The use of a micro-bubble agent to enhance rabbit liver destruction using high intensity focused ultrasound

Liver tissues in New Zealand rabbits were ablated using high intensity focused ultrasound (HIFU, 14300 W/cm(2), 1.0 MHz). The animals were intravenously administered 0.2 ml of micro-bubble agent in the experimental (n=20) group and an isovolumetric normal saline solution in the control (n=27) group before HIFU treatment which was performed as a linear scan. In both groups, the preselected tissue volumes were destroyed without harming the overlying tissues. Necrosis rate (NR, cm(3)/s) was used to reflect the ablation efficiency, which was the tissue volume of occurring coagulative necrosis per 1s HIFU exposure. NR was improved in the experimental group (0.0570+/-0.0433 vs 0.0120+/-0.0122, P=0.0002). Pathological studies confirmed that there were no residual intact targets within the exposed volume. These findings suggested that the introduction of the micro-bubble agent enhanced HIFU liver destruction.     

Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview

The ideal treatment of localized cancer should directly cause an irreversible and complete death of tumor cells without damage to surrounding normal tissue. High intensity focused ultrasound (HIFU) is such a potential treatment, which induces a complete coagulative necrosis of a tumor at depth through the intact skin. The idea that using an extracorporeal source of therapeutic ultrasound was introduced more than 50 years ago [J. Gen. Physiol. 26 (1942) 179]. However, up to now, most of the studies on HIFU have been dealing with animal experiments because this extracorporeal technique is very complicated in clinical applications. The purpose of this study is to introduce Chinese clinical experience of using extracorporeal HIFU for the treatment of patients with various kinds of solid tumor. From December 1997 to October 2001, a total of 1038 patients with solid tumors underwent HIFU ablation in China. Among them, 313 patients were treated at the Chongqing University of Medical Sciences, China. Pathological examination showed that the target region presented clear evidence of cellular destruction. Small blood vessels less than 2 mm in diameter were severely damaged. Follow-up diagnostic imaging revealed that there was no, or reduced, blood supply, and no uptake of radioisotope in the treated tumor after HIFU, both indicating a positive therapeutic response and an absence of viable tumor. Imaging at 6-12 months showed obvious regression of the lesion. Four-year follow-up data were significantly observed in patients with hepatocellular carcinoma, osteosarcoma, and breast cancer. An extremely low major complication rate was noted. It is concluded that HIFU ablation is a safe, effective, and feasible modality for the ablation of carcinomas.     

良性前列腺增生组织对钛宝石激光的吸收和散射特性

研究了经尿道等离子体双极电切除术(PKRP)切除和经尿道前列腺电切术(TURP)切除的前列腺增生(BPH)组织对640, 660, 680, 700, 720, 740, 760, 780, 800, 820, 840, 860和880 nm波长的钛宝石激光的光学特性及其差异,实验采用双积分球测量系统以及反向倍增法获取BPH组织的吸收和散射特性参数。结果表明：PKRP和TURP切除的BPH组织对这1３个不同波长的激光的吸收系数和约化散射系数都是随着激光波长增大而明显减小的,PKRP切除的BPH组织对这同一波长的激光的吸收系数和约化散射系数都明显较TURP切除的BPH组织对相应的波长的激光的吸收系数和约化散射系数要小,PKRP和TURP切除的BPH组织的吸收系数以及约化散射系数的最大值都在640 nm,其值分别为(0.885±0.022)和(0.955±0.024)mm-1以及(1.564±0.039)和(1.658±0.042)mm-1,其差异分别为7.91%以及6.01%,其最小值都在880 nm,其值分别为(0.443±0.011)和(0.455±0.011)mm-1以及(1.117±0.028)和(1.197±0.030)mm-1,其差异分别为2.71%以及7.16%。PKRP和TURP切除的BPH组织对660 nm的吸收系数的差异最大,其值为8.95%,其差异最小在860 nm,其值为1.75%,PKRP和TURP切除的BPH组织对800 nm的约化散射系数的差异最大,其值为9.13%,其差异最小在640 nm,其值为6.01%。     

In vivo proton magnetic resonance spectroscopy of diseased prostate: spectroscopic features of malignant versus benign pathology.

In vivo Proton Magnetic Resonance Spectroscopy appears potentially useful for non-invasive discrimination between benign prostatic hyperplasia (BPH) and prostate carcinoma (PC). Aiming to delimit the range within which spectra from one or the other pathology should occur, and establish extreme spectroscopic features of malignant versus benign prostate disease, we performed endorectal proton MR spectroscopy on 20 patients severely affected of either benign prostatic hyperplasia (BPH) (n = 10) or prostate cancer (PC) (n = 10). They were selected on the basis of the large volume and homogeneity of their lesions, which were histologically confirmed after spectroscopy. Consequently, high-quality short-TE proton spectra with well-resolved metabolite signals, and practically free of volume averaging issues were obtained in all cases. Apart from the typical citrate, creatine, and choline signals of prostate spectra, both BPH and PC spectra showed a peak centered at 3.6 ppm which was assigned to myo-inositol. The intensity of this contribution was found significantly increased in PC cases compared to BPH. Possible relationships between neoplastic transformation and the metabolic pathways in which myo-inositol participates are discussed. Average spectroscopic profiles were calculated for both advanced pathologies, and showed obvious differentiated features. In quantitative terms, the ratio of citrate to choline peak areas as well as that of creatine to myo-inositol appeared as the most convenient to discriminate between advanced PC cases (both ratios below 1.0) and advanced BPH cases (both ratios above 1.0).     

组织凝固性坏死对基于纵向弛豫时间的磁共振测温的影响

高强度聚焦超声（High Intensity Focused Ultrasound,HIFU）治疗肿瘤时,为了保证治疗的安全性和有效性,需要对组织温度分布进行实时监测.磁共振成像（Magnetic Resonance Imaging,MRI）具有对温度敏感的成像参数,可以无创检测组织温度.本文结合组织相变对测温的影响,探讨了磁共振测温（Magnetic Resonance Thermometry,MRT）技术能否用于实时监控HIFU治疗.利用两态快速交换模型,提出在组织凝固性坏死的相变前后,MRI的纵向弛豫时间（T₁）参数与组织温度之间具有不同关系.并通过实验验证了上述假设.相对于传统的磁共振测温方法模型,本文考虑了HIFU治疗过程中组织相变对检测温度的影响,对利用磁共振测温引导HIFU治疗具有重要的参考价值.     

泌尿系统治疗用HIFU换能器的设计

高强度聚焦超声技术是‘种将超声能量聚焦于人体深部组织的狭小区域,形成足够高的声强,使组织瞬时在局部产生高温、无创性局部治疗肿瘤的新技术。近年来,泌尿系统疾病发病率迅速上升,尤其是前列腺疾病发病率高,相关的并发症也较多,已成为威胁男性生命健康的重要疾病。本文应用高强度聚焦超声技术,设计了治疗泌尿系统疾病的线阵换能器。仿真结果证明:该换能器的卢场能量集中,声强峰值尖锐,焦点尺十小,聚焦效果好,可以达到有效无损治疗的目的。     

Hemorrhage control in arteries using high-intensity focused ultrasound: a survival study

High-intensity focused ultrasound (HIFU) has been shown to provide an effective method for hemorrhage control of blood vessels in acute animal studies. The objective of the current study was to investigate the long-term effects of HIFU-induced hemostasis in punctured arteries. The femoral arteries ( approximately 2mm in diameter) of 25 adult anesthetized rabbits were surgically exposed, and either punctured and treated with HIFU (n=15), served as control (no puncture and no HIFU application: n=7), or were punctured and left untreated (n=3). Treated animals were allowed to recover, and examined and/or sacrificed on days 0, 1, 3, 7, 14, 28, and 60 after treatment to obtain ultrasound images and samples of blood and tissue. Hemostasis (arrest of bleeding) was achieved in all 15 of the HIFU-treated arteries. Eleven of the arteries were patent after HIFU treatment, and four arteries were occluded, as determined by Doppler ultrasound. The median HIFU application time to achieve hemostasis was 20s (range 7-55 s) for the patent arteries and 110 s (range 50-134 s) for the occluded arteries. In untreated animals, bleeding had not stopped after 120 s. One of the occluded arteries had reopened by day 14. No immediate or delayed re-bleeding was observed after HIFU treatment. Maximal blood flow velocities were similar in HIFU-treated patent vessels and control vessels. No significant difference in hematocrits was found between HIFU-treated and control groups at different time points after the procedure. Light microscopy observations of the HIFU-treated arteries showed disorganization of adventitia, and coagulation and thinning of the tunica media. The general organization of the adventitia and tunica media recovered to normal appearance within 28 days, with some thinning of the tunica media observed up to day 60. Neointimal hyperplasia was observed on days 14 and 28. The results show that HIFU can produce effective and long-term (up to 60 days) hemostasis of punctured femoral arteries while preserving normal blood flow and vessel wall structure in the majority of vessels.     

High intensity focused ultrasound ablation of goat liver in vivo: Pathologic changes of portal vein and the “heat-sink” effect

The purpose of this study was to evaluate pathological changes of the portal vein (PV) and the effects on main branches of the hepatic PV during HIFU (high-intensity focused ultrasound) sonication when liver tissue adjacent to the main branches of hepatic PV was ablated. Normal liver tissue at 0 mm, 5 mm, 10 mm away from the hepatic portal vein in 50 healthy goats was ablated with magnetic resonance image-guided HIFU (MRgHIFU). MRI showed a non-perfusion region at the target area but did not show any significant changes of the PV immediately after HIFU. The histological examination 1 day after HIFU showed coagulative necrosis at the target area, revealed deep-dyed swelling collagen (CS) fibers and vessel wall fracture (VWF) in the PV adjacent to the target area; however, no CS or VWF was observed in the PV 1 week after HIFU ablation. The energy required to ablate the foci at 0 mm was 21% more than that at 10 mm from the PV (p < 0.05); the energy needed to ablate foci 5 mm away from the PV was 10% more than that at 10 mm from the PV (p < 0.05). We concluded that minor injury of the hepatic portal vein may occur when ablating the adjacent liver tissue, and the acoustic energy deposition is related to the distance to the portal vein.     

The use of ultrasound-stimulated acoustic emission in the monitoring of modulus changes with temperature

It has been previously shown that the amplitude of the ultrasound-stimulated acoustic emission (USAE) signal is sensitive to tissue temperature and, therefore, can help detect it. Its amplitude, however, is sensitive to both acoustical and mechanical parameters, that at most frequencies have opposite effects due to temperature. In this paper, we explore the feasibility of using a frequency shift of the resonant peaks of the USAE signal for monitoring the tissue stiffness variation with temperature. In a numerical simulation, the variation of the frequency shift at different temperatures is shown. Then, in a series of experiments involving a gel phantom and porcine muscle tissue, the frequency shift variation is shown to follow the known stiffness changes due to temperature. It is also shown that this shift indicates reversible changes as well as the onset of thermal coagulative necrosis. The necrosis is marked by a monotonically increasing positive frequency shift. It was thus shown that the USAE spectrum peaks undergo a negative shift (or, downshift) when the stiffness decreases and a positive shift (or, upshift) when the stiffness increases. The experimental frequency shifted around a peak at 22.1-22.5 kHz within a range of -250 to 80 Hz and -200 to 250 Hz for the gel and muscle tissue for the temperatures of 25-70 and 30-70 degrees C, respectively. Simulation and ex vivo experimental results indicate that the USAE frequency shift method can help decouple the mechanical from the acoustical parameter dependence as well as detect the onset of thermal coagulative necrosis.     

Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.     

Imaging findings of solitary fibrous tumor of the prostate: a case report

The imaging findings of a solitary fibrous tumor of the prostate are presented. A 35-year-old male presented with urinary retention and was found on transrectal ultrasonography to have a hypoechoic tumor of the prostate, measuring 5.5 cm in size. Magnetic resonance imaging on, the tumor showed low signal intensity on T1-weighted images and heterogeneous mixed signal intensity on T2-weighted images. Gadolinium-enhanced dynamic study showed gradual enhancement from the periphery to the center, and the enhancement is sustained. On immunohistochemistry, the spindle cells of the tumor showed positive staining for CD34 and bcl-2. Although the tumor was labeled as a low-grade malignancy on account of a low mitotic index (MIB-1 index) of about 5%, the patient developed local recurrence of the tumor with bladder wall invasion 12 months later.     

Differential ultrasonic imaging for the characterization of lesions induced by high intensity focused ultrasound

High intensity focused ultrasound (HIFU) is an effective technique for noninvasive local creating coagulative necrotic lesions in deep target volumes without damage to the overlaying or surrounding tissues. It is very important to detect and evaluate lesions generated by HIFU during treatment procedures. This study describes the development of several differential ultrasonic imaging techniques to characterize lesions based on estimation of relative changes in tissue properties derived from backscattered RF data. A single, spherical HIFU transducer was used to produce lesions in soft tissues. The RF signals were recorded as outputs from a modified diagnostic ultrasound system. After some preprocessing, the integrated backscatter values, which can be used as an indicator of the microstructure and backscattering property of tissues, were calculated before and after HIFU treatment. The differential integrated backscatter values were subsequently used to form images revealing the lesion areas. The differential attenuation imaging with the same RF data was also performed, which has been proposed by a few researchers. The results of the differential integrated backscatter imaging were compared with that of the differential attenuation imaging and the former method offers some advantages over the latter method. The two methods above are both based on spectrum analysis and would spend much computational time. Therefore, some simple digital differential imaging methods, including absolute difference (AD), sum absolute differences (SAD), and sum squared differences (SSD) algorithms, were also proposed to detect HIFU-induced lesions. However, these methods cannot provide the information of the degree of tissue damage. Experiments in vitro bovine muscle and liver validated the method of differential integrated backscatter imaging for the characterization of HIFU-induced lesions. And the AD, SAD, and SSD algorithms can be implemented in real-time during HIFU therapy to visualize the lesions.     

高强度聚焦超声用于肿瘤治疗的研究

高强度聚焦超声（ＨＩＦＵ）能在短时间内使病变组织的温度升至７０℃以上,导致病变组织凝固坏死,是一种具有巨大潜力的、非侵入的、有效的肿瘤治疗手段。本文对ＨＩＦＵ的动物试验、临床应用及治疗装置的研究情况进行了总结,分析了该技术尚存在的问题,最后展望了其应用前景。     

Conventional MR imaging with simultaneous measurements of cerebral blood volume and vascular permeability in ganglioglioma

The conventional MR imaging appearance of gangliogliomas is often variable and nonspecific. Conventional MR images, relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) measurements were reviewed in 20 patients with pathologically proven grade 1 and 2 gangliogliomas (n = 20) and compared to a group of grade 2 low-grade gliomas (n = 30). The conventional MRI findings demonstrated an average lesion size of 4.1 cm, contrast enhancement (n = 19), variable degree of edema, variable mass effect, necrosis/cystic areas (n = 8), well defined (n = 12), signal heterogeneity (n = 9), calcification (n = 4). The mean rCBV was 3.66 +/- 2.20 (mean +/- std) for grade 1 and 2 gangliogliomas. The mean rCBV in a comparative group of low-grade gliomas (n = 30), was 2.14 +/- 1.67. p Value < 0.05 compared with grade 1 and 2 ganglioglioma. The mean K(trans) was 0.0018 +/- 0.0035. The mean K(trans) in a comparative group of low-grade gliomas (n = 30), was 0.0005 +/- 0.001. p Value = 0.14 compared with grade 1 and 2 ganglioglioma. The rCBV measurements of grade 1 and 2 gangliogliomas are elevated compared with other low-grade gliomas. The K(trans), however, did not demonstrate a significant difference. Gangliogliomas demonstrate higher cerebral blood volume compared with other low-grade gliomas, but the degree of vascular permeability in gangliogliomas is similar to other low-grade gliomas. Higher cerebral blood volume measurements can help differentiate gangliogliomas from other low-grade gliomas.     

Effects of water exchange on MRI-based determination of relative blood volume using an inversion-prepared gradient echo sequence and a blood pool contrast medium

A prostate tumor model in rats was used to compare histometric parameters of prostate cancer physiology with those obtained by magnetic resonance imaging (MRI). The study was focused on vascular physiology as reflected by relative blood volume v(b). Histometry and MRI showed a significant increase in mean v(b) in tumor compared to normal prostate tissue (histometry: normal tissue v(b)=0.69+/-0.19%, tumor tissue v(b)=1.10+/-0.31%, P<.001; MRI: normal tissue v(b)=0.67+/-0.23%, tumor tissue v(b)=1.77+/-0.67%, P<.001). The experimental work showed that MRI yielded a 60.9+/-0.76% higher v(b) than histometry in tumors, while no significant difference in v(b) was found between both methods in normal prostate tissue. Water exchange is known to affect signal intensity on contrast-enhanced MRI. This article investigated the influence of water exchange between intravascular and extravascular space to account for the discrepancy in the values of v(b) obtained with a dynamic inversion-prepared gradient echo MRI sequence and histometry in tumor and normal prostate tissue. The expected influence of water exchange on v(b) was modeled by a computer simulation of the MRI signal and compared with experimental results measured with MRI and histometry. The simulation was based on a two-compartment model indicating that v(b) may be overestimated by MRI. The magnitude of overestimation leads from 10% for the slow water exchange regime to 70% for fast water exchange. Since slow water exchange is probably predominant and even if the observed histological differences in tumor tissue are considered, an overestimation of only 15% due to water exchange is predicted by the simulation. Therefore the overestimation of tumor blood volume by MRI of 60.9% compared to histometry seems to be attributable to additional causes besides water exchange.     

组织中去甲肾上腺素的荧光测定法

本文研究了去甲肾上腺素荧光光度测定方法。测定范围在１０－１００ｎｇ则与荧光值呈良好线性关系，λｅｘ／λｅｍ＝４１０ｎｍ／５０５ｎｍ，回收率为９１．６８－９６．６５％，标准偏差平均为６．１％，本法具有准确、简便、快速等特点。     

Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains.

The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.     

Pseudorapidity distributions of charged particles from Au + Au collisions at the maximum RHIC energy,square root[s(NN)] = 200 GeV

We present charged-particle multiplicities as a function of pseudorapidity and collision centrality for the 197Au+197Au reaction at square root[s(NN)] = 200 GeV. For the 5% most central events we obtain dN(ch)/deta/(eta = 0) = 625+/-55 and N(ch)/(-4.7< or =eta < or =4.7) = 4630 +/- 370, i.e., 14% and 21% increases, respectively, relative to square root[s(NN)] = 130 GeV collisions. Charged-particle production per pair of participant nucleons is found to increase from peripheral to central collisions around midrapidity. These results constrain current models of particle production at the highest RHIC energy.     

Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for cancer discrimination

Quantitative, apparent T(2) values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T(2) values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in 10.7 min, resulting in data sets suitable for generating high-quality images with variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T(1)- and T(2)-weighted signal intensities and available histopathology reports, yielded significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging alone, including quantitative T(2) values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time FSE sequences.