Ultrahigh frame rate retrospective ultrasound microimaging and blood flow visualization in mice in vivo

To overcome frame rate limitations in high-frequency ultrasound microimaging, new data acquisition techniques have been implemented for 2-D (B-scan) and color flow visualization. These techniques, referred to as retrospective B-scan imaging (RBI) and retrospective color flow imaging (RCFI) are based on the use of the electrocardiogram (ECG) to trigger signal acquisitions. B-scan and color flow images are reconstructed by retrospectively assembling the processed data on a line-by-line basis. Retrospective techniques are used to produce the first in vivo B-scan and color flow images of mouse carotid arteries at frame rates up to 10,000 fps. Retrospective B-scan images of mouse heart were also produced at frame rates of 1000 fps using a version of RBI implemented on a commercial imaging system (Vevo660, VisualSonics, Toronto, ON, Canada). This technology enables detailed in vivo biomechanical studies of dynamic tissues such as the myocardium of the mouse heart with high temporal resolution.     

A mechanical instrument for 3D ultrasound probe calibration

We present a novel technique for 3D ultrasound probe calibration. The principle of operation is that the beam is aligned with a set of coplanar wires strung across a rigid frame. The probe and frame are mounted on a precision-manufactured mechanical instrument which allows adjustment and measurement of their relative pose. Semi-automatic image processing facilitates alignment of the beam and wires to within a tolerance of around 0.2 mm, despite the considerable beam thickness. The calibration process requires just a single view and relatively little user expertise. In a series of experiments with different ultrasound probes, we demonstrate the technique's high accuracy and precision. The latter is partly due to the elimination of the position sensor, a significant source of measurement noise, from the end-user calibration process.     

活体心肌力学属性的介入超声导管检测:仪器设计

目的研制一种检测心肌生物力学属性的介入超声硬度检测仪,可直接、定量检测活体心肌组织硬度,为心肌病变提供力学相关资料。方法仪器由介入超声硬度检测导管、生理信号单元和主机组成。检测时,在X线透视下,将导管通过犬外周动脉血管进入左心室,印压左室壁,超声检测心肌厚度形变值,压力传感器获得印压力值,根据应力-应变关系,计算得到表征组织硬度的参量。结果应用该仪器进行活体犬心肌硬度检测,成功获取了舒张末期左室心尖部和游离壁心肌硬度值,其值分别为(40.55±4.75)kPa、(36.02±7.03)kPa。结论该仪器为直接定量检测活体心肌硬度提供了方法,可为临床判断心脏的整体和局部舒张、收缩功能异常提供定量检测技术,同时,也可检测其他深部组织硬度改变。     

A new instrument for uncomplicated emergency cricothyrotomy.

A new device for establishing an emergency airway provides sterility, anesthesia, control of bleeding, safe and quick entrance into the cricothyroid space, and adequate air exchange. In addition, the device is compatible with standard anesthetic and resuscitation machines, inexpensive, and small enough to be carried in a pocket.     

A new instrument for serial measurements of elasticity in hypertrophic scar

The "elastometer," a hand-held device, was designed and constructed to permit noninvasive quantification of the elastic properties of normal skin or hypertrophic scar. The instrument utilizes a constant-tension spring and a sensitive strain gauge to distract two loci of skin. Normal skin from 15 dogs was measured in vivo with the elastometer and in vitro using standard tensometry. The results correlated significantly by regression analysis (r = .87, p less than .01, 1/Young's Modulus of Elasticity v percent stretch in vivo). Normal dorsal hand skin was tested elastometrically in six volunteers of both sexes. Values (units: percent stretch) ranged from 29 to 43 with a small standard error (+/- 4%). In nine patients with hypertrophic burn scars, the mean percent stretch was 16.2 +/- 1.8 v 37.9 +/- 6.5 in the mirror-image normal skin. There was no overlap between the two groups. There was a trend towards higher values in older scars. Elastometric measurements have increased appreciably in some burn scars undergoing treatment. The elastometer should be useful in documenting objectively the spontaneous maturation of burn scars and/or their response to treatment.     

转基因小鼠前列腺癌及转移的三维超声微成像

目的:应用三维超声微成像检测转基因小鼠前列腺腺癌(TGMAP)模型的前列腺肿瘤和转移。方法:使用三维超声微成像系统监测TGMAP模型小鼠的前列腺肿瘤生长。通过对TGMAP小鼠前列腺癌的三维超声图像和前列腺癌标本的比较,验证该超声系统检测活体小鼠肿瘤大小的可靠性。结果:超声成像可检测到直径为2.4～14mm的肿瘤和转移。通过三维超声体内测量与尸检获得的肿瘤最大直径的相关系数为0.998,超声诊断的敏感性和特异性均>90%。结论:TGMAP模型的三维超声微成像有望成为小鼠临床前期研究的新的微成像手段。     

A new instrument for use with Nd:YAG in tonsillectomy

In tonsillectomy, unexpected bleeding can be one of the most troublesome surgical procedures to perform. To resolve some inherent problems, we have developed a new elevator with contact Nd:YAG laser probe for blunt dissection around the tonsillar capsule. Of 63 cases of laser tonsillectomies performed over 5 years, 51 cases were performed using conventional contact Nd:YAG laser probe and a chisel type dissector. Tonsillectomy in the remaining 12 cases was undertaken by the newly developed elevator with contact Nd:YAG laser probe. We compared clinical evaluation between laser and conventional procedures. Additionally, the advantage of laser tonsillectomy is discussed.     

Human malaria in immunocompromised mice: new in vivo model for chemotherapy studies

We have recently designed a new Plasmodium falciparum mouse model and documented its potential for the study of immune effector mechanisms. In order to determine its value for drug studies, we evaluated its response to existing antimalarial drugs compared to that observed in humans. Immunocompromised BXN (bg/bg xid/xid nu/nu) mice were infected with either the sensitive NF54 strain or the multiresistant T24 strain and then treated with chloroquine, quinine, mefloquine, or dihydroartemisinin. A parallelism was observed between previously reported human responses and P. falciparum-parasitized human red blood cell (huRBC)--BXN mouse responses to classical antimalarial drugs, measured in terms of speed of decrease in parasitemia and of morphological alterations of the parasites. Mice infected with the sensitive strain were successfully cured after treatment with either chloroquine or mefloquine. In contrast, mice infected with the multiresistant strain failed to be cured by chloroquine or quinine but thereafter responded to dihydroartemisinin treatment. The speed of parasite clearance and the morphological alterations induced differed for each drug and matched previously reported observations, hence stressing the relevance of the model. These data thus suggest that P. falciparum-huRBC-BXN mice can provide a valuable in vivo system and should be included in the short list of animals that can be used for the evaluation of P. falciparum responses to drugs.     

A new ceiling suspension for ultrasound scanners.

A new ceiling suspension for an ultrasound scanner is described, allowing automatic selection of all possible scanning planes by remote control     

Doppler ultrasound tracking instrument for monitoring blood flow velocity

Doppler ultrasound (US) is potentially a valuable method for monitoring changes of blood flow velocity over a period of many minutes or even hours, but is seldom used in this way. One difficulty that may have contributed to this is the problem of maintaining a fixed geometry between the US beam and the blood vessel. A method of improving the success of monitoring might be to actively steer the US beam so as to maintain an adequate signal even when small displacements of the transducer occur. We have designed and built a prototype system for this purpose. The system comprises a continuous-wave phased-array transducer controlled by a purpose-built Doppler unit. The system constantly evaluates the quality of the returning Doppler signal in terms of total power and signal-to-noise ratio (SNR) (evaluated by assessing the quality of derived envelope signals), and steers the ultrasonic beam in a manner so as to improve the signal, should this be necessary. The system was tested in vitro, where the automatic tracking of the Doppler signal doubled the effective beam width of the transducer. Further developments that increase sensitivity and steering range should result in US Doppler systems that are better suited to long-term monitoring.     

Dual instrument for in vivo and ex vivo OCT imaging in an ENT department

A dual instrument is assembled to investigate the usefulness of optical coherence tomography (OCT) imaging in an ear, nose and throat (ENT) department. Instrument 1 is dedicated to in vivo laryngeal investigation, based on an endoscope probe head assembled by compounding a miniature transversal flying spot scanning probe with a commercial fiber bundle endoscope. This dual probe head is used to implement a dual channel nasolaryngeal endoscopy-OCT system. The two probe heads are used to provide simultaneously OCT cross section images and en face fiber bundle endoscopic images. Instrument 2 is dedicated to either in vivo imaging of accessible surface skin and mucosal lesions of the scalp, face, neck and oral cavity or ex vivo imaging of the same excised tissues, based on a single OCT channel. This uses a better interface optics in a hand held probe. The two instruments share sequentially, the swept source at 1300 nm, the photo-detector unit and the imaging PC. An aiming red laser is permanently connected to the two instruments. This projects visible light collinearly with the 1300 nm beam and allows pixel correspondence between the en face endoscopy image and the cross section OCT image in Instrument 1, as well as surface guidance in Instrument 2 for the operator. The dual channel instrument was initially tested on phantom models and then on patients with suspect laryngeal lesions in a busy ENT practice. This feasibility study demonstrates the OCT potential of the dual imaging instrument as a useful tool in the testing and translation of OCT technology from the lab to the clinic. Instrument 1 is under investigation as a possible endoscopic screening tool for early laryngeal cancer. Larger size and better quality cross-section OCT images produced by Instrument 2 provide a reference base for comparison and continuing research on imaging freshly excised tissue, as well as in vivo interrogation of more superficial skin and mucosal lesions in the head and neck patient.OCIS codes: (170.4500) Optical coherence tomography, (170.2150) Endoscopic imaging, (170.3890) Medical optics instrumentation, (170.1610) Clinical applications     

Next-generation Raman tomography instrument for non-invasive in vivo bone imaging

Combining diffuse optical tomography methods with Raman spectroscopy of tissue provides the ability for in vivo measurements of chemical and molecular characteristics, which have the potential for being useful in diagnostic imaging. In this study a system for Raman tomography was developed and tested. A third generation microCT coupled system was developed to combine 10 detection fibers and 5 excitation fibers with laser line filtering and a Cytop reference signal. Phantom measurements of hydroxyapatite concentrations from 50 to 300 mg/ml had a linear response. Fiber placement and experiment design was optimized using cadaver animals with live animal measurements acquired to validate the systems capabilities. Promising results from the initial animal experiments presented here, pave the way for a study of longitudinal measurements during fracture healing and the scaling of the Raman tomography system towards human measurements.OCIS codes: (110.6955) Tomographic imaging, (170.0110) Imaging systems, (170.5660) Raman spectroscopy     

A new scan conversion algorithm for ultrasound compound scanning

An improved scan conversion algorithm for ultrasound compound scanning is proposed. In this algorithm, the input data in the spatial domain is sampled by the concentric square raster sampling (CSRS) method, and the display pixel data are filled by one-dimensional linear interpolation. The reconstruction error of the proposed algorithm is much smaller than that of other algorithms, because only one-dimensional, rather than two-dimensional, interpolation is involved. This algorithm greatly simplifies implementation of a real-time digital scan converter (DSC) for spatial compounding of ultrasound images.     

In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice

Background- Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 and nitric oxide synthases in the acute regulation of BAT blood flow. Methods and Results- Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (1 μg·kg(-1)·min(-1)). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R(2)=0.86, P<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in uncoupling protein 1-deficient mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in uncoupling protein 1-deficient mice than in wild-type mice. Finally, we investigated whether nitric oxide synthases played a role in acute norepinephrine-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of nitric oxide synthase 3 attenuated the norepinephrine-induced increase in BAT blood flow. Conclusions- These results indicate that CU can detect BAT in mice and estimate BAT blood flow in mice with functional differences in BAT.     

A new instrument for measuring clinician satisfaction with electronic health records

A new survey instrument was developed and validated to measure clinician (nurse) satisfaction with electronic health record impact on clinical process. The Health Information Technology Reference-Based Evaluation Framework guided the selection of evaluation dimensions for the survey. Survey questions were gathered from existing health information technology satisfaction surveys that reflected individual evaluation concepts, such as efficiency or benefits. Decisions about data-gathering methods (e.g., item selection) were made based on reviews of literature and surveys of clinician satisfaction with health information technology and expert input. Preliminary instrument validation was accomplished using qualitative and statistical analysis of five repeated sets of responses from clinicians at the pilot site and field administrations repeated twice at electronic health record implementation and paper-based comparison sites and by analyzing convergent evidence from observations and interviews. Reliability was assessed on one sample: 30 graduate nursing students at the single pilot site. Validity was assessed on three separate samples: (1) graduate nursing students (n = 30), (2) field test at a site with electronic health record (n = 39 participants), and (3) field test at a paper-based site (n = 17). The implementation and comparison sites are Program of All-Inclusive Care for the Elderly that provide managed day care for frail elderly. Survey responses were assessed for test-retest reliability, internal consistency, and content and construct validity. The instrument design enables its administration before and after electronic health record implementation. Work to date suggests the instrument is reliable and valid; it is offered to electronic health record evaluators for further testing and application.     

A novel ultrasound indentation system for measuring biomechanical properties of in vivo soft tissue

Technologies for soft tissue analysis are advancing at a rapid place. For instance, elastography, which provides soft tissue strain images, is starting to be tried in clinical practice as a tool for diagnosing cancer. Soft tissue deformation modeling and analysis is also an active area of research that has application in surgery planning and treatment. Typically, quantitative soft tissue analysis uses nominal values of soft tissue biomechanical properties. However, in practice, soft tissue properties can vary significantly between individuals. Hence, for soft tissue methodologies to reach their full potential as patient-specific techniques, there is a need to develop ways to efficiently measure soft tissue mechanical properties in vivo. This paper describes a prototype real-time ultrasound (US) indentation test system developed to meet this need. The system is based on the integration of a force sensor and an optical tracking system with a commercial US machine integrated with a suite of analysis methodologies. In a study on a single-layer phantom, we used the system to compare various methods of estimating linear elastic properties (via a theoretical approximation, 2-D finite element analysis, 3-D finite element analysis and a standard material-testing method). In a second study on a three-layer gelatin phantom, we describe a new finite-element-based inverse solution for recovering the Young's moduli of each layer to show how the system can estimate properties of internal components of soft tissue. Finally, we show how the system can be used to derive a modified quasilinear viscoelastic (QVL) model on real breast tissue.