Multimodal nonlinear endo-microscopy probe design for high resolution,label-free intraoperative imaging

We present a portable, multimodal, nonlinear endo-microscopy probe designed for intraoperative oncological imaging. Application of a four-wave mixing noise suppression scheme using dual wavelength wave plates (DWW) and a polarization-maintaining fiber improves tissue signal collection efficiency, allowing for miniaturization. The probe, with a small 14 mm transversal diameter, includes a customized miniaturized two-axis MEMS (micro-electromechanical system) raster scanning mirror and micro-optics with an illumination laser delivered by a polarization-maintaining fiber. The probe can potentially be integrated into the arms of a surgical robot, such as da Vinci robotic surgery system, due to its minimal cross sectional area. It has the ability to incorporate multiple imaging modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second harmonic generation), and TPEF (two-photon excited fluorescence) in order to allow the surgeon to locate tumor cells within the context of normal stromal tissue. The resolution of the endo-microscope is experimentally determined to be 0.78 µm, a high level of accuracy for such a compact probe setup. The expected resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 µm based on the calculation tolerance allocation using Monte-Carlo simulation. The reported probe is intended for use in laparoscopic or radical prostatectomy, including detection of tumor margins and avoidance of nerve impairment during surgery.OCIS codes: (110.0110) Imaging systems, (220.0220) Optical design and fabrication     

A comparison of the imaging performance of high resolution ultrasound scanners for preclinical imaging

Nine ultrasound transducers from six ultrasound scanners were assessed for their utility for preclinical ultrasound imaging. The transducers were: L8-16, L10-22 (Diasus; Dynamic Imaging Ltd., Livingston, UK); L17-5, L15-7io (iU22; Philips, Seattle, WA, USA), HFL38/13-6 (MicroMaxx; Sonosite Inc., Bothell, WA, USA); il3Lv (Vivid 5; GE, Fairfield, CT, USA), RMV 704 (Vevo 770; Visualsonics Inc., Toronto, Canada) and MS550S, MS550D (Vevo 2100; Visualsonics Inc.). A quantitative analysis of the ultrasound images from all nine transducers employed measurements of the resolution integral as an indication of the versatility and technology of the ultrasound scanners. Two other parameters derived from the resolution integral, the characteristic resolution and depth of field, were used to characterise imaging performance. Six of these transducers were also assessed qualitatively by ultrasonically scanning 59 female common marmosets (Callithrix jacchus) yielding a total of 215 scans. The quantitative measurements for each of the transducers were consistent with the results obtained in the qualitative in vivo assessment. Over a 0-10 mm imaging depth, the values of the resolution integral, characteristic resolution and depth of field, measured using the Edinburgh Pipe Phantom, ranged in magnitude from 7-72, 93-930 μm and 3.3-9.2 mm respectively. The largest resolution integrals were obtained using the Vevo 770 and Vevo 2100 scanners. The Edinburgh Pipe Phantom provides a quantitative method of characterising the imaging performance of preclinical imaging scanners. (E-mail: Carmel.Moran@ed.ac.uk)     

New integrated imaging high intensity focused ultrasound probe for transrectal prostate cancer treatment

The present study proposes a new integrated imaging (II) high-intensity focused ultrasound (HIFU) probe intended as an improvement to the Ablatherm prostate cancer treatment. Because of a perforation in the center of the II probe, the expected lesion differs from the one obtained for the original Ablatherm probe. In this paper, the new geometry and the strategy followed to establish the treatment parameters are presented. The original probe has a 40-mm focal length, a 50-mm aperture and is truncated at 31 mm. The II probe has a 45-mm focal length, a 61-mm aperture, a central perforation of 25 mm and is truncated at 31 mm. Both probes operate at 3 MHz. A mathematical model for lesion prediction was used for setting the treatment parameters for the II probe. These parameters should ensure equivalence between the lesions obtained with the original and II probes. Simulation-obtained parameters were validated by in-vitro and in-vivo (on liver of 70 New Zealand rabbits) experiments. The new II probe was used clinically to treat 30 patients. The mean age was 70.9 +/- 5.3 years (SD), the mean prostate volume 26.9 +/- 7.7 mL and the mean serum prostate specific antigen (PSA) concentration before treatment was 9.2 +/- 5.5 ng/mL. Simulations showed that for the II probe acoustical power and duration when the transducer is inactive should be reduced of 14% and 1s. In-vitro and in-vivo experiments confirmed the equivalence between the lesions obtained with the two probes. The lesion volume obtained under in-vitro conditions (for a traversed tissue depth of 16 mm to the focus) was 5 +/- 0.4 cm(3) and 5.1 +/- 0.5 cm(3) for the original and II probes, respectively. Under in-vivo conditions, the lesion volume (for a traversed tissue depth of 18 mm) was 5.3 +/- 1.1 cm(3) and 5.1 +/- 1.1 cm(3) for the original and II probes, respectively. During the clinical trial, a correction of + 1s in the exposure time was required to recreate the same degree of efficacy observed with the original probe (p = 0.97): 66.7 % of negative biopsies and 75% of patients with PSA at 3 mo < or =1 ng/mL. The morbidity observed was minimal and identical to that observed with the original probe.     

Handheld miniature probe integrating diffuse optical tomography with photoacoustic imaging through a MEMS scanning mirror

We describe a novel dual-modality imaging approach that integrates diffuse optical tomography (DOT) and photoacoustic imaging (PAI) through a miniaturized handheld probe based on microelectromechanical systems (MEMS) scanning mirror. We validate this dual-modal DOT/PAI approach using extensive phantom experiments, and demonstrate its application for tumor imaging using tumor-bearing mice systematically injected with targeted contrast agents.OCIS codes: (110.6960) Tomography, (170.0110) Imaging systems, (170.5120) Photoacoustic imaging     

Intracorporeal imaging and differentiation of living tissue with an ultra-high-frequency ultrasound probe

Intraoperative diagnostic tissue differentiation is expected to be useful clinically. We have fabricated a 3-mm diameter rod-shaped ultrasound (US) probe mounted with a 120-MHz transducer whose lateral resolution is the same as the cellular size of 13 microm. The probe can image a microscopic structure (i.e., the cellular arrangement inside intracorporeal living tissue). We imaged normal kidney tissue of a living mouse and tumor tissue implanted in another mouse kidney. We anesthetized the mice, exteriorized the kidneys, and punctured the kidneys with the probe. Renal corpuscle-like structures were seen in the healthy kidney, but a wavy spindle-like structure was seen in the tumor. The similarity between the ultrasonic images and histological sections taken from the imaged organs demonstrates the possibility of real-time tissue differentiation by ultra-high-frequency US.     

Integrated optical coherence tomography, ultrasound and photoacoustic imaging for ovarian tissue characterization

Ovarian cancer has the lowest survival rate of the gynecologic cancers because it is predominantly diagnosed in Stages III or IV due to the lack of reliable symptoms, as well as the lack of efficacious screening techniques. Detection before the malignancy spreads or at the early stage would greatly improve the survival and benefit patient health. In this report, we present an integrated optical coherence tomography (OCT), ultrasound (US) and photoacoustic imaging (PAI) prototype endoscopy system for ovarian tissue characterization. The overall diameter of the prototype endoscope is 5 mm which is suitable for insertion through a standard 5-12.5mm endoscopic laparoscopic port during minimally invasive surgery. It consists of a ball-lensed OCT sample arm probe, a multimode fiber having the output end polished at 45 degree angle so as to deliver the light perpendicularly for PAI, and a high frequency ultrasound transducer with 35MHz center frequency. System characterizations of OCT, US and PAI are presented. In addition, results obtained from ex vivo porcine and human ovarian tissues are presented. The optical absorption contrast provided by PAI, the high resolution subsurface morphology provided by OCT, and the deeper tissue structure imaged by US demonstrate the synergy of the combined endoscopy and the superior performance of this hybrid device over each modality alone in ovarian tissue characterization.     

超声微探头对浸润型胃癌的诊断价值

目的探讨超声微探头（ultrasound miniature probe,UMP）对浸润型胃癌的诊断价值。方法通过胃镜下对可疑浸润型胃癌进行UMP检查,并与术后及病理结果进行比较,判断UMP的诊断正确率。结果53例UMP,病理及手术证实为中低分化腺癌46例,胃MALT淋巴瘤6例,Mentrier病1例。UMP诊断正确率86.7%。结论UMP是当前应用于浸润型胃癌最有价值的诊断方法。     

Perspectives in vascular ultrasound imaging: tissue characterization, 3D reconstruction and vascular mechanics

Atherosclerosis is a variable morphologic process resulting in heterogeneous plaque components and nonuniform extent and degree of plaque deposition. We and others have developed techniques of arterial imaging, segmental reconstruction and motion analysis to determine regional vascular reactivity in arterial segments having varying and expanding degrees of atherosclerosis. We have developed and validated position registration devices (PRD) for geometric three dimensional reconstruction of coronary and peripheral arteries using intravascular ultrasound. Elaborating upon an algorithm (McKay et al.), we have developed a technique using biplane cine fluoroscopy to identify intravascular ultrasound image catheter coordinates. Initial data demonstrates clinical feasibility for accurate intracoronary three-dimensional ultrasound reconstruction. For intravascular imaging across occlusions, a prototype 20 MHz forward viewing intravascular ultrasound catheter (Cardiovascular Imaging Systems, Sunnyvale, CA) which provides a two dimensional setting distal to the catheter tip, has been developed. Transcutaneous ultrasound has been used for many years to follow atheroma progression. The use of new position registration devices allows for proper orientation such that accurate three dimensional reconstruction of the carotid bifurcation and the ilio-femoral arteries can be performed. Transesophageal echocardiography is used to evaluate different arterial beds and we have shown in familial hyperlipidemic patients undergoing LDL-apheresis, plaque progression, as determined with transesophageal echocardiography, is delayed. The accurate identification of plaque components would allow for better prediction of the effects of lipid modification regimens on plaque progression. We utilized a modified intravascular frequency device for such plaque characterization. Similarly, we are performing Doppler waveform frequency, finite element stress and finite analytic flow analysis. Data obtained from the femoral arteries to determine alterations in shear stress with expanding and eccentric atheroma. Taken together, these techniques should allow for quantitative evaluation of structural and functional characteristics of the arterial wall in different vascular beds.     

小探头超声在食管黏膜下肿瘤诊断中的应用

目的探讨超声微探头在提高食管黏膜下肿瘤诊断率中的价值。方法利用超声微探头和自制水囊,对经常规内镜诊断为食管黏膜下肿瘤的73例患者进行超声内镜检查。结果微型超声探头检查并经病理证实的33例,术后病理诊断与超声内镜诊断符合率93．9％。结论超声微探头和自制水囊检查能清楚显示食管壁各层判断肿瘤起源及浸润层次,对食管黏膜下肿瘤的诊断有较高的临床价值。     

Improved mirror systems for high resolution ultrasonic imaging

High resolution ultrasonic imaging in a water bath, for example breast imaging, demands a transducer of large aperture. Such an aperture is most easily achieved by the use of mirrors. Previous such mirror systems suffered problems from reverberations between and within their component parts. Changes in the design of the system, and the use of thin metal reflectors, reduce these reverberations to an acceptable level. There is no sacrifice in the focusing performance, and losses in the system are minimized.     

超声微探头对胃癌术前分期的诊断价值

目的探讨超声微探头(ultrasonicminiatureprobe,UMP)对胃癌的浸润深度及淋巴结转移的诊断价值。方法通过胃癌术前UMP分期与术后病理分期进行比较,判断术前UMP分期的诊断正确率。结果术前胃癌UMP总T分期准确率为78.6%。对胃壁外淋巴结诊断准确率为80.9%。结论UMP是当前应用于胃癌术前TNM分期最有价值的方法。对治疗方案的选择及肿瘤的可切除性具有重要的临床意义。     

3.0T高分辨率MR血管壁成像评估他汀类药物治疗颅内动脉粥样硬化斑块效果

目的 观察3.0T高分辨率MR血管壁成像（HRMR-VWI）评估他汀类药物治疗颅内动脉粥样硬化斑块效果的价值。方法 回顾47例动脉粥样硬化性脑梗死患者（共64个斑块）规范他汀类药物治疗前及治疗后随访（104~486天）期间头部3.0T HRMR-VWI，根据斑块特征有无变化分为治疗有效组（有效组）和治疗无效组（无效组），以单因素及多因素logistic回归分析筛选影响疗效的因素。结果 有效组45个、无效组19个斑块，组间斑块出血及强化差异均有统计学意义（P均<0.05）；斑块强化为他汀类药物治疗效果的独立影响因素（OR=13.500，P=0.003）。37个前循环斑块中，28个治疗有效、9个治疗无效，其间管腔正性重构、斑块出血及强化差异均有统计学意义（P均<0.05）；斑块强化为前循环斑块疗效的独立影响因素（OR=20.00，P=0.018）。结论 3.0T HRMR-VWI可用于评估他汀类药物治疗颅内动脉硬化斑块效果。     

Photoplethysmographic imaging of high spatial resolution

We present a new method of formation photoplethysmographic images with high spatial resolution from video recordings of a living body in the reflection geometry. The method (patent pending) is based on lock-in amplification of every pixel of the recorded video frames. A reference function required for synchronous detection of cardiovascular pulse waves is formed from the same frames. The method is featured by ability to visualize dynamic changes in cardiovascular pulse wave during the cardiac (or respiratory) cycle. We demonstrate that the system is capable to detect the minimal irritations of the body such as gentle scratching of the skin by own finger.     

离体猪肝组织的高频超声成像研究

目的探讨高频超声成像在组织定征中的应用.方法用高频超声对猪的肝脏组织进行了成像和组织定征的研究,分析了正常和病变肝组织的图像和声参量的差异.结果高频背向散射系数较声速、声衰减更能反映组织结构的变化,高频超声图像具有高的分辨率.结论高频超声成像是生物组织定征的有效手段.     

FEM-based elasticity reconstruction using ultrasound for imaging tissue ablation

Purpose

Success of ablation treatment depends on the accurate placement of the target ablation focus and the complete destruction of the pathological tissue. Thus, monitoring the formation, location, and size of the ablated lesion is essential. As ablated tissue gets stiffer, an option for ablation monitoring is ultrasound elastography, for imaging the tissue mechanical properties. Reconstruction of elasticity distribution can be achieved by solving an inverse problem from observed displacements, based on a deformable tissue model, commonly discretized by the finite element method (FEM). However, available reconstruction techniques are prone to noise and may achieve suboptimal accuracy.

Methods

We propose a novel inverse problem formulation and elasticity reconstruction method, in which both the elasticity parameters and the model displacements are estimated as independent parameters of an unconstrained optimization problem. Total variation regularization of spatial elasticity distribution is introduced in this formulation, providing robustness to noise.

Results

Our approach was compared to state of the art direct and iterative harmonic elastography techniques. We employed numerical simulation studies using various noise and inclusion contrasts, given multiple excitation frequencies. Compared to alternatives, our method leads to a decrease in RMSE of up to 50% and an increase in CNR of up to 11 dB in numerical simulations. The methods were also compared on an ex vivo bovine liver sample that was locally subjected to ablation, for which improved lesion delineation was obtained with our proposed method. Our method takes \(\sim 4\,\hbox {s}\) for \(20\times 20\) reconstruction grid.

Conclusions

We present a novel FEM problem formulation that improves reconstruction accuracy and inclusion delineation compared to currently available techniques.

     

Optimized ultrasound imaging catheters for use in the vascular system

Clinical experience with 6 and 9 Fr ultrasound imaging catheters (UICs) reveals that several transducer and catheter tip varieties are needed for optimum imaging of diseased intravascular sites. Our UIC design has combined established catheter design and very high frequency ultrasound imaging technology to create a versatile, user configured system for intravascular ultrasound imaging. Optimum use requires proper strategic selection of transducer and catheter sizes, frequencies of operation, and interventional accessories.     

Expansion tomography for large volume tissue imaging with nanoscale resolution

Expansion microscopy enables conventional diffraction limit microscopy to achieve super-resolution imaging. However, the enlarged tissue lacks an objective lens with sufficient working distance that can image tissues with whole-brain-scale coverage. Here, we present expansion tomography (ExT) to solve this problem. We have established a modified super-absorbent hydrogel (ExT gel) that possesses high mechanical strength and enables serial sectioning. ExT gel enables tissue and cell imaging and is compatible with various fluorescent labeling strategies. Combining with the high-throughput light-sheet tomography (HLTP) system, we have shown the capability of large volume imaging with nanoscale resolution of mouse brain intact neuronal circuits. The ExT method would allow image samples to support super-resolution imaging of intact tissues with virtually unlimited axial extensions.     

Real-time high resolution laser speckle imaging of cerebral vascular changes in a rodent photothrombosis model

The study of hemodynamic and vascular changes following ischemic stroke is of great importance in the understanding of physiological and pathological processes during the thrombus formation. The photothrombosis model is preferred by researchers in stroke study for its minimal invasiveness, controllable infarct volume and lesion location. Nevertheless, there is a lack in high spatiotemporal resolution techniques for real time monitoring of cerebral blood flow (CBF) changes in 2D-profile. In this study, we implemented a microscopic laser speckle imaging (LSI) system to detect CBF and other vascular changes in the rodent model of photothrombotic stroke. Using a high resolution and high speed CCD (640 × 480 pixels, 60 fps), online image registration technique, and automatic parabolic curve fitting, we obtained real time CBF and blood velocity profile (BVP) changes in cortical vessels. Real time CBF and BVP monitoring has been shown to reveal details of vascular disturbances and the stages of blood coagulation in photothrombotic stroke. Moreover, LSI also provides information on additional parameters including vessel morphologic size, blood flow centerline velocity and CBF spatiotemporal fluctuations, which are very important for understanding the physiology and neurovascular pathology in the photothrombosis model.OCIS codes: (110.6150) Speckle imaging, (170.3880) Medical and biological imaging     

Renal vascular imaging: ultrasound and other modalities

Sonographic evaluation of the genitourinary system is a fast, safe, and effective means to detect renal disease. In conjunction with other modalities, Doppler can depict a variety of abnormalities. However, optimization of Doppler techniques and a solid understanding of Doppler threshold criteria are critical for success, whether in the native or transplanted kidney.