Imager that combines near-infrared diffusive light and ultrasound

We introduce an imaging technique that combines complementary features of ultrasound and near-infrared diffusive light imaging. We achieve the combined technology experimentally by mounting an ultrasound array together with multiple laser source and optical detector fibers upon a hand-held probe. The technique is demonstrated with tissue phantoms wherein both acoustic and optical sensors image the volume underneath the probe. Coregistration of acoustic and optical images is achieved with an accuracy of 0.27+/-0.20cm, approximately half of the image pixel size of our prototype. Accurate determination of target optical absorption is also achieved by use of image segmentation on the ultrasound reconstruction. The combined technique may provide improved breast-cancer detection sensitivity and specificity.     

Noninvasive optical method of measuring tissue and arterial saturation: an application to absolute pulse oximetry of the brain

We present a frequency-domain optical method for real-time noninvasive measurement of absolute tissue and arterial saturation. This method is based on quantitative measurement of the tissue absorption spectrum (for tissue saturation) and of the amplitude of the arterial-pulsation-induced absorption oscillations (for arterial saturation) at eight wavelengths in the range 633-841 nm. We report results obtained from readings taken from the forehead of a healthy volunteer, showing baseline saturation values of 74.7+/-0.2% (tissue) and 96.9+/-0.5% (arterial). These values dropped to minimum values of 71.6+/-0.2% and 90.0+/-0.2% , respectively, after 1 min of reduced inspired oxygen concentration [10% (by volume) O(2) from a baseline value of 21% O(2) ].     

Endoscopically compatible near-infrared photon migration probe

We have developed a 2.3-mm-diameter fiber-optic probe for near-infrared photon migration spectroscopy that can be inserted into the body through an endoscope or biopsy needle. This probe is specifically designed to be inserted into a core biopsy needle to facilitate optical sampling of lesions during breast needle biopsy. This probe was tested on tissue phantoms containing heterogeneities (to stimulate breast lesions) of various sizes and optical properties. Under the conditions tested, the probe can measure the absorption coefficient to within 30% for heterogeneities with radii as small as 10 mm.     

Optical spectra analysis for breast cancer diagnostics

Minimally invasive probe and optical biopsy system based on optical spectra recording and analysis seem to be a promising tool for early diagnostics of breast cancer. Light scattering and absorption spectra are generated continuously as far as the needle-like probe with one emitting and several collecting optical fibers penetrates through the tissues toward to the suspicious area. That allows analyzing not only the state of local site, but also the structure of tissues along the needle trace. The suggested method has the advantages of automated on-line diagnosing and minimal tissue destruction and in parallel with the conventional diagnostic procedures provides the ground for decision-making.     

基于漫反射光谱的组织光学参数测量系统与方法研究

在体组织光学参数测量是生物医学光子学研究重点,不仅为人体成分无创检测、光学成像、光动力疗法等研究提供基础,并且可以快速获取人体光学参数变化,为临床诊断提供依据。研究了利用单一源探距离漫反射光谱在体测量光学参数的测量系统与反构方法。漫反射光谱测量系统由宽谱光源、高分辨光纤光谱仪及光纤探头组成,结构简单,测量方便,可准确快速测量样品漫反射光谱。在光纤探头几何形状基础上,研究了光纤收集及系统传递函数,在此基础上对反构算法进行了校正。光学参数反构算法中正向模型基于Monte Carlo以及神经网络方法,适用光学参数范围大,计算速度快;逆向算法采用主成分分析与非线性建模拟合相结合的方法,可抑制测量噪声影响。在测量系统及反构算法基础上,进行了组织仿体光学参数测量实验,结果表明,利用单一源探距离下漫反射谱,可以较为准确获取吸收系数以及约化散射系数,均方根误差分别达到4.58%以及7.92%。为保证系统测量准确性,测量波长范围应覆盖样品中所含吸收物质吸收峰范围。所研究的在体组织光学参数测量方法为人体成分无创检测及测量条件变化获取提供了基础。     

In vivo estimation of optical properties of rat liver using single-reflectance fiber probe during ischemia and reperfusion

Optical Review - To quantify the changes in optical properties of in vivo rat liver tissue, we applied diffuse reflectance spectroscopy (DRS) system using single-reflectance fiber probe during...     

Investigation of gold-coated bare fiber probe for in situ intra-vitreous coherence domain optical imaging and sensing

We have investigated the usage of gold-plated bare fiber probes for in situ imaging of retinal layers and surrounding ocular tissues using time-domain common-path optical coherence tomography. The fabricated intra-vitreous gold-plated micro-fiber probe can be fully integrated with surgical tools working in close proximity to the tissue to provide subsurface images having a self-contained reference plane independent to the Fresnel reflection between the distal end of the probe and the following medium for achieving reference in typical common-path optical coherence tomography. We have fully characterized the probe in an aqueous medium equivalent to the vitreous humor in the eye and were able to differentiate various functional retinal tissue layers whose thickness is larger than the system’s resolution.     

Quantitative pharmacokinetic analysis of DCE-MRI data without an arterial input function: a reference region model

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumor perfusion, microvascular vessel wall permeability and extravascular-extracellular volume fraction. Analysis of DCE-MRI data is usually based on indicator dilution theory that requires knowledge of the concentration of the contrast agent in the blood plasma, the arterial input function (AIF). A method is presented that compares the tissues of interest (TOI) curve shape to that of a reference region (RR), thereby eliminating the need for direct AIF measurement. By assigning literature values for Ktrans (the blood perfusion-vessel permeability product) and v(e) (extravascular-extracellular volume fraction) in a reference tissue, it is possible to extract the Ktrans and v(e) values for a TOI without knowledge of the AIF. The operational RR equation for DCE-MRI analysis is derived, and its sensitivity to noise and incorrect assignment of the RR parameters is tested via simulations. The method is robust at noise levels of 10%, returning accurate (+/-20% in the worst case) and precise (+/-15% in the worst case) values. Errors in the TOI Ktrans and v(e) values scale approximately linearly with the errors in the assigned RR Ktrans and v(e) values. The methodology is then applied to a Lewis Lung Carcinoma mouse tumor model. A slowly enhancing TOI yielded Ktrans=0.039+/-0.002 min-1 and v(e)=0.46+/-0.01, while a rapidly enhancing region yielded Ktrans=0.35+/-0.05 min-1 and v(e)=0.31+/-0.01. Parametric Ktrans and v(e) mappings manifested a tumor periphery with elevated Ktrans (>0.30 min-1) and v(e) (>0.30) values. The main advantage of the RR approach is that it allows for quantitative assessment of tissue properties without having to obtain high temporal resolution images to characterize an AIF. This allows for acquiring images with higher spatial resolution and/or SNR, and therefore, increased ability to probe tissue heterogeneity.     

Spatiotemporal stability of a femtosecond hard-x-ray undulator source studied by control of coherent optical phonons

We report on the temporal and spatial stability of the first tunable femtosecond undulator hard-x-ray source for ultrafast diffraction and absorption experiments. The 2.5-1 Angstrom output radiation is driven by an initial 50 fs laser pulse employing the laser-electron slicing technique. By using x-ray diffraction to probe laser-induced coherent optical phonons in bulk bismuth, we estimate an x-ray pulse duration of 140+/-30 fs FWHM with timing drifts below 30 fs rms measured over 5 days. Optical control of coherent lattice motion is demonstrated.     

Effects of water exchange on MRI-based determination of relative blood volume using an inversion-prepared gradient echo sequence and a blood pool contrast medium

A prostate tumor model in rats was used to compare histometric parameters of prostate cancer physiology with those obtained by magnetic resonance imaging (MRI). The study was focused on vascular physiology as reflected by relative blood volume v(b). Histometry and MRI showed a significant increase in mean v(b) in tumor compared to normal prostate tissue (histometry: normal tissue v(b)=0.69+/-0.19%, tumor tissue v(b)=1.10+/-0.31%, P<.001; MRI: normal tissue v(b)=0.67+/-0.23%, tumor tissue v(b)=1.77+/-0.67%, P<.001). The experimental work showed that MRI yielded a 60.9+/-0.76% higher v(b) than histometry in tumors, while no significant difference in v(b) was found between both methods in normal prostate tissue. Water exchange is known to affect signal intensity on contrast-enhanced MRI. This article investigated the influence of water exchange between intravascular and extravascular space to account for the discrepancy in the values of v(b) obtained with a dynamic inversion-prepared gradient echo MRI sequence and histometry in tumor and normal prostate tissue. The expected influence of water exchange on v(b) was modeled by a computer simulation of the MRI signal and compared with experimental results measured with MRI and histometry. The simulation was based on a two-compartment model indicating that v(b) may be overestimated by MRI. The magnitude of overestimation leads from 10% for the slow water exchange regime to 70% for fast water exchange. Since slow water exchange is probably predominant and even if the observed histological differences in tumor tissue are considered, an overestimation of only 15% due to water exchange is predicted by the simulation. Therefore the overestimation of tumor blood volume by MRI of 60.9% compared to histometry seems to be attributable to additional causes besides water exchange.     

Retrieval of chromophore concentration in a tissue phantom by diffuse reflectance spectroscopy

This study describes a method for analysis of back reflectance spectroscopic data to estimate the concentration of endogenous or exogenous chromophores of tissue, noninvasively and in real time. In the study, tissue phantoms were prepared using intralipid and two chromophores, indocyanine green and methylene blue. Reduced scattering and absorption coefficients ranges of tissue phantoms were kept in the range of biological tissues. Spectroscopic measurements on the tissue phantoms were carried out using a miniature spectrometer, an optical fiber probe, a halogen tungsten light source and a laptop. Monte Carlo simulations of the experiments were run, and an average optical path lengths of the detected photons were obtained for different absorption and scattering coefficients. The average optical path lengths of the photons were used to estimate concentrations of the chromophores in the tissue phantoms. Scattering and absorption coefficients were estimated with an average error of 4.7 and 5.4%, respectively. The developed method has the potential to be used in diagnosis of pathologic tissues based on the variation of biochemical composition of tissues and in photodynamic therapy to estimate the concentration of photosensitizers.     

Stationary-fiber rotary probe with unobstructed 360° view for optical coherence tomography

A side-scanning fiber probe is a critical component for optical coherence tomography in medical imaging and diagnosis. We propose and fabricate an on-axis rotating probe that performs in situ, circumferential scanning that is shadow-free (not susceptible to shadow effects caused by the motor's wires). A miniature motor that incorporates a bored-out shaft for the optical fiber is located at the distal end of the probe, which results in a more stable and uniform circumferential scan, free from wire-shadow interference effects. More importantly, this design, novel to our knowledge, compared to other probes avoids the insertion losses introduced by optical coupling components and the multitude of optical interfaces, which is very important for sensing weak signals backscattered from structures deep in the tissue.     

Application of a WGM optical fiber probe fabricated by 3D printing technology for glucose concentration measurement

This study proposes a method for manufacturing a whispering gallery mode (WGM) optical fiber probe used for measuring glucose. The principle of the WGM optical fiber probe consists of the bending interference that occurs between the core mode and cladding mode. 3D printing technology was used to create a mold for the optical fiber sensor so that the bent optical fiber sensor was fixed within the mold to ensure a stable bend radius. This method of fabrication allows for easier installation and replacement of the resulting optical fiber compared to WGM optical fiber sensors fabricated by traditional methods. The results of the concentration test showed that as the glucose aqueous solution concentration increased from 0 to 10%, the wavelength was red shifted and the transmission loss gradually increased. At a bend radius of 3.1 mm and an etching diameter of 46 μm, the wavelength sensitivity was 1.475 nm/% and the R-squared value was 0.983, indicating an extremely high sensitivity. These results confirm that the WGM optical fiber probe created in this study can be used to measure glucose concentrations with high sensitivity, and that it is relatively easy to manufacture, install, and replace. Therefore, the proposed WGM optical fiber probe exhibits good performance and is suitable for use as a glucose concentration sensor.     

Prostatic tissue ablation by transrectal high intensity focused ultrasound: histological impact and clinical application

In a phase-I clinical trial the morphologic impact and safety of high-intensity focused ultrasound (HIFU) administered transrectally for tissue ablation in human prostates (n = 54) was evaluated. Location and size of the tissue lesions correlated well with the predefined target area and revealed sharply delineated coagulative necrosis in all cases. Intervening tissues, such as the rectal wall and posterior prostate capsule were invariably intact. In a subsequent phase-II clinical trial safety and efficacy of transrectal HIFU as a novel minimally invasive treatment modality for patients with symptomatic benign prostatic hyperplasia (BPH; n = 102) was determined. The maximum urinary flow rate (Qmax, ml/s) increased from 9.1+/-4.0 to 12.9+/-6.1 (3 months, n=86), 12.7+/-5.1 (6 months, n=78) and 13.3+/-6.1 (12 months, n=56). In the same time period the post void residual volume (ml) decreased from 131+/-115 to 46+/-45, 57+/-46 and 48+/-36 and the AUA symptom score decreased from 24.5+/-4.7 to 13.3+/-4.4, 13.4+/-4.7 and 10.8+/-2.5. A subset of patients (n=30) underwent multichannel pressure flow studies, which demonstrated that transrectal HIFU reduces bladder outflow obstruction. These data demonstrate that transrectal HIFU is capable of inducing coagulative necrosis in the human prostate via a transrectal approach while preserving intervening and adjacent tissue. A 48% improvement of uroflow and a 53% decrease of urinary symptoms 1 year after treatment prove that transrectal HIFU is an effective and safe minimally invasive treatment option for BPH.     

Ultrasound palpation sensor for tissue thickness and elasticity measurement--assessment of transverse carpal ligament

Palpation is a traditional diagnostic procedure for health care professionals to use their fingers to touch and feel the body soft tissues. It is a common clinical approach, though it is rather subjective and qualitative and the palpation results may vary among different people. Tissue ultrasound palpation sensor (TUPS) provides a feasible solution that makes the palpation of soft tissues not subjective feeling any more. It is comprised of an ultrasound transducer together with a load cell to form the finger-sized probe. The probe is used to push against the soft tissue surface to measure the thickness and elasticity of the soft tissues. TUPS has been successfully applied to the assessment of various human tissues. Recently, we have improved TUPS, which can now be linked to personal computer (PC) via universal serial bus (USB) and provide a better user-interface. The information of ultrasound signal and indentation force is displayed on PC in real time during measurement. In this paper, we introduce the recent application of TUPS for the assessment of the transverse carpal ligament. The tissues at the carpal tunnel regions of five normal male subjects were tested using TUPS. The results showed that the average thickness of the tissues covering the carpal tunnel ligament and the tunnel region was 7.98+/-1.05 mm and 9.59+/-1.12 mm, respectively. Under a compression force of 20 N applied by a cylindrical ultrasound indentor with a diameter of 9 mm, the stiffness of the soft tissue layer and the tunnel region was 6.72+/-2.10 N/mm and 15.63+/-8.42 N/mm, respectively. It is expected that TUPS can be a potential tool for non-invasive assessment of carpal tunnel syndrome.     

血液可见吸收光谱与血氧参数神经网络估算法

总血红蛋白浓度和血氧饱和度是两个基本的血氧参数。文章提出了利用内置双光纤微创探头在位测量大鼠脑组织血氧参数的新方法。首先,利用悬乳液(Intralipid)和全血配置不同总血红蛋白浓度的混合溶液,模拟生物组织模型,用光纤光谱仪测试系统测量组织模型在加氧和去氧时的实时吸收光谱,同时用血氧分析仪(OXI meter)对血氧参数定标,建立测试光谱和定标数据样本集。然后,利用人工神经网络建立血液吸收光谱与血氧参数的神经网络模型,训练后的网络模型能根据吸收光谱输出生物组织的血氧参数值,总血红蛋白浓度和血氧饱和度的平均输出误差分别为±4μmol·L-1和±5%。最后,利用神经网络模型对大鼠脑组织血氧参数进行了在位测试实验,测得脑灰质的血氧饱和度为0.60~0.70,脑白质血氧饱和度为0.45~0.55;总血红蛋白浓度在脑皮层(深度1mm)附近最高,平均110μmol·L-1,其余深度脑组织的总血红蛋白浓度为70~90μmol·L-1。这种方法对脑外科微创手术中实时在位测试脑组织血氧参数具有重要的参考意义。     

Quantitative spectroscopy of superficial turbid media

We report a novel diffuse optical spectroscopy probe design for determining optical properties of superficial volumes of turbid samples. The fiber-based probe employs a highly scattering layer placed in contact with the sample of interest. This layer diffuses photons from a collimated light source before they enter the sample and provides a basis for describing light transported in superficial media by the diffusion approximation. We compare the performance of this modified two-layer diffusion model with Monte Carlo simulations. A set of experiments that demonstrate the feasibility of this method in turbid tissue phantoms is also presented. Optical properties deduced by this approach are in good agreement with those derived by use of a benchmark method for determining optical properties. The average interrogation depth of the probe design investigated here is estimated to be less than 1 mm.     

多参量光声成像及其在生物医学领域的应用

光声成像兼具声学成像和光学成像两者的优点, 因而成为近十年来发展最迅速的生物医学成像技术之一. 本文介绍了光声成像的特点及其相对于广泛应用的光学成像技术和声学成像技术的优点; 其次, 解释了光声成像的成像原理, 在此基础上介绍了光声断层成像和光声显微镜这两种典型的光声成像方案, 并介绍了它们的技术特点; 然后, 介绍了光声成像对生物组织的生化特性、组织力学特性、血液流速分布、温度分布参数、微结构特性等多信息参量的提取能力, 及其在生物系统的结构成像、功能成像、代谢成像、分子成像、基因成像等多领域的应用; 最后, 展望了光声成像在生物医学领域的应用潜力并讨论了其局限性.     

FABRICATION AND APPLICATION OF NEAR-FIELD OPTICAL FIBRE PROBE

In this paper, the fabrication of a large cone angle near-field optical fibre probe, using the two-step chemical etching method and bent probe, is introduced, and the controlling parameters of the coated Cr－Al film at the probe tip are presented. The scanning electron microscopy images display that the tip diameter of the uncoated large cone angle fibre probe obtained is less than 50nm, the cone angle over 90°, and the diameter of light aperture at the coated probe tip is less than 100nm. The measured results of the optical transmission efficiency for various probe tips show that the uncoated straight optical fibre probe, film-coated straight probe and film-coated bent probe are 3×10^-1, 2×10^-3, and 1×10^-4 times that of the flat fibre probe, respectively. In addition, the force images and near-field optical images of a standard sample are acquired using a large cone angle and film-coated bent probe.     

Diffuse optical measurement of blood flow in breast tumors

Blood flow contrast between tumor and normal tissues in patients with malignant and benign breast cancer was measured by diffuse optical correlation methods. The measurements were carried out with a hand-held optical probe that was manually scanned over the tumor-bearing breast. Increased blood flow was observed in tumor regions relative to healthy tissue, and control subjects did not exhibit significant blood flow heterogeneity. The measurements introduce a new optical contrast for diffuse optical mammography.