real-time-monitoring-high-intensity-focused-ultrasound-hifu-ablation

Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of <em>In Vitro</em> Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU)

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An ...

Columbia University

Columbia College

There is evidence that quantitative ultrasound (QUS) at the proximal femur involves waves propagating circumferentially in the cortical shell. These waves, in theory, convey information on bone geometrical and material characteristics and thus have the potential to improve fracture risk prediction. In this work, the time-of-flight (TOF) of the first arriving signal (FAS) that corresponds to waves propagating circumferentially is considered. The relationships between the TOF of the FAS and geometrical features of the femoral neck are investigated. Five neck cross-sections from 11 human femurs from females (>65y) were extracted from 3-D X-ray quantitative computed tomography (XR-QCT) datasets. Geometrical parameters including cross-sectional area (CSA), minimum moment of inertia (I(min)) and section modulus (Z) were computed from femoral neck cross-section images. Two-dimensional numerical simulation of US propagation through femoral neck was performed and TOF of the FAS was estimated. TOF was best correlated with I(min): R(2)=0.82 (p=10(-4); RMSE=1390mm(4) [13%]) in the region between proximal and mid-femoral neck and with Z: R(2)=0.55 (p<10(-2); RMSE=480mm(3) [17%]) and CSA: R(2)=0.62 (p<5.10(-3); RMSE=22mm(2) [7%]) in the mid-femoral neck. The results suggest that QUS has the potential to assess proximal femur strength based on estimates of geometrical properties of the cortical shell.

Potential of first arriving signal to assess cortical bone geometry at the Hip with QUS: a model based study.

Velocity of ultrasound waves has proved to be a useful indicator of bone biomechanical competence. A detailed understanding of the dependence of ultrasound parameters such as velocity on bone characteristics is a key to the development of bone quantitative ultrasound (QUS). The objective of this study is to investigate the relative contributions of porosity and mineralized matrix properties to the bulk compressional wave velocity (BCV) along the long bone axis. Cross-sectional slabs from the diaphysis of four human femurs were included in the study. Seven regions of interest (ROIs) were selected in each slab. BCV was measured in through-transmission at 5 MHz. Impedance of the mineralized matrix (Z(m)) and porosity (Por) were obtained from 50 MHz scanning acoustic microscopy. Por and Z(m) had comparable effects on BCV along the bone axis (R=-0.57 and R=0.72, respectively).

Relative contributions of porosity and mineralized matrix properties to the bulk axial ultrasonic wave velocity in human cortical bone.

A significant risk of femoral neck (FN) fracture exists for men and women with an areal bone mineral density (aBMD) higher than the osteoporotic range, as measured with dual-energy X-ray absorptiometry (DXA). Separately measuring the cortical and trabecular FN compartments and combining the results would likely be a critical aspect of enhancing the diagnostic capabilities of a new technique. Because the cortical shell determines a large part of FN strength a novel quantitative ultrasound (QUS) technique that probes the FN cortical compartment was implemented. The sensitivity of the method to variations of FN cortical properties and FN strength was tested. Nine femurs (women, mean age 83 years) were subjected to QUS to measure the through transmission time-of-flight (TOF) at the FN and mechanical tests to assess strength. Quantitative computed tomography (QCT) scans were performed to enable analysis of the dependence of TOF on bone parameters. DXA was also performed for reference. An ultrasound wave propagating circumferentially in the cortical shell was measured in all specimens. Its TOF was not influenced by the properties of the trabecular compartment. Averaged TOF for nine FN measurement positions/orientations was significantly correlated to strength (R2  = 0.79) and FN cortical QCT variables: total BMD (R(2)  = 0.54); regional BMD in the inferoanterior (R2  = 0.90) and superoanterior (R2  = 0.57) quadrants; and moment of inertia (R2  = 0.71). The results of this study demonstrate that QUS can perform a targeted measurement of the FN cortical compartment. Because the method involves mechanical guided waves, the QUS variable is related to the geometric and material properties of the cortical shell (cortical thickness, tissue elasticity, and porosity). This work opens the way to a multimodal QUS assessment of the proximal femur, combining our approach targeting the cortical shell with the existing modality sensitive to the trabecular compartment. In vivo feasibility of our approach has to be confirmed with experimental data in patients.

Quantitative ultrasound of cortical bone in the femoral neck predicts femur strength: results of a pilot study.

Quantitative ultrasound assessment of the cortical compartment of the femur neck (FN) is investigated with the goal of achieving enhanced fracture risk prediction. Measurements at the FN are influenced by bone size, shape and material properties. The work described here was aimed at determining which FN material properties have a significant impact on ultrasound propagation around 0.5 MHz and assessing the relevancy of different models. A methodology for the modeling of ultrasound propagation in the FN, with a focus on the modeling of bone elastic properties based on scanning acoustic microscopy data, is introduced. It is found that the first-arriving ultrasound signal measured in through-transmission at the FN is not influenced by trabecular bone properties or by the heterogeneities of the cortical bone mineralized matrix. In contrast, the signal is sensitive to variations in cortical porosity, which can, to a certain extent, be accounted for by effective properties calculated with the Mori-Tanaka method.

Modeling of femoral neck cortical bone for the numerical simulation of ultrasound propagation.

Harmonic motion imaging for focused ultrasound (HMIFU) utilizes an amplitude-modulated HIFU beam to induce a localized focal oscillatory motion simultaneously estimated. The objective of this study is to develop and show the feasibility of a novel fast beamforming algorithm for image reconstruction using GPU-based sparse-matrix operation with real-time feedback. In this study, the algorithm was implemented onto a fully integrated, clinically relevant HMIFU system. A single divergent transmit beam was used while fast beamforming was implemented using a GPU-based delay-and-sum method and a sparse-matrix operation. Axial HMI displacements were then estimated from the RF signals using a 1-D normalized cross-correlation method and streamed to a graphic user interface with frame rates up to 15 Hz, a 100-fold increase compared to conventional CPU-based processing. The real-time feedback rate does not require interrupting the HIFU treatment. Results in phantom experiments showed reproducible HMI images and monitoring of 22 in vitro HIFU treatments using the new 2-D system demonstrated reproducible displacement imaging, and monitoring of 22 in vitro HIFU treatments using the new 2-D system showed a consistent average focal displacement decrease of 46.7 ±14.6% during lesion formation. Complementary focal temperature monitoring also indicated an average rate of displacement increase and decrease with focal temperature at 0.84±1.15%/(°)C, and 2.03±0.93%/(°)C , respectively. These results reinforce the HMIFU capability of estimating and monitoring stiffness related changes in real time. Current ongoing studies include clinical translation of the presented system for monitoring of HIFU treatment for breast and pancreatic tumor applications.

Sparse matrix beamforming and image reconstruction for 2-D HIFU monitoring using harmonic motion imaging for focused ultrasound (HMIFU) with in vitro validation.

Intracardiac echocardiography (ICE) is a useful imaging modality which is used during RF ablation procedures to identify anatomical structures. Utilizing ICE in conjunction with myocardial elastography (ME) can provide additional information on the mechanical properties of cardiac tissue and provide information on mechanical changes caused by ablation. The objective of this study was to demonstrate that ICE can be used at high frame rate using a diverging beam transmit sequence to image myocardial strain and differentiate myocardial tissue properties before, during, and after ablation for a clinical ablation procedure. In this feasibility study, three normal canines and eight patients with atrial fibrillation (AF) were studied in vivo. A 5.8-MHz ICE transducer was used to image the heart with a diverging beam transmit method achieving 1200 frames per second (fps). Cumulative axial displacement estimation was performed using 1-D cross-correlation with a window size of 2.7 mm and 95% overlap. Axial cumulative strains were estimated in the left atrium (LA) and right atrium (RA) using a least-squares estimator with a kernel of 2 mm on the axial displacements. In the canine case, radial thickening was detected in the lateral wall and in the interatrial septum during LA emptying. For AF patients, the mean absolute strain in the ablated region was lower (6.7 ± 3.1%) than before the ablation (17.4 ± 9.3%) in LA at the end of the LA emptying phase. In the cavotricuspid isthmus (CTI) region, mean absolute strain magnitude at the end of the RA emptying phase was found to be higher during ablation (43.0 ± 18.1%) compared with after ablation (33.7 ± 15.8%). Myocardial strains in the LA of an AF patient were approximately 2.6 times lower in the ablated region than before ablation. This initial feasibility indicates that ME can be used as a new imaging modality in conjunction with ICE in RF ablation guidance and lesion monitoring.

Intracardiac myocardial elastography in canines and humans in vivo.

Noninvasive measurement of mechanical properties of biological tissues in vivo could play a significant role in improving the current understanding of tissue biomechanics. In this study, we propose a method for measuring elastic properties non-invasively by using internal indentation as generated by harmonic motion imaging (HMI). In HMI, an oscillating acoustic radiation force is produced by a focused ultrasound transducer at the focal region, and the resulting displacements are estimated by tracking radiofrequency signals acquired by an imaging transducer. In this study, the focal spot region was modeled as a rigid cylindrical piston that exerts an oscillatory, uniform internal force to the underlying tissue. The HMI elastic modulus EHMI was defined as the ratio of the applied force to the axial strain measured by 1D ultrasound imaging. The accuracy and the precision of the EHMI estimate were assessed both numerically and experimentally in polyacrylamide tissue-mimicking phantoms. Initial feasibility of this method in soft tissues was also shown in canine liver specimens in vitro. Very good correlation and agreement was found between the measured Young's modulus and the HMI modulus in the numerical study (r(2) > 0.99, relative error <10%) and on polyacrylamide gels (r(2) = 0.95, relative error <24%). The average HMI modulus on five liver samples was found to EHMI = 2.62  ±  0.41 kPa, compared to EMechTesting = 4.2  ±  2.58 kPa measured by rheometry. This study has demonstrated for the first time the initial feasibility of a non-invasive, model-independent method to estimate local elastic properties of biological tissues at a submillimeter scale using an internal indentation-like approach. Ongoing studies include in vitro experiments in a larger number of samples and feasibility testing in in vivo models as well as pathological human specimens.

Non-contact, ultrasound-based indentation method for measuring elastic properties of biological tissues using harmonic motion imaging (HMI).

Atrial arrhythmias affect millions of people worldwide. Characterization and study of arrhythmias in the atria in the clinic is currently performed point by point using mapping catheters capable of generating maps of the electrical activation rate or cycle length. In this paper, we describe a new ultrasound-based mapping technique called electromechanical cycle length mapping (ECLM) capable of estimating the electromechanical activation rate, or cycle length, i.e., the rate of the mechanical activation of the myocardium which follows the electrical activation. ECLM relies on frequency analysis of the incremental strain within the atria and can be performed in a single acquisition. ECLM was validated in a canine model paced from the left atrial appendage, against pacing rates within the reported range of cycle lengths previously measured during atrial arrhythmias such as atrial fibrillation. Correlation between the global estimated electromechanical cycle lengths and pacing rates was shown to be excellent (slope = 0.983, intercept = 3.91, r(2) = 0.9999). The effect of the number of cardiac cycles on the performance of ECLM was also investigated and the reproducibility of ECLM was demonstrated (error between consecutive acquisitions for all pacing rates: 6.3 ± 4.3%). These findings indicate the potential of ECLM for noninvasively characterizing atrial arrhythmias and provide feedback on the treatment planning of catheter ablation procedures in the clinic.

Article	Year
Potential of first arriving signal to assess cortical bone geometry at the Hip with QUS: a model based study. Ultrasound in medicine & biology\| PubMed ID: 20350690	2010
Relative contributions of porosity and mineralized matrix properties to the bulk axial ultrasonic wave velocity in human cortical bone. Ultrasonics\| PubMed ID: 22182403	2012
Quantitative ultrasound of cortical bone in the femoral neck predicts femur strength: results of a pilot study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research\| PubMed ID: 22915370	2013
Modeling of femoral neck cortical bone for the numerical simulation of ultrasound propagation. Ultrasound in medicine & biology\| PubMed ID: 24486239	2014
Sparse matrix beamforming and image reconstruction for 2-D HIFU monitoring using harmonic motion imaging for focused ultrasound (HMIFU) with in vitro validation. IEEE transactions on medical imaging\| PubMed ID: 24960528	2014
Intracardiac myocardial elastography in canines and humans in vivo. IEEE transactions on ultrasonics, ferroelectrics, and frequency control\| PubMed ID: 25643083	2015
Non-contact, ultrasound-based indentation method for measuring elastic properties of biological tissues using harmonic motion imaging (HMI). Physics in medicine and biology\| PubMed ID: 25776065	2015
Atrial electromechanical cycle length mapping in paced canine hearts in vivo. IEEE transactions on ultrasonics, ferroelectrics, and frequency control\| PubMed ID: 26168174	2015

Julien Grondin

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