WO2012031235A2

WO2012031235A2 - Methods for characterizing vaginal tissue elasticity and assessment of pelvic organ conditions affecting the vagina

Info

Publication number: WO2012031235A2
Application number: PCT/US2011/050390
Authority: WO
Inventors: Vladimir Egorov; Heather Van Raalte; Armen P. Sarvazyan
Original assignee: Artann Laboratories, Inc.
Priority date: 2010-09-02
Filing date: 2011-09-02
Publication date: 2012-03-08
Also published as: US20120259247A1; US20110196263A1; US8419659B2; WO2012031235A9; EP2611360A2; US8187208B2

Abstract

Methods for assessment of pelvic floor conditions based on tactile imaging are described. The vaginal wall is deformed using a transvaginal probe equipped with tactile pressure sensors and a motion tracking sensor. The vaginal wall coordinates and pressure patterns are obtained during the examination and used to build 3-D tactile image of the vagina and to calculate elasticity modulus profiles and spacing profiles along selected lines inside 3-D tactile image. The profile values at specified locations are then compared with thresholds or profiles for normal conditions of vagina and its support structures. Methods of the invention are disclosed to be used in assessing a risk of pelvic organ prolapse development, estimating an extent of pelvic floor organ traumatic damage after childbirth and estimating an improvement after an interventional procedure.

Description

TITLE

METHODS FOR CHARACTERIZING VAGINAL TISSUE ELASTICITY AND ASSESSMENT OF PELVIC ORGAN CONDITIONS AFFECTING THE VAGINA

CROSS-REFERENCE DATA

[0001] This application claims a priority benefit from a US Patent Application No. 13/083,494 filed 08 April 2011, which in turn claims a priority benefit from a US Patent Application No. 12/874,583 filed 02 September 2010, both of which are incorporated herein in their respective entireties by reference.

FIELD OF THE INVENTION

[0002] The present invention generally relates to methods for characterization of pelvic floor organs and support tissues. More specifically, the invention describes methods for assessment of vaginal tissue elasticity and pelvic organ conditions affecting the vagina such as pelvic organ prolapse, childbirth trauma and reconstructive surgery in women.

BACKGROUND OF THE INVENTION

[0003] The present invention generally relates to objective characterization methods for female pelvic tissues. Specifically, the invention describes methods for characterizing vaginal tissue elasticity and detection of a pelvic organ abnormality. For the purposes of this description, the terms "pelvic organ abnormality", "pelvic floor abnormality" and "vaginal abnormality" are used interchangeably.

[0004] Pelvic organ prolapse (POP) is the descent of the apex of the vagina, including the cervix (or vaginal vault after hysterectomy), anterior vaginal wall, and/or posterior vaginal wall. As prolapse progresses, pelvic organs may become displaced and even protrude outside the vaginal canal. POP is a highly prevalent condition affecting at least 50% of women in the US during their lifetimes. Beyond the physical impact of POP, women with progressing pelvic organ prolapse score poorer on both general and condition-specific quality-of-life scales. In addition, about one third of sexually active women with POP report that their condition interferes with sexual function.

[0005] Women with symptomatic POP who fail or decline conservative management, including pessary use and physical therapy treatment, are candidates for reconstructive surgery. The overall goal for prolapse surgery is to give the most functional repair, while preventing recurrence of the condition and minimizing complications incurred by these repairs. Recurrence is one of the barriers in surgical correction most frustrating to both the surgeon and patient. Failure rates as high as 20-40% have been cited after surgical repair, with over 50% occurring within the first three years. Since many patients with POP have inherently deficient or defective connective tissue, to minimize recurrence of POP many reconstructive surgeons have turned to the use of adjuvant materials for vaginal support. Such materials may include synthetic, allogenic, xenogenic or autologous grafts. Currently, at least 10 synthetic materials are available for vaginal use. Unfortunately, none of the currently available graft materials is ideal for restoration of both optimal support and functionality of the vaginal walls.

[0006] When detera ining the etiology of POP and delineating risk factors for POP, parity has the strongest association with risk of requiring surgery for POP. Pregnancy and childbirth have a tremendous impact on women's vaginal connective tissue, nerves and muscles support within the pelvis due to prolonged pressure, straining and distention forces that are placed on the pelvic tissues. Traumatic changes of the pelvic floor are encountered during childbirth including avulsion of muscle from the supporting bony structure of the pelvis, damage to vaginal support ligaments and muscle atrophy after pelvic nerve damage. Pelvic floor dysfunction, in the form of pelvic floor prolapse (including eystoeele, rectoceie, enterocele and uterine prolapse) and urinary and fecal incontinence are considered inevitable sequelae for some women who experience injuries during childbirth. Compared with nulliparous women, women with one child were 4 times more likely (and those with two children were 8.4 times more likely) to develop pelvic organ prolapse requiring hospital admission and surgical intervention. With the burgeoning elderly population, the latent injuries caused in childbirth will affect more and more women later in life. Although surgery for pelvic organ prolapse is effective in restoring anatomy, functional outcomes have not been as satisfactory and there are many questions regarding underlying biomechanical properties of the pelvis that are currently poorly defined to guide optimal repair.

[0007] Pelvic floor organs and support structures are elements of a biomechanical system providing critically important set of physiological processes. Despite the obvious fact that POP and childbirth damages are caused by structural failures, only recently researchers have begun to conduct a biomechanical analysis of the mechanisms of normal pelvic organ support and failure.

[0008] A critical review of published data on the urogynecologic aspects of female sexual dysfunction demonstrates a lack of standardized instruments for assessing biomechanical conditions of the pelvic floor. There is a need in 3-D imaging of vagina and its surrounding structures and reproducible measurements of vaginal tissue elasticity in-vivo because the tissue elasticity, as a capability to hold load and reversely undergoing to elongation, is the primary mechanical characteristic.

[0009] The high incidence of POP, childbirth damages and the rate of reconstructive surgery also dictate the need for new effective methods for assessment of pelvic organ conditions after reconstructive surgery or other interventional procedures in women. Elasticity imaging of the vagina after reconstructive surgery may allow to quantitatively characterizing the effectiveness of the surgical approach and behavior of materials used for vaginal support in- vivo.

[00010] In the last decade, a new modality for tissue characterization has emerged termed Elasticity imaging or Elastography. Elasticity imaging allows visualization and assessment of mechanical properties of soft tissue. Mechanical properties of tissues, i.e. elastic modulus and viscosity, are highly sensitive to tissue structural changes accompanying various physiological and pathological processes. A change in Young's modulus of tissue during the development of pathological processes could reach hundreds and even thousands of percent. Elasticity imaging is based on generating a stress in the tissue using various static or dynamic means and then measuring resulting strain (displacements in volume) with the use of ultrasound or magnetic resonance imaging. Tactile imaging yields a tissue elasticity map similar to other elastographic techniques. At the same time, tactile imaging, unlike strain imaging, uses stress or pressure data on the surface of tissue under applied load. It mimics manual palpation, because a tactile imaging probe with a pressure sensor array mounted on its face acts similarly to a human finger during a clinical examination by compressing soft tissue with the probe and detecting resulting changes as a surface pressure pattern.

SUMMARY OF THE INVENTION

[00011] The object of the present invention is to overcome the drawbacks of the prior art and provide methods for quantitative and reproducible assessment of vaginal tissue elasticity and pelvic organ conditions affecting the vagina, including methods for estimating a risk of pelvic organ prolapse development.

[00012] Another object of the invention is to provide a method for objective detection of pelvic organ abnormality condition by comparing a calculated elasticity measure against a normal elasticity value obtained from clinical data collected from a number of patients.

[00013] Another object of the invention is to provide methods for characterizing traumatic conditions of pelvic floor structures after childbirth.

[00014] A further yet object of the invention is to provide methods for post-operative assessment of pelvic floor conditions.

[00015] In embodiments, the method for characterizing vaginal tissue elasticity includes steps of deforming a vaginal tissue using a transvaginal probe; obtaining stress and strain data for one or more measurement points of the vaginal tissue; and calculating at least one stress gradient for the vaginal tissue so as to allow objective characterization of its elasticity.

[00016] The transvaginal probe of the invention includes pressure sensors and a motion tracking sensor, which allows recording both stress and strain data for one or more points of the vaginal tissue. In embodiments, stress and strain data recorded for a plurality of measurement points is used to calculate average stress gradient for a preselected area of vagina. The value of the stress gradient may be then compared with a predefined numerical threshold such as for example 3 kPa/cm or with a normal stress gradient obtained from clinical data collected for other patients with known normal or diseased status for the vaginal tissue. Such comparison allows detecting of a pelvic floor abnormality condition is the calculated stress gradient falls below a threshold or a normal value.

[00017] In embodiments, the step of characterizing vaginal tissue elasticity may include composing a vaginal tactile image. One particularly useful way to graphically represent collected stress and strain data is to compile a family of surfaces together forming the vaginal tactile image. Each surface is drawn through locations of the measurement points when deformed at a particular constant level of stress. Selecting a number of different constant stress values defines a number of surfaces for the vaginal tactile image. Each constant stress location of the measurement point may be either an actually recorded location for a particular stress or a calculated location representing an extrapolation from other known locations and stresses assuming a linear model of tissue compression. [00018] In embodiments, methods for assessment of pelvic organ conditions affecting a vagina such as a risk of pelvic organ prolapse development may include the following steps:

(a) conducting examination of vagina by deforming vagina along an anterior vaginal wall and along a posterior vaginal wall using a transvaginal probe;

(b) obtaining pressure patterns and coordinates corresponding thereto for portions of vagina examined with the transvaginal probe;

(c) calculating at least one or both anterior elasticity modulus profile and posterior elasticity modulus profile, these elasticity modulus profiles being defined by at least two or more locations spaced apart in the respective portion of vagina examined with the transvaginal probe;

(d) calculating at least two or more distances between the anterior vaginal wall and the posterior vaginal wall along the vagina which cumulatively define a spacing profile of the vagina; and

(e) estimating a risk of pelvic organ prolapse development by comparing at least one elasticity modulus profile at the two locations against respective predetermined elasticity modulus thresholds for the same two locations as well as by comparing the spacing profile against respective predetermined distance thresholds.

[00019] In embodiments, a similar approach may be taken for assessment of other conditions affecting vagina, such as extent of pelvic support tissue impairment or damage after childbirth or an improvement after an interventional procedure such as surgery for example. Measured elasticity and geometrical parameters such as spacing profiles may be compared to predetermined normal values obtained for a plurality of patients with known clinical history or may be compared for each patient individually using results of previous examinations.

[00020] The details of embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description, drawings and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

[00021] Subject matter is particularly pointed out and distinctly claimed in the concluding portion of the specification. The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:

FIG. 1 illustrates a procedure of examining the vagina with a transvaginal probe;

FIGS 2A through 2C illustrate obtaining stress and strain data resulting from vaginal model tissue deformation and composing a vaginal tactile image;

FIG. 3 is a flow chart illustrating one method for characterizing vaginal tissue elasticity;

FIG. 4 is a flow chart illustrating another method for characterizing vaginal tissue elasticity and detection of pelvic floor abnormality;

FIG. 5 shows an example of transverse, sagittal and coronal cross-sections of a 3-D tactile image of a normal vagina;

FIG. 6 shows an example of transverse, sagittal and coronal cross-sections of a 3-D tactile image for a vagina with confirmed pelvic organ prolapse;

FIG. 7 shows an example of calculated elasticity modulus profiles for the anterior and posterior vaginal walls;

FIG. 8 shows an example of calculated spacing profile for the anterior-posterior vaginal walls;

FIG. 9 is a flow chart illustrating a method for assessment of pelvic organ conditions affecting the vagina which includes the step of estimating a risk of vaginal organ prolapse development;

FIG. 10 is a flow chart illustrating a method for assessment of pelvic organ conditions affecting the vagina which includes the step of estimating traumatic damage after childbirth; and

FIG. 11 is a flow chart illustrating a method for assessment of pelvic organ conditions affecting the vagina which includes the step of estimating an improvement after the interventional procedure.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

[00022] The following description sets forth various examples along with specific details to provide a thorough understanding of claimed subject matter. It will be understood by those skilled in the art, however that claimed subject matter may be practiced without one or more of the specific details disclosed herein. Further, in some circumstances, well-known methods, procedures, systems, components and/or circuits have not been described in detail in order to avoid unnecessarily obscuring claimed subject matter. In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure.

[00023] FIG. 1 illustrates the examination procedure of the invention, which includes inserting a transvaginal probe 10 into a vagina. The probe is equipped with pressure sensors and a motion tracking sensor allowing acquisition of pressures and coordinates for each pressure sensor during vaginal tissue deformation. The examination includes deforming vaginal tissue for example by pressing or sliding the transvaginal probe 10 about at least one measurement point. In embodiments, deforming the tissue is conducted along a plurality of measurement points on either an anterior vaginal wall 16 and/or a posterior vaginal wall 17 from the proximal part such as hymen to the distal part of the vagina such as cervix 18 while using the probe to apply pressure to vaginal walls. Obtained stress and strain data for the measurement points during deformation of vaginal tissue are used for calculating a stress gradient to characterize vaginal tissue elasticity. In embodiments, the stress and strain data is used to compose a vaginal tactile image. For sliding examinations, the range of pressures on the vaginal wall may be selected from about 1 kPa to about 10 kPa. For a compression mode of examination, the range of pressures may be selected to be from about 1 kPa to about 20 kPa. The examination procedure may further include repeating the vaginal tissue deformation resulting from pressing or sliding motion at least two and preferably up to five times while increasing the pressure applied by the transvaginal probe 10 in the predefined range. The examination procedure may further include real-time review of obtained stress and strain data and/or composed vaginal tactile image to provide guidance for an examiner. If an irregularity is discovered, the transvaginal probe 10 may be moved to the location of such irregularity and tissue deformation may be repeated. Full examination of the vagina may take as little as 3-5 minutes. Obtained data is stored in a digital format allowing a post-procedural review of collected data and composed vaginal tactile image.

[00024] Other examination techniques are also applicable for the purposes of the invention. For example, during the examination procedure, the transvaginal probe 10 may be moved along the vaginal axis without applying pressure to vaginal walls so as to record surface pressure at rest for anterior vaginal wall 16 and posterior vaginal wall 17. Also, the transvaginal probe 10 may be used for detecting muscle strength under a vaginal muscular contraction when a patient is instructed to contract appropriate vaginal muscles. The probe 10 may further be moved from hymen to cervix while applying pressure circumferentially to vaginal walls. Obtained data may be stored in a digital format allowing a review of one, two, or three orthogonal cross-sections selected for tactile image of vagina. Tactile images of vagina may be used for calculating elasticity modulus at specified locations or along selected lines and geometrical features. In embodiments, a spacing profile may for example be calculated as a set of distances between anterior and posterior along the vagina in at least two or more such locations.

[00025] In embodiments, the transvaginal probe 10 includes one or multiple pressure sensors forming one or multiple pressure sensor arrays configured for contacting vaginal walls and cervix. As shown in FIG. 1, sensor arrays 12 and/or 13 may be configured for a contact with opposing vaginal walls, e.g. anterior wall 16 and posterior wall 17, as well as a left side and a right side of vagina 11. Pressure sensor array 14 may be configured for a contact with cervix 18. The pressure sensor arrays may be assembled as two-dimensional sensor arrays on the part of the surface of the probe 10 adapted for contacting the vaginal tissue. The pressure- sensitive surface of the probe 10 configured for contacting the vaginal wall may have a rounded shape with a radius of curvature of about. The probe head may measure 50 mm in length, 20 mm in width, and 13 mm in height having an ellipsoidal cross-section. The pressure sensor array may for example comprise 120 (15 x 8) pressure sensors with dimensions of 2.5 mm by 2.5 mm, the entire array of sensors forming the total sensing area of about 40 mm by 20 mm.

[00026] The pressure-sensitive surface of the pressure sensor array 14 may be flat or convex. The motion tracking sensor 15 may be configured to record at least one or more of the three coordinates (X, Y, Z) and/or three angles (Elevation, Rotation, Azimuth) of the transvaginal probe 10. Recording coordinates and angles allows calculating coordinates of all pressure sensors of the probe 10 in a coordinate system tied to pelvic floor bony framework. An electronic unit for data acquisition may be configured to record the pressure array readings and the motion sensor readings, so that in combination, the sensor coordinates and sensor pressure data are recorded at the same time and paired together for placing into 3-D tactile image.

[00027] The motion tracking sensor of the transvaginal probe 10 is preferably a six degrees of freedom sensor allowing obtaining data on three angles and three coordinates, although a sensor with only three degrees of freedom (three angles or three coordinates) may also be used. The tracking sensor provides coordinates of all pressure sensors during the vaginal tissue deformation. In one embodiment, the sensor may provide motion tracking data in a coordinate system related to the pelvic floor skeleton.

[00028] In embodiments, the transvaginal probe 10 is connected with an electronic unit (not shown) and further connected to a monitor such as a laptop computer with a data acquisition card. The electronic unit includes a pressure sensor electronics adapted to communicate with a computer through a communication port. The data acquisition rate may be in the range from 15 up to 30 pressure frames per second.

[00029] The software of the transvaginal probe 10 supports at least three operational modes: data acquisition mode, data management mode, and device management mode. The software allows for real-time visualization of the pressure pattern on the probe head, composed vaginal tactile image and for storing the data in a digital format.

[00030] Deformations of the vaginal wall using different levels of applied pressure results in collecting stress and strain data for the vaginal tissue. Knowing the size of the vaginal probe and its movement inside the vagina allows the system of the invention to relate recorded contact pressure or stress values at each measurement point of the vaginal tissue (as obtained by a pressure sensor) to the geometrical coordinate of that measurement point as it is being displaced by the probe (using the motion tracking data). Therefore, examination the vagina with the transvaginal probe 10 results in a data set of applied pressures and corresponding spatial dislodgements of one or more measurement points for a vaginal tissue. At the end of the vaginal examination, each measurement point may be associated with a particular geometric motion trajectory. Stress data is recorded for at least two or preferably more locations of the measurement point along this trajectory. [00031] Knowing measured stress data and associated geometrical locations for each measurement point allows calculating locations for each measurement point along their respective deformation trajectories for a given value of stress. Such locations may be calculated by extrapolating stress and strain data from measured values using for example a linear model of tissue compression. In embodiments, other more sophisticated models of tissue compression may also be used in place of a simple linear tissue deformation model.

[00032] FIG.2 illustrates obtaining stress and strain data resulting from tissue deformation, composing a vaginal tactile image and calculating a stress gradient. FIG. 2A shows the initial position of the transvaginal probe 10 equipped with a pressure sensor array 11 prior to model tissue deformation. Also shown in FIG. 2B is the transvaginal probe 10 at the point of maximum deformation of the model tissue. FIG. 2C shows a representative tactile image for the deformation of model tissue shown in the lower panel 21.

[00033] For simplicity of explanations, the model tissue illustrated in FIG. 2A is composed of a relatively soft tissue part 25 and a relatively hard tissue part 26. The soft part 25 may have a Young's modulus of 3 kPa while the hard part 26 may have a Young's modulus of 10 kPa. The part 25 is covered by a surface layer 24 which is representative of a vaginal wall. The bottom layer of the model tissue rests on a stationary support 27. Panel 21 shows the transvaginal probe 10 deforming the model tissue by applying compression force in the direction of the arrow 23. This results in deformation of the model tissue so that the tissue part 25 is displaced into a deformed tissue part 30 and the tissue part 26 is displaced into a respective deformed tissue part 31. The surface layer 24 is also displaced into a deformed surface layer 29 under applied force from the transvaginal probe 10. The bottom layer of this theoretical model tissue is not deformed or displaced in any way.

[00034] During the deformation of the surface layer 24 into the deformed surface layer 29, the position and respective contact stress are recorded for each pressure sensor contacting a corresponding measurement point on the surface layer 24 using the pressure sensor array and the motion tracking sensor. Motion tracking data and pressure sensor data together form a set of stress and strain data for the deforming surface layer 24.

[00035] This stress and strain data is then used for composing the vaginal model tissue tactile image 28 shown in FIG. 2B. The three-dimensional vaginal tactile image is defined as a family of constant stress surfaces representing locations of the measurement points when they are under the same level of stress. A two-dimensional vaginal tactile image is a family of curves representing constant tress levels. FIG. 2C shows a cross-section view of the three-dimensional vaginal tactile image in which lines 33-36 represent cross-sections of such surfaces. In the example shown in FIG. 2C, these constant stress surface and corresponding lines 33-36 represent a number of constant stress values increasing for example from 3 kPa to 6 kPa, 8 kPa, and 10 kPa. Other appropriate levels of stress may be selected to be represented as a family of constant stress surfaces.

[00036] As discussed above, not all points on each surface represent actual measurement results. In some cases, the exact geometrical location of a particular measurement point when subjected to a selected constant stress is calculated by extrapolating from measured locations of this measurement point and corresponding stress levels assuming a linear model of tissue compression. In fact, a constant stress surface may not have even a single location where the actual measurement took place as most or even all points of the surface may be calculated from the stress and strain data.

[00037] Other methods of mathematical processing of the stress and strain data are also envisioned to be within the scope of this invention. For example, the stress and strain data obtained for a plurality of measurement points may be treated as a 3-D cloud of data and each of the constant stress surfaces (which may also be referred to as an iso-surface) may be computed mathematically using the entire set of data.

[00038] Elasticity or the capability of substance to be deformed under applied force is defined as the ratio of applied stress to resulting strain. The elasticity image of vagina and surrounding tissue is derived from the stress and strain data collected for a variety of vaginal tissue deformations. The calculation of a ratio of a change in stress value between two near geometrical points of the composed tactile image to a distance between these two points is closely related to the classical definition of elasticity because the distance in the tactile image corresponds to value of resulting strain of a vaginal wall. This ratio is defined as the stress gradient.

[00039] Having a recorded set of stress and strain data allows calculating a stress gradient for a single or multiple measurement points within the vaginal tactile image. Taking a point 37 in FIG. 2C for example, a stress gradient is calculated as a ratio of differences in stress values between points 37 and 39 to the distance between the same points 37 and 39. This stress gradient is characterizing the tissue elasticity around the point 37. The calculated stress gradient has two components: a scalar component represented as a number ascribed to each specific point 37 and a vector component at the same location because in a general case the stress gradient value depends on the direction which is characterized by a vector connecting two points. This stress gradient may be calculated in units of kPa/cm.

[00040] Elasticity of vaginal tissue is assumed to be linear in the range of applied deformations. In that case, increasing levels of contact pressure will result in generally increasing levels of tissue and probe movement. At the same time, the ratio of stress to strain will remain nearly constant between different levels of applied strain and strain. At least two data points are needed to calculate the ratio of stress to strain. Preferably, such ratio is calculated from a plurality of measurements, such as when recording a curve of stress over strain using the probe to deform the tissue at one location. Additional repeated deformations may allow increasing the accuracy of calculations and avoiding artifacts, for example by detecting the average value of the stress gradient.

[00041] The stress gradient may be calculated in a cylindrical coordinate system from vaginal wall surface to deeper tissue, with the longitudinal axis passing through the center of vagina. The stress gradient may also be calculated in an orthogonal coordinate system from vaginal wall surface to deeper tissue in an anterior direction or in a posterior direction.

[00042] FIG. 3 is a flow chart illustrating one method for characterizing vaginal tissue elasticity. The method includes deforming the vaginal tissue by a transvaginal probe about at least a first measurement point in step (a); obtaining stress and strain data for the first measurement point using the transvaginal probe in step (b); and calculating a stress gradient from the stress and strain data to characterize elasticity of vaginal tissue in step (c). The method may further include a step of detecting a pelvic organ abnormality condition if the stress gradient is below a predetermined threshold.

[00043] Step (a) may include deformation of tissue by compression using a transvaginal probe to press against the tissue a range of pressures from about 1 kPa to about 20 kPa. Alternatively, tissue deformation may be done by a repeated sliding of the transvaginal probe over a predetermined area of vaginal tissue while applying increased levels of pressure thereto. At least two such slidings of the probe over the same predetermined area of the vaginal tissue may be conducted. Importantly, each subsequent pressure may be selected to exceed the previous pressure by at least 1 kPa. All applied pressures may be selected to be within a range from about 1 kPa to about 10 kPa. Step (c) may further include calculating an average stress gradient for a preselected zone of vagina and comparing it against a normal stress gradient for the same preselected zone of vagina. Normal stress gradient may be obtained from clinical data for a plurality of patients, optionally adjusting it for age and other factors.

[00044] FIG. 4 is a flow chart illustrating another method for characterizing vaginal tissue elasticity. The method generally includes deforming the vaginal tissue by a transvaginal probe about a plurality of measurement points in step (a); obtaining stress and strain data for each measurement point in step (b) resulting from deformation of tissue in step (a); composing a vaginal tactile image in step (c) using the stress and strain data from step (b), in which the vaginal tactile image is a family of constant stress surfaces, each constant stress surface represents locations of measurement points when the vaginal tissue is under a predefined constant level of stress; and calculating a stress gradient for at least one of the points using the vaginal tactile image to characterize elasticity of vaginal tissue in step (d).

[00045] Step (a) of tissue deforming may include tissue compression or repeated sliding of a transvaginal probe over at least a preselected area of vagina as generally described above for the method illustrated in FIG. 3.

[00046] The plurality of measurement points may be selected to be within an anterior or a posterior wall of vagina. The stress gradient may be calculated as a ratio of stress over strain obtained for the same measurement point. Step (c) may further include a step of detecting a pelvic organ abnormality condition if the stress gradient is below a predetermined threshold. Step (c) may further include calculating an average stress gradient for the plurality of measurement points and comparing it against a normal stress gradient obtained from clinical data for a plurality of patients.

[00047] In embodiments, methods for the assessment of pelvic organ conditions affecting the vagina may employ a deformation of vaginal walls by manually operated transvaginal probe with incorporated pressure sensor arrays and motion tracking sensor, such as described above for example. A number of pressure sensor coordinates in a coordinate system adapted for women pelvic floor together with corresponding pressure sensor signals are used to generate 3-D tactile images of the vagina. The tissue elasticity, such as for example represented by Young's modulus (E), may be calculated from spatial gradients obtained from a 3-D tactile image in the region of interest. Such elasticity modulus may be calculated in one spot or along a specified line forming an elasticity modulus profile. This approach was validated with multiple pelvic floor models built with two-component silicone having known predetermined elasticity distribution. Reproducibility of elasticity measurements with resolution better than 7% and accuracy within 20% for the tissue elasticity range between 2 kPa and 50 kPa was established after operators passed through a training program using pelvic floor models. In comparison with this broad range of elasticity, a capacity of human finger to scale the magnitude of softness of objects is substantially lower (Friedman RM, Hester KD, Green BG, LaMotte RH. Magnitude estimation of softness. Exp Brain Res 2008; 191:133-142.). This points out to a substantial advantage of using the methods of the invention in place of manual examination.

[00048] In embodiments, the pressure pattern on the surface of the vagina wall while deformed by the probe reveals not only elasticity conditions of vaginal wall itself, but an elasticity distribution of underlying structures: higher applied pressure reveals deeper structures surrounding vagina. The pressure patterns on the surface of vaginal walls together with tissue displacement caused by deformation from the probe may be considered as documentation of the current elasticity state of the vaginal walls and surrounding support structures. All acquired pressure patterns form together a 3-D tactile image. The 3-D tactile image of the vagina may be composed using a spatial scalar mapping of the pressure patterns acquired at the vaginal wall under deformation. The spatial mapping technique involves acquisition of probe motion tracking data, which may be transformed into spatial coordinates of each pressure sensor at the contact surface of the vaginal wall where the pressure signals were acquired during in the course of vaginal wall deformation. One practical way to observe a 3-D tactile image of vagina may be to represent it by three orthogonal cross-sections of the vagina as shown in FIG. 5. The primary regions of interest may be the anterior and posterior parts of the vagina, which are represented on the sigittal cross-section (see Sigittal plane in FIG. 5). Circumferential vaginal structures may be better observed in the transverse cross- section (see Transverse plane in FIG. 5). Left and right side support structures may be visualized in coronal cross-section (see Coronal plane in FIG. 5). Calculated tissue elasticity and geometrical measures may be projected on the respective cross-section of the 3-D tactile image to assist in visual interpretation of the examination results and comparison with reference data. Reference data may include prior measurements for the same patient or normal elasticity distributions and normal anatomical sizes obtained for a plurality of patients with known clinical status. Clinical examples of vaginal tactile images are presented in FIG. 5 and FIG. 6.

[00049] Tissue elasticity measures such as Young's modulus (E) may be calculated using a number of approaches, including:

1. comparing spatial gradients in 3-D tactile images of the vagina with the spatial gradients in 3-D tactile images for tissue models of the vagina. Such models may be prequalified to have known distribution of Young's moduli,

2. analyzing load curve for the probe during vaginal wall deformation applying a preexisting tissue deformation model,

3. using mechanical inverse problem solution applied to 3-D tactile image.

[00050] All three approaches require selection of a volume for averaging pressure gradients around the specified location where the tissue elasticity is to be calculated. Typical volume appropriate for that purpose may be in the range of 50-100 mm . The first calculating method from the listed above was used in exemplary results for tissue elasticity presented below.

[00051] FIG. 5 shows exemplary transverse, sagittal and coronal cross-sections of a 3-D tactile image of vagina for a patient with known normal pelvic floor conditions examined with the transvaginal probe. The tactile image of the vagina is presented in the units of pressure (kPa) according to specified grayscale map. 3-D tactile images of the vagina may have also color-scale map, such as the jet map. In embodiments, an operator using touchscreen capabilities of software interface may select geometrical features inside shown cross-sections to be measured, displayed and recorded in a computer-generated examination report. Selected geometrical features may include spacing between anterior and posterior walls, between left and right vaginal walls, distance between any two selected points or size of the specified zone. The operator may also select specific sites for calculation of tissue elasticity features, such as elastic modules, e.g. Young's modulus. Characteristic anatomical measures may be placed in the images and tissue elasticity values (Young's moduli) may be calculated for different sites. Comparison of different locations demonstrates the distribution of tissue elasticity. The sigittal and transverse tactile image cross-sections in FIG. 5 demonstrate strong anterior and posterior vaginal support with anterior-posterior spacing at distal part of about 14 mm. Young's modulus (E) was calculated for areas specified by a rectangular: E = 7 kPa at distal anterior and E = 13 kPa at distal posterior sections of vagina respectively. Right side of vaginal distal part demonstrated E = 10 kPa ( see Transverse plane in FIG. 5).

[00052] FIG. 6 presents exemplary three orthogonal cross-sections of 3-D tactile image for a patient having a prolapse condition confirmed by physical examination. Significant difference can be observed in tissue elasticity and anatomy relatively the normal conditions shown in FIG. 5. In this clinical case, elasticity modulus was determined as E = 1.8 kPa at distal anterior and E = 1.5 kPa at distal posterior sections respectively. Left side of vaginal distal part demonstrated E = 2.8 kPa (Transverse plane in FIG. 6). The anterior-posterior spacing at distal part of vagina was measured as 37 mm (Sagittal plane in FIG. 6).

[00053] FIG. 7 is an illustration of calculating elasticity modulus profiles for the anterior and posterior vaginal walls. The sagittal cross-section of 3-D tactile image of a patient is presented in FIG. 7A. The white rectangles in FIG. 7A denote cross-sections with an average size of 5 mm x 4 mm x 5 mm used for a tactile gradient calculation. The tactile gradient may be calculated in the direction orthogonal to the vaginal wall boundary defined at the constant pressure level of about 1 kPa. Based on experimentation with pelvic floor models built with known Young's modulus distribution of elastic silicone, empirical equations may be derived for transforming the tactile gradient value into Young's modulus. Moving the averaging volume along a predetermined line such as the dashed lines in FIG. 7A and calculating Young's modulus along the same line allows building of the elasticity modulus profile for the anterior vaginal wall (FIG. 7B) and posterior vaginal wall (FIG. 7C). A 5 mm step may be used along the line for the elasticity modulus profile calculation. The line for elasticity profile calculation may be selected along any part of 3-D tactile image of the vagina, e.g. along the left and right vaginal walls. For characterization of elasticity conditions of the vagina and its support structures, a set of locations and threshold values of elasticity modulus for these locations may be introduced, e.g. for middle anterior, middle posterior, distal anterior and distal posterior sections of vagina.

[00054] FIG. 8 is an exemplary illustration of calculating spacing profile for the anterior- posterior vaginal walls. The sagittal cross-section of 3-D tactile image of a patient is presented in FIG. 8A. The dashed lines along the anterior and posterior vaginal walls are iso-lines corresponding to a constant deformation pressure of 1 kPa; these lines define the boundaries of the vaginal walls at rest. The distances between the anterior and posterior walls boundaries, measured in generally orthogonal direction to the vaginal axis, define the spacing profile between the walls. At least two such distances are needed to establish a spacing profile. Greater number of distances improves the accuracy of the spacing profile. In embodiments, moving with a certain step (such as 5 mm) the location along the vaginal axis where the anterior-posterior distance is calculated allows building an anterior-posterior spacing profile (see FIG. 8B). The spacing profile may also be calculated for the left-right sides of the vagina. For characterization of anatomical conditions of the vagina and its support structures, a set of locations and spacing threshold values for these locations may be introduced, e.g. for proximal, middle and distal sections of vagina.

[00055] FIG. 9 is a flow chart illustrating one method for assessment of pelvic organ conditions affecting the vagina, in particular assessing a risk of vaginal organ prolapse development. The transvaginal probe of the invention may be used to assess the risk of development of the pelvic organ prolapse. The method of the invention is based on the notion that elasticity of the pelvic floor tissues starts to change well before the clinically-evident prolapse can be diagnosed. Early warning of the impending prolapse can therefore be obtained by recording the tactile image of the vaginal tissues and detecting the change in elasticity as compared to a predefined normal threshold. Knowing the degree of deviation of the measured values from the threshold may allow estimating a risk of vaginal organ prolapse development and may allow predicting a timeframe for its development.

[00056] In embodiments, methods for assessment of pelvic organ conditions affecting a vagina such as a risk of pelvic organ prolapse development may include the following steps:

(a) conducting examination of vagina by deforming vagina along an anterior vaginal wall and along a posterior vaginal wall using a transvaginal probe as described above;

(b) obtaining pressure patterns and coordinates corresponding thereto for portions of vagina examined with the transvaginal probe, a tactile image of the vagina may then be generated;

(c) calculating using the pressure patterns and coordinates at least one or both anterior elasticity modulus profile and posterior elasticity modulus profile, these elasticity modulus profiles being defined by at least two or more locations spaced apart in the respective portion of vagina examined with the transvaginal probe;

(e) estimating a risk of POP development by comparing at least one elasticity modulus profile at the two or more locations against respective predetermined elasticity modulus thresholds for the same locations as well as by comparing the spacing profile against respective predetermined distance thresholds.

[00057] The values of thresholds may be defined from clinical data for a plurality of patients, in particular, for patients with known clinical diagnosis established by different modalities. The locations for comparing elasticity modulus may be selected to include distal anterior, distal posterior, middle anterior and middle posterior sections of vagina. These locations are known to closely correspond with the pelvic floor support structure. The locations for comparing distances between the anterior and posterior vaginal walls may be selected to include proximal, middle and distal sections of vagina. In embodiments, the risk of POP development may be designated as elevated if the measured elasticity falls below the following elasticity modulus thresholds 4 kPa for the distal anterior, 3.5 kPa for the distal posterior, 8 kPa for the middle anterior and 6 kPa, for the middle posterior sections respectively. The step of calculating a spacing profile may further include calculating vaginal wall coordinates along the vagina at the constant pressure level of about 1 kPa so as to establish physical locations (boundaries) of the vaginal walls at rest. In embodiments, comparison of spacing profile may be done against the distance thresholds of about 15 mm for middle section and about 25 mm for distal section of the vagina respectively. Elevated risk of POP development is detected if the spacing profile exceeds these thresholds.

[00058] In embodiments, the step of estimating the risk of POP development may also include an adjustment based on at least one or more patient-specific factors. Such patient-specific factors may include patient's age, history of childbirth, history of chronic straining to empty bowel or bladder, status of menopause, obesity, history of prior hysterectomy, history of prior pelvic surgery, history of strenuous activity, smoking status, and alcohol use status.

[00059] FIG. 10 is a flow chart illustrating a method for assessment of pelvic organ conditions affecting the vagina, in particular estimating an extent of pelvic support tissue impairment or damage after childbirth. The transvaginal probe of the invention may be used to estimate the traumatic damage. The method is based on a notion that elasticity of the pelvic floor tissues is a good predictor of vaginal tissue deviations from normal conditions including disruptions of support muscles, fascia tissue and ligaments. Knowledge of the degree of tissue damage, which is characterized by elasticity deviation, as well as damage zone size and location, may lead to an effective treatment or an intervention procedure.

[00060] In embodiments, methods for assessment of pelvic organ conditions affecting a vagina may include the following steps:

(a) conducting examination by deforming the vagina along an anterior vaginal wall, along a posterior vaginal wall, along a left side of vagina and along a right side of vagina using a transvaginal probe - as described above in greater detail;

(c) calculating from the pressure patterns and coordinates at least one elasticity modulus profile defined by at least two or more locations spaced apart along vagina. Calculated elasticity modulus profile may include an anterior elasticity modulus profile, a posterior elasticity modulus profile, a left side elasticity modulus profile and a right side elasticity modulus profile;

(d) calculating from the same pressure patterns and coordinates at least one of an anterior- posterior spacing profile or a left-right spacing profile. The anterior-posterior spacing profile may be defined by at least two or more distances between the anterior vaginal wall and the posterior vaginal wall. The left-right spacing profile may be defined by at least two or more distances between the left side and the right side of the vagina; and

(e) estimating extent of pelvic support tissue impairment or damage after childbirth by comparing at least one or more elasticity modulus profiles against normal values such as for example corresponding elasticity modulus profile or profiles obtained for patients known to have no pelvic support tissue impairment or damage. The extent of tissue impairment or damage may be further estimated by comparing at least one or more of the calculated spacing profiles against normal values, for example against a corresponding spacing profile obtained for patients known to have no pelvic support tissue impairment or damage.

[00061] The step of estimating an extent of pelvic floor organ traumatic damage after childbirth may further include detection of a traumatic tissue damage zone and calculating a characteristic zone size of the traumatic tissue damage zone as well as elasticity modulus for the traumatic tissue damage zone using for example one of three approaches listed above. [00062] FIG. 11 is a flow chart illustrating a method for assessment of pelvic organ conditions affecting the vagina, in particular estimating an improvement after an interventional procedure. Using the methods of the invention, the transvaginal probe of the invention may be used to estimate the improvement. The method of the invention is based on a notion that elasticity of the pelvic floor tissues is a good predictor of vaginal tissue conditions because pelvic organ support system including muscles, fascia tissues and ligaments is a biomechanical system responsible for vital physiological processes. One of the basic aims of pelvic floor reconstructive surgery is to correct anatomical deviations by restoring strength and elasticity of pelvic organ support structures. Knowledge of the vaginal tissue and support structure elasticity in-vivo after the surgery may allow quantitative characterization of its outcome.

[00063] The interventional procedure in which the methods of the invention are applicable may include a variety of procedures such as tissue regeneration resulting from injecting muscle cells, tissue regeneration resulting from injecting stem cells, surgical repair of the vaginal wall, surgical repair of muscle structures, surgical implantation of an artificial supporting structure, and surgical implantation of an artificial structure inside a muscle.

[00064] With regard to the elastic properties of the vaginal wall, the methods of the invention may also be useful when assessing the vaginal wall abnormalities including cancerous or precancerous lesions. Vaginal and vulvar cancers are particularly difficult to detect without the application of invasive testing methods such as acetic acid, coloposcopy or direct biopsy techniques. Examination by any available means, even for screening purposes, is highly dependent on physician skill, level of suspicion for an abnormality and limitations of performing the exam. The use of methods of the invention for tissue elasticity quantification with the transvaginal probe may solve this problem because cancerous tissue is known to have increased hardness.

[00065] Although the invention herein has been described with respect to particular embodiments, it is understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.

Claims

1. A method for characterizing elasticity of a vaginal tissue, said method comprising the steps of:

(a) deforming said vaginal tissue by a transvaginal probe about a first measurement point;

(b) obtaining stress and strain data for said first measurement point using said transvaginal probe, said stress and strain data resulting from deformation applied to said vaginal tissue; and

(c) calculating a stress gradient using said stress and strain data to characterize elasticity of said vaginal tissue.

2. The method as in claim 1, wherein said stress gradient is a ratio of said stress over said strain.

3. The method as in claim 1, wherein in said deforming in step (a) includes a first sliding of said transvaginal probe over a predetermined area of said vaginal tissue while applying a first pressure thereto, said deforming further includes at least a second sliding of said probe over said same predetermined area of said vaginal tissue while applying a second pressure thereto, said second pressure exceeding said first pressure by at least 1 kPa.

4. A method for characterizing elasticity of a vaginal tissue, said method comprising the steps of:

(a) deforming said vaginal tissue by a transvaginal probe about a plurality of measurement points;

(b) obtaining stress and strain data for each of said measurement points using said transvaginal probe, said stress and strain data representing said deformation applied to said vaginal tissue;

(c) composing a vaginal tactile image using said stress and strain data, said vaginal tactile image being a family of constant stress surfaces, each of said constant stress surfaces representing locations of said plurality of measurement points when said measurement points are under a predefined constant stress; and

(d) calculating a stress gradient for at least one of said measurement points using said vaginal tactile image to characterize elasticity of said vaginal tissue.

5. A method for assessment of pelvic organ conditions affecting a vagina, said method comprising the steps of: (a) conducting examination of said vagina by deforming said vagina along an anterior vaginal wall and along a posterior vaginal wall using a transvaginal probe;

(b) obtaining pressure patterns and coordinates corresponding thereto for portions of vagina examined with said transvaginal probe;

(c) calculating at least one of anterior elasticity modulus profile or posterior elasticity modulus profile, said elasticity modulus profiles defined by at least two locations spaced apart in said respective portion of vagina examined with said transvaginal probe;

(d) calculating at least two distances between said anterior vaginal wall and said posterior vaginal wall along said vagina defining a spacing profile therefor; and

(e) estimating a risk of pelvic organ prolapse development by comparing said at least one said elasticity modulus profile at said two locations against respective predetermined elasticity modulus thresholds for said same two locations and by comparing said spacing profile against respective predetermined distance thresholds.

6. The method as in claim 5, wherein said locations are selected from a group consisting of distal anterior, distal posterior, middle anterior and middle posterior sections of said vagina.

7. The method as in claim 5, wherein said locations for calculating distances between anterior and posterior vaginal walls are selected from including group consisting of proximal, middle and distal sections of said vagina.

8. The method as in claim 5, wherein said step (e) further includes adjusting said risk using at least one patient-specific factor, said patient-specific factor is selected from a group consisting of patient age, history of childbirth, history of chronic straining to empty bowel or bladder, status of menopause, obesity, history of prior hysterectomy, history of prior pelvic surgery, history of strenuous activity, smoking status, and alcohol use status.

9. A method for assessment of pelvic organ conditions affecting a vagina, said method comprising the steps of:

(a) conducting examination of said vagina by deforming said vagina along an anterior vaginal wall, along a posterior vaginal wall, along a left side of said vagina and along a right side of said vagina using a transvaginal probe;

(c) calculating from said pressure patterns and coordinates at least one elasticity modulus profile defined by at least two locations spaced apart in said vagina, said at least one elasticity modulus profile is selected from a group consisting of anterior elasticity modulus profile, posterior elasticity modulus profile, left side elasticity modulus profile and right side elasticity modulus profile;

(d) calculating from said pressure patterns and coordinates at least one of an anterior-posterior spacing profile or a left-right spacing profile, said anterior-posterior spacing profile is defined by at least two distances between said anterior vaginal wall and said posterior vaginal wall, said left-right spacing profile is defined by at least two distances between said left side and said right side of said vagina; and

(e) estimating extent of pelvic support tissue impairment or damage after childbirth by comparing said at least one elasticity modulus profile with a corresponding elasticity modulus profile obtained for patients known to have no pelvic support tissue impairment or damage and by comparing said at least one calculated spacing profile with a corresponding spacing profile obtained for patients known to have no pelvic support tissue impairment or damage.

10. A method for assessment of pelvic organ conditions affecting a vagina, said method comprising the steps of:

(a) conducting examination of said vagina before and after an interventional procedure by deforming said vagina along an anterior vaginal wall, along a posterior vaginal wall, along a left side of said vagina and along a right side of said vagina using a transvaginal probe;

(b) obtaining pressure patterns and coordinates corresponding thereto for portions of vagina examined with said transvaginal probe before and after said interventional procedure;

(e) estimating an improvement after said interventional procedure by comparing said at least one elasticity modulus profile obtained before said interventional procedure and after thereof, same improvement is further estimated by comparing said at least one spacing profile obtained before said interventional procedure and after thereof.

11. The method as in claim 10, wherein said interventional procedure is selected from a group consisting of: tissue regeneration resulting from injecting muscle cells, tissue regeneration resulting from injecting stem cells, surgical repair of the vaginal wall and surrounding support tissues, surgical repair of muscle structures, surgical implantation of an artificial supporting structure, and surgical implantation of an artificial structure inside a muscle.