Hyperspectral Imaging in Brain Tumor Surgery-Evidence of Machine Learning-Based Performance.

BACKGROUND: Hyperspectral imaging (HSI) has the potential to enhance surgical tissue detection and diagnostics. Definite utilization of intraoperative HSI guidance demands validated machine learning and public datasets that currently do not exist. Moreover, current imaging conventions are dispersed, and evidence-based paradigms for neurosurgical HSI have not been declared. METHODS: We presented the rationale and a detailed clinical paradigm for establishing microneurosurgical HSI guidance. In addition, a systematic literature review was conducted to summarize the current indications and performance of neurosurgical HSI systems, with an emphasis on machine learning-based methods. RESULTS: The published data comprised a few case series or case reports aiming to classify tissues during glioma operations. For a multitissue classification problem, the highest overall accuracy of 80% was obtained using deep learning. Our HSI system was capable of intraoperative data acquisition and visualization with minimal disturbance to glioma surgery. CONCLUSIONS: In a limited number of publications, neurosurgical HSI has demonstrated unique capabilities in contrast to the established imaging techniques. Multidisciplinary work is required to establish communicable HSI standards and clinical impact. Our HSI paradigm endorses systematic intraoperative HSI data collection, which aims to facilitate the related standards, medical device regulations, and value-based medical imaging systems.

Utilizing Grasp Monitoring to Predict Microsurgical Expertise.

INTRODUCTION: Most microsurgical procedures require the surgeon to use tools to grasp and hold fragile objects in the surgical site. Prior research on grasping in surgery has mostly either been in other surgical techniques or used grasping as an auxiliary metric. We focus on microsurgery and investigate what grasping can tell about microsurgical skill and suturing performance. This study lays groundwork for using automatic detection of grasps to evaluate surgical skill. METHODS: Five expert surgeons and six novices completed sutures on a microsurgical training board. Video recordings of the performance were annotated for the number of grasps, while an eye tracker recorded the participants' pupil dilations for cognitive workload assessment. Performance was measured with suturing duration and the University of Western Ontario Microsurgical Skills Assessment instrument (UWOMSA). Differences in skill, suturing performance and cognitive workload were compared with grasping behavior. RESULTS: Novices needed significantly more grasps to complete sutures and failed to grasp more often than the experts. The number of grasps affected the suturing duration more in novices. Decreasing suturing efficiency as measured by UWOMSA instrument was associated with increase in grasps, even when we controlled for overall skill differences. Novices displayed larger pupil dilations when averaged over a sufficiently large sample, and the difference increased after the grasp. CONCLUSIONS: Grasping action during microsurgical procedures can be used as a conceptually simple yet objective proxy in microsurgical performance assessment. If the grasps could be detected automatically, they could be used to aid in computational evaluation of surgical trainees' performance.

Detection improvement of gliomas in hyperspectral imaging of protoporphyrin IX fluorescence - in vitro comparison of visual identification and machine thresholds.

BACKGROUND: 5-aminolevulinic acid (5-ALA) - precursor of protoporphyrin IX (PpIX) - is utilized in fluorescence guided surgery (FGS) of high-grade gliomas. PpIX is used to identify traces of glioma during resection. Visual inspection of the fluorescence seems inaccurate in comparison to optic techniques such as hyperspectral imaging (HSI). AIM: To characterize the limits of PpIX fluorescence detection of (i) visual evaluation and (ii) HSI analysis and to (iii) develop a classification system for visible and non-visible PpIX fluorescence. METHODS: Samples with increasing concentrations (C) of PpIX and non-fluorescent controls were evaluated using a surgical microscope under blue light illumination. Similar samples were imaged with a HSI system tuned to PpIX fluorescence peak wavelength (635 nm) and control (RGB) channels. Samples' intensities were defined, leading to 96 analysed pixels after batching. RESULTS: Three expert neurosurgeons assessed the PpIX samples (n = 16) and controls (n = 8) with unanimous decisions (ICC = 0.704), resulting in 63% recognition rate, 48% sensitivity, 92% specificity, 92% positive predictive value (PPV) and 47% negative predictive value (NPV). HSI image analysis, comparing mean relative values, resulted in 96%, 100%, 86%, 94%, 100%, respectively. Minimum PpIX concentration detection for experts was 0.6-1.8 µmol/l and HSI's 0.03-0.15 µmol/l. CONCLUSIONS: PpIX concentrations of low-grade gliomas, and those reported on glioblastoma infiltration zones, are below experts' detection threshold. HSI analysis exceeds the performance of expert's visual inspection nearly by 20-fold. Hybrid FGS-HSI systems should be investigated in parallel to long-term outcomes. Described methods are applicable as a standard for calibration, testing and development of subvisual FGS techniques.

Eye-Tracking Indicators of Workload in Surgery: A Systematic Review.

BackgroundEye tracking is a powerful tool for unobtrusive and real time assessment of workload in clinical settings. Before the complex eye tracking derived surrogates can be proactively utilized to improve surgical safety, the indications, validity and reliability requires careful evaluation.MethodsWe conducted a systematic review of literature from 2010 to 2020 according to PRISMA guidelines. A search on PubMed, Cochrane, Scopus, Web of science, PsycInfo and Google scholar databases was conducted on July 2020. The following search query was used" ("eye tracking" OR "gaze tracking") AND (surgery OR surgical OR operative OR intraoperative) AND (workload OR stress)". Short papers, no peer reviewed or papers in which eye-tracking methodology was not used to investigate workload or stress factors in surgery, were omitted.ResultsA total of 17 (N = 17) studies were identified eligible to this review. Most of the studies (n = 15) measured workload in simulated setting. Task difficulty and expertise were the most studied factors. Studies consistently showed surgeon's eye movements such as pupil responses, gaze patterns, blinks were associated with the level of perceived workload. However, differences between measurements in operational room and simulated environments have been found.ConclusionPupil responses, blink rate and gaze indices are valid indicators of workload. However, the effect of distractions and non-technical factors on workload is underrepresented aspect in the literature even though recognized as underlying factors in successful surgery.

The effect of virtual reality on temporal bone anatomy evaluation and performance.

PURPOSE: There is only limited data on the application of virtual reality (VR) for the evaluation of temporal bone anatomy. The aim of the present study was to compare the VR environment to traditional cross-sectional viewing of computed tomography images in a simulated preoperative planning setting in novice and expert surgeons. METHODS: A novice (n = 5) and an expert group (n = 5), based on their otosurgery experience, were created. The participants were asked to identify 24 anatomical landmarks, perform 11 distance measurements between surgically relevant anatomical structures and 10 fiducial markers on five cadaver temporal bones in both VR environment and cross-sectional viewings in PACS interface. The data on performance time and user-experience (i.e., subjective validation) were collected. RESULTS: The novice group made significantly more errors (p < 0.001) and with significantly longer performance time (p = 0.001) in cross-sectional viewing than the expert group. In the VR environment, there was no significant differences (errors and time) between the groups. The performance of novices improved faster in the VR. The novices showed significantly faster task performance (p = 0.003) and a trend towards fewer errors (p = 0.054) in VR compared to cross-sectional viewing. No such difference between the methods were observed in the expert group. The mean overall scores of user-experience were significantly higher for VR than cross-sectional viewing in both groups (p < 0.001). CONCLUSION: In the VR environment, novices performed the anatomical evaluation of temporal bone faster and with fewer errors than in the traditional cross-sectional viewing, which supports its efficiency for the evaluation of complex anatomy.

Movement-level process modeling of microsurgical bimanual and unimanual tasks.

PURPOSE: Microsurgical techniques require highly skilled manual handling of specialized surgical instruments. Surgical process models are central for objective evaluation of these skills, enabling data-driven solutions that can improve intraoperative efficiency. METHOD: We built a surgical process model, defined at movement level in terms of elementary surgical actions ([Formula: see text]) and targets ([Formula: see text]). The model also included nonproductive movements, which enabled us to evaluate suturing efficiency and bi-manual dexterity. The elementary activities were used to investigate differences between novice ([Formula: see text]) and expert surgeons ([Formula: see text]) by comparing the cosine similarity of vector representations of a microsurgical suturing training task and its different segments. RESULTS: Based on our model, the experts were significantly more efficient than the novices at using their tools individually and simultaneously. At suture level, the experts were significantly more efficient at using their left hand tool, but the differences were not significant for the right hand tool. At the level of individual suture segments, the experts had on average 21.0 % higher suturing efficiency and 48.2 % higher bi-manual efficiency, and the results varied between segments. Similarity of the manual actions showed that expert and novice surgeons could be distinguished by their movement patterns. CONCLUSIONS: The surgical process model allowed us to identify differences between novices' and experts' movements and to evaluate their uni- and bi-manual tool use efficiency. Analyzing surgical tasks in this manner could be used to evaluate surgical skill and help surgical trainees detect problems in their performance computationally.

Ex Vivo Porcine Models Are Valid for Testing and Training Microsurgical Lumbar Decompression Techniques.

BACKGROUND: Spinal surgeries are the leading causes for patient settlement issues. Recent European Medical Device Regulations aims to reduce complications by enforcing that surgical tools are validated before clinical use. Human cadavers are favored in preclinical use, but due to anatomic variance, decay, and scarce supply, alternative synthetic and animal models are used. This study evaluates the fidelity and validity of porcine models in training and assessment of microsurgical decompressive techniques in the lumbar spine. METHODS: Anatomic dimensions of 10 human and 5 young pig spines were assessed from computed tomography images. Novel "en bloc" fresh-frozen ex vivo porcine model tissues' fidelity and validity for decompressive surgery was evaluated by 3 expert neurosurgeons, in comparison with other models. RESULTS: The pigs' anatomic dimensions were on average 11% smaller than in humans. The pigs' L4-L5 was most alike humans, and the highest similarity was in lamina and spinous process widths, and the skin to posterior longitudinal ligament distance. Dimensional variability was higher in humans (F = 19.06-0.56, P < 0.05). The pigs' tissues were felt as good as living patients and better than cadavers for skin, fascia, bone, facets, ligamentum flavum, and dura, but poor for vessels (experts' intraclass correlation coefficient = 0.696-0.903). The pig models' validity for assessing drills' adverse features (friction, jitter, heating, and soft tissue trauma) was reported to be unanimously excellent. CONCLUSION: Pigs are representative for assessing microsurgical decompression techniques in the lower lumbar spine. The novel "en bloc" pig model can be an asset for industries and clinicians during assessment and training of new spinal techniques.

Cerebrospinal fluid dynamics in idiopathic intracranial hypertension: a literature review and validation of contemporary findings.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. METHOD: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman's criteria, hence referred to as symptomatic controls. RESULTS: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). CONCLUSIONS: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.

Virtual reality improves the accuracy of simulated preoperative planning in temporal bones: a feasibility and validation study.

PURPOSE: Consumer-grade virtual reality (VR) has recently enabled various medical applications, but more evidence supporting their validity is needed. We investigated the accuracy of simulated surgical planning in a VR environment (VR) with temporal bones and compared it to conventional cross-sectional image viewing in picture archiving and communication system (PACS) interface. METHODS: Five experienced otologic surgeons measured significant anatomic structures and fiducials on five fresh-frozen cadaveric temporal bones in VR and cross-sectional viewing. Primary image data were acquired by computed tomography. In total, 275 anatomical landmark measurements and 250 measurements of the distance between fiducials were obtained with both methods. Distance measurements between the fiducials were confirmed by physical measurement obtained by Vernier caliper. The experts evaluated the subjective validity of both methods on a 5-point Likert scale qualitative survey. RESULTS: A strong correlation based on intraclass coefficient was found between the methods on both the anatomical (r > 0.900) and fiducial measurements (r > 0.916). Two-tailed paired t-test and Bland-Altman plots demonstrated high equivalences between the VR and cross-sectional viewing with mean differences of 1.9% (p = 0.396) and 0.472 mm (p = 0.065) for anatomical and fiducial measurements, respectively. Gross measurement errors due to the misidentification of fiducials occurred more frequently in the cross-sectional viewing. The mean face and content validity rating for VR were significantly better compared to cross-sectional viewing (total mean score 4.11 vs 3.39, p < 0.001). CONCLUSION: Our study supports good accuracy and reliability of VR environment for simulated surgical planning in temporal bones compared to conventional cross-sectional visualization.

Parental Alcohol Problems, Parental Divorce, and Type 2 Diabetes in Adulthood: A Longitudinal Prospective Cohort Study in Middle-Aged Men.

OBJECTIVE: Type 2 diabetes is a chronic disease and a serious global public health concern increasing both mortality and morbidity. Previous studies have found evidence for an association between early psychological stress and diabetes later in life. METHODS: This study examined the association between parental alcohol problems and parental divorce and the incidence of type 2 diabetes in Finnish men aged 42 to 61 years (n = 754) in a prospective setting. Information on parental alcohol problems and parental divorce was derived from school records and subjective experiences of the same events from self-rated questionnaires. The average follow-up time for the participants until the first type 2 diabetes diagnosis was 23.3 years (25th-75th percentile, 21.2-27.9 years). RESULTS: Cox regression analyses revealed that parental alcohol problems (hazard ratio = 3.09, 95% confidence interval = 1.38-6.88) were associated with an increased risk of type 2 diabetes during the follow-up, even after adjustment for age, marital status, education, Human Population Laboratory Depression Scale scores, smoking, alcohol consumption, body mass index, and serum high-sensitivity C-reactive protein. In a similar model, parental divorce (hazard ratio = 1.69, 95% confidence interval = 0.40-7.05) was not associated with an increased risk of type 2 diabetes during the follow-up. CONCLUSIONS: Our findings suggest that not all adverse childhood experiences contribute equally to the risk of type 2 diabetes. Parental alcohol problems, but not parental divorce, were associated with an increased risk of type 2 diabetes in men. These findings highlight the need for early interventions targeting parents with excessive alcohol consumption to reduce their offspring's risk of life-style-related disorders.

Kuopio birth cohort - design of a Finnish joint research effort for identification of environmental and lifestyle risk factors for the wellbeing of the mother and the newborn child.

BACKGROUND: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to evaluate the effects of genetics, epigenetics and different risk factors (medication, nutrition, lifestyle factors and environmental aspects) during pregnancy on the somatic and psychological health status of the mother and the child. METHODS: KuBiCo will ultimately include information on 10,000 mother-child pairs who have given their informed consent to participate in this cohort. Identification of foetal health risk factors that can potentially later manifest as disease requires a repository of relevant biological samples and a flexible open up-to-date data handling system to register, store and analyse biological, clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based maternal background data gathered before, during and after the pregnancy and bio-banking of maternal and foetal samples that will be stored in deep freezers. Data from the questionnaires and biological samples will be collected into one electronic database. KuBiCo consists of several work packages which are complementary to each other: Maternal, foetal and placental metabolism and omics; Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and anaesthetics during peripartum period; Environmental effects; Nutrition; and Research ethics. DISCUSSION: This report describes the set-up of the KuBiCo and descriptive analysis from 3532 parturients on response frequencies and feedback to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we describe basic demographic data of the participants (n = 1172). Based on the comparison of demographic data between official national statistics and our descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant women.

Serum copper, zinc and high-sensitivity C-reactive protein in short and long sleep duration in ageing men.

BACKGROUND: Serum levels of zinc and copper have been proposed to associate with sleep duration. Mechanisms, such as inflammatory processes, have been suggested to relate this association. However, earlier studies have been conducted in small sample sizes. Human studies investigating the suggested associations while controlling for potential confounding factors are lacking. METHODS: Population-based data consisted of 2570 men (aged 42-60 years) from Eastern Finland. The participants reported an estimate of their sleep duration. The serum levels of zinc (S-Zn), copper (S-Cu) and high-sensitivity C-reactive protein (hs-CRP) were measured. Analysis of covariance was used for multivariate analyses. RESULTS: S-Zn levels and Zn/Cu ratio were lowest in ≤6h sleep. S-Cu levels were highest in ≥10h sleep. Elevated levels (>3.0mmol/l) of hs-CRP were observed in ≤6h and ≥10h sleep. After adjustments for age, cumulative smoking history (pack-years), alcohol consumption (g/week), Human Population Laboratory depression scale scores, physical activity (kcal/day), cardiometabolic syndrome, and cardiovascular disease history, sleep duration was significantly associated with levels of both S-Cu and hs-CRP. The association with S-Cu remained statistically significant following further adjustment for hs-CRP in the same model. CONCLUSIONS: Our data suggests an association between S-Cu and sleep duration in ageing men. Elevated inflammation (measured as serum hs-CRP) does not explain this relationship. Mechanisms underlying the relationship require further investigation, as S-Cu may contribute to sleep regulation through pro-oxidative processes and copper-dependent N-methyl-d-aspartate receptor activity.

Reduced serum adiponectin levels in alexithymia.

OBJECTIVES: Clinical studies have demonstrated that circulating cytokine profiles may differ between alexithymic and non-alexithymic subjects. We examined whether the levels of adiponectin (µg/ml) and resistin (ng/ml) are independently related to alexithymic features in a population-based sample. METHODS: In 2005, clinical data including laboratory assessments were obtained from a sub-sample (n = 308) of the Kuopio Depression Study general population study including subjects aged 25-64 years. Based on the Toronto Alexithymia Scale score in 1998, 1999, 2001 and 2005, a group of subjects with high alexithymic features (n = 85) was formed and compared with non-alexithymic controls (n = 206). RESULTS: Serum adiponectin levels were significantly lower in subjects with alexithymic features than in non-alexithymic control subjects. No difference was found in resistin levels. Similarly, in a logistic regression model adjusted for age, gender and body mass index (BMI), lowered levels of adiponectin, but not resistin, were associated with an increased likelihood of belonging to the group with alexithymic features. Further adjustments for cardiovascular risk factors (i.e. smoking, BMI, metabolic syndrome, alcohol use, and coronary heart disease), depressive symptoms (Hamilton Depression Rating Scale with 17 items) and the use of antidepressants in addition to age and gender did not change these patterns. CONCLUSIONS: Our findings suggest that a disturbed anti-inflammatory balance may characterize alexithymia. In addition, our results widen the concept of alexithymia and highlight the role of immune system alterations and stress in alexithymic individuals.

Self-reported sleep disturbance is associated with elevated levels of PAI-1 in individuals with a recorded history of depressive symptoms.

BACKGROUND: The majority of depressed individuals report insomnia. Self-reported symptoms of insomnia, in particular, more strongly predict adverse health effects than the actual measured sleep time. The physiological alterations in individuals with insomnia are complex, as both autonomic and endocrine dysfunctions are present. Plasminogen activator inhibitor (PAI)-1 is a stress-related acute-phase reactant that has also been suggested to regulate the circadian rhythm and sleep patterns. It has been suggested to contribute to both depressive symptoms and sleep disorders, although data on the relationships between these parameters are scarce. OBJECTIVE: This study examined the role of self-reported sleep disturbance and its association with PAI-1 among individuals with a history of depressive symptoms. METHODS: Differences in the serum levels of PAI-1 between two groups (group 1: moderate to very severe sleep disturbance, n=37; group 2: mild or no sleep disturbance, n = 90) were examined in a population-based sample of individuals with a recorded history of depressive symptoms. RESULTS: Multivariate analysis controlling for potential confounding factors (age, sex, body mass index, depression severity) showed that each 1-unit increase in PAI-1 (µg/mL) increased the likelihood for belonging to the group with moderate to very severe sleep disturbance by 23% (OR = 1.23, C.I. 95% = 1.04-1.45, p = 0.016). This statistical significance remained after additional adjustments for regular smoking and the use of sleep or lipid-lowering medication. CONCLUSION: Our observations may further clarify the physiological alterations related to sleep disturbance in depressive individuals. In the present study, self-reported sleep disturbance in individuals with a recorded history of depressive symptoms was associated with an elevation of PAI-1. This finding may illustrate the association of subjective sleep disturbance with sympathetic activation. Our study highlights the importance of effects of perceived sleep disturbance on individual homeostasis, and may provide potential directions for research on treatment options.

Serum adipokine levels in adults with a history of childhood maltreatment.

Individuals with a history of childhood maltreatment present increased rates of metabolic disturbances, but the underlying mechanisms for such phenomena are poorly understood. This study examined whether the secretion of adipokines, adipocyte-derived inflammation markers closely associated with metabolic disorders, is altered in individuals with a history of childhood maltreatment. The serum levels of inflammatory markers adiponectin and resistin were measured from 147 general population participants who had a history of adverse mental symptoms, and who also reported their experiences of childhood maltreatment. Participants with experiences of childhood maltreatment (n=30) had lowered levels of serum adiponectin (p=0.007) and resistin (p=0.028). The differences in adiponectin levels persisted in multivariate modeling with adjustments for age, gender, and body mass index (OR for each 1 standard deviation decrease in the serum adiponectin level 2.65, 95% CI 1.31-5.35, p=0.007). Additional adjustments for marital status or a diagnosis of major depressive disorder, or the exclusion of individuals using NSAIDs, oral corticosteroids, or antidepressants did not alter the results. The association between resistin levels and childhood maltreatment did not remain independent in the same models. Our findings suggest that in individuals with previously reported adverse mental symptoms, a history of childhood maltreatment is independently associated with lowered levels of the anti-inflammatory marker adiponectin. This may lead to a lowered anti-inflammatory buffer capacity, which can, in turn, increase the susceptibility to physical and psychological states characterized by pronounced pro-inflammation.

Elevated levels of serum IL-5 are associated with an increased likelihood of major depressive disorder.

BACKGROUND: Inflammatory mediators in both the peripheral circulation and central nervous system (CNS) are dysregulated in major depressive disorder (MDD). Nevertheless, relatively little is known about the role of the T-helper (Th)-2 effector cytokines interleukin (IL)-5 and IL-13 in MDD. METHODS: We examined the serum levels of these cytokines and a Th-1 comparison cytokine, interferon (IFN)-γ, in 116 individuals (MDD, n = 58; controls, n = 58). RESULTS: In our basic multivariate model controlling for the effects of potential confounders on the associations between MDD and the examined cytokines, each 1-unit increase in the serum IL-5 level increased the likelihood of belonging to the MDD group by 76% (OR 1.76, 95% CI 1.03-2.99, p = 0.04; model covariates: age, gender, marital status, daily smoking and alcohol use). The likelihood further increased in models additionally controlling for the effects of the use of antidepressants and NSAIDS, and a diagnosis of asthma. No such associations were detected with regard to IL-13 (OR 1.08, 95% CI 0.96-1.22, p = 0.22) or IFN-γ (OR 1.02, 95% CI 0.99-1.05, p = 0.23). CONCLUSIONS: Elevated levels of IL-5, which uses the neural plasticity-related RAS GTPase-extracellular signal-regulated kinase (Ras-ERK) pathway to mediate its actions in the central nervous system (CNS), could be one of the factors underlying the depression-related changes in CNS plasticity.