Vascular targeted photodynamic therapy with TOOKAD® Soluble (WST11) in localized prostate cancer: efficiency of automatic pre-treatment planning.

Vascular targeted photodynamic therapy (VTP) with WST11 is a novel non-thermal focal treatment for localized prostate cancer that has shown favorable and early efficacy results in previously published studies. In this work, we investigate the efficiency of automatic dosimetric treatment planning. An action model established in a previous study was used in an image-guided optimization scheme to define the personalized optimal light dose for each patient. The calculated light dose is expressed as the number of optical cylindrical fibers to be used, their positions according to an external insertion grid, and the lengths of their diffuser parts. Evaluation of the method was carried out on data collected from 17 patients enrolled in two multi-centric clinical trials. The protocol consisted of comparing the method-simulated necrosis to the result observed on day 7 MR enhanced images. The method performances showed that the final result can be estimated with an accuracy of 10%, corresponding to a margin of 3 mm. In addition, this process was compatible with clinical conditions in terms of calculation times. The overall process took less than 10 min. Different aspects of the VTP procedure were already defined and optimized. Personalized treatment planning definition remained as an issue needing further investigation. The method proposed herein completes the standardization of VTP and opens new pathways for the clinical development of the technique.

Gland and Zonal Segmentation of Prostate on T2W MR Images.

For many years, prostate segmentation on MR images concerned only the extraction of the entire gland. Currently, in the focal treatment era, there is a continuously increasing need for the separation of the different parts of the organ. In this paper, we propose an automatic segmentation method based on the use of T2W images and atlas images to segment the prostate and to isolate the peripheral and transition zones. The algorithm consists of two stages. First, the target image is registered with each zonal atlas image then the segmentation is obtained by the application of an evidential C-Means clustering. The method was evaluated on a representative and multi-centric image base and yielded mean Dice accuracy values of 0.81, 0.70, and 0.62 for the prostate, the transition zone, and peripheral zone, respectively.

3D simulation of pelvic system numerical simulation for a better understanding of the contribution of the uterine ligaments.

INTRODUCTION AND HYPOTHESIS: Genital prolapse remains a complex pathological condition. Physiopathology remains poorly understood, aetiology is multi-factorial, surgery is not always satisfying, as the rate of relapse cannot be overlooked. More over a good anatomical result will not always guarantee functional satisfaction. The aim of our study is to have a better understanding of the involvement of uterine ligaments in pelvic statics via 3D simulation. METHODS: Simulation of pelvic mobility is performed with a validated numerical model in a normal situation (standing up to lying down) or induced pathological ones where parts of the constitutive elements of the model are virtually "cut" independently. Displacements are then discussed. RESULTS: Numerical results have been compared with dynamic MRI for two volunteers. Dynamic sequences had 90 images, and 180 simulations have been validated. Results are coherent with clinical data and the literature, thus validating our mechanical approach. Uterine ligaments are involved in pelvic statics, but their lesions are not sufficient to generate a genital prolapse. Round ligaments play a part in uterine orientation; the utero-sacral ligaments support the uterus when standing up. CONCLUSIONS: Pelvic normal and pathological mobility study via modelling and 3D simulation is a new strategy in understanding the complex multifactorial physiopathology of genital prolapse. This approach must be validated in a larger series of patients. Nevertheless, pelvic ligaments seem to play an important role in statics, especially, in agreement with a literature survey, utero-sacral ligaments in a standing position.

Laser-assisted lipolysis in the treatment of gynecomastia: a prospective study in 28 patients.

Gynecomastia is the most common breast pathology. Numerous excisions and liposuction techniques have been described to correct bilateral male breast enlargement. Recently, there has been a shift from the open approach to minimally invasive techniques. This article reports a 5-year experience using laser-assisted lipolysis (LAL) to treat gynecomastia, and describes the surgical technique. Between January 2006 and December 2010, a total of 28 patients with bilateral gynecomastia were treated with LAL. Patients had a mean age of 36.5 years (range 24 to 56 years). LAL was performed with a 980-nm diode laser (continuous emission, 15 W power, 8-12 kJ total energy per breast) after tumescent anesthetic infiltration. The breast was evaluated objectively by two physicians who compared chest circumference and photographs. Patients were also asked to score the results using a visual analogue scale: 75 to 100 (very good), 50-74 (good), 25 to 49 (fair) and 0 to 24 (poor). The postoperative period for all patients was incident-free. After 6 months, 18 patients (64.3%) scored the results as "very good", 6 as "good" (21.4%), 3 as "fair" (10.7%) and 1 "poor" (3.6%). Mean chest circumferences pre- and postoperatively were, respectively, 117.4 ± 11.1 cm and 103.3 ± 7.5 cm (p < 0.001), corresponding to a mean difference of 14.1 cm. Physicians scored the photographs as "very good" in 22 patients (78.6%), as "good" in five patients (17.9%), and as "fair" in one patient (3.6%). LAL in gynecomastia is safe and produces significant effects on fatty tissue, with a reduction in breast volume, together with significant skin tightening. Provided an appropriate amount of energy is delivered by an experienced operator, the results are both significant and consistent.

Prostate cancer characterization on MR images using fractal features.

PURPOSE: Computerized detection of prostate cancer on T2-weighted MR images. METHODS: The authors combined fractal and multifractal features to perform textural analysis of the images. The fractal dimension was computed using the Variance method; the multifractal spectrum was estimated by an adaptation of a multifractional Brownian motion model. Voxels were labeled as tumor/nontumor via nonlinear supervised classification. Two classification algorithms were tested: Support vector machine (SVM) and AdaBoost. RESULTS: Experiments were performed on images from 17 patients. Ground truth was available from histological images. Detection and classification results (sensitivity, specificity) were (83%, 91%) and (85%, 93%) for SVM and AdaBoost, respectively. CONCLUSIONS: Classification using the authors' model combining fractal and multifractal features was more accurate than classification using classical texture features (such as Haralick, wavelet, and Gabor filters). Moreover, the method was more robust against signal intensity variations. Although the method was only applied to T2 images, it could be extended to multispectral MR.

Zonal segmentation of prostate using multispectral magnetic resonance images.

PURPOSE: To investigate the performance of a new method of automatic segmentation of prostatic multispectral magnetic resonance images into two zones: the peripheral zone and the central gland. METHODS: The proposed method is based on a modified version of the evidential C-means clustering algorithm. The evidential C-means optimization process was modified to introduce spatial neighborhood information. A priori knowledge of the prostate's zonal morphology was modeled as a geometric criterion and used as an additional data source to enhance the differentiation of the two zones. RESULTS: Thirty-one clinical magnetic resonance imaging series were used to validate the method, and interobserver variability was taken into account in assessing its accuracy. The mean Dice Similarity Coefficient was 89% for the central gland and 80% for the peripheral zone, as validated by a consensus from expert radiologist segmentation. CONCLUSIONS: The method was statistically insensitive to variations in patient age, prostate volume and the presence of tumors, which increases its feasibility in a clinical context.

[Photodynamic therapy and prostate cancer]. / Thérapie photodynamique et cancer de la prostate.

PURPOSE: Photodynamic therapy (PDT) is an innovative therapeutic modality in urologic oncology. MATERIAL AND METHODS: We reviewed the current literature on principles and modalities of PDT in prostatic oncology. RESULTS: Focal therapy of prostate cancer is an application field of PDT. Clinical phase II studies are ongoing to determine PDT efficacy and safety in this indication. PDT as salvage treatment after prostatic radiotherapy has been tested. Carcinologic results were promising but important side effects were reported. Individual dosimetric planification is necessary to avoid this toxicity. CONCLUSION: PDT first clinical experience for prostate cancer has showed its technical feasibility. Several research ways are currently in study to improve carcinologic efficacy and to limit potential side effects.

An easy-to-use phantom and protocol for weekly PET quality assessment: a multicenter study.

The authors have developed a simple phantom and dedicated software for the quality assessment of positron emission tomography (PET) scanners. The phantom is a parallelepiped box filled with a relatively low activity 18FDG solution and in which simple test objects are placed. Various image quality parameters are checked, including signal-to-noise ratio, image uniformity, slice thickness, slice sensitivity profile, spatial resolution, and dose calibration accuracy. Automatic image analysis consists in detecting surfaces and objects, defining regions of interest, acquiring reference point coordinates, and establishing gray-scale profiles. The total time needed for quality assessment (preparation and image acquisition) is less than 15 min with 37 MBq (1 mCi) 18FDG. The system's ease of use encourages frequent image quality assessment-for example, the comparison of PET scanners in interdepartment studies and the monitoring and evaluation of possible drifts over time. By way of an example, the authors present weekly quality assessment results obtained over up to 7 months at four PET facilities.

3D delineation of prostate, rectum and bladder on MR images.

In radiotherapy planning, target volumes and organs at risk delineation are a tedious and time-consuming task. In this paper we address a method to assist the radiologist in this task. We developed a 3D deformable model for prostate segmentation and used a seeded region growing algorithm for bladder and rectum delineation on MR images. Evaluation of the methods is made by comparison of the results to manual delineation in 24 patients. The following parameters were measured: volume ratio (V R) (automatic/manual), volume overlap (V O) (ratio of the volume of intersection to the volume of union, optimal value=1), and correctly delineated volume (V C) (percent ratio of the volume of intersection to the manual defined volume, optimal value=100). For prostate the V R, V O and V C were 1.13 (+/-0.1), 0.78 (+/-0.05) and 94.75 (+/-3.3), respectively. For rectum, the V R, V O and V C were 0.97 (+/-0.1), 0.78 (+/-0.06) and 86.52 (+/-5), respectively. V R, V O and V C were 0.95 (+/-0.03), 0.88 (+/-0.03) and 91.29 (+/-3.1) for bladder, respectively.

[Dosimetric evaluation of an automatic segmentation tool of pelvic structures from MRI images for prostate cancer radiotherapy]. / Evaluation dosimétrique d'un outil de délinéation automatique des organes pelviens à partir d'images IRM pour la radiothérapie du cancer prostatique.

PURPOSE: An automatic segmentation tool of pelvic structures from MRI images for prostate cancer radiotherapy was developed and dosimetric evaluation of differences of delineation (automatic versus human) is presented here. MATERIALS AND METHODS: CTV, rectum and bladder were defined automatically and by a physician in 20 patients. Treatment plans based on "automatic" volumes were transferred on "manual" volumes and reciprocally. Dosimetric characteristics of PTV (V(95), minimal, maximal and mean doses), rectum (V(50), V(70), maximal and mean doses) and bladder (V(70), maximal and mean doses) were compared. RESULTS: Automatic delineation of CTV did not significantly influence dosimetric characteristics of "manual" PTV. Rectal V(50) and V(70) were not significantly different; mean rectal dose is slightly superior (43.2 versus 44.4Gy, p=0.02, Student test). Bladder V(70) was significantly superior too (19.3 versus 21.6, p=0.004). Organ-at-risk (OAR) automatic delineation had little influence on their dosimetric characteristics; rectal V(70) was slightly underestimated (20 versus 18.5Gy, p=0.001). CONCLUSION: CTV and OAR automatic delineation had little influence on dosimetric characteristics. Software developments are ongoing to enable routine use and interobserver evaluation is needed.

Interventional therapy procedures assisted by medical imaging and simulation. The experience of U 703 Inserm (Lille France).

Since the early 1990s, minimally invasive techniques have been increasingly used in ever more and diversified fields of application. These techniques have some shared characteristics (predominant role of medical imaging, intensive use of new communication technologies, a multidisciplinary medical and scientific framework, etc.) but also shared specific problems (high-tech tools unfamiliar to the medical users, a major and long period of time for technological development, unavailability of training systems, difficulties in obtaining regulatory approval). For a long time, our Laboratory of Medical Physics (U 703 Inserm) has developed an innovative research activity in biomedical engineering in the field of assisted therapy, medical imaging and medical simulation. This paper presents the general context of interventional therapy procedures assisted by image and simulation and describes our scientific activities based on realistic objectives close to medical practice.

Computer-aided analysis of prostate multiparametric MR images: an unsupervised fusion-based approach.

OBJECTIVE: The aim of this study is to provide an automatic framework for computer-aided analysis of multiparametric magnetic resonance (mp-MR) images of prostate. METHOD: We introduce a novel method for the unsupervised analysis of the images. An evidential C-means classifier was adapted for use with a segmentation scheme to address multisource data and to manage conflicts and redundancy. RESULTS: Experiments were conducted using data from 15 patients. The evaluation protocol consisted in evaluating the method abilities to classify prostate tissues, showing the same behaviour on the mp-MR images, into homogeneous classes. As the actual diagnosis was available, thanks to the correlation with histopathological findings, the assessment focused on the ability to segment cancer foci. The method exhibited global sensitivity and specificity of 70 and 88 %, respectively. CONCLUSION: The preliminary results obtained by these initial experiments showed that the method can be applied in clinical routine practice to help making decision especially for practitioners with limited experience in prostate MRI analysis.

A survey of prostate modeling for image analysis.

Computer technology is widely used for multimodal image analysis of the prostate gland. Several techniques have been developed, most of which incorporate a priori knowledge extracted from organ features. Knowledge extraction and modeling are multi-step tasks. Here, we review these steps and classify the modeling according to the data analysis methods employed and the features used. We conclude with a survey of some clinical applications where these techniques are employed.

An image guided treatment platform for prostate cancer photodynamic therapy.

This study describes a multimodality images based platform to drive photodynamic therapies of prostate cancer using WST 11 TOOKAD Soluble drug. The platform integrates a pre-treatment planning tool based on magnetic resonance imaging and a per-treatment guidance tool based on transrectal ultrasound images. Evaluation of the platform on clinical data showed that prediction of the therapy outcome was possible with an accuracy of 90 %.

Focal therapy of prostate cancer: energies and procedures.

PURPOSE: Over the last years, focal therapy has emerged as an intermediate management technique between radical approaches (radical prostatectomy, external beam radiation, and brachytherapy) and watchful waiting to manage some early stage prostate cancers (CaP). Different energy modalities are being developed. The aim of this study is to review these energy modalities and their indications. MATERIALS AND METHODS: We reviewed the literature to concentrate on the practical aspects of focal therapy for CaP with the following key words: photodynamic therapy, high intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation, electroporation, radio frequency, external beam radiation, organ-sparing approach, focal therapy, CaP, and then by cross-referencing from previously identified studies. RESULTS: Prostatic tumor ablation can be achieved with different energies: freezing effect for cryotherapy, thermal effect using focalized ultrasound for HIFU, and using thermal effect of light for focal laser ablation (FLA) and activation of a photosensitizer by light for PDT, among others. Radio frequency and microwave therapy have been tested in this field and demonstrated their usefulness. Electroporation is currently being developed on preclinical models. External beam radiation with microboost on neoplastic foci is under evaluation. HIFU and cryotherapy require the use of sophisticated and expensive machines and, consequently, the procedure is expensive. Laser techniques seem to be less onerous, with the added advantage of size. CONCLUSIONS: Several energy modalities are being developed to achieve the trifecta of continence, potency, and oncologic efficiency. Those techniques come with low morbidity but clinical experience is limited regarding to oncologic outcome. Comparison of the different focal approaches is complex owing to important heterogeneity of the trials. In the future, it seems likely that each technique will have its own selective indications.

Three-dimensional skeletonization and symbolic description in vascular imaging: preliminary results.

OBJECTIVE: A general method was developed to analyze and describe tree-like structures needed for evaluation of complex morphology, such as the cerebral vascular tree. Clinical application of the method in neurosurgery includes planning of the surgeon's intraoperative gestures. METHOD: We have developed a 3D skeletonization method adapted to tubular forms with symbolic description. This approach implements an iterative Dijkstra minimum cost spanning tree, allowing a branch-by-branch skeleton extraction. The proposed method was implemented using the laboratory software platform (ArtiMed). The 3D skeleton approach was tested on simulated data and preliminary trials on clinical datasets mainly based on magnetic resonance image acquisitions. RESULTS: A specific experimental evaluation plan was designed to test the skeletonization and symbolic description methods. Accuracy was tested by calculating the positioning error, and robustness was verified by comparing the results on a series of 18 rotations of the initial volume. Accuracy evaluation showed a Haussdorff's distance always smaller than 17 voxels and Dice's similarity coefficient greater than 70 %. CONCLUSION: Our method of symbolic description enables the analysis and interpretation of a vascular network obtained from angiographic images. The method provides a simplified representation of the network in the form of a skeleton, as well as a description of the corresponding information in a tree-like view.

An anatomically realistic and adaptable prostate phantom for laser thermotherapy treatment planning.

PURPOSE: To construct a phantom for prostate cancer laser based thermotherapy treatment planning and simulation. METHODS: A realistic and adaptable prostate phantom was designed. It exhibits the following properties: valid and complete description of the prostate anatomy, material with similar optical properties of prostate tissues and compatibility with clinical imaging protocols mainly multiparametric magnetic resonance (MR) and transrectal ultrasound imaging (TRUS). RESULTS: Preliminary experiments with the phantom using an interstitial laser treatment protocol allowed obtaining results similar to those obtained on preclinical model. CONCLUSIONS: These results proved that this phantom could allow a real simulation of laser therapy procedure: target definition and fibers' placement optimization using MR imaging, treatment delivery, and finally treatment monitoring using TRUS imaging.

Efficiency of 5-ALA mediated photodynamic therapy on hypoxic prostate cancer: a preclinical study on the Dunning R3327-AT2 rat tumor model.

OBJECTIVES: To evaluate photodynamic therapy (PDT) using 5-ALA-induced protoporphyrin IX (PPIX) in an in vivo hypoxic tumor model and its monitoring using MRI. MATERIAL AND METHODS: Dunning R3327-AT2 tumors were grafted in the neck of Copenhagen rats. PDT using 150 mg 5-ALA/kg i.v. was performed by focal interstitial illumination of the photosensitized tumor (λ=633 nm; fluence=100 J/cm(2)). MRI at baseline and 2 days after treatment (T1, T2 and dynamic gadolinium enhanced sequences) were performed. Necrosis volumes were determined on post-procedure MRI. Tumors were resected 2 days post-PDT and obtained necrosis was determined histopathologically. Intra-tumoral PPIX distribution was evaluated using confocal microscopy and tissue porphyrin quantification. RESULTS: Twenty rats were treated divided into three groups: continuous (n=7), fractionated illumination (n=7), and a control group receiving only light or only ALA or neither (n=6). Baseline MRI confirmed the hypoxic character of tumors. Necrosis volumes determined on posttreatment MRI were not reproducible and presented with important geometric and volumetric variability. Average necrosis volumes of 0.39 cc (0-0.874 cc) in the continuous group, 0.24 cc (0.107-0.436 cc) in the fractionated group and 0.012 cc (0-0.071 cc) in the control group were observed. Intra-tumoral PPIX distribution was heterogeneous and PPIX quantification revealed low intra-tumoral concentration. CONCLUSION: Necrosis volumes induced by 5-ALA-mediated PDT were highly variable and non reproducible, probably because of lack of intra-tissular oxygen. Photosensitizer was poorly represented inside the tumor and its distribution was heterogeneous. Our study suggests that 5-ALA-mediated PDT might not be the best management option for hypoxic prostatic adenocarcinoma.

ProstAtlas: a digital morphologic atlas of the prostate.

Computer-aided medical interventions and medical robotics for prostate cancer have known an increasing interest and research activity. However before the routine deployment of these procedures in clinical practice becomes a reality, in vivo and in silico validations must be undertaken. In this study, we developed a digital morphologic atlas of the prostate. We were interested by the gland, the peripheral zone and the central gland. Starting from an image base collected from 30 selected patients, a mean shape and most important deformations for each structure were deduced using principal component analysis. The usefulness of this atlas was highlighted in two applications: image simulation and physical phantom design.

Photodynamic therapy in urology: what can we do now and where are we heading?

BACKGROUND: Photodynamic therapy (PDT) is an innovative technique in oncologic urology. Its application appears increasingly realistic to all kind of cancers with technological progress made in treatment planning and light delivery associated with the emergence of novel photosensitizers. The aim of this study is to review applications of this technique in urology. MATERIALS AND METHODS: We reviewed the literature on PDT for urological malignancies with the following key words: photodynamic therapy, prostate cancer, kidney cancer, urothelial cancer, penile cancer and then by cross-referencing from previously identified studies. RESULTS: Focal therapy of prostate cancer is an application of PDT. Clinical studies are ongoing to determine PDT efficacy and safety. PDT as salvage treatment after radiotherapy has been tested. Oncologic results were promising but important side effects were reported. Individual dosimetric planning is necessary to avoid toxicity. PDT was tested to treat superficial bladder carcinoma with promising oncologic results. Serious side effects have limited use of first photosensitizers generation. Second generation of photosensitizer allowed reducing morbidity. For upper urinary tract carcinoma and urethra, data are limited. Few studies described PDT application in penile oncology for conservative management of carcinoma in situ and premalignant lesions. For renal cancer, PDT was only tested on preclinical model despite of its potential application. No data is available concerning PDT application for testicular cancer. CONCLUSION: PDT clinical applications in urology have proved a kind of efficiency balanced with an important morbidity. Development of new photosensitizer generations and improvement in illumination protocols should permit to decrease side effects.