Deep Convolutional Neural Networks Provide Motion Grading for High-Resolution Peripheral Quantitative Computed Tomography of the Scaphoid.

In vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) studies on bone characteristics are limited, partly due to the lack of standardized and objective techniques to describe motion artifacts responsible for lower-quality images. This study investigates the ability of such deep-learning techniques to assess image quality in HR-pQCT datasets of human scaphoids. In total, 1451 stacks of 482 scaphoid images from 53 patients, each with up to six follow-ups within one year, and each with one non-displaced fractured and one contralateral intact scaphoid, were independently graded by three observers using a visual grading scale for motion artifacts. A 3D-CNN was used to assess image quality. The accuracy of the 3D-CNN to assess the image quality compared to the mean results of three skilled operators was between 92% and 96%. The 3D-CNN classifier reached an ROC-AUC score of 0.94. The average assessment time for one scaphoid was 2.5 s. This study demonstrates that a deep-learning approach for rating radiological image quality provides objective assessments of motion grading for the scaphoid with a high accuracy and a short assessment time. In the future, such a 3D-CNN approach can be used as a resource-saving and cost-effective tool to classify the image quality of HR-pQCT datasets in a reliable, reproducible and objective way.

Handheld hyperspectral imaging as a tool for the post-mortem interval estimation of human skeletal remains.

In forensic medicine, estimating human skeletal remains' post-mortem interval (PMI) can be challenging. Following death, bones undergo a series of chemical and physical transformations due to their interactions with the surrounding environment. Post-mortem changes have been assessed using various methods, but estimating the PMI of skeletal remains could still be improved. We propose a new methodology with handheld hyperspectral imaging (HSI) system based on the first results from 104 human skeletal remains with PMIs ranging between 1 day and 2000 years. To differentiate between forensic and archaeological bone material, the Convolutional Neural Network analyzed 65.000 distinct diagnostic spectra: the classification accuracy was 0.58, 0.62, 0.73, 0.81, and 0.98 for PMIs of 0 week-2 weeks, 2 weeks-6 months, 6 months-1 year, 1 year-10 years, and >100 years, respectively. In conclusion, HSI can be used in forensic medicine to distinguish bone materials >100 years old from those <10 years old with an accuracy of 98%. The model has adequate predictive performance, and handheld HSI could serve as a novel approach to objectively and accurately determine the PMI of human skeletal remains.

Localization of Low- and High-Frequency Sounds in Cochlear Implant Recipients Using a Contralateral Hearing Aid.

BACKGROUND AND OBJECTIVES: The ability to localize sounds is partly recovered in patients using a cochlear implant (CI) in one ear and a hearing aid (HA) on the contralateral side. Binaural processing seems effective at least to some extent, despite the difference between electric and acoustic stimulation in each ear. To obtain further insights into the mechanisms of binaural hearing in these listeners, localization of low- and high-frequency sounds was tested. STUDY DESIGN: The study used a within-subject design, where participants were tasked with localizing sound sources in the horizontal plane. The experiment was conducted in an anechoic chamber, where an array of seven loudspeakers was mounted along the 24 azimuthal angle span from -90° to +90°. Stimuli were applied with different frequencies: broadband noise and high- and low-frequency noise. SUBJECTS: Ten CI recipients participated in the study. All had an asymmetric hearing loss with a CI in the poorer ear and an HA on the contralateral side. MAIN OUTCOME MEASURES: Accuracy of sound localization in terms of angular error and percentage of correct localization scores. RESULTS: The median angular error was 40° in bimodal conditions for both broadband noise and high-frequency noise stimuli. The angular error increased to 47° for low-frequency noise stimuli. In the unilaterally aided condition with an HA, only a median angular error of 78° was observed. CONCLUSIONS: Irrespective of the frequency composition of the stimuli, this group of bimodal listeners showed some ability to localize sounds. Angular errors were larger than those reported in the literature for bilateral CI users or single-sided deaf listeners with a CI. In the unilateral listening condition with HA, only localization of sounds was not possible for most subjects.

The influence of intraoperative auditory brainstem responses on vibroplasty coupling-quality and analysis of the impact of different fixation steps on the coupling.

PURPOSE: The Vibrant Soundbridge (VSB) is an established active-middle-ear-implant for patients with moderate-to-profound hearing-loss. This surgery is referred to as "Vibroplasty". Sufficient transfer of the VSB's floating-mass-transducers (FMT) energy to the inner ear is a crucial factor influencing the coupling-quality (CQ). However, assessing CQ is hamper by two issues: the method of CQ-assessment itself and the method of FMT-fixation during Vibroplasty. METHODS: This prospective study explored the influence of intraoperative auditory-brainstem-response (+ ABR) measurements and various fixation methods on postoperative CQ after Vibroplasty as compared to matched-patients after Vibroplasty without intraoperative ABR (-ABR). Propensity-score-matching was performed based on preoperative bone-conduction-pure-tone-average-3 (BC-PTA3) at 1-, 2- and 4 kHz. Primary outcome parameters were postoperative CQ-PTA3, intraoperative ABR threshold for various fixation methods and postoperative BC-PTA3. RESULTS: A total of 28 patients were included, of which 14 were + ABR. Preoperative BC-PTA3, sex, age, and number of previous surgeries did not differ significantly between groups (all p > 0.301). Mean postoperative CQ-PTA3 was significantly better for + ABR (1.8 vs. 12.3 dB-HL; p = 0.006). Mean intraoperative ABR threshold was superior for cartilage-counter-bearing and cartilage-housing compared to additional fixation with injectable-platelet-rich- fibrin (53 vs. 56 & 57 dB-HL, respectively; p = 0.04; η2 = 0.33). Mean postoperative BC-PTA3 did not significantly differ between patients (41.4 vs. 41.8 dB-HL; p = 0.77). A total of 7% of the patients required intraoperative readjustment of the FMT based on unsatisfactory intraoperative ABR threshold. CONCLUSION: Intraoperative ABR measurement resulted in significantly better postoperative CQ. Cartilage-counter-bearing and cartilage-housing were observed to have superior CQ. A total of 7% of the patients could be spared revision-Vibroplasty due to intraoperative ABR measurement.

Prediction of Biliary Complications After Human Liver Transplantation Using Hyperspectral Imaging and Convolutional Neural Networks: A Proof-of-concept Study.

BACKGROUND: Biliary complications (BCs) negatively impact the outcome after liver transplantation. We herein tested whether hyperspectral imaging (HSI) generated data from bile ducts (BD) on reperfusion and machine learning techniques for data readout may serve as a novel approach for predicting BC. METHODS: Tissue-specific data from 136 HSI liver images were integrated into a convolutional neural network (CNN). Fourteen patients undergoing liver transplantation after normothermic machine preservation served as a validation cohort. Assessment of oxygen saturation, organ hemoglobin, and tissue water levels through HSI was performed after completing the biliary anastomosis. Resected BD segments were analyzed by immunohistochemistry and real-time confocal microscopy. RESULTS: Immunohistochemistry and real-time confocal microscopy revealed mild (grade I: 1%-40%) BD damage in 8 patients and moderate (grade II: 40%-80%) injury in 1 patient. Donor and recipient data alone had no predictive capacity toward BC. Deep learning-based analysis of HSI data resulted in >90% accuracy of automated detection of BD. The CNN-based analysis yielded a correct classification in 72% and 69% for BC/no BC. The combination of HSI with donor and recipient factors showed 94% accuracy in predicting BC. CONCLUSIONS: Deep learning-based modeling using CNN of HSI-based tissue property data represents a noninvasive technique for predicting postoperative BC.

Stapedius reflex thresholds obtained in a free sound field as an indicator for over- and understimulation in cochlear implant listeners.

OBJECTIVE: The goal of this study was to determine open field stapedius reflex thresholds (oSRTs) in CI patients with fittings based on subjective loudness ratings. A further objective was to compare these oSRTs and those of eSRT-based fittings that are similar to the oSRTs of normal hearing. DESIGN: Impedance measurements of the ear drum were taken while subjects were wearing their audio processors. The stapedius reflex was elicited by electrical stimulation transmitted through the activated CI system in response to an acoustic stimulus presented in the free sound field. STUDY SAMPLE: Subjects were 50 experienced CI users (n = 57 ears) with CI fittings based on subjective loudness scaling. RESULTS: A reference range for the oSRTs was defined that was identified in CI patients with eSRT-based fittings. Sound levels for stapedius reflex detection were inside the reference target range in 70% of the cases, below the reference range (i.e. down to 40 dB HL) in 20% of the cases, and above the reference range in 10% of the cases. CONCLUSION: Stapedius reflex detection in a free sound field may help detect fittings with too high or too low stimulation levels that might reduce audiological performance.

Comparison of Mid-Infrared Handheld and Benchtop Spectrometers to Detect Staphylococcus epidermidis in Bone Grafts.

Bone analyses using mid-infrared spectroscopy are gaining popularity, especially with handheld spectrometers that enable on-site testing as long as the data quality meets standards. In order to diagnose Staphylococcus epidermidis in human bone grafts, this study was carried out to compare the effectiveness of the Agilent 4300 Handheld Fourier-transform infrared with the Perkin Elmer Spectrum 100 attenuated-total-reflectance infrared spectroscopy benchtop instrument. The study analyzed 40 non-infected and 10 infected human bone samples with Staphylococcus epidermidis, collecting reflectance data between 650 cm-1 and 4000 cm-1, with a spectral resolution of 2 cm-1 (Agilent 4300 Handheld) and 0.5 cm-1 (Perkin Elmer Spectrum 100). The acquired spectral information was used for spectral and unsupervised classification, such as a principal component analysis. Both methods yielded significant results when using the recommended settings and data analysis strategies, detecting a loss in bone quality due to the infection. MIR spectroscopy provides a valuable diagnostic tool when there is a tissue shortage and time is of the essence. However, it is essential to conduct further research with larger sample sizes to verify its pros and cons thoroughly.

Radiomic Assessment of Radiation-Induced Alterations of Skeletal Muscle Composition in Head and Neck Squamous Cell Carcinoma within the Currently Clinically Defined Optimal Time Window for Salvage Surgery-A Pilot Study.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity modulation, the desired radiation-induced effects observed in HNSCC may also be observed as side effects in healthy tissue, e.g., the sternocleidomastoid muscle (SCM). These side effects (e.g., tissue fibrosis) depend on the interval between the completion of RCT and restaging CT. For salvage surgery, the optimal time window for surgery is currently clinically postulated at between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on clinical studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC patients are sparse. The present study quantified tissue alterations in the SCM and paravertebral musculature (PVM) after RCT, applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters, (1) volume, (2) mean positivity of pixels (MPP), and (3) uniformity, were extracted with mint LesionTM in the staging CTs and restaging CTs of 98 HNSCC patients. Of these, 25 were female, the mean age was 62 (±9.6) years, and 80.9% were UICC Stage IV. The mean restaging interval was 55 (±28; range 29-229) days. Only the mean volume significantly decreased after RCT, from 9.0 to 8.4 and 96.5 to 91.9 mL for the SCM and PVM, respectively (both p = 0.007, both Cohen's d = 0.28). In addition, the mean body mass index (BMI) decreased from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p < 0.001; Cohen's d = 0.9). The mean BMI decreased significantly and was correlated with the volume decrease for the SCM (r = 0.27; p = 0.007) and PVM (r = 0.41; p < 0.001). If t-test p-values were adjusted for the BMI decrease, no significant change in volumes for the SCM and PVM was observed (both p > 0.05). The present data support the clinically postulated optimal interval for salvage surgery of 6 to 12 weeks.

Raman spectroscopy for postmortem interval estimation of human skeletal remains: A scoping review.

Estimating postmortem intervals (PMI) is crucial in forensic investigations, providing insights into criminal cases and determining the time of death. PMI estimation relies on expert experience and a combination of thanatological data and environmental factors but is prone to errors. The lack of reliable methods for assessing PMI in bones and soft tissues necessitates a better understanding of bone decomposition. Several research groups have shown promise in PMI estimation in skeletal remains but lack valid data for forensic cases. Current methods are costly, time-consuming, and unreliable for PMIs over 5 years. Raman spectroscopy (RS) can potentially estimate PMI by studying chemical modifications in bones and teeth correlated with burial time. This review summarizes RS applications, highlighting its potential as an innovative, nondestructive, and fast technique for PMI estimation in forensic medicine.

Multicentric study on surgical information and early safety and performance results with the Bonebridge BCI 602: an active transcutaneous bone conduction hearing implant.

AIM: This European multicentric study aimed to prove safety and performance of the Bonebridge BCI 602 in children and adults suffering from either conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided sensorineural deafness (SSD). METHODS: 33 patients (13 adults and 10 children with either CHL or MHL and 10 patients with SSD) in three study groups were included. Patients were their own controls (single-subject repeated measures), comparing the unaided or pre-operative to the 3-month post-operative outcomes. Performance was evaluated by sound field thresholds (SF), word recognition scores (WRS) and/or speech reception thresholds in quiet (SRT) and in noise (SNR). Safety was demonstrated with a device-specific surgical questionnaire, adverse event reporting and stable pure-tone measurements. RESULTS: The Bonebridge BCI 602 significantly improved SF thresholds (+ 25.5 dB CHL/MHL/SSD), speech intelligibility in WRS (+ 68.0% CHL/MHL) and SRT in quiet (- 16.5 dB C/MHL) and in noise (- 3.51 dB SNR SSD). Air conduction (AC) and bone conduction (BC) thresholds remained stable over time. All adverse events were resolved, with none unanticipated. Mean audio processor wearing times in hours [h] per day for the CHL/MHL group were ~ 13 h for adults, ~ 11 h for paediatrics and ~ 6 h for the SSD group. The average surgical length was 57 min for the CHL/MHL group and 42 min for the SSD group. The versatility of the BCI 602 (reduced drilling depth and ability to bend the transition for optimal placement) allows for treatment of normal, pre-operated and malformed anatomies. All audiological endpoints were reached. CONCLUSIONS: The Bonebridge BCI 602 significantly improved hearing thresholds and speech understanding. Since implant placement follows the patient's anatomy instead of the shape of the device and the duration of surgery is shorter than with its predecessor, implantation is easier with the BCI 602. Performance and safety were proven for adults and children as well as for the CHL/MHL and SSD indications 3 months post-operatively.

5-Year Observation Period of Quality of Life After Cochlear Implantation.

BACKGROUND: Only few studies assessed health-related quality of life (HRQoL) in cochlear implant (CI) patients for a period of more than 2 years. Some of these studies indicated that HRQoL might decrease after that period. The goal of our study was to see whether HRQoL indeed decreases or remains stable beyond 2 years after implant activation. METHODS: Twenty-five adults (11 women, 14 men; mean age at implantation: 60 ± 19 yr) with a unilateral CI for profound hearing loss were administered two questionnaires: the Nimjegen Cochlear Implant Questionnaire and the Health Utility Index 3 (HUI 3). The Nimjegen Cochlear Implant Questionnaire total score and the HUI single-attribute utility score of Hearing are measures of hearing-specific HRQoL, whereas the HUI multiattribute utility score is a measure of generic HRQoL. The questionnaires were administered before cochlear implantation and 1, 2, and 5 years after implant activation. RESULTS: Hearing-specific HRQoL was significantly improved at 1 year after implant activation and did not significantly change thereafter. Generic HRQoL also showed significant improvement at 1 year after implant activation, but deteriorated to a clinically relevant degree thereafter. CONCLUSIONS: The significant improvement of hearing-specific HRQoL obtained from cochlear implantation was fully maintained for up to 5 years after implantation. Generic HRQoL of our CI patients, however, fluctuated over time. The decrease of generic HRQoL is supposed to reflect general age-associated health declines.

Improving Spatial Hearing when Wearing Ski Helmets in Order to Increase Safety on Ski Slopes.

This study investigated the effect of a new type of ear pads for ski helmets on the hearing performance of 13 young adults (mean age: 22 years). Free-field hearing thresholds and sound localization performance of the subjects were assessed in three conditions: without helmet, with a conventional helmet and with the modified helmet. Results showed that the modified helmet was superior to the conventional helmet in all respects, but did not allow for a performance level observed without a helmet. Considering the importance of precise hearing and sound localization during alpine skiing, acoustically improved ear pads of ski helmets, as demonstrated in this study, can essentially contribute to enhancing the safety on ski slopes.

Post-Mortem Interval of Human Skeletal Remains Estimated with Handheld NIR Spectrometry.

Estimating the post-mortem interval (PMI) of human skeletal remains is a critical issue of forensic analysis, with important limitations such as sample preparation and practicability. In this work, NIR spectroscopy (NIRONE® Sensor X; Spectral Engines, 61449, Germany) was applied to estimate the PMI of 104 human bone samples between 1 day and 2000 years. Reflectance data were repeatedly collected from eight independent spectrometers between 1950 and 1550 nm with a spectral resolution of 14 nm and a step size of 2 nm, each from the external and internal bone. An Artificial Neural Network was used to analyze the 66,560 distinct diagnostic spectra, and clearly distinguished between forensic and archaeological bone material: the classification accuracies for PMIs of 0−2 weeks, 2 weeks−6 months, 6 months−1 year, 1 year−10 years, and >100 years were 0.90, 0.94, 0.94, 0.93, and 1.00, respectively. PMI of archaeological bones could be determined with an accuracy of 100%, demonstrating the adequate predictive performance of the model. Applying a handheld NIR spectrometer to estimate the PMI of human skeletal remains is rapid and extends the repertoire of forensic analyses as a distinct, novel approach.

Application of Micro-Computed Tomography for the Estimation of the Post-Mortem Interval of Human Skeletal Remains.

It is challenging to estimate the post-mortem interval (PMI) of skeletal remains within a forensic context. As a result of their interactions with the environment, bones undergo several chemical and physical changes after death. So far, multiple methods have been used to follow up on post-mortem changes. There is, however, no definitive way to estimate the PMI of skeletal remains. This research aimed to propose a methodology capable of estimating the PMI using micro-computed tomography measurements of 104 human skeletal remains with PMIs between one day and 2000 years. The present study indicates that micro-computed tomography could be considered an objective and precise method of PMI evaluation in forensic medicine. The measured parameters show a significant difference regarding the PMI for Cort Porosity p < 0.001, BV/TV p > 0.001, Mean1 p > 0.001 and Mean2 p > 0.005. Using a machine learning approach, the neural network showed an accuracy of 99% for distinguishing between samples with a PMI of less than 100 years and archaeological samples.

Hyperspectral Imaging as a Tool for Viability Assessment During Normothermic Machine Perfusion of Human Livers: A Proof of Concept Pilot Study.

Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 (p < 0.001), THI (p < 0.001) and NIR (p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped (p = 0.005) during the observational period. At 12-24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers (p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = -0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP.

Robust and bias-free localization of individual fixed dipole emitters achieving the Cramér Rao bound for applications in cryo-single molecule localization microscopy.

Single molecule localization microscopy (SMLM) has the potential to resolve structural details of biological samples at the nanometer length scale. Compared to room temperature experiments, SMLM performed under cryogenic temperature achieves higher photon yields and, hence, higher localization precision. However, to fully exploit the resolution it is crucial to account for the anisotropic emission characteristics of fluorescence dipole emitters with fixed orientation. In case of slight residual defocus, localization estimates may well be biased by tens of nanometers. We show here that astigmatic imaging in combination with information about the dipole orientation allows to extract the position of the dipole emitters without localization bias and down to a precision of 1 nm, thereby reaching the corresponding Cramér Rao bound. The approach is showcased with simulated data for various dipole orientations, and parameter settings realistic for real life experiments.

Three-Dimensional Single Molecule Localization Microscopy Reveals the Topography of the Immunological Synapse at Isotropic Precision below 15 nm.

T-cells engage with antigen-presenting cells in search for antigenic peptides and form transient interfaces termed immunological synapses. Synapse topography affects receptor binding rates and the mutual segregation of proteins due to size exclusion effects. It is hence important to determine the 3D topography of the immunological synapse at high precision. Current methods provide only rather coarse images of the protein distribution within the synapse. Here, we applied supercritical angle fluorescence microscopy combined with defocused imaging, which allows three-dimensional single molecule localization microscopy (3D-SMLM) at an isotropic localization precision below 15 nm. Experiments were performed on hybrid synapses between primary T-cells and functionalized glass-supported lipid bilayers. We used 3D-SMLM to quantify the cleft size within the synapse by mapping the position of the T-cell receptor (TCR) with respect to the supported lipid bilayer, yielding average distances of 18 nm up to 31 nm for activating and nonactivating bilayers, respectively.

Three-dimensional single molecule localization close to the coverslip: a comparison of methods exploiting supercritical angle fluorescence.

The precise spatial localization of single molecules in three dimensions is an important basis for single molecule localization microscopy (SMLM) and tracking. At distances up to a few hundred nanometers from the coverslip, evanescent wave coupling into the glass, also known as supercritical angle fluorescence (SAF), can strongly improve the axial precision, thus facilitating almost isotropic localization performance. Specific detection systems, introduced as Supercritical angle localization microscopy (SALM) or Direct optical nanoscopy with axially localized detection (DONALD), have been developed to exploit SAF in modified two-channel imaging schemes. Recently, our group has shown that off-focus microscopy, i.e., imaging at an intentional slight defocus, can perform equally well, but uses only a single detection arm. Here we compare SALM, off-focus imaging and the most commonly used 3D SMLM techniques, namely cylindrical lens and biplane imaging, regarding 3D localization in close proximity to the coverslip. We show that all methods gain from SAF, which leaves a high detection NA as the only major key requirement to unlock the SAF benefit. We find parameter settings for cylindrical lens and biplane imaging for highest z-precision. Further, we compare the methods in view of robustness to aberrations, fixed dipole emission and double-emitter events. We show that biplane imaging provides the best overall performance and support our findings by DNA-PAINT experiments on DNA-nanoruler samples. Our study sheds light on the effects of SAF for SMLM and is helpful for researchers who plan to employ localization-based 3D nanoscopy close to the coverslip.

Erratum: Defocused imaging exploits supercritical-angle fluorescence emission for precise axial single molecule localization microscopy: erratum.

[This corrects the article on p. 775 in vol. 11, PMID: 32206395.].