Evaluating the Efficacy of Cervical Tactile Ultrasound Technique as a Predictive Tool for Spontaneous Preterm Birth.

Background: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth. Purpose: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Materials and Methods: Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. Gestational age at delivery was recorded and compared against cervical elasticity. Results: CM examination data were analyzed for 127 women at 240/7 - 286/7 gestational weeks. sPTB was observed in 6.3% of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70 ± 0.26 kPa/mm compared to the term group's 1.63 ± 0.65 kPa/mm with a p-value of 1.1 × 10-4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5 - 100.0). Conclusion: These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe has the potential to predict spontaneous preterm birth in a cost-effective manner.

Predictive Value of Biomechanical Mapping for Pelvic Organ Prolapse Surgery.

OBJECTIVE: This study examined biomechanical changes in pelvic floor after urogynecological surgery. METHODS: This multisite clinical study was designed to explore changes in tissue elasticity, pelvic support, and certain functions (contractive strength, muscle relaxation speed, muscle motility) after pelvic organ prolapse (POP) surgery. A biomechanical mapping of the pelvic floor was performed before and 4 to 6 months after the surgery. The biomechanical data for 52 parameters were acquired by vaginal tactile imaging for manually applied deflection pressures to vaginal walls and pelvic muscle contractions. The two-sample t-test (P < 0.05) was used to test the null hypothesis that presurgery data in group 1 (positive parameter change after surgery) and presurgery data in group 2 (negative parameter change after surgery) belonged to the same distribution. RESULTS: A total of 78 subjects with 255 surgical procedures were analyzed across 5 participating clinical sites. All 52 t-tests for group 1 versus group 2 had P value in the range from 4.0 × 10-10 to 4.3 × 10-2 associating all of the 52 parameter changes after surgery with the presurgical conditions. The P value of before and after surgery correlation ranged from 3.7 × 10-18 to 1.6 × 10-2 for 50 of 52 tests, with Pearson correlation coefficient ranging from -0.79 to -0.27. Thus, vaginal tactile imaging parameters strongly correlated weak pelvic floor presurgery with the positive POP surgery outcome of improved biomechanical properties. CONCLUSIONS: Pelvic organ prolapse surgery, in general, improves the biomechanical conditions and integrity of the weak pelvic floor. The proposed biomechanical parameters can predict changes resulting from POP surgery.

Biomechanical mapping of the female pelvic floor: changes with age, parity and weight.

Quantitative biomechanical characterization of pelvic supportive structures and functions in vivo is thought to provide insight into the pathophysiology of pelvic floor disorders including pelvic organ prolapse (POP). An innovative approach - vaginal tactile imaging - allows biomechanical mapping of the female pelvic floor to quantify tissue elasticity, pelvic support, and pelvic muscle functions. The objective of this study is to explore an extended set of 52 biomechanical parameters to characterize pelvic floor changes with age, parity, and subject weight for normal pelvic floor conditions. 42 subjects with normal pelvic conditions (no POP, no stress urinary incontinence) were included in the data analysis from an observational, case-controlled study. The Vaginal Tactile Imager (VTI) was used with an analytical software package to automatically calculate 52 biomechanical parameters for 8 VTI test procedures (probe insertion, elevation, rotation, Val-salva maneuver, voluntary muscle contractions in 2 planes, relaxation, and reflex contraction). The ranges, mean values, and standard deviations for all 52 VTI parameters were established. 12 VTI parameters were identified as statistically sen-sitive (p < 0.05; t-test) to the subject age; 9 parameters were identified as statistically sensitive (p < 0.05; t-test) to the subject parity; no sensitivity was found to subject weight. Among the 12 parameters sensitive to women's age, 6 parameters show changes (decrease) in tissue elasticity and 6 parameters show weakness in pelvic muscle functions with age. Among the 9 parameters sensitive to parity, 5 parameters show changes (decrease) in tissue elasticity and 4 parameters show weakness in pelvic muscle functions after giving birth. The biomechanical mapping of the female pelvic floor with the VTI provides a unique set of parameters characterizing pelvic changes with age and parity. These objectively measurable biomechanical transformations of pelvic tissues, support structures, and functions may be used in future research and practical applications.

Quantitative Assessment and Interpretation of Vaginal Conditions.

INTRODUCTION: Few means exist to provide quantitative and reproducible assessment of vaginal conditions from biomechanical and functional standpoints. AIM: To develop a new approach for quantitative biomechanical characterization of the vagina. METHODS: Vaginal tactile imaging (VTI) allows biomechanical assessment of soft tissue and function along the entire length of the anterior, posterior, and lateral vaginal walls. This can be done at rest, with applied vaginal deformation, and with pelvic muscle contraction. RESULTS: Data were analyzed for 42 subjects with normal pelvic floor support from an observational case-controlled clinical study. The average age was 52 years (range = 26-90 years). We introduced 8 VTI parameters to characterize vaginal conditions: (i) maximum resistance force to insertion (newtons), (ii) insertion work (millijoules), (iii) maximum stress-to-strain ratio (elasticity; kilopascals per millimeter), (iv) maximum pressure at rest (kilopascals), (v) anterior-posterior force at rest (newtons), (vi) left-right force at rest (newtons), (vii) maximum pressure at muscle contraction (kilopascals), and (viii) muscle contraction force (newtons). We observed low to moderate correlation of these parameters with subject age and no correlation with subject weight. 6 of 8 parameters demonstrated a P value less than .05 for 2 subject subsamples divided by age (≤52 vs >52 years), which means 6 VTI parameters change with age. CONCLUSIONS: VTI allows biomechanical and functional characterization of the vaginal conditions that can be used for (i) understanding "normal" vaginal conditions, (ii) quantification of the deviation from normality, (iii) personalized treatment (radiofrequency, laser, or plastic surgery), and (iv) assessment of the applied treatment outcome. Egorov V, Murphy M, Lucente V, et al. Quantitative Assessment and Interpretation of Vaginal Conditions. Sex Med 2018;6:39-48.

Objective Differences in Colonoscopy Technique Between Trainee and Expert Endoscopists Using the Colonoscopy Force Monitor.

BACKGROUND: Learning to perform colonoscopy safely and effectively is central to gastroenterology fellowship programs. The application of force to the colonoscope is an important part of colonoscopy technique. AIMS: We compared force application during colonoscopy between novice and expert endoscopists using a novel device to determine differences in colonoscopy technique. METHODS: This is an observational cohort study designed to compare force application during colonoscopy between novice and experienced trainees, made up of gastroenterology fellows from two training programs, and expert endoscopists from both academic and private practice settings. RESULTS: Force recordings were obtained for 257 colonoscopies by 37 endoscopists, 21 of whom were trainees. Experts used higher average forward forces during insertion compared to all trainees and significantly less clockwise torque compared to novice trainees. CONCLUSIONS: We present significant, objective differences in colonoscopy technique between novice trainees, experienced trainees, and expert endoscopists. These findings suggest that the colonoscopy force monitor is an objective tool for measuring proficiency in colonoscopy. Furthermore, the device may be used as a teaching tool in training and continued medical education programs.

Multi-frequency axial transmission bone ultrasonometer.

The last decade has seen a surge in the development of axial transmission QUS (Quantitative UltraSound) technologies for the assessment of long bones using various modes of acoustic waves. The condition of cortical bones and the development of osteoporosis are determined by numerous mechanical, micro-structural, and geometrical or macro-structural bone properties like hardness, porosity and cortical thickness. Such complex manifestations of osteoporosis require the evaluation of multiple parameters with different sensitivities to the various properties of bone that are affected by the disease. This objective may be achieved by using a multi-frequency ultrasonic examination The ratio of the acoustic wavelength to the cortical thickness can be changed by varying the frequency of the ultrasonic pulse propagating through the long bone that results in the change in composition of the induced wave comprised of a set of numerous modes of guided, longitudinal, and surface acoustic waves. The multi-frequency axial transmission QUS method developed at Artann Laboratories (Trenton, NJ) is implemented in the Bone Ultrasonic Scanner (BUSS). In the current version of the BUSS, a train of ultrasonic pulses with 60, 100, 400, 800, and 1200 kHz frequencies is used. The developed technology was tested on a variety of bone phantoms simulating normal, osteopenic, and osteoporotic bones. The results of this study confirm the feasibility of the multi-frequency approach for the assessment of the processes leading to osteoporosis.

Osteoporosis detection in postmenopausal women using axial transmission multi-frequency bone ultrasonometer: clinical findings.

The objective of this study was to evaluate if the Bone UltraSonic Scanner (BUSS) can detect osteoporosis in postmenopausal women. BUSS is an axial transmission multi-frequency ultrasonometer for acquisition of wave propagation profiles along the proximal anterior tibia. We derived 10 diagnostically significant BUSS parameters that were then compared with the DXA spine T-score, which was used in this study as the "gold standard" for the assessment of osteoporosis (T-score<-2.5). BUSS wave parameters were studied in 331 postmenopausal women examined by 9 trained operators at 3 clinical sites with use of 3 devices. The efficiency of each BUSS parameter in osteoporosis detection was assessed using a receiver operating characteristic curve analysis. Area under the curve (AUC) for each of 10 parameters ranged from 58.1% to 70.2%. Using these parameters a linear classifier was derived which provided at its output 83.0% AUC, 87.7% sensitivity and 63.2% specificity to DXA-identified osteoporosis. The results of this study confirm BUSS's capability to detect osteoporosis in postmenopausal women.

Modeling and in vitro experimental validation for kinetics of the colonoscope in colonoscopy.

Colonoscopy is the most sensitive and specific means for detection of colon cancers and polyps. To make colonoscopy more effective several problems must be overcome including: pain associated with the procedure, the risk of perforation, and incomplete intubation colonoscopy. Technically, these problems are the result of loop formation during colonoscopy. Although, several solutions such as modifying the stiffness of the colonoscope, using an overtube and developing image-guided instruments have been introduced to resolve the looping problem, the results of these systems are not completely satisfactory. A new paradigm to overcome loop formation is proposed that is doctor-assistive colonoscopy. In this approach, the endoscopists performance is enhanced by providing using a kinetic model that provides information such as the shape of the scope, direction of the colon and forces exerted within certain sections. It is expected that with the help of this model, the endoscopist would be able to adjust the manipulation to avoid loop formation. In the present studies, the kinetic model is developed and validated using an ex vivo colonoscopy test-bed with a comprehensive kinematic and kinetic data collection. The model utilizes an established colon model based on animal tissue with position tracking sensors, contact force sensors for the intraluminal portion of the scope and a Colonoscopy Force Monitor for the external insertion tube.

Characterization of forces applied by endoscopists during colonoscopy by using a wireless colonoscopy force monitor.

BACKGROUND: To perform a colonoscopy, the endoscopist maneuvers the colonoscope through a series of loops by applying force to the insertion tube. Colonoscopy insertion techniques are operator dependent but have never been comprehensively quantified. OBJECTIVE: To determine whether the Colonoscopy Force Monitor (CFM), a device that continually measures force applied to the insertion tube, can identify different force application patterns among experienced endoscopists. DESIGN: Observational study of 6 experienced endoscopists performing routine diagnostic and therapeutic colonoscopy in 30 patients. SETTING: Outpatient ambulatory endoscopy center. PATIENTS: Adult male and female patients between 30 and 75 years of age undergoing routine colonoscopy. INTERVENTIONS: CFM monitoring of force applied to the colonoscope insertion tube during colonoscopy. MAIN OUTCOME MEASUREMENTS: Maximum and mean linear and torque force, time derivative of force, combined linear and torque vector force, and total manipulation time. RESULTS: The CFM demonstrates differences among endoscopists for maximum and average push/pull and mean torque forces, time derivatives of force, combined push/torque force vector, and total manipulation time. Endoscopists could be grouped by force application patterns. LIMITATIONS: Only experienced endoscopists using conscious sedation in the patients were studied. Sample size was 30 patients. CONCLUSIONS: This study demonstrates that CFM allows continuous force monitoring, characterization, and display of similarities and differences in endoscopic technique. CFM has the potential to facilitate training by enabling trainees to assess, compare, and quantify their techniques and progress.

Differentiation of benign and malignant breast lesions by mechanical imaging.

Mechanical imaging yields tissue elasticity map and provides quantitative characterization of a detected pathology. The changes in the surface stress patterns as a function of applied load provide information about the elastic composition and geometry of the underlying tissue structures. The objective of this study is the clinical evaluation of breast mechanical imager for breast lesion characterization and differentiation between benign and malignant lesions. The breast mechanical imager includes a probe with pressure sensor array, an electronic unit providing data acquisition from the pressure sensors and communication with a touch-screen laptop computer. We have developed an examination procedure and algorithms to provide assessment of breast lesion features such as hardness related parameters, mobility, and shape. A statistical Bayesian classifier was constructed to distinguish between benign and malignant lesions by utilizing all the listed features as the input. Clinical results for 179 cases, collected at four different clinical sites, have demonstrated that the breast mechanical imager provides a reliable image formation of breast tissue abnormalities and calculation of lesion features. Malignant breast lesions (histologically confirmed) demonstrated increased hardness and strain hardening as well as decreased mobility and longer boundary length in comparison with benign lesions. Statistical analysis of differentiation capability for 147 benign and 32 malignant lesions revealed an average sensitivity of 91.4% and specificity of 86.8% with a standard deviation of +/-6.1%. The area under the receiver operating characteristic curve characterizing benign and malignant lesion discrimination is 86.1% with the confidence interval ranging from 80.3 to 90.9%, with a significance level of P = 0.0001 (area = 50%). The multisite clinical study demonstrated the capability of mechanical imaging for characterization and differentiation of benign and malignant breast lesions. We hypothesize that the breast mechanical imager has the potential to be used as a cost effective device for cancer diagnostics that could reduce the benign biopsy rate, serve as an adjunct to mammography and to be utilized as a screening device for breast cancer detection.

Prostate mechanical imaging: a new method for prostate assessment.

OBJECTIVES: To evaluate the ability of prostate mechanical imaging (PMI) technology to provide an objective and reproducible image and to assess the prostate nodularity. METHODS: We evaluated the PMI device developed by Artann Laboratories in a pilot clinical study. For the 168 patients (ages 44 to 94) who presented to an urologist for prostate evaluation, PMI-produced images and assessment of prostate size, shape, consistency/hardness, mobility, and nodularity were compared with digital rectal examination (DRE) findings. The PMI and DRE results were further tested for correlation against a transrectal ultrasound of the prostate (TRUS) guided biopsy for a subgroup of 21 patients with an elevated prostate-specific antigen level. RESULTS: In 84% of the cases, the PMI device was able to reconstruct three-dimensional (3D) and 2D cross-sectional images of the prostate. The PMI System and DRE pretests were able to determine malignant nodules in 10 and 6 patients, respectively, of the 13 patients with biopsy-confirmed malignant inclusions. The PMI System findings were consistent with all 8 biopsy negative cases, whereas the DRE had 1 abnormal reading for this group. The correlation between PMI and DRE detection of palpable nodularity was 81%, as indicated by the area under the receiver operating characteristic curve. Estimates of the prostate size provided by PMI and DRE were statistically significantly correlated. CONCLUSIONS: The PMI has the potential to enable a physician to obtain, examine, and store a 3D image of the prostate based on mechanical and geometrical characteristics of the gland and its internal structures.

Ultrasound velocity in human muscle in vivo: perspective for edema studies.

The present study examines the association of the changes in ultrasound velocity measured at 1 MHz using 1.5 micros duration tone burst in the human soleus muscle in vivo with several pathologies including patients with chronic renal failure (CRF) and disorders of the cardiovascular system. Total 127 subjects were investigated, with approximately equal number of male and female subjects uniformly distributed by age, from 15 to 70 years old. Since molecular composition of the tissue is thought to have greater effect on the bulk ultrasound velocity, potential contribution of both water and fat, two main variable components of a muscle, were taken into account. Observed negative correlation of ultrasound velocity with the body mass index was considered a result of an elevated fat content. Based on the obtained data, presence of leg edemas results in a measurably lower ultrasound velocity in the soleus muscle. Unless patients had visibly detected leg edema, no difference between healthy individuals, patients with chronic heart failure, or CRF was found. Despite relatively high individual variations in velocity, ranging from 1530 to 1615 m/s, a statistically significant gender correlated difference between average values of the velocity was observed. No dependence of velocity on subject age was detected. An indirect confirmation of the muscle fluid homeostasis was revealed in patients with CRF undergoing hemodialysis procedure. After hemodialysis, a significantly smaller increase (0.3% in average) of ultrasound velocity in the soleus muscle was observed than otherwise could be expected if a uniform relative loss of total body fluids was assumed (1-1.3%). In general, the study findings set a premise for using ultrasound velocity as a potential quantitative parameter for edema assessment.

Ultrasonic assessment of tissue hydration status.

Tissue water content is an important diagnostic parameter that can be used for estimation of water loss in muscles such as common dehydration during high endurance exercises. It could be also applied for evaluation of the increased fluids content in the tissue caused by the variety of pathological conditions or edemas. Ultrasonic method for tissue water content monitoring is based on the premise that the speed of a bulk or compression sound wave is determined mainly by the molecular content of the tissue. Most soft tissues, including muscles that consist of about 70-80% water, exhibit shift of the ultrasound velocity associated with the change in their water content. In the present paper, we tested the feasibility of assessing changes in tissue water content by measurements of ultrasound velocity in ex vivo animal muscle tissues. An increase in the ultrasound velocity correlated with the volumetric water loss in the tissue was observed when other tissue components (proteins, fat) remained constant. Possibility to assess muscle dehydration with 1% accuracy was confirmed in model dehydration experiments, where ultrasound velocity slope of about 3 m/s per 1% of water loss was revealed at measurement error less than 2 m/s. Hence, the ultrasonic approach can provide basis for a convenient, lightweight system in sports medicine for monitoring total body hydration during long-term endurance exercise in hot conditions, as well as for edemas monitoring and other medical applications.

Use of multiple acoustic wave modes for assessment of long bones: model study.

Multiple acoustic wave mode method has been proposed as a new modality in axial bone QUS. The new method is based on measurement of ultrasound velocity at different ratio of wavelength to the bone thickness, and taking into account both bulk and guided waves. It allows assessment of changes in both the material properties related to porosity and mineralization as well as the cortical thickness influenced by resorption from inner layers, which are equally important in diagnostics of osteoporosis and other bone osteopenia. Developed method was validated in model studies using a dual-frequency (100 and 500 kHz) ultrasound device. Three types of bone phantoms for long bones were developed and tested: (1) tubular specimens from polymer materials to model combined changes of material stiffness and cortical wall thickness; (2) layered specimens to model porosity in compact bone progressing from endosteum towards periosteum; (3) animal bone specimens with both cortical and trabecular components. Observed changes of the ultrasound velocity of guided waves at 100 kHz followed gradual changes in the thickness of the intact cortical layer. On the other hand, the bulk velocity at 500 kHz remained nearly constant at the different cortical layer thickness but was affected by the material stiffness. Similar trends were observed in phantoms and in fragments of animal bones.

Fluorescence analysis of receptor-G protein interactions in cell membranes.

The dynamics of G protein heterotrimer complex formation and disassembly in response to nucleotide binding and receptor activation govern the rate of responses to external stimuli. We use a novel flow cytometry approach to study the effects of lipid modification, isoform specificity, lipid environment, and receptor stimulation on the affinity and kinetics of G protein subunit binding. Fluorescein-labeled myristoylated Galpha(i1) (F-alpha(i1)) was used as the ligand bound to Gbetagamma in competition binding studies with differently modified Galpha subunit isoforms. In detergent solutions, the binding affinity of Galpha(i) to betagamma was 2 orders of magnitude higher than for Galpha(o) and Galpha(s) (IC50 of 0.2 nM vs 17 and 27 nM, respectively), while in reconstituted bovine brain lipid vesicles, binding was slightly weaker. The effects of receptor on the G protein complex were assessed in alpha(2A)AR receptor expressing CHO cell membranes into which purified betagamma subunits and F-alpha(i1) were reconstituted. These cell membrane studies led to the following observations: (1) binding of alpha subunit to the betagamma was not enhanced by receptor in the presence or absence of agonist, indicating that betagamma contributed essentially all of the binding energy for alpha(i1) interaction with the membrane; (2) activation of the receptor facilitated GTPgammaS-stimulated detachment of F-alpha(i1) from betagamma and the membrane. Thus flow cytometry permits quantiatitive and real-time assessments of protein-protein interactions in complex membrane environments.