Crediting multi-authored papers to single authors

A fair assignment of credit for multi-authored publications is a long-standing issue in scientometrics. In the calculation of the $h$-index, for instance, all co-authors receive equal credit for a given publication, independent of a given author's contribution to the work or of the total number of co-authors. Several attempts have been made to distribute the credit in a more appropriate manner. In a recent paper, Hirsch has suggested a new way of credit assignment that is fundamentally different from the previous ones: All credit for a multi-author paper goes to a single author, the called ``$\alpha$-author'', defined as the person with the highest current $h$-index not the highest $h$-index at the time of the paper's publication) (J. E. Hirsch, Scientometrics 118, 673 (2019)). The collection of papers this author has received credit for as $\alpha$-author is then used to calculate a new index, $h_{\alpha}$, following the same recipe as for the usual $h$ index. The objective of this new assignment is not a fairer distribution of credit, but rather the determination of an altogether different property, the degree of a person's scientific leadership. We show that given the complex time dependence of $h$ for individual scientists, the approach of using the current $h$ value instead of the historic one is problematic, and we argue that it would be feasible to determine the $\alpha$-author at the time of the paper's publication instead. On the other hand, there are other practical considerations that make the calculation of the proposed $h_{\alpha}$ very difficult. As an alternative, we explore other ways of crediting papers to a single author in order to test early career achievement or scientific leadership.Comment: 6 pages, 4 figure

Clinical translation of quantitative MRI techniques in Neuroradiology

The overall objective of the present work is the translation of advanced qMRI techniques from the research environment into the field of clinical neuroimaging. In this context, qMRI is defined as the application of absolute quantitative measures that are extracted from in vivo MRI data. These can be used to describe biophysical characteristics and processes and thereby enhance the diagnostic power of qualitative, “weighted” imaging that is primarily used in the clinical setting. The feasibility, usefulness, and limitations of five qMRI techniques were investigated in different CNS pathologies (brain tumours, ischaemic stroke, migraine, brain/skull malformations) and in the description of normal brain maturation in infants and young children. The translation of new imaging methods from “bench to bedside” involves several steps, and the presented studies are located at different stages in this process. Studies 1 and 2 are examples of a relatively early stage. At the time of publication, pH-weighted APT imaging had been tested preclinically and in smaller cohorts of patients, but not in acute stroke, where anaerobic glycolysis and tissue acidosis is highly prevalent. In study 1, it was postulated that APT imaging could be a novel approach to demonstrate oligaemia in hyperacute stroke, allowing a more detailed description of tissue at risk. For acceleration purposes, sequence parameters were optimised by using computer simulations and subsequently validated in healthy subjects. Ten acute stroke patients were included (7 < 4 hours, 3 < 24 hours after symptom onset). As expected, the APT effect was significantly decreased in ischaemic regions compared to normal white matter (p=0.03) and APT values tended to be lower in the final infarct volume (p=0.10). In study 2, APT imaging was moved to a different pathology, also characterised by hypoperfusion, tissue hypoxia, and anaerobic glycolysis. Here, the metabolic changes during the migraine aura of a patient with FHM were investigated for the first time using APT imaging. The patient developed clear tissue acidosis and blood flow disturbances in the absence of ischaemia in the affected cerebral hemisphere, possibly caused by CSD, i.e. the state of neuronal inhibition that is supposed to be the pathophysiological basis of migraine aura. The studies were not designed to provide a statistical conclusion, but to identify technical strengths and weaknesses of this imaging technique. Study 6 also represents an early phase of clinical translation. Here, a new postprocessing approach was developed to achieve absolute metrics for the measurement of dynamic processes on CINE MRI, a time-resolved method to visualise moving structures in vivo, e.g. in cardiac, bowel, or foetal imaging. Usually movement is evaluated qualitatively and to date objective quantitative approaches are missing. In this study, a measuring method (voxel intensity distribution method, VIDM) for subtle movements was developed and applied in 27 children with Chiari and other brain/skull malformations, where cerebellar tissue herniates dynamically through the foramen magnum following CSF pulsatility. The degree of movement was compared using VIDM and visually derived, clinically accepted linear measurements on CINE sequences. In 85% of the patients, VIDM showed significantly more cerebellar displacement (p=0.002) compared to simple visual assessments, although this did not correlate with the clinical outcome parameters (hydrocephalus or syringomyelia; Pearson’s correlation coefficient -0.28; p=0.16). It is suggested that VIDM might be a valuable tool to detect and measure subtle dynamic processes in the CNS, but extracranial applications are also very likely. Study 3 and 7 represent validation studies of methods that have been presented in clinical data before. In study 3, 2HG MRS was used in 35 patients suspected for cerebral gliomas to determine the IDH mutational status that today is an integral part of the WHO brain tumour classification system. For this study, a dedicated MRS sequence was used and the routine imaging protocol was extended by only 6 min. The sensitivity/specificity for determining the IDH mutational status was 89.5% and 81.3%, respectively. It could be concluded that 2HG MRS is an easily applicable supplement to standard imaging protocols that allows presurgical diagnostics and opens up for more detailed assessment during treatment. In study 7, T1 maps were generated from clinical MRI data using the MP2RAGE sequence, a technique extensively applied in neuroscience, but little in the clinical setting. The technical parameters were adapted to find a balance between short acquisition times, high signal-to-noise, and reliable T1 values to quantify myelin maturation in 94 children up to the age of 6 years. The assessment of adequate myelination is a central part of paediatric imaging diagnostics, but is to date done by evaluating images qualitatively. The aim was to validate the MP2RAGE-based T1 mapping technique for the assessment of normal myelination, and data were compared to those of children with various CNS pathologies. Additionally, the diagnostic power of the MP2RAGE was pointed out for the qualitative assessment of regular myelination and brain pathologies. The purpose of study 4 and 5 was to improve the diagnostic confidence of perfusion-weighted DCE maps. DCE is a well-established technique outside the CNS, but is used less in neuroimaging due to a number of technical issues. Here, postprocessing was addressed with the aim to reduce noise in the resultant parameter maps. Two curve-fitting methods, the Levenberg-Marquardt (LM) algorithm and a Baysian method (BM), were compared in digital phantoms and in 42 glioma patients applying two compartmental models (extended Toft’s, ETM, and 2-compartment- exchange model, 2CXM). The image quality was assessed with regard to tumour discrimination and overall impression of the images. Moreover, the diagnostic performance to differentiate high-grade from low-grade gliomas was investigated. The image quality of parameter maps generated by BM was significantly improved compared to LM (p<0.001), and the 2CXM- based maps were higher rated, regardless of the fitting method. The diagnostic performance to differentiate tumour grades was excellent for Ktrans and Vp (p<0.001). This was not affected by the fitting method for the leakage parameter Ktrans, whereas Vp was improved when using BM. These studies suggest that using BM to derive perfusion parameters from DCE data are superior to LM, hopefully leading to higher diagnostic confidence and acceptance in the clinical community. Clinical imaging diagnostics benefits without doubt from the integration of quantitative information gained by qMRI, thereby increasing reproducibility and reliability and enabling the objective comparison to normative and patient databases. Each step of the clinical translation process is essential to show opportunities, identify areas of optimisation, and to reveal challenges and limitations. After further development APT imaging is today available on standard MRI platforms, and BM-based curve fitting of perfusion data has been implemented in postprocessing software programmes. T1 maps of normal myelination in children are made publicly available and may be a first step towards an automated tool to detect myelination disorders more efficiently

Extended experience in parieto-occipital expansion surgery by meander technique—clinical and radiological evaluation

Introduction: Brachycephaly and anterior and posterior plagiocephaly appear as an isolated entity or manifest in syndromic conditions. In severe cases, possible treatment options currently comprise either cranioplasty or osteogenetic distraction. The aim of this paper is to retrospectively review the perioperative course of a series of children treated by posterior meander expansion technique at our institution with focus on the course of postoperative intracranial volume and eventual tonsillar descent evolution. Methods: Forty-two children received a posterior cranial vault remodeling by means of a posterior meander technique during a 7-year period. Hospital records were reviewed, and pre- and postoperative MRIs were analyzed for intracranial volume, cephalic and asymmetry index, and tonsillar position over time. Results: Median age at surgery was 11.5 months (range 17 days-10 years). Nineteen children had a symmetrical cranial deformity, twenty-three an asymmetrical synostosis. Half of the cohort showed a syndromic condition. Transfusions were administered in the majority (92.2%) of the cases. A significant postoperative increase of intracranial volume was present from 1188.9 ± 370.4 cm(3) to 1324.8 ± 352.9 cm(3) (p < 0.001). The asymmetry index showed a significant improvement postoperatively: 0.86 ± 0.06 versus 0.91 ± 0.05 (p < 0.001), while the cephalic index showed a non-statistical change (0.91 ± 0.11 versus 0.88 ± 0.08). Tonsillar herniation, bilateral or homolateral, showed no significant changes at early control, while a nonsignificant amelioration of tonsillar descent was seen among children older than 12 months at late imaging follow-up. Conclusion: Among the osteoplastic techniques, the posterior meander technique offers several advantages, such as early mobilization of the child, less bony defects, absence of implants, and a small complication rate. However, further comparative studies among different surgical techniques are needed

Dynamic effective elasticity of melanoma cells under shear and elongational flow confirms estimation from force spectroscopy

The detection and enrichment of circulating melanoma cells is a challenge, as the cells are very heterogeneous in terms of their biomechanical properties and surface markers. In addition, there is a lack of valid and reliable biomarkers predicting progress and therapeutic response. In this study, we analyze the elasticity of A375 melanoma cells by applying force spectroscopy and a microfluidic method. To identify and eventually separate freely circulating tumor cells, it is crucial to know their physical properties precisely. First, we use standard AFM force spectroscopy, where the elasticity of the cells is calculated from indentation with a pyramidal tip. To extend the limits of the measurements with a tip, we then use cantilevers without a tip to apply force over a larger area of the cells. The resulting Young’s moduli are slightly lower and vary less without the tip, presumably because of the spatial inhomogeneity of the cells. Finally, we implement our microfluidic method: we measure single cell elasticity by analyzing their deformation in high-speed micrographs while passing a stenosis. Combining the force field and the change in shape provides the basis for a stress–strain diagram. The results from the microfluidic deformation analysis were well in accordance with the results from force spectroscopy. The microfluidic method, however, provides advantages over conventional methods, as it is less invasive and less likely to harm the cell during the measurement. The whole cell is measured as one entity without having contact to a stiff substrate, while force spectroscopy is limited to the contact area of the tip, and in some cases dependent of the cell substrate interaction. Consequently, microfluidic deformation analysis allows us to predict the overall elastic behavior of the whole, inhomogeneous cell in three-dimensional force fields. This method may contribute to improve the detection of circulating melanoma cells in the clinical practice

Assessment of myelination in infants and young children by T1 relaxation time measurements using the magnetization-prepared 2 rapid acquisition gradient echoes sequence

Background: Axonal myelination is an important maturation process in the developing brain. Increasing myelin content correlates with the longitudinal relaxation rate (R1=1/T1) in magnetic resonance imaging (MRI). Objective: By using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) on a 3-T MRI system, we provide R1 values and myelination rates for infants and young children. Materials and methods: Average R1 values in white and grey matter regions in 94 children without pathological MRI findings (age range: 3 months to 6 years) were measured and fitted by a saturating-exponential growth model. For comparison, R1 values of 36 children with different brain pathologies are presented. The findings were related to a qualitative evaluation using T2, magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and MP2RAGE. Results: R1 changes rapidly in the first 16 months of life, then much slower thereafter. R1 is highest in pre-myelinated structures in the youngest subjects, such as the posterior limb of the internal capsule (0.74-0.76 +/- 0.04 s(-1)) and lowest for the corpus callosum (0.37-0.44 +/- 0.03 s(-1)). The myelination rate is fastest in the corpus callosum and slowest in the deep grey matter. R1 is decreased in hypo- and dysmyelination disorders. Myelin maturation is clearly visible on MP2RAGE, especially in the first year of life. Conclusion: MP2RAGE permits a quantitative R1 mapping method with an examination time of approximately 6 min. The age-dependent R1 values for children without MRI-identified brain pathologies are well described by a saturating-exponential function with time constants depending on the investigated brain region. This model can serve as a reference for this age group and to search for indications of subtle pathologies. Moreover, the MP2RAGE sequence can also be used for the qualitative assessment of myelinated structures

Tumor load rather than contrast enhancement is associated with the visual function of children and adolescents with optic pathway glioma – a retrospective Magnetic Resonance Imaging study

Introduction: Optic pathway gliomas are often asymptomatic tumors occurring in children with neurofibromatosis type 1 (NF1 + OPG) or sporadically (spOPG). Treatment is usually prompted by visual loss and/or tumor progression on MRI. The aim of this study was to investigate the relationship between visual acuity (VA), tumor growth, and contrast enhancement to provide more distinct indications for the administration of gadolinium-based contrast agents. Methods: Tumor load was retrospectively measured and enhancement semi-quantitatively scored on 298 MRIs of 35 patients (63% NF1 + OPG). Spearman rank correlation between tumor load and enhancement was calculated and a linear mixed model used to examine the influence of tumor load and enhancement on corresponding VA tests (LogMAR). Results: The optic nerve width in NF1 + OPGs was strongly associated with VA (regression coefficient 0.75; confidence interval 0.61-0.88), but weakly with enhancement (0.06; -0.04-0.15). In spOPGs, tumor volume and optic nerve width were more relevant (0.31; -0.19-0.81 and 0.39; 0.05-0.73) than enhancement (0.09; -0.09-0.27). Conclusions: Tumor load measures may be more relevant for the surveillance of optic pathway gliomas than enhancement, given that VA is the relevant outcome parameter. Regular contrast administration should therefore be questioned in these patients

First experience with augmented reality neuronavigation in endoscopic assisted midline skull base pathologies in children

Introduction: Endoscopic skull base approaches are broadly used in modern neurosurgery. The support of neuronavigation can help to effectively target the lesion avoiding complications. In children, endoscopic-assisted skull base surgery in combination with navigation systems becomes even more important because of the morphological variability and rare diseases affecting the sellar and parasellar regions. This paper aims to analyze our first experience on augmented reality navigation in endoscopic skull base surgery in a pediatric case series. Patients and methods: A retrospective review identified seventeen endoscopic-assisted endonasal or transoral procedures performed in an interdisciplinary setting in a period between October 2011 and May 2020. In all the cases, the surgical target was a lesion in the sellar or parasellar region. Clinical conditions, MRI appearance, intraoperative conditions, postoperative MRI, possible complications, and outcomes were analyzed. Results: The mean age of our patients was 14.5 ± 2.4 years. The diagnosis varied, but craniopharyngiomas (31.2%) were mostly represented. AR navigation was experienced to be very helpful for effectively targeting the lesion and defining the intraoperative extension of the pathology. In 65% of the oncologic cases, a radical removal was proven in postoperative MRI. The mean follow-up was 89 +/- 79 months. There were no deaths in our series. No long-term complications were registered; two cerebrospinal fluid (CSF) fistulas and a secondary abscess required further surgery. Conclusion: The implementation of augmented reality to endoscopic-assisted neuronavigated procedures within the skull base was feasible and did provide relevant information directly in the endoscopic field of view and was experienced to be useful in the pediatric cases, where anatomical variability and rarity of the pathologies make surgery more challenging

Management of pineal region tumors in a pediatric case series

Pineal region tumors commonly present with non-communicating hydrocephalus. These heterogeneous histological entities require different therapeutic regimens. We evaluated our surgical experience concerning procurance of a histological diagnosis, management of hydrocephalus, and choice of antitumoral treatment. We analyzed the efficacy of neuroendoscopic biopsy and endoscopic third ventriculocisternostomy (ETV) in patients with pineal region tumors between 2006 and 2019 in a single-center retrospective cross-sectional study with regard to diagnostic yield, hydrocephalus treatment, as well as impact on further antitumoral management. Out of 28 identified patients, 23 patients presented with untreated hydrocephalus and 25 without histological diagnosis. One patient underwent open biopsy, and 24 received a neuroendoscopic biopsy with concomitant hydrocephalus treatment if necessary. Eighteen primary ETVs, 2 secondary ETVs, and 2 ventriculoperitoneal shunts (VPSs) were performed. Endoscopic biopsy had a diagnostic yield of 95.8% (23/24) and complication rates of 12.5% (transient) and 4.2% (permanent), respectively. ETV for hydrocephalus management was successful in 89.5% (17/19) with a median follow-up of more than 3 years. Following histological diagnosis, 8 patients (28.6%) underwent primary resection of their tumor. Another 9 patients underwent later-stage resection after either adjuvant treatment (n = 5) or for progressive disease during observation (n = 4). Eventually, 20 patients received adjuvant treatment and 7 were observed after primary management. One patient was lost to follow-up. Heterogeneity of pineal region tumor requires histological confirmation. Primary biopsy of pineal lesions should precede surgical resection since less than a third of patients needed primary surgical resection according to the German pediatric brain tumor protocols. Interdisciplinary decision making upfront any treatment is warranted in order to adequately guide treatment

Non-destructive assay of nuclear waste containers using muon scattering tomography in the Horizon2020 CHANCE project

Methods for the non-destructive assay of nuclear waste drums are of great importance to the nuclear waste management community, especially where loss in continuity of knowledge about the content of drums happened or chemical processes altering the contents of the drums may occur. Muon scattering tomography has been shown to be a promising technique for the non-destructive assay of nuclear waste drums in a safe way. By measuring tracks of muons entering and leaving the probed sample and extracting scattering angles from the tracks, it is possible to draw conclusions about the contents of the sample and its spatial arrangement. Within the CHANCE project, a newly built large-scale mobile detector system for scanning and imaging the contents of nuclear waste drums using atmospheric muons is currently undergoing commissioning