Evaluation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated bombesin-based radioantagonist for the labeling with single-photon emission computed tomography, positron emission tomography, and therapeutic radionuclides

PURPOSE: G protein-coupled receptor agonists are being used as radiolabeled vectors for in vivo localization and therapy of tumors. Recently, somatostatin-based antagonists were shown to be superior to agonists. Here, we compare the new [111In/68Ga]-labeled bombesin-based antagonist RM1 with the agonist [111In]-AMBA for targeting the gastrin-releasing peptide receptor (GRPR). EXPERIMENTAL DESIGN: IC50, Kd values, and antagonist potency were determined using PC-3 and HEK-GRPR cells. Biodistribution and imaging studies were done in nude mice transplanted with the PC-3 tumor. The antagonist potency was assessed by evaluating the effects on calcium release and on receptor internalization monitored by immunofluorescence microscopy. RESULTS: The IC50 value of [(nat)In]-RM1 was 14 +/- 3.4 nmol/L. [(nat/111)In]-RM1 was found to bind to the GRPR with a Kd of 8.5 +/- 2.7 nmol/L compared with a Kd of 0.6 +/- 0.3 nmol/L of [111In]-AMBA. A higher maximum number of binding site value was observed for [111In]-RM1 (2.4 +/- 0.2 nmol/L) compared with [111In]-AMBA (0.7 +/- 0.1 nmol/L). [(nat)Lu]-AMBA is a potent agonist in the immunofluorescence-based internalization assay, whereas [(nat)In]-RM1 is inactive alone but efficiently antagonizes the bombesin effect. These data are confirmed by the calcium release assay. The pharmacokinetics showed a superiority of the radioantagonist with regard to the high tumor uptake (13.4 +/- 0.8% IA/g versus 3.69 +/- 0.75% IA/g at 4 hours after injection. as well as to all tumor-to-normal tissue ratios. CONCLUSION: Despite their relatively low GRPR affinity, the antagonists [111In/68Ga]-RM1 showed superior targeting properties compared with [111In]-AMBA. As found for somatostatin receptor-targeting radiopeptides, GRP-based radioantagonists seem to be superior to radioagonists for in vivo imaging and potentially also for targeted radiotherapy of GRPR-positive tumors.

Range of motion after computed tomography-based simulation of intertrochanteric corrective osteotomy in cases of slipped capital femoral epiphysis: comparison of uniplanar flexion osteotomy and multiplanar flexion, valgisation, and rotational osteotomies

BACKGROUND: Various osteotomy techniques have been developed to correct the deformity caused by slipped capital femoral epiphysis (SCFE) and compared by their clinical outcomes. The aim of the presented study was to compare an intertrochanteric uniplanar flexion osteotomy with a multiplanar osteotomy by their ability to improve postoperative range of motion as measured by simulation of computed tomographic data in patients with SCFE. METHODS: We examined 19 patients with moderate or severe SCFE as classified based on slippage angle. A computer program for the simulation of movement and osteotomy developed in our laboratory was used for study execution. According to a 3-dimensional reconstruction of the computed tomographic data, the physiological range was determined by flexion, abduction, and internal rotation. The multiplanar osteotomy was compared with the uniplanar flexion osteotomy. Both intertrochanteric osteotomy techniques were simulated, and the improvements of the movement range were assessed and compared. RESULTS: The mean slipping and thus correction angles measured were 25 degrees (range, 8-46 degrees) inferior and 54 degrees (range, 32-78 degrees) posterior. After the simulation of multiplanar osteotomy, the virtually measured ranges of motion as determined by bone-to-bone contact were 61 degrees for flexion, 57 degrees for abduction, and 66 degrees for internal rotation. The simulation of the uniplanar flexion osteotomy achieved a flexion of 63 degrees, an abduction of 36 degrees, and an internal rotation of 54 degrees. CONCLUSIONS: Apart from abduction, the improvement in the range of motion by a uniplanar flexion osteotomy is comparable with that of the multiplanar osteotomy. However, the improvement in flexion for the simulation of both techniques is not satisfactory with regard to the requirements of normal everyday life, in contrast to abduction and internal rotation. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Comparison of intraoral radiography and limited cone beam computed tomography for the assessment of root-fractured permanent teeth

AIM: To compare intraoral occlusal (OC) and periapical (PA) radiographs vs. limited cone beam computed tomography (CBCT) in diagnosing root-fractured permanent teeth. MATERIAL AND METHODS: In 38 patients (mean age 24 years, range 8-52 years) with 44 permanent teeth with horizontal root fractures, intraoral radiographs (PA and OC) and limited CBCT were used to evaluate the location (apical, middle, cervical third of the root) and angulation of the fracture line. Furthermore, the conventional radiographs and CBCT images were compared for concordance of fracture location. RESULTS: In the PA and OC radiographs, 28 fractures (63.6%) were located in the middle third of the root, 11 (25.0%) in the apical third and 5 (11.4%) in the cervical third. The PA/OC radiographs and the sagittal CBCT images (facial aspect) yielded the same level of root fracture in 70.5% of cases (31 teeth; 95% CI: 54.1-82.7%). The PA/OC radiographs and sagittal CBCT images (palatal aspect) showed the same level of root fracture in 31.8% of cases. There was a statistically significant association between the angle at which the root fracture line intersected the axis of the tooth and the level of root fracture in the facial aspect of the sagittal CBCT images. CONCLUSIONS: The diagnosis of the location and angulation of root fractures based on limited CBCT imaging differs significantly from diagnostic procedures based on intraoral radiographs (PA/OC) alone. The clinical significance for treatment strategies and for the prognosis of root-fractured teeth has to be addressed in future studies.

A comparison between two-dimensional and three-dimensional cephalometry on frontal radiographs and on cone beam computed tomography scans of human skulls

The aim of this study was to evaluate whether measurements performed on conventional frontal radiographs are comparable to measurements performed on three-dimensional (3D) models of human skulls derived from cone beam computed tomography (CBCT) scans and if the latter can be used in longitudinal studies. Cone beam computed tomography scans and conventional frontal cephalometric radiographs were made of 40 dry human skulls. From the CBCT scan a 3D model was constructed. Standard cephalometric software was used to identify landmarks and to calculate ratios and angles. The same operator identified 10 landmarks on both types of cephalometric radiographs, and on all images, five times with a time interval of 1 wk. Intra-observer reliability was acceptable for all measurements. There was a statistically significant and clinically relevant difference between measurements performed on conventional frontal radiographs and on 3D CBCT-derived models of the same skull. There was a clinically relevant difference between angular measurements performed on conventional frontal cephalometric radiographs, compared with measurements performed on 3D models constructed from CBCT scans. We therefore recommend that 3D models should not be used for longitudinal research in cases where there are only two-dimensional (2D) records from the past.

Postmortem multislice computed tomography and magnetic resonance imaging of odontoid fractures, atlantoaxial distractions and ascending medullary edema

Non-invasive imaging methods are increasingly entering the field of forensic medicine. Facing the intricacies of classical neck dissection techniques, postmortem imaging might provide new diagnostic possibilities which could also improve forensic reconstruction. The aim of this study was to determine the value of postmortem neck imaging in comparison to forensic autopsy regarding the evaluation of the cause of death and the analysis of biomechanical aspects of neck trauma. For this purpose, 5 deceased persons (1 female and 4 male, mean age 49.8 years, range 20-80 years) who had suffered odontoid fractures or atlantoaxial distractions with or without medullary injuries, were studied using multislice computed tomography (MSCT), magnetic resonance imaging (MRI) and subsequent forensic autopsy. Evaluation of the findings was performed by radiologists, forensic pathologists and neuropathologists. The cause of death could be established radiologically in three of the five cases. MRI data were insufficient due to metal artefacts in one case, and in another, ascending medullary edema as the cause of delayed death was only detected by histological analysis. Regarding forensic reconstruction, the imaging methods were superior to autopsy neck exploration in all cases due to the post-processing possibilities of viewing the imaging data. In living patients who suffer medullary injury, follow-up MRI should be considered to exclude ascending medullary edema.

Virtopsy: forensic traumatology of the subcutaneous fatty tissue; multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) as diagnostic tools

Traumatic lesions of the subcutaneous fatty tissue provide important clues for forensic reconstruction. The interpretation of these patterns requires a precise description and recording of the position and extent of each lesion. During conventional autopsy, this evaluation is performed by dissecting the skin and subcutaneous tissues in successive layers. In this way, depending on the force and type of impact (right angle or tangent), several morphologically distinct stages of fatty tissue damage can be differentiated: perilobular hemorrhage (I), contusion (II), or disintegration (III) of the fat lobuli, and disintegration with development of a subcutaneous cavity (IV). In examples of virtopsy cases showing blunt trauma to the skin and fatty tissue, we analyzed whether these lesions can also be recorded and classified using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). MSCT has proven to be a valuable screening method to detect the lesions, but MRI is necessary in order to properly differentiate and classify the grade of damage. These noninvasive radiological diagnostic tools can be further developed to play an important role in forensic examinations, in particular when it comes to evaluating living trauma victims.

Cone Beam and Micro-Computed Tomography Validation of Manual Array Insertion for Minimally Invasive Cochlear Implantation

Delivering cochlear implants through a minimally invasive tunnel (1.8 mm in diameter) from the mastoid surface to the inner ear is referred to as direct cochlear access (DCA). Based on cone beam as well as micro-computed tomography imaging, this in vitro study evaluates the feasibility and efficacy of manual cochlear electrode array insertions via DCA. Free-fitting electrode arrays were inserted in 8 temporal bone specimens with previously drilled DCA tunnels. The insertion depth angle, procedural time, tunnel alignment as well as the inserted scala and intracochlear trauma were assessed. Seven of the 8 insertions were full insertions, with insertion depth angles higher than 520°. Three cases of atraumatic scala tympani insertion, 3 cases of probable basilar membrane rupture and 1 case of dislocation into the scala vestibuli were observed (1 specimen was damaged during extraction). Manual electrode array insertion following a DCA procedure seems to be feasible and safe and is a further step toward clinical application of image-guided otological microsurgery.

Impacted maxillary canines and root resorptions of neighbouring teeth: a radiographic analysis using cone-beam computed tomography

The study analyses the location of impacted maxillary canines and factors influencing root resorptions of adjacent teeth using cone-beam computed tomography (CBCT). In addition, the interrater reliability between observers of two different dental specialties for radiographic parameters will be evaluated. CBCT images of patients who were referred for radiographic localization of impacted maxillary canines and/or suspicion of root resorptions of adjacent teeth were included. The study analysed the exact three-dimensional location of the impacted canines in the anterior maxilla, frequency and extent of root resorptions, and potential influencing factors. To assess interrater agreement, Cohen's correlation parameters were calculated. This study comprises 113 patients with CBCT scans, and 134 impacted canines were analysed retrospectively. In the patients evaluated, 69 impacted canines were located palatally (51.49 per cent), 41 labially (30.60 per cent), and 24 (17.91 per cent) in the middle of the alveolar process. Root resorptions were found in 34 lateral incisors (25.37 per cent), 7 central incisors (5.22 per cent), 6 first premolars (4.48 per cent), and 1 second premolar (0.75 per cent). There was a significant correlation between root resorptions on adjacent teeth and localization of the impacted canine in relation to the bone, as well as vertical localization of the canine. Interrater agreement showed values of 0.546-0.877. CBCT provides accurate information about location of the impacted canine and prevalence and degree of root resorption of neighbouring teeth with high interrater correlation. This information is of great importance for surgeons and orthodontists for accurate diagnostics and interdisciplinary treatment planning.

Experimental characterization of cement–bentonite interaction using core infiltration techniques and 4D computed tomography

Deep geological storage of radioactive waste foresees cementitious materials as reinforcement of tunnels and as backfill. Bentonite is proposed to enclose spent fuel drums, and as drift seals. The emplacement of cementitious material next to clay material generates an enormous chemical gradient in pore water composition that drives diffusive solute transport. Laboratory studies and reactive transport modeling predict significant mineral alteration at and near interfaces, mainly resulting in a decrease of porosity in bentonite. The goal of this project is to characterize and quantify the cement/bentonite skin effects spatially and temporally in laboratory experiments. A newly developed mobile X-ray transparent core infiltration device was used, which allows performing X-ray computed tomography (CT) periodically without interrupting a running experiment. A pre-saturated cylindrical MX-80 bentonite sample (1920 kg/m3 average wet density) is subjected to a confining pressure as a constant total pressure boundary condition. The infiltration of a hyperalkaline (pH 13.4), artificial OPC (ordinary Portland cement) pore water into the bentonite plug alters the mineral assemblage over time as an advancing reaction front. The related changes in X-ray attenuation values are related to changes in phase densities, porosity and local bulk density and are tracked over time periodically by non-destructive CT scans.

Location and dimensions of the mental foramen: a radiographic analysis by using cone-beam computed tomography

INTRODUCTION The mental foramen (MF) is an important landmark in dentistry. Knowledge of its position is central to perform block anesthesia of the mental nerve or to avoid nerve damage during surgical procedures in the premolar area of the mandible. The present radiographic study aimed at evaluating the location and dimension of the MF and measuring distances to neighboring structures by using limited cone-beam computed tomography (CBCT). METHODS Sagittal, axial, and coronal CBCT images of 142 patients (26 bilateral and 116 unilateral cases) were retrospectively screened to determine the location of the MF with respect to adjacent teeth and to take linear measurements of the size of the MF and its distances to the upper and lower borders of the mandible. In addition, the course and angulation of the mental canal exiting the MF were assessed. RESULTS The majority of MF (56%) were located apically between the 2 premolars, and another 35.7% of MF were positioned below the second premolar. On average, the MF was localized 5.0 mm from the closest root of the adjacent tooth (range, 0.3-9.8 mm). The mean size of the MF showed a height of 3.0 mm and a length of 3.2 mm; however, individual cases showed large differences in height (1.8-5.1 mm) and in length (1.8-5.5 mm). All mental canals exiting the MF demonstrated an upward course in the coronal plane, with 70.1% of the mental canal presenting an anterior loop (AL) in the axial view. The mean extension of AL in cases with an AL was 2.3 mm. CONCLUSIONS This study is consistent with previous radiographic studies regarding size and location of MF and distances between MF and adjacent anatomic structures. The assessed bilateral cases showed a high intraindividual concordance for certain features when comparing right and left sides.

[Cone beam computed tomography in endodontics: a review for daily clinical practice]

Since the introduction of cone beam computed tomography (CBCT), this 3-dimensional diagnostic imaging technique has been established in a growing number of fields in dental medicine. It has become an important tool for both diagnosis and treatment planning, and is also able to support endodontic treatments. However, the higher effective dose of ionizing radiation compared to conventional 2-dimensional radiographs is not justifiable in every case. CBCT allows for a more precise diagnosis of periapical lesions, root fractures as well as external and internal resorptions. Concerning the utility of CBCT in treatment planning decisions, the gain of information through 3-dimensional imaging for any of these pathologies has to be evaluated carefully on an individual basis. Moreover, radioopaque materials such as root canal filling and posts often create artefacts, which may compromise diagnosis. The aim of this review is to summarize the possibilities and limits of CBCT imaging in endodontology as well as introduce guidelines for daily clinical practice. Furthermore, the article presents possible therapeutic advantages of preexisting CBCT scans for root canal treatments.