Work-related musculoskeletal pain and discomfort in laparoscopic surgeons: an international multispecialty survey.

INTRODUCTION: As laparoscopic surgery is used more widely across the globe and within multiple surgical specialties the potential impact on surgeons is yet to be fully quantified. Maintenance of uncomfortable body positions may lead to work-related musculoskeletal disorders (WMSD) in surgeons, with potential knock-on effects. METHODS: An international open online survey of multispecialty laparoscopic surgeons was carried out, designed and reported in accordance with the CHERRIES checklist for internet e-survey research. There was no paid advertising and no incentives offered. RESULTS: A total of 259 surgeons from 9 specialties and 32 countries answered the survey, with 90% reporting pain attributable to performing laparoscopic surgery. All training grades were represented. Longer average operative duration and a greater number of years in practice were both associated with a significantly higher prevalence of pain. Surgeons with a pre-existing injury were significantly more likely to report pain than those without. Twenty per cent of surgeons would consider early retirement owing to pain. CONCLUSIONS: The impact on surgeons of performing laparoscopic surgery is significant, even given the limitations of an open survey. Innovations such as robotic surgery and improved ergonomic education may reduce the incidence of WMSD in surgeons, to mitigate both the personal effects on surgeons and the wider effect on the future surgical workforce.

A systematic review of point-of-care abdominal ultrasound scans performed by general surgeons in paediatric patients.

BACKGROUND/PURPOSE: Bedside point-of-care ultrasound scans are a cheap, quick and safe diagnostic tool. There is increasing evidence for the use of point-of-care surgeon-performed ultrasound scans in adults, however there are fewer studies of its use in children. This systematic review aims to provide an up-to-date summary of the evidence behind surgeon-performed ultrasound scans in paediatric surgery. METHODS: The PubMed database was used to conduct this systematic review between the dates 1 Jan 1980 to 1 June 2020 (last search: 1 June 2020). Seven primary research studies were included in this review. RESULTS: There is good evidence for the use of ultrasound scans in appendicitis and hypertrophic pyloric stenosis. Training times are easily achievable and transferable within a surgical department. CONCLUSIONS: Although the use of surgeon-performed bedside ultrasound scans has been described in appendicitis and hypertrophic pyloric stenosis, more research is required to embed this into clinical practice, particularly in low volume centres such as district general hospitals. A robust training programme is also recommended to incorporate ultrasound scans into clinical practice.

Identifying the optimal developmental age of human pluripotent stem cell-derived midbrain dopaminergic progenitors for transplantation in a rodent model of Parkinson's disease.

Donor cell age can have a significant impact on transplantation outcomes. Despite the rapid advancement of human pluripotent stem cell (hPSC)-derived dopaminergic (DA) progenitors to the clinic for transplantation into Parkinson's Disease (PD), surprisingly limited data exists regarding the influence of cellular age on neural graft survival, composition, and integration. Here we examined the impact of transplanting ventral midbrain (VM) progenitors at varying days of differentiation (from day 13-30) into a rodent PD model, comparing two hPSC lines (an embryonic and an induced pluripotent cell line, hESC and hiPSC, respectively). Both hPSC lines expressed GFP under the promoter PITX3 enabling specific tracking of graft-derived DA neurons. Post-mortem analysis at 6 months revealed larger grafts from Day19 (D19), D22 and D25 progenitors, yet contained a higher proportion of non-DA and poorly specified (FOXA2-) cells. While D13 and D30 progenitors yielded smaller grafts. D13-derived grafts had the highest DA neuron proportion and proportionally more GIRK2+ DA neurons, the subpopulation critical for motor function. These younger progenitor grafts maintained their capacity to innervate developmentally relevant DA targets, with increased innervation capacity per DA neuron, collectively resulting in restoration of motor deficits with equal or greater proficiency than older donor cells. While donor age effects were reproducible for a given hPSC line and trends were similar between the two hPSC lines, grafts of D13 hiPSC-derived progenitors showed a 6-fold greater density of DA neurons compared to D13 hESC-derived grafts, highlighting between-line variability. These findings show that hPSC-derived VM donor age has a direct impact on graft survival, composition and maturation, and that careful assessment, on a line-to-line basis is required prior to translation.

Incidence of Deep Venous Thrombosis and Sickle Cell Disease in Patients Undergoing Spinal Surgery in South Gujarat, India: A Prospective Observational Study.

Introduction: Our objective of this study was to assess the incidence of Deep Venous Thrombosis in patients including those with sickle cell disease who underwent spine surgery, and also to determine the association of Sickle Cell Disease as a clinical predictor for Deep Venous Thrombosis in spinal surgery patients. Materials and methods: All patients who underwent spinal surgery from January 2016 to October 2016 were included in this study. Detailed history, demographic data, physical findings, pre-operative haematological and radiological investigations were documented. All the patients underwent daily clinical evaluation for clinical signs of Deep Venous Thrombosis and also underwent a post-operative venous Doppler and D-dimer test. Results: Seventy-nine consecutive patients were included in the study with the mean age of 41 years. All patients had normal venous Doppler pre-operatively. A total of 2.5% patients had deep vein thrombosis in bilateral lower limbs while 2 patients (2.5%) had evidence of venous stasis but no thrombosis on Doppler ultrasound done post-operatively. Nine patients (11.4%) were sickle cell positive from which 4 patients showed evidence of Deep Venous Thrombosis or Venous Stasis. D-dimer was positive in 5 (8.3%) patients which included 4 patients with Sickle Cell Disease. Conclusion: This study concludes that Sickle Cell Disease is a risk factor for developing Deep Venous Thrombosis in patients undergoing spinal surgery. The study also concludes the effectiveness of mechanical prophylaxis in preventing Deep Venous Thrombosis and recommends pharmacological prophylaxis after assessing the risk profile or positive D-dimer test.

Development and Validation of a Risk-Adapted Scoring Model for Metachronous Upper Tract Urothelial Carcinoma following Radical Cystectomy.

PURPOSE: The incidence and risk factors for metachronous upper tract urothelial carcinoma (UTUC) following radical cystectomy (RC) remain incompletely defined, which has limited the ability to individualize postoperative surveillance. MATERIALS AND METHODS: A retrospective review of 2 institutional registries was performed to identify patients undergoing RC for urothelial carcinoma. Multivariable Cox proportional hazard models for metachronous post-RC UTUC were developed in one institutional data set and validated in the second institutional data set. A post-RC UTUC risk score was then developed from these models. RESULTS: A total of 3,170 RC patients were included from the training cohort and 959 RC patients from the validation cohort. At a median followup after RC of 4.6 years (IQR 2.1-8.7), 167 patients were diagnosed with UTUC. On multivariable analysis in the training cohort, risk factors for metachronous UTUC were the presence of positive urothelial margin (HR 2.60, p <0.01), history of bacillus Calmette-Guérin treatment prior to RC (HR 2.20, p <0.01), carcinoma in situ at RC (HR 2.01, p <0.01) and pre-RC hydronephrosis (HR 1.48, p=0.04). These factors had similar discriminative capacity in the training and validation cohorts (C-statistic 0.71 and 0.73, respectively). A UTUC risk score was developed with these variables which stratified patients into low (0 points), intermediate (1-3 points), and high risk (4+ points) for post-RC UTUC, with respective 5-year UTUC-free survivals of 99%, 96%, 89% in the training cohort and 98%, 96%, and 91% in the validation cohort. CONCLUSIONS: We developed and validated a risk score for post-RC UTUC that may optimize UTUC surveillance protocols after RC.

Effectiveness of two tobacco cessation methods among TB patients.

BACKGROUND: Tobacco and TB are the world´s two greatest public health problems. Exposure to tobacco has been shown to be associated with higher risk of acquiring TB and adverse outcomes such as relapse and TB mortality.OBJECTIVE: To assess and compare self-reported tobacco quit status and biochemically verified cotinine levels among TB patients at different time intervals among two study groups.METHODS: A cluster, randomised controlled trial was conducted on TB patients attending DOTS centres in Delhi, India, who reported using tobacco in any form. Participants were assigned into one of two treatment groups. Centres were randomly assigned to two intervention groups: 1) integrated intervention using behavioural counselling with nicotine replacement therapy (NRT) gum, and 2) intervention using behavioural counselling alone (50 each in intervention and control group). The subjects were followed at Week 1, Month 1, Month 3 and Month 6 for tobacco cessation.RESULTS: At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting tobacco than those who received the conventional TB treatment alone (78.7% vs. 57.8%; P < 0.03).CONCLUSION: DOTS with tobacco use dependence treatment was successful in our study in helping TB patients to quit tobacco dependence and should therefore be offered to every tobacco user.

Predictors of Poor Functional Status in Adult Fontan Patients Living at Moderate Altitude.

Patients who have undergone Fontan palliation have reduced exercise tolerance measured by maximal oxygen consumption (VO2 max). Declining exercise capacity is associated with increased morbidity and mortality. The impact of hemodynamics and other variables on this population's functional status is not well understood. This study sought to identify variables that predict low VO2 max in Fontan patients living at moderate altitude (5,000-8,000 feet). We performed a retrospective cohort study of 44 adult Fontan patients living at moderate altitude who had undergone cardiopulmonary exercise testing (CPET) and cardiac catheterization. We evaluated hemodynamic parameters measured during catheterization, imaging results, and laboratory studies for correlation with VO2 max measured during CPET. Our study cohort (median age 30 years, 52% female) had exercise impairment with mean VO2 max of 21.6 mL/kg/min. Higher trans-pulmonary gradient (TPG) (p < 0.001) and mean pulmonary artery (PA) pressure (p = 0.013) were predictors of lower maximal and submaximal VO2. Higher BNP values correlated with lower VO2 max (p = 0.01). Platelet count, GGT, albumin, and pulmonary vasodilator therapy did not correlate with VO2 max. None of the studied variables were associated with higher minute ventilation to peak carbon dioxide production (VE/VCO2 slope) or change in VO2 max over time. In conclusion, higher TPG and mean PA pressure predicted lower exercise tolerance amongst our cohort of adult Fontan patients living at moderate altitude. Future studies are needed to determine if these clinical variables represent viable therapeutic targets that could result in improved exercise tolerance and outcomes in patients with Fontan circulation.

A case of Infective Native (Abdominal) Aortic Aneurysm Caused by Streptococcus Agalactiae: An Updated Literature Review Based on New Nomenclature.

The management of abdominal aortic aneurysms (AAA) has evolved significantly with the advent of endovascular strategies. Thus, there has been a decline in the number of open AAA repairs once an endovascular option is available. There have also been reports of successful endovascular management of infective native aortic aneurysms (INAA)1, previously called mycotic aneurysms2. The rarity of this condition makes its management a challenging one as there are no standard guidelines. The European Society of Vascular Surgery has suggested that the nomenclature be changed from mycotic aneurysms as this can be misleading to standardise reporting1. The authors' present a case of a 67-year old male who presented during the peak of the Corona Virus pandemic with constitutional gastrointestinal symptoms. He was subsequently diagnosed with an INAA and successfully managed with open Neo-Aorto Iliac System reconstruction with a homograft3. The report highlights various strategies used in the surgical approach and their benefits in the management of INAA. Furthermore, a literature review of Streptococcus (Streptococcus agalactiae) species as a rare cause of INAA and how these cases were managed are also highlighted.

A systematic review of point-of-care abdominal ultrasound scans performed by general surgeons.

BACKGROUND: Ultrasound is an established imaging modality in general surgery. With the increasing use of bedside point-of-care ultrasounds, general surgeons have been incorporating this skill into their clinical practice. This systematic review provides an up-to-date summary of the evidence for abdominal ultrasound scans performed by general surgeons to diagnose intra-abdominal pathology. METHODS: Two independent reviewers searched the PubMed database between 1 January 1980 and 1 June 2020. Articles about surgeon-performed abdominal ultrasound in adult patients were included. Studies on trauma and vascular surgery were excluded. RESULTS: 26 articles met the inclusion criteria, presented as a narrative analysis. There was good evidence for the use of surgeon-performed ultrasound, particularly in gallstone-related diseases and moderate evidence for the use of ultrasound in appendicitis. Further evidence is required for point-of-care ultrasounds for other pathologies such as diverticulitis and groin hernias. Ultrasound training for general surgeons is variable with notable heterogeneity across studies. CONCLUSION: A standardised training programme for general surgeons will greatly improve confidence and skill. There is good evidence for the use of bedside ultrasound by general surgeons in the acute and elective setting with reduced time to definitive treatment and fewer unnecessary hospital admissions.

Peritonsillar abscess drainage: using oropharyngeal endoscopy as a therapeutic adjunct and training tool.

BACKGROUND: Peritonsillar abscess, or quinsy, is one of the most common emergency presentations to ENT departments, and is the most common deep tissue infection of the head and neck. In the UK, junior members of the ENT team are regularly required to independently assess, diagnose and treat patients with peritonsillar aspiration or incision and drainage. ISSUE: Inexperienced practitioners can stumble at several obstacles: poor access due to trismus; poor lighting; difficulty in learning the therapeutic procedure; and difficulty in accurately documenting findings and treatment. SOLUTION: To counter these and other difficulties, the authors describe the routine use of video endoscopy as a training tool and therapeutic adjunct in the management of quinsy.

Liver Resection for Giant Hepatic Cavernous Hemangioma.

Liver hemangiomas are common. Giant liver hemangiomas are rare and symptomatic patients require treatment. Surgery is the curative procedure. Other options such as intra-arterial embolization may be used to decrease the volume and bleeding of these lesions. Three cases of giant liver hemangioma were treated with liver resection, one with left lateral hepatectomy and two with right lateral hepatectomy. All patients had made an uneventful recovery with no recurrence at 3-year follow-up. Most hemangiomas are small, asymptomatic, and do not require any treatment. Liver resection is a safe and effective treatment for giant hemangiomas.

Major colorectal resection is feasible using a new robotic surgical platform: the first report of a case series.

BACKGROUND: The number of abdominal procedures performed via a robotic-assisted approach is increasing as potential advantages of the modality are recognised. We report the first in human case series of major colorectal resection performed using a new system, Versius®, and assess the feasibility of its use. METHODS: The initial cases performed using Versius® at a single centre in the UK were included in the study. Anonymised data were prospectively collected including patient demographics, operative details and postoperative outcomes. RESULTS: Twenty-three operations were performed, including left (n = 14) and right (n = 9)-sided colonic resections. Rectal mobilisation was performed in 13. Fifty-seven percent of the patients were male, with a malignant indication for surgery in 70% of cases. Overall mean age was 59.1 ± 15.3 (range 23-89) years. Overall mean body mass index was 28.9 ± 5.2 with a mean of 31.3 ± 4.5 for left-sided resections. The median console operating time was 166 min (range 75-320 min). All malignant cases had negative resection margins and the mean lymph node yield was 18 (SD 9.4). Only one operation (4%) was converted from robotic to open approach. Postoperative length of stay was a median of 5 days (range 3-34 days) and there were no readmissions within 30 days. CONCLUSIONS: These results compare favourably with the literature on existing robotic systems and also conventional laparoscopic surgery; hence, we believe that this series indicates the Versius® system is feasible for use in major colorectal resection. These early results from a robot-naïve centre show exciting promise for an expanding robotic market and highlight the need for further evaluation.

Epigenetic Mechanisms and Events in Gastric Cancer-Emerging Novel Biomarkers.

Gastric cancer is one of the most common malignancy worldwide. The various genetic and epigenetic events have been found to be associated with its carcinogenesis. The epigenetic is a heritable and transient/reversible change in the gene expression that is not accompanied by modification in the DNA sequence. This event is characterized by the alteration in the promoter CpG island of the gene or histone modification. These events are associated with silencing of critical tumor suppressor gene and activation of oncogenes leading to carcinogenesis. The DNA methylation is a chemical change in the DNA sequence that most commonly occurs at cytosine moiety of CpG dinucleotide and histone, primarily on N- terminal tail that ultimately effect the interaction of DNA with chromatin modifying protein.Hypermethylation of tumor suppressor genes and global hypomethylation of oncogenes are widely studied epigenetic modifications. There are large number of publish reports regarding epigenetic events involving gastric cancer. These changes are potentially useful in identifying markers for early diagnosis and management of this lethal malignancy. Also, role of specific miRNAs and long non coding RNAs in regulation of gene expression is gaining interest and is a matter of further investigation. In this review, we aimed to summarize major epigenetic events (DNA methylation) in gastric cancer along with alteration in miRNAs and long non coding RNAs which plays an important role in pathology of this poorly understood malignancy.

C-arm Positioning Using Virtual Fluoroscopy for Image-Guided Surgery.

INTRODUCTION: Fluoroscopically guided procedures often involve repeated acquisitions for C-arm positioning at the cost of radiation exposure and time in the operating room. A virtual fluoroscopy system is reported with the potential of reducing dose and time spent in C-arm positioning, utilizing three key advances: robust 3D-2D registration to a preoperative CT; real-time forward projection on GPU; and a motorized mobile C-arm with encoder feedback on C-arm orientation. METHOD: Geometric calibration of the C-arm was performed offline in two rotational directions (orbit α, orbit ß). Patient registration was performed using image-based 3D-2D registration with an initially acquired radiograph of the patient. This approach for patient registration eliminated the requirement for external tracking devices inside the operating room, allowing virtual fluoroscopy using commonly available systems in fluoroscopically guided procedures within standard surgical workflow. Geometric accuracy was evaluated in terms of projection distance error (PDE) in anatomical fiducials. A pilot study was conducted to evaluate the utility of virtual fluoroscopy to aid C-arm positioning in image guided surgery, assessing potential improvements in time, dose, and agreement between the virtual and desired view. RESULTS: The overall geometric accuracy of DRRs in comparison to the actual radiographs at various C-arm positions was PDE (mean ± std) = 1.6 ± 1.1 mm. The conventional approach required on average 8.0 ± 4.5 radiographs spent "fluoro hunting" to obtain the desired view. Positioning accuracy improved from 2.6° ± 2.3° (in α) and 4.1° ± 5.1° (in ß) in the conventional approach to 1.5° ± 1.3° and 1.8° ± 1.7°, respectively, with the virtual fluoroscopy approach. CONCLUSION: Virtual fluoroscopy could improve accuracy of C-arm positioning and save time and radiation dose in the operating room. Such a system could be valuable to training of fluoroscopy technicians as well as intraoperative use in fluoroscopically guided procedures.

Intraoperative evaluation of device placement in spine surgery using known-component 3D-2D image registration.

Intraoperative x-ray radiography/fluoroscopy is commonly used to assess the placement of surgical devices in the operating room (e.g. spine pedicle screws), but qualitative interpretation can fail to reliably detect suboptimal delivery and/or breach of adjacent critical structures. We present a 3D-2D image registration method wherein intraoperative radiographs are leveraged in combination with prior knowledge of the patient and surgical components for quantitative assessment of device placement and more rigorous quality assurance (QA) of the surgical product. The algorithm is based on known-component registration (KC-Reg) in which patient-specific preoperative CT and parametric component models are used. The registration performs optimization of gradient similarity, removes the need for offline geometric calibration of the C-arm, and simultaneously solves for multiple component bodies, thereby allowing QA in a single step (e.g. spinal construct with 4-20 screws). Performance was tested in a spine phantom, and first clinical results are reported for QA of transpedicle screws delivered in a patient undergoing thoracolumbar spine surgery. Simultaneous registration of ten pedicle screws (five contralateral pairs) demonstrated mean target registration error (TRE) of 1.1 ± 0.1 mm at the screw tip and 0.7 ± 0.4° in angulation when a prior geometric calibration was used. The calibration-free formulation, with the aid of component collision constraints, achieved TRE of 1.4 ± 0.6 mm. In all cases, a statistically significant improvement (p < 0.05) was observed for the simultaneous solutions in comparison to previously reported sequential solution of individual components. Initial application in clinical data in spine surgery demonstrated TRE of 2.7 ± 2.6 mm and 1.5 ± 0.8°. The KC-Reg algorithm offers an independent check and quantitative QA of the surgical product using radiographic/fluoroscopic views acquired within standard OR workflow. Such intraoperative assessment could improve quality and safety, provide the opportunity to revise suboptimal constructs in the OR, and reduce the frequency of revision surgery.

Registration of MRI to intraoperative radiographs for target localization in spinal interventions.

Decision support to assist in target vertebra localization could provide a useful aid to safe and effective spine surgery. Previous solutions have shown 3D-2D registration of preoperative CT to intraoperative radiographs to reliably annotate vertebral labels for assistance during level localization. We present an algorithm (referred to as MR-LevelCheck) to perform 3D-2D registration based on a preoperative MRI to accommodate the increasingly common clinical scenario in which MRI is used instead of CT for preoperative planning. Straightforward adaptation of gradient/intensity-based methods appropriate to CT-to-radiograph registration is confounded by large mismatch and noncorrespondence in image intensity between MRI and radiographs. The proposed method overcomes such challenges with a simple vertebrae segmentation step using vertebra centroids as seed points (automatically defined within existing workflow). Forwards projections are computed using segmented MRI and registered to radiographs via gradient orientation (GO) similarity and the CMA-ES (covariance-matrix-adaptation evolutionary-strategy) optimizer. The method was tested in an IRB-approved study involving 10 patients undergoing cervical, thoracic, or lumbar spine surgery following preoperative MRI. The method successfully registered each preoperative MRI to intraoperative radiographs and maintained desirable properties of robustness against image content mismatch and large capture range. Robust registration performance was achieved with projection distance error (PDE) (median ± IQR) = 4.3 ± 2.6 mm (median ± IQR) and 0% failure rate. Segmentation accuracy for the continuous max-flow method yielded dice coefficient = 88.1 ± 5.2, accuracy = 90.6 ± 5.7, RMSE = 1.8 ± 0.6 mm, and contour affinity ratio (CAR) = 0.82 ± 0.08. Registration performance was found to be robust for segmentation methods exhibiting RMSE <3 mm and CAR >0.50. The MR-LevelCheck method provides a potentially valuable extension to a previously developed decision support tool for spine surgery target localization by extending its utility to preoperative MRI while maintaining characteristics of accuracy and robustness.

Performance evaluation of MIND demons deformable registration of MR and CT images in spinal interventions.

Accurate intraoperative localization of target anatomy and adjacent nervous and vascular tissue is essential to safe, effective surgery, and multimodality deformable registration can be used to identify such anatomy by fusing preoperative CT or MR images with intraoperative images. A deformable image registration method has been developed to estimate viscoelastic diffeomorphisms between preoperative MR and intraoperative CT using modality-independent neighborhood descriptors (MIND) and a Huber metric for robust registration. The method, called MIND Demons, optimizes a constrained symmetric energy functional incorporating priors on smoothness, geodesics, and invertibility by alternating between Gauss-Newton optimization and Tikhonov regularization in a multiresolution scheme. Registration performance was evaluated for the MIND Demons method with a symmetric energy formulation in comparison to an asymmetric form, and sensitivity to anisotropic MR voxel-size was analyzed in phantom experiments emulating image-guided spine-surgery in comparison to a free-form deformation (FFD) method using local mutual information (LMI). Performance was validated in a clinical study involving 15 patients undergoing intervention of the cervical, thoracic, and lumbar spine. The target registration error (TRE) for the symmetric MIND Demons formulation (1.3 ± 0.8 mm (median ± interquartile)) outperformed the asymmetric form (3.6 ± 4.4 mm). The method demonstrated fairly minor sensitivity to anisotropic MR voxel size, with median TRE ranging 1.3-2.9 mm for MR slice thickness ranging 0.9-9.9 mm, compared to TRE = 3.2-4.1 mm for LMI FFD over the same range. Evaluation in clinical data demonstrated sub-voxel TRE (<2 mm) in all fifteen cases with realistic deformations that preserved topology with sub-voxel invertibility (0.001 mm) and positive-determinant spatial Jacobians. The approach therefore appears robust against realistic anisotropic resolution characteristics in MR and yields registration accuracy suitable to application in image-guided spine-surgery.

MIND Demons for MR-to-CT Deformable Image Registration In Image-Guided Spine Surgery.

PURPOSE: Localization of target anatomy and critical structures defined in preoperative MR images can be achieved by means of multi-modality deformable registration to intraoperative CT. We propose a symmetric diffeomorphic deformable registration algorithm incorporating a modality independent neighborhood descriptor (MIND) and a robust Huber metric for MR-to-CT registration. METHOD: The method, called MIND Demons, solves for the deformation field between two images by optimizing an energy functional that incorporates both the forward and inverse deformations, smoothness on the velocity fields and the diffeomorphisms, a modality-insensitive similarity function suitable to multi-modality images, and constraints on geodesics in Lagrangian coordinates. Direct optimization (without relying on an exponential map of stationary velocity fields used in conventional diffeomorphic Demons) is carried out using a Gauss-Newton method for fast convergence. Registration performance and sensitivity to registration parameters were analyzed in simulation, in phantom experiments, and clinical studies emulating application in image-guided spine surgery, and results were compared to conventional mutual information (MI) free-form deformation (FFD), local MI (LMI) FFD, and normalized MI (NMI) Demons. RESULT: The method yielded sub-voxel invertibility (0.006 mm) and nonsingular spatial Jacobians with capability to preserve local orientation and topology. It demonstrated improved registration accuracy in comparison to the reference methods, with mean target registration error (TRE) of 1.5 mm compared to 10.9, 2.3, and 4.6 mm for MI FFD, LMI FFD, and NMI Demons methods, respectively. Validation in clinical studies demonstrated realistic deformation with sub-voxel TRE in cases of cervical, thoracic, and lumbar spine. CONCLUSIONS: A modality-independent deformable registration method has been developed to estimate a viscoelastic diffeomorphic map between preoperative MR and intraoperative CT. The method yields registration accuracy suitable to application in image-guided spine surgery across a broad range of anatomical sites and modes of deformation.