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The dissertation consists of three peer-reviewed publications and is related to the basic research of autism spectrum disorder (ASD), especially the assessment of changes in brain function using functional magnetic resonance imaging (fMRI). The purpose was to discover possible differences in cued and spontaneous brain activity in autistic child and adolescent participants compared to typically developing controls. We used blood oxygen level dependent (BOLD) fMRI imaging of the brain, with which the participants were examined at rest and while looking at facial expressions. The resting state (RS) fMRI data artifacts were reduced, and brain networks were identified using independent component analysis. In addition, the RS was analyzed 1) over the entire measurement period using the regional homogeneity (ReHo) method, which measures local connectivity, and 2) based on the states of different brain networks grouped into shorter periods using the co-activation patterns (CAP) method. Statistically significant differences between groups were found in RS, more clearly with the CAP method. Also, significant differences in brain activity were found between the groups regarding the observation of facial expressions. The dissertation increases the understanding of changes in brain networks related to the autism spectrum, strengthening and supplementing previous research results. Based on our results, analyses of brain networks grouped into similar activation phases of shorter duration are worth further development. The new information can help develop earlier and more accurate imaging diagnostics, tentatively recognizing possible intervention target brain networks and evaluating therapeutic effects., Tiivistelmä Väitöskirja koostuu kolmesta vertaisarvioidusta julkaisusta ja liittyy autismikirjon kehityshäiriön perustutkimukseen, erityisesti aivotoiminnan muutosten arviointiin toiminnallisen magneettikuvauksen (functional MRI, fMRI) avulla. Tutkimuksen tarkoituksena oli selvittää stimuloidun ja spontaanin aivotoiminnan mahdollisia eroavaisuuksia lasten ja nuorten autismikirjossa neurotyypillisiin verrokkeihin nähden. Tutkimusmenetelmänä käytettiin veren happipitoisuudesta riippuvaista aivojen fMRI-kuvausta, jolla osallistujia tutkittiin levossa sekä heidän katsellessaan kasvojen ilmeitä. Itsenäisten komponenttien analyysilla (ICA) vähennettiin lepotilan fMRI-datan häiriöitä ja tunnistettiin aivoverkostoja. Lisäksi lepotilaa analysoitiin 1) koko mittausjakson ajalta signaalien alueellista homogeenisuutta ts. aivojen paikallista kytkennällisyyttä mittaavalla regional homogeneity (ReHo) -menetelmällä ja 2) eri aivoverkostojen tilojen perusteella lyhyemmiksi ajanjaksoiksi ns. yhtäaikaisten aktivaatioiden kuvioihin (co-activation patterns; CAP) ryhmiteltyinä. Näissä löydettiin tilastollisesti merkittäviä ryhmien välisiä eroja, selkeämmin CAP-menetelmällä. Myös kasvojen ilmeiden tarkkailuun liittyen havaittiin tilastollisesti merkittäviä aivotoiminnan eroja ryhmien välillä. Väitöskirja lisää ymmärrystä autismikirjoon liittyvistä aivoverkostojen muutoksista vahvistaen ja täydentäen aiempia tutkimustuloksia. Sen perusteella samankaltaisiin lyhempikestoisiin aktivaatiovaiheisiin ryhmiteltyjen aivoverkostojen analyyseja kannattaa kehittää. Uusi tieto voi auttaa varhaisemman ja tarkemman kuvantamisdiagnostiikan kehittämisessä, tarvittaessa oikeisiin aivoverkostoihin kohdennetuissa interventioissa ja niiden vaikutusten arvioinnissa ja seurannassa.

This paper presents a study on a monitoring vest embedded with multiple flexible ultrawideband (UWB) antenna elements used for detection of possible breast cancer tissue. The cancer detection is based on identifying differences in the UWB radio channel characteristics between several on-body antennas located around the breast. The antennas are small-sized, made of flexible material, operating at whole UWB band as well as in the ISM 2.4 GHz band, thus can be used in portable telemedicine applications. Additionally, the paper presents realistic simulation results on the impact of the cancer tissue on the signal propagation and channel characteristics at different frequency ranges using an anatomical voxel model. The simulations are carried out using electromagnetic simulation software CST Studio Suite, including power flow analysis and radio channel evaluations. The results show that, such as, tumor of size 1 cm causes a clear difference in a signal propagation through a breast tissue, which can be seen in a power flow variation in the vicinity of the cancerous area. This can be also seen both in frequency and time domain channel characteristics between different on-body antennas. The promising results show that flexible UWB antenna vest could be developed for self-monitoring of breast health and initial detection of breast cancers.

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.

When using ionizing radiation, justification must always be considered due to the possibility of radiation-promoted carcinogenesis. The radiation-induced lifetime risk of cancer mortality is higher in young age. A radiological examination is justified when the benefit to the patient is greater than the expected harm. Although the risk to an individual is small, the concern is attributed to the rapid increase in collective radiation doses, especially related to increased use of CT. Radiographies are still the most frequent examinations using ionizing radiation. The radiation dose of lumbar spine radiography is among the highest, and the radiation is delivered to radiation-sensitive organs. Imaging referral guidelines have been developed to support referrers in selecting and justifying radiological procedures. The purpose of this study was to follow up the effects of active guideline implementation, including education, on the volume and appropriateness of CTs and lumbar spine radiographs on young people in Oulu University Hospital and of spine radiographs in adults in primary care. Furthermore, the aim was to evaluate whether inappropriate lumbar spine radiographs in Oulu University Hospital had relevant findings. A statistically significant reduction in the number of CTs in young people was seen in lumbar spine (-80%), cervical spine (-48%) and head (-21%). The number of all spine radiographs decreased significantly; that of lumbar spine radiographs in university hospital by 37% and spine radiographs in primary care by 51%. The justification of performed examinations improved or remained unchanged in all categories. A significant change was seen in overall appropriateness of CTs, from 71% to 87%. The appropriateness of lumbar spine examinations in Oulu University Hospital and of lumbar spine radiographs in primary care improved significantly. However, the level of appropriateness of different spine radiographs in primary care remained low even after the int, Tiivistelmä Ionisoivasta säteilystä aiheutuvien haittavaikutusten, erityisesti syöpäriskin, vuoksi ionisoivalle säteilylle altistavilla kuvantamistutkimuksilla tulee olla oikeutus. Säteilystä aiheutuvan elinikäisen syöpäkuoleman riski on suurempi nuorilla. Tutkimus on oikeutettu, kun siitä potilaalle odotettavissa oleva hyöty on suurempi kuin säteilyaltistukseen liittyvä haitta. Vaikka yksilön riski on pieni, väestön nopeasti lisääntyvä kollektiivinen säteilyannos aiheuttaa huolta erityisesti tietokonetomografiatutkimusten (TT) lisääntymiseen liittyen. Tavanomaisia röntgentutkimuksia tehdään kuitenkin edelleen määrällisesti eniten. Lannerangan röntgentutkimus on yksi korkea-annoksisimmista ja siinä säteily kohdistuu säteilyherkille alueille. Kuvantamistutkimusten lähettämissuositukset on kehitetty tukemaan lähettäviä lääkäreitä sopivan ja oikeutetun tutkimuksen valitsemisessa. Tämän tutkimuksen tarkoitus oli seurata lähettämissuositusten ja koulutuksen vaikutusta kuvantamismääriin ja oikeutukseen nuorten TT-tutkimusten ja lannerangan röntgentutkimusten suhteen Oulun yliopistollisessa sairaalassa ja aikuisten rangan röntgentutkimusten suhteen perusterveydenhuollossa. Lisäksi tarkoitus oli selvittää, onko lähettämissuositusten vastaisissa lannerangan röntgentutkimuksissa merkittäviä kuvantamislöydöksiä. Nuorten TT-tutkimusten määrä aleni tilastollisesti merkitsevästi lannerangan (-80 %), kaularangan (-48 %) ja pään (-21 %) TT-tutkimuksissa. Myös rangan röntgentutkimusten määrä laski merkitsevästi: lannerangan röntgentutkimukset vähenivät yliopistosairaalassa 37 % ja rangan röntgentutkimukset perusterveydenhuollossa 51 %. Oikeutettujen tutkimusten osuus lisääntyi tai pysyi ennallaan. Nuorten oikeutettujen TT-tutkimusten osuus kasvoi merkitsevästi, 71 %:sta 87 %:iin. Myös lannerangan TT-tutkimusten oikeutus yliopistosairaalassa ja lannerangan röntgentutkimusten oikeutus sekä yliopistosairaalassa että perusterveydenhuollossa parantui merkitsevästi. Oikeutettujen rangan r

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.

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). Conclusions: Our study showed a significant and independent association between MC and clinically relevant LBP.

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.

Introduction: Adverse events in radiology are quite rare, but they do occur. Radiation safety regulations and the law obligate organizations to report certain adverse events, harm and near misses, especially events related to patients’ health and safety. The aim of this study was to describe and analyse incidents related to radiation safety issues reported in Finland. Methods: The data were collected from incident reports documented by radiology personnel concerning notifications of abnormal events in medical imaging made to the Radiation and Nuclear Safety Authority between 2010 and 2017. During these eight years, 312 reports were submitted. Only events reported from radiology departments were included; nuclear medicine, radiotherapy and animal radiology cases were excluded. The final number of reports was 293 (94%). Results: The majority of the 293 approved reports were related to computed tomography (CT, 68.3%) and to X-ray examinations (27.6%). Altogether 82.9% of those irradiated were adults, most of whom were exposed to unnecessary radiation through CT (86.5%), 5.5% were children, and 4.4% pregnant women. The most common effective dose of unnecessary radiation was 1 mSv or less (89.7% of all examinations). The highest effective doses were reported in CT (from under 1 mSv–20 mSv and above). The reasons for the adverse events were incorrect identification (32%), incorrect procedure, site or side (30%); and human errors or errors of knowledge (20%). Conclusion: Adverse events occurred especially in CT examinations. It is important to collect and analyse incident data, assess the harmful events, learn from them and aim to reduce adverse events. Implications for practice: This study emphasizes the need for radiological personnel to obtain evidence-based information on adverse events and focus on training to improve patient safety.

Lumbar degenerative bone marrow changes, Modic changes (MC), are visible in the bone marrow adjacent to the degenerated intervertebral discs in magnetic resonance imaging (MRI). MC are categorized into three types: Type 1 (MC1) appears as inflamed bone marrow and is composed mainly of fibrovascular tissue proliferation, Type 2 (MC2) appears as fat and is composed of yellow fat replacement, and Type 3 (MC3) appears as dense bone and is composed of highly mineralized, sclerotic bone marrow. This thesis investigated the associations of MC with bone turnover in bone scintigraphy and with prospective low back symptoms, and the treatment response of MC to a single intravenous infusion of zoledronic acid (ZA), an osteoporosis drug. Bone scintigraphy is a method of nuclear imaging which shows active bone turnover as increased tracer uptake in the skeleton. Patients who had undergone lumbar MRI and bone scintigraphy within six months of each other in 2007–2008 were included in the study. Bone turnover was increased in the area of MC1 more often than in other MC types. This reflects the inflammatory nature of MC1 and is consistent with increased vascularity and bone turnover. Patients with MC and low back symptoms were followed for over a two-year period. MC1 was associated with pain intensity and disability, whereas the same correlation was not found for MC2. In a randomized controlled trial, the effect of ZA on MC was compared with that of intravenous saline. MRI was examined at baseline and approximately 12 months after the infusion. A trend of MC1 converting to MC2, and a reduction in the volume of MC1 was noted as a result of ZA. In conclusion, MC1 is more consistently associated with increased bone turnover and low back symptoms than other MC types. ZA may offer an alternative treatment for MC1. However, more research must be conducted to confirm the benefits of ZA., Tiivistelmä Selkärangan välilevyrappeumaan liittyvät selkänikamien luuydinmuutokset näkyvät magneettikuvauksessa (MK) ja niitä kutsutaan Modic-muutoksiksi. Modic-muutokset jaetaan kolmeen tyyppiin: tyyppi 1 (MC1) on tulehduksellisen näköinen ja sisältää korostunutta verisuonitusta ja luuturvotusta, tyyppi 2 (MC2) sisältää rasvoittunutta luuydintä ja tyyppi 3 (MC3) sisältää mineraalipitoisuudeltaan korostunutta, skleroottista luuydintä. Tämä väitöskirjatutkimus sisältää kolme osatyötä, joissa on tutkittu Modic-muutosten yhteyttä luun aineenvaihduntaan luustokartassa, yhteyttä kipuun ja toimintakyvyn laskuun kahden vuoden seurantatutkimuksessa sekä hoitovastetta suonensisäiseen kerta-annoshoitoon tsoledronihapolla. Luustokartta on isotooppitutkimuksen muoto, joka osoittaa kiihtyneen luun aineenvaihdunnan korostuneena merkkiainekertymänä. Tutkimusotoksen potilailta oli kuvattu alaselän MK ja luustokartta 6kk sisällä toisistaan vuosina 2007–2008. Tutkimuksessa havaittiin MC1:n alueella muita Modic-tyyppejä useammin kiihtynyttä luun aineenvaihduntaa, joka sopii muutoksen tulehdukselliseen ilmiasuun ja kudosnäytteissä aiemmin todettuun verisuonituksen lisääntymiseen. Kahden vuoden seurantatutkimuksessa potilailla oli alaselkäoireita ja Modic-muutoksia. Tutkimuksessa havaittiin MC1:n olevan yhteydessä alaselkäkipuun ja toimintakyvyn laskuun, kun taas vastaavaa yhteyttä ei todettu MC2:n suhteen. Satunnaistetussa kaksoissokkotutkimuksessa verrattiin tsoledronihappoa lumelääkkeeseen Modic-muutosten hoidossa alaselkäkipuisilla potilailla. 12 kuukautta kerta-annoshoidon jälkeen tehdyssä MK:ssa todettiin tsoledronihapporyhmässä MC1:n muuttumista MC2:n suuntaan ja MC1:n tilavuuden pienentymistä, mutta muutokset eivät olleet tilastollisesti merkitseviä. Tutkimusten yhteenvetona voidaan todeta, että MC1 liittyy muita MC- tyyppejä useammin kiihtyneeseen luun aineenvaihduntaan ja alaselkäoireisiin. Tsoledronihappo saattaa tarjota hoitovaihtoehdon MC1:lle, mutta tämän vahvistaminen va

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. Materia 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.

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.

Objective: Epilepsy causes measurable irregularity over a range of brain signal frequencies, as well as autonomic nervous system functions that modulate heart and respiratory rate variability. Imaging dynamic neuronal signals utilizing simultaneously acquired ultra-fast 10 Hz magnetic resonance encephalography (MREG), direct current electroencephalography (DC-EEG), and near-infrared spectroscopy (NIRS) can provide a more comprehensive picture of human brain function. Spectral entropy (SE) is a nonlinear method to summarize signal power irregularity over measured frequencies. SE was used as a joint measure to study whether spectral signal irregularity over a range of brain signal frequencies based on synchronous multimodal brain signals could provide new insights in the neural underpinnings of epileptiform activity. Methods: Ten patients with focal drug-resistant epilepsy (DRE) and ten healthy controls (HC) were scanned with 10 Hz MREG sequence in combination with EEG, NIRS (measuring oxygenated, deoxygenated, and total hemoglobin: HbO, Hb, and HbT, respectively), and cardiorespiratory signals. After pre-processing, voxelwise SEMREG was estimated from MREG data. Different neurophysiological and physiological subfrequency band signals were further estimated from MREG, DC-EEG, and NIRS: fullband (0–5 Hz, FB), near FB (0.08–5 Hz, NFB), brain pulsations in very-low (0.009–0.08 Hz, VLFP), respiratory (0.12–0.4 Hz, RFP), and cardiac (0.7–1.6 Hz, CFP) frequency bands. Global dynamic fluctuations in MREG and NIRS were analyzed in windows of 2 min with 50% overlap. Results: Right thalamus, cingulate gyrus, inferior frontal gyrus, and frontal pole showed significantly higher SEMREG in DRE patients compared to HC. In DRE patients, SE of cortical Hb was significantly reduced in FB (p = .045), NFB (p = .017), and CFP (p = .038), while both HbO and HbT were significantly reduced in RFP (p = .038, p = .045, respectively). Dynamic SE of HbT was reduced in DRE patients in RF

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.

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 0.6 s (± 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 2 min window analysis, there was large variability over subjects as ranging between 1–10 sec. 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 0.0 s 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

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

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.

Osteoarthritis (OA) is a common degenerative musculoskeletal disease highly prevalent in aging societies worldwide. Traditionally, knee OA is diagnosed using conventional radiography. However, structural changes of articular cartilage or menisci cannot be directly evaluated using this method. On the other hand, ultrasound is a promising tool able to provide direct information on soft tissue degeneration. The aim of our study was to systematically determine the site-specific diagnostic performance of semi-quantitative ultrasound grading of knee femoral articular cartilage, osteophytes and meniscal extrusion, and of radiographic assessment of joint space narrowing and osteophytes, using MRI as a reference standard. Eighty asymptomatic and 79 symptomatic subjects with mean age of 57.7 years were included in the study. Ultrasound performed best in the assessment of femoral medial and lateral osteophytes, and medial meniscal extrusion. In comparison to radiography, ultrasound performed better or at least equally well in identification of tibio-femoral osteophytes, medial meniscal extrusion and medial femoral cartilage morphological degeneration. Ultrasound provides relevant additional diagnostic information on tissue-specific morphological changes not depicted by conventional radiography. Consequently, the use of ultrasound as a complementary imaging tool along with radiography may enable more accurate and cost-effective diagnostics of knee osteoarthritis at the primary healthcare level.