山口 匡

Many aspects of medical imaging require innovative measures to improve the quality of diagnosis and treatment. The FERMI Project is promoting these innovations through new developments and improvements of high-dimension, high-definition, quantification of physical or physiological parameters of biological objects and integration of multimodal medical images. The FERMI Project consists of three sub projects: (1) development of essential imaging technologies in medicine; (2) development of dynamic imaging technologies; and (3) integration of spatial information in medical treatment. In this paper, some ongoing research studies are reviewed. These include: ultrasound-based tissue characterization; magnetic resonance elastography; 4D-MRI reconstruction; knee motion analysis from X-ray fluoroscopy and CT images; projector-based assistance for laparoscopic surgery; and a surgical navigation system with three-dimensional ultrasound imaging.

Laparoscopic surgery is a challenging surgical operation because inside information about the target organ cannot be fully understood from the laparoscopic image. In this study, a fusion technique of surface information of a laparoscope and inside blood vessel information of ultrasound is proposed for guidance during laparoscopic surgery. The proposed technique can display the blood vessel depth inside of the target organ by projecting the ultrasonic image over a laparoscopic image. The registration of the laparoscopic and ultrasonic images is performed by registering the surface of the target organ, which is found in the ultrasonic volumetric data and stereoscopic images acquired by the stereo laparoscope. The performance of the proposed technique was evaluated experimentally using a tissue-mimicking phantom. The total computation time was 8.61 s on a personal computer (Xeon processor, 3 GHz CPU). The location of the blood vessel including depth information permits the visualization of risky areas during laparoscopic surgery.

Ultrasound imaging is ideally suited for early-stage assessments of liver steatosis and fibrosis, but conventional ultrasound B-mode images do not display quantitative tissue information because conventional ultrasound formation does not incorporate modeling of the complex interactions between ultrasound and liver tissue in normal and diseased states. In this study, two normal, two fatty, and two fibrotic rat livers were harvested, fixed, and embedded in paraffin. For each specimen, a single, central, 10-m thin section was placed on a microscope slide and scanned in two dimensions (2-D) using a modified scanning acoustic microscope (AMS-50SI; Honda Elec.) incorporating transducers operating at 80- and 250-MHz center frequencies. RF echo signals were digitized with 8-bit precision at a sampling frequency of 2-GHz. 2-D quantitative images of speed of sound (SOS) and attenuation were obtained (2.4 mm x 2.4 mm and 0.6 mm x 0.6 mm using the 80 and 250-MHz transducers, respectively) All images contained 300 x 300 pixels. The SOS and the attenuation values were calculated by averaging all values within 11 regions of interest (ROIs) from each 2-D image of all six livers. At 250-MHz, the SOS and attenuation values of normal, fatty, and fibrotic livers were 1622 +/- 32, 1591 +/- 20, 1700 +/- 44 m/s and 5.70 +/- 0.62, 8.38 +/- 0.51, 7.90 +/- 1.00 dB/mm respectively. The differences in SOS and attenuation values among liver types were greater at 250-MHz than at 80-MHz because of the improved spatial resolution, which allowed more-optimal placement of ROIs to contain only fatty or fibrotic tissue.

Laparoscopic surgery remains a challenging procedure because visualization of the internal target organ cannot be achieved from the laparoscopic image. We have proposed a laparoscopic surgery support method relying on three-dimensional (3D) images reconstructed using a stereo laparoscope and a 3D ultrasound system. The aim of this study is to develop a visualization system providing depth information about blood vessels within the liver. The shape and depth information of blood vessels are then correctly superimposed on a 2D laparoscopic image on the basis following careful registration. The coordinates of the laparoscope and the ultrasound are registered by aligning the two 3D liver surface shapes obtained by a stereo laparoscope and an ultrasonic diagnostic equipment with a mechanically moved convex probe using multiple image processing techniques. Then, the shape and depth information within the liver are calculated, and color-coded blood vessel depth information is superimposed on the original 2D laparoscopic image. In a phantom experiment, the registered 3D images were the mean squared error (MSE) of 5.89 +/- 3.11 mm. The 2D laparoscopic image was superimposed the color-coded depth of the blood vessels segmented from the 3D ultrasonic data. The calculation of depth information had the MSE of 1.88 +/- 1.40 mm.

Proper staging and treatment of cancer require accurate detection of lymph-node metastases, but current histological methods fail to detect small, but clinically significant metastases. We used novel 3D quantitative ultrasound (QUS) methods to identify metastatic regions in freshly excised lymph nodes from cancer patients. Individual lymph nodes were scanned in 3D using a 26-MHz, single-element, F2 transducer with a 12-mm focal length. QUS methods quantified the backscatter coefficient to yield four estimates in cylindrical regions of interest (ROIs) having equal lengths and diameters ranging from 0.4 to 1 mm. To optimize the tradeoff between QUS-estimate quality and the spatial resolution of the estimates, the effect of ROI size on estimate bias and variance was investigated using a database of 101 lymph nodes of colorectal-cancer patients. Estimates were combined using linear-discriminant approaches and ROC curves were computed to assess classification performance. A Bayesian approach was used to convert the discriminant scores to 3D cancer-probability estimates throughout each lymph node. Analysis indicated that ROIs with a 0.8-mm length and diameter improved spatial resolution and minimally degraded estimate quality with an average variance increase of <20% for each estimate. The area under the ROC curve remained greater than 0.92 for all ROI sizes. Our QUS methods potentially can reduce the rate of false-negative determinations drastically by efficiently guiding pathologists to suspicious regions in lymph nodes, and having the best possible spatial resolution while retaining adequate estimate quality is critical.

Laparoscopic surgery is one of the most challenging surgical operations, because inside information about the target organ cannot be fully understood from the laparoscopic image. Therefore, a fusion technique of laparoscopic and ultrasonic images is proposed for guidance during laparoscopic surgery. The proposed technique can display the internal organ structure by overlaying a three-dimensional (3D) ultrasonic image over a 3D laparoscopic image, which is acquired using a stereo laparoscope. The registration of the 3D images is performed by registering the surface of the target organ, which is found in the two 3D images without requiring the use of an external position detecting device. The proposed technique was evaluated experimentally using a tissue-mimicking phantom. Results obtained led to registration accuracy better than 2 cm. The total computation time was 3.1 min on a personal computer (Xeon processor, 3 GHz CPU). The structural information permits the visualization of target organs during laparoscopic surgery. (C) 2012 The Japan Society of Applied Physics

Our group is developing a method based on 3D high-frequency ultrasound (HFU) and 3D quantitative ultrasound (QUS) to help pathologists detect micrometastases in freshly-excised lymph nodes of patients with histologically-proven primary cancer. From a signal and image processing perspective, we report on our efforts to acquire and classify lymph-node tissue based on 3D QUS parameter estimates. We evaluated classifier performance against gold-standard histology. Using our database of 134 abdominal cancer-free nodes and 26 fully cancerous abdominal nodes, a conservative threshold gave a sensitivity and specificity of 99.3% and 73.1%, respectively. We also constructed a 3D cancer-likelihood map of a partially metastatic lymph node and compared that map with histology. This representation potentially can be useful for guiding pathologists to suspicious regions requiring histological evaluation.

Histopathological detection of metastases in dissected lymph nodes of cancer patients is critical to proper staging and management but current histological methods fail to detect small, but clinically-relevant, metastases. Quantitative ultrasound (QUS) permits characterization of tissue microstructure using system-independent estimates. In this study, more than 250 freshly-excised lymph nodes were evaluated using specifically designed QUS methods that demonstrated an ability to guide pathologists towards suspicious regions using an interactive and easy-to-use GUI called Lymph Explorer. Radio-frequency (RF) data were acquired in 3D using a 26-MHz transducer and RF data were processed to yield 13 QUS estimates associated with tissue microstructure. The 13 QUS estimates were combined using a linear discriminant classifier to derive cancer-probability estimates and classification performance was assessed using ROC methods. For gastrointestinal nodes, the areas under the ROC curves (AUCs) exceeded 0.95. Slightly poorer results (AUCs 0.85) were obtained for nodes of breast-cancer patients. Lymph Explorer can interactively display any three orthogonal cross-sectional B-mode images with overlaid color-coded cancer probabilities. In particular, Lymph Explorer permitted localization of small metastases in some partially-metastatic cases. The QUS approach integrated with Lymph Explorer potentially could drastically reduce the current rate of false-negative determinations by efficiently guiding pathologists to suspicious regions in dissected lymph nodes.

Purpose: Recent surgical techniques have been advancing under endoscopic view and insufflation of carbon dioxide gas to expand the abdominal cavity. Isotonic fluid could be one candidate for expanding cavities to facilitate surgical maneuvering. We tested the feasibility and drawbacks of replacement of irrigating materials using a porcine model (water-filled laparoendoscopic surgery [WAFLES]).Materials and Methods: Laparoscopic cholecystectomy was performed in two porcine models using instillation of sorbitol solution as irrigant. Solution irrigation was performed through one of four ports, with drainage via another port. Conventional forceps equipped with a monopolar electrode for electrocautery, laparoscope, video processor, ultrasound, and transducer for measuring intraabdominal pressure were used.Results: Laparoscopic cholecystectomy was successfully undertaken with the following benefits: (1) clear observation of the dissecting plane throughout maneuvering; (2) control of oozing and spilled bile by irrigation and suction; and (3) ultrasonographic and laparoscopic images can be obtained simultaneously without any restriction to probe location. However, two disadvantages should be noted: (1) difficulties in managing floating organs and (2) interruption of vision by blood.Conclusions: WAFLES provides some benefits for endoscopic surgery with proper devices, including apparatuses for irrigation and suction. Efficient irrigation and selection of proper irrigant and apparatuses are required to establish an acceptable procedure.

The detection of metastases in freshly-excised lymph nodes from cancer patients during lymphadenectomy is critically important for cancer staging, treatment, and optimal patient management. Currently, conventional histologic methods suffer a high rate of false-negative determinations because pathologists cannot evaluate each excised lymph nodes in its entirety. Therefore, lymph nodes are undersampled and and small but clinically relevant metastatic regions can be missed. In this study, quantitative ultrasound (QUS) methods using high-frequency transducers (i.e., > 20 MHz) were developed and evaluated for their ability to detect and guide pathologists towards suspicious regions in lymph nodes. A custom laboratory scanning system was used to acquire radio-frequency (RF) data in 3D from excised lymph nodes using a 26-MHz center-frequency transducer. Overlapping 1-mm cylindrical regions-of-interest (ROIs) of the RF data were processed to yield 13 QUS estimates quantifying tissue microstructure and organization. These QUS methods were applied to more than 260 nodes from more than 160 colorectal-, gastric-, and breast-cancer patients. Cancer-detection performance was assessed for individual estimates and linear combinations of estimates. ROC results demonstrated excellent classification. For colorectal-and gastric-cancer nodes, the areas under the ROC curves (AUCs) were greater than 0.95. Slightly poorer results (AUC=0.85) were obtained for breast-cancer nodes. Images based on QUS parameters also permitted localization of cancer foci in some micrometastatic cases.

医用超音波の分野において,断層画像に含まれるスペックルノイズを除去し,病変組織の量や分布の様子を詳細に捉えたいという要求が強い.本論文では,肝エコー信号に含まれるスペックルノイズと生体組織構造を反映したエコー信号との独立性を指標とし,独立成分分析(ICA)による肝臓病変の組織構造抽出法を提案する.一枚のエコー画像から組織構造とは独立した信号成分であるスペックルノイズを除去するため,同様のノイズを付加情報として用いることでICAを適用した.計算機シミュレーションによる基礎検討では,正負の値をもつ出力の負部に組織構造を反映した情報が抽出され,実際のエコーデータにおいても同様に線維構造が抽出されることを確認した.また,付加情報として与えるノイズの性質は照射超音波の音場特性で決定されるため,音場の違いが解析結果に与える影響について検討を行ったところ,エコー信号の分解能や減衰率に依存した出力が得られ,独立性を指標とした新たな組織構造抽出法の可能性が示された.

In the clinical diagnosis of liver fibrosis using ultrasound B-mode images, there are some differences between individual doctors' diagnosis results. Hence, the realization of a quantitative diagnosis method using ultrasonic echo signals is strongly required. The probability density function (PDF) of the echo signal envelope is an important factor for ultrasound tissue characterization (TC). To realize the quantitative diagnosis of the stage of liver fibrosis, we proposed an amplitude distribution model using two Rayleigh distributions. We have been studying the possibility of the quantitative estimation of liver fibrosis by using this model. In this paper, we present the evaluation results of liver fibrosis for clinical data using the amplitude distribution model. Then, we present the stability of the quantitative estimation method of liver fibrosis using the amplitude distribution model by a simulation, and compare the results using the simulation and clinical data. Stability evaluation has enabled the estimation of the progress of liver fibrosis considering statistical dispersion. (C) 2011 The Japan Society of Applied Physics

High-frequency quantitative ultrasound (QUS) permits characterization of tissue microstructure using system-independent estimates. In this study, freshly-excised lymph nodes from cancer patients were evaluated using specifically designed three-dimensional (3D) QUS methods. The long-term objective was to develop 3D QUS methods for detecting metastases. Detection of metastases is critically important for cancer staging and treatment planning. A custom laboratory scanning system was used to acquire radio-frequency (RF) data in 3D from excised lymph nodes using a 26-MHz center-frequency transducer. Overlapping 1-mm cylindrical regions-of-interest (ROIs) of the RF data were processed to yield 13 QUS estimates associated with tissue microstructure. QUS estimates were obtained from more than 250 nodes from more than 150 colorectal-, gastric-, and breast-cancer patients. Cancer-detection performance was assessed for individual estimates and linear combinations of estimates. ROC results demonstrated excellent classification. For colorectal-and gastric-cancer nodes, the areas under the ROC curves (AUCs) were above 0.94. Slightly poorer results (AUC 0.87) were obtained for breast nodes. Images based on QUS parameters also permitted localization of cancer foci in some micrometastatic cases. Therefore, these advanced 3D QUS methods potentially can be valuable for detecting small metastatic foci in dissected lymph nodes.

Coming up with a quantitative diagnosis method for liver fibrosis using ultrasound would be highly significant. To permit tissue characterization using the characteristics of the echo signal such as power spectrum, texture parameters, local attenuation, and statistical characteristics, the relation between complicated scatterer structures and the echo signal must be understood.In this study, we analyzed the property of the echo amplitude envelope using computer-simulated scatterer models. These models mimicked various liver conditions to evaluate our quantitative parametric imaging methods. Statistical echo characteristics changed with the density of the heterogeneous scatterer buried in a speckle.The new analysis method for a medium in which some tissues are embedded was proposed in consideration of analysis results from computer simulations. In the new method, it is possible to eliminate the influence of a cyst or veins and to detect the existence of fibers more clearly than in previous methods.

The oxygen distribution in Ni(2)Si and NiSi films formed during a two-step silicidation process was analyzed by time-of-flight secondary ion mass spectrometry (TOF-SIMS). TOF-SIMS mass spectra revealed that both silicon and nickel reacted with oxygen at the Ni(2)Si surface. In addition, silicon nitride was formed at the surface by the reaction of silicon with nitrogen in the TiN capping layer during the first silicidation annealing. The amount of nitrogen at the NiSi surface varied with silicidation annealing temperature and with the formation conditions of the TiN capping layer. We also showed that a small amount of oxygen was penetrated into the NiSi film and strongly affected the level of junction leakage current in n(+)-p junctions in n-channel MOSFETs. The oxygen concentration in the NiSi film decreased with an increase in the amount of nitrogen at the NiSi surface. (C) 2010 Elsevier Ltd. All rights reserved.

The probability density function (PDF) of the echo signal envelope is animportant factor for ultrasound tissue characterization (TC). Fibrotic tissue isinhomogeneous therefore, its envelope PDF cannot be accurately modeled by asingle PDF. Additionally, some regions have variable scatterer densities. Inorder to detect and characterize the fibrotic liver quantitatively, we examinedthe relationship between the scatterer distribution and the PDF of echoenvelopes of inhomogeneous scattering media using computer simulations. Then,the analysis parameters in the simulated fiber tissue were successfully used tocharacterize fibrosis in clinical data sets. © 2010 IEEE.

Since the clinical diagnosis based on ultrasonic B-mode images is dependent on the skill of the doctor, the realization of a quantitative diagnostic method using ultrasound echo signals is highly required. We have been investigating the quantitative diagnostic technique mainly on hepatic diseases. In this paper, we present a new analysis method using echo signals for the quantitative estimation of liver fibrosis. To quantitatively determine the stage of liver fibrosis, we propose a model in which the probability density function of echo amplitude is expressed as a combination of two Rayleigh distributions. These two Rayleigh distributions correspond to the echo components from the normal and diseased tissues. In addition, using this amplitude distribution model of echo amplitude, we present the estimation method to obtain the amount of fibrous tissue and stage of fibrotic degeneration of the liver from moments about mean of the echo amplitude. Basic examination using clinical images suggest that the quantitative estimation of liver fibrosis based on a combination of Rayleigh distributions is valid. (C) 2010 The Japan Society of Applied Physics

At present, percutaneous liver biopsy is the gold standard in assessing liver fibrosis such as hepatitis and cirrhosis, but there could be sampling error, and specimens might not represent the state of the whole liver accurately because only about 0.002% of the organ is sampled. In this research, we propose the three-dimensional fiber structure extraction echo filter to realize a quantitative ultrasonic diagnosis. The filter is designed based on a statistical theory, and it is possible to reduce the noise contained in a back scattered ultrasonic echo signal, and to visualize the structure of a fiber.

OBJECTIVE. The purpose of this study was to evaluate the degree of liver fibrosis in patients with chronic hepatitis C by use of a method in which the homogeneity of the tissue texture of the liver on B-mode ultrasound images is analyzed on the basis of results of a statistical chi-square test of the echo amplitudes. The method includes an algorithm for removing small structures, such as cross sections of the thin vessels, in the background texture to minimize differences in analysis results between users.SUBJECTS AND METHODS. Analysis was performed on images of 148 patients with histologically proven chronic hepatitis C without cirrhosis. The peak value of the C-m(2) (modified chi-square distribution) histogram was calculated from B-mode ultrasound images, and the resulting value was compared with the histologic fibrosis grade.RESULTS. The peak C-m(2) histogram value for grade F3 fibrosis was higher than that for grades F0 and F1 (p < 0.0001) and F2 (p = 0.0003). The value for grade F2 was higher than that for grades F0 and F1 (p = 0.0027). The values gradually increased with an increase in liver fibrosis grade, although no difference was found between grades F0 and F1.CONCLUSION. The grades of liver fibrosis in patients with chronic hepatitis C are well discriminated with the B-mode ultrasound-based analysis algorithm without discrimination between grades F0 and F1. Findings on conventional ultrasound images may reflect progression of liver fibrosis even in the absence of cirrhosis.

In order to diagnose fibrosis quantitatively, a technique to extract fiber structure and suppress speckle from the echo data acquired using available clinical ultrasonic diagnostic instruments would be very valuable. To meet this need, we propose to apply independent component analysis (ICA) to separate the signals returning from clinical tissue fiber structures from the speckle signals. To use ICA and to remove speckle, data acquired from a normal tissue-mimicking phantom are acquired to characterize speckle and used to correct for speckle in clinical echo-signal data. Results showed satisfactory separation of speckle signals and fiber-tissue echo signals. However, results indicated that the ability of the ICA algorithm to correctly image fiber tissue structures depended greatly on whether the speckle in the clinical and tissue-mimicking images had same properties. ©2009 IEEE.

An acoustic method in air has the potential to allow for the fast and accurate characterization of objects in air. Nevertheless, it is difficult to identify acoustic signals clearly because of environmental noises and the scattering of signals on the object surface. Therefore, it is required to establish a sensing system, which enables measurements in air. In this paper, we present the object detection using an M-sequence signal in an indoor environment. Using the M-sequence signal enabled the improvement in signal-to-noise (SN) ratio and the stable measurement of reflected waves that cannot be detected using a conventional impulse. The noise and reverberation components are included in the received signals and reflected waves from the target. We confirmed that in the case of a high-order-M-sequence signal, target detectability is limited by reverberation. In addition, we eliminated the reverberation component from the received signals using the signals without the target in the reverberation limited case and determined the reflection characteristics of the target. [DOI: 10.1143/JJAP.47.4325]

Deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) are serious problem of total knee replacement (TKR). These diseases may be caused by a thrombus formed during the TKR operation. Therefore, understanding the flow volume of thrombus is important for curing and preventing PTE. In this paper, we tried to understanding the situation of the flow of thrombus by using transesophageal echocardiography movies. We applied the signal processing technique the FSET to extract the anomalous information from ultrasonic echo image. As a result of processing, the time change of the flow volume of thrombus was confirmed.

本論文では, 現在の超音波診断に用いられている断層画像(Bモード画像)に含まれるエコー情報と肝硬変の進行に伴う組織散乱体構造変化との関係を, シミュレーション画像と臨床画像を用いて検討している.病変進行度の異なる複数のBモード画像を用い, 画像中の様々な領域から得られるエコーの振幅分布特性を算出し, 基本となるレイリー分布との比較を行った.その結果, ランダムな散乱体からの情報からなる正常肝の画像は, 病変の進行とともに病変組織特有の散乱体分布情報が混在した画像に変化していくことがわかり, 病変進行と散乱体構造変化及びエコー情報変化の間には定量的な関係があることが確認された.

The cirrhotic liver has many fibrotic tissue structures known as nodule structures. Understanding this characteristic in diseased tissue is important for quantitative diagnosis. In this paper, we present a technique to extract quantitative three-dimensional information from a cirrhotic liver. Consecutive two-dimensional images acquired by fan like scanning were processed using constant false alarm rate (CFAR). The 2D processed images are accumulated to obtain 3D information. The nodular structure is clear in the constructed images.

The human liver is composed of small hexagonal structures known as the liver lobules. In this paper, we propose a modeling technique for the change of the scatterer distribution on liver tissue considering the liver lobule structure to obtain cirrhotic liver images of the continuous stage. We calculate the squared difference between the Rayleigh distribution and the probability density of the echo amplitude of each cirrhosis image. The difference increases with the progression of cirrhosis. These results agree well with the results obtained from clinical liver cirrhosis images. It is found that the proposed modeling technique is valid for analyzing the relationship between the change of characteristics of biological tissue and change of B-mode image on the progression of liver cirrhosis.