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Biomedical subjects

Jean-Yves Chapelon

Publications and source records attributed to Jean-Yves Chapelon.

15 recordsLinked to original sources

Control of prostate cancer by transrectal HIFU in 227 patients.

PURPOSE: To evaluate the results of high-intensity focused ultrasound (HIFU) treatment of localized prostate cancer with reference to disease-related prognostic factors. MATERIALS AND METHODS: Patients with T1-2 localized prostate cancers, prostate specific antigen (PSA) 1 ng/ml with three consecutive rises. RESULTS: The study included 227 patients. Mean follow-up was 27+/-20 months (12-121 months). Eighty-six percent had negative control biopsies. Median nadir PSA was 0.10 ng/ml. The actuarial 5-year disease-free survival rate (DFSR), combining pathologic and biochemical outcomes, was 66%. DFSR showed a significant decrease when stratified according to initial PSA level: 90% with PSA <or=4 ng/ml versus 57% and 61% with PSA between 4.1 and 10, and between 10.1 and 15 ng/ml, respectively. Incontinence and bladder neck stricture decreased with the treatment procedure standardization from 28% and 31% to 9% and 6%, respectively. CONCLUSIONS: HIFU for localized prostate cancer offered high control of local disease with low morbidity. The ability to repeat the HIFU treatment is of major interest.

Aged↗

Evaluation of color Doppler in guiding prostate biopsy after HIFU ablation.

OBJECTIVE: Transrectal ultrasound cannot accurately depict early cancer recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. We evaluated transrectal color Doppler (CD) in guiding post-HIFU prostate biopsy. METHODS: Prostate CD-guided sextant biopsies were obtained in 82 patients who had undergone prostate HIFU ablation for cancer, 24 of whom had hormone therapy before the treatment. At the time of biopsy, a subjective CD score was given to all biopsy sites (0=no flow; 1=minimal flow; 2=suspicious flow pattern). CD findings were compared with biopsy results. RESULTS: CD was a significant predictor of biopsy findings, according to univariate and multivariate site-by-site analysis. However, only 36 of 94 sites with residual cancer had positive CD findings, and thus, negative CD findings should not preclude random biopsy. There was a significant interaction between CD diagnostic capability and a history of hormone therapy before HIFU treatment. CD was a significant and independent predictor of biopsy findings in patients who had not received hormone therapy (odds ratio: 4.4; 95%CI: 2.5-7.9; p<0.0001), but not in those who had (odds ratio: 1.3; 95%CI: 0.5-3.4; p>0.5). CONCLUSION: Biopsy taken in CD-positive sites were 4.4 times more likely to contain cancer in patients who did not receive hormone therapy. CD could not reliably depict cancer recurrence in patients with history of hormone therapy.

Aged↗

In vitro experimental study on the treatment of superficial venous insufficiency with high-intensity focused ultrasound.

A major cause of superficial venous insufficiency is valvular dysfunction in the great saphenous vein. Dilation of the annulus inhibits valve closure preventing reflux in the vein. This study suggests curing dilation by shrinking the collagen fibers in the vein wall using high-intensity focused ultrasound. An in vitro feasibility study was carried out on 20 segments of human saphenous vein. A spherical probe was used to create two 9-mm-long exposure regions on the vein wall in each segment. The focal point of the sound field was moved mechanically along the vein. Different combinations of in situ acoustic intensity and sound source speeds were tested. A contraction index, which expresses the retraction of the vein after ultrasound exposure, was measured between 7 (+/-1) and 24 (+/-8)%. Histologic analysis verified the absence of vein rupture, vein perforation and tissue carbonisation after ultrasound exposure.

Acoustics↗

Intraluminal high intensity ultrasound treatment in the esophagus under fast MR temperature mapping: in vivo studies.

New curative and palliative treatments are needed to respond to the poor prognosis of esophageal cancer. The purpose of this study was to determine whether magnetic resonance imaging (MRI) and MR thermometry can be used to monitor the thermal ablation induced by an intraluminal high-intensity ultrasound applicator positioned in the esophagus. Experiments were performed in vivo in 2 pig esophagi (25 thermal lesions per pig). Respiratory gated or cardiac gated MR thermometry was performed with segmented echo-planar imaging gradient echo sequences. All MR acquisitions were performed without susceptibility artifacts or radiofrequency interference with the ultrasound device. The experimental procedure proposed for accurate measurement of temperature in the esophagus was found to achieve an SD of +/- 1.5 degrees C for respiratory gating and +/- 3.1 degrees C for cardiac gating. Gd-enhanced T(1)-weighted images were used to depict coagulation necrosis. Autopsy was performed immediately after the treatment. Ultrasound effects were inspected visually, and the dimensions of the lesions in the liver neighboring the esophagus were compared with those determined on the MRI images. The visually assessed thermal lesions showed good correlation with the MRI data (10% mean volume difference). The feasibility of esophageal thermal ablation using intraluminal high-intensity ultrasound and of on-line MR temperature monitoring was demonstrated.

Animals↗

Monitoring the formation of thermal lesions with heat-induced echo-strain imaging: a feasibility study.

We investigated the feasibility of using echo-strain images to visualize the extent of high-intensity ultrasound (US)-induced thermal lesions during their formation. Echo-strain, defined as the relative deformation of the backscattered ultrasonic signal, is due to tissue expansion and to changes in the speed of sound during heating. First, a theoretical framework was developed to predict the influence of these effects on the echo signal. Then, a simulation tool was developed to create simulated echo-strain images in thermal lesions. Finally, experimental echo-strain images were acquired in 10 porcine liver samples in vitro for various exposure durations and ultrasonic intensities (resulting in lesions that extended 3 to 8 mm deep from the surface). For this purpose, radiofrequency (RF) frames were acquired at 8 frames per s while heating. For each consecutive pair of RF frames, an echo-strain image was calculated using standard elastographic processing. The echo-strain images were cumulated and displayed. The experimental echo-strain images were compared with gross pathology. The (isoechoic) lesions were visible both in simulated and in experimental cumulated echo-strain images as apparent expansion areas (tensile echo-strain), whereas surrounding tissues exhibited apparent compression. The tensile echo-strain area underestimated the lesion in simulations, but was representative of the lesion in experiments. High correspondence was found between the lesion depth measured from experimental cumulative echo-strain images (y) and from gross pathology (x) (Pearson's correlation = 0.90, linear regression y = x-0.1 mm, residual error = 0 +/- 0.9 mm). We hypothesized that significant tissue expansion made the thermal lesions highly visible in the experimental echo-strain images. In two cases, the ultrasonic intensity was too low to induce a lesion, and the corresponding experimental echo-strain images showed no visible lesion. We conclude that cumulative echo-strain images have the potential to monitor the formation of high-intensity US-induced thermal lesions.

Algorithms↗

Synergistic inhibitory effect of high-intensity focused ultrasound combined with chemotherapy on Dunning adenocarcinoma.

OBJECTIVE: To evaluate the therapeutic effect of high-intensity focused ultrasound (HIFU) combined with chemotherapy (paclitaxel + estramustine) on AT2 Dunning adenocarcinoma, as no satisfactory treatment for localized prostate cancer is available for patients with a poor prognosis, e.g. stage T3, a high Gleason score, or a prostate-specific antigen level of >15 ng/mL. MATERIALS AND METHODS: Forty-one Dunning AT2 tumour-bearing Copenhagen rats were divided into four groups, i.e. control, chemotherapy, HIFU, and chemotherapy + HIFU (the last three treated for 1 week). The growth in tumour volume was recorded for 3 weeks, the point at which tumour volume was considered to have doubled (doubling time). The growth curves of each group were plotted and evaluated statistically. RESULTS: At 30 days of follow-up the distributions of tumour volume with treatment group were significantly different (P < 0.001); volumes were significantly greater in the control than in the chemotherapy-only or in the HIFU-only group (both P = 0.006). The greatest difference was between the chemotherapy + HIFU and the control group. The tumour doubling times were 13.2 days for HIFU-only, 31.2 days for chemotherapy + HIFU and 7.7 days for the controls. CONCLUSION: These results suggest that this combined therapy could be useful for treating patients with high-risk prostate cancer.

Adenocarcinoma↗

[Haemostatic efficacy of a high intensity focused ultrasound applicator in lower pole partial nephrectomy in the pig].

OBJECTIVE: To evaluate the haemostatic property of a high intensity focused ultrasound (HIFU) applicator in lower pole partial nephrectomy in a porcine model. MATERIALS AND METHODS: An applicator with a flat HIFU transducer operating at a frequency of 3.78 MHz was designed. Nine female pigs weighing between 35 and 39 kg were used. The kidneys of 5 pigs were used to characterize basic lesions, study haemostatic efficacy and measure the temperature rise in treated tissues. The following 4 pigs were treated by HIFU prior to bilateral lower pole partial nephrectomy. Treatment consisted of circumferential juxtaposition of basic lesions in the lower pole with vascular clamping. Haemostatic efficacy was evaluated immediately and 30 minutes after lower pole resection. RESULTS: A 50-second ultrasound pulse with an intensity of 26 W/cm2 induced a full thickness lesion of the kidney, between 22 and 36 mm. Lesions were reproducible. The temperature rise observed in treated tissues was 62 +/- 12, 59 +/- 9 and 58 +/- 11 degrees C at distances of 15, 20 and 25 mm from the transducer, respectively. All lower pole partial nephrectomies were exsanguinated, except for one case (12.5%), in which a central renal artery was not controlled. CONCLUSIONS: Our HIFU applicator is an excellent haemostatic tool ensuring effective coagulation of the renal parenchyma, allowing dry lower pole partial nephrectomy. Improvement of the ergonomics of this applicator and adaptation to laparoscopy are currently under investigation.

Animals↗

Can color doppler predict the uniformity of HIFU-induced prostate tissue destruction?

BACKGROUND: Tissue blood perfusion influences the results of some hyperthermia and thermotherapy procedures, but its role in the outcome of prostate cancer treatment by high-intensity focused ultrasound (HIFU) has not been evaluated yet. We evaluated preoperative prostate color Doppler as a predictor of the efficacy of HIFU treatment. METHODS: Thirty-five patients underwent pre- and post-contrast color Doppler examination of the prostate before HIFU treatment. Specific software was used to calculate, on color Doppler images, the color pixel density (CPD), and the specific flow (SF, i.e., mean velocity x CPD) in different regions of interest. Post-treatment sextant biopsies were obtained in 31 patients, 5.8 +/- 2.8 months after HIFU treatment. RESULTS: No significant correlation was found between the uniformity of HIFU-induced tissue destruction observed on control biopsies and the pre-treatment CPD/SF values in any region of interest, either before or after contrast injection. On the other hand, history of radiation therapy was significantly associated with homogeneous tissue destruction and history of hormone therapy was significantly associated with incomplete tissue destruction. CONCLUSIONS: Color Doppler cannot predict the uniformity of HIFU-induced tissue destruction. History of radiation therapy was found to be a factor of favorable prognosis and history of hormone therapy was found to be a factor of poor prognosis in our population.

Aged↗

High-intensity focused ultrasound for localized thyroid-tissue ablation: preliminary experimental animal study.

OBJECTIVE: Thyroid surgery is common and complications are not rare. High-intensity focused ultrasound (HIFU) could be a possible minimally invasive alternative to surgery. The aim of this study was to assess the feasibility of using HIFU to obtain localized ablation of thyroid tissue without affecting neighboring structures. METHODS: The ewe was chosen as the model because its thyroid is easily accessible, with a size comparable to the human gland. An HIFU device designed to treat human prostate cancer was used. Eight ewes were anesthetised and their thyroids were ablated with ultrasound-guided HIFU. HIFU was generated by a 3-MHz spherical piezocomposite transducer that delivered an average of 24 (range, 9-44) ultrasound pulses per lobe covering a mean volume of 0.7 cm(3) (range, 0.2-1.8). RESULTS: Ewes were sacrificed 6-13 days after HIFU treatment and the anterior part of the neck was fixed in formalin before macroscopic and microscopic examinations. Adverse events occurred mainly for the first treated ewes before the energy delivered to the thyroid tissues was fully mastered: one animal died 3 days after HIFU, most probably because of inhalation pneumonia; the ultrasound beam hit adjacent organs in three animals. As expected, typical histologic lesions of the thyroid were obtained: central coagulative necrosis with ghost vesicular structures, disappearance of the nuclei, and cytoplasmic flocculation. At the periphery of the necrotic zone, a cell reaction was observed with fibroblastic granulation tissue, mononuclear cell infiltrate and regenerating thyroid tissue. CONCLUSION: The results of this preliminary study confirm the possibility of using HIFU in order to destroy a defined area in thyroid tissue. Future experiments in ewes will be focused on the safety of the method by refining the HIFU parameters and by developing a new equipment specially built for the thyroid.

Anesthesia↗

Improving the use of vibro-acoustography for brachytherapy metal seed imaging: a feasibility study.

Vibro-acoustography method is explored for detecting and imaging brachytherapy metal seeds in gel phantoms. In a previous paper, we have shown that some immersed objects' resonance frequencies could be detected by vibro-acoustography. Here, we use this idea to optimize the vibro-acoustic excitation of two different sized brass seeds implanted in an agar gel phantom. In the experiments, the best excitation vibration frequencies were determined either by calculating fundamental resonance frequencies for each of the seeds or the experimental optimal resonance frequency of the gel. The resulting vibro-acoustography images demonstrate remarkable contrast in acoustic emission amplitude compared with images obtained at nonresonance frequencies. Results suggest the possible application of vibro-acoustography for directing prostate brachytherapy seed implantation treatment.

Algorithms↗

[Potentiation of focal ultrasound treatment of prostate adenocarcinoma by concomitant chemotherapy with estramustine phosphate and paclitaxel].

STUDY OBJECTIVES: To demonstrate a synergistic action between high intensity focal ultrasound (HIFU) and combination chemotherapy with paclitaxel and estramustine phosphate (EMP) on a prostate cancer model. MATERIAL AND METHODS: The animal model used in this study was the Copenhagen rat and the tumour model is a Dunning R 3327-AT 2 hormone-independent prostatic adenocarcinoma cell line. Chemotherapy was administered once a week for 4 weeks according to 2 modalities: low-dose with paclitaxel 2 mg/kg/day, 1 day per week and EMP 50 mg/kg/day, 3 days per week; or high-dose with paclitaxel 3 mg/kg/day, 1 day per week and EMP 75 mg/kg/day, 3 days per week. Treatment with HIFU was performed at the second week and only 55% of the tumour volume was treated. The study was conducted on 42 rats divided into 6 arms: Control, HIFU, low-dose paclitaxel-EMP, high-dose paclitaxel-EMP, HIFU + low-dose paclitaxel-EMP and HIFU + high-dose paclitaxel-EMP. Study endpoints were the course of tumour volume and animal survival. RESULTS: After two weeks of treatment, a statistically significant difference for tumour volume was observed between the various arms of the study (p < 0.0001). The HIFU-chemotherapy arm and, to a lesser degree, the chemotherapy only arm, presented the lowest tumour progression. CONCLUSION: The combination of HIFU + paclitaxel-EMP is more effective than treatment with HIFU alone or paclitaxel-EMP alone on growth of the Dunning tumour, right from the first weeks of treatment.

Adenocarcinoma↗

Detection of object resonances by vibro-acoustography and numerical vibrational mode identification.

Chalk sphere and cylinder resonance frequencies related to compressional and bending modes were detected in water, using vibro-acoustography, a relatively new imaging technique. The variable (radiation) force of low-frequency excitation, produced by intersecting two primary focused ultrasound waves with slightly different frequencies, forces the object to vibrate. The low-frequency acoustic emission field, resulting from object vibration, was detected by a hydrophone. By fixing the object at the focus of the ultrasound beam and sweeping the frequency of one of the primary beams within a chosen bandwidth, it was possible to detect some of the resonance frequencies (those related to compressional and bending modes) via variations in acoustic emission amplitude. Experimental results showed excellent agreement with finite element calculations. This method can be used to characterize the presence of heterogeneities in various media, in the field of materials science or biology.

Journal Article↗

[Results of transrectal focused ultrasound for the treatment of localized prostate cancer (120 patients with PSA < or + 10ng/ml].

OBJECTIVES: To evaluate the efficacy of high intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer in a population of potentially curable patients. MATERIALS AND METHODS: 120 patients with clinical stage T1-T2 prostate cancer with an initial PSA < or = 10 ng/ml and not candidates for radical prostatectomy were treated by HIFU (ABLATHERM, EDAP S.A.). Clinical failure was defined by the need for adjuvant therapy (endocrine or external beam radiotherapy). Progressive disease (laboratory failure) was strictly defined by identification of residual cancer on follow-up biopsies (regardless of the PSA) or by 3 successive elevations of PSA (when follow-up biopsies were negative) with a velocity greater than 0.75 ng/ml/year. Progression-free survival rates were calculated according to the Kaplan-Meier method. Success rates stratified according to risk factors were compared by Log-rank tests. RESULTS: The patients presented the following characteristics on inclusion: mean age: 71.2 +/- 5.34 years, PSA: 5.67 +/- 2.47 ng/ml, prostatic volume: 33.6 +/- 16.5 cc, stage: T1:61, T2:59, Gleason score 2-6: 77, 7-10: 43. The mean number of HIFU session per patient was 1.5 +/- 0.7. The mean duration of catheterization was 9 days and the mean follow-up was 27 months (range: 3-96 months). Follow-up biopsies did not reveal any residual cancer in 103 patients (86%). A residual cancer was identified in 17 patients, but only 6 patients required adjuvant therapy (endocrine: n = 2, radiotherapy: n = 4), corresponding to a clinical success rate of 95%. Progression-free survival for the whole patient population was 76.9%. A significant difference (p < 0.05) was observed between patients with a Gleason score between 2 and 6 (85.4%) and patients with a Gleason score between 7 and 10 (61.3%). CONCLUSION: These results show that high intensity focused ultrasound is a treatment option achieving similar results to those of other non-surgical treatments for prostate cancer.

Aged↗

Ultrasonic elastography using sector scan imaging and a radial compression.

Elastography is an imaging technique based on strain estimation in soft tissues under quasi-static compression. The stress is usually created by a compression plate, and the target is imaged by an ultrasonic linear array. This configuration is used for breast elastography, and has been investigated both theoretically and experimentally. Phenomena such as strain decay with tissue depth and strain concentrations have been reported. However in some in vivo situations, like prostate or blood vessels imaging, this set-up cannot be used. We propose a device to acquire in vivo elastograms of the prostate. The compression is applied by inflating a balloon that covers a transrectal sector probe. The 1D algorithm used to calculate the radial strain fails if the center of the imaging probe does not correspond to the center of the compressor. Therefore, experimental elastograms are calculated with a 2D algorithm that accounts for tangential displacements of the tissue. In this article, in order to gain a better understanding of the image formation process, the use of ultrasonic sector scans to image the radial compression of a target is investigated. Elastograms of homogeneous phantoms are presented, and compared with simulated images. Both show a strain decay with tissue depth. Then experimental and simulated elastograms of a phantom that contains a hard inclusion are presented, showing that strain concentrations occur as well. A method to compensate for strain decay and therefore to increase the contrast of the strain elastograms is proposed. It is expected that such information will help to interpret and possibly improve the elastograms obtained via radial compression.

Algorithms↗

Optimizing the shape of ultrasound transducers for interstitial thermal ablation.

Heat deposition by interstitial routes, especially with ultrasound-based instruments, is becoming a valuable therapeutic option for the treatments of sites, which are difficult to access from outside of the body. The active part of most interstitial ultrasound applicators described in the literature is logically tubular to induce cylindrical volumes of coagulation necrosis. Because the pressure generated by such tubular transducers falls off rapidly with radial distance, we previously proposed using a rotating plane transducer. For a plane wave, the pressure fall-off is only due to attenuation, which makes deeper lesions and shorter treatment times possible. This work represents an advance in the development of ultrasound applicators designed for interstitial applications. This new applicator used a rotating slightly focused transducer. A brief theoretical analysis resulted in the choice of a long focal distance of 22 mm to obtain a nearly constant pressure all along the therapeutic depth. To experimentally validate this focal distance, pressure measurements were made in a tissue mimicking liquid phantom and the results were compared with those obtained with a plane transducer. In vitro experiments showed that necrosis could be induced at a depth of 15 mm. In the same conditions, the greatest depth attained with a plane transducer was only 10 mm. Because each individual lesion is narrower, more lesions and more time are required to necrose a cylindrical volume. The main advantage of this new type of applicator is that it can be used to induce necrosis at a greater depth without varying either the frequency, the intensity or the transducer cooling efficiency.

Acoustics↗