Thoracic radiotherapy treatment planning with cine PET/CT

Purpose: Respiratory motion causes substantial uncertainty in radiotherapy treatment planning. Four-dimensional computed tomography (4D-CT) is a useful tool to image tumor motion during normal respiration. Treatment margins can be reduced by targeting the motion path of the tumor. The expense and complexity of 4D-CT, however, may be cost-prohibitive at some facilities. We developed an image processing technique to produce images from cine CT that contain significant motion information without 4D-CT. The purpose of this work was to compare cine CT and 4D-CT for the purposes of target delineation and dose calculation, and to explore the role of PET in target delineation of lung cancer. Methods: To determine whether cine CT could substitute 4D-CT for small mobile lung tumors, we compared target volumes delineated by a physician on cine CT and 4D-CT for 27 tumors with intrafractional motion greater than 1 cm. We assessed dose calculation by comparing dose distributions calculated on respiratory-averaged cine CT and respiratory-averaged 4D-CT using the gamma index. A threshold-based PET segmentation model of size, motion, and source-to-background was developed from phantom scans and validated with 24 lung tumors. Finally, feasibility of integrating cine CT and PET for contouring was assessed on a small group of larger tumors. Results: Cine CT to 4D-CT target volume ratios were (1.05±0.14) and (0.97±0.13) for high-contrast and low-contrast tumors respectively which was within intraobserver variation. Dose distributions on cine CT produced good agreement (< 2%/1 mm) with 4D-CT for 71 of 73 patients. The segmentation model fit the phantom data with R2 = 0.96 and produced PET target volumes that matched CT better than 6 published methods (-5.15%). Application of the model to more complex tumors produced mixed results and further research is necessary to adequately integrate PET and cine CT for delineation. Conclusions: Cine CT can be used for target delineation of small mobile lesions with minimal differences to 4D-CT. PET, utilizing the segmentation model, can provide additional contrast. Additional research is required to assess the efficacy of complex tumor delineation with cine CT and PET. Respiratory-averaged cine CT can substitute respiratory-averaged 4D-CT for dose calculation with negligible differences.

Thoracic target volume delineation using various maximum-intensity projection computed tomography image sets for stereotactic body radiation therapy

The motion of lung tumors during respiration makes the accurate delivery of radiation therapy to the thorax difficult because it increases the uncertainty of target position. The adoption of four-dimensional computed tomography (4D-CT) has allowed us to determine how a tumor moves with respiration for each individual patient. Using information acquired during a 4D-CT scan, we can define the target, visualize motion, and calculate dose during the planning phase of the radiotherapy process. One image data set that can be created from the 4D-CT acquisition is the maximum-intensity projection (MIP). The MIP can be used as a starting point to define the volume that encompasses the motion envelope of the moving gross target volume (GTV). Because of the close relationship that exists between the MIP and the final target volume, we investigated four MIP data sets created with different methodologies (3 using various 4D-CT sorting implementations, and one using all available cine CT images) to compare target delineation. It has been observed that changing the 4D-CT sorting method will lead to the selection of a different collection of images; however, the clinical implications of changing the constituent images on the resultant MIP data set are not clear. There has not been a comprehensive study that compares target delineation based on different 4D-CT sorting methodologies in a patient population. We selected a collection of patients who had previously undergone thoracic 4D-CT scans at our institution, and who had lung tumors that moved at least 1 cm. We then generated the four MIP data sets and automatically contoured the target volumes. In doing so, we identified cases in which the MIP generated from a 4D-CT sorting process under-represented the motion envelope of the target volume by more than 10% than when measured on the MIP generated from all of the cine CT images. The 4D-CT methods suffered from duplicate image selection and might not choose maximum extent images. Based on our results, we suggest utilization of a MIP generated from the full cine CT data set to ensure a representative inclusive tumor extent, and to avoid geometric miss.

Genetic Control of Plant Development by Overriding a Geometric Division Rule

Formative cell divisions are critical for multicellular patterning. In the early plant embryo, such divisions follow from orienting the division plane. A major unanswered question is how division plane orientation is genetically controlled, and in particular whether this relates to cell geometry. We have generated a complete 4D map of early Arabidopsis embryogenesis and used computational analysis to demonstrate that several divisions follow a rule that uses the smallest wall area going through the center of the cell. In other cases, however, cell division clearly deviates from this rule, which invariably leads to asymmetric cell division. By analyzing mutant embryos and through targeted genetic perturbation, we show that response to the hormone auxin triggers a deviation from the ``shortest wall'' rule. Our work demonstrates that a simple default rule couples division orientation to cell geometry in the embryo and that genetic regulation can create patterns by overriding the default rule.

Reproducibility and accuracy of linear measurements on dental models derived from cone-beam computed tomography compared with digital dental casts.

INTRODUCTION The aim of this study was to determine the reproducibility and accuracy of linear measurements on 2 types of dental models derived from cone-beam computed tomography (CBCT) scans: CBCT images, and Anatomodels (InVivoDental, San Jose, Calif); these were compared with digital models generated from dental impressions (Digimodels; Orthoproof, Nieuwegein, The Netherlands). The Digimodels were used as the reference standard. METHODS The 3 types of digital models were made from 10 subjects. Four examiners repeated 37 linear tooth and arch measurements 10 times. Paired t tests and the intraclass correlation coefficient were performed to determine the reproducibility and accuracy of the measurements. RESULTS The CBCT images showed significantly smaller intraclass correlation coefficient values and larger duplicate measurement errors compared with the corresponding values for Digimodels and Anatomodels. The average difference between measurements on CBCT images and Digimodels ranged from -0.4 to 1.65 mm, with limits of agreement values up to 1.3 mm for crown-width measurements. The average difference between Anatomodels and Digimodels ranged from -0.42 to 0.84 mm with limits of agreement values up to 1.65 mm. CONCLUSIONS Statistically significant differences between measurements on Digimodels and Anatomodels, and between Digimodels and CBCT images, were found. Although the mean differences might be clinically acceptable, the random errors were relatively large compared with corresponding measurements reported in the literature for both Anatomodels and CBCT images, and might be clinically important. Therefore, with the CBCT settings used in this study, measurements made directly on CBCT images and Anatomodels are not as accurate as measurements on Digimodels.

Complication sévère d’une contention collée linguale mandibulaire

Le collage d’un fil torsadé souple sur les faces linguales des six dents antérieures mandibulaires est une modalité de contention couramment utilisée. Les complications sont rares mais peuvent être assez sérieuses pour provoquer des dégâts biologiques. Cet article présente une complication sérieuse d’un fil de contention torsadé souple, collé en lingual. Quatre ans après son traitement orthodontique, un homme de 20 ans a consulté pour la rupture d’un fil de contention torsadé souple. L’examen clinique a montré un torque radiculo-vestibulaire d’environ 35° d’une dent. Une image en tomographie volumique à faisceau conique (Cone-Beam Computed Tomography ou CBCT) a montré que la racine et l’apex de la dent étaient presque totalement hors de l’os du côté vestibulaire. Étonnamment, la vitalité de la dent était préservée. La dent a été ramenée presque jusqu’à sa position initiale; cliniquement, seule une récession gingivale a persisté. Les orthodontistes et les dentistes devraient être conscients des complications possibles des contentions collées. Les patients devraient être clairement informés de la manière dont les problèmes peuvent être détectés à un stade précoce.

Three-dimensional imaging methods for quantitative analysis of facial soft tissues and skeletal morphology in patients with orofacial clefts: a systematic review.

BACKGROUND Current guidelines for evaluating cleft palate treatments are mostly based on two-dimensional (2D) evaluation, but three-dimensional (3D) imaging methods to assess treatment outcome are steadily rising. OBJECTIVE To identify 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate. DATA SOURCES Literature was searched using PubMed (1948-2012), EMBASE (1980-2012), Scopus (2004-2012), Web of Science (1945-2012), and the Cochrane Library. The last search was performed September 30, 2012. Reference lists were hand searched for potentially eligible studies. There was no language restriction. STUDY SELECTION We included publications using 3D imaging techniques to assess facial soft tissue or skeletal morphology in patients older than 5 years with a cleft lip with/or without cleft palate. We reviewed studies involving the facial region when at least 10 subjects in the sample size had at least one cleft type. Only primary publications were included. DATA EXTRACTION Independent extraction of data and quality assessments were performed by two observers. RESULTS Five hundred full text publications were retrieved, 144 met the inclusion criteria, with 63 high quality studies. There were differences in study designs, topics studied, patient characteristics, and success measurements; therefore, only a systematic review could be conducted. Main 3D-techniques that are used in cleft lip and palate patients are CT, CBCT, MRI, stereophotogrammetry, and laser surface scanning. These techniques are mainly used for soft tissue analysis, evaluation of bone grafting, and changes in the craniofacial skeleton. Digital dental casts are used to evaluate treatment and changes over time. CONCLUSION Available evidence implies that 3D imaging methods can be used for documentation of CLP patients. No data are available yet showing that 3D methods are more informative than conventional 2D methods. Further research is warranted to elucidate it.

Localization of impacted maxillary canines and root resorption of neighbouring teeth: a study assessing the diagnostic value of panoramic radiographs in two groups of observers.

OBJECTIVES To assess the diagnostic value of panoramic views (2D) of patients with impacted maxillary canines by a group of trained orthodontists and oral surgeons, and to quantify the subjective need and reasons for further three-dimensional (3D) imaging. MATERIALS AND METHODS The study comprises 60 patients with panoramic radiographs (2D) and cone beam computed tomography (CBCT) scans (3D), and a total of 72 impacted canines. Data from a standardized questionnaire were compared within (intragroup) and between (intergroup) a group of orthodontists and oral surgeons to assess possible correlations and differences. Furthermore, the questionnaire data were compared with the findings from the CBCT scans to estimate the correlation within and between the two specialties. Finally, the need and reasons for further 3D imaging was analysed for both groups. RESULTS When comparing questionnaire data with the analysis of the respective CBCT scans, orthodontists showed probability (Pr) values ranging from 0.443 to 0.943. Oral surgeons exhibited Pr values from 0.191 to 0.946. Statistically significant differences were found for the labiopalatal location of the impacted maxillary canine (P = 0.04), indicating a higher correlation in the orthodontist group. The most frequent reason mentioned for the further need of 3D analysis was the labiopalatal location of the impacted canines. Oral surgeons were more in favour of performing further 3D imaging (P = 0.04). CONCLUSIONS Orthodontists were more likely to diagnose the exact labiopalatal position of impacted maxillary canines when using panoramic views only. Generally, oral surgeons more often indicated the need for further 3D imaging.

Incidental findings on cone beam computed tomography scans in cleft lip and palate patients.

OBJECTIVES Cone beam computed tomography (CBCT) is frequently used in treatment planning for alveolar bone grafting (ABG) and orthognathic surgery in patients with cleft lip and palate (CLP). CBCT images may depict coincident findings. The aim of this study was to assess the prevalence of incidental findings on CBCT scans in CLP patients. SUBJECTS AND METHODS Initial CBCTs taken from consecutive patients (n = 187; mean age 11.7 years, range 6.9-45) with a non-syndromic orofacial cleft from January 2006 until June 2012 were systematically evaluated. Twenty-eight patients (mean age 19.3 years, range 13.2-30.9) had been subjected to ABG before their first CBCT was taken; 61 patients had a CBCT before and after ABG. Sinuses, nasopharynx, oropharynx, throat, skull, vertebrae, temporomandibular joint (TMJ), maxilla and mandible were checked for incidental findings. RESULTS On 95.1 % of the CBCTs, incidental findings were found. The most prevalent were airway/sinus findings (56.1 %), followed by dental problems, e.g. missing teeth (52 %), nasal septum deviation (34 %), middle ear and mastoid opacification, suggestive for otitis media (10 %) and (chronic) mastoiditis (9 %), abnormal TMJ anatomy (4.9 %) and abnormal vertebral anatomy (1.6 %). In the 28 patients whose first CBCT was taken at least 2 years after ABG, bone was still present in the reconstructed cleft area except in 2 out of 12 patients with a bilateral CLP. The ABG donor site (all bone grafts were taken from the chin area) was still recognizable in over 50 % of the patients. Based on the CBCT findings, 10 % of the patients were referred for further diagnosis and 9 % for further treatment related to dental problems. CONCLUSION Incidental findings are common on CBCTs. Compared with the literature, CLP patients have more dental, nasal and ear problems. Thus, whenever a CBCT is available, this scan should be reviewed by all specialists in the CLP team focusing on their specific background knowledge concerning symptoms and treatment of these patients. CLINICAL RELEVANCE The high number of findings indicates that CBCT imaging is a helpful tool in the treatment of CLP patients not only related to alveolar bone grafting and orthognathic surgery but it also provides diagnostic information for almost all specialties involved in CLP treatment.

Incidence of anatomical variations and disease of the maxillary sinuses as identified by cone beam computed tomography: a systematic review.

PURPOSE To analyze available evidence on the incidence of anatomical variations or disease of the maxillary sinuses as identified by cone beam computed tomography (CBCT) in dentistry. MATERIALS AND METHODS A focused question was developed to search the electronic databases MEDLINE, EMBASE, the Cochrane Oral Health Group Trials Register, and CENTRAL and identify all relevant papers published between 1980 and January 19, 2013. Unpublished literature at ClinicalTrials.gov, in the National Research Register, and in the Pro-Quest Dissertation Abstracts and Thesis database was also included. Studies were included irrespective of language. These results were supplemented by hand and gray literature searches. RESULTS Twenty-two studies were identified. Twenty were retrospective cohort studies, one was a prospective cohort study, and one was a case control study. The main indication for CBCT was dental implant treatment planning, and the majority of studies used a small field of view for imaging. The most common anatomical variations included increased thickness of the sinus membrane, the presence of sinus septa, and pneumatization. Reported sinus disease frequency varied widely, ranging from 14.3% to 82%. There was a wide range in the reported prevalence of mucosal thickening related to apical pathology, the degree of lumenal opacification, features of sinusitis, and the presence of retention cysts and polyps. More pathologic findings in the maxillary sinus were reported in men than in women, and the medial wall and sinus floor were most frequently affected. CONCLUSION CBCT is used primarily to evaluate bony anatomy and to screen for overt pathology of the maxillary sinuses prior to dental implant treatment. Differences in the classification of mucosal findings are problematic in the consistent and valid assessment of health and disease of the maxillary sinus.

Bone dimensions in the posterior mandible: a retrospective radiographic study using cone beam computed tomography. Part 2- analysis of edentulous sites.

A precise radiographic evaluation of the local bone dimensions and morphology is important for preoperative planning of implant placement. The purpose of this retrospective study was to analyze dimensions and morphology of edentulous sites in the posterior mandible using cone beam computed tomography (CBCT) images. This retrospective radiographic study measured the bone width (BW) of the mandible at three locations on CBCT scans for premolars (PM1, PM2) and molars (M1, M2): at 1 mm and 4 mm below the most cranial point of the alveolar crest (BW1, BW2) and at the superior border of the mandibular canal (BW3). Furthermore, the height (H) of the alveolar process (distance between the measuring points BW1 and BW3), as well as the presence of lingual undercuts, were analyzed. A total of 56 CBCTs met the inclusion criteria, resulting in a sample size of 127 cross sections. There was a statistically significant increase from PM1 to M2 for the BW2 (P < .001), which was not present for BW1 and BW3 values. For the height of the alveolar process, the values exhibited a decrease from PM1 to M2 sites. Sex was a statistically significant parameter for H (P = .001) and for BW1 (P = .03). Age was not a statistically significant parameter for bone width (BW1: P = .37; BW2: P = .31; BW3: P = .51) or for the height of the alveolar process (P = .41) in the posterior mandible. Overall, 73 (57.5%) edentulous sites were evaluated to be without visible lingual undercuts; 13 (10.2%) sites exhibited lingual undercuts classified as influential for implant placement. Precise evaluation of the alveolar crest by cross-sectional imaging is of great value to analyze vertical and buccolingual bone dimensions in different locations in the posterior mandible. In addition, CBCTs are valuable to diagnosing the presence of and potential problems caused by lingual undercuts prior to implant placement.

Dacryocystography using cone beam CT in patients with lacrimal drainage system obstruction.

PURPOSE To assess the usefulness of cone beam CT (CBCT) for dacryocystography (DCG) using either direct syringing or passive application of contrast medium. METHODS Ten consecutive patients with epiphora who had CBCT-DCG in a sitting position were retrospectively analyzed. CBCT-DCGs were performed using 2 techniques: direct syringing with contrast medium or using the passive technique, where patients received 3 drops of contrast medium into the conjunctival sac before CBCT-DCG. Clinical and radiologic diagnoses were compared for both groups. RESULTS The 10 patients (men = 3) had a mean age of 63.2 years. Both techniques proved to be simple procedures with good delineation of the bone, soft tissue, and the contrast medium in the lacrimal system. No side effects were noted. CONCLUSIONS CBCT-DCG is a useful alternative to determine the localization of stenosis in patients with chronic epiphora.

Three-dimensional study of nasopalatine canal morphology: a descriptive retrospective analysis using cone-beam computed tomography

PURPOSE For dental implant treatment planning and placement, a precise anatomic description of the nasopalatine canal (NC) is necessary. This descriptive retrospective study evaluated dimensions of the NC and buccal bone plate (BBP) and the tridimensional association of the anatomic variants of NC, using cone-beam computed tomography (CBCT). METHODS This study included 230 CBCTs. Sagittal slices were used for measurements of the NC and BBP and to evaluate shape and direction-course of the NC. Coronal slices were used to assess NC shape and axial slices to assess number of incisive foramina and foramina of Stenson. RESULTS Mean NC length was 12.34 ± 2.79 mm, statistically significant differences were detected between genders (p < 0.001). Mean BBP length was 20.87 ± 3.68 mm, statistically significant differences were found for the dental status (p < 0.001) and mean BBP width was 6.83 ± 1.28 mm, significant differences were detected between genders (p < 0.001). Mean nasopalatine angle was 73.33° ± 8.11°, significant differences were found in sagittal and coronal classifications. The most prevalent canal was: cylindrical sagittal shape (48.2 %); slanted-straight direction-course (57.6 %); Ya-type coronal shape (42.4 %); and one foramen incisive with two Stenson's foramina (1-2) (50.9 %). Sagittal shape was associated with sagittal direction-course (p < 0.001). Coronal shape was associated with axial classification (p < 0.001). CONCLUSIONS The NC anatomy is highly variable. Gender is related to the NC length and BBP width, while dental status is related to BBP length. There was an association between the different sagittal classifications of the NC and between the coronal shape and axial classification.

Cone beam computed tomography in implant dentistry: a systematic review focusing on guidelines, indications, and radiation dose risks.

PURPOSE The aim of the paper is to identify, review, analyze, and summarize available evidence in three areas on the use of cross-sectional imaging, specifically maxillofacial cone beam computed tomography (CBCT) in pre- and postoperative dental implant therapy: (1) Available clinical use guidelines, (2) indications and contraindications for use, and (3) assessment of associated radiation dose risk. MATERIALS AND METHODS Three focused questions were developed to address the aims. A systematic literature review was performed using a PICO-based search strategy based on MeSH key words specific to each focused question of English-language publications indexed in the MEDLINE database retrospectively from October 31, 2012. These results were supplemented by a hand search and gray literature search. RESULTS Twelve publications were identified providing guidelines for the use of cross-sectional radiography, particularly CBCT imaging, for the pre- and/or postoperative assessment of potential dental implant sites. The publications discovered by the PICO strategy (43 articles), hand (12), and gray literature searches (1) for the second focus question regarding indications and contraindications for CBCT use in implant dentistry were either cohort or case-controlled studies. For the third question on the assessment of associated radiation dose risk, a total of 22 articles were included. Publication characteristics and themes were summarized in tabular format. CONCLUSIONS The reported indications for CBCT use in implant dentistry vary from preoperative analysis regarding specific anatomic considerations, site development using grafts, and computer-assisted treatment planning to postoperative evaluation focusing on complications due to damage of neurovascular structures. Effective doses for different CBCT devices exhibit a wide range with the lowest dose being almost 100 times less than the highest dose. Significant dose reduction can be achieved by adjusting operating parameters, including exposure factors and reducing the field of view (FOV) to the actual region of interest.

Esthetic outcomes following immediate and early implant placement in the anterior maxilla: a systematic review.

PURPOSE The objectives of this systematic review are (1) to quantitatively estimate the esthetic outcomes of implants placed in postextraction sites, and (2) to evaluate the influence of simultaneous bone augmentation procedures on these outcomes. MATERIALS AND METHODS Electronic and manual searches of the dental literature were performed to collect information on esthetic outcomes based on objective criteria with implants placed after extraction of maxillary anterior and premolar teeth. All levels of evidence were accepted (case series studies required a minimum of 5 cases). RESULTS From 1,686 titles, 114 full-text articles were evaluated and 50 records included for data extraction. The included studies reported on single-tooth implants adjacent to natural teeth, with no studies on multiple missing teeth identified (6 randomized controlled trials, 6 cohort studies, 5 cross-sectional studies, and 33 case series studies). Considerable heterogeneity in study design was found. A meta-analysis of controlled studies was not possible. The available evidence suggests that esthetic outcomes, determined by esthetic indices (predominantly the pink esthetic score) and positional changes of the peri-implant mucosa, may be achieved for single-tooth implants placed after tooth extraction. Immediate (type 1) implant placement, however, is associated with a greater variability in outcomes and a higher frequency of recession of > 1 mm of the midfacial mucosa (eight studies; range 9% to 41% and median 26% of sites, 1 to 3 years after placement) compared to early (type 2 and type 3) implant placement (2 studies; no sites with recession > 1 mm). In two retrospective studies of immediate (type 1) implant placement with bone graft, the facial bone wall was not detectable on cone beam CT in 36% and 57% of sites. These sites had more recession of the midfacial mucosa compared to sites with detectable facial bone. Two studies of early implant placement (types 2 and 3) combined with simultaneous bone augmentation with GBR (contour augmentation) demonstrated a high frequency (above 90%) of facial bone wall visible on CBCT. Recent studies of immediate (type 1) placement imposed specific selection criteria, including thick tissue biotype and an intact facial socket wall, to reduce esthetic risk. There were no specific selection criteria for early (type 2 and type 3) implant placement. CONCLUSIONS Acceptable esthetic outcomes may be achieved with implants placed after extraction of teeth in the maxillary anterior and premolar areas of the dentition. Recession of the midfacial mucosa is a risk with immediate (type 1) placement. Further research is needed to investigate the most suitable biomaterials to reconstruct the facial bone and the relationship between long-term mucosal stability and presence/absence of the facial bone, the thickness of the facial bone, and the position of the facial bone crest.

Synthesis and cellular characterization of novel isoxazolo- and thiazolohydrazinylidene-chroman-2,4-diones on cancer and non-cancer cell growth and death

Coumarins are extensively studied anticoagulants that exert additional effects such as anticancerogenic and even anti-inflammatory. In order to find new drugs with anticancer activities, we report here the synthesis and the structural analysis of new coumarin derivatives which combine the coumarin core and five member heterocycles in hydrazinylidene-chroman-2,4-diones. The derivatives were prepared by derivatization of the appropriate heterocyclic amines which were used as electrophiles to attack the coumarin ring. The structures were characterized by spectroscopic techniques including IR, NMR, 2D-NMR and MS. These derivatives were further characterized especially in terms of a potential cytotoxic and apoptogenic effect in several cancer cell lines including the breast and prostate cancer cell lines MCF-7, MDA-MB-231, PC-3, LNCaP, and the monocytic leukemia cell line U937. Cell viability was determined after 48 h and 72 h of treatment with the novel compounds by MTT assay and the 50% inhibitory concentrations (EC50 values) were determined. Out of the 8 novel compounds screened for reduced cell viability, 4c, 4d and 4e were found to be the most promising and effective ones having EC50 values that were several fold reduced when compared to the reference substance 4-hydroxycoumarin. However, the effects were cancer cell line dependent. The breast cancer MDA-MB-231 cells, the prostate cancer LNCaP cells, and U937 cells were most sensitive, MCF-7 cells were less sensitive, and PC-3 cells were more resistant. Reduced cell viability was accompanied by increased apoptosis as shown by PARP-1 cleavage and reduced activity of the survival protein kinase Akt. In summary, this study has identified three novel coumarin derivatives that in comparison to 4-hydroxycoumarin have a higher efficiency to reduce cancer cell viability and trigger apoptosis and therefore may represent interesting novel drug candidates