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Background: Microtia is a congenital malformation of the auricle that affects approximately 4 of every 10,000 live newborns. Radiographic film paper is traditionally employed to bidimensionally trace the structures of the contralateral healthy ear in a quasi-artistic manner. Anatomical points provide linear and angular measurements. However, this technique proves time-consuming, subjectivity-rich, and greatly dependent on surgeon expertise. Hence, it's susceptible to shape errors and misplacement. Methods: We present an innovative clinical workflow that combines 3D printing and augmented reality (AR) to increase objectivity and reproducibility of these procedures. Specifically, we introduce patient-specific 3D cutting templates and remodeling molds to carve and construct the cartilaginous framework that will conform the new ear. Moreover, we developed an in-house AR application compatible with any commercial Android tablet. It precisely guides the positioning of the new ear during surgery, ensuring symmetrical alignment with the healthy one and avoiding time-consuming intraoperative linear or angular measurements. Our solution was evaluated in one case, first with controlled experiments in a simulation scenario and finally during surgery. Results: Overall, the ears placed in the simulation scenario had a mean absolute deviation of 2.2 ± 1.7 mm with respect to the reference plan. During the surgical intervention, the reconstructed ear was 3.1 mm longer and 1.3 mm wider with respect to the ideal plan and had a positioning error of 2.7 ± 2.4 mm relative to the contralateral side. Note that in this case, additional morphometric variations were induced from inflammation and other issues intended to be addressed in a subsequent stage of surgery, which are independent of our proposed solution. Conclusions: In this work we propose an innovative workflow that combines 3D printing and AR to improve ear reconstruction and positioning in microtia correction procedures. Our implementation in the surgical workflow showed good accuracy, empowering surgeons to attain consistent and objective outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Up to date, there has been a lack of software infrastructure to connect 3D Slicer to any augmented reality (AR) device. This work describes a novel connection approach using Microsoft HoloLens 2 and OpenIGTLink, with a demonstration in pedicle screw placement planning. Methods: We developed an AR application in Unity that is wirelessly rendered onto Microsoft HoloLens 2 using Holographic Remoting. Simultaneously, Unity connects to 3D Slicer using the OpenIGTLink communication protocol. Geometrical transform and image messages are transferred between both platforms in real time. Through the AR glasses, a user visualizes a patient's computed tomography overlaid onto virtual 3D models showing anatomical structures. We technically evaluated the system by measuring message transference latency between the platforms. Its functionality was assessed in pedicle screw placement planning. Six volunteers planned pedicle screws' position and orientation with the AR system and on a 2D desktop planner. We compared the placement accuracy of each screw with both methods. Finally, we administered a questionnaire to all participants to assess their experience with the AR system. Results: The latency in message exchange is sufficiently low to enable real-time communication between the platforms. The AR method was non-inferior to the 2D desktop planner, with a mean error of 2.1 ± 1.4 mm. Moreover, 98% of the screw placements performed with the AR system were successful, according to the Gertzbein–Robbins scale. The average questionnaire outcomes were 4.5/5. Conclusions: Real-time communication between Microsoft HoloLens 2 and 3D Slicer is feasible and supports accurate planning for pedicle screw placement. [ABSTRACT FROM AUTHOR]

Background: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. Methods: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. Results: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. Conclusions: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams. [ABSTRACT FROM AUTHOR]

Purpose: Augmented Reality (AR) has the potential to simplify ultrasound (US) examinations which usually require a skilled and experienced sonographer to mentally align narrow 2D cross-sectional US images in the 3D anatomy of the patient. This work describes and evaluates a novel approach to track retroreflective spheres attached to the US probe using an inside-out technique with the AR glasses HoloLens 2. Finally, live US images are displayed in situ on the imaged anatomy. Methods: The Unity application UltrARsound performs spatial tracking of the US probe and attached retroreflective markers using the depth camera integrated into the AR glasses—thus eliminating the need for an external tracking system. Additionally, a Kalman filter is implemented to improve the noisy measurements of the camera. US images are streamed wirelessly via the PLUS toolkit to HoloLens 2. The technical evaluation comprises static and dynamic tracking accuracy, frequency and latency of displayed images. Results: Tracking is performed with a median accuracy of 1.98 mm/1.81 ∘ for the static setting when using the Kalman filter. In a dynamic scenario, the median error was 2.81 mm/1.70 ∘ . The tracking frequency is currently limited to 20 Hz. 83% of the displayed US images had a latency lower than 16 ms. Conclusions: In this work, we showed that spatial tracking of retroreflective spheres with the depth camera of HoloLens 2 is feasible, achieving a promising accuracy for in situ visualization of live US images. For tracking, no additional hardware nor modifications to HoloLens 2 are required making it a cheap and easy-to-use approach. Moreover, a minimal latency of displayed images enables a real-time perception for the sonographer. [ABSTRACT FROM AUTHOR]

Background: The integration of 3D printing technology in hospitals is evolving toward production models such as point-of-care manufacturing. This study aims to present the results of the integration of 3D printing technology in a manufacturing university hospital. Methods: Observational, descriptive, retrospective, and monocentric study of 907 instances of 3D printing from November 2015 to March 2020. Variables such as product type, utility, time, or manufacturing materials were analyzed. Results: Orthopedic Surgery and Traumatology, Oral and Maxillofacial Surgery, and Gynecology and Obstetrics are the medical specialties that have manufactured the largest number of processes. Working and printing time, as well as the amount of printing material, is different for different types of products and input data. The most common printing material was polylactic acid, although biocompatible resin was introduced to produce surgical guides. In addition, the hospital has worked on the co-design of custom-made implants with manufacturing companies and has also participated in tissue bio-printing projects. Conclusions: The integration of 3D printing in a university hospital allows identifying the conceptual evolution to "point-of-care manufacturing." [ABSTRACT FROM AUTHOR]

Purpose: 3D-printed patient-specific instruments have become a useful tool to improve accuracy in pelvic tumour resections. However, their correct placement can be challenging in some regions due to the morphology of the bone, so it is essential to be aware of the possible placement errors in each region. In this study, we characterize these errors in common pelvic osteotomies. Methods: We conducted an experiment with 9 cadaveric specimens, for which we acquired a pre-operative computed tomography scan. Small PSIs were designed for each case following a realistic surgical approach for four regions of the pelvis: iliac crest (C), supra-acetabular (S), ischial (I), and pubic (P). Final surgical placement was based on a post-operative scan. The resulting positions were compared with pre-operative planning, obtaining translations, rotations, and maximum osteotomy deviations in a local reference frame defined based on the bone's morphology. Results: Mean translations and rotations in the direction of the osteotomy plane were as follows: C = 5.3 mm, 6.7°; S = 1.8 mm, 5.1°; I = 1.5 mm, 3.4°; P = 1.8 mm, 3.5°. Mean translations in the remaining axes were below 2 mm. Maximum osteotomy deviations (75% of cases) were below 11.8 mm in C (7.8 mm for half-length), 7.8 mm in S (5.5 mm for half-length), 5.5 mm in I, and 3.7 mm in P. Conclusion: We have characterized placement errors for small PSIs in four regions of the pelvis. Our results show high errors in C and S PSIs in the direction of the resection plane's normal, and thus large osteotomy deviations. Deviations in short osteotomies in S, I and P and placement errors in the remaining directions were low. The PSIs used in this study are biocompatible and can be produced with a desktop 3D printer, thus minimizing manufacturing cost. [ABSTRACT FROM AUTHOR]

Purpose: Surgical correction of metopic craniosynostosis typically involves open cranial vault remodeling. Accurate translation of the virtual surgical plan into the operating room is challenging due to the lack of tools for intraoperative analysis of the surgical outcome. This study aimed to evaluate the feasibility of using a hand-held 3D photography device for intraoperative evaluation and guidance during cranial vault surgical reconstruction. Methods: A hand-held structured light scanner was used for intraoperative 3D photography during five craniosynostosis surgeries, obtaining 3D models of skin and bone surfaces before and after the remodeling. The accuracy of this device for 3D modeling and morphology quantification was evaluated using preoperative computed tomography imaging as gold-standard. In addition, the time required for intraoperative 3D photograph acquisition was measured. Results: The average error of intraoperative 3D photography was 0.30 mm. Moreover, the interfrontal angle and the transverse forehead width were accurately measured in the 3D photographs with an average error of 0.72 degrees and 0.62 mm. Surgeon's feedback indicates that this technology can be integrated into the surgical workflow without substantially increasing surgical time. Conclusion: Hand-held 3D photography is an accurate technique for objective quantification of intraoperative cranial vault morphology and guidance during metopic craniosynostosis surgical reconstruction. This noninvasive technique does not substantially increase surgical time and does not require exposure to ionizing radiation, presenting a valuable alternative to computed tomography imaging. The proposed methodology can be integrated into the surgical workflow to assist during cranial vault remodeling and ensure optimal surgical outcomes. [ABSTRACT FROM AUTHOR]

Craniosynostosis must often be corrected using surgery, by which the affected bone tissue is remodeled. Nowadays, surgical reconstruction relies mostly on the subjective judgement of the surgeon to best restore normal skull shape, since remodeled bone is manually placed and fixed. Slight variations can compromise the cosmetic outcome. The objective of this study was to describe and evaluate a novel workflow for patient-specific correction of craniosynostosis based on intraoperative navigation and 3D printing. The workflow was followed in five patients with craniosynostosis. Virtual surgical planning was performed, and patient-specific cutting guides and templates were designed and manufactured. These guides and templates were used to control osteotomies and bone remodeling. An intraoperative navigation system based on optical tracking made it possible to follow preoperative virtual planning in the operating room through real-time positioning and 3D visualization. Navigation accuracy was estimated using intraoperative surface scanning as the gold-standard. An average error of 0.62 mm and 0.64 mm was obtained in the remodeled frontal region and supraorbital bar, respectively. Intraoperative navigation is an accurate and reproducible technique for correction of craniosynostosis that enables optimal translation of the preoperative plan to the operating room. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a multi-platform automatic software tool for full processing of fMRI rodent studies. Existing tools require the usage of several different plug-ins, a significant user interaction and/or programming skills. Based on a user-friendly interface, the tool provides statistical parametric brain maps (t and Z) and percentage of signal change for user-provided regions of interest. The tool is coded in MATLAB (MathWorks(®)) and implemented as a plug-in for SPM (Statistical Parametric Mapping, the Wellcome Trust Centre for Neuroimaging). The automatic pipeline loads default parameters that are appropriate for preclinical studies and processes multiple subjects in batch mode (from images in either Nifti or raw Bruker format). In advanced mode, all processing steps can be selected or deselected and executed independently. Processing parameters and workflow were optimized for rat studies and assessed using 460 male-rat fMRI series on which we tested five smoothing kernel sizes and three different hemodynamic models. A smoothing kernel of FWHM = 1.2 mm (four times the voxel size) yielded the highest t values at the somatosensorial primary cortex, and a boxcar response function provided the lowest residual variance after fitting. fMRat offers the features of a thorough SPM-based analysis combined with the functionality of several SPM extensions in a single automatic pipeline with a user-friendly interface. The code and sample images can be downloaded from https://github.com/HGGM-LIM/fmrat . [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in glucose brain metabolism after deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) in a rat model of obesity. Procedures: Ten obese male Zucker rats were divided into two groups: LHA-control and LHA-DBS. Concentric bipolar platinum-iridium electrodes were implanted bilaterally. After 7 days, DBS was applied for 15 days. Weight and food and water intake were monitored. 2-Deoxy-2-[F]fluoro-D-glucose ([F]FDG) PET-CT imaging studies were performed the day after the end of DBS. Differences in glucose uptake between the groups were assessed with statistical parametric mapping. Results: A difference in weight gain of 3.19 percentage points was found between groups. Average food consumption during the first 15 days was lower in DBS-treated animals than in non-stimulated animals. DBS increased metabolism in the mammillary body, subiculum-hippocampal area, and amygdala, while a decrease in metabolism was recorded in the thalamus, caudate, temporal cortex, and cerebellum. Conclusions: DBS produced significant changes in brain regions associated with the control of food intake and the brain reward system. DBS seems to normalize the impaired hippocampal functioning that has been described in obese rats. The smaller weight gain in the DBS group suggests that this technique could be considered an option for the treatment of obesity. [ABSTRACT FROM AUTHOR]

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Purpose: To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence.Procedures: The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[¹⁸F]fluoro-D-: glucose (FDG) uptake were studied by positron emission tomography.Results: The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP.Conclusions: These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated. [ABSTRACT FROM AUTHOR]

Rationale: The study of the different effects on brain metabolism between typical and atypical antipsychotics would aid in understanding their mechanisms of action. Clozapine is of special interest, since it is one of the most effective antipsychotic drugs and demonstrates a distinctive mechanism of action in pre-clinical studies with respect to typical neuroleptics. Objective: To study the differences in cerebral activity induced by clozapine as compared to those produced by haloperidol. Methods: [18F]Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) scans were obtained in the resting condition before and after 6 months of treatment with clozapine in 22 treatment-resistant patients with schizophrenia. Before inclusion, patients had been chronically treated with classical drugs, and all of them received haloperidol during the last month. Data were analyzed with statistical parametric mapping (SPM '99) methods, comparing pre-treatment and post-treatment conditions. The association between the changes in symptom scores and metabolism was also assessed to corroborate the functional relevance of possible metabolic changes. Results: Clozapine decreased prefrontal and basal ganglia activity, and increased occipital metabolism, including primary and association visual areas. The change in negative symptoms was related with the decrease of basal ganglia activity; the improvement in disorganization related to the metabolic decrease in the motor area, and the change in positive symptoms was associated to the increase of activity in the visual area. Conclusions: These results show that haloperidol and clozapine produce different patterns of metabolic changes in schizophrenia. Compared to the haloperidol baseline, clozapine inhibited the metabolic activity of the prefrontal and motor cortical regions and basal ganglia and induced a higher activation of the visual cortex. The improvement in disorganization, negative and positive syndromes with... [ABSTRACT FROM AUTHOR]

The interpretation of the huge number of results in schizophrenia research using neuroimaging is uncertain. However, the simultaneous use of complimentary data obtained with these techniques may yield more relevant information in this regard. In this paper, we present a series of studies performed by our group in two schizophrenic samples with the use of structural (magnetic resonance imaging (MRI), functional [glucose positron emission tomography (PET) and N-acetylaspartate (NAA) magnetic resonance spectroscopy] and neurophysiological techniques (the P300 event-related potential). Transversal and longitudinal measurements were performed. The integrated vision of the results so obtained allows us to propose the hypothesis of a neurodevelopmentally determined state of prefrontal disinhibition, in which the degree of atrophy would directly relate to the metabolic rate. This state would already be present in the first stages of illness and could have neurotoxic consequences in the long term. This would explain the findings of an association between sulcal cerebrospinal fluid (CSF) and illness duration and decreased NAA levels in chronic but not in recent-onset cases. The prefrontal disinhibition would over stimulate the limbic system and the hippocampus would become over activated, the metabolic rate at this level being inversely related to P300 amplitude. Clozapine showed a more selective and intense action on that hyperactive metabolic tone than haloperidol. [ABSTRACT FROM AUTHOR]

A correction to the article "Response to Deep Brain Stimulation in the Lateral Hypothalamic Area in a Rat Model of Obesity: In Vivo Assessment of Brain Glucose Metabolism," by María Luisa Soto-Montenegro, Javier Pascau, and Manuel Desco that was published in the 2014 issue is presented.

A correction to the article "Chronic Cannabinoid Administration to Periadolescent Rats Modulates the Metabolic Response to Acute Cocaine in the Adult Brain" is presented.