The conventional protocol vs. a protocol including illumination with a fabric-based biophotonic device (the Phosistos protocol) in photodynamic therapy for actinic keratosis: a randomized, controlled, noninferiority clinical study.

BACKGROUND: Topical photodynamic therapy (PDT) using methyl aminolaevulinate is a noninvasive treatment option suitable to treat clinical and subclinical actinic keratosis (AK) over a large area (field cancerization). The most widely used, conventional protocol in Europe includes illumination with a red-light lamp. This illumination commonly causes pain, and patients often cannot complete the treatment. OBJECTIVES: The aims of this paper are twofold. The first aim is to introduce a novel protocol, the Phosistos protocol (P-PDT), which includes illumination with a fabric-based biophotonic device. The second and major aim is to assess the noninferiority, in terms of efficacy for PDT of AK, of P-PDT compared with the conventional protocol (C-PDT). METHODS: A randomized, controlled, multicentre, intraindividual clinical study was conducted. Forty-six patients with grade I-II AK of the forehead and scalp were treated with P-PDT on one area (280 AK lesions) and with C-PDT on the contralateral area (280 AK lesions). The primary end point was the lesion complete response (CR) rate at 3 months, with an absolute noninferiority margin of -10%. Secondary end points included pain scores, incidence of adverse effects and cosmetic outcome. RESULTS: Three months following treatment, the lesion CR rate of P-PDT was noninferior to that of C-PDT (79·3% vs. 80·7%, respectively; absolute difference -1·6%; one-sided 95% confidence interval -4·5% to infinity). The noninferiority of P-PDT to C-PDT in terms of the lesion CR rate remained at the 6-month follow-up (94·2% vs. 94·9%, respectively; absolute difference -0·6%; one-sided 95% confidence interval -2·7% to infinity). Moreover, the pain score at the end of illumination was significantly lower for P-PDT than for C-PDT (mean ± SD 0·3 ± 0·6 vs. 7·4 ± 2·3; P < 0·001). CONCLUSIONS: P-PDT is noninferior to C-PDT in terms of efficacy for treating AK of the forehead and scalp and resulted in much lower pain scores and fewer adverse effects. What's already known about this topic? Topical photodynamic therapy using methyl aminolaevulinate is effective for treating actinic keratosis. In Europe, the conventional protocol involves illumination with a red-light lamp. Unfortunately, pain is often experienced by patients undergoing this protocol. An alternative protocol that uses daylight illumination has recently been shown to be as effective as the conventional protocol while being nearly painless. However, this alternative protocol can be conducted only in suitable weather conditions. What does this study add? The Phosistos protocol is demonstrated to be as effective as the conventional protocol, nearly as painless as the daylight protocols and suitable year round for treatment of actinic keratosis.

Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the noninferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.

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.

Combining a deformable model and a probabilistic framework for an automatic 3D segmentation of prostate on MRI.

PURPOSE: Accurate localization and contouring of prostate are crucial issues in prostate cancer diagnosis and/or therapies. Although several semi-automatic and automatic segmentation methods have been proposed, manual expert correction remains necessary. We introduce a new method for automatic 3D segmentation of the prostate gland from magnetic resonance imaging (MRI) scans. METHODS: A statistical shape model was used as an a priori knowledge, and gray levels distribution was modeled by fitting histogram modes with a Gaussian mixture. Markov fields were used to introduce contextual information regarding voxels' neighborhoods. Final labeling optimization is based on Bayesian a posteriori classification, estimated with the iterative conditional mode algorithm. RESULTS: We compared the accuracy of this method, free from any manual correction, with contours outlined by an expert radiologist. In 12 cases, including prostates with cancer and benign prostatic hypertrophy, the mean Hausdorff distance and overlap ratio were 9.94 mm and 0.83, respectively. CONCLUSION: This new automatic prostate MRI segmentation method produces satisfactory results, even at prostate's base and apex. The method is computationally feasible and efficient.

Volume quantification by fuzzy logic modelling in freehand ultrasound imaging.

INTRODUCTION: Many algorithms exist for 3D reconstruction of data from freehand 2D ultrasound slices. These methods are based on interpolation techniques to fill the voxels from the pixels. For quantification purposes, segmentation is involved to delineate the structure of interest. However, speckle and partial volume effect errors can affect quantification. OBJECTIVE: This study aimed to assess the effect of the combination of a fuzzy model and 3D reconstruction algorithms of freehand ultrasound images on these errors. METHODS: We introduced a fuzzification step to correct the initial segmentation, by weighting the pixels by a distribution function, taking into account the local gray levels, the orientation of the local gradient, and the local contrast-to-noise ratio. We then used two of the most wide-spread reconstruction algorithms (pixel nearest neighbour (PNN) and voxel nearest neighbour (VNN)) to interpolate and create the volume of the structure. Finally, defuzzification was used to estimate the optimal volume. VALIDATION: B-scans were acquired using 5 MHz and 8 MHz ultrasound probes on ultrasound tissue-mimicking phantoms. Quantitative evaluation of the reconstructed structures was done by comparing the method output to the real volumes. Comparison was also done with classical PNN and VNN algorithms. RESULTS: With the fuzzy model quantification errors were less than 4.3%, whereas with classical algorithms, errors were larger (10.3% using PNN, 17.2% using VNN). Furthermore, for very small structures (0.5 cm(3)), errors reached 24.3% using the classical VNN algorithm, while they were about 9.6% with the fuzzy VNN model. CONCLUSION: These experiments prove that the fuzzy model allows volumes to be determined with better accuracy and reproducibility, especially for small structures (<3 cm(3)).

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.

3D mutifractal analysis: a new tool for epileptic fit sources detection in SPECT images.

One of the imaging modalities used for the diagnosis of epilepsy is SPECT (Single-Photon Emission Computed Tomography). Ictal and interictal images are registered to MR images (SISCOM (Substracted Ictal Spect COregistred to MR) to delineate the sources. However, in some cases and for many reasons, the used method does not lead to precise delimitation of epileptic fit sources. In this case, works have been investigated on group's studies or in combining others modalities like EEG (Electroencephalography). This study investigates the possibility of using a mathematic model for the image texture to detect the changes on SPECT images. Beyond encouraging preliminary results concerning the multifractal analysis to distinguish volunteers and epileptic patients, our aim was to detect sources by the singularity spectrum compute. The experiment is divided into two phases. First, we developed a 3D method for the singularity spectrum compute. In the test phase, we applied this multifractal spectrum to the sources detection on SPECT images. The results obtained on a base of seven patients show that the proposed method is encouraging. Indeed, the detections of epileptic fit sources obtained were in agree with the expert diagnostic.

Combining MIP images and fuzzy set principles for vessels segmentation: application to TOF MRA and CE-MRA.

In this paper, we introduce an approach for selective segmentation of vascular structure which has been applied for intracranial vessels. Based on MIP and fuzzy set principles, this approach brings good results while segmentation is achieved rapidly. The added value of this approach is a minimal user interaction and the taking into account of the volume partial effect. This approach has been evaluated following different experiment: phantom tests, clinical data, and methods comparison.

Comparison between shifted Spearman rank correlation test and SPM in fMRI.

A new improving method to compute Spearman rank correlation test has been developed. This method is based on the use of a response to stimulation delay referred by many authors. Visual results tend to prove the method efficiency which is confirmed by obtained overlap rates; moreover this method can easily be adapted in a clinical context.

New time-shifted Z-score and Student's test in fMRI.

A new approach to compute z-score and Student's test in functional MRI has been developed. This approach tends to involve standard z-score and Student's test computation. This approach is based on the delay of the response compared to the stimulation introduced by many authors. The results obtained prove the methods efficiency; moreover these methods can be easily adapted in a clinical context. This paper presents the new computation and the validation.

Ultrasound image registration for patient setup in conformal radiotherapy of prostate cancer.

The goal of 3D conformal radiotherapy (CRT) is to conform the high dose region to the target volume while sparing surrounding normal tissue. Knowledge about the mobility of organs relative to the bony anatomy and to the reference position is of great importance when daily positioning patient. In this work we present a method to monitor patient setup during CRT of prostate cancer. The method is based on ultrasound tracking and matching with planning modality.