Lung ventillation measurements using ultrasound

Information

  • Patent Grant
  • 9211110
  • Patent Number
    9,211,110
  • Date Filed
    Monday, March 17, 2014
    10 years ago
  • Date Issued
    Tuesday, December 15, 2015
    9 years ago
Abstract
An ultrasound-based system determines dynamic strain measurements over a surface using ultrasound speckle analysis that allows for accurate measurement of surface area displacement. The system additionally determines an approximate displacement along a third axis, the z-axis. From these, an estimation of a local volume change is determined. In this way, a volume change can be determined for the lung or any other region of interest.
Description
BACKGROUND OF THE DISCLOSURE

1. Field of the Disclosure


The disclosure relates to measuring changes in lung volume and, more particularly, to techniques for measuring changes in lung volume using ultrasound transducers.


2. Brief Description of Related Technology


Respiratory failure is common with premature births and is a leading cause for the prevalence of ventilatory assistance among infants. For example, approximately 25% of premature neonates require mechanical ventilation due to respiratory failure. Healthcare professionals must take particular care in treating the premature neonates, because of this prevalence of the lung immaturity and the resulting harmful effects. This includes monitoring lung volume changes in neonates receiving mechanical ventilation to assess the effectiveness and safety of therapeutic treatments.


Yet, despite the respiratory problems in premature infants and neonates, presently there are no benign, reliable ways to monitor local ventilation in this population. For decades, researchers have suggested techniques for monitoring lung performance in infants, but there have been no significant breakthroughs, certainly not in terms of producing cost effective, reliable solutions. Part of the problem is the physiology involved, especially for infants. Neonates experience poor gas exchange because of atelectasis and obstructive airway disease, caused by a lack of pulmonary surfactant and immature airways. Advancements in treatment of these conditions have occurred, especially with the advent of antenatal steroid therapy and exogenous surfactant administration. But despite these treatments, large percentages of neonates still require high-frequency ventilation (HFV).


One of the problems with neonate treatment, and one of the reasons why lung volume measurement techniques are sought after is the occurrence of lung injury produced by mechanical ventilation. A condition called bronchopulmonary dysplasia (BPD) results from the effects of positive pressure ventilation and other factors required for the treatment of respiratory distress syndrome (RDS). This is not uncommon with fragile patient populations of others on ventilators, that an effective treatment option can cause other secondary conditions. In this example, the principal causes of the secondary condition (BPB) relate directly to uncertainties involved in optimizing lung volume. The issues are compounded further, however, by the myriad of different ventilators and ventilatory modes employed to ventilate infants.


As to HFV in particular, this is a type of ventilation technique that uses small tidal volumes delivered at extremely rapid rates, typically 10-20 Hz. HFV techniques have been compared and contrasted with conventional mechanical ventilation (CMV). Animal studies have suggested that HFV has fewer complications than CMV, by reducing ventilator-induced lung injury. HFV, also, has better gas exchange in the presence of air leaks; and HFV decreases oxygen requirements. However, developing a proper strategy for HFV treatment remains elusive. The technique is still highly controversial. There is no standardize criteria for optimal use of HFV; and this problem is exacerbated by the lack of accurate clinical measurements of lung volume.


SUMMARY OF THE INVENTION

The background description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventor, to the extent it is described in this background section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.


The present application provides techniques for determining local lung strain and lung volume, and more specifically changes in lung volume, using ultrasound imaging. Ultrasound speckle tracking and strain imaging are combined with techniques for determining z-axis displacement to arrive at clinically accurate measurements of local lung volume.


In some examples, two-dimensional (2D) ultrasound speckle imaging techniques are used to determine an approximated surface area change; and the z-axis displacement is determined from separate a sensor array or other technique to independently determine physical displacement. The system may be implemented with multiple, small 2D array ultrasound transducers attached to a patient's (e.g., an infant's) chest similar to ECG leads. These will then be able to monitor local ventilation at distributed sites in real time across both lungs. These sensors could also be used in determining z-axis displacement, through a process of approximating osculating circles to the lung surface. The result is a dual-mode technique for measuring lung volume changes.


The technique may determine volume changes, between inspiration and expiration, over the entire lung or the technique may analyze a selectable portion of the lung, for example, by segmenting the ultrasound images and sensor array to a particular location.


The techniques are benign and can be applied routinely in a neonatal intensive care unit (NICU) setting. Although, more broadly, the techniques may be generalized to a monitoring method for local ventilation of any patient pool, from infant to adult. The techniques may be implemented as standalone systems or integrated with mechanical ventilation machines. The techniques may be used for diagnostic or therapeutic purposes. The techniques may be designed to provide alarm indications to attending medical personal, may be used to database patient responsiveness to treatment, may assist in diagnosis of respiratory conditions, or may provide automated instructions to a treatment apparatus.


In accordance with an example, provided is a method of determining change in the volume of a target sample, the method comprising: receiving, at an imaging processing machine, ultrasound images of a two-dimensional area corresponding to the target sample, where a first ultrasound image is taken at a first time period and a second ultrasound image is taken at a second time period after the first time period; determining, at the imaging processing machine, a change in strain value of the target sample over the two-dimensional area, wherein the strain value is determined from comparing the first ultrasound image to the second ultrasound image, wherein the first ultrasound image and the second ultrasound image are speckle-containing images; determining, at the imaging processing machine, and from the change in strain value, an xy-plane change in area of the target sample between the first time period and the second time period; determining, at the imaging processing machine, an approximate physical z-axis displacement over the two-dimensional area by approximating a change in local curvature of the two-dimensional area between the first time period and the second time period; and determining, at the imaging processing machine, a volume displacement of the target sample from the approximate physical z-axis displacement and the change in strain value.


In accordance with another example, an apparatus comprises: an imaging processing machine having a processor and a memory, wherein the processor is configured to execute instructions that when executed cause the imaging processing machine: to receive ultrasound images of a two-dimensional area corresponding to the target sample, where a first ultrasound image is taken at a first time period and a second ultrasound image is taken at a second time period after the first time period; to determine a change in strain value of the target sample over the two-dimensional area, wherein the strain value is determined from comparing the first ultrasound image to the second ultrasound image; to determine from the change in strain value, an xy-plane change in area of the target sample between the first time period and the second time period; to determine an approximate physical z-axis displacement over the two-dimensional area by approximating a change in local curvature of the two-dimensional area between the first time period and the second time period; and to determine a volume displacement of the target sample from the approximate physical z-axis displacement and the change in strain value.





BRIEF DESCRIPTION OF THE DRAWINGS

The figures described below depict various aspects of the system and methods disclosed herein. It should be understood that each figure depicts an embodiment of a particular aspect of the disclosed system and methods, and that each of the figures is intended to accord with a possible embodiment thereof. Further, wherever possible, the following description refers to the reference numerals included in the following figures, in which features depicted in multiple figures are designated with consistent reference numerals.



FIGS. 1A and 1B are plots of strain along two orthogonal directions obtained from a 1 dimensional transducer;



FIGS. 2A and 2B are ultrasound images of the lung during full expiration (FIG. 2A) and full inspiration (FIG. 2B), in accordance with an example;



FIG. 3 is flow diagram of a process for determining lung volume change, in accordance with an example; and



FIG. 4 illustrates an example lung volume analysis system, in accordance with an example.



FIG. 5 illustrates an example handheld ultrasound device for determining long volume using a one-dimensional ultrasound transducer, in accordance with an example.



FIG. 6 illustrates an example handheld ultrasound device for determining long volume using a two-dimensional ultrasound transducer, in accordance with an example.





DETAILED DESCRIPTION

The techniques described herein rely upon ultrasound imaging to determine dynamic strain measurements of the lung surface and extend well beyond conventional strain measurement. The techniques may determine strain using ultrasound speckle analysis that allows for accurate measurement of surface area displacement. The techniques additionally approximate displacement along a third axis, the z-axis, from which an estimation of a local volume change may be achieved. Indeed, in this way, the present techniques result from an unexpected application of ultrasound strain imaging. Conventionally, ultrasound strain imaging has been used to measure only tissue hardness in multiple organ systems and disease processes, including cardiac wall and heart function, breast tumor analysis, thyroid mass assessment, deep venous thrombosis aging, lymph node metastases, renal transplant rejection, testicular tumor evaluation, and prostate tumor assessment. These applications have been attempted with varying degrees of success.


The present technique uses speckle tracking to calculate the strain in ultrasound. For example, using pattern matching techniques, we can track speckle motion in moving tissue to sub-wavelength accuracies. The tracking technology is robust and accurate; and speckle-tracking based strain imaging is available on most clinical ultrasound units. However, while strain imaging has been used to measure tissue hardness, deformation is different. Unlike tissue hardness, deformation, generally speaking, depends on a variety of external factors that will affect measurements. Stresses applied to a patient, boundary conditions for the organ, a patient's weight, organ size, etc. can all affect the deformation of an organ.


With the present techniques, we show that strain imaging may be used effectively for measuring local lung ventilation, in particular changes in lung volume. Data from the strain imaging is directly convertible to local ventilation, with positive strain data expressing expansion of the lung volume and negative strain data expressing contraction. In this way, the present techniques provide a solution to the local lung ventilation quandary, where conventional ventilators can measure the total air displacement and the pressure used to displace the gas, but cannot determine where the gas is actually going within the patient. These ventilators determine the actual impact on the lung, leaving the local distribution of the gas in the lungs unknown.


The present techniques provide a new targeted application of ultrasound speckle tracking and strain imaging, lung strain. These techniques derive from using ultrasound to solve a major problem in an organ system that is only rarely even considered a legitimate target for ultrasound. We base this on the following expression:










ɛ
=


Δ





l

l


,




(
1
)








where ε is strain, l is an arbitrary length and Δl is the change in the length based on some deformation, such a respiratory motion. In this way, we show that strain directly correlates to deformation. We extend this linear strain to volume strain to provide relative changes in lung volume or ventilation. The result is












Δ





V

V

=



i







ɛ
i



,




(
2
)








where V is volume, ΔV is change in volume, εi is linear strain in the ith direction where i=x, y, or z. Thus, from Equation (2), if V is considered a small local volume element defined by the ultrasound image, then the sum of the strains in three (3) directions multiplied by the imaged volume element will give ΔV.


In some examples, 2D ultrasound transducer arrays may be used to obtain a near complete map of lung ventilation. These transducer arrays may be placed around a neonate's chest, similar to ECG leads, and spaced apart based on the size of the volume area desired. In another example, 1D ultrasound transducers probes may be used to take multiple measurements at different locations on the lung. For this later example, the probes may be used to simulate a 2D array, for example, by taking a first measurement along a first one-dimensional axis and then rotating the probe to take a second measurement along an orthogonal direction, from which the orthogonal strain measurement is then determined.



FIG. 5 illustrates an example handheld ultrasound device 100 that may be used to determine a change in volume of a target sample 101, such as the lung or bladder. The device 100 includes a handheld controller 102 that includes an image processing machine having a processor and embedded memory. The handheld controller 102 has a display 104 for displaying ultrasound images captured by an ultrasound transducer 106 (with scanhead 107) coupled to the controller 102 through a wired connection, such as a Universal Serial Business (USB) connector 108. In the illustrated example, the transducer 106 is a 1D transducer. However, 2D transducers and 3D ultrasound devices may be used instead. In some examples, using a USB connector allows for interchanging the transducer 106 for another transducer, 1D or 2D or what are described as 3D ultrasound or 4D ultrasound devices. In some examples, the transducer 106 may be connected wirelessly to the controller 102, using a wireless communication protocol such as any of the IEEE 802.11 standards, 802.11a, b, g, n, ac, or ad. Other example wireless communication modalities include IEEE 802.15 standard, known as “Bluetooth,” and near field communication (NFC) standards used for smart devices. The controller 102 may perform the strain measurements and volume determinations discussed herein. While in other examples, the controller 102 may be part of an overall imaging processing apparatus that includes an external machine, with dedicated processor, coupled to the controller 102, wirelessly or wired, to receive preliminary ultrasound data and process that data to determine changes in strain values, across an xy-plane and the z-axis displacement.



FIG. 6 illustrates another device 200 similar to that of the device 100, but showing a controller 202 and 2D ultrasound transducer 204, with scanhead 206. It will be appreciated that the ultrasound transducer may be implemented with a linear array, phased array, convex array, 2D array, 3D ultrasound device array, or 4D ultrasound device array, by way of example. As discussed herein, like the device 100, the device 200 can be moved over a subject to detect lung ventilation, functioning in some respects as an ultrasound stethoscope. In some example implementations of a 1D measurement, the devices herein may be used to obtain a localized one dimensional strain value. For example, a 1D ultrasound transducer may be used to collect data at two different times from which the system is able to determine a one dimensional strain value and convert that value into an indication of a localized ventilation. For example, this 1D strain/ventilation measure could be part of a binary ventilation system, that identifies whether the subject is ventilating or not, ventilating at a maximal amount or not, ventilating over a specific ventilation range, ventilating in a range of concern (too fast or two slow), etc. Indeed, while examples are described herein in reference to 2D ultrasound transducers, the techniques herein described can be implemented using 1D transducers as well. These one dimensional strain/ventilation determinations may be performed at a single location on a subject or on multiple locations on a subject. Beyond these one dimensional strain and ventilation determinations, in some examples, these 1D ultrasound transducers may be used for additionally determining volume displacements in accordance with examples discussed herein. For example, the 1D transducers can be used to collect 1D strain data along orthogonal directions and then at different times to develop a two dimensional strain data.


In some examples, the devices 100 and 200 represent example manifestations of the environment 10, the machine 12, and/or any of the machines 70-1-70-n. Indeed, any of these processing devices are included by use of the term “system” (e.g., an imaging system), as used herein. That is, it will be understood that the techniques described herein as implemented on a system may be implemented fully or partially on the devices 100 or 200, the computer 12, any of the remote computers 70-1-70-n, or any suitable other devices. And reference to operations on any of the environment 10, the machine 12, and/or any of the machines 70-1-70-n shall also include implementation on any other of the environment 10, the machine 12, and/or any of the machines 70-1-70-n.



FIGS. 1A and 1B show a local map for individual breaths in a patient produced from a processed ultrasound signal from the lung surface in two-orthogonal directions (FIG. 1A and FIG. 1B), achieved by rotating a 1D ultrasound transducer, such as the transducer 106. This plot is a direct measure of local lung expansion and contraction, in the two examined directions over time. Each plot of FIGS. 1A and 1B were taken over different breaths and each oscillates in strains over about 2-3 s. The max strains were very similar, approximately 35% as shown.


In any event, whether a 1D transducer or a 2D ultrasound transducer array is used, two of the strain components from Equation (2) are obtained by tracking two orthogonal strains along the lung surface with respiration. The third component normal to the lung surface, i.e., along the z-axis, is tracked in a different manner.


Ultrasound will not enter the air-filled lung. Yet, in some examples, a system is able to track the change in the radius of curvature of a local osculating circle centered in a sample region. The z-axis displacement may be determined different ways depending on the transducers and sensor configurations. For example, using a 1D ultrasound array (such as in the device 100 or the system 1000 implemented with a 1D array), where one may not be able to acquire orthogonal directions simultaneously along principal directions, the system may approximate the z-axis displacement by first identifying near orthogonal space curves along the lung surface by rotating the transducer similar to FIGS. 2A and 2B. The system may identify the lung surface from the ultrasound image, since it is moving and it is a total reflector of ultrasound. The system may be configured to identify the lung surface at extreme positions, for example at full inspiration and full expiration. The system may then determine osculating circles corresponding to the lung surface, e.g., by radially fitting to a portion of the lung surface, after which a z-axis displacement, e.g., a radial difference along a direction orthogonal to the portion of the lung surface, is determined. In the example of 2D ultrasound arrays, orthogonal acquisitions along principal direction can be acquired simultaneously. Therefore, space curves can be fit from the ultrasound images using continuous functions, such as cubic functions. The system can then take the second derivatives of the cubic at the center point in each direction as the curvature at that point. The system can then take the average of the two curvatures to obtain a mean curvature, which can be inverted to get the instantaneous mean radius of curvature. This example technique is similar to fitting osculating circles at the points of second order contact in the orthogonal directions and using the radii of the circles to calculate the instantaneous radii of curvature. In any event, the system can then use the temporal fluctuation of these instantaneous mean radius of curvature values around the temporal mean radius of curvature, normalized by the temporal mean radius of curvature, as an estimate of the strain in the normal direction. From this, the system is able to calculate volume strain.


From examining changes in the radius of curvature between two states, for example between inspiration (FIG. 2A) and expiration (FIG. 2B), it is possible to estimate the strain along the z-axis. In an example, FIGS. 2A and 2B may represent ultrasound images on the display 104. The illustrated example shows measurement of the radius of curvature in near full inspiration and full expiration by re-calculating the centers of the local osculating circles at those two instances. In this way, the radii of curvature of the set of osculating circles can be tracked throughout respiration. The mean value of the radii may be set as the zero strain reference point, such that the instantaneous strain in the z direction, εz(t), is












ɛ
z



(
t
)


=



r


(
t
)


-


r







r





,




(
3
)








where r(t) is the instantaneous local mean radius of curvature and <r> is the temporal mean radius of curvature.


It is noted that, for a particular target, there may be different radii of curvature along different orthogonal planes. Essentially, the approximating osculating circle may be direction dependent, especially for smaller circles associated with neonates and infants. We can overcome such directional dependence, by measuring two potentially-different radii of curvatures, along different directions. In some examples, the system can estimate two curvatures, C where C=1/r. The system can average the curvatures to obtain a mean curvature or multiply them to obtain the Gaussian curvature. By inverting the mean curvature or inverting the square root of the Gaussian curvature, two estimates of a radius of curvature for the lung surface may be obtained. Using these relationships, the system can calculate the local ventilation over time by comparing the time dependency, as described herein.


Other techniques for determining changes in z-axis displacement include using an accelerometer, for example, an accelerometer embedded in the ultrasound transducer devices 106 or 204, such as embedded within the scanhead 107 and 206, respectively. The accelerometer would detect changes in movement, position, and/or pressure from, which the controller would determine z-axis displacement. In other examples, a biometric sensor, such as an activity monitory, may be embedded within the ultrasound transducer to determine z-axis displacement. In yet other examples, the accelerometer-based sensor (or other biometric sensor) may be contained within another device, such as a dedicated sensor device or a handheld or wearable “smart” device, such as smartphone or activity monitor. In some examples, the accelerometer may be within a case or housing for a handheld or wearable such device.


The accelerometer may be a single axis detection accelerometer (e.g., z-axis). In other examples, the accelerometer may detect movement in three orthogonal axes (e.g., x-, y-, and z-axes). In such examples, xy detection data may be combined with the ultrasound xy data to refine measurements of changes in area across the xy-plane. The accelerometer may be triggered to automatically perform scanning (e.g., z-axis scanning), in response to sensing the depression of the accelerometer into a subject. When embedded in an ultrasound device, that sensing may result from being depressed into the subject.


Either the accelerometer or the ultrasound transducer itself can be designed to detect the orientation of the embedded sensor and/or of the probe itself in some examples. That orientation data may be used to optimize volume measurement determinations, for example, by applying resizing and stretching on collected data. In some examples, the orientation of the accelerometer is separately controllable through the controller.



FIG. 3 illustrates an example process 1000 for determining changes in lung volume and as may be implemented in an imaging processing system, described further below. As noted the process 1000 may be implemented in whole or in part by any of the devices 100 and 200 and the computer 12. The process 1000, as described, determines strain, e.g., a local strain, from which lung volume change data may be determined. That local strain may be used in the determination of other characteristics of a target, as well, or as a proxy for lung volume.


Initially, at a block 1002, ultrasound transducers, either 2D array transducers or single 1D transducers, are positioned on a subject for image collection over a sample region. The transducers may be placed topically on the surface patient's skin, for example; although the particular techniques are not limited to a particular type of ultrasound image pickup. The particular locations of the transducers may also be determined based on the number of transducers being used to collect volumetric data, the size of the patient, the perceived size of the organ, the amount of intervening tissue between the upper skin surface and the lungs, and any prior information that might suggest variations in ventilation such as an underlying tumor, pneumonia, or atelectasis. Furthermore, the transducers are positioned for tracking, e.g., speckle tracking, in two orthogonal directions, such that the local strain can be determined from two-dimension tracking.


In some examples, the preferred locations of the ultrasound transducers may be determined from a 3D CT scan or other medical imaging modality, such as from a PET scanner, MRI, or etc. Indeed, in some applications it may be desirable, even with the cost effectiveness of the present techniques, to have simultaneous measurement of both ultrasound speckle images and other medical image data, for example to allow better registration of image data, more accurate and more developed tracking for treatment purposes, for example. Tracking may be assisted by the use of metallic markers visible in through both ultrasound and CT imaging systems, which may be used to register image data between the two modalities. Use of another medical imaging modality can also be used for calibrating the ultrasound system upon start up; although preferably ultrasound systems are calibrated at the factory or personalized, historical imaging data from the patient is used to determine optimum transducer location and operating thresholds.


At a block 1004, the imaging system determines thresholds for use in speckle tracking from the ultrasound images. For example, the block 1004 may set a threshold for backscattered signal strength, to be used in speckle tracking a comparison between two different ultrasound speckle images. Additionally, the mechanical index (MI) threshold for the ultrasound transducers may be provided at block 1004, where a range of MI<0.3 was chosen for some examples. While the actual MI values can vary, MI values or approximately 0.3 and below were chosen to prevent any chance of bioeffect especially given the neonatal population. Values for MI considerably below the 0.3 will be desired for numerous applications.


At a block 1006, ultrasound speckle images are captured over a sample area (see, e.g., FIG. 2 generally coinciding with a planar region across the xy-plane, and at different sampling times. The spacing between sampling times may be adjusted manually or may be determined automatically by the system. It is desired, in some examples, to collect speckle images at a full inspiration and then again at full expiration, to assess total lung volume changes. Thus, the block 1006 may collect speckle images at a sufficiently high frequency to identify, from the resulting data set, when the maximum and minimum lung volumes are achieved, and then identify these points amongst the image data stored from the captures overall. However, in other examples, real-time continuous capturing would be used.


At a block 1008, the process 1000 performs a strain determination, over the 2D sample area defined by the xy-area, based on the speckle image data collected from block 1006. This strain may be determined at each of a plurality of different sub-regions within the sample area, defined by the number of transducers and transducer spacing. The strain determinations of each of the sub-regions will then represent local ventilation at each of the sampled sites. The local strain at the lung surface is determined directly from 2D data taken by 2D ultrasound transducer arrays or from 1D transducer probes imaging along two orthogonal directions. In some examples, the strain data may be directly used to assess the condition of the target region, for example as a substitute indicator for lung volume changes. However, in the illustrated example, at the block 1008, the system may further determine from the strain values, a change in area of a two-dimensional area. For example, the block 1008 may determine an xy-plane change in area between two different speckle imaging time frames.


With strain determined over a two-dimensional area, a block 1010 now determines a physical displacement, along the z-axis, of the sample region at the different sample times corresponding to those of the block 1008. This may be done based on image data, as discussed. For example, the image processing system may define an osculating circle for the ultrasound images collected at each location of the ultrasound transducer to define a local curvature that changes from inspiration to expiration. By defining osculating circles at the surface and at inspiration and expiration, the image processor system may estimate a mean radius of these circles, where a change in radius of the mean radius will define a strain in the Z direction.


In other examples, the block 1010 collects data from an accelerator or other biometric sensor device and determines z-axis displacement.


The process 1000 will collect data over numerous cycles, via blocks 1004-1008, to help reduce variation and noise in data collection. The number of cycles can be set based on the number of transducers, the physiology of the patient, the need to avoid bioeffects, etc. In some examples, 10-20 cycles of data were collected at an MI<0.3, although higher MI values are contemplated. Furthermore, these blocks can perform statistically significant analyses on the collected data, to more accurately determine strain and the radii for osculating circles. Such statistically significant analysis may include averaging data, high and/or low threshold filtering, skewness analysis, kurtosis analysis, or a combination thereof.


At a block 1012, the system 1000 determines the change in volume between at least two different sample points, based on the xy-plane strain determination and the z-axis strain determination and applying Equations 1-3 above. The change may be stored in a database and provided to medical practitioners through a display, such as through the imaging processing system, or to an treatment system, such as a ventilator system, using a block 1014. In some examples, the ultrasound volume data may be displayed over an ultrasound image, for example by mapping approximate physical z-axis displacements onto an ultrasound image of the two-dimensional area for display. Such mapping could be achieved by overlaying a displacement vector, osculating circles, or other graphic to display z-axis displacement.


The process 1000 may be modified in various ways. For example, when using a 1D ultrasound transducer, even obtaining orthogonal data by rotating the scanhead 90° at each scanning site, the typical surface area insonified may be on the order of 2×2 cm. Because this may overestimate lung volume areas for neonates, the process can subsample smaller regions, as desired. Ultrasound access to the lung shouldn't be a problem, since we can easily scan between ribs. With a 2D array for the scanning, orthogonal samples may be acquired simultaneously, allowing faster, theoretically more accurate estimation of the radius of curvature changes from each orthogonal direction.


These measurements may be taken statically at full-inspiration and full-expiration, or at any two given speckle imaging times. However, the system may also be integrated with HFV ventilation treatments. In these examples, the block 1006 may receive a triggering signal from an HFV system, where that signal indicates the frequency or period of the ventilation treatment. In response, ultrasound speckle images may be synchronized (or clocked) with the timing of the HFV. Like the block 1006, the block 1010 may be triggered by a signal from an HFV system or other external ventilation system. Such triggering allows for more real-time assessment of lung ventilation and responsive to treatments, allowing medical personnel to more precisely know the ventilation distributions and measurement reproducibility throughout the lung for different tidal volumes. Examples ranges of detection are 30 Hz or lower, and in particular 15 Hz.


The accuracy of the volume change determination can be affected not only by the size and position of the osculating approximately circles, but by the number of such circles. When using multiple transducers simultaneously on a sample region, spacing the transducers too far apart, and the osculating circles will have larger gaps between them, leaving more of the lung to be approximated in volume change, but not actually measured. Although strain assessment over the entire 2D area may be achieved for these regions, exact approximation of the x-axis displacement will not be. Therefore, more transducers or denser or larger transducer arrays may be used, if desired, for more accurate measurement of displacement along the z-axis. Correlations between ultrasound speckle and osculating circles analysis and actual volumetric changes in the lung may be performed by comparing this data against CT, PET, MRI or other sample scan images, capable of volumetric analysis.


In some examples, other sensors could be used in addition to the ultrasound transducers and for the purposes of separately determining a z-axis displacement, either individually or in conjunction with the ultrasound transducers. For example, accelerometer sensors may be used with or within the ultrasound transducers to provide mapping of z-axis displacements over a respiratory cycle. The displacements could be measured, for example, from a mean position. Another sensor would be a mechanical displacement gauge with or within the ultrasound transducer to assist in calculation of the z-axis displacement.


Finally, binary measurements of expansion and contraction should still be correct even if the magnitudes are incorrect. Such measurements should distinguish areas of air trapping from truly ventilating lung. Thus if the underlying lung just translates, but the strain is zero, it is not being ventilated. This would correspond to air trapping.


The techniques herein may be used with any type of 1D or 2D ultrasound transducer. These include linear array and curved array transducers, steerable transducers, whether based on pulse wave or continuous wave Doppler, color Doppler, harmonic imaging, or any other ultrasound modality, preferably capable of producing speckle imaging. The technique could be used with 3D ultrasound devices, to determine approximating osculating circles, although 1D and 2D transducers generally should be more cost effective and more amenable to real time imaging.



FIG. 4 illustrates an example lung volume analysis system for performing a lung volume determination in accordance with the teachings hereinabove. The techniques described above may be coded, in software, hardware, firmware, or combination thereof, for execution on a computing device such as that illustrated in FIG. 4. Generally, FIG. 4 illustrates an example of a suitable computing system environment 10 to interface with a medical professional or other user to analyze medical data, in particular ultrasound image data captured at the point of assessment or from a stored database of historical image data. It should be noted that the computing system environment 10 is only one example of a suitable computing environment and is not intended to suggest any limitation as to the scope of use or functionality of the method and apparatus of the claims.


An exemplary system for implementing the blocks of the method (FIG. 3) and apparatus includes a general-purpose computing device in the form of a computer 12. Components of computer 12 may include, but are not limited to, a processing unit 14 and a system memory 16. The computer 12 may operate in a networked environment using logical connections to one or more remote computers, such as remote computers 70-1, 70-2, . . . 70-n, via a local area network (LAN) 72 and/or a wide area network (WAN) 73 via a modem or other network interface 75. These remote computers 70 may include other computers like computer 12, but in some examples, these remote computers 70 include one or more of (i) a medical imaging system, (ii) a signal records database systems, (iii) a scanner, and/or (iv) a signal filtering system.


In the illustrated example, the computer 12 is connected to an image processing machine, labeled machine 70-1. The machine 70-1 may be a stand-alone ultrasound system, having ultrasound transducers (i.e., 2D arrays and/or 1D probes) and a processing machine for performing ultrasound imaging operation, including transmitting stimulation signals, collecting image data and z-axis displacement data, performing signal analysis on collected data, such as noise filtering, statistical analysis, etc., and storing (and/or buffering) that data and transmitting the same to the computer 12 for further analysis and strain and volume determination. In other examples, a series of ultrasound transducers may be connected directly to the computer 12, which would then control operation of the transducers, perform the data processing and storage functions, in place of the remote system 70-1.


Computer 12 typically includes a variety of computer readable media that may be any available media that may be accessed by computer 12 and includes both volatile and nonvolatile media, removable and non-removable media. The system memory 16 includes computer storage media in the form of volatile and/or nonvolatile memory such as read only memory (ROM) and random access memory (RAM). The ROM may include a basic input/output system (BIOS). RAM typically contains data and/or program modules that include operating system 20, application programs 22, other program modules 24, and program data 26. These programs may include implementation of the blocks of process 1000. The computer 12 may also include other removable/non-removable, volatile/nonvolatile computer storage media such as a hard disk drive, a magnetic disk drive that reads from or writes to a magnetic disk, and an optical disk drive that reads from or writes to an optical disk.


A user may enter commands and information into the computer 12 through input devices such as a keyboard 30 and pointing device 32, commonly referred to as a mouse, trackball or touch pad. Other input devices (not illustrated) may include a microphone, joystick, game pad, satellite dish, scanner, or the like. These and other input devices are often connected to the processing unit 14 through a user input interface 35 that is coupled to a system bus, but may be connected by other interface and bus structures, such as a parallel port, game port or a universal serial bus (USB). A monitor 40 or other type of display device may also be connected to the processor 14 via an interface, such as a video interface 42. In addition to the monitor, computers may also include other peripheral output devices such as speakers 50 and printer 52, which may be connected through an output peripheral interface 55.


Generally, the techniques herein may be coded in any computing language for execution on computer 12. Ultrasound speckle image data and z-axis displacement data may be obtained from the remote computers 70-1, 70-2, . . . 70-n and stored loaded on to any of the computer storage devices of computer 12. Once such data is obtained, a user may input or select the condition parameters through an input mechanism as described. Although, in other examples, the condition parameters may be pre-selected or automatically determined, for example, based on a particular type of analysis that is to be performed. The output of the executable program may be displayed on a display (e.g., a monitor 40), sent to a printer 52, stored for later use by the computer 12, or offloaded to another system, such as one of the remote computers 70. The output may be in the form of an image, a graph, a table or any combination thereof, by way of example. Operations of the system may be recorded in a log database for future reference as shown. This log database may be accessed at subsequent times.


The various blocks, operations, and techniques described above may be implemented in hardware, firmware, software, or any combination of hardware, firmware, and/or software. When implemented in hardware, some or all of the blocks, operations, techniques, etc. may be implemented in, for example, a custom integrated circuit (IC), an application specific integrated circuit (ASIC), a field programmable logic array (FPGA), a programmable logic array (PLA), etc.


When implemented in software, the software may be stored in any computer readable memory such as on a magnetic disk, an optical disk, or other storage medium, in a RAM or ROM or flash memory of a computer, processor, hard disk drive, optical disk drive, tape drive, etc. Likewise, the software may be delivered to a user or a system via any known or desired delivery method including, for example, on a computer readable disk or other transportable computer storage mechanism or via communication media. Communication media typically embodies computer readable instructions, data structures, program modules or other data in a modulated data signal such as a carrier wave or other transport mechanism. The term “modulated data signal” means a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, and not limitation, communication media includes wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, radio frequency, infrared and other wireless media. Thus, the software may be delivered to a user or a system via a communication channel such as a telephone line, a DSL line, a cable television line, a wireless communication channel, the Internet, etc. (which are viewed as being the same as or interchangeable with providing such software via a transportable storage medium).


Moreover, while the present invention has been described with reference to specific examples, which are intended to be illustrative only and not to be limiting of the invention, it will be apparent to those of ordinary skill in the art that changes, additions and/or deletions may be made to the disclosed embodiments without departing from the spirit and scope of the invention.


Thus, although certain apparatus constructed in accordance with the teachings of the invention have been described herein, the scope of coverage of this patent is not limited thereto. On the contrary, this patent covers all embodiments of the teachings of the invention fairly falling within the scope of the appended claims either literally or under the doctrine of equivalents.

Claims
  • 1. A method of determining change in volume of a target sample, the method comprising: receiving, at an imaging processing machine, ultrasound images of a two-dimensional area corresponding to the target sample, where a first ultrasound image is taken at a first time period and a second ultrasound image is taken at a second time period after the first time period;determining, at the imaging processing machine, a change in strain value of the target sample over the two-dimensional area, wherein the strain value is determined from comparing the first ultrasound image to the second ultrasound image, wherein the first ultrasound image and the second ultrasound image are speckle-containing images;determining, at the imaging processing machine, and from the change in strain value, an xy-plane change in area of the target sample between the first time period and the second time period;determining, at the imaging processing machine, an approximate physical z-axis displacement over the two-dimensional area by approximating a change in local curvature of the two-dimensional area between the first time period and the second time period; anddetermining, at the imaging processing machine, a volume displacement of the target sample from the approximate physical z-axis displacement and change in strain value.
  • 2. The method of claim 1, wherein determining an approximate physical z-axis displacement further comprises: defining at least one osculating circle at a region of the two-dimensional area of the target sample;determining an initial radius of the at least one osculating circle at the first time period and a second radius of the at least one osculating circle at the second time period; anddetermining the approximate physical z-axis displacement from a change between the initial radius and the second radius.
  • 3. The method of claim 2, further comprising: defining a plurality of osculating circles at for the two-dimensional area of the target sample;determining for each of the osculating circles changes in radii between the first time period and the second time period; anddetermining the approximate physical z-axis displacement as a mean of the determined changes in radii for the plurality of osculating circles.
  • 4. The method of claim 3, wherein the plurality of osculating circles have the same initial radius of curvature at the first time period.
  • 5. The method of claim 3, wherein at least some of the plurality of osculating circles have a different initial radius of curvature at the first time period.
  • 6. The method of claim 3, wherein osculating circles corresponding to a central region of the two-dimensional area have a larger initial radius of curvature than osculating circles corresponding to a peripheral region of the two-dimensional area.
  • 7. The method of claim 3, wherein the osculating circles are defined along two orthogonal directions of the two-dimensional area, wherein the each osculating circle is defined by a principal curvature determined from an ultrasound image of a two-dimensional area corresponding to the target sample.
  • 8. The method of claim 3, further comprising performing a statistically significant analysis of the determined changes in radii for the plurality of osculating circles to identify a subset of significance for the changes in radii, the method comprising determining the approximate physical z-axis displacement as mean of the subset of significance for the changes in radii.
  • 9. The method of claim 8, wherein the statistically significant analysis comprises a averaging data, high and/or low threshold filtering, skewness analysis, kurtosis analysis, or a combination thereof.
  • 10. The method of claim 3, further comprising: determining a plurality of approximate physical z-axis displacements over the two-dimensional area; andmapping the plurality of approximate physical z-axis displacements onto an ultrasound image of the two-dimensional area for display.
US Referenced Citations (246)
Number Name Date Kind
3823708 Lawhorn Jul 1974 A
3861387 Lawhorn et al. Jan 1975 A
3882853 Gofman et al. May 1975 A
5474070 Ophir Dec 1995 A
5722412 Pflugrath et al. Mar 1998 A
5817024 Ogle et al. Oct 1998 A
5893363 Little et al. Apr 1999 A
6068602 Tham et al. May 2000 A
6135961 Pflugrath et al. Oct 2000 A
6203498 Bunce et al. Mar 2001 B1
6325759 Pelissier Dec 2001 B1
D456509 Schultz Apr 2002 S
6364839 Little et al. Apr 2002 B1
6371918 Bunce Apr 2002 B1
6383139 Hwang et al. May 2002 B1
6416475 Hwang et al. Jul 2002 B1
D461895 Barnes et al. Aug 2002 S
6447451 Wing et al. Sep 2002 B1
6471651 Hwang et al. Oct 2002 B1
D468433 Wagner et al. Jan 2003 S
D471281 Baura et al. Mar 2003 S
D475138 Baura et al. May 2003 S
6558326 Pelissier May 2003 B2
6561986 Baura et al. May 2003 B2
6569101 Quistgaard et al. May 2003 B2
6575908 Barnes et al. Jun 2003 B2
6602201 Hepp et al. Aug 2003 B1
6604630 Cabatic et al. Aug 2003 B1
6636754 Baura et al. Oct 2003 B1
6648826 Little et al. Nov 2003 B2
6817982 Fritz et al. Nov 2004 B2
6835177 Fritz et al. Dec 2004 B2
6846288 Nagar et al. Jan 2005 B2
6851392 Zan et al. Feb 2005 B2
6911008 Pelissier et al. Jun 2005 B2
D509900 Barnes et al. Sep 2005 S
6962566 Quistgaard et al. Nov 2005 B2
6979292 Kanayama et al. Dec 2005 B2
6984284 Yin et al. Jan 2006 B2
D518574 Chaggares Apr 2006 S
D520139 Chaggares May 2006 S
D520140 Chaggares May 2006 S
7043293 Baura May 2006 B1
7052460 Liu et al. May 2006 B2
7068867 Adoram et al. Jun 2006 B2
D525363 Chaggares Jul 2006 S
7072706 Baumgardner et al. Jul 2006 B2
D531316 Chaggares Oct 2006 S
7133713 Zan Nov 2006 B2
7149576 Baura et al. Dec 2006 B1
7169108 Little et al. Jan 2007 B2
D538432 Diener et al. Mar 2007 S
D541942 Hirson et al. May 2007 S
7214107 Powell et al. May 2007 B2
D544962 Diener et al. Jun 2007 S
7230368 Lukacs et al. Jun 2007 B2
7251524 Hepp et al. Jul 2007 B1
7255678 Mehi et al. Aug 2007 B2
7274325 Fattah et al. Sep 2007 B2
D558351 Diener et al. Dec 2007 S
D559390 Diener et al. Jan 2008 S
7426904 Zan et al. Sep 2008 B2
7434542 Zan et al. Oct 2008 B2
7449640 Coleman Nov 2008 B2
D591423 Diener et al. Apr 2009 S
D592750 Diener et al. May 2009 S
D592760 Diener et al. May 2009 S
7534211 Hwang et al. May 2009 B2
7549961 Hwang Jun 2009 B1
7570989 Baura et al. Aug 2009 B2
7588541 Floyd et al. Sep 2009 B2
7591786 Holmberg et al. Sep 2009 B2
7604596 Hwang et al. Oct 2009 B2
7643040 Gabrielson et al. Jan 2010 B1
D609349 Pelissier et al. Feb 2010 S
7686766 Quistgaard et al. Mar 2010 B2
7694814 Cristobal et al. Apr 2010 B1
7727153 Fritz et al. Jun 2010 B2
7740586 Hwang et al. Jun 2010 B2
7750536 Chaggares et al. Jul 2010 B2
7798963 White et al. Sep 2010 B2
7804970 Hippe et al. Sep 2010 B2
D625014 Hansen et al. Oct 2010 S
D625015 Hansen et al. Oct 2010 S
7808156 Chaggares et al. Oct 2010 B2
7809400 Hwang Oct 2010 B1
7819807 Barnes et al. Oct 2010 B2
7830069 Lukacs et al. Nov 2010 B2
7841575 Sliger Nov 2010 B1
7849250 Diener et al. Dec 2010 B2
7867168 Little et al. Jan 2011 B2
7883276 Davidson et al. Feb 2011 B2
7901358 Mehi et al. Mar 2011 B2
7950971 Hobet et al. May 2011 B2
7978461 Diener et al. Jul 2011 B2
7996688 Little Aug 2011 B2
8016419 Zhang et al. Sep 2011 B2
8052606 Barnes et al. Nov 2011 B2
8066642 Little et al. Nov 2011 B1
8078256 Zan Dec 2011 B2
8088070 Pelissier et al. Jan 2012 B2
8088071 Hwang et al. Jan 2012 B2
8090065 Gabrielson et al. Jan 2012 B2
8107694 Hamilton et al. Jan 2012 B2
D654178 Antonio et al. Feb 2012 S
8128050 Sliger Mar 2012 B1
8137278 Lundberg et al. Mar 2012 B2
D657361 Goodwin et al. Apr 2012 S
8147408 Bunce et al. Apr 2012 B2
8164011 Dunbar Apr 2012 B1
8199685 Hwang Jun 2012 B2
8213467 Little et al. Jul 2012 B2
8216146 Hwang et al. Jul 2012 B2
8226562 Pelissier et al. Jul 2012 B2
8237601 Dunbar et al. Aug 2012 B2
8275449 White et al. Sep 2012 B2
8284015 Van Eyck et al. Oct 2012 B1
8298144 Burcher Oct 2012 B2
8310133 Brown et al. Nov 2012 B2
8316518 Lukacs et al. Nov 2012 B2
8317714 Hendriks et al. Nov 2012 B2
8343289 Chaggares et al. Jan 2013 B2
8353833 Dogra et al. Jan 2013 B2
8355554 Ma et al. Jan 2013 B2
20010056235 Quistgaard et al. Dec 2001 A1
20020007119 Pelissier Jan 2002 A1
20020014420 Schultz et al. Feb 2002 A1
20020016545 Quistgaard et al. Feb 2002 A1
20020143256 Wing et al. Oct 2002 A1
20020177774 Hwang et al. Nov 2002 A1
20030009102 Quistgaard et al. Jan 2003 A1
20030013965 Quistgaard et al. Jan 2003 A1
20030013966 Barnes et al. Jan 2003 A1
20030078501 Barnes et al. Apr 2003 A1
20030141205 Cabatic et al. Jul 2003 A1
20030163047 Little et al. Aug 2003 A1
20030195418 Barnes et al. Oct 2003 A1
20030199762 Fritz et al. Oct 2003 A1
20040102705 Zan et al. May 2004 A1
20040116808 Fritz et al. Jun 2004 A1
20040122314 Fattah et al. Jun 2004 A1
20040122319 Mehi et al. Jun 2004 A1
20040122324 Zan Jun 2004 A1
20040133110 Little et al. Jul 2004 A1
20040138564 Hwang et al. Jul 2004 A1
20040150963 Holmberg et al. Aug 2004 A1
20040152982 Hwang et al. Aug 2004 A1
20040193047 Pelissier et al. Sep 2004 A1
20040227429 Yin et al. Nov 2004 A1
20040236219 Liu et al. Nov 2004 A1
20050096528 Fritz et al. May 2005 A1
20050119555 Fritz et al. Jun 2005 A1
20050131291 Floyd et al. Jun 2005 A1
20050197543 Zan et al. Sep 2005 A1
20050215878 Zan Sep 2005 A1
20050228287 Little et al. Oct 2005 A1
20050265267 Hwang Dec 2005 A1
20050272183 Lukacs et al. Dec 2005 A1
20060025684 Quistgaard et al. Feb 2006 A1
20060058652 Little Mar 2006 A1
20060058655 Little Mar 2006 A1
20060241446 White et al. Oct 2006 A1
20060241448 Liu et al. Oct 2006 A1
20060241461 White et al. Oct 2006 A1
20070038088 Rich et al. Feb 2007 A1
20070049822 Bunce et al. Mar 2007 A1
20070066898 Hendriks et al. Mar 2007 A1
20070071266 Little et al. Mar 2007 A1
20070085452 Coleman Apr 2007 A1
20070093715 Hippe et al. Apr 2007 A1
20070116373 Hwang et al. May 2007 A1
20070121769 Gabrielson et al. May 2007 A1
20070182287 Lukacs et al. Aug 2007 A1
20070185396 Zan Aug 2007 A1
20070196005 White et al. Aug 2007 A1
20070205697 Chaggares et al. Sep 2007 A1
20070205698 Chaggares et al. Sep 2007 A1
20070222339 Lukacs et al. Sep 2007 A1
20070232907 Pelissier et al. Oct 2007 A1
20070232910 Hwang et al. Oct 2007 A1
20070232915 Pelissier et al. Oct 2007 A1
20070238954 White et al. Oct 2007 A1
20070239001 Mehi et al. Oct 2007 A1
20070270694 Pelissier et al. Nov 2007 A1
20080015420 Zan et al. Jan 2008 A1
20080015438 Mehi et al. Jan 2008 A1
20080071149 Rich Mar 2008 A1
20080099638 Diener et al. May 2008 A1
20080104300 Diener et al. May 2008 A1
20080137922 Catallo et al. Jun 2008 A1
20080141107 Catallo et al. Jun 2008 A1
20080183079 Lundberg Jul 2008 A1
20080287789 Hwang et al. Nov 2008 A1
20090043199 Pelissier et al. Feb 2009 A1
20090043203 Pelissier et al. Feb 2009 A1
20090043204 Pelissier et al. Feb 2009 A1
20090043205 Pelissier et al. Feb 2009 A1
20090069681 Lundberg et al. Mar 2009 A1
20090069725 Diener et al. Mar 2009 A1
20090093719 Pelissier et al. Apr 2009 A1
20090108710 Brown et al. Apr 2009 A1
20090198132 Pelissier et al. Aug 2009 A1
20090270722 Floyd et al. Oct 2009 A1
20090275835 Hwang et al. Nov 2009 A1
20100049050 Pelissier et al. Feb 2010 A1
20100053197 Gabrielson et al. Mar 2010 A1
20100081930 Dunbar Apr 2010 A1
20100090877 Dunbar et al. Apr 2010 A1
20100092131 Davidson et al. Apr 2010 A1
20100094132 Hansen et al. Apr 2010 A1
20100121189 Ma et al. May 2010 A1
20100121190 Pagoulatos et al. May 2010 A1
20100121196 Hwang et al. May 2010 A1
20100130855 Lundberg et al. May 2010 A1
20100156244 Lukacs et al. Jun 2010 A1
20100260398 Ma et al. Oct 2010 A1
20100274131 Barnes et al. Oct 2010 A1
20100298704 Pelissier et al. Nov 2010 A1
20100298705 Pelissier et al. Nov 2010 A1
20100298709 Needles et al. Nov 2010 A1
20100298712 Pelissier et al. Nov 2010 A1
20110021919 Mehi et al. Jan 2011 A1
20110054292 Hirson et al. Mar 2011 A1
20110054321 White et al. Mar 2011 A1
20110057545 Chaggares et al. Mar 2011 A1
20110144494 Mehi et al. Jun 2011 A1
20110160590 Waki Jun 2011 A1
20110196237 Pelissier et al. Aug 2011 A1
20110245659 Ma et al. Oct 2011 A1
20110249878 Pagoulatos et al. Oct 2011 A1
20110273059 Brown et al. Nov 2011 A1
20120016316 Zhuang et al. Jan 2012 A1
20120165674 Abe Jun 2012 A1
20120195161 Little et al. Aug 2012 A1
20120220876 Hwang Aug 2012 A1
20120226161 Pelissier et al. Sep 2012 A1
20120232380 Pelissier et al. Sep 2012 A1
20120243367 Hwang et al. Sep 2012 A1
20120283567 Chono Nov 2012 A1
20120289829 Barnes et al. Nov 2012 A1
20120289835 Hwang Nov 2012 A1
20120296210 Pelissier et al. Nov 2012 A1
20120316404 Zan Dec 2012 A1
20120330158 Sawayama Dec 2012 A1
20130006110 Hwang et al. Jan 2013 A1
20130010908 Gabrielson et al. Jan 2013 A1
Non-Patent Literature Citations (45)
Entry
Bell et al., “High-frequency ventilation compared to conventional positive-pressure ventilation in the treatment of hyaline membrane disease in primates,” Crit Care Med. 12(9):764-768 (1984).
Boros et al., “Comparison of High-Frequency Oscillatory Ventilation and High-Frequency Jet Ventilation in Cats With Normal Lungs,” Pediatr Pulmonol. 7(1):35-41 (1989).
Bunnell High-Frequency Ventilation: General Concepts. In: Donn SM, Sinha SK, eds. Neonatal respiratory care, 2nd edition. Philadelphia: Mosby, p. 222-30 (2006).
Carlon et al., “Physiologic implications of high frequency jet ventilation techniques,” Crit Care Med. 11(7):508-14 (1983).
Church, et al. “Evaluation of the Threshold for Lung Hemorrhage by Diagnostic Ultrasound and a Proposed New Safety Index,” Ultrasound Med Biol. 33(5):810-8 (2007).
Cools et al., “Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants,” Cochrane Database Syst Rev. (3):CD000104 (2009).
Crowley, “Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994,” Am J Obstet Gynecol. 173:322-35 (1995).
D'Hooge, et al. “Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations,” Eur J Echocardiogr. 1(3):154-70 (2000).
Doyley “Model-based elastography: a survey of approaches to the inverse elasticity problem,” Phys Med Biol. 57(3):R35-73 (2012).
Galban et al., “CT-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression,” Nature Med. 18(11):1711-1715 (2012).
Garra, et al. “Elastography of Breast Lesions: Initial Clinical Results,” Radiology 202:79-86 (1997).
Goddi, et al. “Real-time tissue elastography for testicular lesion assessment,” Eur Radiol. 22(4):721-30 (2012).
Graustein WC. Differential Geometry. Mineola, N. Y.: Dover, 1962: 109.
Hall, et al. “In Vivo Real-Time Freehand Palpation Imaging,” Ultrasound in Medicine and Biology. 29(3):427-35 (2003).
Jackson, et al. “Effect of high-frequency ventilation on the development of alveolar edema in premature monkeys at risk for hyaline membrane disease,” Am Rev Respir Dis. 143(4 Pt 1):865-71 (1991).
Varghese, “Consolidation and Innovation: Driving the Global Mechanical Ventilator Markets.” Published Jun. 20, 2007. Frost and Sullivan.
Krah, “Anatomy of the mammalian lung”, In: Fenn WO, Rahn H, eds. Handbook of Physiology Washington, D.C.: American Physiological Society (1964).
Lampland, et al. “The role of high-frequency ventilation in neonates: evidence-based recommendations,” Clin Perinatol. 34(1):129-144 (2007).
Lichtenstein, “Ultrasound examination of the lungs in the intensive care unit,” Pediatr Crit Care Med. 10(6):693-8 (2009).
Liggins, et al. “A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants,” Pediatrics 50(4):515-25 (1972).
Lubinski, et al. “Adaptive strain estimation using retrospective processing,” IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 46:97-107 (1999).
Lubinski, et al. “Speckle tracking methods for ultrasonic elasticity imaging using short time correlation,” IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 46:82-96 (1999).
Lucking, et al. “High-frequency ventilation versus conventional ventilation in dogs with right ventricular dysfunction,” Crit Care Med 14(9):798-801 (1986).
Lyshchik, et al. “Cervical lymph node metastases: diagnosis at sonoelastography—initial experience,” Radiology 243:258-67 (2007).
Lyshchik, et al. “Thyroid gland tumor diagnosis at US elastography,” Radiology 202-211 (2005).
Meyer, et al. “Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations,” Med Image Anal. 1(3):195-206 (1997).
Miller, “Induction of pulmonary hemorrhage in rats during diagnostic ultrasound,” Ultrasound Med Biol. 38(8):1476-82 (2012).
Nikischin, et al. “A New Method to Analyze Lung Compliance When Pressure-Volume Relationship is Nonlinear,” Am. J. Respir. Crit. Care Med 158(4):1052-1060 (1998).
Ophir, et al. “Elastography: a quantitative method for imaging the elasticity of biological tissues,” Ultrasonic Imaging 13:111-34 (1991).
Pallwein, et al. “Real-time elastography for detecting prostate cancer: preliminary experience,” BJU Int. 100(1):42-6 (2007).
Reinhardt, et al. “Registration-based estimates of local lung tissue expansion compared to xenon CT measures of specific ventilation,” Med Image Anal. 12(6):752-63 (2008).
Rubin, et al. “Sonographic elasticity imaging of acute and chronic deep venous thrombosis in humans,” J. Ultrasound Med., 25(9):1179-86 (2006).
Rubin, et al. “Clinical application of sonographic elasticity imaging for aging of deep venous thrombosis: preliminary findings,” J Ultrasound Med. 22(5):443-8 (2003).
Rubin, et al. “Potential Use of Ultrasound Speckle Tracking for Motion Management During Radiotherapy,” J Ultrasound Med 31:469-481 (2012).
Safety Group of the British Medical Ultrasound Society. Statement on the safe use, and potential hazards of diagnostic ultrasound 2000, reconfirmed Oct. 2007; Available from: <http://www.bmus.org/about-ultrasound/au-safetystatement.asp>.
Simbruner, et al. “Respiratory compliance of newborns after birth and its prognostic value for the course and outcome of respiratory distress,” Respiration 43(6):414-23 (1982).
Soll, “Prophylactic natural surfactant extract for preventing morbidity and mortality in preterm infants,” Cochrane Database Syst Rev. 2:CD000511 (2000).
Stefanidis, et al. “Basic principles and current applications of lung ultrasonography in the intensive care unit,” Respirology 16:249-56 (2011).
Strategic Analysis of World Mechanical Ventilators. Published Mar. 5, 2005, Frost and Sullivan.
Sybrecht, et al. “Influence of posture on flow dependence of distribution of inhaled 133Xe boli,” J Appl Physiol. 41(4):489-96 (1976).
Thompson, et al. “High-frequency oscillation compared with standard ventilation in pulmonary injury model,” J Appl Physiol. 52(3):543-8 (1982).
U.S. Medical Ventilator Market. Published Aug. 16, 2001, Frost and Sullivan.
Wegener, et al. “Measurement of lung density by computed tomography,” J Comput Assist Tomogr 2(3):263-73 (1978).
Weitzel, et al., “Feasibility of applying ultrasound strain imaging to detect renal transplant chronic allograft nephropathy,” Kidney International 65:733-6 (2004).
Zhong, et al. “Measurement of regional compliance using 4DCT images for assessment of radiation treatment,” Med Phys 38(3):1567-78 (2011).
Related Publications (1)
Number Date Country
20140316266 A1 Oct 2014 US
Provisional Applications (1)
Number Date Country
61799484 Mar 2013 US