A new immunometabolic perspective of intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is a common finding on spine imaging that increases in prevalence with age. IVD degeneration is a frequent cause of low back pain, which is a leading cause of disability. The process of IVD degeneration consists of gradual structural change accompanied by severe alterations in metabolic homeostasis. IVD degeneration, like osteoarthritis, is a common comorbidity in patients with obesity and type 2 diabetes mellitus, two metabolic syndrome pathological conditions in which adipokines are important promoters of low-grade inflammation, extracellular matrix degradation and fibrosis. Impairment in white adipose tissue function, due to the abnormal fat accumulation in obesity, is characterized by increased production of specific pro-inflammatory proteins such as adipokines by white adipose tissue and of cytokines such as TNF by immune cells of the stromal compartment. Investigations into the immunometabolic alterations in obesity and type 2 diabetes mellitus and their interconnections with IVD degeneration provide insights into how adipokines might affect the pathogenesis of IVD degeneration and impair IVD function and repair. Toll-like receptor-mediated signalling has also been implicated as a promoter of the inflammatory response in the metabolic alterations associated with IVD and is thus thought to have a role in IVD degeneration. Pathological starvation, obesity and adipokine dysregulation can result in immunometabolic alterations, which could be targeted for the development of new therapeutics.

Magnetic resonance imaging-guided biopsies in children.

BACKGROUND: Magnetic resonance imaging (MRI) is used far less as an imaging-guided method for percutaneous biopsies than computed tomography (CT) and ultrasound (US), despite its imaging benefits, particularly in children. PURPOSE: To evaluate the feasibility, accuracy and safety of MRI-guided biopsies in paediatric patient population. MATERIAL AND METHODS: The retrospective study included 57 consecutive paediatric patients (<18 years old). A percutaneous core needle biopsy (PCNB) or trephine biopsy was performed in 53 cases, and an additional fine-needle aspiration biopsy (FNAB) in 26 cases. In 4 cases, a stand-alone FNAB was taken. Biopsies were performed with 0.23 T open and 1.5 T closed MRI scanners. Statistical methods used for confidence intervals and p-values were Wilson score method and chi-square test. RESULTS: The overall diagnostic accuracy of histologic biopsy was 0.94, with sensitivity 0.82, specificity 1.00, positive predictive value (PPV) 1.00 and negative predictive value (NPV) 0.92. In histological bone biopsies, diagnostic accuracy was 0.96, with sensitivity 0.86, specificity 1.00, PPV 1.00 and NPV 0.94. The FNAB sample diagnosis was associated with the histological diagnosis in 79% of cases. There were no major primary complications and only a few late complications. After biopsy, 83% of the children were ambulatory in 6 h. Anti-inflammatory drugs and paracetamol provided satisfactory pain relief in 96% of the patients after biopsy. Most outpatients (71%) were discharged from hospital either on the same day or 1 day later. CONCLUSION: MRI is a technically feasible, accurate and safe guidance tool for performing percutaneous biopsies in children.

Co-activation pattern alterations in autism spectrum disorder-A volume-wise hierarchical clustering fMRI study.

INTRODUCTION: There has been a growing effort to characterize the time-varying functional connectivity of resting state (RS) fMRI brain networks (RSNs). Although voxel-wise connectivity studies have examined different sliding window lengths, nonsequential volume-wise approaches have been less common. METHODS: Inspired by earlier co-activation pattern (CAP) studies, we applied hierarchical clustering (HC) to classify the image volumes of the RS-fMRI data on 28 adolescents with autism spectrum disorder (ASD) and their 27 typically developing (TD) controls. We compared the distribution of the ASD and TD groups' volumes in CAPs as well as their voxel-wise means. For simplification purposes, we conducted a group independent component analysis to extract 14 major RSNs. The RSNs' average z-scores enabled us to meaningfully regroup the RSNs and estimate the percentage of voxels within each RSN for which there was a significant group difference. These results were jointly interpreted to find global group-specific patterns. RESULTS: We found similar brain state proportions in 58 CAPs (clustering interval from 2 to 30). However, in many CAPs, the voxel-wise means differed significantly within a matrix of 14 RSNs. The rest-activated default mode-positive and default mode-negative brain state properties vary considerably in both groups over time. This division was seen clearly when the volumes were partitioned into two CAPs and then further examined along the HC dendrogram of the diversifying brain CAPs. The ASD group network activations followed a more heterogeneous distribution and some networks maintained higher baselines; throughout the brain deactivation state, the ASD participants had reduced deactivation in 12/14 networks. During default mode-negative CAPs, the ASD group showed simultaneous visual network and either dorsal attention or default mode network overactivation. CONCLUSION: Nonsequential volume gathering into CAPs and the comparison of voxel-wise signal changes provide a complementary perspective to connectivity and an alternative to sliding window analysis.

Critical evaluation of deep neural networks for wrist fracture detection.

Wrist Fracture is the most common type of fracture with a high incidence rate. Conventional radiography (i.e. X-ray imaging) is used for wrist fracture detection routinely, but occasionally fracture delineation poses issues and an additional confirmation by computed tomography (CT) is needed for diagnosis. Recent advances in the field of Deep Learning (DL), a subfield of Artificial Intelligence (AI), have shown that wrist fracture detection can be automated using Convolutional Neural Networks. However, previous studies did not pay close attention to the difficult cases which can only be confirmed via CT imaging. In this study, we have developed and analyzed a state-of-the-art DL-based pipeline for wrist (distal radius) fracture detection-DeepWrist, and evaluated it against one general population test set, and one challenging test set comprising only cases requiring confirmation by CT. Our results reveal that a typical state-of-the-art approach, such as DeepWrist, while having a near-perfect performance on the general independent test set, has a substantially lower performance on the challenging test set-average precision of 0.99 (0.99-0.99) versus 0.64 (0.46-0.83), respectively. Similarly, the area under the ROC curve was of 0.99 (0.98-0.99) versus 0.84 (0.72-0.93), respectively. Our findings highlight the importance of a meticulous analysis of DL-based models before clinical use, and unearth the need for more challenging settings for testing medical AI systems.

T2 -weighted magnetic resonance imaging texture as predictor of low back pain: A texture analysis-based classification pipeline to symptomatic and asymptomatic cases.

Low back pain is a very common symptom and the leading cause of disability throughout the world. Several degenerative imaging findings seen on magnetic resonance imaging are associated with low back pain but none of them is specific for the presence of low back pain as abnormal findings are prevalent among asymptomatic subjects as well. The purpose of this population-based study was to investigate if more specific magnetic resonance imaging predictors of low back pain could be found via texture analysis and machine learning. We used this methodology to classify T2 -weighted magnetic resonance images from the Northern Finland Birth Cohort 1966 data to symptomatic and asymptomatic groups. Lumbar spine magnetic resonance imaging was performed using a fast spin-echo sequence at 1.5 T. Texture analysis pipeline consisting of textural feature extraction, principal component analysis, and logistic regression classifier was applied to the data to classify them into symptomatic (clinically relevant pain with frequency ≥30 days and intensity ≥6/10) and asymptomatic (frequency ≤7 days, intensity ≤3/10, and no previous pain episodes in the follow-up period) groups. Best classification results were observed applying texture analysis to the two lowest intervertebral discs (L4-L5 and L5-S1), with accuracy of 83%, specificity of 83%, sensitivity of 82%, negative predictive value of 94%, precision of 56%, and receiver operating characteristic area-under-curve of 0.91. To conclude, textural features from T2 -weighted magnetic resonance images can be applied in low back pain classification.

Magnetic resonance imaging of avascular necrosis of the femoral head: predictive findings of total hip arthroplasty.

BACKGROUND: Avascular osteonecrosis of the femoral head (AVNFH) is an ischemic condition which despite different treatments often leads to collapse of the femoral head and to total hip arthroplasty. However, the magnetic resonance imaging findings predisposing to disease progression and total hip arthroplasty are somewhat elusive. PURPOSE: To evaluate the magnetic resonance imaging findings of AVNFH and to assess the patterns of findings which may predict total hip arthroplasty. MATERIALS AND METHODS: A retrospective study was conducted with a total of 18 diagnosed AVNFH treated with core decompression combined with intraosseous stem cell treatment. After treatment, magnetic resonance imaging follow-ups were done at three-month and one-year follow-up or until total hip arthroplasty. Association Research Circulation Osseous classification and magnetic resonance imaging findings such as the size and the location of the AVNFH, bone marrow edema in femoral neck, effusion and subchondral fracture were evaluated. RESULTS: Hips advancing to total hip arthroplasty have more often bone marrow edema in femoral neck (90% vs. 0%), adjacent to necrotic lesion (100% vs. 43%) and in acetabulum (90% vs. 14%), but also subchondral fractures (70% vs. 0%), effusion (80% vs. 29%), and synovitis (80% vs. 14,3%). The greater size and the lateral weight-bearing location of the necrotic lesion also predicted future total hip arthroplasty. CONCLUSION: Hips advancing to total hip arthroplasty have often a combination of pathognomonic AVNFH imaging findings compared to hips not advancing to total hip arthroplasty.

The variability of functional MRI brain signal increases in Alzheimer's disease at cardiorespiratory frequencies.

Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer's disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly differentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fluid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans.

Association Between Modic Changes and Low Back Pain in Middle Age: A Northern Finland Birth Cohort Study.

STUDY DESIGN: A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966). OBJECTIVE: The aim of this study was to evaluate the association between the type, size, and location of lumbar Modic changes (MC), and prolonged disabling low back pain (LBP). SUMMARY OF BACKGROUND DATA: LBP is the leading cause of disability worldwide and it affects all age- and socioeconomical groups. Only a small proportion of LBP patients are diagnosed with a specific cause: In most cases no single nociceptive cause for the pain can be identified. MC are visualized in magnetic resonance imaging (MRI) as a signal intensity change in vertebral bone marrow and have been proposed to represent a specific degenerative imaging phenotype associated with LBP. MC can be classified into several subtypes, of which inflammatory Type 1 (MC1) is suggested as being more likely to be associated with LBP. METHODS: We assessed lumbar MRI (n = 1512) for the presence, type, and size of MC. The associations of MC characteristics with prolonged (≥30 days during the past year) and disabling (bothersomeness of LBP at least 6 on a 0-10 Numeric Rating Scale) LBP, evaluated at the time of imaging at 47 years, were analyzed using binary logistic regression, adjusted for sex, BMI, smoking, educational status, lumbar disc degeneration, and disc herniations. RESULTS: Any MC and MC1 were associated with prolonged disabling LBP (odds ratio [OR] after full adjustments 1.50 [95% confidence interval, CI 1.05-2.15] and 1.50 [95% CI 1.10-2.05], respectively). Furthermore, MC covering the whole anterior-posterior direction or the whole endplate, as well as the height of MC, were significantly associated with prolonged disabling LBP (OR after full adjustments 1.59 [95% CI 1.14-2.20], 1.67 [95% CI 1.13-2.46] and 1.26 [95% CI 1.13-1.42], respectively). CONCLUSION: Our study showed a significant and independent association between MC and clinically relevant LBP. LEVEL OF EVIDENCE: 3.

Does bone scintigraphy show Modic changes associated with increased bone turnover?

PURPOSE: Our purpose was to evaluate whether Modic changes (MC) revealed in lumbar MRI are associated with increased tracer uptake shown in bone scintigraphy. To our knowledge, this has not previously been studied. METHODS: We included patients with MC shown in lumbar MRI and bone scintigraphy performed within six months before or after MRI. Exclusion criteria included metastasis and other specific lesions in the area of interest such as discitis, tumors or fractures. We compared the level and type of MC to the degree of tracer uptake shown in bone scintigraphy. Tracer uptake was assessed both visually and quantitatively. We calculated the lesion-to-normal-bone ratios between the MC area with increased tracer uptake and the vertebra with normal tracer uptake. We used linear mixed models in statistical analyses. RESULTS: Our study sample consisted of 93 patients (aged 37-86) with 299 MC (28 Type 1 (M1), 50 mixed Type 1/2 (M1/2), 3 mixed Type 1/3 (M1/3), 211 Type 2 (M2), 6 mixed Type 2/3 (M2/3), and 1 Type 3 (M3)). Of all the MC, 26 (93 %) M1, 34 (64 %) in the combined M1/2 and M1/3 group, and 11 (5 %) in the combined M2, M2/3 and M3 group showed increased tracer uptake. The mean lesion-to-normal-bone ratio was higher for lesions with a Type 1 component (M1, M1/2 and M1/3) than for other types, at 1.55 (SD 0.16) for M1; 1.44 (SD 0.21) for combined M1/2 and M1/3; and 1.28 (SD 0.11) for combined M2, M2/3 and M3; p = 0.001). CONCLUSION: In most cases, MC with a Type 1 component showed increased tracer uptake in bone scintigraphy. This indicates that bone turnover is accelerated in the M1 area.

The effect of interventions on appropriate use of lumbar spine radiograph and CT examinations in young adults and children: a three-year follow-up.

BACKGROUND: According to international guidelines, radiological examinations of the lumbar spine are of limited value and do not improve clinical outcome unless there are clinical red flags present suggesting serious pathology. Nevertheless, the utilization of lumbar spine imaging remains high. PURPOSE: To follow up the effects of active referral guideline implementation and education on the number and appropriateness of lumbar spine radiographs and computed tomography (CT) examinations in young patients and to evaluate whether the appropriate radiographs have more significant findings. MATERIAL AND METHODS: Referral guidelines for spine examinations and info pocket cards on radiation protection were distributed to referring practitioners. Educational lectures were provided annually. The number of lumbar spine radiographs and CT examinations on patients aged <35 years was analyzed before and three years after the interventions. Appropriateness and findings of 313 radiographs and appropriateness of 117 CT scans of the lumbar spine were assessed. RESULTS: The number of lumbar spine radiographs and CT scans decreased significantly after the interventions and the level remained unchanged during the follow-up (-33% and -72%, respectively, P < 0.001). Appropriateness improved significantly in radiographs from 2005 to 2009 (65% vs. 85%) and in CT scans already from 2005 to 2007 (23% vs. 63%). Radiographs that were in accordance with the guidelines had more significant findings compared to radiographs that were not; in young adults, this was 56% versus 21% (P < 0.001). CONCLUSION: A combination of interventions can achieve a sustained reduction in the number of lumbar spine examinations and improve appropriateness. Inappropriate lumbar spine radiographs do not seem to contain significant findings that would affect patient care.

The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging.

The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini-Hochberg (B-H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.

Parents' received and expected information about their child's radiation exposure during radiographic examinations.

BACKGROUND: Despite regulations, insufficient information is provided to adult patients prior to their radiologic examinations. Information regarding paediatric patients has not been systematically studied. OBJECTIVE: To survey parents' experience and wishes for information in connection with their child's radiographic examination. MATERIALS AND METHODS: We provided a questionnaire to consenting parents of children younger than 12 years old at a university hospital. The questionnaire asked parents about the information obtained from the referrer prior to the radiograph, the chance to discuss with the referrer and their wishes regarding future information. Forty-one parents responded to the survey. Twenty-five children were referred for radiography of extremities, the others for dental, body and skull examinations. RESULTS: Altogether 34/41 (83%, 95% confidence interval [CI] 69-91%) parents said they received adequate information on the purpose of the examination, 8/35 (23%, 95% CI 12-39%) on other options and 3/41 (7%, 95% CI 3-19%) on radiation dose. Ten of 41 parents (24%, 95% CI 12-40%) said they were aware of radiation exposure. The number of previous radiology examinations was not sufficiently discussed. The communication was scored as mean 6.5 (95% CI 5.8-7.1) on a scale from 4 (poor) to 10 (excellent). Thirty-eight of 40 (95%, 95% CI 84-99%) of parents expected information on the purpose, 35/40 (88%, 95% CI 74-95%) on radiation dose and 31/40 (78%, 95% CI 63-88%) on other options. Symbols of radiation and corresponding period of natural background radiation are preferred to convey the dose. A referrer is the preferred source of information. CONCLUSION: Parents did not feel adequately informed prior to their child's radiographic examination. Parents expect more information about the purpose, dose and alternative tests.

Discrepancies in interpretation of night-time emergency computed tomography scans by radiology residents.

BACKGROUND: In many emergency radiology units, most of the night-time work is performed by radiology residents. Residents' preliminary reports are typically reviewed by an attending radiologist. Accordingly, it is known that discrepancies in these preliminary reports exist. PURPOSE: To evaluate the quality of night-time computed tomography (CT) interpretations made by radiology residents in the emergency department. MATERIAL AND METHODS: Retrospectively, 1463 initial night-time CT interpretations given by a radiology resident were compared to the subspecialist's re-interpretation given the following weekday. All discrepancies were recorded and classified into different groups regarding their possible adverse effect for the emergency treatment. The rate of discrepancies was compared between more and less experienced residents and between different anatomical regions. RESULTS: The overall rate of misinterpretations was low. In 2.3% (33/1463) of all night-time CT interpretations, an important and clinically relevant diagnosis was missed. No fatalities occurred due to CT misinterpretations during the study. The total rate of discrepancies including clinically irrelevant findings such as anatomical variations was 12.2% (179/1463). Less experienced residents were more likely to miss the correct diagnosis than more experienced residents (18.3% vs. 10.9%, odds ratio [OR] = 1.82, P = 0.001). Discrepancies were more common in body CT interpretations than in neurological CTs (18.1% vs. 9.1%, OR = 2.30, P < 0.0001). CONCLUSION: The rate of clinically important misinterpretations in CT examinations by radiology residents was found to be low. Experience helps in lowering the rate of misinterpretations.

Fluctuations of the EEG-fMRI correlation reflect intrinsic strength of functional connectivity in default mode network.

Both functional magnetic resonance imaging (fMRI) and electrophysiological recordings have revealed that resting-state functional connectivity is temporally variable in human brain. Combined full-band electroencephalography-fMRI (fbEEG-fMRI) studies have shown that infraslow (<.1 Hz) fluctuations in EEG scalp potential are correlated with the blood-oxygen-level-dependent (BOLD) fMRI signals and that also this correlation appears variable over time. Here, we used simultaneous fbEEG-fMRI to test the hypothesis that correlation dynamics between BOLD and fbEEG signals could be explained by fluctuations in the activation properties of resting-state networks (RSNs) such as the extent or strength of their activation. We used ultrafast magnetic resonance encephalography (MREG) fMRI to enable temporally accurate and statistically robust short-time-window comparisons of infra-slow fbEEG and BOLD signals. We found that the temporal fluctuations in the fbEEG-BOLD correlation were dependent on RSN connectivity strength, but not on the mean signal level or magnitude of RSN activation or motion during scanning. Moreover, the EEG-fMRI correlations were strongest when the intrinsic RSN connectivity was strong and close to the pial surface. Conversely, weak fbEEG-BOLD correlations were attributable to periods of less coherent or spatially more scattered intrinsic RSN connectivity, or RSN activation in deeper cerebral structures. The results thus show that the on-average low correlations between infra-slow EEG and BOLD signals are, in fact, governed by the momentary coherence and depth of the underlying RSN activation, and may reach systematically high values with appropriate source activities. These findings further consolidate the notion of slow scalp potentials being directly coupled to hemodynamic fluctuations.

Quantitative MRI of Human Cartilage In Vivo: Relationships with Arthroscopic Indentation Stiffness and Defect Severity.

Objective To investigate the association of cartilage defect severity, as determined by the International Cartilage Repair Society (ICRS) grading with indentation stiffness and T2 relaxation time of magnetic resonance imaging (MRI), a biomarker for the integrity of articular cartilage. Design Twenty-one patients scheduled for arthroscopic were included in the study. Prior to arthroscopy, subjects underwent quantitative MRI of articular cartilage, namely T2 relaxation time mapping at 1.5 T. Within 2 months, subjects underwent arthroscopy, which also included ICRS grading and measurement of arthroscopic indentation stiffness. Arthroscopic evaluations and T2 mapping at anterior, central, and posterior medial and lateral femoral condyles were correlated using a colocalization scheme. Differences in Young's modulus, as derived by indentation tests, and T2 times between ICRS grades were analyzed using Mann-Whitney's U or Kruskal-Wallis H tests. The correlation between modulus and T2 times was analyzed using Spearman's rank correlation coefficients. Results Modulus and T2 showed significant topographical variation. In the anterior region of interest (ROI) on the medial condyle the modulus showed a negative association with ICRS grade ( P = 0.040) and the T2 times were longer in ICRS grade 2 compared with grades 0 and 1 ( P = 0.047). Similar, but nonsignificant associations were found in the central ROI on the medial condyle. No significant correlations were observed between the indentation modulus and T2 times. Conclusions Cartilage degeneration is identified both with mechanical indentation and T2 mapping in MRI. However, in this study, indentation stiffness and T2 relaxation time in vivo, were not associated.

The effect of zoledronic acid on type and volume of Modic changes among patients with low back pain.

BACKGROUND: Modic changes (MC) are associated with low back pain (LBP). In this study, we compared changes in size and type of MC, after a single intravenous infusion of 5 mg zoledronic acid (ZA) or placebo, among chronic LBP patients with MC on magnetic resonance imaging (MRI), and evaluated whether the MRI changes correlate with symptoms. METHODS: All patients (N = 19 in ZA, 20 in placebo) had MRI at baseline (0.23-1.5 T) and at one year (1.5-3 T). We evaluated the level, type and volume of all the MC. The MC were classified into M1 (M1 (100%)), predominating M1 (M1/2 (65:35%)) or predominating M2 (M1/2 (35:65%)), and M2 (M2 (100%)). The first two were considered M1-dominant, and the latter two M2-dominant. Volumes of M1 and M2 were calculated separately for the primary MC, which was assumed to cause the symptoms, and the other MC. We analysed the one-year treatment differences in M1 and M2 volumes using analysis of covariance with adjustments for age, sex, body mass index, and smoking. The correlations between the MRI changes and the changes in LBP symptoms were analysed using Pearson correlations. RESULTS: In the ZA group, 84.2% of patients had M1-dominant primary MC at baseline, compared to 50% in the placebo group (p = 0.041). The primary MC in the ZA group converted more likely to M2-dominant (42.1% ZA, 15% placebo; p = 0.0119). The other MC (15 ZA, 8 placebo) were on average 42% smaller and remained largely M2-dominant. The M1 volume of the primary MC decreased in the ZA group, but increased in the placebo group (-0.83 cm3 vs 0.91 cm3; p = 0.21). The adjusted treatment difference for M1 volume was -1.9 cm3 (95% CI -5.0 to 1.2; p = 0.22) and for M2 volume 0.23 cm3 (p = 0.86). In the MC that remained M1-dominant, volume change correlated positively with increased symptoms in the placebo group, whereas the correlations were negative and weak in the ZA group. CONCLUSIONS: Zoledronic acid tended to speed up the conversion of M1-dominant into M2-dominant MC and decrease the volume of M1-dominant MC, although statistical significance was not demonstrated. TRIAL REGISTRATION: The registration number in ClinicalTrials.gov is NCT01330238 and the date of registration February 11, 2011.

Structure-symptom relationship with wide-area ultrasound scanning of knee osteoarthritis.

The aetiology of knee pain in osteoarthritis (OA) is heterogeneous and its relationship with structural changes and function is unclear. Our goal was to determine the prevalence of wide-area scanned ultrasound-defined knee OA structural features and their association with pain and functional impairment in 79 symptomatic and 63 asymptomatic subjects. All subjects underwent ultrasound knee wide-area scanning and the severity of articular cartilage degeneration, the presence and size of osteophytes, and meniscal extrusion were evaluated. Subjects filled in a self-administrated questionnaire on present knee pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) on clinical symptoms and function over the past week. Cartilage changes were the most prevalent followed by lateral meniscal extrusion, osteophytes and medial meniscal extrusion. The global femoral cartilage grade associated strongly with pain and the WOMAC index. Site-specifically, early medial cartilage changes and thinning in sulcus and lateral site were associated with symptoms. The presence of femoral lateral osteophytes was also associated with both outcomes. Using the novel wide-area ultrasound scanning technique, we were able to confirm the negative impact of femoral cartilage OA changes on clinical symptoms. Presence, not necessarily size, of lateral femoral osteophytes was also associated with increased pain and disability.

Real-time monitoring of human blood-brain barrier disruption.

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 µV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.

Combined spatiotemporal ICA (stICA) for continuous and dynamic lag structure analysis of MREG data.

This study investigated lag structure in the resting-state fMRI by applying a novel independent component (ICA) method to magnetic resonance encephalography (MREG) data. Briefly, the spatial ICA (sICA) was used for defining the frontal and back nodes of the default mode network (DMN), and the temporal ICA (tICA), which is enabled by the high temporal resolution of MREG (TR=100ms), was used to separate both neuronal and physiological components of these two spatial map regions. Subsequently, lag structure was investigated between the frontal (DMNvmpf) and posterior (DMNpcc) DMN nodes using both conventional method with all-time points and a sliding-window approach. A rigorous noise exclusion criterion was applied for tICs to remove physiological pulsations, motion and system artefacts. All the de-noised tICs were used to calculate the null-distributions both for expected lag variability over time and over subjects. Lag analysis was done for the three highest correlating denoised tICA pairs. Mean time lag of 0.6s (± 0.5 std) and mean absolute correlation of 0.69 (± 0.08) between the highest correlating tICA pairs of DMN nodes was observed throughout the whole analyzed period. In dynamic 2min window analysis, there was large variability over subjects as ranging between 1-10sec. Directionality varied between these highly correlating sources an average 28.8% of the possible number of direction changes. The null models show highly consistent correlation and lag structure between DMN nodes both in continuous and dynamic analysis. The mean time lag of a null-model over time between all denoised DMN nodes was 0.0s and, thus the probability of having either DMNpcc or DMNvmpf as a preceding component is near equal. All the lag values of highest correlating tICA pairs over subjects lie within the standard deviation range of a null-model in whole time window analysis, supporting the earlier findings that there is a consistent temporal lag structure across groups of individuals. However, in dynamic analysis, there are lag values exceeding the threshold of significance of a null-model meaning that there might be biologically meaningful variation in this measure. Taken together the variability in lag and the presence of high activity peaks during strong connectivity indicate that individual avalanches may play an important role in defining dynamic independence in resting state connectivity within networks.

Justification and active guideline implementation for spine radiography referrals in primary care.

Background Spinal disorders are a major public health problem. Appropriate diagnostic imaging is an essential part in the management of back complaints. Nevertheless, inappropriate imaging increases population collective dose and health costs without improving outcome. Purpose To determine the effects of active implementation of referral guidelines on the number and justification of spine radiography in primary care in one city. Material and Methods Specified guidelines for spine radiography were distributed to referring practitioners altogether three times during the study period. Educational lectures were provided before the guidelines were taken into use. The guidelines were also made available via the intranet. The number of spine radiography referrals during similar 6-month periods in the year preceding the interventions and the following 2 years was analyzed. Justification of 448 spine radiographs was assessed similarly. Results After interventions, the total number of spine radiography examinations decreased by 48% (P < 0.001) and that of cervical spine radiography by 46% ( P < 0.001), thoracic spine by 53% ( P < 0.001), and lumbar spine by 47% ( P < 0.001). The results persisted after 1-year follow-up. Before interventions, 24% of the cervical, 46% of the thoracic, and 32% of the lumbar spine radiography referrals were justified. After interventions, only justification of lumbar spine radiography improved significantly, 64% being justified ( P = 0.005). Conclusion Spine radiography in primary care can be reduced significantly by active referral guideline implementation. The proportion of inappropriate radiography was unexpectedly high. Thus, further education and studies concerning the appropriate use of spinal radiography seems to be needed.