Radiological age assessment based on clavicle ossification in CT: enhanced accuracy through deep learning.

BACKGROUND: Radiological age assessment using reference studies is inherently limited in accuracy due to a finite number of assignable skeletal maturation stages. To overcome this limitation, we present a deep learning approach for continuous age assessment based on clavicle ossification in computed tomography (CT). METHODS: Thoracic CT scans were retrospectively collected from the picture archiving and communication system. Individuals aged 15.0 to 30.0 years examined in routine clinical practice were included. All scans were automatically cropped around the medial clavicular epiphyseal cartilages. A deep learning model was trained to predict a person's chronological age based on these scans. Performance was evaluated using mean absolute error (MAE). Model performance was compared to an optimistic human reader performance estimate for an established reference study method. RESULTS: The deep learning model was trained on 4,400 scans of 1,935 patients (training set: mean age = 24.2 years ± 4.0, 1132 female) and evaluated on 300 scans of 300 patients with a balanced age and sex distribution (test set: mean age = 22.5 years ± 4.4, 150 female). Model MAE was 1.65 years, and the highest absolute error was 6.40 years for females and 7.32 years for males. However, performance could be attributed to norm-variants or pathologic disorders. Human reader estimate MAE was 1.84 years and the highest absolute error was 3.40 years for females and 3.78 years for males. CONCLUSIONS: We present a deep learning approach for continuous age predictions using CT volumes highlighting the medial clavicular epiphyseal cartilage with performance comparable to the human reader estimate.

Automated localization of the medial clavicular epiphyseal cartilages using an object detection network: a step towards deep learning-based forensic age assessment.

BACKGROUND: Deep learning is a promising technique to improve radiological age assessment. However, expensive manual annotation by experts poses a bottleneck for creating large datasets to appropriately train deep neural networks. We propose an object detection approach to automatically annotate the medial clavicular epiphyseal cartilages in computed tomography (CT) scans. METHODS: The sternoclavicular joints were selected as structure-of-interest (SOI) in chest CT scans and served as an easy-to-identify proxy for the actual medial clavicular epiphyseal cartilages. CT slices containing the SOI were manually annotated with bounding boxes around the SOI. All slices in the training set were used to train the object detection network RetinaNet. Afterwards, the network was applied individually to all slices of the test scans for SOI detection. Bounding box and slice position of the detection with the highest classification score were used as the location estimate for the medial clavicular epiphyseal cartilages inside the CT scan. RESULTS: From 100 CT scans of 82 patients, 29,656 slices were used for training and 30,846 slices from 110 CT scans of 110 different patients for testing the object detection network. The location estimate from the deep learning approach for the SOI was in a correct slice in 97/110 (88%), misplaced by one slice in 5/110 (5%), and missing in 8/110 (7%) test scans. No estimate was misplaced by more than one slice. CONCLUSIONS: We demonstrated a robust automated approach for annotating the medial clavicular epiphyseal cartilages. This enables training and testing of deep neural networks for age assessment.

Distribution of nickel and chromium containing particles from tattoo needle wear in humans and its possible impact on allergic reactions.

BACKGROUND: Allergic reactions to tattoos are amongst the most common side effects occurring with this permanent deposition of pigments into the dermal skin layer. The characterization of such pigments and their distribution has been investigated in recent decades. The health impact of tattoo equipment on the extensive number of people with inked skin has been the focus of neither research nor medical diagnostics. Although tattoo needles contain high amounts of sensitizing elements like nickel (Ni) and chromium (Cr), their influence on metal deposition in skin has never been investigated. RESULTS: Here, we report the deposition of nano- and micrometer sized tattoo needle wear particles in human skin that translocate to lymph nodes. Usually tattoo needles contain nickel (6-8%) and chromium (15-20%) both of which prompt a high rate of sensitization in the general population. As verified in pig skin, wear significantly increased upon tattooing with the suspected abrasive titanium dioxide white when compared to carbon black pigment. Additionally, scanning electron microscopy of the tattoo needle revealed a high wear after tattooing with ink containing titanium dioxide. The investigation of a skin biopsy obtained from a nickel sensitized patient with type IV allergy toward a tattoo showed both wear particles and iron pigments contaminated with nickel. CONCLUSION: Previously, the virtually inevitable nickel contamination of iron pigments was suspected to be responsible for nickel-driven tattoo allergies. The evidence from our study clearly points to an additional entry of nickel to both skin and lymph nodes originating from tattoo needle wear with an as yet to be assessed impact on tattoo allergy formation and systemic sensitization.

DNA Barcoding in Forensic Entomology - Establishing a DNA Reference Library of Potentially Forensic Relevant Arthropod Species.

Throughout the years, DNA barcoding has gained in importance in forensic entomology as it leads to fast and reliable species determination. High-quality results, however, can only be achieved with a comprehensive DNA barcode reference database at hand. In collaboration with the Bavarian State Criminal Police Office, we have initiated at the Bavarian State Collection of Zoology the establishment of a reference library containing arthropods of potential forensic relevance to be used for DNA barcoding applications. CO1-5P' DNA barcode sequences of hundreds of arthropods were obtained via DNA extraction, PCR and Sanger Sequencing, leading to the establishment of a database containing 502 high-quality sequences which provide coverage for 88 arthropod species. Furthermore, we demonstrate an application example of this library using it as a backbone to a high throughput sequencing analysis of arthropod bulk samples collected from human corpses, which enabled the identification of 31 different arthropod Barcode Index Numbers.

Life-threatening events in patients with pheochromocytoma.

OBJECTIVE: Pheochromocytomas are rare chromaffin cell-derived tumors causing paroxysmal episodes of headache, palpitation, sweating and hypertension. Life-threatening complications have been described in case reports and small series. Systematic analyses are not available. We took an opportunity of a large series to make a survey. DESIGN AND METHODS: We analyzed records of patients diagnosed with pheochromocytomas in three geographically spread German referral centers between 2003 and 2012 (n=135). RESULTS: Eleven percent of the patients (ten women, five men) required in-hospital treatment on intensive care units (ICUs) due to complications caused by unsuspected pheochromocytomas. The main reasons for ICU admission were acute catecholamine induced Tako-Tsubo cardiomyopathy (n=4), myocardial infarction (n=2), acute pulmonary edema (n=2), cerebrovascular stroke (n=2), ischemic ileus (n=1), acute renal failure (n=2), and multi organ failure (n=1). One patient required extracorporeal membrane oxygenation due to a hypertensive crisis with lung edema occurring during delivery (n=1). Two patients died of refractory shock and pheochromocytomas were found postmortem. Two patients were treated by emergency surgery. Compared to pheochromocytoma patients without life-threatening events (n=120), patients with complications had a significant larger maximal tumor diameter (7.0 vs 4.5 cm, P<0.01), higher levels of catecholamines (20- vs ninefold upper limit of normal, P<0.01), and tended to be younger (42 vs 51 years, P=0.05). CONCLUSION: Although pheochromocytomas are rare, they are likely to be associated with a life-threatening situation. Clinicians have to be aware of these situations and perform a timely diagnosis.

Black tattoos entail substantial uptake of genotoxicpolycyclic aromatic hydrocarbons (PAH) in human skin and regional lymph nodes.

Hundreds of millions of people worldwide have tattoos, which predominantly contain black inks consisting of soot products like Carbon Black or polycyclic aromatic hydrocarbons (PAH). We recently found up to 200 µg/g of PAH in commercial black inks. After skin tattooing, a substantial part of the ink and PAH should be transported to other anatomical sites like the regional lymph nodes. To allow a first estimation of health risk, we aimed to extract and quantify the amount of PAH in black tattooed skin and the regional lymph nodes of pre-existing tattoos. Firstly, we established an extraction method by using HPLC-DAD technology that enables the quantification of PAH concentrations in human tissue. After that, 16 specimens of human tattooed skin and corresponding regional lymph nodes were included in the study. All skin specimen and lymph nodes appeared deep black. The specimens were digested and tested for 20 different PAH at the same time.PAH were found in twelve of the 16 tattooed skin specimens and in eleven regional lymph nodes. The PAH concentration ranged from 0.1-0.6 µg/cm2 in the tattooed skin and 0.1-11.8 µg/g in the lymph nodes. Two major conclusions can be drawn from the present results. Firstly, PAH in black inks stay partially in skin or can be found in the regional lymph nodes. Secondly, the major part of tattooed PAH had disappeared from skin or might be found in other organs than skin and lymph nodes. Thus, beside inhalation and ingestion, tattooing has proven to be an additional, direct and effective route of PAH uptake into the human body.

Algorithm-based coagulation management of catastrophic amniotic fluid embolism.

Amniotic fluid embolism (AFE) is a rare, but often catastrophic, complication of pregnancy and associated with severe coagulopathy. We present an algorithm-based approach in managing coagulopathy and hemorrhage in a fatal case of histopathologically proven AFE. Thrombelastometry was used for rapid evaluation of the coagulation status. Stop of extensive hyperfibrinolysis with tranexamic acid, stabilization of initial clot formation with high-dose fibrinogen and platelet transfusions, and use of prothrombin complex concentrate together with a 1: 1 transfusion regimen of red packed cells and fresh frozen plasma was successful to control diffuse bleeding and restore clot firmness after hysterectomy. Stable clotting situation was maintained despite further clinical deterioration and development of multiple organ failure in this patient.

Widespread axonal damage in the brain of drug abusers as evidenced by accumulation of beta-amyloid precursor protein (beta-APP): an immunohistochemical investigation.

BACKGROUND: In drug abusers, white matter changes have been described by neuroimaging analyses in different brain regions. A specific pattern of involvement or a predominance of a specific brain region could not be drawn. AIMS: To examine alterations of the white matter as a possible morphological substrate of the neuroimaging findings. METHODS: Brain specimens of 30 polydrug abusers and 20 controls were obtained at autopsy. The white matter from 11 different brain regions was analysed by means of immunohistochemistry for beta-amyloid precursor protein (beta-APP), a marker of axonal damage. FINDINGS: In the white matter of polydrug abusers, beta-APP-immunopositive accumulations were increased significantly compared to controls. They were more prominent in the brains of younger drug abusers than in those of the elderly. With the exception of five cases (four polydrug abusers and one control case), there were no significant white matter changes seen on myelin-stained sections, but there was a concomitant microglial activation. CONCLUSIONS: Our results show a significant axonal damage in the brains of polydrug abusers, which might represent the morphological substrate of a chronic-progressive drug-induced toxic-metabolic process. It is yet to be established if the observed changes are responsible for the alterations seen in different neuroimaging analyses and which drugs of abuse might be of major pathogenetic significance.

Alterations of the vascular basal lamina in the cerebral cortex in drug abuse: a combined morphometric and immunohistochemical investigation.

In drug abusers, white matter hyperintensities, perfusion deficits, and metabolic disturbances are detected by neuroimaging analyses in different brain regions. A specific pattern of involvement or a predominance of a specific brain region cannot be drawn. To examine changes of the cerebral microvasculature as a possible morphological substrate of the neuroimaging findings, brain specimens of 12 polydrug abusers and 8 controls were obtained at autopsy. The basal lamina of blood vessels from the frontal, temporal, parietal, and occipital lobes was analysed by means of immunohistochemistry for collagen type IV. The numerical density of vessels was determined in the gray and white matter, and their staining intensity was rated using a three-point scale. In the gray and white matter of polydrug abusers, the number of vessels showing strong immunoreactivity for collagen type IV was significantly reduced, whereas the number of vessels with mild and moderate immunoreactivity was increased as compared to controls. The total numerical density of vessels was not significantly changed. Our results show a significant reduction in immunoreactivity for collagen type IV in the brains from polydrug abusers compared to controls, which may be due to a thinning of the basal lamina of cerebral vessels. The data of the present study show morphological changes of the basal lamina in the brain of polydrug abusers, which might represent the morphological substrate of a disturbed blood-brain barrier. However, it remains yet to be established if the observed changes are responsible for the alterations seen in different neuroimaging analyses and which drug might be of major pathogenetic significance.

Quantification of C2 cervical spine rotatory fixation by X-ray, MRI and CT.

Atlanto-axial rotatory displacement is known to be a cause of childhood torticollis and may as well be responsible for chronic neck pain after rear-end automobile collisions. The objective was to determine whether quantification of C2 malrotation is possible by plain radiographs in comparison to CT as the golden standard. MR imaging was evaluated as to whether it was of equal value in the detection of bony landmarks. C2 vertebra of five human cadaveric cervical spine specimens, ligamentously intact, were rotated using a Steinmann pin in steps of 5 degrees up to 15 degrees right and 15 degrees left. Plain radiographs, CT and MRI images were taken in each rotational step. Data were analyzed for quantification of C2 rotation by three independent examiners. A rotation of 5 degrees led to a spinous process deviation (SPD) from the midline of 3 mm as measured on an a.p. plain radiograph. A coefficient of rotation was calculated (1.62 degrees mm(-1)). Data analyzed by three examiners revealed a small coefficient of variation (0.03). MRI and CT measurements showed comparable results for the quantification of rotation; however, in both techniques the 15 degrees rotation was underestimated. Quantification of upper cervical spine malrotation was possible on plain radiographs using the SPD and a rotation coefficient. MRI and CT were equally successful in the assessment of C2 malrotation.

The neuropathology of cocaine abuse.

Cocaine abuse represents a worldwide significant forensic issue as it is becoming widely recognized as one of the most dangerous illicit drugs in common use today. Besides cardiovascular complications, psychiatric and neurologic symptoms are the most common manifestations of cocaine toxicity. The latter include seizures, movement disorders and cerebrovascular complications. In chronic cocaine abusers morphological, physiological, and neurochemical abnormalities have been demonstrated by using neuroradiological techniques such as computed tomography, magnetic resonance imaging, positron emission tomography or single photon emission computed tomography. The spectrum of neuropathologic changes encountered in the brains of cocaine abusers is broad, but the major findings consist of ischemic and hemorrhagic stroke, subarachnoid and intracerebral hemorrhages and cerebral ischemia. Especially persons with underlying arteriovenous malformation or aneurysm are at risk for such events. Except for a few instances of vasculitis, the etiology of cocaine-related cerebrovascular accidents is still unclear. Besides pharmacologically-induced vasospasm, impaired hemostasis and platelet function and decreased cerebral blood flow have been proposed. At the cellular level, abnormalities in the expression of transcription factors and changes of brain neurotransmitter systems have been reported.