In vivo fluorescence lifetime optical projection tomography

We demonstrate the application of fluorescence lifetime optical projection tomography (FLIM-OPT) to in vivo imaging of lysC:GFP transgenic zebrafish embryos (Danio rerio). This method has been applied to unambiguously distinguish between the fluorescent protein (GFP) signal in myeloid cells from background autofluorescence based on the fluorescence lifetime. The combination of FLIM, an inherently ratiometric method, in conjunction with OPT results in a quantitative 3-D tomographic technique that could be used as a robust method for in vivo biological and pharmaceutical research, for example as a readout of Förster resonance energy transfer based interactions.OCIS codes: (170.3650) Lifetime-based sensing, (170.6900) Three-dimensional microscopy, (170.6920) Time-resolved imaging, (170.6960) Tomography     

模型基础的迭代重建算法优化腹部静脉成像质量

目的 探讨应用模型基础的迭代重建(MBIR)算法优化腹部CT静脉成像(CTV)图像质量的价值.方法 应用自动管电流调节技术对27例可疑腹部病变患者行腹部CT扫描,分别采用滤波反投影技术(FBP组)、50％自适应统计迭代重建(ASiR组)和MBIR(MBIR组)3种算法对原始数据进行重建;测量背部肌肉、背部脂肪、肝实质、胰腺实质、脾实质的噪声及CT值,计算门静脉、胰静脉、脾静脉及下腔静脉的CNR;采用5分制对图像质量进行评分.采用方差分析和秩和检验对数据进行统计学分析.结果 3组图像CT值的差异无统计学意义(P均＞0.05).MBIR组图像噪声低于ASiR组(P＜0.001),而二者均低于FBP组(P均＜0.05);与FBP组图像相比,ASiR组和MBIR组图像噪声分别降低28.61％和53.53％,CNR分别增加40.92％和158.85％.MBIR组、ASiR组和FBP组的主观评分分别为(4.64±0.31)分、(3.74±0.54)分及(3.22±0.60)分,差异有统计学意义(P=0.008).结论 MBIR重建算法可以明显提高腹部CTV图像质量,并具有降低腹部CTV辐射剂量的潜能.     

Hyperspectral image reconstruction for diffuse optical tomography

We explore the development and performance of algorithms for hyperspectral diffuse optical tomography (DOT) for which data from hundreds of wavelengths are collected and used to determine the concentration distribution of chromophores in the medium under investigation. An efficient method is detailed for forming the images using iterative algorithms applied to a linearized Born approximation model assuming the scattering coefficient is spatially constant and known. The L-surface framework is employed to select optimal regularization parameters for the inverse problem. We report image reconstructions using 126 wavelengths with estimation error in simulations as low as 0.05 and mean square error of experimental data of 0.18 and 0.29 for ink and dye concentrations, respectively, an improvement over reconstructions using fewer specifically chosen wavelengths.     

Model-based optical coherence tomography angiography enables motion-insensitive vascular imaging

We present a significant step toward ultrahigh-resolution, motion-insensitive characterization of vascular dynamics. Optical coherence tomography angiography (OCTA) is an invaluable diagnostic technology for non-invasive, label-free vascular imaging in vivo. However, since it relies on detecting moving cells from consecutive scans, high-resolution OCTA is susceptible to tissue motion, which imposes challenges in resolving and quantifying small vessels. We developed a novel OCTA technique named ultrahigh-resolution factor angiography (URFA) by modeling repeated scans as generative latent variables, with a common variance representing shared features and a unique variance representing motion. By iteratively maximizing the combined log-likelihood probability of these variances, the unique variance is largely separated. Meanwhile, features in the common variance are decoupled, in which vessels with dynamic flow are extracted from tissue structure by integrating high-order factors. Combined with Gabor-domain optical coherence microscopy, URFA successfully extracted high-resolution cutaneous vasculature despite severe involuntary tissue motion and scanner oscillation, significantly improving the visualization and characterization of micro-capillaries in vivo. Compared with the conventional approach, URFA reduces motion artifacts by nearly 50% on average, evaluated on local differences.     

Optimization of 360 degrees projection fluorescence molecular tomography

Fluorescence tomography of tissues has been generally limited to systems that require fixed geometries or measurements employing fibers. Certain technological advances however, have more recently allowed the development of complete-projection 360 degrees tomographic approaches using non-contact detection and illumination. Employing multiple illumination projections and CCD cameras as detection devices vastly increases the information content acquired, posing non-trivial computational and experimental requirements. In this paper, we use singular-value analysis to optimize experimental parameters relevant to the design and operation of emerging 360 degrees fluorescence molecular tomography (FMT) methods and systems for small animal imaging. We present the theoretical and experimental methodology, optimization results and their experimental validation. We further discuss how these results can be employed to improve the performance of existing FMT systems and guide the design of new systems.     

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     

Effective optode configuration for the image reconstruction in diffuse optical tomography

The influence of the configuration of the optodes on the images of diffuse optical tomography (DOT) was investigated using 3D numerical simulations. 3D distributions of the absorption coefficients in a spherical object were reconstructed from the numerically simulated measurement data for various configurations of the optodes. When the optodes were placed in a plane containing a target which strongly absorbs light, the target could be reconstructed with good localization. For good reconstruction of the target, it was found to be very important that the optode configuration was optimized in order to detect light propagating through the target effectively. The simulations also showed that the optode configuration affects the quality of the reconstructed images and that some prior information about the measured object improved the DOT images. Finally the simulation results were verified by a phantom experiment.     

Regression-based neural network for improving image reconstruction in diffuse optical tomography

Diffuse optical tomography (DOT) is a non-invasive imaging technique utilizing multi-scattered light at visible and infrared wavelengths to detect anomalies in tissues. However, the DOT image reconstruction is based on solving the inverse problem, which requires massive calculations and time. In this article, for the first time, to the best of our knowledge, a simple, regression-based cascaded feed-forward deep learning neural network is derived to solve the inverse problem of DOT in compressed breast geometry. The predicted data is subsequently utilized to visualize the breast tissues and their anomalies. The dataset in this study is created using a Monte-Carlo algorithm, which simulates the light propagation in the compressed breast placed inside a parallel plate source-detector geometry (forward process). The simulated DL-DOT system''s performance is evaluated using the Pearson correlation coefficient (R) and the Mean squared error (MSE) metrics. Although a comparatively smaller dataset (50 nos.) is used, our simulation results show that the developed feed-forward network algorithm to solve the inverse problem delivers an increment of ∼30% over the analytical solution approach, in terms of R. Furthermore, the proposed network''s MSE outperforms that of the analytical solution''s MSE by a large margin revealing the robustness of the network and the adaptability of the system for potential applications in medical settings.     

Parametric level set reconstruction methods for hyperspectral diffuse optical tomography

A parametric level set method (PaLS) is implemented for image reconstruction for hyperspectral diffuse optical tomography (DOT). Chromophore concentrations and diffusion amplitude are recovered using a linearized Born approximation model and employing data from over 100 wavelengths. The images to be recovered are taken to be piecewise constant and a newly introduced, shape-based model is used as the foundation for reconstruction. The PaLS method significantly reduces the number of unknowns relative to more traditional level-set reconstruction methods and has been show to be particularly well suited for ill-posed inverse problems such as the one of interest here. We report on reconstructions for multiple chromophores from simulated and experimental data where the PaLS method provides a more accurate estimation of chromophore concentrations compared to a pixel-based method.     

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.     

Accelerated image reconstruction in fluorescence molecular tomography using dimension reduction

With the development of charge-coupled device (CCD) camera based non-contact fluorescence molecular tomography (FMT) imaging systems, multi projections and densely sampled fluorescent measurements used in subsequent image reconstruction can be easily obtained. However, challenges still remain in fast image reconstruction because of the large computational burden and memory requirement in the inverse problem. In this work, an accelerated image reconstruction method in FMT using principal components analysis (PCA) is presented to reduce the dimension of the inverse problem. Phantom experiments are performed to verify the feasibility of the proposed method. The results demonstrate that the proposed method can accelerate image reconstruction in FMT almost without quality degradation.OCIS codes: (170.3010) Image reconstruction techniques, (170.6960) Tomography, (100.3190) Inverse problems, (170.3880) Medical and biological imaging, (170.3660) Light propagation in tissues, (290.1990) Diffusion, (290.7050) Turbid media     

Adaptive dynamic analysis-based optical coherence tomography angiography for blood vessel projection artifact suppression

Optical coherence tomography angiography (OCTA) for blood vessel 3-D structure imaging suffers from blood vessel projection artifacts/tail artifacts when using a long decorrelation time (e.g., repeat B-scan acquisition in regular OCTA) or loss of micro vessel signal when using a short decorrelation time. In this work, we developed an adaptive first-order field autocorrelation function (g₁) analysis-based technique to suppress the projection artifacts under macro vessels while enhancing the dynamic signal of micro vessels. The proposed method is based on the differences of the decorrelation rate and the phase variations of g₁ between the vessel voxels and the artifacts regions. A short or long decorrelation time was applied to obtain the dynamic index of the projection artifacts region or the blood vessel region, respectively. Compared to the slab subtraction-based post-image processing-based techniques, the proposed approach addresses this problem on a physical basis and shows the ability to suppress the projection artifacts while enhancing the detection of the micro vessels.     

High resolution optical projection tomography platform for multispectral imaging of the mouse gut

Optical projection tomography (OPT) is a powerful tool for three-dimensional imaging of mesoscopic biological samples with great use for biomedical phenotyping studies. We present a fluorescent OPT platform that enables direct visualization of biological specimens and processes at a centimeter scale with high spatial resolution, as well as fast data throughput and reconstruction. We demonstrate nearly isotropic sub-28 µm resolution over more than 60 mm³ after reconstruction of a single acquisition. Our setup is optimized for imaging the mouse gut at multiple wavelengths. Thanks to a new sample preparation protocol specifically developed for gut specimens, we can observe the spatial arrangement of the intestinal villi and the vasculature network of a 3-cm long healthy mouse gut. Besides the blood vessel network surrounding the gastrointestinal tract, we observe traces of vasculature at the villi ends close to the lumen. The combination of rapid acquisition and a large field of view with high spatial resolution in 3D mesoscopic imaging holds an invaluable potential for gastrointestinal pathology research.     

全模型迭代重建算法评价125I粒子植入术后CT图像

目的 探讨全模型迭代重建（IMR）算法评价¹²⁵I粒子植入术后图像的应用价值。方法 收集接受¹²⁵I粒子植入术及术后CT随访的16例腹部肿瘤患者,对扫描原始数据分别以滤波反投影法（FBP）、IMR和高级重建迭代（iDose⁴）算法进行重建,比较3种重建方法图像的噪声、伪影指数（AI）、CNR和主观评分。结果 FBP重建图像的噪声、CNR及AI分别为（58.65±4.03） HU、1.09±0.43和51.60±9.23,iDose⁴图像分别为（48.38±5.34） HU、1.29±0.48和43.77±4.91,IMR图像分别为（41.46±3.44） HU、1.58±0.56和38.51±4.64,3种重建方法图像的噪声、CNR及AI两两比较差异均有统计学意义（P均<0.05）。IMR图像的主观图像质量评分显著高于FBP和iDose⁴算法图像（调整后P<0.001,P=0.011）。结论 IMR算法获得的图像质量较高,可有效减少¹²⁵I粒子伪影,为¹²⁵I粒子植入术后随访与疗效评估提供了更佳方法。     

Comparison of filtered back projection and iterative reconstruction in diagnosing appendicitis at 2-mSv CT

Purpose

To compare radiologists’ diagnostic performance and confidence, and subjective image quality between filtered back projection (FBP) and iterative reconstruction (IR) at 2-mSv appendiceal CT.

Methods

The institutional review board approved this retrospective study and waived the requirement for informed consent. We included 107 adolescents and young adults (age, 29.8 ± 8.5 years; 64 females) undergoing 2-mSv CT for suspected appendicitis. Appendicitis was pathologically confirmed in 42 patients. Seven readers with different experience levels independently reviewed the CT images reconstructed using FBP and IR (iDose⁴, Philips). They rated both the likelihood of appendicitis and subjective image quality on 5-point Likert scales. Diagnostic confidence was assessed using the likelihood of appendicitis, proportion of indeterminate interpretations, and 3-point normal appendix visualization score. We used receiver operating characteristic analyses, Wilcoxon’s signed-rank tests, and McNemar’s tests.

Results

The pooled area under the receiver operating characteristic curve (AUC) was 0.96 for both FBP and IR (95% CI for the difference, ?0.02, 0.02; P = 0.73). The AUC difference was not significant in any of the individual readers (P ≥ 0.21). For the majority of the readers, the diagnostic confidence was not significantly different between the two reconstruction methods. Subjective image quality tended to be higher with IR for all readers (P ≤ 0.70), showing significant differences for four readers (P ≤ 0.040).

Conclusion

When diagnosing appendicitis at 2-mSv CT in adolescents and young adults, FBP and IR were comparable in radiologists’ diagnostic performance and confidence while IR exhibited higher subjective image quality than FBP.

     

Dual-modality optical coherence tomography and fluorescence tethered capsule endomicroscopy

OCT tethered capsule endomicroscopy (TCE) is an emerging noninvasive diagnostic imaging technology for gastrointestinal (GI) tract disorders. OCT measures tissue reflectivity that provides morphologic image contrast, and thus is incapable of ascertaining molecular information that can be useful for improving diagnostic accuracy. Here, we introduce an extension to OCT TCE that includes a fluorescence (FL) imaging channel for attaining complementary, co-registered molecular contrast. We present the development of an OCT-FL TCE capsule and a portable, plug-and-play OCT-FL imaging system. The technology is validated in phantom experiments and feasibility is demonstrated in a methylene blue (MB)-stained swine esophageal injury model, ex vivo and in vivo.     

Remote focal scanning optical projection tomography with an electrically tunable lens

We describe a remote focal scanning technique for optical projection tomography (OPT) implemented with an electrically tunable lens (ETL) that removes the need to scan the specimen or objective lens. Using a 4× objective lens the average spatial resolution is improved by ∼46% and the light collection efficiency by a factor of ∼6.76, thereby enabling increased acquisition speed and reduced light dose. This convenient implementation is particularly appropriate for lower magnifications and larger sample diameters where axial objective scanning would encounter problems with speed and stability.OCIS codes: (170.6900) Three-dimensional microscopy, (170.6960) Tomography     

比较以自适应性统计迭代重建技术和滤过反投影重建的低剂量腹部CT的图像质量

目的比较应用自适应性统计迭代重建技术(ASIR)和滤过反投影(FBP)两种重建技术获得不同低剂量腹部CT扫描图像的质量及对病变的优化显示。方法选取22例临床诊断肝脏占位而接受腹部增强扫描的患者,在常规动脉期扫描后门静脉期分别以150mAs和100mAs对病变中心上下10cm范围进行连续扫描,分别用FBP及3个水平(30%、50%、70%)的ASIR重建图像,测量并比较图像噪声及容积CT剂量指数(CIDIvol),并对所得图像进行图像质量评分。结果与FBP相比,ASIR可降低图像噪声,减少伪影,增加诊断信心度(P<0.001)。采用150mAs及100mAs扫描时,30%ASIR和50%ASIR图像的诊断信心度评分较好,CIDIvol分别为12.74mGy、8.59mGy,均低于常规扫描剂量(P<0.05)。150mAs时,与FBP比较,30%ASIR、50%ASIR和70%ASIR重建图像中,肝实质、背景肌肉及门静脉的平均噪声均有所降低,分别为(18.74%、30.39%、41.49%)、(18.73%、30.67%、41.85%)、(22.66%、37.14%、43.61%);100mAs时,则分别降低(20.37%、32.22%、43.32%)、(18.63%、30.48%、41.57%)和(21.39%、35.09%、45.72%)。100mAs-30%ASIR图像噪声与150mAs-FBP图像噪声差异无统计学意义(P>0.05),而扫描剂量降低32.96%。结论采用ASIR重建算法可有效提高图像质量,降低腹部CT扫描辐射剂量。     

Depth-resolved model-based reconstruction of attenuation coefficients in optical coherence tomography

We present a method, based on a single scattering model, to calculate the attenuation coefficient of each pixel in optical coherence tomography (OCT) depth profiles. Numerical simulations were used to determine the model’s response to different depths and attenuation coefficients. Experiments were performed on uniform and layered phantoms with varying attenuation coefficients. They were measured by a 1300 nm OCT system and their attenuation coefficients were evaluated by our proposed method and by fitting the OCT slope as the gold standard. Both methods showed largely consistent results for the uniform phantoms. On the layered phantom, only our proposed method accurately estimated the attenuation coefficients. For all phantoms, the proposed method largely reduced the variability of the estimated attenuation coefficients. The method was illustrated on an in-vivo retinal OCT scan, effectively removing common imaging artifacts such as shadowing. By providing localized, per-pixel attenuation coefficients, this method enables tissue characterization based on attenuation coefficient estimates from OCT data.OCIS codes: (110.3010) Image reconstruction techniques, (110.3200) Inverse scattering, (110.4500) Optical coherence tomography, (170.4500) Optical coherence tomography, (170.4580) Optical diagnostics for medicine, (170.6935) Tissue characterization     

A dual-modality optical coherence tomography and fluorescence lifetime imaging microscopy system for simultaneous morphological and biochemical tissue characterization

Most pathological conditions elicit changes in the tissue optical response that may be interrogated by one or more optical imaging modalities. Any single modality typically only furnishes an incomplete picture of the tissue optical response, hence an approach that integrates complementary optical imaging modalities is needed for a more comprehensive non-destructive and minimally-invasive tissue characterization. We have developed a dual-modality system, incorporating optical coherence tomography (OCT) and fluorescence lifetime imaging microscopy (FLIM), that is capable of simultaneously characterizing the 3-D tissue morphology and its biochemical composition. The Fourier domain OCT subsystem, at an 830 nm center wavelength, provided high-resolution morphological volumetric tissue images with an axial and lateral resolution of 7.3 and 13.4 μm, respectively. The multispectral FLIM subsystem, based on a direct pulse-recording approach (upon 355 nm laser excitation), provided two-dimensional superficial maps of the tissue autofluorescence intensity and lifetime at three customizable emission bands with 100 μm lateral resolution. Both subsystems share the same excitation/illumination optical path and are simultaneously raster scanned on the sample to generate coregistered OCT volumes and FLIM images. The developed OCT/FLIM system was capable of a maximum A-line rate of 59 KHz for OCT and a pixel rate of up to 30 KHz for FLIM. The dual-modality system was validated with standard fluorophore solutions and subsequently applied to the characterization of two biological tissue types: postmortem human coronary atherosclerotic plaques, and in vivo normal and cancerous hamster cheek pouch epithelial tissue.