A clinical validation study for the feasibility and reliability of three-dimensional ultrasound-ultrasound automatic image registration.

PURPOSE: The purpose of our study was to assess the feasibility and reliability of 3D ultrasound-ultrasound (US-US) automatic registration-based analysis of the hepatic vessel tree (VT) (3D VT-based automatic registration) in clinical applications. MATERIALS AND METHODS: A total of 70 pairs of 3D ultrasound data were acquired from the livers of 10 healthy volunteers enrolled in the study. An automatic registration method was applied to the acquired volumetric data pairs, and anatomic landmarks were picked by an experienced sonographer as 'ground truth'. The influences of respiration phase, subject posture, and liver lobe on data acquisition and scan volumetric angle on the registration accuracy and robustness were investigated. The registration time, success rate, median registration error distance, and sonographer's subjective feedback were assessed. RESULTS: The time required for the 3D VT-based automatic registration was approximately 15∼20 s. Overall, the success rate for the hepatic vessel-based registration was 71% (50/70), and the median registration error distance was 1.72 mm (0.57∼4.71 mm). When the influential factors were well controlled, the optimal registration accuracy (median registration error distance = 1.22 mm) could be obtained with an excellent success rate of 100% (10/10). According to the subjective assessment of the sonographer, over 90% (45/50) of the automatic registration results were not inferior to the ground truth. Among them, 42% (21/50) were superior to the fusion results from the ground truth. CONCLUSIONS: The results suggest that the 3D VT-based automatic registration is feasible and reliable and has potential for guidance and evaluation of intraoperative ablation of hepatocellular carcinoma.

Tagged template deformation.

Model-based approaches are very popular for medical image segmentation as they carry useful prior information on the target structure. Among them, the implicit template deformation framework recently bridged the gap between the efficiency and flexibility of level-set region competition and the robustness of atlas deformation approaches. This paper generalizes this method by introducing the notion of tagged templates. A tagged template is an implicit model in which different subregions are defined. In each of these subregions, specific image features can be used with various confidence levels. The tags can be either set manually or automatically learnt via a process also hereby described. This generalization therefore greatly widens the scope of potential clinical application of implicit template deformation while maintaining its appealing algorithmic efficiency. We show the great potential of our approach in myocardium segmentation of ultrasound images.

Semiautomatic volumetric tumor segmentation for hepatocellular carcinoma: comparison between C-arm cone beam computed tomography and MRI.

RATIONALE AND OBJECTIVES: To evaluate the precision and reproducibility of a semiautomatic tumor segmentation software in measuring tumor volume of hepatocellular carcinoma (HCC) before the first transarterial chemo-embolization (TACE) on contrast-enhancement magnetic resonance imaging (CE-MRI) and intraprocedural dual-phase C-arm cone beam computed tomography (DP-CBCT) images. MATERIALS AND METHODS: Nineteen HCCs were targeted in 19 patients (one per patient) who underwent baseline diagnostic CE-MRI and an intraprocedural DP-CBCT. The images were obtained from CE-MRI (arterial phase of an intravenous contrast medium injection) and DP-CBCT (delayed phase of an intra-arterial contrast medium injection) before the actual embolization. Three readers measured tumor volumes using a semiautomatic three-dimensional volumetric segmentation software that used a region-growing method employing non-Euclidean radial basis functions. Segmentation time and spatial position were recorded. The tumor volume measurements between image sets were compared using linear regression and Student's t-test, and evaluated with intraclass-correlation analysis (ICC). The inter-rater Dice similarity coefficient (DSC) assessed the segmentation spatial localization. RESULTS: All 19 HCCs were analyzed. On CE-MRI and DP-CBCT examinations, respectively, 1) the mean segmented tumor volumes were 87 ± 8 cm(3) (2-873) and 92 ± 10 cm(3) (1-954), with no statistical difference of segmented volumes by readers of each tumor between the two imaging modalities and the mean time required for segmentation was 66 ± 45 seconds (21-173) and 85 ± 34 seconds (17-214) (P = .19); 2) the ICCs were 0.99 and 0.974, showing a strong correlation among readers; and 3) the inter-rater DSCs showed a good to excellent inter-user agreement on the spatial localization of the tumor segmentation (0.70 ± 0.07 and 0.74 ± 0.05, P = .07). CONCLUSION: This study shows a strong correlation, a high precision, and excellent reproducibility of semiautomatic tumor segmentation software in measuring tumor volume on CE-MRI and DP-CBCT images. The use of the segmentation software on DP-CBCT and CE-MRI can be a valuable and highly accurate tool to measure the volume of hepatic tumors.

Direct quantification of cell-associated HIV DNA in isolated rectal and blood memory CD4 T cells revealed their similar and low infection levels in long-term treated HIV-infected patients.

To evaluate the contribution of CD4 T cells from blood and gut compartments to the HIV-1 reservoir, we directly quantified cell-associated HIV DNA in isolated rectal (R-) and peripheral blood (PB-) memory CD4 T cells from 11 successfully long-term treated patients. Proportion of activated (CD25(+); CD69(+); and HLA-DR(+)) and CCR5 expressing CD4 T cells were markedly higher in rectal tissue compared with blood. However, HIV-1 infection levels of R- and PB-memory CD4 T cells did not significantly differ (medians: 4000 and 2100 copies per million cells) after effective long-term viral control, suggesting that each of these 2 compartments does not contribute in a similar fashion to the total HIV reservoir.

Comparison of semi-automatic volumetric VX2 hepatic tumor segmentation from cone beam CT and multi-detector CT with histology in rabbit models.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare tumor volume in a VX2 rabbit model as calculated using semiautomatic tumor segmentation from C-arm cone-beam computed tomography (CBCT) and multidetector computed tomography (MDCT) to the actual tumor volume. MATERIALS AND METHODS: Twenty VX2 tumors in 20 adult male New Zealand rabbits (one tumor per rabbit) were imaged with CBCT (using an intra-arterial contrast medium injection) and MDCT (using an intravenous contrast injection). All tumor volumes were measured using semiautomatic three-dimensional volumetric segmentation software. The software uses a region-growing method using non-Euclidean radial basis functions. After imaging, the tumors were excised for pathologic volume measurement. The imaging-based tumor volume measurements were compared to the pathologic volumes using linear regression, with Pearson's test, and correlated using Bland-Altman analysis. RESULTS: Average tumor volumes were 3.5 ± 1.6 cm(3) (range, 1.4-7.2 cm(3)) on pathology, 3.8 ± 1.6 cm(3) (range, 1.3-7.3 cm(3)) on CBCT, and 3.9 ± 1.6 (range, 1.8-7.5 cm(3)) on MDCT (P < .001). A strong correlation between volumes on pathology and CBCT and also with MDCT was observed (Pearson's correlation coefficient = 0.993 and 0.996, P < .001, for CBCT and MDCT, respectively). Bland-Altman analysis showed that MDCT tended to overestimate tumor volume, and there was stronger agreement for tumor volume between CBCT and pathology than with MDCT, possibly because of the intra-arterial contrast injection. CONCLUSIONS: Tumor volume as measured using semiautomatic tumor segmentation software showed a strong correlation with the "real volume" measured on pathology. The segmentation software on CBCT and MDCT can be a useful tool for volumetric hepatic tumor assessment.

Registration of free-breathing 3D+t abdominal perfusion CT images via co-segmentation.

Dynamic contrast-enhanced computed tomography (DCE-CT) is a valuable imaging modality to assess tissues properties, particularly in tumours, by estimating pharmacokinetic parameters from the evolution of pixels intensities in 3D+t acquisitions. However, this requires a registration of the whole sequence of volumes, which is challenging especially when the patient breathes freely. In this paper, we propose a generic, fast and automatic method to address this problem. As standard iconic registration methods are not robust to contrast intake, we rather rely on the segmentation of the organ of interest. This segmentation is performed jointly with the registration of the sequence within a novel co-segmentation framework. Our approach is based on implicit template deformation, that we extend to a co-segmentation algorithm which provides as outputs both a segmentation of the organ of interest in every image and stabilising transformations for the whole sequence. The proposed method is validated on 15 datasets acquired from patients with renal lesions and shows improvement in terms of registration and estimation of pharmacokinetic parameters over the state-of-the-art method.

Incorporating shape variability in image segmentation via implicit template deformation.

Implicit template deformation is a model-based segmentation framework that was successfully applied in several medical applications. In this paper, we propose a method to learn and use prior knowledge on shape variability in such framework. This shape prior is learnt via an original and dedicated process in which both an optimal template and principal modes of variations are estimated from a collection of shapes. This learning strategy requires neither a pre-alignment of the training shapes nor one-to-one correspondences between shape sample points. We then generalize the implicit template deformation formulation to automatically select the most plausible deformation as a shape prior. This novel framework maintains the two main properties of implicit template deformation: topology preservation and computational efficiency. Our approach can be applied to any organ with a possibly complex shape but fixed topology. We validate our method on myocardium segmentation from cardiac magnetic resonance short-axis images and demonstrate segmentation improvement over standard template deformation.

Joint co-segmentation and registration of 3D ultrasound images.

Contrast-enhanced ultrasound (CEUS) allows a visualization of the vascularization and complements the anatomical information provided by conventional ultrasound (US). However, these images are inherently subject to noise and shadows, which hinders standard segmentation algorithms. In this paper, we propose to use simultaneously the different information coming from 3D US and CEUS images to address the problem of kidney segmentation. To that end, we introduce a generic framework for joint co-segmentation and registration that seeks objects having the same shape in several images. From this framework, we derive both an ellipsoid co-detection and a model-based co-segmentation algorithm. These methods rely on voxel-classification maps that we estimate using random forests in a structured way. This yields a fast and fully automated pipeline, in which an ellipsoid is first estimated to locate the kidney in both US and CEUS volumes and then deformed to segment it accurately. The proposed method outperforms state-of-the-art results (by dividing the kidney volume error by two) on a clinically representative database of 64 images.

Quantitative and volumetric European Association for the Study of the Liver and Response Evaluation Criteria in Solid Tumors measurements: feasibility of a semiautomated software method to assess tumor response after transcatheter arterial chemoembolization.

PURPOSE: To show that hepatic tumor volume and enhancement pattern measurements can be obtained in a time-efficient and reproducible manner on a voxel-by-voxel basis to provide a true three-dimensional (3D) volumetric assessment. MATERIALS AND METHODS: Magnetic resonance (MR) imaging data obtained from 20 patients recruited for a single-institution prospective study were retrospectively evaluated. All patients had a diagnosis of hepatocellular carcinoma (HCC) and underwent drug-eluting beads (DEB) transcatheter arterial chemoembolization for the first time. All patients had undergone contrast-enhanced MR imaging before and after DEB transcatheter arterial chemoembolization; poor image quality excluded 3 patients, resulting in a final count of 17 patients. Volumetric RECIST (vRECIST) and quantitative EASL (qEASL) were measured, and segmentation and processing times were recorded. RESULTS: There were 34 scans analyzed. The time for semiautomatic segmentation was 65 seconds±33 (range, 40-200 seconds). vRECIST and qEASL of each tumor were computed<1 minute for each. CONCLUSIONS: Semiautomatic quantitative tumor enhancement (qEASL) and volume (vRECIST) assessment is feasible in a workflow-efficient time frame. Clinical correlation is necessary, but vRECIST and qEASL could become part of the assessment of intraarterial therapy for interventional radiologists.

HIV-1 genome is often defective in PBMCs and rectal tissues after long-term HAART as a result of APOBEC3 editing and correlates with the size of reservoirs.

OBJECTIVES: Precise characterization of viruses present in reservoirs in long-term pretreated patients will be a major issue to consider in the context of viral eradication. We assessed the frequency of defective viruses present in cellular reservoirs. METHODS: Peripheral blood mononuclear cells (PBMCs) and rectal biopsy samples were compared between five patients on successful long-term highly active antiretroviral therapy (HAART) (>7 years without blips) and five untreated patients. Molecular cloning and sequencing of the reverse transcriptase region were used to detect the presence of and quantify in-frame stop codons in HIV quasi-species. The relationship between the size of the reservoir and the frequency of defective genomes was assessed. RESULTS: Defective genomes were systematically detected in all patients on long-term HAART in both compartments (PBMCs and rectal tissues), with a higher level of defective genomes per sample compared with PBMCs of untreated patients. A high level of defective genomes was correlated with a small size of HIV proviral DNA. Regarding the nucleotide context, guanine (G) to adenine (A) substitution at tryptophan positions was responsible for the appearance of 89% of all in-frame stop codons in the context of G-to-A hypermutation, likely reflecting APOBEC3 footprints on the viral genome. CONCLUSIONS: We propose a scenario whereby defective genomes accumulate during HAART treatment, eventually reaching a viral extinction threshold. In the context of viral eradication, measurement of the relative amounts of defective and non-defective viruses (by molecular cloning and ultradeep sequencing) should be used as a new criterion for eradicating HIV.

Real-time 3D image segmentation by user-constrained template deformation.

We describe an algorithm for 3D interactive image segmentation by non-rigid implicit template deformation, with two main original features. First, our formulation incorporates user input as inside/outside labeled points to drive the deformation and improve both robustness and accuracy. This yields inequality constraints, solved using an Augmented Lagrangian approach. Secondly, a fast implementation of non-rigid template-to-image registration enables interactions with a real-time visual feedback. We validated this generic technique on 21 Contrast-Enhanced Ultrasound images of kidneys and obtained accurate segmentation results (Dice > 0.93) in less than 3 clicks in average.

Automatic detection and segmentation of kidneys in 3D CT images using random forests.

Kidney segmentation in 3D CT images allows extracting useful information for nephrologists. For practical use in clinical routine, such an algorithm should be fast, automatic and robust to contrast-agent enhancement and fields of view. By combining and refining state-of-the-art techniques (random forests and template deformation), we demonstrate the possibility of building an algorithm that meets these requirements. Kidneys are localized with random forests following a coarse-to-fine strategy. Their initial positions detected with global contextual information are refined with a cascade of local regression forests. A classification forest is then used to obtain a probabilistic segmentation of both kidneys. The final segmentation is performed with an implicit template deformation algorithm driven by these kidney probability maps. Our method has been validated on a highly heterogeneous database of 233 CT scans from 89 patients. 80% of the kidneys were accurately detected and segmented (Dice coefficient > 0.90) in a few seconds per volume.

Comprehensive segmentation of cine cardiac MR images.

A typical Cardiac Magnetic Resonance (CMR) examination includes acquisition of a sequence of short-axis (SA) and long-axis (LA) images covering the cardiac cycle. Quantitative analysis of the heart function requires segmentation of the left ventricle (LV) SA images, while segmented LA views allow more accurate estimation of the basal slice and can be used for slice registration. Since manual segmentation of CMR images is very tedious and time-consuming, its automation is highly required. In this paper, we propose a fully automatic 2D method for segmenting LV consecutively in LA and SA images. The approach was validated on 35 patients giving mean segmentation error smaller than one pixel, both for LA and SA, and accurate LV volume measurements.

Prevalence of anal cytologic abnormalities in a French referral population: a prospective study with special emphasis on HIV, HPV, and smoking.

PURPOSE: Studying anal cytology to detect intraepithelial neoplasia has been demonstrated to be useful in highly selected populations. This study was designed to determine the frequency of abnormal smears in a wide sample of patients consulting for anorectal symptoms. METHODS: An anal smear was proposed during each consultation during a three-month period. RESULTS: A total of 205 patients (112 females) were included. After the consultation, visible condylomas were detected in 12 (6 percent) of the cases. Two hundred three (99 percent) smears were able to be analyzed. No case of high-grade squamous intraepithelial lesion was found. Four cases of low-grade squamous intraepithelial lesion were found, all in HIV patients with a history of condylomatous lesions. Forty smears were interpreted as atypical squamous cells of undetermined significance and 159 were normal. The prevalence in this population of low-grade squamous intraepithelial lesion was 19 percent (4/21) in HIV seropositive males, and 15 percent (4/26) in the case of a past history of condyloma. The factors associated with an abnormal smear (low-grade squamous intraepithelial lesion or atypical squamous cells of undetermined significance) were a history of anal condylomatous lesions (odd ratio, 4.9; range, 2.1-11.5), HIV seropositivity (odd ratio, 4; range, 1.6-9.9), and smoking (odd ratio, 2.1; range, 1.1-11.5). CONCLUSIONS: This work confirms that the frequency of low-grade squamous intraepithelial lesion is raised in HIV-seropositive males and also where there is a history of condyloma, which corroborates the necessity for regular monitoring and screening of these patients at risk. This study also suggests that the use of tobacco is associated with anal cytologic abnormalities.

Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis--an effective but not risk-free procedure: a prospective study of 33 patients.

PURPOSE: This prospective study evaluated the efficacy and safety of local formalin application in chronic refractory radiation-induced hemorrhagic proctitis. METHODS: All patients were treated under anesthesia by direct application of 4 percent formalin to the affected rectal areas. RESULTS: The study included 33 patients (17 women) and was conducted between January 1994 and December 2001. There were 11 anal cancers (33 percent), 11 prostate cancers, 9 cervical or endometrial cancers, 1 bladder cancer, and 1 rectal cancer. The mean number of daily rectal bleeds was 2.7 (range, 0.5-15). Nineteen patients (58 percent) were blood transfusion dependent. Twenty-three patients had only one formalin application and 10 patients required a second application because of the persistent bleeding. The treatment was effective in 23 cases (70 percent): 13 patients had complete cessation of bleeding and 10 patients had only minor bleeding. Six anal or rectal strictures occurred: 4 patients had been treated for anal cancer (36 percent) and 2 patients had been treated for other cancers (9 percent). None of the strictures was malignant. Anal incontinence worsened in 5 patients of the 11 who had been treated for anal cancer (45 percent) and occurred in 4 of the 22 other patients (18 percent). CONCLUSION: Formalin application is an effective treatment for chronic radiation-induced hemorrhagic proctitis. However, local morbidity is not negligible. This result may be related to the high proportion of anal cancers in the series. In our opinion, therefore, formalin application should be reserved for severe hemorrhagic proctitis refractory to medical treatment and should be thoroughly discussed in cases of anorectal radiation-induced stricture, prior anal incontinence, or treated anal cancer.