrasound system to obtain real-time co-registered PAT and US images. This system was validated with several phantom studies before use in a clinical trial. PAT and US raw data from 30 ovarian cancer patients was used to extract spectral and statistical features for training and testing classifiers for automatic diagnosis. For some challenging cases, the region of interest selection was improved by reconstructing co-registered Doppler images. This study will be continued in order to obtain quantitative tissue properties using US-guided PAT

    Photoacoustic tomography: fundamentals, advances and prospects

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    Optical microscopy has been contributing to the development of life science for more than three centuries. However, due to strong optical scattering in tissue, its in vivo imaging ability has been restricted to studies at superficial depths. Advances in photoacoustic tomography (PAT) now allow multiscale imaging at depths from sub-millimeter to several centimeters, with spatial resolutions from sub-micrometer to sub-millimeter. Because of this high scalability and its unique optical absorption contrast, PAT is capable of performing anatomical, functional, molecular and fluid-dynamic imaging at various system levels, and is playing an increasingly important role in fundamental biological research and clinical practice. This Review discusses recent technical progress in PAT and presents corresponding applications. It ends with a discussion of several prospects and their technical challenges

    Towards combined x-ray and optical mammography

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    Optical contrast, dependent upon haemodynamics and thus providing physiological information, is complementary to radiographic contrast. Combined x-ray and optical mammography screening could provide increased specificity over either system alone. Medical imaging equipment is routinely characterised and tested using tissue equivalent phantoms. A novel phantom material is presented: a solution of polyvinyl alcohol in ethanol and water freeze-thawed to produce a solid yet elastically compressible gel. The x-ray attenuation, mechanical and optical properties of these gels can be accurately adjusted over appropriate ranges so as to mimic cancerous or healthy breast tissues. Modulated imaging in both optical and x-ray acquisitions is also considered. An x-ray system capable of optimising dose distribution has previously been developed at UCL. Overall images are obtained by aligning multiple images from smaller sensors. The effects that this type of acquisition has on spatial resolution are discussed. Two considerations are made: (i) is there a minimum size sensor whose modulation transfer function (MTF) can accurately be determined? (ii) does the MTF of an overall image differ significantly from those of its constituent images? The smaller a sensor becomes, the harder it is to determine its MTF accurately, and the resolution of overall images is slightly poorer than those of individual sensor images. Nonetheless these effects are small and should not hinder the development of such systems. Whilst similar dose considerations do not apply to optical tomography, modulated imaging still presents potential benefits. A method of visualising intensity data in order to localise regions of heterogenous absorption is presented using both simulated and experimental data. Objective functions designed to quantify the visibility of these heterogeneities are proposed and it is shown that optimal distributions of source power, that maximise these, can be found. It is proposed that such techniques might allow optical acquisitions to be performed more rapidly

    Computer-Aided, Multi-Modal, and Compression Diffuse Optical Studies of Breast Tissue

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    Diffuse Optical Tomography and Spectroscopy permit measurement of important physiological parameters non-invasively through ~10 cm of tissue. I have applied these techniques in measurements of human breast and breast cancer. My thesis integrates three loosely connected themes in this context: multi-modal breast cancer imaging, automated data analysis of breast cancer images, and microvascular hemodynamics of breast under compression. As per the first theme, I describe construction, testing, and the initial clinical usage of two generations of imaging systems for simultaneous diffuse optical and magnetic resonance imaging. The second project develops a statistical analysis of optical breast data from many spatial locations in a population of cancers to derive a novel optical signature of malignancy; I then apply this data-derived signature for localization of cancer in additional subjects. Finally, I construct and deploy diffuse optical instrumentation to measure blood content and blood flow during breast compression; besides optics, this research has implications for any method employing breast compression, e.g., mammography
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