Elastography System Research Articles

Downgrading Breast Imaging Reporting and Data System categories in ultrasound using strain elastography and computer-aided diagnosis system: a multicenter, prospective study.

To determine whether adding elastography strain ratio (SR) and a deep learning based computer-aided diagnosis (CAD) system to breast ultrasound (US) can help reclassify Breast Imaging Reporting and Data System (BI-RADS) 3 and 4a-c categories and avoid unnecessary biopsies. This prospective, multicentre study included 1049 masses (691 benign, 358 malignant) with assigned BI-RADS 3 and 4a-c between 2020 and 2022. CAD results was dichotomized possibly malignant vs. benign. All patients underwent SR and CAD examinations and histopathological findings were the standard of reference. Reduction of unnecessary biopsies (biopsies in benign lesions) and missed malignancies after reclassified (new BI-RADS 3) with SR and CAD were the outcome measures. Following the routine conventional breast US assessment, 48.6% (336 of 691 masses) underwent unnecessary biopsies. After reclassifying BI-RADS 4a masses (SR cut-off <2.90, CAD dichotomized possibly benign), 25.62% (177 of 691 masses) underwent an unnecessary biopsies corresponding to a 50.14% (177 vs. 355) reduction of unnecessary biopsies. After reclassification, only 1.72% (9 of 523 masses) malignancies were missed in the new BI-RADS 3 group. Adding SR and CAD to clinical practice may show an optimal performance in reclassifying BI-RADS 4a to 3 categories, and 50.14% masses would be benefit by keeping the rate of undetected malignancies with an acceptable value of 1.72%. Leveraging the potential of SR in conjunction with CAD holds immense promise in substantially reducing the biopsy frequency associated with BI-RADS 3 and 4A lesions, thereby conferring substantial advantages upon patients encompassed within this cohort.

Viscoelasticity quantification of cancerous tongue using intraoral optical coherence elastography: a preliminary study

Quantifying the biomechanical properties of the tongue is significant for early diagnosis of tongue carcinoma. Therefore, an intraoral optical coherence elastography system based on a miniature probe was proposed here to evaluate the viscoelasticity of in vivo tongue for the first time. Results of experiments with Sprague-Dawley rats indicate that considerable elasticity diversity occurred between cancerous and normal tongues, and the corresponding ratio of their Young’s modulus was evaluated to be 3.74. It is also found that, viscosity in diseased tissue is smaller than that in normal tissue. Additionally, healthy, transitional and cancerous regions in the cancerous tongue can be distinguished easily by calculating viscoelasticity characteristics. Based on this preliminary attempt, our method with advantages of noninvasive, high-resolution, high-sensitivity and real-time detection and convenient operation may have good potential to become a useful tool for tongue carcinoma assessment after further optimization.

Spatial mapping of corneal biomechanical properties using wave-based optical coherence elastography.

Quantifying the mechanical properties of the cornea can provide valuable insights into the occurrence and progression of keratoconus, as well as the effectiveness of corneal crosslinking surgery. This study presents a non-contact and non-invasive wave-based optical coherence elastography system that utilizes air-pulse stimulation to create a two-dimensional map of corneal elasticity. Homogeneous and dual concentration phantoms were measured with the sampling of 25 × 25 points over a 6.6 × 6.6 mm2 area, to verify the measurement capability for elastic mapping and the spatial resolution (0.91 mm). The velocity of elastic waves distribution of porcine corneas before and after corneal crosslinking surgery were further mapped, showing a significant change in biomechanics in crosslinked region. This system features non-invasiveness and high resolution, holding great potential for application in ophthalmic clinics.

Motion-artifact-free single shot two-beam optical coherence elastography system.

The assessment of the biomechanical properties of the skin using various imaging techniques has been used as a diagnostic tool in dermatology. Optical coherence elastography (OCE) is one of the techniques that allows for the measurement of elastic properties. OCE relies on measuring tissue displacements induced by external sources. Measuring the tissue's mechanical properties in vivo using OCE is often challenging due to bulk tissue movement. This study aimed to develop an OCE system that allows for minimizing the effects of bulk tissue movements. To achieve this, we designed a two-beam OCE system that simultaneously measures the tissue displacement at two locations on the sample. This allows for cancelling the effect of the tissue bulk movement, which is common to both measurement points. We used a piezoelectric transducer to generate surface acoustic waves (SAW) in the sample. The velocity of the excited waves, which is proportional to the rigidity of the sample, was measured by calculating the phase delay of the SAW at two locations on the sample. Simultaneous measurement at two locations was achieved by dividing a single light beam into two by focusing on the sample at two different locations. The two beams travel different optical path lengths, and the reflected signals were depth encoded in a single optical coherence tomography scan using a single reference beam. The system was characterized using different tissue-mimicking phantoms and the skin of healthy volunteers at the wrist and the palm. We achieved an approximately 50-fold increase in phase sensitivity measurement. We designed a simple two-beam OCE system that effectively minimizes the effect of tissue movement. We believe that the presented system will find immediate applications in the clinic to monitor the progression of systemic sclerosis disease.

Palm-Sized Wireless Transient Elastography System with Real-Time B-Mode Ultrasound Imaging Guidance: Toward Point-of-Care Liver Fibrosis Assessment.

Transient elastography (TE), recommended by the WHO, is an established method for characterizing liver fibrosis via liver stiffness measurement (LSM). However, technical barriers remain towards point-of-care application, as conventional TE requires wired connections, possesses a bulky size, and lacks adequate imaging guidance for precise liver localization. In this work, we report the design, phantom validation, and clinical evaluation of a palm-sized TE system that enables simultaneous B-mode imaging and LSM. The performance of this system was validated experimentally using tissue-equivalent reference phantoms (1.45-75 kPa). Comparative studies against other liver elastography techniques, including conventional TE and two-dimensional shear wave elastography (2D-SWE), were performed to evaluate its reliability and validity in adults with various chronic liver diseases. Intra- and inter-operator reliability of LSM were established by an elastography expert and a novice. A good agreement was observed between the Young's modulus reported by the phantom manufacturer and this system (bias: 1.1-8.6%). Among 121 patients, liver stiffness measured by this system and conventional TE were highly correlated (r = 0.975) and strongly agreed with each other (mean difference: -0.77 kPa). Inter-correlation of this system with conventional TE and 2D-SWE was observed. Excellent-to-good operator reliability was demonstrated in 60 patients (ICCs: 0.824-0.913). We demonstrated the feasibility of employing a fully integrated phased array probe for reliable and valid LSM, guided by real-time B-mode imaging of liver anatomy. This system represents the first technical advancement toward point-of-care liver fibrosis assessment. Its small footprint, along with B-mode guidance capability, improves examination efficiency and scales up screening for liver fibrosis.

Quantitative assessment of corneal elasticity distribution after FS-LASIK using optical coherence elastography.

Quantifying corneal elasticity after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) procedure plays an important role in improving surgical safety and quality, since some latent complications may occur ascribing to changes in postoperative corneal biomechanics. Nevertheless, it is suggested that current research has been severely constrained due to the lack of an accurate quantification method to obtain postoperative corneal elasticity distribution. In this paper, an acoustic radiation force optical coherence elastography system combined with the improved phase velocity algorithm was utilized to realize elasticity distribution images of the in vivo rabbit cornea after FS-LASIK under various intraocular pressure levels. As a result, elasticity variations within and between the regions of interest could be identified precisely. This is the first time that elasticity imaging of in vivo cornea after FS-LASIK surgery was demonstrated, and the results suggested that this technology may hold promise in further exploring corneal biomechanical properties after refractive surgery.

Quantification of Cervical Elasticity During Pregnancy Based on Transvaginal Ultrasound Imaging and Stress Measurement.

To overcome these limitations, we develop a quantitative cervical elastography system by adding a stress sensor to a clinically used transvaginal ultrasound imaging system. We record the cervical deformation in B-mode images and measure the probe-surface stress through the sensor. Then we quantify the strain using a customized algorithm and estimate the cervical Young's modulus through stress-strain linear regression. In phantom experiments, we demonstrate the system's high accuracy (alignment with the quasi-static compression method, p-value = 0.369 > 0.05), robustness (alignment between 60°- and 90°-contact measurements, p-value = 0.638 > 0.05), repeatability (consistency of single sonographers' measurements, coefficient of variation < 0.06), and reproducibility (alignment between two sonographers' measurements, Pearson correlation coefficient = 0.981). Applying it to pregnant participants, we observe significant cervical softening (p-value < 0.001): Young's modulus decreases 3.95% weekly and its geometric mean value during the first (11 to 13 weeks), second, and third trimesters are 13.07 kPa, 7.59 kPa, and 4.40 kPa, respectively. The proposed system is accurate, robust, and safe, and enables longitudinal and inter-examiner comparisons. The system applies to different ultrasound machines with minor software updates, which allows for studies of cervical softening patterns in pregnancy for larger populations, facilitating insights into conditions such as preterm birth.

A Portable Single-sided Magnetic Resonance Elastography System for Biological Tissues

A Portable Single-sided Magnetic Resonance Elastography System for Biological Tissues

Multiscale elasticity mapping of biological samples in 3D at optical resolution

The mechanical properties of biological tissues have emerged as an integral determinant of tissue function in health and disease. Nonetheless, characterizing the elasticity of biological samples in 3D and at high resolution remains challenging. Here, we present a µElastography platform: a scalable elastography system that maps the elastic properties of tissues from cellular to organ scales. The platform leverages the use of a biocompatible, thermo-responsive hydrogel to deliver compressive stress to a biological sample and track its resulting deformation. By surrounding the specimen with a reference hydrogel of known Young's modulus, we are able to map the absolute values of elastic properties in biological samples. We validate the experimental and computational components of the platform using a hydrogel phantom and verify the system's ability to detect internal mechanical heterogeneities. We then apply the platform to map the elasticity of multicellular spheroids and the murine lymph node. With these applications, we demonstrate the platform's ability to map tissue elasticity at internal planes of interest, as well as capture mechanical heterogeneities neglected by most macroscale characterization techniques. The µElastography platform, designed to be implementable in any biology lab with access to 3D microscopy (e.g., confocal, multiphoton, or optical coherence microscopy), will provide the capability to characterize the mechanical properties of biological samples to labs across the large community of biological sciences by eliminating the need of specialized instruments such as atomic force microscopy. Statement of significanceUnderstanding the elasticity of biological tissues is of great importance, but characterizing these properties typically requires highly specialized equipment. Utilizing stimulus-responsive hydrogels, we present a scalable, hydrogel-based elastography method that uses readily available reagents and imaging modalities to generate resolved maps of internal elasticity within biomaterials and biological samples at optical resolution. This new approach is capable of detecting internal stiffness heterogeneities within the 3D bulk of samples and is highly scalable across both imaging modalities and biological length scales. Thus, it will have significant impact on the measurement capabilities of labs studying engineered biomaterials, mechanobiology, disease progression, and tissue engineering and development.

Quantitative Evaluation of Biomechanical Properties of the Tongue Using a Shaker-Based Optical Coherence Elastography System

Biomechanical properties of the tongue play a significant role in maintaining its normal physiological state. Although some techniques have been used to evaluate the tongue’s elasticity, they are limited in clinical detection because of low-resolution and invasive injuries. Here, a shaker-based optical coherence elastography technique that possesses features of high resolution, high sensitivity, and non-destructive imaging was designed and applied to the elastic detection of the tongue for the first time. Repeated experiments were conducted on the in vivo beagle tongue whose shear modulus and Young’s modulus were quantified by visualization of the shear wave propagation, which indicates that our technique is reliable and operable, and may be potentially utilized in clinical fields with further refinement.

Poster Session: Experimental assessment of scleral anisotropy using multi-meridian air-coupled ultrasonic optical coherence elastography.

Scleral biomechanics plays a key role in the understanding of myopia progression. In this study, we characterized the elastic properties of sclera using an air-coupled ultrasonic (ACUS) optical coherence elastography (OCE) system. New Zealand rabbit eyes (n=7) were measured (<24hr postmortem) in four scleral locations: superior/inferior temporal (ST, IT), and superior/inferior nasal (SN, IN) maintaining an intraocular pressure of 15 mmHg. Elastic waves were induced in the sclera, and wave propagation velocity and shear modulus were measured along two directions: circumferential (superior-inferior) and meridional (nasal-temporal). Wave velocity in scleral tissue ranged from 6 to 24 m/s and shear modulus from 11 to 150 kPa. Velocity was significantly higher (p<.001) in the circumferential vs. meridional directions in the following locations: ST:15.83±2.85 vs 9.43±1.68 m/s, IT:15.00±3.98 vs 8.93±1.53 m/s; SN:16.79±4.30 vs 9.27±1.47 m/s; and IN:13.92±3.85 vs 8.57±1.46 m/s. The average shear modulus in the circumferential was also significantly higher (p<.001) than in the meridional direction for all locations: 65.37±6.04 vs 22.55±1.36 kPa. These results show that the rabbit sclera is mechanically anisotropic with higher rigidity in the circumferential direction compared to the meridional direction. ACUS-OCE is a promising non-invasive method to quantify the biomechanical changes in scleral tissue for future studies involving myopia treatments.

Contributed Session II: Detecting subclinical keratoconus by mapping corneal biomechanics using wave-based optical coherence elastography.

The detection of subclinical keratoconus in human corneas remains a challenging task. It is hypothesized that the focal reduction in biomechanical properties of the cornea would be the primary initiating event of keratoconus before changes in topography and pachymetry are manifested. We propose to use an air-couple ultrasonic optical coherence elastography system to map the elasticity of the corneas of 15 patients with a clinical diagnosis of keratoconus (KC) in one eye, and subclinical keratoconus (SK) in the fellow eye. The fully non-contact system excites the corneal apex to produce Lamb wave propagation and measures wave speed and average corneal thickness along 16 semi-meridians. Measurements in 30 human healthy subjects (control group: CG, N = 60 corneas) defined a baseline of normal biomechanics in two biomarkers: Spatial Anisotropy of Wave Speed (SAWS < 0.207), and the Speed-Thickness Index (STI > 0). SAWS was significantly higher in KC (0.353, p < 0.001) and SK (0.249, p < 0.001) corneas when compared to the CG. Moreover, STI maps show abnormal elasticity in SK (STI = -1.22) and KC (STI = -0.375) compared to the CG. Our results show important biomechanical differences in SAWS and STI between normal, subclinical, and advanced stages of keratoconus, suggesting those as potential biomarkers to identify "at-risk" corneas before changes in topography and pachymetry become evident.

Value of TI-RADS and elastography strain ratio in predicting malignant thyroid nodules: experience from a single center in Egypt

IntroductionThyroid nodules are highly prevalent in the general population; therefore, it is crucial to discriminate benign from malignant nodules. A practical thyroid imaging reporting and data system (TI-RADS) for thyroid nodules and ultrasound elastography are valuable tools not only for characterization of nodules but also for the selection of tumors for fine-needle aspiration cytology (FNAC).ObjectiveThis study aimed to evaluate the diagnostic accuracy of US evaluation in the prediction of malignant thyroid nodules and evaluate the role of the elastography score, strain ratio (SR), and the TI-RADS scoring system as non-invasive tools in differentiation between malignant and benign thyroid nodules.Material and methodsA total of 1269 patients were evaluated between February 2017 and April 2020 by a single expert thyroid ultrasound operator. The final diagnosis was achieved from cytological and/or histological evaluation and follow-up for at least 1 year.ResultsThere were 1088 females and 181 males with a mean age of 44 ± 10 SD. The final diagnosis was 1197 benign nodules and 72 malignant nodules. Most malignant nodules were scored elastography score 4 (83.3%) and TI-RADS category 5 (86.11%). We found that nodules with antero-posterior to transverse (A-P/T) diameter > 1, have 21 times more risk to be malignant than those with A-P/T diameter < 1, patients with solitary thyroid nodules have 4.5 times to develop malignancy compared to those with multinodular goiter (MNG), nodules with absent halo have 4 times more risk of malignancy. Furthermore, microcalcifications in thyroid nodules increase the risk of malignancy 9 times compared to those without calcifications. SR was found to be an excellent discriminator to differentiate between benign and malignant nodules with P < 0.001. Also, we found that for every unit increase in SR, the risk of malignancy increased by 20%. We reported that the accuracy of ultrasonography in the detection of malignant thyroid nodules had a sensitivity of 89%, specificity of 98%, 70% PPV, and 99.3% NPV, with an overall accuracy of 97.2%.ConclusionThe application of ultrasonographic non-invasive criteria for thyroid nodules in clinical practice might significantly reduce the number of unnecessary FNAC. Elastography, SR, and TI-RADS classification could be good predictors for malignant thyroid nodules.

Retinal imaging in animal models: Searching for biomarkers of neurodegeneration.

There is a pressing need for novel diagnostic and progression biomarkers of neurodegeneration. However, the inability to determine disease duration and stage in patients with Alzheimer's disease (AD) hinders their discovery. Because animal models of disease allow us to circumvent some of these limitations, they have proven to be of paramount importance in clinical research. Due to the clear optics of the eye, the retina combined with optical coherence tomography (OCT) offers the perfect opportunity to image neurodegeneration in the retina in vivo, non-invasively, directly, quickly, and inexpensively. Based on these premises, our group has worked towards uncovering neurodegeneration-associated changes in the retina of the triple-transgenic mouse model of familial AD (3×Tg-AD). In this work, we present an overview of our work on this topic. We report on thickness variations of the retina and retinal layers/layer aggregates caused by healthy aging and AD-like conditions and discuss the implications of focusing research efforts solely on retinal thickness. We explore what other information is embedded in the OCT data, extracted based on texture analysis and deep-learning approaches, to further identify biomarkers that could be used for early detection and diagnosis. We were able to detect changes in the retina of the animal model of AD as early as 1 month of age. We also discuss our work to develop an optical coherence elastography system to measure retinal elasticity, which can be used in conjunction with conventional OCT. Finally, we discuss the potential application of these technologies in human patients and the steps needed to make OCT a helpful screening tool for the detection of neurodegeneration.

Simultaneous Assessment of the Whole Eye Biomechanics Using Ultrasonic Elastography.

Current elastography techniques in the field of ophthalmology usually target one specific tissue, such as the cornea or the sclera. However, the eye is an inter-related organ, and some ocular diseases can alter the biomechanical properties of multiple anatomical structures. Hence, there is a need to develop an imaging tool that can non-invasively, quantitatively, and accurately characterize dynamic changes among these biomechanical properties. A high resolution ultrasound elastography system was developed to achieve this goal. The efficacy and accuracy of the system was first validated on tissue-mimicking phantoms while mechanical testing measurements served as the gold standard. Next, an in vivo elevated intraocular pressure (IOP) model was established in rabbits to further test our system. In particular, elastography measurements were obtained at 5 IOP levels, ranging from 10 mmHg to 30 mmHg in 5 mmHg increments. Spatial-temporal maps of the multiple ocular tissues (cornea, lens, iris, optic nerve head, and peripapillary sclera) were obtained. The spatial-temporal maps were acquired simultaneously for the ocular tissues at the 5 different IOP levels. The statistical analysis of the elastic wave speed was presented for ocular tissues. Finally, the mapping for the elastic wave speed of each ocular component was acquired at each IOP level. Our elastography system can concurrently assess the biomechanical properties of multiple ocular structures and detect changes in biomechanical properties associated with changes in IOP. This system provides a novel tool to measure and quantify the biomechanical properties of the whole eye.

Evaluation of Residual Corneal Stromal Bed Elasticity by Optical Coherence Elastography Based on Acoustic Radiation Force

Despite the rapidly growing popularity of laser vision correction (LVC) in the correction of myopia, its quantitative evaluation has not been thoroughly investigated. In this paper, an acoustic radiation force–optical coherence elastography (ARF-OCE) system was proposed to evaluate LVC by measuring the residual stromal bed (RSB) elasticity, because it is directly relevant to the RSB thickness that is critical to maintaining normal corneal function. As expected, the Young’s modulus of the RSB was calculated, then its relationship with the RSB thickness was determined. More significantly, a specific thickness was revealed in which the Young’s modulus changed dramatically, which may imply that there is a high risk of complication caused by over-cutting of the cornea. To the best of our knowledge, this is the first ARF-OCE imaging of the RSB, which may help to determine the safe RSB thickness and thus may help us to quantitatively assess LVC surgery.

Acoustic radiation force optical coherence elastography: A preliminary study on biomechanical properties of trabecular meshwork.

Evaluating biomechanical properties of trabecular meshwork (TM) is of great significance for understanding the mechanism of aqueous humor circulation and its relationship to some eye diseases such as glaucoma; however, there is almost no relevant study due to the lack of clinical measurement tool. In this paper, an acoustic radiation force optical coherence elastography (ARF-OCE) system is developed with the advantages of noninvasive detection, high resolution, high sensitivity, and high-speed imaging, by which elastic modulus of the porcine and human TMs is accurately quantified. As the first OCE imaging of TM, our study demonstrates that ARF-OCE may be an effective approach to advance the research of diseases related to aqueous humor circulation.

Fully quantitative numeric cervical elastography outperforms cervical length for PTB prediction in asymptomatic patients

To test a novel, fully quantitative cervical elastography system (FQ-CES) for preterm birth prediction and compare predictive characteristics to cervical length in asymptomatic patients. This is a prospective longitudinal cohort study of asymptomatic pregnant patients who underwent FQ-CES in the first, second, and third trimesters.We invented FQ-CES, which modifies a transvaginal ultrasound probe to quantify both pressure applied and tissue deformation, thereby yielding a fully quantified strain-based elastography system that provides a numeric quantification (Young’s modulus) of cervical tissue stiffness. This system is operator independent and can be compared across patients and within patients over time. Singleton pregnancies were included and imaging to obtain both FQ-CES and cervical length (CL) was performed at 11-23 weeks of pregnancy. Percentile rank of log-scaled Young’s modulus (logYM) was calculated, and patients were dichotomized into high and low cervical stiffness by the optimal significance of chi-square test. Prediction performance by FQ-CES and CL for preterm delivery < 37 weeks was assessed using ROC curves A total of 87 patients were included. The 15th percentile (logYM) was identified as the optimal cut-point to define low cervical stiffness. Patients with low cervical stiffness had a significantly higher risk for PTB than those with normal cervical stiffness (>15th percentile) (RR=2.9 95%CI [1.4, 6.1]). The FQ-CES was overall more predictive of PTB than cervical length (AUC 0.69 versus 0.53) (p=0.18) (Table and Figure). The predictive characteristics of FQ-CES logYM ≤ 15th percentile for PTB were: sensitivity 31%, specificity 91%, positive predictive value 50%, and negative predictive value 83%. FQ-CES performed at 11-23 weeks of pregnancy has better performance for preterm birth prediction than cervical length and could be used to refine risk stratification both clinically and for targeted enrollment in PTB intervention trials.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Fully quantitative cervical elastography demonstrates detectable differences in cervical remodeling patterns by parity

To utilize a novel, fully quantitative cervical elastography system (FQ-CES) to numerically measure cervical stiffness and examine how physiologic cervical remodeling differs in nulliparous versus multiparous patients.

Development of Non-Invasive, Low Cost, Infrasonic Swept Source Optical Coherence Elastography System for Strain Imaging

Development of Non-Invasive, Low Cost, Infrasonic Swept Source Optical Coherence Elastography System for Strain Imaging