Cancer Diagnostics Using Dynamic Near Infrared Optical Imaging And Fluorescent Contrast Agents
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Cancer Diagnostics Using Dynamic Near Infrared Optical Imaging And Fluorescent Contrast Agents
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Author : Mikhail Gurfinkel
language : en
Publisher:
Release Date : 2006
Cancer Diagnostics Using Dynamic Near Infrared Optical Imaging And Fluorescent Contrast Agents written by Mikhail Gurfinkel and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with categories.
A new optical imaging modality has been developed for small animal in vivo imaging of near-infrared fluorescence resulting from fluorescent contrast agents specifically targeted to molecular markers of cancer. The imaging system is comprised of an intensified charge-coupled device (ICCD) for the detection of ultra-low levels of re-emitted fluorescence following the delivery of an expanded beam of excitation light. The design of the ICCD detection system allows for both continuous wave (CW) and frequency-domain modes of operation. Since the accurate acquisition of frequency-domain photon migration (FDPM) data is important for tomographic imaging, the imaging system was also validated using experimentally obtained FDPM measurements of homogenous turbid media and diffusion theory to obtain estimates of the optical properties characteristic of the media. The experiments demonstrated that the absorption and reduced scattering coefficients are determined least accurately when relative measurements of average light intensity I rel [over] DC are employed either alone or in a combination with relative modulation amplitude data I rel [over] AC and/or relative phase shift data [theta] [superscript]rel. However, when FDPM measurements of [theta] [superscript]rel are employed either alone or in combination with I rel [over] AC data, the absorption and reduced scattering coefficients may be found accurate to within 15% and 11%, respectively, of the values obtained from standard single-pixel measurements; a result that suggests that FDPM data obtained from an ICCD detection system may in fact be useful in tomographic imaging. Furthermore, intensified-detection allows for sub-second exposure times, permitting the acquisition of dynamic fluorescence images immediately following administration of the contrast agent. Experimental results demonstrate that when coupled with a suitable pharmacokinetic model describing targeted dye distribution throughout the body, dynamic fluorescence imaging may be used to discriminate spontaneous canine adenocarcinoma from normal mammary tissue. A separate experiment demonstrates that pharmacokinetic analysis of dynamic fluorescence images enables one to estimate the rate constant governing Kaposi's sarcoma tumor uptake of an [alpha subscriptV beta]3 integrin-targeted dye and integrin receptor turnover rate. The rate constant for uptake was calculated to be 0.16-sec−1 while the turnover rate of the integrin receptor was estimated to occur within 24-hours.
Dynamic Fluorescence Imaging With Molecular Agents For Cancer Detection
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Author : Sun Kuk Kwon
language : en
Publisher:
Release Date : 2010
Dynamic Fluorescence Imaging With Molecular Agents For Cancer Detection written by Sun Kuk Kwon and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Non-invasive dynamic optical imaging of small animals requires the development of a novel fluorescence imaging modality. Herein, fluorescence imaging is demonstrated with sub-second camera integration times using agents specifically targeted to disease markers, enabling rapid detection of cancerous regions. The continuous-wave fluorescence imaging acquires data with an intensified or an electronmultiplying charge-coupled device. The work presented in this dissertation (i) assessed dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK) models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii) compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR) vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence imaging with two different fluorescent contrast agents. PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation. Target to background ratio (TBR) and PK analysis for two different tumor cell lines showed that while Kaposi's sarcoma (KS1767) exhibited early and rapid uptake of Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences and early uptake rates similar to the contralateral normal tissue regions. The differences may be due to different compartment location of the target. A comparison of fluorescence imaging with NIR vs. red light excitable fluorescent dyes demonstrates that NIR dyes are associated with less background signal, enabling rapid tumor detection. In contrast, animals injected with red light excitable fluorescent dyes showed high autofluorescence. Dual-wavelength fluorescence images were acquired using a targeted 111In- DTPA-K(IRDye800)-c(KRGDf) to selectively detect tumor angiogenesis and an untargeted Cy5.5 to image lymphatics. After acquiring the experimental data, fluorescence image-guided surgery was performed. Dynamic, multi-wavelength fluorescence imaging was accomplished using a liquid crystal tunable filter (LCTF). Excitation light was used for reflectance images with a LCTF transmitting a shorter wavelength than the peak in the excitation light spectrum. Therefore, images can be dynamically acquired alternating frame by frame between emission and excitation light, which should enable image-guided surgery.
Evaluation Of Near Infrared Contrast Agents For Cancer Detection Using Optical Imaging Techniques
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Author : Akram Abuteen
language : en
Publisher:
Release Date : 2016
Evaluation Of Near Infrared Contrast Agents For Cancer Detection Using Optical Imaging Techniques written by Akram Abuteen and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
Near Infrared Fluorescent Optical Lymphography For Cancer Diagnostics
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Author : Jessica Perea Houston
language : en
Publisher:
Release Date : 2007
Near Infrared Fluorescent Optical Lymphography For Cancer Diagnostics written by Jessica Perea Houston and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with categories.
A new molecular imaging modality has been developed to detect and locate positive axillary and sentinel lymph nodes non-invasively in breast cancer patients undergoing lymphoscintigraphy. The modality is based on fluorescent photon detection to locate the presence of indocyanine green (ICG) in the lymph subsequent to peritumoral injection of ICG into the breast. The imaging system consists of a gain-modulated intensified charge-coupled device (ICCD) camera, which captures low-intensity, near-infrared, and frequency-modulated photons. A four-fold "optical lymphography" study was conducted to (1) Examine fluorescence depth penetration and ICCD system accuracy at clinically relevant depths, (2) Compare image quality of the ICCD system vs. conventional gamma imaging, (3) Measure ICG pharmacokinetics in vivo, and (4) Develop a clinical protocol while examining pre-clinical factors such as the outcome of combining ICG with sulfur colloids used in lymphoscintigraphy. The frequency-domain ICCD system was found to precisely detect modulation amplitude, I [subscript AC], and phase, [theta], at depths up to 9 cm and with I [subscript AC] accuracy less than 20% and [theta] less than 2° using an 80-mW laser incident on phantoms having ranging tissue optical properties. Significant differences in the mean depth of penetration owing to 0.62-ns lifetime and 100-MHz frequency increases were detected. An in vivo optical vs. nuclear image quality comparison demonstrated statistically similar (alpha]=0.05) target-to-background ratios for optical (1.4+/-0.3) and nuclear (1.5+/-0.2). Alternatively, resulting image signal-to-noise ratios (SNR) from the ICCD system were greater than that achieved with a conventional gamma camera (Pvalue“0.01). Analysis of SNR versus contrast showed greater sensitivity of optical over nuclear imaging for subcutaneous tumors. In vivo and rapid detection of ICG in the blood-stream of nude mice was accomplished with a home-built avalanche photodiode dynamic fluorescence measurement system. Intensity data upon i.v. injection were regressed with a pharmacokinetic model describing the partitioning of ICG from the blood to the surrounding tissues. ICG blood-clearance was detected approximately 15 min after injection. Lastly, a human subject protocol was written, practiced, and federally approved for the application of optical lymphography. Furthermore, ICG was unaffected when mixed with sulfur colloids thus supporting the feasibility for combining fluorescence imaging with lymphoscintigraphy in breast cancer patients.
Optimization Of Near Infrared Bifunctional Cancer Imaging And Photodynamic Therapy Agents Through Structure Activity Relationship Studies
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Author :
language : en
Publisher:
Release Date : 2014
Optimization Of Near Infrared Bifunctional Cancer Imaging And Photodynamic Therapy Agents Through Structure Activity Relationship Studies written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Cancer imaging has an important role in the detection and diagnosis both before and after anti-cancer treatment. In certain clinical interventions such as surgery, there remains an unmet need to have real time imaging techniques which can assist the surgeon in complete resection of tumors. In highly inflamed areas such as tumor margins, it can be exceptionally difficult to distinguish between normal and malignant tissue. Fluorescence optical imaging is a real time imaging modality which could aid in distinguishing tumor and non-tumor tissue through the use of tumor specific fluorescence agents (fluorophores). The practice of using these fluorophores to assist in discerning malignant tissue is a clinical practice known as image guided therapy. This technique is still being validated and can be improved upon with the use of better fluorophores which would allow clinicians to detect malignant cells deeper in tissue. Deeper detection can occur through the use of near-infrared (NIR) fluorophores which absorb light at wavelengths where there is little interference and hindrance from endogenous light absorbers present in patient. Additionally, another light based intraoperative practice such as photodynamic therapy (PDT) might be further able to enhance long term survival outcomes. PDT could work in this setting to further destroy cancerous tissue but in a less invasive manner than surgery. Previous work from our laboratory has revolved around the deep red absorbing chlorophyll-a derivate 3-(1'-hexyloxy)ethyl-3-devinyl-pyropheophorbide-a (HPPH). In our laboratory's work, we have shown that HPPH is an exceedingly well tolerated second generation photosensitizer which can effectively improve survival outcome with PDT.^Our laboratory used these abilities of HPPH and in the first of its kind study, HPPH was conjugated to a NIR absorbing cyanine dye (CD) to develop a single agent which could use long wavelength light for selective fluorescence detection and PDT treatment of tumors. While imaging and treatment was successful with this compound, it also had a few drawbacks. One of the problems encountered was the high amount of bifunctional drug required to successfully treat the tumor by PDT verses the HPPH alone. It is believed that this was due to quenching of singlet oxygen by the CD upon activation of the PS and also due to energy transfer through F©œrster Resonance Energy Transfer (FRET). Therefore, we hypothesize that structure activity relationship studies (SAR) on a series of imaging and therapeutic agents will enable us to develop a single agent with near infrared fluorescence image guided photodynamic therapy.^One strategy to develop an image guided agent through a new porphyrin-cyanine dye conjugate is to develop a more tumor selective cyanine dye. In Aim I of this work we used structure activity relationship (SAR) to design and synthesize a series of IR820 cyanine dye derivatives with various functional groups around their periphery. Favorable in vivo tumor selectivity over normal tissue, retention time in tumor, and photophysical properties all factored into determining which of those substituents would be further pursued. These studies showed that introduction of 4-aminophenylthiol to IR820 resulted in the most favorable cyanine dyes being created. Substitution of the amine functionality or removal of the sulfur group gave suboptimal results thereby validating the importance of the entire 4-aminophenylthioether group.^While not as substantial in yielding a favorable cyanine dye, studies from Aim I also showed N-alkyl sufonate was preferential over N-alkylcarboxylic acid and that modification occurring meso to the 4-aminophenylthiol did not greatly alter the favorable drug profile. To further improve our lab's approach to a making image guided agents, Aim II sought to overcome the deficiencies of the photosensitizer-cyanine dye conjugate by complexing the heavy metals indium, gallium, and palladium within the porphyrin core. This approach was taken because previous studies have shown that metallation can reduce FRET and also increase singlet oxygen yields. Our studies showed that indium and palladium compounds generated more singlet oxygen than the non-metallated HPPH-CD and also reduced FRET. However, it was the introduction of indium within the HPPH of the conjugate that had the most favorable effects. Studies with the In(III)HPPH-CD compound showed favorable in vivo tumor selectivity and high in vitro/vivo PDT efficacy. In attempts to further improve upon In(III)HPPH-CD, the effect of varying the linker length between the porphyrin and CD were analyzed. Extending the linker length was thought to increase the spatial separation between the HPPH from CD moieties. This effect was seen with the longest linker length compound of 6 carbons as reduction in FRET and photobleaching were shown in vitro. However, in vivo PDT efficacy studies ultimately showed limited benefits in extending the linker length versus the original In(III)HPPH-CD. As the lead compound, in depth studies were performed with In(III)HPPH-CD to examine its toxicity profile. While well tolerated at the therapeutic dose, histopathological renal lesions were noted during post-mortem necropsy examinations in animals dosed with high amounts of drug. This renal toxicity is believed to be caused by free indium and therefore we are assessing ways to resolve this issue through administration of purer compound and delivery of more tumor selective agents. The final approach of this study for the development of NIR image guided agents was to use the NIR absorbing bacteriochlorin class of photosensitizers. Through preliminary SAR studies previously performed in our laboratory, two lead candidates were established. In Aim III of this work, full biological analysis was performed on the methyl ester and carboxylic acid derivatives of 3-(1-butoxy)ethyl-3-deacetylbacteriopurpurin-18-N-butylimide. Early in vitro studies examining uptake and PDT efficacy suggested the carboxylic acid derivative to be an improved agent over the methyl ester analog.^However, when tested in vivo, the methyl ester compound was observed to have significantly higher tumor selectivity which in turn resulted in >60% long term PDT survival outcome in tumor bearing mice vs. 14% with the carboxylic acid derivative. In addition to in vivo PDT efficacy, the methyl ester bacteriochlorin was also found to have minimal phototoxicity in normal tissue, favorable biodistribution as measured by 14C radiotracing, and minimal drug toxicity. Another observation from this study was that the lead bacteriochlorin exists as an epimeric mixture of two stereoisomers and their purification by HPLC was also performed. While in vivo work is still in preliminary phases, in vitro studies suggest minimal differences exist between the two isomers and the epimeric mixture. Overall, we have demonstrated the benefit that rational drug design through SAR can have on the development of bifunctional agents which can be used for both fluorescence optical imaging and photodynamic therapy. The compounds established from this work have been designed to have favorable optical imaging capabilities, tumor selectivity, and therapeutic potential. It is these characteristics that make the agents ideal candidates for further studies into their ability to be used as real time image guided therapeutic agents for the improvement of long term survival rates.
Concurrent Mr Nir Imaging For Breast Cancer Diagnosis
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Author :
language : en
Publisher:
Release Date : 2005
Concurrent Mr Nir Imaging For Breast Cancer Diagnosis written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005 with categories.
The primary objective of this research program is to investigate concurrent near infrared (NTR) optical and magnetic resonance (MR) imaging for breast cancer diagnosis. The NIR diffuse optical imaging offers novel criteria for cancer differentiation with the ability to measure (in vivo) oxygenation and vascularization state, the uptake and release of contrast agents and chromophore concentrations with high sensitivity. However, NIR diffuse optical tomography is inherently a low spatial resolution imaging modality due to diffuse nature of light photons. Alternatively, MRI provides high spatial resolution with excellent tissue discrimination, but has limited ability to monitor hemoglobin dynamics and other contrast mechanisms that optical imaging provides. Therefore, concurrent MRI-NIR optical imaging brings together the most advantageous aspects of the two imaging modalities for breast cancer diagnosis.
Assessment Of Optical Transmission And Image Contrast At Infrared Wavelengths Using Tissue Simulating Phantoms And Biological Tissues
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Author : Khushbu Dipak Patel
language : en
Publisher:
Release Date : 2017
Assessment Of Optical Transmission And Image Contrast At Infrared Wavelengths Using Tissue Simulating Phantoms And Biological Tissues written by Khushbu Dipak Patel and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with Diagnostic imaging categories.
In vivo fluorescence imaging is an emerging technique with potential for usage in non-invasive cancer screening, surveillance, real-time surgical guidance, and staging. Fluorescence imaging uses the interaction of non-ionizing optical radiation with endogenous fluorophores or fluorescent labels to provide real-time wide-field images of tissue structure and/or functional components. When imaging in vivo, excitation light must travel through overlying tissue to reach the fluorescent target and emitted fluorescence must then propagate back through the overlying tissue in order to be imaged onto a camera. Recently, fluorescent contrast agents have been developed with excitation and emission wavelengths in the near infrared (NIR) spectrum (~700 - 1,000 nm) in order to minimize attenuation and maximize the measured signal from tissue. While several clinical trials have shown the potential benefits of NIR contrast agents over visible fluorophores, there may still be room for improvement by moving to even longer wavelengths. As scattering is reduced as wavelength increases, some researchers are investigating fluorophores that emit in the short-wave infrared (SWIR) wavelength region (~1,000 - 2,300 nm). This study focuses on examining optical transmission and image contrast at NIR wavelengths and SWIR wavelengths to determine which wavelength region may be optimal for development of fluorescent contrast agents. Transmission and contrast measurements were performed on both tissue simulating phantoms and real biological tissues using 780 nm, 980 nm, and 1550 nm wavelengths. From the experiments conducted, it appears that fluorophore emissions should be chosen based on the goals of the specific application. For an application that requires simple detection of signal, near infrared wavelengths will be better as they can be detected with higher signal levels. For an application that focuses on imaging fluorophore-labeled tissues, short-wave infrared wavelengths will be the better option as they provided better image contrast.
Fluorescence Enhanced Optical Tomography On Breast Phantoms With Measurements Using A Gain Modulated Intensified Ccd Imaging System
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Author : Anuradha Godavarty
language : en
Publisher:
Release Date : 2005
Fluorescence Enhanced Optical Tomography On Breast Phantoms With Measurements Using A Gain Modulated Intensified Ccd Imaging System written by Anuradha Godavarty and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005 with categories.
Fluorescence-enhanced optical imaging using near-infrared (NIR) light developed for in-vivo molecular targeting and reporting of cancer provides promising opportunities for diagnostic imaging. However, prior to the administration of unproven contrast agents, the benefits of fluorescence-enhanced optical imaging must be assessed in feasibility phantom studies. A novel intensified charge-coupled device (ICCD) imaging system has been developed to perform 3-D fluorescence tomographic imaging in the frequency-domain using near-infrared contrast agents. This study is unique since it (i) employs a large tissue-mimicking phantom (~1087 cc), which is shaped and sized to resemble a female breast and part of the extended chest wall region, and (ii) enables rapid data acquisition in the frequency-domain by using a gain-modulated ICCD camera. Diagnostic 3-D fluorescence-enhanced optical tomography is demonstrated using 0.5-1 cc single and multiple targets contrasted from their surrounding by [mu]M concentrations of Indocyanine green (ICG) in the breast-shaped phantom (10 cm diameter), under varying conditions of target-to-background absorption contrast ratios (1:0 and 100:1) and target depths (up to 3 cm deep). Boundary surface fluorescence measurements of referenced amplitude and phase shift were used along with the coupled diffusion equation of light propagation in order to perform 3-D image reconstructions using the approximate extended Kalman filter (AEKF) algorithm, and hence differentiate the target from the background based on fluorescent optical contrast. Detection of single and multiple targets is demonstrated under various conditions of target depths (up to 2 cm deep), absorption optical contrast ratio (1:0 and 100:1), target volumes (0.5-1 cc), and multiple targets (up to three 0.5 cc targets). The feasibility of 3-D image reconstructions from simultaneous multiple point excitation sources are presented. Preliminary lifetime imaging studies with 1:2 and 2:1 optical contrast in fluorescence lifetime of the contrast agents is also demonstrated. The specificity of the optical imager is further assessed from homogeneous phantom studies containing no fluorescently contrasted targets. While nuclear imaging currently provides clinical diagnostic opportunities using radioactive tracers, molecular targeting of tumors using non-ionizing NIR contrast agents tomographically imaged using the frequency-domain ICCD imaging system could possibly become a new method of diagnostic imaging.
Development And Applications Of Novel Fluorescent Molecular Probe Strategies
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Author : Dolonchampa Maji
language : en
Publisher:
Release Date : 2017
Development And Applications Of Novel Fluorescent Molecular Probe Strategies written by Dolonchampa Maji and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with Electronic dissertations categories.
Optical imaging and spectroscopy technologies offer the ability to provide structural and functional information in a fast, low-cost, ionizing radiation free, highly sensitive and high throughput fashion. The diverse contrast mechanisms and complementary imaging platforms form the foundation for the application of optical imaging in pre-clinical studies of pathophysiological development as well as direct clinical application as a tool for diagnosis and therapy. Fluorescence imaging techniques have been one of the most rapidly adopted methods in biology and biomedicine. Visualization of biological processes and pathologic conditions at the cellular and tissue levels largely relies on the use of exogenous fluorophores or their bioconjugates. Some fluorescent molecular probes provide usable contrast for disease diagnosis due to their responsiveness to interactions with other molecular species and/or immediate microenvironment. As a result, understanding exogenous fluorescent contrast mechanisms will allow the development of efficient strategies for biomedical fluorescence imaging. The present work focuses on exploring novel fluorescent molecular probe strategies for imaging cancer and cardiovascular diseases. We have developed a platform for synthesizing activatable fluorescent molecular probes using the fluorescence quenching properties of copper (II) ions. We used these activatable probes for rapid imaging of cancerous tissue in vivo in mice. While developing these molecular probes, we discovered an unexpected molecular interaction that yields stable dimeric molecules. This finding can potentially enable the development of new molecular entities for modifying the signaling properties of fluorescent dyes to minimize background fluorescence. Although planar fluorescence imaging methods using exogenous molecular probes provide rapid information about molecular processes in vivo, extraction of depth information require complex data acquisition and image analysis methods. By designing a dual emission fluorescent probe incorporating two spectrally different fluorophore systems, we developed a method to successfully estimate the depth of fluorescent inclusions from planar imaging data and demonstrated the potential of using this approach to locate a blood vessel and tumorous tissue in mouse in vivo. An important feature of fluorescence methods is the availability of various techniques that provide complementary information. Combining the fluorescence intensity and lifetime properties of a biologically targeted near infrared fluorescent probe, we demonstrate an effective way to distinguish specific from nonspecific uptake mechanisms in cancer cells, an approach that can be translated in vivo. Alternatively, dynamic fluorescence imaging technique expands the scope of applications to include detection and estimation of the size of circulating cancer cells and clusters. The approach developed in this work could allow longitudinal monitoring of these cells, which are implicated in cancer metastases. To circumvent the shallow penetration of light using optical methods, we developed multimodal imaging approaches by incorporating a radionuclide for nuclear imaging into a broad spectrum near infrared fluorescent tumor targeting agent. This molecular construct allows for noninvasive whole body nuclear imaging of tumors, followed by fluorescence image guided resection. In each of these areas, novel fluorescent molecular probes were developed, characterized and applied to solve critical biomedical problems.
Three Dimensional Near Infrared Optical Imaging Using Ultrasound Guidance For Breast Cancer Detection And Diagnosis
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Author : Minming Huang
language : en
Publisher:
Release Date : 2004
Three Dimensional Near Infrared Optical Imaging Using Ultrasound Guidance For Breast Cancer Detection And Diagnosis written by Minming Huang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with Electronic dissertations categories.
This dissertation focuses on the study of three-dimensional near-infrared (NIR) imaging reconstruction using ultrasound localization for breast cancer detection and diagnosis. With the 3D NIR forward model for reflection geometry built and investigated, successful reconstruction of both absorption and scattering coefficients has been obtained and evaluated using both a phantom study and initial clinic data. In this work, we first introduce a dual mesh optical reconstruction method with depth correction using a priori ultrasound information. It can significantly improve the reconstructed absorption distributions in deeper target layers. Clinical results have shown improved correlation between reconstructed total hemoglobin concentrations and the histological micorvessel density counts. Next, a combined Tikhonov regularization and dual mesh scheme based on finite element method (FEM) is proposed to solve the inter-parameter cross talk between the scattering coefficient and absorption coefficient. In this approach, the optimal regularization factor is given by the standard L-curve. Different regularization factors have been assigned to the target region and non-target region to incorporate the priori target information from the co-registered ultrasound images. Both phantom experiments and clinic examples have shown that this new approach has the ability to reconstruct the absorption and diffusion coefficients simultaneously, and the reconstructed target absorption and diffusion maps have no depth dependence effect. Finally, a simple two-layer model is generated and studied to solve a clinical issue related to the chest wall, which is a mixture of bones and muscles. For small breasts, the chest wall appears within 2–3 cm distance from the skin surface. As a result, the simple one layer model is not accurate. Furthermore, for some cases, there is also an obvious chest wall mismatch between the reference site and lesion site. To solve this clinical issue, a simplified two-layer model is generated and a fitting method is adopted to estimate the optical properties of both layers. Then a correction method is applied to correct for the chest wall mismatch between the lesion site and reference site. With this scheme, phantom targets located on top of the chest wall phantom layer can be reconstructed with good contrast and resolution.