MRI-monitored cryosurgery in the rabbit brain

The inability to observe the transient, irregular shape of the frozen region that develops during cryosurgery has inhibited the application of this surgical technique to the treatment of tumors in the brain and deep in visceral organs. We used proton NMR spin-echo and spoiled gradient-echo imaging to monitor the development of frozen lesions during cryosurgery in the rabbit brain and the resulting postervosurgical changes up to 4 hr after freezing. Spoiled gradient-echo images (TE = 14 ms; TR = 50 ms) were acquired during freezing and thawing at a rate of 15 s/slice. Although the frozen region itself is invisible in MR images, its presence is distinguished easily from the surrounding unfrozen soft tissue because of the large contrast difference between frozen and unfrozen regions. T₂-weighted spin-echo images (TE = 100 ms, TR = 2 s) obtained after thawing suggest that edema forms first at the margin of the region that was frozen (cryolesion) and then moves into the region's core. Histological examination showed complete necrosis in the cryolesion and a sharp transition to undamaged tissue at the margin of the lesion and its image. Blood-brain barrier (BBB) damage was investigated using gadolinium-DTPA. The region of edema in the T₂-weighted spin-echo images was coincident with the area of BBB damage in the Gd-DTPA-enhanced T₁-weighted spin-echo images (TE = 33 ms, TR = 400 ms) and both were distinguishable as areas of high signal relative to the surrounding normal tissue. The results of these experiments indicate that MR can both effectively monitor the cryosurgical freezing and thawing cycle and characterize the postcryosurgical changes in tissue during follow-up.     

低温微创手术治疗探头周围组织温度分布研究

采用低温方法对人体深部肿瘤进行杀伤时,既要求对肿瘤组织有最大的杀伤效果,又要保证正常组织,特别是一些重要器官组织,能免受冷冻伤害。文中对冷冻治疗探头形成冰球的大小、以及冻结界面周围组织温度分布进行传热分析和测试,以给出安全区和危险区的范围,这可以为外科手术医生设计低温手术方案提供参考依据。     

Effect of fasting and food intake on magnetization transfer of human liver tissue

Magnetization transfer (MT) technique is a promising method in differential diagnosis of diseases in parenchymal tissues. Basic knowledge about circumstances and elementary factors that influence MT and its parameters is still insufficient, however. Having a meal before the magnetic resonance (MR) examination could change liver MT parameters compared to fasting state through alteration in liver perfusion, blood flow, and content of portal blood (proteins and other derivates from a meal). If MT parameters can be altered by a meal, then MR liver studies should always be performed after fasting. Before MRI examinations we examined three healthy volunteers after a high-fat meal with Doppler ultrasound technique to find out duration and magnitude of changes in portal blood flow. Duration of ≥50% increased peak-flow value compared to fasting state in portal vein was >90 min, which is enough for our MR examination. With a low-field 0.1-T MR imager we examined 10 healthy volunteers after a short (range from 3 h 45 min to 17 h 30 min) fast and also immediately after a high-fat meal. Magnetization transfer parameters, magnetization transfer ratio (MTR) and magnetization transfer rate R_wm of liver tissue were determined. MTR changed significantly (Student paired two-tailed t-test, p = .0044) after a meal, but R_wm did not (p = .0952). We recommend a 4 h fast before MR examination that aims to determine the MTR of liver tissue.     

Quantitative MR temperature monitoring of high-intensity focused ultrasound therapy

A new quantitative method has been developed for real-time mapping of temperature changes induced by high intensity focused ultrasound (HIFU). It is based on the temperature dependence of the T1 relaxation time and the equilibrium magnetization. To calibrate the temperature measurement, the functional relationship between T1 and temperature was examined in different samples of porcine muscle and fatty tissue. The method was validated by a comparison of calculated temperature maps with fiber-optic measurements in heated muscle tissue. The experiment showed that the accuracy of the MR method for temperature measurements is better than 1 degree C. Since the acquisition time of the employed MR sequence takes only 3 s per slice and the calculation of the temperature map can be performed within seconds, the imaging technique works nearly in real-time. The temperature measurement could be realized during HIFU showing no disturbances by ultrasound sonication. In comparison to other MR approaches, the advantages of the introduced method lie in a sufficient accuracy and time resolution combined with a reasonable robustness against motion as well as the feasibility for temperature monitoring in fatty tissues.     

Validation of estimated 3D temperature maps during hepatic cryo surgery.

A simple model for estimating temperature distribution within the frozen region during cryo ablation was tested for accuracy. Freezing experiments were conducted in both ex vivo and in vivo porcine livers. Temperature was measured during freezing using a fiber-optic temperature sensor. Three-dimensional MR images were obtained at the end of each freezing cycle. From the MR image volumes, three-dimensional temperature maps were calculated numerically using a simplified bio-heat model. Estimated temperatures were compared to measured temperatures. The median difference between measured and estimated temperature was 3.03 degrees C. The median distance from a sensor element to the closest point on a isotherm surface with the corresponding estimated temperature was 0.70 mm. The accuracy of this model is acceptable. Temperature maps as outlined here may be used for monitoring of cryotherapy in order to increase clinical effectiveness.     

Improved image contrast with mangafodipir trisodium (MnDPDP) during MR-guided percutaneous cryosurgery of the liver

The present study was undertaken to measure the gain observed in the liver-to-tumor contrast of perioperative images when using mangafodipir trisodium, a liver-specific contrast agent, during percutaneous cryosurgery of the liver performed under the guidance of magnetic resonance images. Retrospective quantitative analyses of MR images were performed on eleven patients having a total of 30 liver tumors treated by MR-guided percutaneous cryosurgery. An initial group of four patients were treated with no contrast agent, and was compared with a second group of 7 patients who received an intravenous injection of 5 microM/kg of mangafodipir for their cryosurgery. The percutaneous cryosurgery was monitored under the near-real-time-imaging mode of a 0.5T open-configuration MRI system using a T(1)-weighted Gradient-recalled echo pulse sequence. A significant improvement in the liver-to-tumor contrast-to-noise ratio was observed with mangafodipir (p < 0.05, paired t test) in 0.5T preoperative images. Along with the stability of the mangafodipir contrast enhancement during the entire cryosurgical procedure, the resulting gain in contrast allowed for better visualizing the presence of residual untreated tumor margins at the periphery of the cryosurgery iceball directly from perioperative images acquired with patients under narcosis. Consequently, it not only became easier for the interventionalist to determine the need for an additional cryoprobe to increase the size of the iceball during the procedure, but also to decide on the appropriate end point of the cryosurgery.     

The use of view angle tilting to reduce distortions in magnetic resonance imaging of cryosurgery

Susceptibility artifacts from magnetic resonance (MR)-compatible cryoprobes can distort MR images of iceballs. In this work, we investigate the ability of view angle tilting (VAT) to correct susceptibility induced distortions in MR images of cryosurgery. The efficacy of VAT was tested in an ex vivo bovine liver model of cryosurgery using MR-compatible cryoprobes. Artifacts on high bandwidth fast spin echo images of freezing obtained with and without VAT were compared with photographs of the actual iceball shape and size. In vivo imaging with VAT was demonstrated during percutaneous MR-guided cryosurgery of pig liver and brain. VAT was most successful in reducing probe and iceball distortions when the imaging plane was normal to the cryoprobe, and the cryoprobe was perpendicular to the main magnetic field of the scanner. VAT had the greatest benefit when used to correct MR images of freezing when the surface of the iceball was relatively near to the cryoprobe. For large iceballs, the artifact was small so the VAT correction was less important. We conclude that VAT significantly reduced distortions in the shape of the signal void corresponding to the extent of freezing visualized during MR-guided cryosurgery. This improved ability to visualize the exact location of the cryoprobe, as well as the precise shape of the iceball, particularly during initial freezing when the iceball is small, has potential to significantly improve the accuracy of MR-guided cryosurgery of small lesions, and the accuracy of MR-assisted temperature calculations that are based on precise imaging of the probe location, and boundary geometry of the iceball.     

A multi-gate time-of-flight technique for estimation of temperature distribution in heated tissue: theory and computer simulation

Non-invasive determination of temperature distribution in biological media is important in many heating-related studies, such as thermal treatment. In this paper, we present an in vitro ultrasound technique for estimation of temperature distribution in heated tissue. Our technique consists of two major steps: (1) using multiple time gates to track echo signals scattered from tissue regions at different depths; (2) estimating temperature distribution based on heating-induced changes of arrival times of echo signals scattered from the targeted tissue regions. We use the conventional cross-correlation approach to track echoes. For temperature estimation, we have developed an iterative method that takes into account the influences of thermal expansion and heating-induced change in the speed of sound on the time of flight. We have introduced a concept of thermal sensitivity of the time of flight and used it to derive a theoretical formula that relates the achievable accuracy on the estimation of tissue temperature to seven parameters. The seven parameters are tissue thermal sensitivity of the time of flight, signal-to-noise ratio, bandwidth and center frequency of the signal, degree of signal decorrelation induced by changes in tissue physical properties during tissue heating, and widths and spacing of the time gates. We tested our technique by computer simulation, using a random discrete scatterer model and temperature distribution data acquired in our laser heating experiments on prostate tissue of live dog. Simulation results showed that our technique could accurately estimate the temperature distribution in the heated tissue. Our technique is fast in terms of computation and could be used as a research tool for in vitro real-time monitoring of temperature distribution in tissue under hyperthermal heating.     

HIFU治疗中换能器驱动电功率变化机制及规律*

高强度聚焦超声(HIFU)治疗中的驱动电功率对治疗效率起着非常关键的作用,驱动电功率控制的精准性势必会影响治疗的效率和安全性。前期研究表明：HIFU治疗过程中焦域瞬态物理特性的变化会导致换能器的负载阻抗发生变化,进而影响HIFU驱动电功率,但驱动电功率与焦域瞬态物理特性之间的影响关系及规律尚不明确。该文基于电压、电流传感器、空化检测探头和温度传感器等器件,构建了一种HIFU治疗中驱动电功率实时监测及焦域声空化、温度检测系统。基于该实验研究系统,以离体牛心组织作为HIFU辐照对象,分别研究了HIFU焦域温度变化、声空化及组织损伤与驱动电功率之间的变化关系及规律。研究结果表明：当焦域温度升高时,驱动电功率缓慢上升,驱动电功率与温度变化有良好的相关性;当空化产生时,驱动电功率出现明显的波动;当组织出现损伤时,驱动电功率呈陡然下降的变化。三种情景下,驱动电功率变化有明显区别,这有望为区分HIFU治疗过程中焦域处发生损伤和空化以及实时监测靶组织损伤程度提供一种新的解决方案。     

Application of fuzzy c-means segmentation technique for tissue differentiation in MR images of a hemorrhagic glioblastoma multiforme

The application of a raw data-based, operator-independent MR segmentation technique to differentiate boundaries of tumor from edema or hemorrhage is demonstrated. A case of a glioblastoma multiforme with gross and histopathologic correlation is presented. The MR image data set was segmented into tissue classes based on three different MR weighted image parameters (T₁-, proton density-, and T₂-weighted) using unsupervised fuzzy c-means (FCM) clustering algorithm technique for pattern recognition. A radiological examination of the MR images and correlation with fuzzy clustering segmentations was performed. Results were confirmed by gross and histopathology which, to the best of our knowledge, reports the first application of this demanding approach. Based on the results of neuropathologic correlation, the application of FCM MR image segmentation to several MR images of a glioblastoma multiforme represents a viable technique for displaying diagnostically relevant tissue contrast information used in 3D volume reconstruction. With this technique, it is possible to generate segmentation images that display clinically important neuroanatomic and neuropathologic tissue contrast information from raw MR image data.     

Referenceless PRFS MR Thermometry Using Partial Separability Model

Many areas of magnetic resonance (MR)-guided thermal therapy research would benefit from temperature maps with high spatial and temporal resolution. Conventional thermometry relies on the subtraction of baseline images, which makes it sensitive to tissue motion and frequency drift during the course of treatment. For another case is the limit of magnetic resonance imaging sampling speed, it is hard to accurately achieve MR thermometry with high spatiotemporal resolution especially for dynamic organs. To address these issues, a novel method for MR thermometry is presented by exploiting the data redundancy based on partial separability (PS) model and the referenceless thermometry. The PS model highly sparse sample two datasets in the (k–t) space for image reconstruction, which respectively determine the spatial and temporal resolutions. After the phase information is extracted from the images reconstructed by the PS model, the background phase outside the heated region from each acquired phase image through a polynomial fitting is estimated. Extrapolation of the polynomial to the heated region serves as the background phase estimate, which is then subtracted from the actual phase. The thermometry results showed that this method could accurately capture the dynamic change of MR thermometric images with 1.5 mm × 1.5 mm spatial resolution and 250 ms temporal resolution, respectively. The in vivo experiment of MR-guided high intensity focused ultrasound research and the cardiac dynamic MR thermometry are shown to demonstrate the benefits of the proposed method in high spatiotemporal resolution MR thermometry.     

Quantitative assessment of macromolecular concentration during direct infusion into an agarose hydrogel phantom using contrast-enhanced MRI

Convection-enhanced delivery (CED), that is, direct tissue infusion, has emerged as a promising local drug delivery method for treating diseases of the nervous system. Determination of the spatial distribution of therapeutic agents after infusion is important in evaluating the efficacy of treatment, optimizing infusion protocols and improving the understanding of drug pharmacokinetics. In this study, we provide a methodology to determine the concentration distribution of Gd-labeled tracers during infusion using contrast-enhanced magnetic resonance imaging (MRI). To the best of our knowledge, MR studies that quantify concentration profiles for CED have not been previously reported. The methodology utilizes intrinsic material properties (T₁ and R₁) and reduces the effect of instrumental factors (e.g., inhomogeneity of MR detection field). As a methodology investigation, this study used an agarose hydrogel phantom as a tissue substitute for infusion. An 11.1-T magnet system was used to image infusion of Gd-DTPA-labeled albumin (Gd-albumin) into the hydrogel. By using data from preliminary scans, Gd-albumin distribution was determined from the signal intensity of the MR images. As a validation test, MR-derived concentration profiles were found comparable to both results measured directly using quantitative optical imaging and results from a computational transport model in porous media. In future studies, the developed methodology will be used to quantitatively monitor the distribution of Gd tracer following infusion directly into tissues.     

Study of biodistribution of enflurane in rats with in vivo 19F MRI.

In vivo 19F magnetic resonance imaging (MRI) of anesthetized rats enabled us to visualize the biodistribution of fluorinated anesthetics and to document the changes in MR signals in the body during the induction and the elimination phase of anesthesia. The authors examined in vivo 19F MRI in rats anesthetized with concentrations of 1.75-2.0% enflurane and demonstrated its in vivo distribution with concomitant 1H and 13C MRI to verify the anatomical correlation. Distinct 19F MR signals were acquired predominantly from the systemic adipose tissue and the liver. Additionally, the temporal changes in the tissue during and after anesthesia were characterized with in vivo 19F MRI in 6.4 min of the acquisition time. The 19F MR signals increased with time after anesthesia; however, the signals from the adipose tissue were apparently stronger than those from the liver. Following the discontinuation of inhalation, the MR signals in the liver decreased far more rapidly than those from the adipose tissue. When the animal woke up and began to move, the MR signals were still visible in the adipose tissue. These results confirmed the fact that enflurane dissolves preferentially in the adipose tissue and remains when the anesthetic effect disappears. Additionally, 19F MR signals of the liver during the elimination phase might reflect the concentration of enflurane in the blood.     

A fully automatic three-step liver segmentation method on LDA-based probability maps for multiple contrast MR images

Automatic 3D liver segmentation in magnetic resonance (MR) data sets has proven to be a very challenging task in the domain of medical image analysis. There exist numerous approaches for automatic 3D liver segmentation on computer tomography data sets that have influenced the segmentation of MR images. In contrast to previous approaches to liver segmentation in MR data sets, we use all available MR channel information of different weightings and formulate liver tissue and position probabilities in a probabilistic framework. We apply multiclass linear discriminant analysis as a fast and efficient dimensionality reduction technique and generate probability maps then used for segmentation. We develop a fully automatic three-step 3D segmentation approach based upon a modified region growing approach and a further threshold technique. Finally, we incorporate characteristic prior knowledge to improve the segmentation results. This novel 3D segmentation approach is modularized and can be applied for normal and fat accumulated liver tissue properties.     

基于电阻抗层析成像的高强度聚焦超声温度监测技术

作为一种对正常组织无损伤且不易引起癌细胞转移的非入侵肿瘤治疗手段,高强度聚焦超声(HIFU)治疗过程中焦域的温度监测是实现剂量精准控制的关键.本文基于生物组织的温度-电阻抗的关系,将电阻抗层析成像(EIT)和HIFU治疗相结合,提出了一种利用组织焦平面的表面电压实现电阻抗重构的检测技术.建立了HIFU治疗和EIT综合系统模型,在考虑组织的声吸收条件下,对三维Helmholtz方程在柱坐标下的声场计算进行了二维简化,并引入Pennes生物热传导方程来计算HIFU焦域的声压和温升分布特性;引入生物组织的温度-电阻抗关系,基于麦克斯韦电磁场理论,建立了具有温度分布HIFU焦域的电流和电压计算模型,利用恒流注入的边界条件实现电场计算,获得焦平面的表面电压分布.在数值计算中,利用实验聚焦换能器参数,模拟了在固定声功率下组织焦域的声场和温度场分布,以及中心和偏心聚焦条件下不同治疗时刻的电导率分布;然后通过对称电极的循环电流注入,计算了组织模型焦平面内的电流密度和电势分布,获得了焦平面圆周分布的表面电极电压;进一步采用修正的牛顿-拉夫逊算法,利用32×32的表面电极电压实现了焦平面内电导率分布的重建.结果表明,基于温度-电阻抗关系的EIT电导率重建技术不但能准确定位HIFU焦域中心,还能恢复HIFU治疗中焦域的温度分布,证明了EIT用于HIFU治疗中温度监测的可行性,为其疗效评估和剂量控制提供了一种无创电阻抗测量和成像新方法.     

Wavelet transforms in estimating scatterer spacing from ultrasound echoes

Ultrasound echoes from organs such as the liver display resolvable periodicity due to regular scattering centers within tissue. The spacing among such scattering centers has been proposed as a signature to characterize diffuse and focal diseases of the liver. Even though it is highly desirable to be able to estimate an inter-scatterer-spacing (ISS) distribution, current methods can estimate only the mean value of scatterer spacing (MSS) over a tissue length. In this paper, we propose a wavelet transform-based technique that is capable of estimating the location of each scattering center, making it possible to obtain the ISS distribution. We represent liver tissue with a point scatterer model, and show, via computer simulations, that the use of multi-scale information in the wavelet scale-space allows us to estimate the locations of regular scattering centers. We show that both the observation noise and random ultrasound returns from unresolvable tissue microstructure can be removed successfully in the wavelet domain via the properties of the modulus maxima sequence of observation across different scales.     

Monitoring of temperature variation in the focal region of an ultrasonic transducer

A method for remote monitoring of temperature in the focal region of a high-intensity ultrasonic transducer is described. Results of measurements and theoretical simulation are presented. The measurements were conducted on a polymer sample with thermophysical and acoustic parameters close to the properties of a soft biological tissue. The sample was heated by a focused piezoelectric transducer with different values of radiation power. The delay of a probe pulse transmitted through the heated region perpendicularly to the axis of the intense ultrasonic beam was detected. The local character of temperature measurements was provided by focusing the probe pulse at the heated region. The application of an additional transducer installed confocally with the probing one provided an opportunity to enhance the precision of measurements. An analysis was conducted on the basis of a numerical solution of the heat conduction equation. The function of thermal sources in the heat conduction equation was calculated according to the results of measuring the pressure distribution in the focal region of the heating transducer. The experimental data obtained agree well with the results of simulation and demonstrate a fundamental possibility of using the proposed ultrasonic technique for remote temperature measurements.     

Effect of temperature increase and freezing on intravascular elastography

Intravascular ultrasound (IVUS) elastography is a technique that assesses the local strain in the vessel wall and plaque. The strain is an important parameter for characterization of different plaque components. These regions are related to plaque vulnerability. IVUS elastography was validated in vitro using human coronary and femoral arteries. These experiments were performed on specimens that were stored frozen and measured at room temperature for practical issues. The aim of this study is to determine the influence of freezing and measuring the tissues at room temperature (23 degrees C instead of 37 degrees C) on the elastic properties. Four human coronary, one carotid and one femoral arteries were first measured at 23 degrees C and next at 37 degrees C. Additionally they were stored at -80 degrees C for up to 24 h and finally measured at 23 degrees C. Acquisitions at intraluminal pressures of 80 and 100 mmHg were performed using an EndoSonics 20 MHz Visions catheter. Elastograms were determined from the IVUS rf-data (sampled at 100 MHz in 12 bits) that were obtained from a digital interface. Qualitative and quantitative analysis of the elastograms obtained from fresh and frozen specimens measured at 23 degrees C reveals that storage of the specimen at -80 degrees C has no significant influence. In vitro experiments can be performed at room temperature after storage of the tissue at -80 degrees C without significant affection of the information with respect to measuring fresh ex vivo material at body temperature.     

Multifrequency Diagnostics of a Vibrationally Equilibrium CO2-Containing Gas Mixture

We present a technique which makes it possible to simultaneously determine the temperature T and the partial pressure of carbon dioxide in a vibrationally equilibrium gas mixture at atmospheric pressure by using the experimentally measured spectral distribution of the absorption factor at the oscillation lines of a tunable CO₂ laser. The technique developed can be employed for monitoring both the energy efficiency and the ecological purity of the processes of combustion of large amounts of hydrocarbon fuels accompanied by release to the atmosphere of combustion products containing carbon dioxide.     

Temperature rise induced by an annular focused transducer with a wide aperture angle in multi-layer tissue

In order to improve the operability and accuracy of high-intensity focused ultrasound(HIFU), an annular focused transducer, whereby a B-ultrasound probe is placed in its center, is used to realize the real time monitoring and control of the treatment. In this paper, the spheroidal beam equation(SBE) was used to calculate the sound field by an annular focused transducer with a wide aperture angle to first derive the heat deposition and the Pennes equation was used to calculate the temperature field in multi-layer tissue. We studied the effect of different parameters on the temperature of the tissues. The result shows that the focal length has a significant influence on both maximum liver temperature rise and skin temperature rise, and both increase with the increase in the focal length. When the frequency increases, the temperature rise first undergoes a rapid increase before gradually reaching a maximum, and then finally decreasing. The temperature rise increases while the inner radius decreases or the sound pressure increases. By choosing suitable parameters, the proper temperature rise both on the target tissue and skin via an annular focused transducer with a wide aperture angle can be obtained.