Vivo Feasibility Research Articles

In Vivo Feasibility of Arterial Embolization with a New Permanent Agar-agar-Based Agent.

Evaluate the safety and efficacy of an eco-friendly permanent agar-agar-based embolization agent (ABEA) (EmboBio®) for intra-arterial use. Six pigs embolized with one ABEA torpedo (6 lower polar renal and 6 lumbar arteries) and one coil (6 lower polar renal and 6 lumbar arteries). Technical success was defined as a complete occlusion with no residual flow in DSA. Short-term endpoints included safety (non-targeted embolization), ease of use (embolization preparation time, occlusion time), and DSA controls at day 7, month 1, and month 3. Tissue reaction was assessed via [18F]-FDG PET/CT at month 2 and histological study at month 3. ABEA torpedoes achieved immediate and persistent occlusion at month 3 for all kidney and lumbar embolizations (n = 12/12). Control coils had technical success for 12/12, with a persistent occlusion at month 3 for 2/12. No off-target embolization occurred. ABEA torpedoes demonstrate faster occlusion (ABEA: 6 ± 4s; coils: 427 ± 469s; p = 0.0022, n = 12) and preparation times (ABEA: 96.9 1 ± 23s; coils: 150.33 ± 58s; p = 0.0432, n = 12) after device placement than coil. No significant difference in inflammation between ABEA and coil groups at month 2 (ABEA: 3.35e-6 ± 1.7e-6%ID/mm3; coils: 2.24e-6 ± 8.5e-7%ID/mm3; p = 0.5) on PET imaging. These results were confirmed by histological analysis at month 3. Permanent dry foam torpedo comprising agar-agar is effective for arterial embolization. In animal model, one ABEA torpedo demonstrates a faster and more persistent occlusion than one fiber coil. Not applicable.

Abstract No. 514 In Vivo Feasibility of Arterial Embolization with a New Permanent Dry Foam Comprising Agar-Agar (EmboBio)

Abstract No. 514 In Vivo Feasibility of Arterial Embolization with a New Permanent Dry Foam Comprising Agar-Agar (EmboBio)

Bacteremia Prevention during Periodontal Treatment-An In Vivo Feasibility Study.

The link between periodontitis and systemic diseases has increasingly become a focus of research in recent years. In this context, it is reasonable-especially in vulnerable patient groups-to minimize bacteremia during periodontal treatment. The aim of the present in vivo feasibility study was to investigate the possibility of laser-based bacteremia prevention. Patients with stage III, grade B generalized periodontitis were therefore treated in a split-mouth design either with prior 445 nm laser irradiation before nonsurgical periodontal therapy or without. During the treatments, clinical (periodontal measures, pain sensation, and body temperature), microbiological (sulcus samples and blood cultures before, 25 min after the start, and 10 min after the end of treatment), and immunological parameters (CRP, IL-6, and TNF-α) were obtained. It was shown that periodontal treatment-related bacteremia was detectable in both patients with the study design used. The species isolated were Schaalia georgiae, Granulicatella adiacens, and Parvimonas micra. The immunological parameters increased only slightly and occasionally. In the laser-assisted treatments, all blood cultures remained negative, demonstrating treatment-related bacteremia prevention. Within the limitations of this feasibility study, it can be concluded that prior laser disinfection can reduce bacteremia risk during periodontal therapy. Follow-up studies with larger patient numbers are needed to further investigate this effect, using the study design presented here.

Accuracy of Computerized Optical Impression Making in Fabrication of Removable Dentures for Partially Edentulous Jaws: An In Vivo Feasibility Study.

The use of computerized optical impression making (COIM) for the fabrication of removable dentures for partially edentulous jaws is a rising trend in dental prosthetics. However, the accuracy of this method compared with that of traditional impression-making techniques remains uncertain. We therefore decided to evaluate the accuracy of COIM in the context of partially edentulous jaws in an in vivo setting. Twelve partially edentulous patients with different Kennedy classes underwent both a conventional impression (CI) and a computerized optical impression (COI) procedure. The CI was then digitized and compared with the COI data using 3D analysis software. Four different comparison situations were assessed: Whole Jaw (WJ), Mucosa with Residual Teeth (M_RT), Isolated Mucosa (IM), and Isolated Abutment Teeth (AT). Statistical analyses were conducted to evaluate group differences by quantifying the deviation values between the CIs and COIs. The mean deviations between the COIs and CIs varied significantly across the different comparison situations, with mucosal areas showing higher deviations than dental hard tissue. However, no statistically significant difference was found between the maxilla and mandible. Although COIM offers a no-pressure impression method that captures surfaces without irritation, it was found to capture mucosa less accurately than dental hard tissue. This discrepancy can likely be attributed to software algorithms that automatically filter out mobile tissues. Clinically, these findings suggest that caution is required when using COIM for prosthetics involving mucosal tissues as deviations could compromise the fit and longevity of the prosthetic appliance. Further research is warranted to assess the clinical relevance of these deviations.

Ultrafast Myocardial Principal Strain Ultrasound Elastography During Stress Tests: In Vitro Validation and In Vivo Feasibility.

Objective myocardial contractility assessment during stress tests aims to improve the diagnosis of myocardial ischemia. Tissue Doppler imaging (TDI) or optical flow (OF) speckle tracking echocardiography (STE) has been used to quantify myocardial contractility at rest. However, this is more challenging during stress tests due to image decorrelation at high heart rates. Moreover, stress tests imply a high frame rate which leads to a limited lateral field of view. Therefore, a large lateral field-of-view robust ultrafast myocardial regularized OF-TDI principal strain estimator has been developed for high-frame-rate echocardiography of coherently compounded transmitted diverging waves. The feasibility and accuracy of the proposed estimator were validated in vitro (using sonomicrometry as the gold standard) and in vivo stress experiments. Compared with OF strain imaging, the proposed estimator improved the accuracy of principal major and minor strains during stress tests, with an average contrast-to-noise ratio improvement of 4.4 ± 2.7 dB ( p -value < 0.01). Moreover, there was a significant correlation and a very close agreement between the proposed estimator and sonomicrometry for tested heart rates between 60 and 180 beats per minute (bpm). The averages ± standard deviations (STD) of R2 and biases ± STD between them were 0.96 ± 0.04 ( p -value < 0.01) and 0.01 ± 0.03% in the axial direction, respectively; and 0.94 ± 0.02 ( p -value < 0.01) and 0.04 ± 0.06% in the lateral direction, respectively. These results suggest that the proposed estimator could be useful clinically to provide an accurate and quantitative 2-D large lateral field-of-view myocardial strain assessment at high heart rates during stress echocardiography.

Blood Flow Quantification with High-Frame-Rate, Contrast-Enhanced Ultrasound Velocimetry in Stented Aortoiliac Arteries: In Vivo Feasibility.

Local flow patterns influence stent patency, while blood flow quantification in stents is challenging. The aim of this study was to investigate the feasibility of 2-D blood flow quantification using high-frame-rate, contrast-enhanced ultrasound (HFR-CEUS) and particle image velocimetry (PIV), or echoPIV, in patients with aortoiliac stents. HFR-CEUS measurements were performed at 129 locations in 62 patients. Two-dimensional blood flow velocity fields were obtained using echoPIV. Visual inspection was performed by five observers to evaluate feasibility. The contrast-to-background ratio and average vector correlation were calculated and compared between stented and native vessel segments. Flow quantification with echoPIV was feasible in 128 of 129 locations (99%), with optimal quantification in 40 of 129 locations (31%). Partial quantification was achieved in 88 of 129 locations (68%), where one or multiple limiting issues occurred (not related to the stent) including loss of correlation during systole (57/129), short vessel segments (20/129), loss of contrast during diastole (20/129) and shadow regions (20/129). The contrast-to-background ratio and vector correlation were lower downstream in the imaged blood vessel, independent of the location of the stent. In conclusion, echoPIV was feasible in stents placed in the aortoiliac region, and the stents did not adversely affect flow tracking.

Image-Free Fast Ultrasound for Measurement of Local Pulse Wave Velocity: In Vitro Validation and In Vivo Feasibility.

Local pulse wave velocity (PWV), a metric of the target artery's stiffness, has been emerging in its clinical value and adoption. State-of-the-art ultrasound technologies used to evaluate local PWV based on pulse waves' features are sophisticated, non-real-time, and are not amenable for field and resource-constrained settings. In this work, we present an image-free ultrasound system to measure local PWV in real-time by employing a pair of ultrasound transducer elements. An in vitro study was performed on the arterial phantom to: 1) characterize the design aspects of the system and 2) validate its accuracy against beat-by-beat (invasive) local PWV measured by a reference dual-element catheter. Furthermore, a repeatability and reproducibility study on 33 subjects (21-52 years) investigated the in vivo measurement feasibility from the carotid artery. With the experimentally deduced optimal design (frame-rate =500 Hz, RF sampling rate =125 MHz, LPF cutoff =14 Hz, and order =4 ), the system yielded repeatable beat-to-beat measurements (variability =1.9 % and over 15 cycles) and achieved a high accuracy (root-mean-square-error =0.19 m/s and absolute-percentage-error =2.4 %) over a wide range of PWVs (2.7-11.4 m/s) from the phantom. Subsequently, on human subjects, the intra- and inter-operator PWV measurements were highly repeatable (intraclass correlation coefficient ). The system does not impose a demand for special processors with high-computational power while offering real-time feedback on acquisition and measurement quality and provides local PWV online. Future large population and animal studies are required to establish the device's clinical usability.

Detection of Inflammatory and Homeostasis Biomarkers after Selective Removal of Carious Dentin-An In Vivo Feasibility Study.

Deep carious dentin lesions induce an immune reaction within the pulp-dentin complex, leading to the release of cytokines, which might be suitable biomarkers in pulp diagnostics. This in vivo feasibility study determines the concentration of different cytokines after selective removal of carious infected dentin (SCR). In our methodology, paired samples are obtained from 21 patients—each of them with two deep carious lesions at posterior teeth without clinical symptoms. After SCR, lesions are randomly assigned to treatment strategy: Group 1 (11 patients): Carious dentin is covered either with BiodentineTM (n = 11) or gutta-percha (n = 11) before using the adhesive OptibondTM FL. Group 2 (10 patients): The adhesives ClearfilTM SE Protect Bond (n = 10) or ClearfilTM SE Bond 2 (n = 10) are directly applied. Prepared cavities are rinsed with phosphate buffered saline containing 0.05% Tween 20 (10X) for five minutes immediately after SCR (visit 1) and eight weeks later (visit 2). Rinsing liquid is regained. Concentrations of IL-1β, IL-6, IL-10, C-reactive protein (CRP), TNF-α, IFN-γ, TIMP-1, -2, and MMP-7, -8, -9 are assessed by customized multiplex assays, evaluated with fluorescence analyzer. Non-parametric statistical analysis (Wilcoxon, Mann–Whitney U Test, p < 0.05) is performed (SPSS 25). Our results show that concentrations of CRP, IL-1β, IL-6, TIMP-1, -2, and MMPs were detectable. Median concentrations of CRP, IL-1β und IL-6 were significantly higher in visit 1 (304.9, 107.4, 3.8 pg/mL), compared to visit 2 (67.8, 2.3, 0.0 pg/mL; pi < 0.001). The study revealed that the non-invasive determination of cytokines from prepared dental cavities is possible.

Real-Time Light-Guided Vocal Fold Injection: An In Vivo Feasibility Study in a Canine Model.

ObjectivesThe transcutaneous approach is a good option for office-based vocal fold injection (VFI). However, precise localization requires extensive experience because the needle tip is invisible in small and complex laryngeal spaces. Recently, real-time light-guided VFI (RL-VFI) was proposed as a new technique that allows simultaneous injection under precise needle localization by light guidance. Herein, we aimed to verify the feasibility of RL-VFI in an in vivo canine model and explored its clinical usefulness.MethodsThe device for RL-VFI comprised a light source (light-emitting diode modules [10 W] of red color [650 nm]) and injectors (1.5 inches, 23 gauge). An adult male beagle was used for the experiment. After tracheostomy, a rigid laryngoscope was inserted and suspended to expose the larynx. A flexible naso-laryngoscopy system was used to visualize the vocal folds.ResultsRL-VFI was performed using various transcutaneous approaches, including the cricothyroid, transthyroid, and transhyoid approaches. Light guidance helped identify the path of the needle and prevent inadvertent penetration. The location of the needle tip was accurately indicated by the light. The illuminated needle could be easily placed at the intended points in the vocal fold with real-time visual-motor feedback. Hyaluronic acid could be simultaneously injected lateral to the vocal process under light guidance without manipulation of the device.ConclusionRL-VFI was found to be safe and feasible in an in vivo canine model, providing precise localization and visual-motor feedback. The clinical application of RL-VFI is expected to improve the safety and precision of VFI.

Cherenkov Luminescence Imaging for Assessment of Radioactive Plaque Position in Brachytherapy of Uveal Melanoma: An In Vivo Feasibility Study.

PurposeTo study the feasibility of using Cherenkov luminescence imaging (CLI) to evaluate and document ruthenium-106 plaque position during brachytherapy of uveal melanoma.MethodsRuthenium-106 decays by emitting high-energy beta particles. When the electrons pass through the eye, Cherenkov radiation generates a faint light that can be captured by highly sensitive cameras. Patients undergoing ruthenium-106 plaque brachytherapy for posteriorly located choroidal melanoma were examined by CLI, which was performed in complete darkness with an electron multiplying charged-coupled device camera mounted on a fundus camera modified for long exposures.ResultsTen patients with tumors ranging from 5.8 to 13.0 mm in largest basal diameter and 2.0 to 4.6 mm in height were included. The plaques had an activity between 0.035 and 0.089 MBq/mm2 at the time of examination (1–4 days after implantation). CLI revealed the actual plaque position by displaying a circular area of light in the fundus corresponding with the plaque area. The Cherenkov light surrounded the tumor as a halo, which showed some asymmetry when the plaque was slightly displaced. The light intensity correlated positively with plaque activity and negatively with tumor pigmentation. Exposure times between 30 and 60 seconds were required to display the plaque position and delineate the tumor area. The long exposures made it difficult to maintain stable eye fixation and optimal image quality.ConclusionsCLI is a novel method to assess and document ruthenium-106 plaque position in brachytherapy for uveal melanoma.Translational RelevanceOcular CLI may provide relevant radiation data during and after implantation of radioactive plaques, thus improving the accuracy of episcleral brachytherapy.

In Vivo Feasibility of Arterial Embolization with Permanent and Absorbable Suture: The FAIR-Embo Concept.

Arterial embolization has been shown to be effective and safe for the management of bleeding, especially for postpartum and pelvic traumatic bleeding. We propose to evaluate the proof of concept of feasibility and effectiveness of arterial embolization with absorbable and non-absorbable sutures in a porcine model. In the acute setting (n = 1), several different arteries (mesenteric, splenic, pharyngeal, kidney) were embolized using non-absorbable sutures (NAS): Mersutures™ braided sutures (polyethylene terephthalate). In the chronic setting (n = 3), only lower pole renal arteries were embolized. On the right side, NAS was used, whereas on the left side embolization was realized with absorbable suture (AS): Vicryl® braided suture (polyglactin 910). The chronic group was followed for 3months. The pigs received contrast-enhanced CT the day before embolization (D-1), after the embolization (D0), at 1 month and 3 months after embolization (M1 and M3); digital subtraction angiography (DSA) was done at D0 and M3 and histological analysis at M3. All vascular targets were effectively embolized without any pre- or postoperative complications. Both DSAs and CTs at M3 showed a 100% recanalization rate for the AS embolization and a partial reversal rate for the NAS embolization. A renal hypotrophy in the embolized region was observed during both the M1 and M3 scans for both sutures (AS and NAS) with a clear hypotrophy for the NAS embolized kidney. Embolization by AS and NAS (FAIR-Embo) is a feasible and effective treatment which opens up the possibility of global use of this inexpensive and widely available embolization agent.

In Vivo Feasibility Study of an Intra-Atrial Blood Pump for Partial Support of the Left Ventricle.

We are designing an intra-atrial pump (IAP) that will be affixed to the atrial septum and support the compromised left ventricle (LV) in patients with early-stage heart failure without harming the ventricular tissue. It will operate in parallel with the LV, drawing blood from the left atrium and unloading the LV. In previous hydraulic and hemodynamic studies, different blade geometries were tested for the IAP, and the hemodynamic results obtained using a mock circulatory loop showed that the IAP can successfully reduce end-diastolic volume and increase the total systemic flow rate. In the current study, we used a bovine model to validate the in vitro hemodynamic results and better understand how the IAP interacts with the cardiovascular system in vivo. Because this was the first study assessing the complete device in a living system, it was also necessary to determine the best manufacturing techniques and ideal sensor placements. In the bovine model, we were able to successfully implant the IAP across the atrial septum with the outflow graft connected to a peripheral artery. The implanted IAP was capable of providing partial support (1-3 L/min) in vivo. These results indicate that atrial cannulation is feasible and creates a beneficial hemodynamic environment.

Confocal Laser Endomicroscopy and Optical Coherence Tomography for the Diagnosis of Prostate Cancer: A Needle-Based, In Vivo Feasibility Study Protocol (IDEAL Phase 2A).

BackgroundFocal therapy for prostate cancer has been proposed as an alternative treatment to whole-gland therapies in selected men to diminish side effects in localized prostate cancer. As nowadays imaging cannot offer complete prostate cancer disease characterization, multicore systematic biopsies are recommended (transrectal or transperineal). Optical imaging techniques such as confocal laser endomicroscopy and optical coherence tomography allow in vivo, high-resolution imaging. Moreover, they can provide real-time visualization and analysis of tissue and have the potential to offer additive diagnostic information.ObjectiveThis study has 2 separate primary objectives. The first is to assess the technical feasibility and safety of in vivo focal imaging with confocal laser endomicroscopy and optical coherence tomography. The second is to identify and define characteristics of prostate cancer and normal prostate tissue in confocal laser endomicroscopy and optical coherence tomography imaging by comparing these images with the corresponding histopathology.MethodsIn this prospective, in vivo feasibility study, needle-based confocal laser endomicroscopy and optical coherence tomography imaging will be performed before transperineal template mapping biopsy or radical prostatectomy. First, confocal laser endomicroscopy and optical coherence tomography will be performed in 4 patients (2 for each imaging modality) undergoing transperineal template mapping biopsy to assess the feasibility and safety of confocal laser endomicroscopy and optical coherence tomography. If proven to be safe and feasible, confocal laser endomicroscopy and optical coherence tomography will be performed in 10 patients (5 for each imaging modality) undergoing radical prostatectomy. Confocal laser endomicroscopy and optical coherence tomography images will be analyzed by independent, blinded observers. Confocal laser endomicroscopy– and optical coherence tomography–based qualitative and quantitative characteristics and histopathology will be compared. The study complies with the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) stage 2a recommendations.ResultsAt present, the study is enrolling patients and results and outcomes are expected in 2019.ConclusionsConfocal laser endomicroscopy and optical coherence tomography are promising optical imaging techniques that can visualize and analyze tissue structure, possible tumor grade, and architecture in real time. They can potentially provide real-time, high-resolution microscopic imaging and tissue characteristics of prostate cancer in conjunction with magnetic resonance imaging or transrectal ultrasound fusion-guided biopsy procedures. This study will provide insight into the feasibility and tissue-specific characteristics of confocal laser endomicroscopy and optical coherence tomography for real-time optical analysis of prostate cancer.Trial RegistrationClinicalTrials.gov NCT03253458; https://clinicaltrials.gov/ct2/show/NCT03253458 (Archived by WebCite at http://www.webcitation.org/6z9owM66B)Registered Report IdentifierRR1-10.2196/9813

Quantitative Analysis of Helical Flow with Accuracy Using Ultrasound Speckle Image Velocimetry: In Vitro and in Vivo Feasibility Studies

Venous valve dysfunction and induced secondary abnormal flows are closely associated with venous diseases. Thus, detailed analysis of venous valvular flow is invaluable from biological and medical perspectives. However, most of the previous studies on venous perivalvular flows were based on qualitative analysis. On the contrary, quantitative analysis of perivalvular flows has not been fully understood. In this study, we used the ultrasound speckle image velocimetry (SIV) technique, which utilizes the speckle patterns of red blood cells (RBCs) created by ultrasound waves to measure 3-D valvular flows quantitatively. The flow structures obtained with the proposed SIV technique for an in vitro model were compared with those obtained by numerical simulation and the color Doppler method to validate the measurement accuracy of the ultrasound SIV technique. Blood flow in the human great saphenous vein was then measured at various distances from the valve with and without exercise. 3-D valvular flow was analyzed in accordance with the dimensionless index, helical intensity. The results obtained by the proposed method matched well with those obtained by numerical simulation and the color Doppler method. The hemodynamic characteristics of 3-D valvular helical flow which were analyzed experimentally using the SIV method would be used for quantitative diagnosis of venous valvular diseases.

Swine Atrioventricular Node Ablation Using Stereotactic Radiosurgery: Methods and In Vivo Feasibility Investigation for Catheter-Free Ablation of Cardiac Arrhythmias.

BackgroundLinear accelerator–based stereotactic radiosurgery delivered to cardiac arrhythmogenic foci could be a promising catheter‐free ablation modality. We tested the feasibility of in vivo atrioventricular (AV) node ablation in swine using stereotactic radiosurgery.Methods and ResultsFive Large White breed swine (weight 40–75 kg; 4 females) were studied. Single‐chamber St Jude pacemakers were implanted in each pig. The pigs were placed under general anesthesia, and coronary/cardiac computed tomography simulation scans were performed to localize the AV node. Cone beam computed tomography was used for target positioning. Stereotactic radiosurgery doses ranging from 35 to 40 Gy were delivered by a linear accelerator to the AV node, and the pigs were followed up with weekly pacemaker interrogations to observe for potential electrocardiographic changes. Once changes were observed, the pigs were euthanized, and pathology specimens of various tissues, including the AV node and tissues surrounding the AV node, were taken to study the effects of radiation. All 5 pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic inspection did not reveal damage to the myocardium, and pigs had preserved systolic function on echocardiography. Immunostaining revealed fibrosis in the target region of the AV node, whereas no fibrosis was detected in the nontargeted regions.ConclusionsCatheter‐free radioablation using linear accelerator–based stereotactic radiosurgery is feasible in an intact swine model.

Glass-Fiber-based MR-safe Guidewire for MR Imaging-guided Endovascular Interventions: In Vitro and Preclinical in Vivo Feasibility Study.

Purpose To evaluate glass-fiber-based guidewires that are safe for magnetic resonance (MR) imaging-guided endovascular interventions by using a phantom and an in vivo swine model. Materials and Methods MR imaging-safe guidewires were made from micropultruded glass and/or aramid fibers and epoxy resin with diameters of 0.89 mm (0.035 inch) for standard and stiff guidewires and 0.36 mm (0.014 inch) for micro guidewires. MR imaging visibility and mechanical properties were assessed in a pulsatile flow model. After approval was obtained from the institutional animal care and use committee, MR imaging guidewires were evaluated for standard endovascular procedures in nine pigs. Real-time steady-state free-precession sequences were used for MR imaging-guided catheterization, balloon dilation, and stent implantation into aorto-iliac/visceral arteries and the vena cava (temporal resolution, five images per second; and spatial resolution, 150-mm field of view, and 128 × 128 matrix) with a 1.5-T clinical imager. Visualization with the guidewires was rated on a four-point scale, handling was rated on a three-point scale, and catheterization times for different vessel regions were determined by two interventional radiologists. Afterward, handling ratings and catheterization times were obtained for standard nitinol guidewires during x-ray-based fluoroscopy. Cannulation times, signal intensity in each vessel region, and visualization and handling ratings were measured for the MR imaging guidewires. Bland-Altman analysis was performed for inter- and intraobserver variability of cannulation time. Spearman rank correlation was used to compare handling of MR imaging guidewires and standard nitinol guidewires. Results MR imaging guidewires were characterized by good to excellent visibility, with a continuous artifact of 2 mm in diameter and 4 × 8-mm ball-shaped tip marker. Stiffness, flexibility, and guidance reflected comparable times for all in vitro and in vivo procedures with both the MR imaging and standard nitinol guidewires. Standard and micro MR imaging guidewires were most suitable for the iliac crossover maneuver. Phantom visceral artery cannulation was easier with standard and micro MR imaging guidewires. The stiff MR imaging guidewire provided the best support for cannulation of the swine aorta and vena cava. All interventional procedures were performed successfully without complications. Conclusion Preliminary results showed that the use of glass-fiber-based guidewires for evaluation of MR imaging-guided endovascular interventions is technically feasible and safe in a swine model, and potentially, in humans. © RSNA, 2017 Online supplemental material is available for this article.

Non-Invasive Identification of Vulnerable Atherosclerotic Plaques Using Texture Analysis in Ultrasound Carotid Elastography: An In Vivo Feasibility Study Validated by Magnetic Resonance Imaging

The aims of this study were to quantify the textural information of strain rate images in ultrasound carotid elastography and evaluate the feasibility of using the textural features in discriminating stable and vulnerable plaques with magnetic resonance imaging as an in vivo reference. Ultrasound radiofrequency data were acquired in 80 carotid plaques from 52 patients, mainly in the longitudinal imaging view, and axial strain rate images were estimated with an ultrasound carotid elastography technique based on an optical flow algorithm. Four textural features of strain rate images—contrast, homogeneity, correlation and angular second moment—were derived based on the gray-level co-occurrence matrix in plaque regions to quantify the deformation distribution pattern. Conventional elastographic indices based on the magnitude of the absolute strain rate, such as the maximum, mean, median, standard deviation and 99th percentile of the axial strain rate, were also obtained for comparison. Composition measurement with magnetic resonance imaging identified 30 plaques as vulnerable and the other 50 as stable. The four textural features, as well as the magnitude of strain rate images, significantly differed between the two groups of plaques. The best performing features for plaque classification were found to be the contrast and 99th percentile of the absolute strain rate, with a comparative area under the receiver operating characteristic curve of 0.81; a slightly higher maximum accuracy of plaque classification can be achieved by the textural feature of contrast (83.8% vs. 81.3%). The results indicate that the use of texture analysis in plaque classification is feasible and that larger local deformations and higher level of complexity in deformation patterns (associated with the elastic or stiffness heterogeneity of plaque tissues) are more likely to occur in vulnerable plaques.

High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography.

Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters.

Computer-Aided Prostate Cancer Detection Using Ultrasound RF Time Series: In Vivo Feasibility Study.

This paper presents the results of a computer-aided intervention solution to demonstrate the application of RF time series for characterization of prostate cancer, in vivo. We pre-process RF time series features extracted from 14 patients using hierarchical clustering to remove possible outliers. Then, we demonstrate that the mean central frequency and wavelet features extracted from a group of patients can be used to build a nonlinear classifier which can be applied successfully to differentiate between cancerous and normal tissue regions of an unseen patient. In a cross-validation strategy, we show an average area under receiver operating characteristic curve (AUC) of 0.93 and classification accuracy of 80%. To validate our results, we present a detailed ultrasound to histology registration framework. Ultrasound RF time series results in differentiation of cancerous and normal tissue with high AUC.

Potential of Magnetic Resonance-guided Focused Ultrasound for Intracranial Hemorrhage: An In Vivo Feasibility Study

Because of the paucity of effective treatments for intracranial hemorrhage (ICH), the mortality rate remains at 40%-60%. A novel application of magnetic resonance-guided focused ultrasound (MRgFUS) for ICH may offer an alternative noninvasive treatment through the precise delivery of FUS under real-time MR imaging (MRI) guidance. The purpose of the present study was to optimize the parameters for rapid, effective, and safe trans-skull large clot liquefaction using invivo porcine and exvivo human skull models to provide a clinically relevant proof of concept. The transcranial effectiveness of MRgFUS was tested exvivo by introducing a porcine blood clot into a human skull, without introducing tissue plasminogen activator (tPA). We used an experimental human head device to deliver pulsed FUS sonications at an acoustic power of 600-900W for 5-10seconds. A 3-mL clot was also introduced in a porcine brain and sonicated invivo with one 5-second pulse of 700W through a bone window or with 3000W when treated through an exvivo human skull. Treatment targeting was guided by MRI, and the tissue temperature was monitored online. Liquefied volumes were measured as hyperintense regions on T2-weighted MR images. In both invivo porcine blood clot through a craniectomy model and the porcine clot in an exvivo human skull model targeted clot liquefaction was achieved, with only marginal increase in temperature in the surrounding tissue. Our results demonstrate the feasibility of fast, efficient, and safe thrombolysis in an invivo porcine model of ICH and in 2 exvivo models using a human skull, without introducing tPA. Future studies will further optimize parameters and assess the nature of sonication-mediated versus natural clot lysis, the risk of rebleeding, the potential effect on the adjacent parenchyma, and the chemical and toxicity profiles of resulting lysate particles.