Explainable artificial intelligence for human-machine interaction in brain tumor localization

Primary malignancies in adult brains are globally fatal. Computer vision, especially recent developments in artificial intelligence (AI), have created opportunities to automatically characterize and diagnose tumor lesions in the brain. AI approaches have provided scores of unprecedented accuracy in different image analysis tasks, including differentiating tumor-containing brains from healthy brains. AI models, however, perform as a black box, concealing the rational interpretations that are an essential step towards translating AI imaging tools into clinical routine. An explainable AI approach aims to visualize the high-level features of trained models or integrate into the training process. This study aims to evaluate the performance of selected deep-learning algorithms on localizing tumor lesions and distinguishing the lesion from healthy regions in magnetic resonance imaging contrasts. Despite a significant correlation between classification and lesion localization accuracy (R = 0.46, p = 0.005), the known AI algorithms, examined in this study, classify some tumor brains based on other non-relevant features. The results suggest that explainable AI approaches can develop an intuition for model interpretability and may play an important role in the performance evaluation of deep learning models. Developing explainable AI approaches will be an essential tool to improve human–machine interactions and assist in the selection of optimal training methods.publishedVersio

Is the presence of foraminal stenosis associated with outcome in lumbar spinal stenosis patients treated with posterior microsurgical decompression

Background We aim to investigate associations between preoperative radiological findings of lumbar foraminal stenosis with clinical outcomes after posterior microsurgical decompression in patients with predominantly central lumbar spinal stenosis (LSS). Methods The study was an additional analysis in the NORDSTEN Spinal Stenosis Trial. In total, 230 men and 207 women (mean age 66.8 (SD 8.3)) were included. All patients underwent an MRI including T1- and T2-weighted sequences. Grade of foraminal stenosis was dichotomized into none to moderate (0–1) and severe (2–3) category using Lee’s classification system. The Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and numeric rating scale (NRS) for back and leg pain were collected at baseline and at 2-year follow-up. Primary outcome was a reduction of 30% or more on the ODI score. Secondary outcomes included the mean improvement on the ODI, ZCQ, and NRS scores. We performed multivariable regression analyses with the radiological variates foraminal stenosis, Pfirrmann grade, Schizas score, dural sac cross-sectional area, and the possible plausible confounders: patients’ gender, age, smoking status, and BMI. Results The cohort of 437 patients presented a high degree of degenerative changes at baseline. Of 414 patients with adequate imaging of potential foraminal stenosis, 402 were labeled in the none to moderate category and 12 in the severe category. Of the patients with none to moderate foraminal stenosis, 71% achieved at least 30% improvement in ODI. Among the patients with severe foraminal stenosis, 36% achieved at least 30% improvement in ODI. A significant association between severe foraminal stenosis and less chance of reaching the target of 30% improvement in the ODI score after surgery was detected: OR 0.22 (95% CI 0.06, 0.83), p=0.03. When investigating outcome as continuous variables, a similar association between severe foraminal stenosis and less improved ODI with a mean difference of 9.28 points (95%CI 0.47, 18.09; p=0.04) was found. Significant association between severe foraminal stenosis and less improved NRS pain in the lumbar region was also detected with a mean difference of 1.89 (95% CI 0.30, 3.49; p=0.02). No significant association was suggested between severe foraminal stenosis and ZCQ or NRS leg pain. Conclusion In patients operated with posterior microsurgical decompression for LSS, a preoperative severe lumbar foraminal stenosis was associated with higher proportion of patients with less than 30% improvement in ODI.publishedVersio

Postoperative Dural Sac Cross-Sectional Area as an Association for Outcome After Surgery for Lumbar Spinal Stenosis: Clinical and Radiological Results From the NORDSTEN-Spinal Stenosis Trial

Objective - The aim was to investigate the association between postoperative dural sac cross-sectional area (DSCA) after decompressive surgery for lumbar spinal stenosis and clinical outcome. Furthermore, to investigate if there is a minimum threshold for how extensive a posterior decompression needs to be to achieve a satisfactory clinical result. Summary of Background Data - There is limited scientific evidence for how extensive lumbar decompression needs to be to obtain a good clinical outcome in patients with symptomatic lumbar spinal stenosis. Materials and Methods - All patients were included in the Spinal Stenosis Trial of the NORwegian Degenerative spondylolisthesis and spinal STENosis (NORDSTEN)-study. The patients underwent decompression according to three different methods. DSCA measured on lumbar magnetic resonance imaging at baseline and at three months follow-up, and patient-reported outcome at baseline and at two-year follow-up were registered in a total of 393 patients. Mean age was 68 (SD: 8.3), proportion of males were 204/393 (52%), proportion of smokers were 80/393 (20%), and mean body mass index was 27.8 (SD: 4.2). The cohort was divided into quintiles based on the achieved DSCA postoperatively, the numeric, and relative increase of DSCA, and the association between the increase in DSCA and clinical outcome were evaluated. Results - At baseline, the mean DSCA in the whole cohort was 51.1 mm2 (SD: 21.1). Postoperatively the area increased to a mean area of 120.6 mm2 (SD: 46.9). The change in Oswestry disability index in the quintile with the largest DSCA was −22.0 (95% CI: −25.6 to −18), and in the quintile with the lowest DSCA the Oswestry disability index change was −18.9 (95% CI: −22.4 to −15.3). There were only minor differences in clinical improvement for patients in the different DSCA quintiles. <p<Conclusion - Less aggressive decompression performed similarly to wider decompression across multiple different patient-reported outcome measures at two years following surgery

Surgery in Degenerative Spondylolisthesis: Does fusion improve outcome in subgroups? A secondary analysis from a randomized trial (NORDSTEN trial)

BACKGROUND CONTEXT Patients with spinal stenosis and degenerative spondylolisthesis are treated surgically with decompression alone or decompression with fusion. However, there is debate regarding which subgroups of patients may benefit from additional fusion. PURPOSE To investigate possible treatment effect modifiers and prognostic variables among patients operated for spinal stenosis and degenerative spondylolisthesis. DESIGN A secondary exploratory study using data from the Norwegian Degenerative Spondylolisthesis and Spinal Stenosis (NORDSTEN-DS) trial. Patients were randomized to decompression alone or decompression with instrumented fusion. PATIENT SAMPLE The sample in this study consists of 267 patients from a randomized multicenter trial involving 16 hospitals in Norway. Patients were enrolled from February 12, 2014, to December 18, 2017. The study did not include patients with degenerative scoliosis, severe foraminal stenosis, multilevel spondylolisthesis, or previous surgery. OUTCOME MEASURES The primary outcome was an improvement of ≥ 30% on the Oswestry Disability Index score (ODI) from baseline to 2-year follow-up. METHODS When investigating possible variables that could modify the treatment effect, we analyzed the treatment arms separately. When testing for prognostic factors we analyzed the whole cohort (both treatment groups). We used univariate and multiple regression analyses. The selection of variables was done a priori, according to the published trial protocol. RESULTS Of the 267 patients included in the trial (183 female [67%]; mean [SD] age, 66 [7.6] years), complete baseline data for the variables required for the present analysis were available for 205 of the 267 individuals. We did not find any clinical or radiological variables at baseline that modified the treatment effect. Thus, none of the commonly used criteria for selecting patients for fusion surgery influenced the chosen primary outcome in the two treatment arms. For the whole cohort, less comorbidity (American Society of Anesthesiologists Classification [ASA], OR = 4.35; 95% confidence interval (CI [1.16–16.67]) and more preoperative leg pain (OR = 1.23; CI [1.02–1.50]) were significantly associated with an improved primary outcome. CONCLUSIONS In this study on patients with degenerative spondylolisthesis, neither previously defined instability criteria nor other pre-specified baseline variables were associated with better clinical outcome if fusion surgery was performed. None of the analyzed variables can be applied to guide the decision for fusion surgery in patients with degenerative spondylolisthesis. For both treatment groups, less comorbidity and more leg pain were associated with improved outcome 2 years after surgery.publishedVersio

Acute kidney injury due to cytokine storm in patients with COVID-19 infection

Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 represents usually a variety range of symptoms related to influenza-like syndrome and respiratory tract infections. Likewise, kidney involvement and acute kidney injury (AKI) were reported in many previous studies. Although a hypovolemic circulation would be the most common reason in patients with AKI, some strong proofs are suggesting a cytokine storm due to immune system exaggeration and inflammation-mediated tubular injury in COVID-19 infections. The inflammatory response in cytokine storm leads to the high release of cytokines mostly including TNFα, IL-1β, IL-6, INFγ, IL-2, IL-7, and endothelial mediators. The main culprits in the AKI and consequent organ failure are resident leukocytes in specific tissues, activated following the cytokine release, and systemic inflammatory response. AKI management and cytokine profile evaluation should be highly emphasized in patients with COVID-19 to prevent the progression of chronic kidney disease or permanent renal failure. Treatment options in COVID-19 regarding no specific drugs should be supportive and based on stabilizing the patients; however, combination therapy with different antiviral have shown promising outcomes. As a result, utilizing the anti-TNFα and anti-IL-1 agents should be noticed if indicated. Additionally, the hematopoietic stem cell transplantation is a curative approach

Effect of Aerobic Exercise on the Expression of Ppargc-1α and SIRT1 in Cardiac Muscle of Diabetic Male Wistar Rats

Background: Type 2 diabetic patients have an abnormally high rate of mortality due to cardiovascular diseases. Given the adverse impact of diabetes on mitochondrial biogenesis in heart cells and the role of exercise on mitochondrial biogenesis signaling, this study investigated the effect of eight weeks of aerobic exercise on PGC-1a and SIRT1 gene expression in the myocardium of diabetic male Wistar rats. Materials and Methods: This experimental study was conducted on 24 adult male Wistar rats (eight weeks old and weighing 278.26±18.06g), which were randomly assigned to three groups of healthy control (n=8), diabetic control (n=8), and diabetes+aerobic exercise (n=8). The exercise protocol consisted of eight weeks of exercise, three sessions a week, starting with 10 minutes of running at a speed of 10m/s in the first week and ultimately reaching 40 minutes of running at a speed of 18m/s in the eighth week. The changes were analyzed using the one-way analysis of variance and Tukey’s post hoc test. Results: Significant differences were observed between the groups in terms of body mass (P=0.0001), fasting glucose (P=0.004), serum insulin (P=0.023), and myocardial Ppargc- 1α expression (P=0.031). The post hoc test represented a notable weight decrease in the diabetic control group (P=0.001) and the diabetic exercise group (P=0.001) compared to the healthy control group. The results also showed a significant increase in the glucose level of the diabetic control group compared to the healthy control group (P=0.008) and a notable decrease in the diabetic exercise group’s glucose level in comparison with the diabetic control group (P=0.001). A significant decrease was also observed in the insulin level of the diabetic exercise group compared to the diabetic control group (P=0.034). The results of the post hoc test for Ppargc-1α expression changes showed significantly increased myocardial Ppargc-1α expression in the diabetic exercise group compared to the diabetic control group (P=0.009). No significant change was detected in the expression of SIRT1 (P=0.075). Conclusion: The findings suggest that exercise positively affects insulin resistance and weight changes by regulating genes related to mitochondrial biogenesis

Explainable artificial intelligence for human-machine interaction in brain tumor localization

Primary malignancies in adult brains are globally fatal. Computer vision, especially recent developments in artificial intelligence (AI), have created opportunities to automatically characterize and diagnose tumor lesions in the brain. AI approaches have provided scores of unprecedented accuracy in different image analysis tasks, including differentiating tumor-containing brains from healthy brains. AI models, however, perform as a black box, concealing the rational interpretations that are an essential step towards translating AI imaging tools into clinical routine. An explainable AI approach aims to visualize the high-level features of trained models or integrate into the training process. This study aims to evaluate the performance of selected deep-learning algorithms on localizing tumor lesions and distinguishing the lesion from healthy regions in magnetic resonance imaging contrasts. Despite a significant correlation between classification and lesion localization accuracy (R = 0.46, p = 0.005), the known AI algorithms, examined in this study, classify some tumor brains based on other non-relevant features. The results suggest that explainable AI approaches can develop an intuition for model interpretability and may play an important role in the performance evaluation of deep learning models. Developing explainable AI approaches will be an essential tool to improve human–machine interactions and assist in the selection of optimal training methods

Is T2 mapping reliable in evaluation of native and repair cartilage tissue of the knee?

Purpose To evaluate the effect of imaging plane and experience of observers on the reliability of T2 mapping of native and repair cartilage tissue of the knee. Methods Fifteen consecutive patients from two randomised controlled trials (RCTs) were included in this cross-sectional study. Patients with an isolated knee cartilage lesion were randomised to receive either debridement or microfracture (RCT 1) or debridement or autologous chondrocyte implantation (RCT 2). T2 mapping was performed in coronal and sagittal planes two years postoperatively. A musculoskeletal radiologist, a resident of radiology and two orthopaedic surgeons measured the T2 values independently. Intraclass Correlation Coefficient (ICC) with 95% Confidence Intervals was used to calculate the inter- and intraobserver agreement. Results Mean age for the patients was 36.8 ± 11 years, 8 (53%) were men. The overall interobserver agreement varied from poor to good with ICCs in the range of 0.27– 0.76 for native cartilage and 0.00 – 0.90 for repair tissue. The lowest agreement was achieved for evaluations of repair cartilage tissue. The estimated ICCs suggested higher inter- and intraobserver agreement for radiologists. On medial femoral condyles, T2 values were higher for native cartilage on coronal images (p < 0.001) and for repair tissue on sagittal images (p < 0.001). Conclusions The reliability of T2 mapping of articular cartilage is influenced by the imaging plane and the experience of the observers. This influence may be more profound for repair cartilage tissue. This is important to consider when using T2 mapping to measure outcomes after cartilage repair surgery. Trial registration ClinicalTrials.gov, NCT02637505 and NCT02636881, registered December 2015. Level of evidence II, based on prospective data from two RCTs

Clinical and MRI findings in lumbar spinal stenosis: baseline data from the NORDSTEN study

Purpose The aim was to describe magnetic resonance imaging findings in patients planned for lumbar spinal stenosis surgery. Further, to describe possible associations between MRI findings and patient characteristics with patient reported disability or pain. Methods The NORDSTEN spinal stenosis trial included 437 patients planned for surgical decompression of LSS. The following MRI findings were evaluated before surgery: morphological (Schizas) and quantitative (cross-sectional area) grade of stenosis, disk degeneration (Pfirrmann), facet joint tropism and fatty infiltration of the multifidus muscle. Patients were dichotomized into a moderate or severe category for each radiological parameter classification. A multivariable linear regression analysis was performed to investigate the association between MRI findings and preoperative scores for Oswestry Disability Index, Zurich Claudication Questionnaire and Numeric rating scale for back and leg pain. The following patient characteristics were included in the analysis: gender, age, smoking and weight. Results The percentage of patients with severe scores was as follows: Schizas (C + D) 71.3%, cross-sectional area (< 75 mm2) 86.8%, Pfirrmann (4 + 5) 58.1%, tropism (≥ 15°) 11.9%, degeneration of multifidus muscle (2–4) 83.7%. Regression coefficients indicated minimal changes in severity of symptoms when comparing the groups with moderate and severe MRI findings. Only gender had a significant and clinically relevant association with ODI score. Conclusion In this cross-sectional study, the majority of the patients had MRI findings classified as severe LSS changes, but the findings had no clinically relevant association with patient reported disability and pain at baseline. Patient characteristics have a larger impact on disability and pain than radiological findings.publishedVersio

Change in lumbar lordosis after decompressive surgery in lumbar spinal stenosis patients and associations with patient related outcomes 2 years after surgery : radiological and clinical results from the NORDSTEN spinal stenosis trial

Study design: A prospective cohort study. Objective: The aim was to investigate changes in lumbar lordosis (LL) and its association to changes in patient reported outcome measures (PROMs) after decompressive surgery for lumbar spinal stenosis (LSS). Summary of background: Few studies have addressed change in LL after decompression surgery for LSS in relation to outcomes. Method: Pre- and postoperative data from 310 patients having standing x-ray both before and 2 years after surgery were included. The patients were grouped based on the change in LL preoperatively to 2 years after surgery; group 1: &lt;5 degrees (n=196), group 2: ≥5 &lt;10 degrees (n=55) or group 3: ≥10 degrees (n=59) of change in LL. The changes in function, disability and pain were assessed by the Oswestry Disability Index (ODI), Numeric Rating Scale (NRS), and the Zurich claudication questionnaire (ZCQ). The three groups were compared regarding baseline variables using the ANOVA test for continuous variables and the chi-square test for categorical variables. The groups were further compared with a likelihood ratio test in relation to changes in PROMs 2 year after surgery and outcomes were adjusted for respective baseline PROMs, age, sex, smoking, BMI, Schizas and Pfirrmann scores. Results: LL was significantly changed at group level 2 years after surgery with a mean difference of 2.2 (SD 9.4) degrees (P=0.001). The three LL change groups did not show any significant differences in patient characteristics, function, disability, and pain at baseline. The two groups with a change of more than 5 degrees in LL 2 year after surgery (group 2 and 3) had significantly greater improvements in ODI (P=0.022) and ZCQ function (P=0.016) in the adjusted analyses, but was not significant for back and leg pain Conclusion: Changed LL after decompressive surgery for LSS was associated with improved ODI and physical function