Singular value decomposition based regularization prior to spectral mixing improves crosstalk in dynamic imaging using spectral diffuse optical tomography

The spectrally constrained diffuse optical tomography (DOT) method relies on incorporating spectral prior information directly into the image reconstruction algorithm, thereby correlating the underlying optical properties across multiple wavelengths. Although this method has been shown to provide a solution that is stable, the use of conventional Tikhonov-type regularization techniques can lead to additional crosstalk between parameters, particularly in linear, single-step dynamic imaging applications. This is due mainly to the suboptimal regularization of the spectral Jacobian matrix, which smoothes not only the image-data space, but also the spectral mapping space. In this work a novel regularization technique based on the singular value decomposition (SVD) is presented that preserves the spectral prior information while regularizing the Jacobian matrix, leading to dramatically reduced crosstalk between the recovered parameters. Using simulated data, images of changes in oxygenated and deoxygenated hemoglobin concentrations are reconstructed via the SVD-based approach and compared with images reconstructed by using non-spectral and conventional spectral methods. In a 2D, two wavelength example, it is shown that the proposed approach provides a 98% reduction in crosstalk between recovered parameters as compared with conventional spectral reconstruction algorithms, and 60% as compared with non-spectrally constrained algorithms. Using a subject specific multilayered model of the human head, a noiseless dynamic simulation of cortical activation is performed to further demonstrate such improvement in crosstalk. However, with the addition of realistic noise in the data, both non-spectral and proposed algorithms perform similarly, indicating that the use of spectrally constrained reconstruction algorithms in dynamic DOT may be limited by the contrast of the signal as well as the noise characteristics of the system.OCIS codes: (110.6960) Tomography, (170.2655) Functional monitoring and imaging, (170.3010) Image reconstruction techniques, (170.3660) Light propagation in tissues     

多层螺旋CT对弥漫性泛细支气管炎的诊断价值

目的分析弥漫性泛细支气管炎（DPB）的多层螺旋CT表现,提高对本病的诊断准确性。方法回顾性分析本院收治13例弥漫性泛细支气管炎的多层螺旋CT表现。结果13例中12例病变呈弥漫性分布,1例呈局限性分布。其多层螺旋CT表现：（1）弥漫性细粟粒样影伴树芽征,无融合趋势13例;（2）小气道的支气管扩张12例,合并有黏液栓3例;（3）小斑片状实变影8例、小空洞影2例,肺间质纤维化3例;（4）有副鼻窦炎病史11例,最常累及上颌窦;（5）DPB治疗前后CT变化,经治疗1~3个月后复查,病变有不同程度吸收。结论DPB的多层螺旋CT表现有一定的特征性,对DPB的诊断具有重要的作用。     

Shape-parameterized diffuse optical tomography holds promise for sensitivity enhancement of fluorescence molecular tomography

A fundamental approach to enhancing the sensitivity of the fluorescence molecular tomography (FMT) is to incorporate diffuse optical tomography (DOT) to modify the light propagation modeling. However, the traditional voxel-based DOT has been involving a severely ill-posed inverse problem and cannot retrieve the optical property distributions with the acceptable quantitative accuracy and spatial resolution. Although, with the aid of an anatomical imaging modality, the structural-prior-based DOT method with either the hard- or soft-prior scheme holds promise for in vivo acquiring the optical background of tissues, the low robustness of the hard-prior scheme to the segmentation error and inferior performance of the soft-prior one in the quantitative accuracy limit its further application. We propose in this paper a shape-parameterized DOT method for not only effectively determining the regional optical properties but potentially achieving reasonable structural amelioration, lending itself to FMT for comparably improved recovery of fluorescence distribution.OCIS codes: (170.3880) Medical and biological imaging, (170.6960) Tomography, (170.3010) Image reconstruction techniques     

Video-rate fluorescence diffuse optical tomography for in vivo sentinel lymph node imaging

We have developed a fiber-based, video-rate fluorescence diffuse optical tomography (DOT) system for noninvasive in vivo sentinel lymph node (SLN) mapping. Concurrent acquisition of fluorescence and reference signals allowed the efficient generation of ratio-metric data for 3D image reconstruction. Accurate depth localization and high sensitivity to fluorescent targets were established in to depths of >10 mm. In vivo accumulation of indocyanine green (ICG) dye was imaged in the region of the SLN following intradermal injection into the forepaw of rats. These results suggest that video-rate fluorescence DOT has significant potential as a clinical tool for noninvasive mapping of SLN.     

彩色多普勒超声联合超声光散射成像技术在乳腺肿块诊断中的价值

目的联合应用彩色多普勒超声及超声光散射断层成像技术,探讨其在乳腺肿块诊断中的临床价值。方法选取中国医科大学附属第一医院乳腺外科行外科手术或麦默通治疗的117例女性患者,其中共179个乳腺包块,术前超声常规检查乳腺包块,彩色多普勒超声探查血流分级情况,同时超声光散射系统测量总血红蛋白浓度,每种方法分别计算敏感度、特异度、准确度、阳性预测值和阴性预测值,组间对乳腺肿物诊断准确度的比较采用χ2检验。结果彩色多普勒超声诊断乳腺肿块的敏感度、特异度、准确度、阳性预测值和阴性预测值分别为77.1％、78.9％、78.2％、70.1％和84.3％,超声光散射成像技术诊断乳腺肿块的敏感度、特异度、准确度、阳性预测值和阴性预测值分别为92.8％、67.0％、76.2％、64.4％和93.6％,超声光散射成像技术联合彩色多普勒超声诊断乳腺肿块的敏感度、特异度、准确度、阳性预测值和阴性预测值分别为95.6％、83.5％、93.4％、78.8％和96.8％。单独彩色多普勒超声与单独超声光散射成像技术诊断乳腺疾病的准确度差异无统计学意义（χ2＝0.06,P＞0.05）,而彩色多普勒超声联合超声光散射成像技术与单独彩色多普勒超声或单独超声光散射成像技术诊断乳腺疾病的准确度差异有统计学意义（χ2＝6.49,P＜0.05;χ2＝7.80,P＜0.05）。结论彩色多普勒超声与超声光散射成像技术的联合应用可提高乳腺肿块的诊断准确度,对临床诊断乳腺肿块提供了新的辅助诊断方法。     

超声光散射成像在乳腺良恶性肿块鉴别诊断中的应用价值

目的：探讨超声光散射成像技术在乳腺良恶性肿块鉴别诊断中的应用价值。方法：回顾性分析采用OPTIMUS对随机选取的48例乳腺疾病患者的58个肿块进行检查,结果与病理对照,分析超声光散射成像的应用价值。应用高频超声、光散射成像及二者联合分别计算诊断的敏感性、特异性和准确性,并绘制受试者工作特征（Receiver operating characteristic,ROC）,计算曲线下面积（Area under the curve,AUC）。结果：58个乳腺肿块术后及穿刺活检病理诊断良性31个、恶性27个,高频超声联合光散射成像诊断58个乳腺肿块中良性30个、恶性28个,诊断敏感性、特异性和准确性分别为96.3%、93.5%、94.8%。结论：高频超声联合光散射成像不仅从形态方面对肿块做出诊断,还能在功能方面对乳腺肿块做出诊断,明显提高了诊断准确率,对于临床早发现、早治疗提供一定的帮助。     

Split operator method for fluorescence diffuse optical tomography using anisotropic diffusion regularisation with prior anatomical information

Fluorescence diffuse optical tomography (fDOT) is an imaging modality that provides images of the fluorochrome distribution within the object of study. The image reconstruction problem is ill-posed and highly underdetermined and, therefore, regularisation techniques need to be used. In this paper we use a nonlinear anisotropic diffusion regularisation term that incorporates anatomical prior information. We introduce a split operator method that reduces the nonlinear inverse problem to two simpler problems, allowing fast and efficient solution of the fDOT problem. We tested our method using simulated, phantom and ex-vivo mouse data, and found that it provides reconstructions with better spatial localisation and size of fluorochrome inclusions than using the standard Tikhonov penalty term.     

Combined hemoglobin and fluorescence diffuse optical tomography for breast tumor diagnosis: a pilot study on time-domain methodology

A combined time-domain fluorescence and hemoglobin diffuse optical tomography (DOT) system and the image reconstruction methods are proposed for enhancing the reliability of breast-dedicated optical measurement. The system equipped with two pulsed laser diodes at wavelengths of 780 nm and 830 nm that are specific to the peak excitation and emission of the FDA-approved ICG agent, and works with a 4-channel time-correlated single photon counting device to acquire the time-resolved distributions of the light re-emissions at 32 boundary sites of tissues in a tandem serial-to-parallel mode. The simultaneous reconstruction of the two optical (absorption and scattering) and two fluorescent (yield and lifetime) properties are achieved with the respective featured-data algorithms based on the generalized pulse spectrum technique. The performances of the methodology are experimentally assessed on breast-mimicking phantoms for hemoglobin- and fluorescence-DOT alone, as well as for fluorescence-guided hemoglobin-DOT. The results demonstrate the efficacy of improving the accuracy of hemoglobin-DOT based on a priori fluorescence localization.OCIS codes: (170.3880) Medical and biological imaging, (170.6960) Tomography, (170.6920) Time-resolved imaging, (170.3010) Image reconstruction techniques     

Anatomical atlas-guided diffuse optical tomography of brain activation

We describe a neuroimaging protocol that utilizes an anatomical atlas of the human head to guide diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median-nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject-specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of diffuse optical tomography images of brain activation.     

Quantification in time-domain diffuse optical tomography using Mellin-Laplace transforms

Simulations and phantom measurements are used to evaluate the ability of time-domain diffuse optical tomography using Mellin-Laplace transforms to quantify the absorption perturbation of centimetric objects immersed at depth 1-2 cm in turbid media. We find that the estimated absorption coefficient varies almost linearly with the absorption change in the range of 0-0.15 cm⁻¹ but is underestimated by a factor that depends on the inclusion depth (~2, 3 and 6 for depths of 1.0, 1.5 and 2.0 cm respectively). For larger absorption changes, the variation is sublinear with ~20% decrease for δμ_a = 0.37 cm⁻¹. By contrast, constraining the absorption change to the actual volume of the inclusion may considerably improve the accuracy and linearity of the reconstructed absorption.OCIS codes: (170.6920) Time-resolved imaging, (110.6960) Tomography, (100.3010) Image reconstruction techniques, (110.0113) Imaging through turbid media, (030.5260) Photon counting, (230.5160) Photodetectors     

Incremental prognostic value of computed tomography in stroke: rationale and design of the IMPACTS study

This study was designed to determine the prognostic value of coronary computed tomography angiography (CCTA) in ischemic stroke patients and to identify any incremental risk stratification benefits of CCTA findings compared with coronary artery calcium scoring (CACS) and traditional Framingham risk scores (FRS) in ischemic stroke patients without chest pain. IMPACTS is a prospective, multicenter, observational cohort study in which at least seven centers in Korea will participate. All participants will be enrolled in this study after providing informed consent. Nine hundred total ischemic stroke patients without chest pain will be enrolled and will undergo CACS and CCTA. All participants will be followed-up for a minimum of 24 months to determine the endpoints. The primary endpoint will be occurrence of major adverse cardiovascular events (MACEs), defined as all-cause mortality, cardiovascular death, myocardial infarction, or cardiovascular events requiring hospitalization and revascularization either by percutaneous coronary intervention or by coronary artery bypass graft after 90 days of index testing during the follow-up period. Patient enrollment should be completed within 2.5 years. We plan to analyze and identify the CCTA predictors of MACEs. In addition, we will compare several models used to assess independent relationships between the variables and MACEs using a shared frailty model and therefore determine the incremental prognostic value of CCTA findings compared with either the CACS or FRS. The results of IMPACTS will provide valuable information for risk stratification with CCTA in ischemic stroke patients without chest pain.     

Comparison of different metrics for analysis and visualization in spectroscopic optical coherence tomography

Spectroscopic Optical Coherence Tomography (S-OCT) extracts depth resolved spectra that are inherently available from OCT signals. The back scattered spectra contain useful functional information regarding the sample, since the light is altered by wavelength dependent absorption and scattering caused by chromophores and structures of the sample. Two aspects dominate the performance of S-OCT: (1) the spectral analysis processing method used to obtain the spatially-resolved spectroscopic information and (2) the metrics used to visualize and interpret relevant sample features. In this work, we focus on the second aspect, where we will compare established and novel metrics for S-OCT. These concepts include the adaptation of methods known from multispectral imaging and modern signal processing approaches such as pattern recognition. To compare the performance of the metrics in a quantitative manner, we use phantoms with microsphere scatterers of different sizes that are below the system’s resolution and therefore cannot be differentiated using intensity based OCT images. We show that the analysis of the spectral features can clearly separate areas with different scattering properties in multi-layer phantoms. Finally, we demonstrate the performance of our approach for contrast enhancement in bovine articular cartilage.OCIS codes: (170.4500) Optical coherence tomography, (300.0300) Spectroscopy, (290.5850) Scattering, particles, (180.0180) Microscopy, (170.3880) Medical and biological imaging     

Spectroscopic detection improves multi-color quantification in fluorescence tomography

Simultaneous detection of several biological processes in vivo is a common requirement in biomedical and biological applications, and in order to address this issue the use of multiple fluorophores is usually the method of choice. Existing methodologies however, do not provide quantitative feedback of multiple fluorophore concentrations in small animals in vivo when their spectra overlap, especially when imaging the whole body in 3D. Here we present an approach where a spectroscopic module has been implemented into a custom-built Fluorescence Molecular Tomography (FMT) system. In contrast with other multispectral approaches, this multimodal imaging system is capable of recording the fluorescence spectra from each illumination point during a tomographic measurement. In situ spectral information can thus be extracted and used to improve the separation of overlapping signals associated with different fluorophores. The results of this new approach tested on both in vitro and in vivo experiments are presented, proving that accurate recovery of fluorophore concentrations can be obtained from multispectral tomography data even in the presence of high autofluorescence.     

Depth-recognizable time-domain fluorescence molecular tomography in reflective geometry

Conventional fluorescence molecular tomography (FMT) reconstruction requires photons penetrating the whole object, which limits its applications to small animals. However, by utilizing reflective photons, fluorescence distribution near the surface could be reconstructed regardless of the object size, which may extend the applications of FMT to surgical navigation and so on. Therefore, time-domain reflective fluorescence molecular tomography (TD-rFMT) is proposed in this paper. The system excites and detects the emission light from the same angle within a field of view of 5 cm. Because the detected intensities of targets depend strongly on the depth, the reconstruction of targets in deep regions would be evidently affected. Therefore, a fluorescence yield reconstruction method with depth regularization and a weighted separation reconstruction strategy for lifetime are developed to enhance the performance for deep targets. Through simulations and phantom experiments, TD-rFMT is proved capable of reconstructing fluorescence distribution within a 2.5-cm depth with accurate reconstructed yield, lifetime, and target position(s).     

Dynamic diffuse optical tomography imaging of peripheral arterial disease

Peripheral arterial disease (PAD) is the narrowing of arteries due to plaque accumulation in the vascular walls. This leads to insufficient blood supply to the extremities and can ultimately cause cell death. Currently available methods are ineffective in diagnosing PAD in patients with calcified arteries, such as those with diabetes. In this paper we investigate the potential of dynamic diffuse optical tomography (DDOT) as an alternative way to assess PAD in the lower extremities. DDOT is a non-invasive, non-ionizing imaging modality that uses near-infrared light to create spatio-temporal maps of oxy- and deoxy-hemoglobin in tissue. We present three case studies in which we used DDOT to visualize vascular perfusion of a healthy volunteer, a PAD patient and a diabetic PAD patient with calcified arteries. These preliminary results show significant differences in DDOT time-traces and images between all three cases, underscoring the potential of DDOT as a new diagnostic tool.OCIS codes: (170.3880) Medical and biological imaging, (170.6960) Tomography     

Doppler velocity detection limitations in spectrometer-based versus swept-source optical coherence tomography

Recent advances in Doppler techniques have enabled high sensitivity imaging of biological flow to measure blood velocities and vascular perfusion. Here we compare spectrometer-based and wavelength-swept Doppler OCT implementations theoretically and experimentally, characterizing the lower and upper observable velocity limits in each configuration. We specifically characterize the washout limit for Doppler OCT, the velocity at which signal degradation results in loss of flow information, which is valid for both quantitative and qualitative flow imaging techniques. We also clearly differentiate the washout effect from the separate phenomenon of phase wrapping. We demonstrate that the maximum detectable Doppler velocity is determined by the fringe washout limit and not phase wrapping. Both theory and experimental results from phantom flow data and retinal blood flow data demonstrate the superiority of the swept-source technique for imaging vessels with high flow rates.     

Improved bioluminescence and fluorescence reconstruction algorithms using diffuse optical tomography, normalized data, and optimized selection of the permissible source region

Reconstruction algorithms are presented for two-step solutions of the bioluminescence tomography (BLT) and the fluorescence tomography (FT) problems. In the first step, a continuous wave (cw) diffuse optical tomography (DOT) algorithm is used to reconstruct the tissue optical properties assuming known anatomical information provided by x-ray computed tomography or other methods. Minimization problems are formed based on L1 norm objective functions, where normalized values for the light fluence rates and the corresponding Green's functions are used. Then an iterative minimization solution shrinks the permissible regions where the sources are allowed by selecting points with higher probability to contribute to the source distribution. Throughout this process the permissible region shrinks from the entire object to just a few points. The optimum reconstructed bioluminescence and fluorescence distributions are chosen to be the results of the iteration corresponding to the permissible region where the objective function has its global minimum This provides efficient BLT and FT reconstruction algorithms without the need for a priori information about the bioluminescence sources or the fluorophore concentration. Multiple small sources and large distributed sources can be reconstructed with good accuracy for the location and the total source power for BLT and the total number of fluorophore molecules for the FT. For non-uniform distributed sources, the size and magnitude become degenerate due to the degrees of freedom available for possible solutions. However, increasing the number of data points by increasing the number of excitation sources can improve the accuracy of reconstruction for non-uniform fluorophore distributions.     

Improved bioluminescence and fluorescence reconstruction algorithms using diffuse optical tomography, normalized data, and optimized selection of the permissible source region

Reconstruction algorithms are presented for two-step solutions of the bioluminescence tomography (BLT) and the fluorescence tomography (FT) problems. In the first step, a continuous wave (cw) diffuse optical tomography (DOT) algorithm is used to reconstruct the tissue optical properties assuming known anatomical information provided by x-ray computed tomography or other methods. Minimization problems are formed based on L1 norm objective functions, where normalized values for the light fluence rates and the corresponding Green’s functions are used. Then an iterative minimization solution shrinks the permissible regions where the sources are allowed by selecting points with higher probability to contribute to the source distribution. Throughout this process the permissible region shrinks from the entire object to just a few points. The optimum reconstructed bioluminescence and fluorescence distributions are chosen to be the results of the iteration corresponding to the permissible region where the objective function has its global minimum This provides efficient BLT and FT reconstruction algorithms without the need for a priori information about the bioluminescence sources or the fluorophore concentration. Multiple small sources and large distributed sources can be reconstructed with good accuracy for the location and the total source power for BLT and the total number of fluorophore molecules for the FT. For non-uniform distributed sources, the size and magnitude become degenerate due to the degrees of freedom available for possible solutions. However, increasing the number of data points by increasing the number of excitation sources can improve the accuracy of reconstruction for non-uniform fluorophore distributions.OCIS codes: (170.6960) Tomography, (170.3880) Medical and biological imaging     

Cramer-Rao analysis of steady-state and time-domain fluorescence diffuse optical imaging

Using a Cramer-Rao analysis, we study the theoretical performances of a time and spatially resolved fDOT imaging system for jointly estimating the position and the concentration of a point-wide fluorescent volume in a diffusive sample. We show that the fluorescence lifetime is a critical parameter for the precision of the technique. A time resolved fDOT system that does not use spatial information is also considered. In certain cases, a simple steady-state configuration may be as efficient as this time resolved fDOT system.