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.

An unusual case of galactorrhea in a postmenopausal woman complicating breast reduction

Galactorrhea is a relatively common condition, but has rarely been seen following breast reduction surgery. To date there are only seven cases reported in the literature, all in premenopausal women. Postsurgical galactorrhea is a diagnosis of exclusion and differential diagnosis is extensive. Common causes should be excluded first. We present the case of a 56-year-old postmenopausal woman who underwent bilateral breast reduction and developed galactorrhea 2 months postoperatively. MRI scan of the skull as well as Thyroid-Stimulating Hormone (TSH), prolactin levels were normal. She was on long-term hormonal replacement therapy. Because of suspected nerve-related pain in her right breast she was commenced on amitriptyline. We hypothesise that galactorrhea may have been caused by underlying neuroma or irritation of the anterior branch of the T4 intercostal nerve or hormonal replacement therapy or a combination of both.

Survivors with bad outcome after hypoxic-ischaemic encephalopathy: full-term neonates compare unfavourably with children

Hypoxic-ischaemic encephalopathy (HIE) is of major importance in neonatal and paediatric intensive care with regard to mortality and long-term morbidity. Our aim was to analyse our data in full-term neonates and children with special regard to withdrawal of life support and bad outcome. PATIENTS: All patients with HIE admitted to our unit from 1992-96 were analysed. Criteria for HIE were presence of a hypoxic insult followed by coma or altered consciousness with or without convulsions. Severity of HIE was assessed in neonates using Sarnat stages, and in children the duration of coma. In the majority of cases staging was completed with electrophysiological studies. Outcome was described using the Glasgow Outcome Scale. Bad outcome was defined as death, permanent vegetative state or severe disability, good outcome as moderate disability or good recovery. RESULTS: In the neonatal group (n = 38) outcome was significantly associated with Sarnat stages, presence of convulsions, severely abnormal EEG, cardiovascular failure, and multiple organ dysfunction (MOD). A bad outcome was observed in 27 cases with 14 deaths and 13 survivors. Supportive treatment was withdrawn in 14 cases with 9 subsequent deaths. In the older age group (n = 45) outcome was related to persistent coma of 24-48 h, severely abnormal EEG, cardiovascular failure, liver dysfunction and MOD. A bad outcome was found in 36 cases with 33 deaths and 3 survivors. Supportive treatment was withdrawn in 15 instances, all followed by death. CONCLUSIONS: Overall, neonates and older patients did not differ with regard to good or bad outcome. However, in the neonatal group there were significantly more survivors with bad outcome, either overall or after withdrawal of support. Possible explanations for this difference include variability of hypoxic insult, maturational and metabolic differences, and the more compliant neonatal skull, which prevents brainstem herniation.

Rare retinal haemorrhages in translational accidental head trauma in children

PURPOSE: The characteristic findings in accidental head injury consist of linear skull fracture, epidural haematoma, localized subdural haematoma, or cortical contusion because of a linear or translational impact force. Retinal haemorrhages have been found, although uncommon, in accidental head trauma. METHODS: We performed a retrospective study of 24 consecutive cases of children with severe head injuries caused by falls. Inclusion criteria were skull fractures and/or intracranial haemorrhages documented by computerized tomography. All patients underwent a careful ophthalmic examination including dilated indirect fundoscopy within the first 48 h following admission. RESULTS: No retinal haemorrhages could be found in patients whose accidents were plausible and physical and imaging findings were compatible with reported histories. Excessive bilateral retinal haemorrhages were found in only three children with the typical signs of shaken baby syndrome. In eight children, trauma had led to orbital roof fractures. CONCLUSIONS: Retinal haemorrhages were not found in any of the patients with accidental trauma despite the severity of their head injuries. Hence, we add more evidence that there are strong differences between the ocular involvement in accidental translational trauma and those in victims of non-accidental trauma. Fall-related injuries carry a very low risk of retinal haemorrhages.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease

OBJECT: The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. METHODS: Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. RESULTS: Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. CONCLUSIONS: This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

A complementary radiographic projection of the equine temporomandibular joint

The complexity of the equine skull makes the temporomandibular joint a difficult area to evaluate radiographically. The goal of this study was to determine the optimal angle for a complementary radiographic projection of the equine temporomandibular joint based on a computed tomography (CT) cadaver study. CT was performed on six equine cadaver heads of horses that were euthanized for other reasons than temporomandibular joint disease. After the CT examination, 3D reconstruction of the equine skull was performed to subjectively determine the angle for a complementary radiographic projection of the temporomandibular joint. The angle was measured on the left and right temporomandibular joint of each head. Based on the measurements obtained from the CT images, a radiographic projection of the temporomandibular joint in a rostra-145 degrees ventral-caudodorsal oblique (R45 degrees V-CdDO) direction was developed by placing the X-ray unit 30 degrees laterally, maintaining at the same time the R45 degrees V-CdDO angle (R45 degrees V30 degrees L-CdDLO). This radiographic projection was applied to all cadaver heads and on six live horses. In three of the live horses abnormal findings associated with the temporomandibular joint were detected. We conclude that this new radiographic projection of the temporomandibular joint provides superior visualization of the temporomandibular joint space and the articular surface of the mandibular condyle.

Bone conduction in Thiel-embalmed cadaver heads

INTRODUCTION Sound can reach the inner ear via at least two different pathways: air conduction and bone conduction (BC). BC hearing is used clinically for diagnostic purposes and for BC hearing aids. Research on the motion of the human middle ear in response to BC stimulation is typically conducted using cadaver models. We evaluated middle ear motion of Thiel-embalmed whole-head specimens in terms of linearity, reproducibility, and consistency with the reported middle ear motion of living subjects, fresh cadaveric temporal bones, and whole-heads embalmed with a Non-Thiel solution of salts. METHODS We used laser Doppler vibrometry to measure the displacement of the skull, the umbo, the cochlear promontory, the stapes, and the round window in seven ears from four human whole-head specimens embalmed according to Thiel's method. The ears were stimulated with a Baha(®) implanted behind the auricle. RESULTS The Thiel model shows promontory velocity similar to that reported in the literature for whole-heads embalmed with a Non-Thiel solution of salts (0- to 7-dB difference). The Thiel heads' relative velocity of the stapes with respect to the promontory was similar to that of fresh cadaver temporal bones (0- to 4-dB difference). The velocity of the umbo was comparable in Thiel-embalmed heads and living subjects (0- to 10-dB difference). The skull and all middle ear elements measured responded linearly to different stimulation levels, with an average difference less than 1 dB. The variability of repeated measurements for both short- (2 h; 4 dB) and long-term (4-16 weeks; 6 dB) repetitions in the same ear, and the difference between the two ears of the same donor (approximately 10 dB) were lower than the inter-individual difference (up to 25 dB). CONCLUSION Thiel-embalmed human whole-head specimens can be used as an alternative model for the study of human middle ear mechanics secondary to BC stimulation. At some frequencies, differences from living subjects must be considered.

Estimation of tool pose based on force-density correlation during robotic drilling

The application of image-guided systems with or without support by surgical robots relies on the accuracy of the navigation process, including patient-to-image registration. The surgeon must carry out the procedure based on the information provided by the navigation system, usually without being able to verify its correctness beyond visual inspection. Misleading surrogate parameters such as the fiducial registration error are often used to describe the success of the registration process, while a lack of methods describing the effects of navigation errors, such as those caused by tracking or calibration, may prevent the application of image guidance in certain accuracy-critical interventions. During minimally invasive mastoidectomy for cochlear implantation, a direct tunnel is drilled from the outside of the mastoid to a target on the cochlea based on registration using landmarks solely on the surface of the skull. Using this methodology, it is impossible to detect if the drill is advancing in the correct direction and that injury of the facial nerve will be avoided. To overcome this problem, a tool localization method based on drilling process information is proposed. The algorithm estimates the pose of a robot-guided surgical tool during a drilling task based on the correlation of the observed axial drilling force and the heterogeneous bone density in the mastoid extracted from 3-D image data. We present here one possible implementation of this method tested on ten tunnels drilled into three human cadaver specimens where an average tool localization accuracy of 0.29 mm was observed.

Feasibility of Using EMG for Early Detection of the Facial Nerve During Robotic Direct Cochlear Access

HYPOTHESIS Facial nerve monitoring can be used synchronous with a high-precision robotic tool as a functional warning to prevent of a collision of the drill bit with the facial nerve during direct cochlear access (DCA). BACKGROUND Minimally invasive direct cochlear access (DCA) aims to eliminate the need for a mastoidectomy by drilling a small tunnel through the facial recess to the cochlea with the aid of stereotactic tool guidance. Because the procedure is performed in a blind manner, structures such as the facial nerve are at risk. Neuromonitoring is a commonly used tool to help surgeons identify the facial nerve (FN) during routine surgical procedures in the mastoid. Recently, neuromonitoring technology was integrated into a commercially available drill system enabling real-time monitoring of the FN. The objective of this study was to determine if this drilling system could be used to warn of an impending collision with the FN during robot-assisted DCA. MATERIALS AND METHODS The sheep was chosen as a suitable model for this study because of its similarity to the human ear anatomy. The same surgical workflow applicable to human patients was performed in the animal model. Bone screws, serving as reference fiducials, were placed in the skull near the ear canal. The sheep head was imaged using a computed tomographic scanner and segmentation of FN, mastoid, and other relevant structures as well as planning of drilling trajectories was carried out using a dedicated software tool. During the actual procedure, a surgical drill system was connected to a nerve monitor and guided by a custom built robot system. As the planned trajectories were drilled, stimulation and EMG response signals were recorded. A postoperative analysis was achieved after each surgery to determine the actual drilled positions. RESULTS Using the calibrated pose synchronized with the EMG signals, the precise relationship between distance to FN and EMG with 3 different stimulation intensities could be determined for 11 different tunnels drilled in 3 different subjects. CONCLUSION From the results, it was determined that the current implementation of the neuromonitoring system lacks sensitivity and repeatability necessary to be used as a warning device in robotic DCA. We hypothesize that this is primarily because of the stimulation pattern achieved using a noninsulated drill as a stimulating probe. Further work is necessary to determine whether specific changes to the design can improve the sensitivity and specificity.

Investigations on an egyptian coffin and mummified head from Burgdorf Museum, Switzerland - A case of a historical puzzle

In the Burgdorf Museum of Ethnology, a mummy rests in a coffin. According to the inventory book, it was purchased from the Cairo Egyptian museum in 1926. The coffin was now examined by Egyptologists and the mummy was radiocarbon dated and examined by Anthropologists. The aim of the study was to compare the results and to check whether mummy and coffin actually belong together. The skull was examined morphological-anthropologically and by CT as a “blank sample”. Coffin and skull imply that the individual was female. The coffin dates to the Ptolemaic period. Only skull bones are preserved, the ethmoid is damaged. CT images Show resinous substances, bone fragments and brain remnants inside the skull. The ethmoid bone was probably foraminated during the mummification process and thus ended up inside the skull. The individual was mummified between the New Kingdom and the Ptolemaic period. Due to its style, it is most probable that the coffin comes from the Gamhud necropolis. The Burgdorf museum of ethnology inventory book chronicles were largely falsified by the examinations. There is a time gap between coffin and the mummy, there are two possible interpretations: the body was mummified with older linen, or the mummy and the coffin do not belong together. The authors strongly advise further investigations.

THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY

Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of impact and damage can include scalp laceration, skull fraction, cerebral contusions and lacerations as well as intracranial hemorrhage. Following the initial insult, a delayed response occurs and is characterized by hypoxia, ischemia, cerebral edema, and infection. During secondary brain injury, a series of neuroinflammatory events are triggered that can produce additional damage but may also help to protect nervous tissue from invading pathogens and help to repair the damaged tissue. Brain microglia and astrocytes become activated and migrate to the site of injury where these cells secrete immune mediators such as cytokines and chemokines. CC-chemokine receptor 5 (CCR5) is a member of the CC chemokine receptor family of seven transmembrane G protein coupled receptors. CCR5 is expressed in the immune system and is found in monocytes, leukoctyes, memory T cells, and immature dendritic cells. Upon binding to its ligands, CCR5 functions in the chemotaxis of these immune cells to the site of inflammation. In the CNS, CCR5 and its ligands are expressed in multiple cell types. In this study, I investigated whether CCR5 expression is altered in brain after traumatic brain injury. I examined the time course of CCR5 protein expression in cortex and hippocampus using quantitative western analysis of tissues from injured rat brain after mild impact injury. In addition, I also investigated the cellular localization of CCR5 before and after brain injury using confocal microscopy. I have observed that after brain injury CCR5 is upregulated in a time dependent manner in neurons of the parietal cortex and hippocampus. The absence of CCR5 expression in microglia and its delayed expression in neurons after injury suggests a role for CCR5 in neuronal survival after injury.

THE EXPRESSION AND CELLULAR LOCALIZATION OF CC-CHEMOKINE RECEPTOR 5 (CCR5) AFTER TRAUMATIC BRAIN INJURY

Traumatic brain injury results from a primary insult and secondary events that together result in tissue injury. This primary injury occurs at the moment of impact and damage can include scalp laceration, skull fraction, cerebral contusions and lacerations as well as intracranial hemorrhage. Following the initial insult, a delayed response occurs and is characterized by hypoxia, ischemia, cerebral edema, and infection. During secondary brain injury, a series of neuroinflammatory events are triggered that can produce additional damage but may also help to protect nervous tissue from invading pathogens and help to repair the damaged tissue. Brain microglia and astrocytes become activated and migrate to the site of injury where these cells secrete immune mediators such as cytokines and chemokines. CC-chemokine receptor 5 (CCR5) is a member of the CC chemokine receptor family of seven transmembrane G protein coupled receptors. CCR5 is expressed in the immune system and is found in monocytes, leukoctyes, memory T cells, and immature dendritic cells. Upon binding to its ligands, CCR5 functions in the chemotaxis of these immune cells to the site of inflammation. In the CNS, CCR5 and its ligands are expressed in multiple cell types. In this study, I investigated whether CCR5 expression is altered in brain after traumatic brain injury. I examined the time course of CCR5 protein expression in cortex and hippocampus using quantitative western analysis of tissues from injured rat brain after mild impact injury. In addition, I also investigated the cellular localization of CCR5 before and after brain injury using confocal microscopy. I have observed that after brain injury CCR5 is upregulated in a time dependent manner in neurons of the parietal cortex and hippocampus. The absence of CCR5 expression in microglia and its delayed expression in neurons after injury suggests a role for CCR5 in neuronal survival after injury.

The Development and Implementation of an Anthropomorphic Head Phantom for the Assessment of Proton Therapy Treatment Procedures

Proton therapy has become an increasingly more common method of radiation therapy, with the dose sparing to distal tissue making it an appealing option, particularly for treatment of brain tumors. This study sought to develop a head phantom for the Radiological Physics Center (RPC), the first to be used for credentialing of institutions wishing to participate in clinical trials involving brain tumor treatment of proton therapy. It was hypothesized that a head phantom could be created for the evaluation of proton therapy treatment procedures (treatment simulation, planning, and delivery) to assure agreement between the measured dose and calculated dose within ±5%/3mm with a reproducibility of ±3%. The relative stopping power (RSP) and Hounsfield Units (HU) were measured for potential phantom materials and a human skull was cast in tissue-equivalent Alderson material (RLSP 1.00, HU 16) with anatomical airways and a cylindrical hole for imaging and dosimetry inserts drilled into the phantom material. Two treatment plans, proton passive scattering and proton spot scanning, were created. Thermoluminescent dosimeters (TLDs) and film were loaded into the phantom dosimetry insert. Each treatment plan was delivered three separate times. Each treatment plan passed our 5%/3mm criteria, with a reproducibility of ±3%. The hypothesis was accepted and the phantom was found to be suitable for remote audits of proton therapy treatment facilities.

BMP-SIGNALING REGULATES A COMMON TRANSCRIPTIONAL PROGRAM TO CONTROL FACIAL FORM AND SKELETAL MORPHOGENESIS

Much of the craniofacial skeleton, such as the skull vault, mandible and midface, develops through direct, intramembranous ossification of the cranial neural crest (CNC) derived progenitor cells. Bmp-signaling plays critical roles in normal craniofacial development, and Bmp4 deficiency results in craniofacial abnormalities, such as cleft lip and palate. We performed an in depth analysis of Bmp4, a critical regulator of development, disease, and evolution, in the CNC. Conditional Bmp4 overexpression, using a tetracycline regulated Bmp4 gain of function allele, resulted in facial form changes that were most dramatic after an E10.5 Bmp4 induction. Expression profiling uncovered a signature of Bmp4 induced genes (BIG) composed predominantly of transcriptional regulators controlling self-renewal, osteoblast differentiation, and negative Bmp autoregulation. The complimentary experiment, CNC inactivation of Bmp2, Bmp4, and Bmp7, resulted in complete or partial loss of multiple CNC derived skeletal elements revealing a critical requirement for Bmp-signaling in membranous bone and cartilage development. Importantly, the BIG signature was reduced in Bmp loss of function mutants indicating similar Bmp-regulated target genes underlying facial form modulation and normal skeletal morphogenesis. Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG signature, including Satb2, Smad6, Hand1, Gadd45g and Gata3 that was bound by Smad1/5 in the developing mandible revealing direct, Smad-mediated regulation. These data indicate that Bmp-signaling regulates craniofacial skeletal development and facial form by balancing self-renewal and differentiation pathways in CNC progenitors.

Genetic analysis of factors regulating mesenchymal cell fates

Formation of cartilage and bone involves sequential processes in which undifferentiated mesenchyme aggregates into primordial condensations which subsequently grow and differentiate, resulting in morphogenesis of the adult skeleton. While much has been learned about the structural molecules which comprise cartilage and bone, little is known about the nuclear factors which regulate chondrogenesis and osteogenesis. MHox is a homeobox-containing gene which is expressed in the mesenchyme of facial, limb, and vertebral skeletal precursors during mouse embryogenesis. MHox expression has been shown to require epithelial-derived signals, suggesting that MHox may regulate the epithelial-mesenchymal interactions required for skeletal organogenesis. To determine the functions of MHox, we generated a loss-of-function mutation in the MHox gene. Mice homozygous for a mutant MHox allele exhibit defects of skeletogenesis, involving the loss or malformation of craniofacial, limb and vertebral skeletal structures. The affected skeletal elements are derived from the cranial neural crest, as well as somitic and lateral mesoderm. Analysis of the mutant phenotype during ontogeny demonstrated a defect in the formation or growth of chondrogenic and osteogenic precursors. These findings provide evidence that MHox regulates the formation of preskeletal condensations from undifferentiated mesenchyme. In addition, generation of mice doubly mutant for the MHox and S8 homeobox genes reveal that these two genes interact to control formation of the limb and craniofacial skeleton. Mice carrying mutant alleles for S8 and MHox exhibit an exaggeration of the craniofacial and limb phenotypes observed in the MHox mutant mouse. Thus, MHox and S8 are components of a combinatorial genetic code controlling generation of the skeleton of the skull and limbs. ^