Multimodal imaging in radiotherapy: Focus on adaptive therapy and quality control.

Improved computer resources in radiation oncology department have greatly facilitated the integration of multimodal imaging into the workflow of radiation therapy. Nowadays, physicians have highly informative imaging modalities of the anatomical region to be treated. These images contribute to the targeting accuracy with the current treatment device, impacting both segmentation or patient's positioning. Additionally, in a constant effort to deliver personalized care, many teams seek to confirm the benefits of adaptive radiotherapy. The published works highlight the importance of registration algorithms, particularly those of elastic or deformable registration necessary to take into account the anatomical evolutions of the patients during the course of their therapy. These algorithms, often considered as "black boxes", tend to be better controlled and understood by physicists and physicians thanks to the generalization of evaluation and validation methods. Given the still significant development of medical imaging techniques, it is foreseeable that multimodal registration needs require more efficient algorithms well integrated within the flow of data.

Superficial temporal artery-middle cerebral artery anastomosis patency correlates with cerebrovascular reserve in adult moyamoya syndrome patients.

OBJECTIVES: To evaluate the effectiveness of superficial temporal artery-middle cerebral artery (STA-MCA) bypass in improving cerebrovascular reserve (CVR) in Moyamoya syndrome. PATIENTS AND METHODS: This prospective study included 10 consecutive patients treated for Moyamoya syndrome by STA-MCA bypass in our institution between June 2016 and January 2018. Perfusion MRI, transcranial Doppler and 99m Tc-HMPAO SPECT with acetazolamide challenge were performed before and after treatment to evaluate perfusion and cerebrovascular reserve. STA-MCA bypass was indicated for patients with history of ischemic or hemorrhagic stroke and when CVR was diminished on both transcranial Doppler and 99m Tc-HMPAO SPECT with acetazolamide challenge or brain perfusion was deteriorated on MRI. RESULTS: Bypass anastomosis was patent in all patients at end of surgery. One patient presented partial postoperative sensorimotor deficit related to an ischemic lesion in the frontal cortical area. One patient presented regressive chronic subdural hematoma without neurological deficit. Three months after treatment, CVR was significantly improved in 8 patients and unchanged in 2, probably related to low flow. Further follow-up found CVR deterioration in 1 patient, with anastomosis occlusion at 1 year. CONCLUSION: Our data suggest that improvement in cerebral perfusion and CVR depends on flow in the STA-MCA anastomosis in patients with Moyamoya syndrome. Systematic long-term follow-up of anastomosis flow, brain perfusion and CVR improves quantification of the benefit of STA-MCA anastomosis in terms of disease progression.

A novel experimental setup for evaluating the stiffness of ankle foot orthoses.

OBJECTIVE: The purpose of this study was the construction of a new semi-automated experimental setup for the evaluation of the stiffness of ankle foot orthoses (AFOs) around an axis aligned to the anatomical ankle joint during the second rocker of the gait. The setup, developed in close collaboration with the orthopedic device company V!GO NV (Wetteren, Belgium), allows measurement of plantarflexion and dorsiflexion in the sagittal plane for a maximal range of motion of 50° (- 25° plantarflexion up to 25° dorsiflexion) in a non-destructive way. RESULTS: The mechanical properties of four 3D printed AFOs are investigated, based on the ranges of motion derived from the gait assessment of the patients when they walked with their AFO. The reliability of the stiffness measures was studied by the evaluation of the test-retest repeatability and the intra-tester and inter-tester variability. These studies revealed that the ankle stiffness can be measured with high reliability (ICC = 0.94-1.00). The obtained outcomes indicate that the experimental setup could be applied to measure the ankle stiffness of any topology of AFOs and, in the future, help finding the correlation with the information coming from the gait assessment of the patients.

Using X-rays in photodynamic therapy: an overview.

Photodynamic therapy is a therapeutic option to treat cancer and other diseases. PDT is used every day in dermatology, and recent developments in the treatment of glioblastoma, mesothelioma or prostate have demonstrated the efficacy of this modality. In order to improve the efficacy of PDT, different strategies are under development, such as the use of targeted PS or nanoparticles to improve selectivity and the design of light devices to better monitor the light dose. Due to the low penetration of light into tissue, another way to improve the efficacy of PDT to treat deep tumors is the use of upconversion NPs or bi-photon absorption compounds. These compounds can be excited in the red part of the spectrum. A relatively new approach, which we will call PDTX, is the use of X-rays instead of UV-visible light for deeper penetration into tissue. The principle of this technique will be described, and the state-of-art literature concerning this modality will be discussed. First, we will focus on various photosensitizers that have been used in combination with X-ray irradiation. To improve the efficacy of this modality, nanoparticles have been designed that allow the conversion of high-energy ionizing radiation into UV-visible light; these are potential candidates for the PDTX approach. They will be discussed at the end of this review.

Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients.

PURPOSE: Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. METHODS: Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. RESULTS: Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. CONCLUSIONS: An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs required for thoracic radiation therapy has been presented and clinically evaluated. The introduction of the proposed system in clinical routine may offer valuable new option to radiation oncologists in performing RTP.

Impact of consensus contours from multiple PET segmentation methods on the accuracy of functional volume delineation.

PURPOSE: The aim of this study was to evaluate the impact of consensus algorithms on segmentation results when applied to clinical PET images. In particular, whether the use of the majority vote or STAPLE algorithm could improve the accuracy and reproducibility of the segmentation provided by the combination of three semiautomatic segmentation algorithms was investigated. METHODS: Three published segmentation methods (contrast-oriented, possibility theory and adaptive thresholding) and two consensus algorithms (majority vote and STAPLE) were implemented in a single software platform (Artiview®). Four clinical datasets including different locations (thorax, breast, abdomen) or pathologies (primary NSCLC tumours, metastasis, lymphoma) were used to evaluate accuracy and reproducibility of the consensus approach in comparison with pathology as the ground truth or CT as a ground truth surrogate. RESULTS: Variability in the performance of the individual segmentation algorithms for lesions of different tumour entities reflected the variability in PET images in terms of resolution, contrast and noise. Independent of location and pathology of the lesion, however, the consensus method resulted in improved accuracy in volume segmentation compared with the worst-performing individual method in the majority of cases and was close to the best-performing method in many cases. In addition, the implementation revealed high reproducibility in the segmentation results with small changes in the respective starting conditions. There were no significant differences in the results with the STAPLE algorithm and the majority vote algorithm. CONCLUSION: This study showed that combining different PET segmentation methods by the use of a consensus algorithm offers robustness against the variable performance of individual segmentation methods and this approach would therefore be useful in radiation oncology. It might also be relevant for other scenarios such as the merging of expert recommendations in clinical routine and trials or the multiobserver generation of contours for standardization of automatic contouring.

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.

Recent advances in cerebrovascular simulation and neuronavigation for the optimization of intracranial aneurysm clipping.

Endovascular treatment of intracranial aneurysms (IAs) has improved to the extent that in some instances such an approach has now become safer than surgery. This has dramatically changed clinical practice by reducing the volume and increasing the complexity of IAs referred for open surgical treatment. We review the simulation techniques and dedicated vascular neuronavigation systems that have been developed to maintain the quality of aneurysm clipping in this context. Simulation of surgical approaches was made possible by the introduction of high-resolution 3D imaging techniques such as three-dimensional CT angiography (3D-CTA) and three-dimensional digital subtraction angiography (3D-DSA), enabling reproduction of the craniotomy and rotation of the vascular tree according to the orientation of the operative microscope. A virtual simulator for compiling such data, the Dextroscope®, is now available for this purpose. Simulation of final clipping has been investigated through virtual or physical models, enabling anticipation of aneurysm deformation during clip application and selection of the appropriate clip(s) in terms of number, size, shape and orientation. To improve surgical dissection guidance, specific cerebrovascular neuronavigation procedures have been developed based on 3D-CTA or 3D-DSA. These help make the operation secure by accurately predicting the location and orientation of an aneurysm within its parenchymal and vascular environment. Future simulators dedicated to cerebrovascular procedures will need to integrate representation of the brain surface and biomechanical modeling of brain and aneurysm wall deformation under retraction or during clipping. They should contribute to training and maintenance of surgical skills, thereby optimizing the quality of surgical treatment in this field.

Dijkstra's algorithm applied to 3D skeletonization of the brain vascular tree: evaluation and application to symbolic.

This paper describes the methodology and the evaluation of a 3D skeletonization algorithm applied on brain vascular structure. This method is based on the application of the minimum cost-spanning tree using Dijkstra's algorithm and seems well appropriate to tubular objects. We briefly describe the different steps, from the segmentation to the skeleton analysis. Besides, we propose an original evaluation scheme of the method based on digital phantom and clinical data. The final aim of this work is to provide a symbolic description framework applied to cerebro-vascular structures.

[Image registration: principles, validation and routine practice]. / Recalage d'images pour la délinéation: principes, validation et pratique en routine.

The registration of multimodality images to help the drawings of the targets is often used. Today, there is no quality control well known for this tool. This article described the methods for registration and the criteria for validation. In the other hand, the routine practice of centre Oscar Lambret with mutual information and visual validation only is described.

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)).

Towards an accurate and robust method based on fuzzy logic principles for the reconstruction and quantification of large volumes from MR and CT images.

The authors have previously evaluated a new method of volume reconstruction and quantification from MR images, based on fuzzy logic (FL) principles. The technique is evaluated here for larger and more complex structures by investigating its accuracy and robustness using MR and CT images. Four large (50-71 cm(3)) and complex (e.g. mimicking a prostate) structures were created and imaged on MR and CT scanners, both with increasing slice thickness. Contours were delineated to generate 112 volumes. MR and CT images were processed using the FL method and a "classical" method of reconstruction on research software. In addition, the CT images were also processed on commercial virtual simulation software. Calculated volumes were compared with actual volumes. The mean +/- standard deviation of the relative variations in calculated target volume using the FL method was found to be 4.4%+/-2.8%, whereas with the "classical" method it was 23.7%+/-6% from axial MR images and 23.3%+/-9.8% from CT images. With the "classical" method, the relative variations in calculated volumes rise with increasing slice thickness, and the displayed volumes show deformations in the longitudinal direction. With the FL method, the volume calculation is not sensitive to the slice thickness and so the deformations are minimal. When used with MR images, our FL method of volume reconstruction is accurate and robust with respect to changes in slice thickness. For CT images, the results are encouraging but some work is still needed to improve the accuracy of the FL method.

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.

A new method based on both fuzzy set and possibility theories for tumor volume segmentation on PET images.

A new automatic method for tumor volume segmentation on PET images has been developed. The method introduced in this paper is based on previous works in MRA segmentation and involves both fuzzy set and possibility theories. Visual results prove the method efficiency which is confirmed by obtained Jaccard index.

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.

Lung liquid clearance in newborn lamb: MRI methods and preliminary results.

To study the lung water clearance in vivo at the time of the birth, MR experiments were conducted on newborn lamb immediately after uterine incision deliverance. Images obtained with a fast spin echo sequence enable to quantify lung liquid each 5 minutes during 30 minutes then each 10 minutes for 1.5 hour. From the lung contours, pulmonary volume, pulmonary water, and spatial gradient of pulmonary water were studied. At 2 hours of life, the total pulmonary water content was still high and the liquid clearance was slower in the lower part of the lung. Air inflation increased the size of the distal airways and shifted liquid from the lung lumen towards the pulmonary interstitial tissue. The pulmonary water wash-out was belated and the passage to the aerial life was performed by progressive liberation of the superior pulmonary spaces, water flowing out by gravity toward the lower spaces.

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.

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.