S. Philippou

Ultrasonic multifeature tissue characterization for prostate diagnostics.

A new system for prostate diagnostics based on multifeature tissue characterization is proposed. Radiofrequency (RF) ultrasonic echo data are acquired during the standard transrectal ultrasound (US) imaging examination. Nine spectral, texture, first order and morphologic parameters are calculated and fed into two adaptive neuro-fuzzy inference systems (FIS) working in parallel. The outputs of the FISs are fed into a postprocessing procedure evaluating contextual information before being combined to form a malignancy map in which areas of high cancer probability are marked in red. The malignancy map is presented to the physician during the examination to improve the early detection of prostate cancer. The system has been evaluated on 100 patients undergoing radical prostatectomy. The ROC curve area using leave-one-out cross-validation over patients is A(Z) = 0.86 when distinguishing between hyperechoic and hypoechoic tumors and normal tissue and A(Z) = 0.84 when distinguishing between isoechoic tumors and healthy tissue, respectively. Tumors that are not visible in the conventional B-mode image can be located. Diagnosis of the prostate carcinoma using multifeature tissue characterization in combination with US imaging allows the detection of tumors at an early stage. Also, biopsy guidance and therapy planning can be improved.

A new system for the acquisition of ultrasonic multicompression strain images of the human prostate in vivo

We describe a novel recording system for the acquisition of multicompression strain images of the human prostate in vivo. The force at the tip of an ultrasonic transrectal probe is measured continuously, and ultrasonic RF-images are acquired consecutively at specified levels of compression. The acquired image sequence is processed by conventional cross-correlation techniques to obtain time shift estimates and corresponding strain images. We present phantom measurements as well as in vivo results and discuss the advantages and restrictions of the proposed system.

Ultrasound elastography for the age determination of venous thrombi: Evaluation in an animal model of venous thrombosis

The exact age determination of venous thrombi is important if thrombolytic therapy or surgical thrombectomy is considered. Clinical symptoms as well as duplex-ultrasound and phlebography are unreliable in this respect and do not allow an exact age estimation. Ultrasound elastography can provide information about the elastic properties of thrombi. Since thrombus elasticity decreases with age due to the organisation process, it should be possible to use elastography to stage the degree of organisation and thereby determine the age of venous thrombi. Experimental venous thrombi aging 1, 3, 6, 9, 12 and 15 days were created in a porcine model by laparoscopic ligation of the infrarenal Vena cava in combination with transfemoral infusion of thrombin. The thrombosed iliac veins were explanted and embedded in gelatine, after that they underwent examination by ultrasound elastography. In addition, histological evaluation of the thrombi was performed. Elastography demonstrated a decline in thrombus elasticity between days 6 and 12 with the 12-day-old thrombi being about 3 times harder then the 6-day-old thrombi. This correlated with the histological findings, which demonstrated a marked increase in fibroblast and collagen production in the clots during this time, with the 12- and 15-day thrombi showing signs of advanced organisation. In conclusion, in an experimental setting, ultrasound elastography was helpful in determining the exact age of venous thrombi. The differences in elasticity were most pronounced between days 6 and 12, which is also the most relevant time frame when considering invasive therapies in human venous thrombosis.

Ultrasonic multifeature tissue characterization for the early detection of prostate cancer

The incidence of the prostate carcinoma is one of the highest cancer risks in men in the western world. Its position in cancer mortality statistics is also among the highest. The prostate carcinoma is only curable at an early stage. Therefore, early detection is extremely important. At an early stage the prostate carcinoma is limited to the prostate capsule and can hence be cured performing radical prostatectomy. The different types of diagnostics that are used today (digital rectal examination, transrectal ultrasound and PSA value analysis) lack reliability and are therefore not sufficient. Even a combination of these three methods is not sufficiently reliable. Diagnosis of the prostate carcinoma using multi-feature tissue characterization in combination with ultrasound allows the detection of tumors at an early stage. Also biopsy guidance and planning can be improved. This results in reduced costs for cancer treatment.

Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues: factors influencing renal carcinogenesis induced by xenobiotics

Abstract. In general, the biological activation of nephrocarcinogenic chlorinated hydrocarbons proceeds via conjugation with glutathione. It has mostly been assumed that the main site of initial conjugation is the liver, followed by a mandatory transfer of intermediates to the kidney. It was therefore of interest to study the enzyme activities of subgroups of glutathione transferases (GSTs) in renal cancers and the surrounding normal renal tissues of the same individuals (n=21). For genotyping the individuals with respect to known polymorphic GST isozymes the following substrates with differential specificity were used: 1-chloro-2,4-dinitrobenzene for overall GST activity (except GST θ); 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole for GST α; 1,2-dichloro-4-nitro-benzene for GST µ; ethacrynic acid and 4-vinylpyridine for GST π; and methyl chloride for GST θ. In general, the normal tissues were able to metabolize the test substrates. A general decrease in individual GST enzyme activities was apparent in the course of cancerization, and in some (exceptional) cases individual activities, expressed in the normal renal tissue, were lost in the tumour tissue. The GST enzyme activities in tumours were independent of tumour stage, or the age and gender of the patients. There was little influence of known polymorphisms of GSTM1, GSTM3 and GSTP1 upon the activities towards the test substrates, whereas the influence of GSTT1 polymorphism on the activity towads methyl chloride was straightforward. In general, the present findings support the concept that the initial GST-dependent bioactivation step of nephrocarcinogenic chlorinated hydrocarbons may take place in the kidney itself. This should be a consideration in toxicokinetic modelling.

Ultrasonic Tissue Characterization for Prostate Diagnostics: Spectral Parameters vs. Texture Parameters. Sonohistologie für die Prostatadiagnostik: Vergleich von Spektral- und Texturparametern

An ultrasonic multi-feature tissue characterizing system for the detection of prostate cancer is presented. The system is based on the processing of radio frequency (RF) ultrasonic echo data. Data from 100 patients was acquired in a clinical study. Parameters are extracted from the RF echo data and classified using two adaptive network-based fuzzy inference systems (FIS) working in parallel as a nonlinear classifier. Next to spectral parameters, conventional texture parameters are calculated using demodulated and log-compressed echo data. In the first approach, the classifier is trained on both, spectral and texture parameters. In the second approach, the classifier is only trained on texture parameters. Classification results of both approaches are compared and it is demonstrated, that only the use of spectral parameters yields satisfying classification results. Results of a minimum distance classifier (MDC) are presented for comparison with the fuzzy inference system. For the final fuzzy inference systems used in this approach, the area under the ROC curve is between 84% and 86% for the combined approach and between 70% and 74% for the approach based on texture parameters only.

Diagnosis of prostate carcinoma using multicompression strain imaging: data acquisition and first in vivo results

We present a new system for the acquisition of ultrasonic multicompression strain images of the human prostate in vivo. A mechanical force applied to the tip of an ultrasonic transrectal probe is measured continuously and ultrasonic RF-images are acquired consecutively at specified levels of tissue compression. An iterative phase-zero estimation method is used to obtain time delay estimates and the corresponding strain images from the acquired image sequence. We present phantom measurements as well as first in vivo results which are in good agreement to histological findings. Lateral tissue motion artifacts are corrected by a novel local companding method.

Mixed malignant germ cell tumour of the liver

Abstract Germ cell tumours of the liver are rare neoplasms, with fewer than 20 cases reported in the literature following presentation as teratomas, choriocarcinomas or yolk sac tumours. We report a 52-year-old patient who complained of upper abdominal pain and anorexia. Ultrasonography and computed tomography of the abdomen revealed a large hepatic mass. Among the laboratory values we found elevated levels of alpha-fetoprotein and beta-chorionic gonadotropin. Repeated biopsies via CT scan, laparoscopy and laparotomy disclosed a poorly differentiated adenocarcinoma. Subsequently liver function deteriorated and, on the basis of clinical data highly suggestive of a malignant germ cell tumour, a modified chemotherapeutic protocol (PEI) was initiated. The elevated levels of alpha-fetoprotein and beta-chorionic gonadotropin declined rapidly, but the patient died 10 days later of liver dysfunction and bronchopneumonia. Subsequent autopsy confirmed the initial clinical diagnosis of a multilocular extragonadal malignant germ cell tumour of the liver with components of choriocarcinoma and embryonal carcinoma.

Neuro-fuzzy inference system for ultrasonic multifeature tissue characterization for prostate diagnostics

The incidence of the prostate carcinoma is one of the highest cancer risks in men in the western world. Its position in cancer mortality statistics is also among the highest. The different types of diagnostics that are used today lack reliability and are therefore not sufficient. Diagnosis of the prostate carcinoma using multifeature tissue characterization in combination with ultrasound allows the detection of tumors at an early stage and thus can aid the conducting physician in finding a diagnosis. Spatially resolved parameters and contextual information are used for the classification. Next to hypo- and hyperechoic tumors, also isoechoic tumors can be visualized.

Real Time Strain Imaging — a new Ultrasonic Method for Cancer Detection: First Study Results

Prostate tumors can have a higher mechanical hardness than the surrounding tissue. During the digital rectal exam this can be used not only to detect the hypertrophy but also localized hardenings. The examination by digital palpation is inaccurate and even in combination with PSAvalue and a transrectal ultrasonic examination the result is often not reliable. Ultrasound strain imaging is able to measure and visualize the elastic properties of a tissue region and hence is an adequate supplement for commonly used diagnostic procedures. We have developed a real time system for elastographic mechanical tissue assessment of the prostate which can be used for the transrectal ultrasonic examination for navigation and diagnosis. During the examination a sequence of ultrasonic images is acquired while the organ is slightly compressed by the ultrasound probe. Using a numerical analysis of image pairs of the acquired sequence the tissue strain is calculated which represents the spatial elasticity distribution of a specific cross-section of the organ and which are able to distinguish hard areas in the tissue. We present results from several patients. which show, that real time strain imaging is able to detect tumor-like areas which are inconspicuous in the bmode image. The results correspond to the histological specimens. After the evaluation of 130 patients using a prospective study we found the specificity for cancer detection to be approximately 84% and a sensitivity of approximately 76 %. Furthermore the tumor location and extend was correctly predicted in most of the investigated patients using our real time strain imaging. SIGNAL PROCESSING Strain imaging was first described by Ophir in 1991 [1], but could not easily be clinically applied so far, because the described method had no real time capability. To use it in a clinical setting we invented a time efficient algorithm, called “phase root seeking” [2], which in a current system is able to calculate up to 30 strain images per second using a conventional desktop PC. Similar to [1], time shifts are estimated using a discrete number of windows at discrete depths. The time shift τm,k of the k-th window of two A-lines centered around tk = k∆T is estimated by the following iterative formula L k m k m , 1 , 0 , , − τ = τ (1)