Characterization, number, and spatial organization of nerve fibers in the human cervical vagus nerve and its superior cardiac branch.

BACKGROUND: Electrical stimulation of the vagus nerve (VN) is a therapy for epilepsy, obesity, depression, and heart diseases. However, whole nerve stimulation leads to side effects. We examined the neuroanatomy of the mid-cervical segment of the human VN and its superior cardiac branch to gain insight into the side effects of VN stimulation and aid in developing targeted stimulation strategies. METHODS: Nerve specimens were harvested from eight human body donors, then subjected to immunofluorescence and semiautomated quantification to determine the signature, quantity, and spatial distribution of different axonal categories. RESULTS: The right and left cervical VN (cVN) contained a total of 25,489 ± 2781 and 23,286 ± 3164 fibers, respectively. Two-thirds of the fibers were unmyelinated and one-third were myelinated. About three-quarters of the fibers in the right and left cVN were sensory (73.9 ± 7.5 % versus 72.4 ± 5.6 %), while 13.2 ± 1.8 % versus 13.3 ± 3.0 % were special visceromotor and parasympathetic, and 13 ± 5.9 % versus 14.3 ± 4.0 % were sympathetic. Special visceromotor and parasympathetic fibers formed clusters. The superior cardiac branches comprised parasympathetic, vagal sensory, and sympathetic fibers with the left cardiac branch containing more sympathetic fibers than the right (62.7 ± 5.4 % versus 19.8 ± 13.3 %), and 50 % of the left branch contained sensory and sympathetic fibers only. CONCLUSION: The study indicates that selective stimulation of vagal sensory and motor fibers is possible. However, it also highlights the potential risk of activating sympathetic fibers in the superior cardiac branch, especially on the left side.

Arterio-venous Anastomoses of the Sucquet-Hoyer Type: Complexity and Distribution in the Human Dermis.

Our study aims at providing detailed information on numbers, form, and spatial distribution of arterio-venous anastomoses of the Sucquet-Hoyer type in the dermis of the nail bed, nail fold corner, thumb pad, arm, nose, glabella, lip, and ear. It further aims at providing a system, which relies on objective morphologic criteria for classifying Sucquet-Hoyer canals (SHCs). Using high-resolution episcopic microscopy (HREM), digital volume data of eight samples of each skin region were produced. Virtual three-dimensional (3D) models of the dermally located SHCs were created, and their 3D tortuosity (τ) values were determined. Dermal SHCs were identified in all 24 finger samples and in 1 lip sample. Beneath a field of 2 × 2 mm2, an average of four were located in the nail bed, three in the dermis of the thumb pad, and one in the dermis of the nail fold corner. Only a single dermal SHC was found in one lip sample. No SHCs were observed in the dermis of the other samples. The τ values of the SHCs ranged from 1.11 to 10. Building on these values, a classification system was designed, which distinguishes four SHC classes. The dermal distribution of the SHCs of different classes was similar in all specimens.

Axillary arch (of Langer): A large-scale dissection and simulation study based on unembalmed cadavers of body donors.

Connective or muscular tissue crossing the axilla is named axillary arch (of Langer). It is known to complicate axillary surgery and to compress nerves and vessels transiting from the axilla to the arm. Our study aims at systematically researching the frequency, insertions, tissue composition and dimension of axillary arches in a large cohort of individuals with regard to gender and bilaterality. In addition, it aims at evaluating the ability of axillary arches to cause compression of the axillary neurovascular bundle. Four hundred axillae from 200 unembalmed and previously unharmed cadavers were investigated by careful anatomical dissection. Identified axillary arches were examined for tissue composition and insertion. Length, width and thickness were measured. The relation of the axillary arch and the neurovascular axillary bundle was recorded after passive arm movements. Twenty-seven axillae of 18 cadavers featured axillary arches. Macroscopically, 15 solely comprised muscular tissue, six connective tissue and six both. Their average length was 79.56 mm, width 7.44 mm and thickness 2.30 mm. One to three distinct insertions were observed. After passive abduction and external rotation of the arm, 17 arches (63%) touched the neurovascular axillary bundle. According to our results, 9% of the Central European population feature an axillary arch. Approximately 50% of it bilaterally. A total of 40.74% of the arches have a thickness of 3 mm or more and 63% bear the potential of touching or compressing the neuromuscular axillary bundle upon arm movement.

Ultrasound-Guided Injections for Treatment of Facial Paralysis Sequelae: A Randomized Study on Body Donors.

BACKGROUND: Botulinum toxin injection is the accepted standard treatment for synkinesis and gustatory hyperlacrimation in patients with facial paralysis. However, poor injection accuracy can result in inconsistent treatment outcomes, variable treatment durations, and complications. Ultrasound guidance should increase injection accuracy in the facial region; however, this has not been proven. METHODS: Twenty-six hemifaces of nonembalmed cadavers were studied in a randomized split-face manner. Ink was injected with ultrasound or landmark guidance into the lacrimal gland and three common synkinetic muscles: the orbicularis oculi, depressor anguli oris, and mentalis. Injection accuracy was evaluated using several measures. RESULTS: Using ultrasound guidance, most ink (>50%) was found inside the correct target in 88% of cases, compared with 50% using landmark guidance ( P < 0.001). This was most pronounced in the lacrimal gland (62% versus 8%), depressor anguli oris (100% versus 46%), and mentalis (100% versus 54%) ( P < 0.05). All ink was found inside the correct target (no ink outside) in 65% using ultrasound guidance versus 29% without ( P < 0.001). Injection accuracy (any ink in target) was 100% when using ultrasound guidance versus 83% without ( P < 0.01). Twenty-three percent of the landmark-guided depressor anguli oris injections stained the facial artery ( P = 0.22). CONCLUSIONS: Ultrasound guidance significantly increased injection accuracy and reduced the amount of ink lost in the surrounding tissue compared with landmark guidance. Clinical trials are needed to explore the effects of ultrasound guidance on treatment outcome, duration, and complications in patients with facial paralysis.

Preoperative assessment of depressor anguli oris to prevent myectomy failure: An anatomical study using high-resolution ultrasound.

BACKGROUND: Myectomies of the lower lip depressor muscles have unexplained high failure rates. This study aimed to examine the depressor anguli oris (DAO) muscle using high-resolution ultrasound to identify potential anatomical explanations for surgical failures and to determine the accuracy of utilizing preoperative ultrasound assessment to improve myectomies. METHODS: Anatomical features of DAO and the surrounding anatomy were examined in 38 hemifaces of human body donors using high-resolution ultrasound and dissection. RESULTS: The ultrasound and dissection measurements showed the DAO muscle width to be 16.2 ± 2.9 versus 14.5 ± 2.5 mm, respectively, and the location of the lateral muscle border 54.4 ± 5.7 versus 52.3 ± 5.4 mm lateral to the midline. In 60% of the cases, the facial artery was either completely covered by lateral DAO muscle fibers or was found to be in direct contact with the lateral border. Significant muscle fiber continuity was present between the DAO and surrounding muscles in 5% of cases, whereas continuity between the depressor labii inferioris and surrounding muscles was considerably more common and pronounced. CONCLUSIONS: High-resolution ultrasound can accurately reveal important preoperative anatomical information in myectomies. Two potential explanations for the surgical failures were discovered: an overlap of lateral DAO muscle fibers over the facial artery could lead to inadequate resections and continuity with the surrounding muscles might lead to muscle function takeover despite adequate resections. Both can be uncovered preoperatively by the surgeon through a brief, directed ultrasound examination, which may allow for modification of the surgical plan to reduce surgical failure.

Effects of Tulp4 deficiency on murine embryonic development and adult phenotype.

Genetically engineered mouse models have the potential to unravel fundamental biological processes and provide mechanistic insights into the pathogenesis of human diseases. We have previously observed that germline genetic variation at the TULP4 locus influences clinical characteristics in patients with myeloproliferative neoplasms. To elucidate the role of TULP4 in pathological and physiological processes in vivo, we generated a Tulp4 knockout mouse model. Systemic Tulp4 deficiency exerted a strong impact on embryonic development in both Tulp4 homozygous null (Tulp4-/-) and heterozygous (Tulp4+/-) knockout mice, the former exhibiting perinatal lethality. High-resolution episcopic microscopy (HREM) of day 14.5 embryos allowed for the identification of multiple developmental defects in Tulp4-/- mice, including severe heart defects. Moreover, in Tulp4+/- embryos HREM revealed abnormalities of several organ systems, which per se do not affect prenatal or postnatal survival. In adult Tulp4+/- mice, extensive examinations of hematopoietic and cardiovascular features, involving histopathological surveys of multiple tissues as well as blood counts and immunophenotyping, did not provide evidence for anomalies as observed in corresponding embryos. Finally, evaluating a potential obesity-related phenotype as reported for other TULP family members revealed a trend for increased body weight of Tulp4+/- mice. RESEARCH HIGHLIGHTS: To study the role of the TULP4 gene in vivo, we generated a Tulp4 knockout mouse model. Correlative analyses involving HREM revealed a strong impact of Tulp4 deficiency on murine embryonic development.

The influence of censorship laws on Viennese anatomy textbooks from the outgoing 18th century until after the student revolution of 1848 in Austrian absolutism.

INTRODUCTION: Anatomy textbooks´ connection to the rigid censoring laws enacted by Habsburg rulers, was never sufficiently investigated. Using anatomy textbooks written at the University of Vienna, our article aims at investigating the influence of censorship laws on the anatomy textbooks in Vienna between 1786 and 1865. METHODS: In our case study we compared legal text and archival sources (source material A) with seven prefaces of textbooks written by Viennese anatomists (source material B). The prefaces were comparatively investigated by applying the following questions based on source material A: (1) What motives for writing the textbooks were indicated by the anatomists in the prefaces? (2) What legal or other influences were mentioned as motives that point to a connection to the censorship regulations installed? (3) Referring to changing censorship guidelines is there a change in the mentioned audience? RESULTS: Our results are that we found evidence for censorship regulations (source material A) in the prefaces (source material B). Also, the motives for writing those textbooks changed over time because of changing censorship regulations. CONCLUSION: Our findings show that Viennese anatomy textbooks were part of the Austrian censorship laws in the investigated period with a timely correlation between the appointment as professor and the publication of the textbooks and prefaces (indirectly) referring to censorship laws. The academic tradition of writing textbooks arose from this system, when freedom of speech stood in opposition to the absolute Habsburg reign. Thus, when working with historical anatomy textbooks it is important to reflect on their censorship heritage.

Pre-clinical evaluation of APrevent® VOIS for unilateral vocal fold paralysis medialization.

Objective: To evaluate the concept and efficacy of an adjustable implant (Prototype SH30: porcine implant and APrevent® VOIS: human concept) for treatment of unilateral vocal fold paralysis (UVFP) via in vivo mini-pig studies, human computed tomographic (CT) and magnetic resonance (MR) image analysis, ex-vivo aerodynamic and acoustic analysis. Methods: Feasibility testing and prototype implantation were performed using in-vivo UVFP porcine model (n = 8), followed by a dimensional finding study using CT and MR scans of larynges (n = 75) for modification of the implant prototypes. Acoustic and aerodynamic measurements were recorded on excised canine (n = 7) larynges with simulated UVFP before and after medialization with VOIS-Implant. Results: The prototype showed in the in-vivo UVFP porcine model an improved glottic closure from grade 6 incomplete closure to complete closure (n = 5), to grade 2 incomplete closure (n = 2) and grade 3 incomplete closure (n = 1). On human CT/MR scans the identification of the correct size was successful in 97.3% using the thyroid cartilage alar "distance S" as the only parameter, which is an important step towards procedure standardization and implant design. Results were confirmed with implantation in human laryngeal cadavers (n = 44). Measurements of the acoustic and aerodynamic effects after implantation showed a significant decreased phonation threshold pressure (p = .0187), phonation threshold flow (p = .0001) and phonation threshold power (p = .0046) on excised canine larynges with simulated UVFP. Percent jitter and percent shimmer decreased (p = .2976; p = .1771) but not significant. Conclusions: Based on the preclinical results four sizes, differing in medial length, implant width and expansion direction of silicone cushions, seem to be enough to satisfy laryngeal size variations. This concept is significantly effective in medializing UVFP and improving the aerodynamic and acoustic qualities of phonation as reported in a preliminary clinical outcome study with long-term implantation. Level of Evidence: N/A.

The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes ≤1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

Corrigendum: Mapping the functional anatomy and topography of the cardiac autonomic innervation for selective cardiac neuromodulation using MicroCT.

[This corrects the article DOI: 10.3389/fcell.2022.968870.].

Lossy Image Compression in a Preclinical Multimodal Imaging Study.

The growing use of multimodal high-resolution volumetric data in pre-clinical studies leads to challenges related to the management and handling of the large amount of these datasets. Contrarily to the clinical context, currently there are no standard guidelines to regulate the use of image compression in pre-clinical contexts as a potential alleviation of this problem. In this work, the authors study the application of lossy image coding to compress high-resolution volumetric biomedical data. The impact of compression on the metrics and interpretation of volumetric data was quantified for a correlated multimodal imaging study to characterize murine tumor vasculature, using volumetric high-resolution episcopic microscopy (HREM), micro-computed tomography (µCT), and micro-magnetic resonance imaging (µMRI). The effects of compression were assessed by measuring task-specific performances of several biomedical experts who interpreted and labeled multiple data volumes compressed at different degrees. We defined trade-offs between data volume reduction and preservation of visual information, which ensured the preservation of relevant vasculature morphology at maximum compression efficiency across scales. Using the Jaccard Index (JI) and the average Hausdorff Distance (HD) after vasculature segmentation, we could demonstrate that, in this study, compression that yields to a 256-fold reduction of the data size allowed to keep the error induced by compression below the inter-observer variability, with minimal impact on the assessment of the tumor vasculature across scales.

Retroauricular lymph node flap: An anatomic and surgical feasibility study.

BACKGROUND: The study investigated the anatomy of the retroauricular lymph node (LN) flap and evaluate its surgical feasibility as a new donor site for a free LN flap in lymphedema surgery. METHODS: Twelve adult cadavers were examined. The course and perfusion of the anterior auricular artery (AAA) and the location and sizes of the retroauricular LNs were studied. RESULTS: The AAA was available in 87% and absent in 13% specimens. The AAA's origin had a mean vertical distance of 12.2 ± 6.9 mm and a mean horizontal distance of 19.1 ± 4.2 mm from the superior attachment of the ear. The mean diameter of the AAA was 0.8 ± 0.2 mm. The mean number of LN per region was 7.7 ± 2.3, with an average LN size of 4.1 ± 1.9 × 3.2 ± 1.7 mm. The LN were categorized into anterior (G1) and posterior (G2) groups, with a total of 59 and 10 LN, respectively. In a cluster analysis, three LN clusters could be detected across the anterior group (G1). CONCLUSIONS: The retroauricular LN flap is a delicate but feasible flap with reliable anatomy, containing a mean of 7.7 LNs.

Distal Nerve Transfers in High Peroneal Nerve Lesions: An Anatomical Feasibility Study.

The peroneal nerve is one of the most commonly injured nerves of the lower extremity. Nerve grafting has been shown to result in poor functional outcomes. The aim of this study was to evaluate and compare anatomical feasibility as well as axon count of the tibial nerve motor branches and the tibialis anterior motor branch for a direct nerve transfer to reconstruct ankle dorsiflexion. In an anatomical study on 26 human body donors (52 extremities) the muscular branches to the lateral (GCL) and the medial head (GCM) of the gastrocnemius muscle, the soleus muscle (S) as well as the tibialis anterior muscle (TA) were dissected, and each nerve's external diameter was measured. Nerve transfers from each of the three donor nerves (GCL, GCM, S) to the recipient nerve (TA) were performed and the distance between the achievable coaptation site and anatomic landmarks was measured. Additionally, nerve samples were taken from eight extremities, and antibody as well immunofluorescence staining were performed, primarily evaluating axon count. The average diameter of the nerve branches to the GCL was 1.49 ± 0.37, to GCM 1.5 ± 0.32, to S 1.94 ± 0.37 and to TA 1.97 ± 0.32 mm, respectively. The distance from the coaptation site to the TA muscle was 43.75 ± 12.1 using the branch to the GCL, 48.31 ± 11.32 for GCM, and 19.12 ± 11.68 mm for S, respectively. The axon count for TA was 1597.14 ± 325.94, while the donor nerves showed 297.5 ± 106.82 (GCL), 418.5 ± 62.44 (GCM), and 1101.86 ± 135.92 (S). Diameter and axon count were significantly higher for S compared to GCL as well as GCM, while regeneration distance was significantly lower. The soleus muscle branch exhibited the most appropriate axon count and nerve diameter in our study, while also reaching closest to the tibialis anterior muscle. These results indicate the soleus nerve transfer to be the favorable option for the reconstruction of ankle dorsiflexion, in comparison to the gastrocnemius muscle branches. This surgical approach can be used to achieve a biomechanically appropriate reconstruction, in contrast to tendon transfers which generally only achieve weak active dorsiflexion.

Surgical Anatomy of Temporalis Muscle Transfer with Fascia Lata Augmentation for the Reanimation of the Paralyzed Face: A Cadaveric Study.

Background The temporalis muscle flap transfer with fascia lata augmentation (FLA) is a promising method for smile reconstruction after facial palsy. International literature lacks a detailed anatomical analysis of the temporalis muscle (TPM) combined with fascia lata (FL) augmentation. This study aims to describe the muscle's properties and calculate the length of FL needed to perform the temporalis muscle flap transfer with FLA. Methods Twenty nonembalmed male (m) and female (f) hemifacial cadavers were dissected to investigate the temporalis muscle's anatomy. Results The calculated minimum length of FL needed is 7.03cm (f) and 5.99cm (m). The length of the harvested tendon is 3.16cm/± 1.32cm (f) and 3.18/± 0.73cm (m). The length of the anterior part of the temporalis muscle (aTPM) is 4.16/± 0.80cm (f) and 5.30/± 0.85cm (m). The length of the posterior part (pTPM) is 5.24/± 1.51cm (f) and 6.62/± 1.03cm (m). The length from the most anterior to the most posterior point (aTPMpTPM) is 8.60/± 0.98cm (f) and 10.18/± 0.79cm (m). The length from the most cranial point to the distal tendon (cTPMdT) is 7.90/± 0.43cm (f) and 9.79/± 1.11cm (m). Conclusions This study gives basic information about the temporalis muscle and its anatomy to support existing and future surgical procedures in their performance. The recommended minimum length of FL to perform a temporalis muscle transfer with FLA is 7.03cm for female and 5.99cm for male, and minimum width of 3 cm. We recommend harvesting some extra centimeters to allow adjusting afterward.

Ultrasound Detection of the Axillary Arch as a Cause of Thoracic Outlet Syndrome: A Prospective Dissection-Controlled Cadaver Study.

Ultrasound as a diagnostic tool in thoracic outlet syndrome (TOS) is becoming increasingly important. The aim of this study was to investigate the diagnostic value of ultrasound in detecting the axillary arch, an ancillary muscle potentially causing TOS. Two hundred upper limbs of 100 fresh, non-frozen, non-embalmed body donors were screened for axillary arches. Sonographic findings were validated by anatomic dissection. Twelve axillary arches were found in 200 upper extremities, corresponding to a prevalence of 8.0% per individual and 6.0% per upper extremity investigated. Ultrasound had low diagnostic performance in identifying axillary arches, with a sensitivity of 66.7% and specificity of 95.7%. There was a tendency to identify more easily arches consisting of purely muscle tissue. Axillary arch thickness, its cross-sectional area and the predominant tissue type were associated with compression of the neurovascular bundle during shoulder elevation. Ultrasound seems to have limited potential to identify axillary arches. However, arches consisting predominantly of muscle tissue may be identified more easily and were associated with compression of neurovascular structures, thus potentially causing symptoms. Further clinical trials are needed to clarify the true value of ultrasound in patients with symptoms of TOS.

Selective ansa cervicalis nerve transfer to the marginal mandibular nerve for lower lip reanimation: An anatomical study in cadavers and a case report.

BACKGROUND: Donor nerve options for lower lip reanimation are limited in patients undergoing oncological resection of the facial nerve. The ansa cervicalis nerve (ACN) is an advantageously situated donor with great potential but has not been examined in detail. In the current study, the anatomical technical feasibility of selective ACN to marginal mandibular nerve (MMN) transfer for restoration of lower lip tone and symmetry was explored. A clinical case is presented. METHODS: Dissections were conducted in 21 hemifaces in non-embalmed human cadavers. The maximal harvestable length of ACN was measured and transfer to MMN was simulated. A 28-year-old male underwent ACN-MMN transfer after parotidectomy (carcinoma) and was evaluated 12 months post-operatively (modified Terzis' Lower Lip Grading Scale [25 observers] and photogrammetry). RESULTS: The harvestable length of ACN was 100 ± 12 mm. A clinically significant anatomical variant ("short ansa") was present in 33% of cases (length: 37 ± 12 mm). Tensionless coaptation was possible in all cases only when using a modification of the surgical technique in "short ansa" cases (using an infrahyoid muscle nerve branch as an extension). The post-operative course of the clinical case was uneventful without complications, with improvement in tone, symmetry, and function at the lower lip at 12-month post-operative follow-up. CONCLUSIONS: Selective ACN-MMN nerve transfer is anatomically feasible in facial paralysis following oncological ablative procedures. It allows direct nerve coaptation without significant donor site morbidity. The clinical case showed good outcomes 12 months post-operatively. A strategy when encountering the "short ansa" anatomical variant in clinical cases is proposed.

Spinal cord from body donors is suitable for multicolor immunofluorescence.

Immunohistochemistry is a powerful tool for studying neuronal tissue from humans at the molecular level. Obtaining fresh neuronal tissue from human organ donors is difficult and sometimes impossible. In anatomical body donations, neuronal tissue is dedicated to research purposes and because of its easier availability, it may be an alternative source for research. In this study, we harvested spinal cord from a single organ donor 2 h (h) postmortem and spinal cord from body donors 24, 48, and 72 h postmortem and tested how long after death, valid multi-color immunofluorescence or horseradish peroxidase (HRP) immunohistochemistry is possible. We used general and specific neuronal markers and glial markers for immunolabeling experiments. Here we showed that it is possible to visualize molecularly different neuronal elements with high precision in the body donor spinal cord 24 h postmortem and the quality of the image data was comparable to those from the fresh organ donor spinal cord. High-contrast multicolor images of the 24-h spinal cords allowed accurate automated quantification of different neuronal elements in the same sample. Although there was antibody-specific signal reduction over postmortem intervals, the signal quality for most antibodies was acceptable at 48 h but no longer at 72 h postmortem. In conclusion, our study has defined a postmortem time window of more than 24 h during which valid immunohistochemical information can be obtained from the body donor spinal cord. Due to the easier availability, neuronal tissue from body donors is an alternative source for basic and clinical research.