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Abstract Interval breast cancers are diagnosed between scheduled screenings and differ in many respects from screening-detected cancers. Studies comparing the survival of patients with interval and screening-detected cancers have reported differing results. The aim of this study was to investigate the radiological and histopathological features and growth rates of screening-detected and interval breast cancers and subsequent survival. This retrospective study included 942 female patients aged 50–69 years with breast cancers treated and followed-up at Kuopio University Hospital between January 2010 and December 2016. The screening-detected and interval cancers were classified as true, minimal-signs, missed, or occult. The radiological features were assessed on mammograms by one of two specialist breast radiologists with over 15 years of experience. A χ2 test was used to examine the association between radiological and pathological variables; an unpaired t test was used to compare the growth rates of missed and minimal-signs cancers; and the Kaplan–Meier estimator was used to examine survival after screening-detected and interval cancers. Sixty occult cancers were excluded, so a total of 882 women (mean age 60.4 ± 5.5 years) were included, in whom 581 had screening-detected cancers and 301 interval cancers. Disease-specific survival, overall survival and disease-free survival were all worse after interval cancer than after screening-detected cancer (p

Objectives: To examine the background parenchymal enhancement (BPE) levels in peri-menopausal breast MRI compared with pre- and post-menopausal breast MRI. Methods: This study included 562 patients (55.8±12.3 years) who underwent contrast-enhanced dynamic breast MRI between 2011 and 2015 for clinical indications. We evaluated the BPE level, amount of fibroglandular tissue (FGT), and social and clinical variables. The inter-reader agreement for the amount of FGT and the BPE level was evaluated using interclass correlation coefficients. Associations between the BPE level and body mass index (BMI), ages of menarche and menopause, childbirth history, number of children, and the amount of FGT were determined using Spearman’s correlation coefficients or Mann-Whitney U-test. Pearson’s χ2 test was used to assess the difference in the frequency of BPE categories among the age-groups. Results: The inter-reader agreement was 0.864 for the amount of FGT and 0.840 for the BPE level, both indicating almost perfect agreement. The BPE level showed a weak positive correlation with the amount of FGT (Spearman’s ρ=0.271, P

IntroductionIn this prospective cohort study over 40 years we investigated the effect of childhood attention-deficit/hyperactivity disorder (ADHD) and subthreshold ADHD on cognitive performance in adulthood.MethodsThe cohort comprised individuals with mild perinatal risks. Childhood ADHD group (cADHD, n = 39) was compared to a group with subthreshold childhood attention or hyperactivity symptoms (cAP; n = 79), a group with similar perinatal risks but no ADHD symptoms (n = 255), and to controls without ADHD symptoms or perinatal risks (n = 69). The groups were assessed with multiple neuropsychological measures in domains of verbal reasoning, perceptual skills, memory, working memory, attention, executive functions, and speed. Group-level differences and frequencies of deficient functioning were analyzed.ResultsOverall, the groups’ performance differed in all cognitive domains at age 40. Verbal reasoning, perceptual skills, memory, and speed had the largest effect sizes (0.51–0.62). The cADHD group’s performance was lower than the other groups’ on 13 out of 21 measures. The cAP group performed poorer than controls on five measures. In the cADHD group, 23% had three or more deficient cognitive domains, compared to 4–6% in the other groups.DiscussionChildhood ADHD is associated with impaired cognitive functioning in adulthood on several cognitive domains whereas childhood subthreshold ADHD is linked to fewer cognitive deficits. Task complexity was linked to poorer performance within the ADHD group. Our results add to the scarce longitudinal evidence of cognitive outcomes related to childhood ADHD and subthreshold symptoms.

Abstract Objectives Multiparametric magnetic resonance imaging (mMRI) is the modality of choice in the imaging of ovarian cancer (OC). We aimed to investigate the feasibility of different types of regions of interest (ROIs) in the measurement of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging in OC patients treated with neoadjuvant chemotherapy (NACT). Methods We retrospectively enrolled 23 consecutive patients with advanced OC who had undergone NACT and mMRI. Seventeen of them had been imaged before and after NACT. Two observers independently measured the ADC values in both ovaries and in the metastatic mass by drawing on a single slice of (1) freehand large ROIs (L-ROIs) covering the solid parts of the whole tumour and (2) three small round ROIs (S-ROIs). The side of the primary ovarian tumour was defined. We evaluated the interobserver reproducibility and statistical significance of the change in tumoural pre- and post-NACT ADC values. Each patient’s disease was defined as platinum-sensitive, semi-sensitive, or resistant. The patients were deemed either responders or non-responders. Results The interobserver reproducibility of the L-ROI and S-ROI measurements ranged from good to excellent (ICC range: 0.71–0.99). The mean ADC values were significantly higher after NACT in the primary tumour (L-ROI p

Abstract Background The use of point-of-care ultrasound (POCUS) is increasing. Numerous investigators have evaluated the learning curves in POCUS, but there are no published studies on how emergency physicians perceive their own competence level with this skill. Methods A nationwide survey amongst Finnish emergency physicians was conducted. The respondents reported their use of POCUS and how it has affected their clinical decision-making. The number of POCUS examinations performed was compared to the self-assessed skill level with different applications. Cut-off values were determined for the number of examinations required to acquire a good self-assessed skill level in each POCUS application. The correlation between self-confidence and the self-estimated skill level was analyzed. Several different statistical methods were used, such as Student’s t-test, Pearson’s correlation test, Loess method and ROC curve analysis. Results A total of 134 out of 253 Finnish emergency medicine specialists and residents (52%) responded to the survey. The most commonly used POCUS applications were POCUS-assisted procedures, pleural effusion and pneumothorax, inferior vena cava and lower extremity deep venous thrombosis. The initial rate of perceived skill acquisition was very steep with the curve flattening with greater skill and more experience. The number of examinations performed to reach a self-assessed good competence varied from seven to 75 with different applications. The lowest cut-off point for self-assessed good competence was obtained for rapid ultrasound for the shock and hypotension-protocol and the highest for focused cardiac examinations. There was an excellent correlation between self-confidence and the self-assessed skill level. Conclusions The Finnish emergency practitioners’ self-assessed development of POCUS skills parallels the previously published learning curves of POCUS. The correlation of self-confidence and the self-assessed skill level was found to be excellent. These findings add information on the development of perceived POCUS skills amongst emergency physicians and could complement a formal performance assessment.

Abstract Breast density, which is a measure of the relative amount of fibroglandular tissue within the breast area, is one of the most important breast cancer risk factors. Accurate segmentation of fibroglandular tissues and breast area is crucial for computing the breast density. Semiautomatic and fully automatic computer-aided design tools have been developed to estimate the percentage of breast density in mammograms. However, the available approaches are usually limited to specific mammogram views and are inadequate for complete delineation of the pectoral muscle. These tools also perform poorly in cases of data variability and often require an experienced radiologist to adjust the segmentation threshold for fibroglandular tissue within the breast area. This study proposes a new deep learning architecture that automatically estimates the area-based breast percentage density from mammograms using a weight-adaptive multitask learning approach. The proposed approach simultaneously segments the breast and dense tissues and further estimates the breast percentage density. We evaluate the performance of the proposed model in both segmentation and density estimation on an independent evaluation set of 7500 craniocaudal and mediolateral oblique-view mammograms from Kuopio University Hospital, Finland. The proposed multitask segmentation approach outperforms and achieves average relative improvements of 2.88% and 9.78% in terms of F-score compared to the multitask U-net and a fully convolutional neural network, respectively. The estimated breast density values using our approach strongly correlate with radiologists’ assessments with a Pearson’s correlation of $$r = 0.90$$ r = 0.90 (95% confidence interval [0.89, 0.91]). We conclude that our approach greatly improves the segmentation accuracy of the breast area and dense tissues; thus, it can play a vital role in accurately computing the breast density. Our density estimation model considerably reduces the time and effort needed to estimate density values from mammograms by radiologists and therefore, decreases inter- and intra-reader variability.

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is associated with negative life outcomes and recent studies have linked it to increased mortality. These studies have examined nationwide registers or clinic-referred samples and mostly included participants up until the age of 30. No studies have investigated mortality associated with subthreshold levels of ADHD symptoms. Our aim was to analyze mortality in a perinatal risk cohort of 46-year-old adults with childhood ADHD (cADHD) and milder childhood attention problems (including hyperactivity and inattention; cAP) compared with a group with similar birth risks but no or low levels of childhood ADHD symptoms (Non-cAP). Causes of death obtained from a national register were examined. Methods Mortality was analyzed with Cox proportional hazard models for all-cause mortality, cause-specific mortality (natural and unnatural causes), and age-specific mortality (under and over age 30). All models were adjusted with gender. The total n in the study was 839 (cADHD n = 115; cAP n = 216; Non-cAP n = 508). Results By the age of 46, 11 (9.6%) deaths occurred in the cADHD group, 7 (3.2%) in the cAP group, and 20 (3.9%) in the Non-cAP group. The cADHD group had the highest mortality risk (adjusted hazard ratio = 2.15; 95% CI 1.02, 4.54). Mortality was not elevated in the cAP group (adjusted hazard ratio = 0.72; 95% CI .30, 1.72). Mortality in the cADHD group was mainly attributed to unnatural causes of death (adjusted hazard ratio = 2.82; 95% CI 1.12, 7.12). The mortality risk in the cADHD group was sixfold before age 30 (adjusted hazard ratio = 6.20; 95% CI 1.78, 21.57). Conclusions Childhood ADHD was associated with a twofold risk of premature death by the age of 46 in this prospective longitudinal cohort study. Our results corroborate previous findings and the morbidity of ADHD. Subthreshold levels of childhood ADHD symptoms were not linked to increased mortality. Our results suggest that mortality risk is higher in young than middle adulthood. Future studies should examine mortality associated with ADHD in different ages in adulthood to identify those in greatest risk of premature death.

Abstract Background Despite the new lymphatic imaging methods, there is still a need for a straightforward method of detecting lymphatic abnormalities. Our goal was to investigate the feasibility of applying a contrast enhanced ultrasound (CEUS) procedure as a new approach for visualising the superficial lymphatic vessels of the upper limb. Methods Thirty healthy volunteers were examined with CEUS after bilateral intradermal injection of Sonazoid® contrast agent in distal antebrachium. We registered factors affecting intradermal injections, imaging of the superficial lymphatic vessels and the enhancement time of contrast agent reaching the levels of elbow and axilla. Results CEUS imaging of superficial lymphatic vessels was successful in 59 of 60 upper limbs (98.3%). Median [interquartile ranges] enhancement times of contrast agent to reach the elbow (right 18 s [11–25], left 15 s [12–25]) and axilla (right 77 s [33–118], left 66 s [42–115]) were equally fast. Successful intradermal injections were found to result in two types of contrast enhancement (strong or moderate), while the enhancement time depended on the type of the successful injection. No major differences in enhancement times were observed related to sex, body mass index, age, or side of the arm. Conclusions The superficial lymphatic pathways of the upper limb can be visualised with CEUS imaging. Since enhancement time is dependent on the success of intradermal injections, one must pay attention to the injection technique. Further studies are needed to evaluate the method in patients with lymphatic function disorders such as breast cancer therapy related lymphoedema.

Purpose: Progressive myoclonic epilepsy, type 1A (EPM1, Unverricht-Lundborg disease), is a rare neurodegenerative autosomal recessive disorder characterized by stimulus-sensitive and action myoclonus and tonic-clonic epileptic seizures. Patients develop neurological symptoms, including ataxia, intention tremor, and dysarthria, over time, with relatively limited and nonspecific MRI atrophy findings. The effects of the disease on brain metabolism are largely unknown. Method: Eighteen EPM1 patients (9 M, 9F) underwent clinical evaluation and neuropsychological testing, which included the assessment of intellectual ability, verbal memory, and psychomotor and executive functions. Magnetic resonance spectroscopy (MRS) and imaging (MRI) were performed on a 1.5 T MRI system. 2D MRS chemical shift imaging (CSI) maps (TE = 270) were obtained from the following regions of the brain: basal ganglia, thalamus, insula, splenium, and occipital white and gray matter, and N-acetyl-aspartate (NAA)-, choline (Cho)-, and lactate (Lac)-to-creatine (Cr) ratios were analyzed. Ten healthy age-and sex-matched subjects (5M, 5F) were used as controls for MRS. Results: We found significant brain metabolic changes involving lactate, NAA, and choline, which are widespread in the basal ganglia, thalamic nuclei, insula, and occipital areas of EPM1 patients. Changes, especially in the right insula, basal ganglia, and thalamus, were associated with intellectual abilities and impairment of the psychomotor and executive functions of EPM1 patients. Conclusion: Multiple brain metabolic alterations suggest the presence of neurodegeneration associated with EPM1 progression. The changes in metabolite ratios are associated with the neurocognitive dysfunction caused by the disease. However, the role of MRS findings in understanding pathophysiology of EPM1 warrants further studies.

PurposeTo evaluate whether 1) the intratumoral apparent diffusion coefficients (ADCs) change during cervical cancer treatment and 2) the pretreatment ADC values or their change after treatment predict the treatment outcome or overall survival of patients with cervical cancer.MethodsWe retrospectively enrolled 52 patients with inoperable cervical cancer treated with chemoradiotherapy, who had undergone diffusion weighted MRI before treatment and post external beam radiotherapy (EBRT) and concurrent chemotherapy. A subgroup of patients (n = 28) underwent altogether six consecutive diffusion weighted MRIs; 1) pretreatment, 2) post-EBRT and concurrent chemotherapy; 3-5) during image-guided brachytherapy (IGBT) and 6) after completing the whole treatment course. To assess interobserver and intertechnique reproducibility two observers independently measured the ADCs by drawing freehand a large region of interest (L-ROI) covering the whole tumor and three small ROIs (S-ROIs) in areas with most restricted diffusion.ResultsReproducibility was equally good for L-ROIs and S-ROIs. The pretreatment ADCs were higher in L-ROIs (883 mm2/s) than in S-ROIs (687 mm2/s, P < 0.001). The ADCs increased significantly between the pretreatment and post-EBRT scans (L-ROI: P < 0.001; S-ROI: P = 0.001). The ADCs remained significantly higher than pretreatment values during the whole IGBT. Using S-ROIs, greater increases in ADCs between pretreatment and post-EBRT MRI predicted better overall survival (P = 0.018).ConclusionADC values significantly increase during cervical cancer treatment. Greater increases in ADC values between pretreatment and post-EBRT predicted better overall survival using S-ROIs. Standardized methods for timing and delineation of ADC measurements are advocated in future studies.

Abstract We propose a novel multi-level dilated residual neural network, an extension of the classical U-Net architecture, for biomedical image segmentation. U-Net is the most popular deep neural architecture for biomedical image segmentation, however, despite being state-of-the-art, the model has a few limitations. In this study, we suggest replacing convolutional blocks of the classical U-Net with multi-level dilated residual blocks, resulting in enhanced learning capability. We also propose to incorporate a non-linear multi-level residual blocks into skip connections to reduce the semantic gap and to restore the information lost when concatenating features from encoder to decoder units. We evaluate the proposed approach on five publicly available biomedical datasets with different imaging modalities, including electron microscopy, magnetic resonance imaging, histopathology, and dermoscopy, each with its own segmentation challenges. The proposed approach consistently outperforms the classical U-Net by 2%, 3%, 6%, 8%, and 14% relative improvements in dice coefficient, respectively for magnetic resonance imaging, dermoscopy, histopathology, cell nuclei microscopy, and electron microscopy modalities. The visual assessments of the segmentation results further show that the proposed approach is robust against outliers and preserves better continuity in boundaries compared to the classical U-Net and its variant, MultiResUNet.

Abstract Background Brain atrophy appears during the progression of multiple sclerosis (MS) and is associated with the disability caused by the disease. Methods We investigated global and regional grey matter (GM) and white matter (WM) volumes, WM lesion load, and corpus callosum index (CCI), in benign relapsing‐remitting MS (BRRMS, n = 35) with and without any treatment and compared those to aggressive relapsing‐remitting MS (ARRMS, n = 46). Structures were analyzed by using an automated MRI quantification tool (cNeuro®). Results The total brain and cerebral WM volumes were larger in BRRMS than in ARRMS (p = .014, p = .017 respectively). In BRRMS, total brain volumes, regional GM volumes, and CCI were found similar whether or not disease‐modifying treatment (DMT) was used. The total (p = .033), as well as subcortical (p = .046) and deep WM (p = .041) lesion load volumes were larger in BRRMS patients without DMT. Cortical GM volumes did not differ between BRRMS and ARRMS, but the volumes of total brain tissue (p = .014) and thalami (p = .003) were larger in patients with BRRMS compared to ARRMS. A positive correlation was found between CCI and whole‐brain volume in both BRRMS (r = .73, p

Maternal diabetes mellitus in pregnancy is associated with impairments in memory functions of the offspring in childhood and adolescence but has not been studied in adulthood. The association of perinatal hypoglycemia with memory has not been studied in adulthood either. The combined sequelae of these two risk factors have not been directly compared. We studied general cognitive ability and memory functions in a prospective follow-up of a cohort born in 1971 to 1974. The sample included participants exposed to prenatal hyperglycemia (n = 24), perinatal hypoglycemia (n = 19), or both (n = 7). It also included controls with no early risks (n = 82). We assessed the participants' Intelligence quotient (IQ), working memory, and immediate and delayed recall of both verbal and visual material at the age of 40. We did not find significant differences in IQ or the memory tests between the groups. We did identify an interaction (p = 0.03) of the early risk with the type of digit span task: compared to the controls, the participants exposed to perinatal hypoglycemia had a larger difference between the forward digit span, a measure of attention, and the backward digit span, a measure of working memory processing (p = 0.022). The interaction remained significant when birth weight was controlled for (p = 0.026). Thus, in this small cohort, prenatal hyperglycemia, perinatal hypoglycemia, and their combination appeared relatively benign disorders. The association of these conditions with neurocognitive impairments in adulthood remains unconfirmed. The significance of the working memory difference needs to be verified with a larger sample.

Objectives: In thoracic aortic aneurysm (TAA) of the ascending aorta (AA), AA is progressively dilating due to the weakening of the aortic wall. Predicting and preventing aortic dissections and ruptures in TAA continues to be challenging, and more accurate assessment of the AA dilatation, identification of high-risk patients, and timing of repair surgery are required. We investigated whether wall shear stress (WSS) predicts pathological and biomechanical changes in the aortic wall in TAA.Methods: The study included 12 patients with bicuspid (BAV) and 20 patients with the tricuspid aortic valve (TAV). 4D flow magnetic resonance imaging (MRI) was performed a day before aortic replacement surgery. Biomechanical and histological parameters, including assessing of wall strength, media degeneration, elastin, and cell content were analyzed from the resected AA samples.Results: WSSs were greater in the outer curves of the AA compared to the inner curves in all TAA patients. WSSs correlated with media degeneration of the aortic wall (ρ = -0.48, p < 0.01), elastin content (ρ = 0.47, p < 0.01), and aortic wall strength (ρ = -0.49, p = 0.029). Subsequently, the media of the outer curves was thinner, more rigid, and tolerated lower failure strains. Failure values were shown to correlate with smooth muscle cell (SMC) density (ρ = -0.45, p < 0.02), and indicated the more MYH10+ SMCs the lower the strength of the aortic wall structure. More macrophages were detected in patients with severe media degeneration and the areas with lower WSSs.Conclusion: The findings indicate that MRI-derived WSS predicts pathological and biomechanical changes in the aortic wall in patients with TAA and could be used for identification of high-risk patients.

Abstract Background The aim of this retrospective study was to determine whether diagnosing a deep venous thrombosis (DVT) in primary health care using limited compression ultrasound (LCUS) can save resources compared to referring these patients to hospital. According to the current literature, LCUS is as safe as a standard protocol based on a whole-leg ultrasound (US). Methods We created a standardized patient for this cost-analysis model based on 76 patients that were referred to hospital for a suspected DVT. Travel distance to the health care centre and hospital was calculated based on the home address. Hospital costs were acquired from the hospital price list and Finnish legislation. Time spent in the hospital was retrieved from hospital statistics. Time spent in the health care centre and travelling were estimated and monetized based on average salary. The cost of participating physicians attending a US training course was estimated based on the national average salary of a general practitioner as well as the course participation fee. A cost-minimization modeling was performed for this standardized patient comparing the total costs, including private and public costs, of standard and LCUS strategies. Results The total costs per patient of standard and LCUS pathways were 1151.52€ and 301.94€ [difference 849.59€ (95% CI 800.21€–898.97€, p

Abstract Background The aim of this study was to retrospectively determine whether teaching limited compression ultrasound (LCUS) to general practitioners (GP) would reduce the number of patients with a suspected lower extremity DVT referred to a hospital for ultrasound (US) examination. According to the current literature, an LCUS protocol is a safe way to diagnose or exclude lower extremity deep venous thrombosis (DVT) and a good option to radiologist-performed whole-leg ultrasound (US), especially in remote health care units where there may be a limited availability of radiological services. Methods Between 2015 and 2016, altogether 13 GPs working in the same primary care unit were trained in LCUS for DVT diagnostics. The number of annual referrals due to a suspected DVT from Saarikka primary care unit to the closest hospital was evaluated before and after training. The incidence of DVT was considered to be constant. Thus, the reduction of referrals was attributed to the fact that these patients were diagnosed and treated in primary health care. Incidence rate ratio of hospital referrals was calculated. As a measure of safety, all patients diagnosed with a pulmonary embolism in the nearest hospital were evaluated to determine if they had undergone LCUS by a GP in primary care. Results Before training in 2014, there were 60 annual referrals due to a suspected DVT; in 2017, after training, the number was reduced to 16, i.e., a 73.3% decrease. The incidence of referrals decreased from 3.21 to 0.89 per 1000 person-years. (IRR 3.58, 95% CI 2.04–6.66, p

Abstract Objective The aim of the present study was to compare the levels of serum neurofilament light chain (sNfL) in frontotemporal lobar degeneration (FTLD) patients of different clinical subtypes (bvFTD, PPA, and FTLD‐MND) and with or without the C9orf72 repeat expansion, and to correlate sNfL levels to disease progression, assessed by the brain atrophy rate and survival time. Methods The sNfL levels were determined from 78 FTLD patients (C9orf72 repeat expansion carriers [n = 26] and non‐carriers [n = 52]) with Single Molecule Array (SIMOA). The progression of brain atrophy was evaluated using repeated T1‐weighted MRI scans and the survival time from medical records. Results In the total FTLD cohort, sNfL levels were significantly higher in C9orf72 repeat expansion carriers compared to non‐carriers. Considering clinical phenotypes, sNfL levels were higher in the C9orf72 repeat expansion carriers than in the non‐carriers in bvFTD and PPA groups. Furthermore, sNfL levels were the highest in the FTLD‐MND group (median 105 pg/mL) and the lowest in the bvFTD group (median 27 pg/mL). Higher sNfL levels significantly correlated with frontal cortical atrophy rate and subcortical grey matter atrophy rate. The higher sNfL levels also associated with shorter survival time. Interpretation Our results indicate that the C9orf72 repeat expansion carriers show elevated sNFL levels compared to non‐carriers and that the levels differ among different clinical phenotypes of FTLD. Higher sNfL levels correlated with a shorter survival time and cortical and subcortical atrophy rates. Thus, sNfL could prove as a potential prognostic biomarker in FTLD.

PurposeTo assess the ability of 2D-Shear wave elastography (2D-SWE) to evaluate its reproducibility, to define the optimal orientation and size of the region of interest (ROI), and to differentiate benign from malignant inguinal lymph nodes (LNs).MethodThirty-two suspicious inguinal LNs from 21 patients were evaluated with 2D-SWE. SWE measurements were obtained in two orthogonal planes. To investigate reproducibility, sensitivity and specificity, circular ROIs with a diameter of 1 mm, 2 mm, 3 mm and 5 mm were placed on the cortex of the LNs. Additionally, one freehand ROI was drawn covering majority of the LN. Two observers performed five sets of SWE measurements for each ROI size. All LNs underwent core needle biopsy or were surgically removed.ResultsThe 3 mm ROI for Mean-E in axial plane showed high interrater agreement [intraclass correlation coefficient (ICC) 0.899] with the cut-off value of 7.31 kPa resulting in 88.9% sensitivity and 60.9% specificity for differentiating malignant from benign LNs. In benign LNs, mean elasticity of the ROI was lower (7.68 ± 3.82 kPa; range, 3.41-15.40 kPa) compared to the malignant LNs (15.81 ± 10.61 kPa; range, 3.86-36.45 kPa).ConclusionsThe most reproducible way to measure stiffness in inguinal LNs is a 3 mm circular ROI centered on the cortex of the LN in axial plane. Elasticity values were higher in the malignant LNs reflecting the stiffer nature of the metastatic LNs. 2D-SWE offers a noninvasive ultrasonographic tool to assess superficial inguinal lymph nodes with high reproducibility.

Aims: There are very few detailed post-mortem studies on idiopathic normal-pressure hydrocephalus (iNPH) and there is a lack of proper neuropathological criteria for iNPH. This study aims to update the knowledge on the neuropathology of iNPH and to develop the neuropathological diagnostic criteria of iNPH. Methods: We evaluated the clinical lifelines and post-mortem findings of 29 patients with possible NPH. Pre-mortem cortical brain biopsies were taken from all patients during an intracranial pressure measurement or a cerebrospinal fluid (CSF) shunt surgery. Results: The mean age at the time of the biopsy was 70±8 SD years and 74±7 SD years at the time of death. At the time of death, 11/29 patients (38%) displayed normal cognition or mild cognitive impairment (MCI), 9/29 (31%) moderate dementia and 9/29 (31%) severe dementia. Two of the demented patients had only scarce neuropathological findings indicating a probable hydrocephalic origin for the dementia. Amyloid-β (Aβ) and hyperphosphorylated τ (HPτ) in the biopsies predicted the neurodegenerative diseases so that there were 4 Aβ positive/low Alzheimer’s disease neuropathological change (ADNC) cases, 4 Aβ positive/intermediate ADNC cases, 1 Aβ positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HPτ/PSP and primary age-related tauopathy (PART) case, 1 Aβ/HPτ and low ADNC/synucleinopathy case and 1 case with Aβ/HPτ and high ADNC. The most common cause of death was due to cardiovascular diseases (10/29, 34%), followed by cerebrovascular diseases or subdural hematoma (SDH) (8/29, 28%). Three patients died of a postoperative intracerebral hematoma (ICH). Vascular lesions were common (19/29, 65%). Conclusions: We update the suggested neuropathological diagnostic criteria of iNPH, which emphasize the rigorous exclusion of all other known possible neuropathological causes of dementia. Despite the first 2 probable cases reported here, the issue of “hydrocephalic dementia” as an independent entity still requires further confirmation. Extensive sampling (with fresh frozen tissue including meninges) with age-matched neurologically healthy controls is highly encouraged.

Abstract Background The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (general health advice). This study reports exploratory analyses of brain MRI measures. Methods FINGER targeted 1260 older individuals from the general Finnish population. Participants were 60–77 years old, at increased risk for dementia but without dementia/substantial cognitive impairment. Brain MRI scans were available for 132 participants (68 intervention, 64 control) at baseline and 112 participants (59 intervention, 53 control) at 2 years. MRI measures included regional brain volumes, cortical thickness, and white matter lesion (WML) volume. Cognition was assessed at baseline and 1- and 2-year visits using a comprehensive neuropsychological test battery. We investigated the (1) differences between the intervention and control groups in change in MRI outcomes (FreeSurfer 5.3) and (2) post hoc sub-group analyses of intervention effects on cognition in participants with more versus less pronounced structural brain changes at baseline (mixed-effects regression models, Stata 12). Results No significant differences between the intervention and control groups were found on the changes in MRI measures. Beneficial intervention effects on processing speed were more pronounced in individuals with higher baseline cortical thickness in Alzheimer’s disease signature areas (composite measure of entorhinal, inferior and middle temporal, and fusiform regions). The randomization group × time × cortical thickness interaction coefficient was 0.198 (p = 0.021). A similar trend was observed for higher hippocampal volume (group × time × hippocampus volume interaction coefficient 0.1149, p = 0.085). Conclusions The FINGER MRI exploratory sub-study did not show significant differences between the intervention and control groups on changes in regional brain volumes, regional cortical thicknesses, or WML volume after 2 years in at-risk elderly without substantial impairment. The cognitive benefits on processing speed of the FINGER intervention may be more pronounced in individuals with fewer structural brain changes on MRI at baseline. This suggests that preventive strategies may be more effective if started early, before the occurrence of more pronounced structural brain changes. Trial registration ClinicalTrials.gov, NCT01041989. Registered January 5, 2010.

The development of the organization of the motor representation areas in children and adolescents is not well-known. This cross-sectional study aimed to provide an understanding for the development of the functional motor areas of the upper extremity muscles by studying healthy right-handed children (6–9 years, n = 10), preadolescents (10–12 years, n = 13), adolescents (15–17 years, n = 12), and adults (22–34 years, n = 12). The optimal representation site and resting motor threshold (rMT) for the abductor pollicis brevis (APB) were assessed in both hemispheres using navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed at 110% of the rMT while recording the EMG of six upper limb muscles in the hand and forearm. The association between the motor map and manual dexterity (box and block test, BBT) was examined. The mapping was well-tolerated and feasible in all but the youngest participant whose rMT exceeded the maximum stimulator output. The centers-of-gravity (CoG) for individual muscles were scattered to the greatest extent in the group of preadolescents and centered and became more focused with age. In preadolescents, the CoGs in the left hemisphere were located more laterally, and they shifted medially with age. The proportion of hand compared to arm representation increased with age (p = 0.001); in the right hemisphere, this was associated with greater fine motor ability. Similarly, there was less overlap between hand and forearm muscles representations in children compared to adults (p

PurposeThis single-center study compared three threshold settings for automated analysis of the ischemic core (IC) and penumbral volumes using computed tomographic perfusion, and their accuracy for predicting final infarct volume (FIV) in patients with anterior circulation acute ischemic stroke (AIS).MethodsFifty-two consecutive AIS patients undergoing mechanical thrombectomy (November 2015-March 2018) were included. Perfusion images were retrospectively analyzed using a single CT Neuro perfusion application (syngo.via 4.1, Siemens Healthcare GmbH). Three threshold values (S1-S3) were derived from another commercial package (RAPID; iSchema View) (S1), up-to-date syngo.via default values (S2), and adapted values for syngo.via from a reference study (S3). The results were compared with FIV determined by non-contrast CT.ResultsThe median IC volume (mL) was 24.6 (interquartile range: 13.7-58.1) with S1 and 30.1 (20.1-53.1) with S2/S3. After removing the contralateral hemisphere from the analysis, the median IC volume decreased by 1.33(0-3.14) with S1 versus 9.13 (6.24-14.82) with S2/S3. The median penumbral volume (mL) was 74.52 (49.64-131.91), 77.86 (46.56-99.23), and 173.23 (125.86-200.64) for S1, S2, and S3, respectively. Limiting analysis to the affected hemisphere, the penumbral volume decreased by 1.6 (0.13-9.02), 19.29 (12.59-26.52), and 58.33 mL (45.53-74.84) for S1, S2, and S3, respectively. The correlation between IC and FIV was highest in patients with successful recanalization (n = 34, r = 0.784 for S1; r = 0.797 for S2/S3).ConclusionOptimizing thresholds significantly improves the accuracy of estimated IC and penumbral volumes. Current recommended values produce diversified results. International guidelines based on larger multicenter studies should be established to support the standardization of volumetric analysis in clinical decision-making.

PurposeThe apparent diffusion coefficient (ADC) is increasingly used to characterize breast cancer. The peritumor/tumor ADC ratio is suggested to be a reliable and generally applicable index. However, its overall prognostication value remains unclear. We aimed to evaluate the associations between the peritumor/tumor ADC ratio and histopathological biomarkers and published prognostic tools in patients with invasive breast cancer.Materials and methodsThis prospective study included 88 lesions (five bilateral) in 83 patients with primary invasive breast cancer who underwent preoperative 3.0-T magnetic resonance imaging. The lowest intratumoral mean ADC value on the slice with the largest tumor cross-sectional area was designated the tumor ADC, and the highest mean ADC value on the peritumoral breast parenchymal tissue adjacent to the tumor border was designated the peritumor ADC. The peritumor/tumor ADC ratio was then calculated. The tumor and peritumor ADC values and peritumor/tumor ADC ratios were compared with histopathological parameters using an unpaired t test, and their correlations with published prognostic tools were evaluated with Pearson's correlation coefficient.ResultsThe peritumor/tumor ADC ratio was significantly associated with tumor size (pConclusionThe peritumor/tumor ADC ratio was correlated with histopathological biomarkers in patients with invasive breast cancer, showed significant correlations with published prognostic indexes, and may provide an easily applicable imaging index for the preoperative prognostic evaluation of breast cancer.

Aims: We assessed the value of automated MRI quantification methods in the differential diagnosis of behavioral-variant frontotemporal dementia (bvFTD) from Alzheimer disease (AD), Lewy body dementia (LBD), and subjective memory complaints (SMC). We also examined the role of the C9ORF72-related genetic status in the differentiation sensitivity. Methods: The MRI scans of 50 patients with bvFTD (17 C9ORF72 expansion carriers) were analyzed using 6 quantification methods as follows: voxel-based morphometry (VBM), tensor-based morphometry, volumetry (VOL), manifold learning, grading, and white-matter hyperintensities. Each patient was then individually compared to an independent reference group in order to attain diagnostic suggestions. Results: Only VBM and VOL showed utility in correctly identifying bvFTD from our set of data. The overall classification sensitivity of bvFTD with VOL + VBM achieved a total sensitivity of 60%. Using VOL + VBM, 32% were misclassified as having LBD. There was a trend of higher values for classification sensitivity of the C9ORF72 expansion carriers than noncarriers. Conclusion: VOL, VBM, and their combination are effective in differential diagnostics between bvFTD and AD or SMC. However, MRI atrophy profiles for bvFTD and LBD are too similar for a reliable differentiation with the quantification methods tested in this study.

Our aim was to investigate the association between behavioral symptoms of agitation, disinhibition, irritability, elation, and aberrant motor behavior to frontal brain volumes in a cohort with various neurodegenerative diseases. A total of 121 patients with mild cognitive impairment (MCI, n = 58), Alzheimer's disease (AD, n = 45) and behavioral variant frontotemporal dementia (bvFTD, n = 18) were evaluated with a Neuropsychiatric Inventory (NPI). A T1-weighted MRI scan was acquired for each participant and quantified with a multi-atlas segmentation method. The volumetric MRI measures of the frontal lobes were associated with neuropsychiatric symptom scores with a linear model. In the regression model, we included CDR score and TMT B time as covariates to account for cognitive and executive functions. The brain volumes were corrected for age, gender and head size. The total behavioral symptom score of the five symptoms of interest was negatively associated with the volume of the subcallosal area (β = −0.32, p = 0.002). High disinhibition scores were associated with reduced volume in the gyrus rectus (β = −0.30, p = 0.002), medial frontal cortex (β = −0.30, p = 0.002), superior frontal gyrus (β = −0.28, p = 0.003), inferior frontal gyrus (β = −0.28, p = 0.005) and subcallosal area (β = −0.28, p = 0.005). Elation scores were associated with reduced volumes of the medial orbital gyrus (β = −0.30, p = 0.002) and inferior frontal gyrus (β = −0.28, p = 0.004). Aberrant motor behavior was associated with atrophy of frontal pole (β = −0.29, p = 0.005) and the subcallosal area (β = −0.39, p < 0.001). No significant associations with frontal brain volumes were found for agitation and irritability. We conclude that the subcallosal area may be common neuroanatomical area for behavioral symptoms in neurodegenerative diseases, and it appears to be independent of disease etiology.

BackgroundHypoxia significantly influences treatment response and clinical outcome in solid tumors. A noninvasive marker for hypoxia will help physicians in treatment planning and encourage the efficient use of hypoxia targeted therapies. The purpose of this study was to investigate whether pharmacokinetic dynamic contrast-enhanced (DCE) perfusion parameters are associated with a specific marker of hypoxia, hypoxia-inducible factor 1 alpha (HIF-1α) in ovarian cancer (OC).Materials and methodsThirty-eight patients with primary OC were enrolled in this prospective study approved by the local ethical committee. Patients underwent dynamic gadolinium-enhanced 3.0 T MRI as part of their staging investigations. Pharmacokinetic perfusion parameters, including a rate constant for transfer of contrast agent from plasma to extravascular extracellular space (EES) (Ktrans) and a rate constant from EES to plasma (Kep), were measured by drawing two types of regions of interest (ROIs): a large solid lesion (L-ROI) and a solid, most enhancing small area (S-ROI) (NordicICE platform). Tissue samples for immunohistochemical analysis were collected during surgery. Kruskal-Wallis, Mann-Whitney U and Chi-square tests were used in statistical analyses. Receiver Operating Characteristic curve analyzes were done for DCE parameters to discriminate high HIF-1α expression.ResultsPharmacokinetic perfusion parameters Ktrans and Kep were inversely associated with HIF-1α expression (Ktrans L-ROI P = 0.021; Ktrans S-ROI P = 0.018 and Kep L-ROI P = 0.032; Kep S-ROI P = 0.033). Ktrans and Kep showed good accuracy in identifying high HIF-1α expression (AUC = 0.832 Ktrans L-ROI; 0.840 Ktrans S-ROI; 0.808 Kep L-ROI and 0.808 Kep L-ROI).ConclusionThis preliminary study demonstrated that pharmacokinetic DCE-MRI perfusion parameters are associated with the hypoxia specific marker, HIF-1α in OC. DCE-MRI may be a useful supplementary tool in the characterization of OC tumors in a staging investigation.

Background: Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. Aims: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). Methods: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases. We utilized data from neuropsychological tests, volumetric magnetic resonance imaging, single-photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype. The DSI classification results were calculated with a combination of leave-one-out cross-validation and bootstrapping. A DSF visualization of a FTD patient is presented as an example. Results: The DSI distinguishes controls from FTD (area under the receiver-operator curve, AUC = 0.99) and AD (AUC = 1.00) very well and achieves a good differential diagnosis between AD and FTD (AUC = 0.89). In subsamples of autopsy-confirmed cases (AUC = 0.97) and clinically diagnosed cases (AUC = 0.94), differential diagnosis of AD and FTD performs very well. Conclusions: DSI is a promising computer-assisted biomarker approach for aiding in the diagnostic process of dementing diseases. Here, DSI separates controls from dementia and differentiates between AD and FTD.

PURPOSE:To evaluate the malignancy rate and diagnostic performance of galactography in patients with pathological nipple discharge (PND) after negative clinical breast examination, mammography and ultrasound. MATERIALS AND METHODS:We retrospectively evaluated all galactograms obtained between January 2006 and December 2014 in women with PND. Galactographic findings were classified into 6 groups according to a modified Galactogram Image Classification system (GICS) to comply with the breast imaging reporting and data system classification. Observers were blinded to the final histology and clinical outcome at the time of analysis. MRI was performed as a problem solving ancillary examination. Imaging findings, pathological diagnosis and follow-up data were evaluated. The diagnostic performance of MRI and technically successful galactography in the detection of neoplastic or risk lesions were separately calculated. RESULTS:A total of 146 patients with PND (mean age, 51.5 years; range, 17-93) were examined. Malignant lesions were detected in only 4 patients (2.7%) and risk-lesions in 5 patients (3.4%). Only one low-grade ductal carcinoma in situ was missed by galactography (GICS 1) and MRI. MRI examinations were performed in 21 (14.4%) patients; one of these patients (4.8%) had a malignant finding (GICS 0), two (9.5%) had risk-lesions (GICS 2 and 5). In the detection of neoplastic or risk lesions the sensitivity and specificity of galactography were 77.4% and 75.7% and of MRI 85.7% and 71.4%, consecutively. CONCLUSION:The malignancy rate is negligible if clinical, mammography, ultrasound and galactography examinations are negative. Galactography remains a practical, valuable and cost-effective examination procedure. If galactography is technically unsuccessful, MRI should be considered as an additional ancillary tool to evaluate the possible etiology of symptoms, but the routine use of MRI in all patients cannot be justified.

AIMS:A chronically elevated level of von Willebrand factor (vWF) is a common finding in patients with cardiovascular diseases. Obesity is a well-recognized risk factor for thrombotic cardiovascular complications including ischemic stroke, and it has been linked with increased plasma vWF. We evaluated whether elevated plasma levels of vWF associate with areas of visceral (VAT), pericardial (PAT), and subcutaneous adipose tissue (SAT) compartments in patients with acute/subacute stroke. METHODS AND RESULTS:A total of 69 patients with stroke of suspected cardiogenic etiology were examined. The plasma level of vWF antigen (vWF-ag) was measured both in the acute phase and in the chronic phase three months after stroke. The areas of VAT and/or PAT were assessed with computed tomography. As expected, in stroke patients, the levels of plasma vWF-ag were significantly higher than in the national reference population both in the acute and in the chronic phase. The level of vWF-ag in the chronic phase correlated with the amounts of VAT and PAT, but not with subcutaneous adipose tissue. CONCLUSIONS:These results agree with previous observations of the chronic inflammation/prothrombotic tendency in patients with cerebrovascular disease. Future studies should seek to clarify the role of visceral type adipose tissue in the pathophysiology of ischemic stroke.

The majority of intracardiac thrombi form in the left atrial appendage (LAA). Enlargement of this structure, together with certain morphological features, may indicate a predisposition to the formation of thrombi and subsequent cardioembolic stroke. Thus far, studies on LAA morphology have largely focused on those patients with atrial fibrillation (AF). Taking a different approach, we investigated the variation in LAA morphology in a consecutive patient population with and without AF. We evaluated 808 consecutive patients (529 females; mean age 52.5±9.9 years) who underwent coronary artery computed tomography angiography (CCTA), the majority of whom (749) had no history of AF. We assessed the length, lobe number, and morphological classification of their LAAs. Demographic data and medical histories were collated from medical records and then correlated with LAA morphology. The proportions of each of the four morphological classes of LAA for the overall vs. non-AF population were: WindSock, 62.3/61.5%; Cactus, 18.6/18.8%; ChickenWing, 10.0/10.0%; and CauliFlower, 9.2/9.6%. Age (p

To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT) using a comprehensive 3.0T- magnetic resonance urography (MRU) protocol versus triple-phase computed tomography urography (CTU).During the study period (January-2014 through December-2015), all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test.Twenty patients (39 UUT excreting units) were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU) and 87.2% (with CTU) and >75% visualization in 100% (3.0T-MRU) and 93.6% (CTU). Mean CTU effective radiation dose was 9.2 mSv.Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients.ClinicalTrials.gov NCT02606513.

Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p

The etiology of an ischemic stroke remains undetermined in 20-35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.Altogether 58 patients (mean age 57.7 ± 10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered.Mean VAT area was significantly higher in stroke patients (205 ± 103 cm2 for men and 168 ± 99 cm2 for women) compared to all reference populations (P < 0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors.Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.

Apparent diffusion coefficient (ADC) values are increasingly reported in breast MRI. As there is no standardized method for ADC measurements, we evaluated the effect of the size of region of interest (ROI) to diagnostic utility and correlation to prognostic markers of breast cancer.This prospective study was approved by the Institutional Ethics Board; the need for written informed consent for the retrospective analyses of the breast MRIs was waived by the Chair of the Hospital District. We compared diagnostic accuracy of ADC measurements from whole-lesion ROIs (WL-ROIs) to small subregions (S-ROIs) showing the most restricted diffusion and evaluated correlations with prognostic factors in 112 consecutive patients (mean age 56.2±11.6 years, 137 lesions) who underwent 3.0-T breast MRI.Intra- and interobserver reproducibility were substantial (κ = 0.616-0.784; Intra-Class Correlation 0.589-0.831). In receiver operating characteristics analysis, differentiation between malignant and benign lesions was excellent (area under curve 0.957-0.962, cut-off ADC values for WL-ROIs: 0.87×10-3 mm2s-1; S-ROIs: 0.69×10-3 mm2s-1, P

The left atrial appendage (LAA) is the typical origin for intracardiac thrombus formation. Whether LAA morphology is associated with increased stroke/TIA risk is controversial and, if it does, which morphological type most predisposes to thrombus formation. We assessed LAA morphology in stroke patients with cryptogenic or suspected cardiogenic etiology and in age- and gender-matched healthy controls. LAA morphology and volume were analyzed by cardiac computed tomography in 111 patients (74 males; mean age 60 ± 11 years) with acute ischemic stroke of cryptogenic or suspected cardiogenic etiology other than known atrial fibrillation (AF). A subgroup of 40 patients was compared to an age- and gender-matched control group of 40 healthy individuals (21 males in each; mean age 54 ± 9 years). LAA was classified into four morphology types (Cactus, ChickenWing, WindSock, CauliFlower) modified with a quantitative qualifier. The proportions of LAA morphology types in the main stroke group, matched stroke subgroup, and control group were as follows: Cactus (9.0%, 5.0%, 20.0%), ChickenWing (23.4%, 37.5%, 10.0%), WindSock (47.7%, 35.0%, 67.5%), and CauliFlower (19.8%, 22.5%, 2.5%). The distribution of morphology types differed significantly (P

OBJECTIVES: Left atrial appendage (LAA) dilatation and morphology may influence an individual's risk for intracardiac thrombi and ischemic stroke. LAA size and morphology can be evaluated using cardiac computed tomography (cCT). The present study evaluated the reproducibility of LAA volume and morphology assessments. METHODS: A total of 149 patients (47 females; mean age 60.9±10.6 years) with suspected cardioembolic stroke/transient ischemic attack underwent cCT. Image quality was rated based on four categories. Ten patients were selected from each image quality category (N = 40) for volumetric reproducibility analysis by two individual readers. LAA and left atrium (LA) volume were measured in both two-chamber (2CV) and transversal view (TV) orientation. Intertechnique reproducibility was assessed between 2CV and TV (200 measurement pairs). LAA morphology (A = Cactus, B = ChickenWing, C = WindSock, D = CauliFlower), LAA opening height, number of LAA lobes, trabeculation, and orientation of the LAA tip was analysed in all study subjects by three individual readers (447 interobserver measurement pairs). The reproducibility of volume measurements was assessed by intra-class correlation (ICC) and the reproducibility of LAA morphology assessments by Cohen's kappa. RESULTS: The intra-observer and interobserver reproducibility of LAA and LA volume measurements was excellent (ICCs>0.9). The LAA (ICC = 0.954) and LA (ICC = 0.945) volume measurements were comparable between 2CV and TV. Morphological classification (ĸ = 0.24) and assessments of LAA opening height (ĸ = 0.1), number of LAA lobes (ĸ = 0.16), trabeculation (ĸ = 0.15), and orientation of the LAA tip (ĸ = 0.37) was only slightly to fairly reproducible. CONCLUSIONS: LA and LAA volume measurements on cCT provide excellent reproducibility, whereas visual assessment of LAA morphological features is challenging and results in unsatisfactory agreement between readers.

BACKGROUND: Left atrial appendage (LAA) volume has been shown to be increased in patients with acute cryptogenic stroke. Atrial fibrillation (AF) is a well-recognized risk factor but it is not the only one associated with LAA enlargement. The aim of the study was to clarify the multifactorial etiology of LAA enlargement in cardiogenic stroke/TIA patients without AF. METHODS: Altogether 149 patients with suspected cardioembolic stroke/TIA (47 females; mean age 61 years) underwent cardiac CT. Diagnosed AF on admittance was an exclusion criteria but 24-hour Holter ambulatory ECG revealed paroxysmal AF (PAF) in 20 patients. Body surface area adjusted LAA volume was evaluated. Eighteen different variables were registered including general characteristics, definite and potential causal risk factors for ischemic stroke/TIA, clinical echoparameters and CT based cardiac volumetric and adipose tissue measurements. A stepwise linear regression analysis was performed to achieve a model adjusted for the number of predictors of LAA volume increase. RESULTS: In linear regression analysis, the best model accounted for 30% of the variability in LAA volume, including PAF (19%) and enlarged left atrial volume (6%), enlarged left ventricle end-systolic diameter (3%) and decreased pericardial adipose tissue (2%). No multi-colinearity between variables was observed. In addition to PAF, no other definitive or potential causal risk factors could account for the LAA volume in these patients. CONCLUSIONS: LAA volume increase seems to be poorly associated with currently known stroke/TIA risk factors, except for AF. Targeting more comprehensive ECG monitoring for stroke patients with increased LAA volume should be considered.

Progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessively inherited neurodegenerative disorder characterized by young onset age, myoclonus and tonic-clonic epileptic seizures. At the time of diagnosis, the visual assessment of the brain MRI is usually normal, with no major changes found later. Therefore, we utilized texture analysis (TA) to characterize and classify the underlying properties of the affected brain tissue by means of 3D texture features. Sixteen genetically verified patients with EPM1 and 16 healthy controls were included in the study. TA was performed upon 3D volumes of interest that were placed bilaterally in the thalamus, amygdala, hippocampus, caudate nucleus and putamen. Compared to the healthy controls, EPM1 patients had significant textural differences especially in the thalamus and right putamen. The most significantly differing texture features included parameters that measure the complexity and heterogeneity of the tissue, such as the co-occurrence matrix-based entropy and angular second moment, and also the run-length matrix-based parameters of gray-level non-uniformity, short run emphasis and long run emphasis. This study demonstrates the usability of 3D TA for extracting additional information from MR images. Textural alterations which suggest complex, coarse and heterogeneous appearance were found bilaterally in the thalamus, supporting the previous literature on thalamic pathology in EPM1. The observed putamenal involvement is a novel finding. Our results encourage further studies on the clinical applications, feasibility, reproducibility and reliability of 3D TA.

BACKGROUND: Ischemic strokes without a well-defined etiology are labeled as cryptogenic, and account for 30-40% of strokes in stroke registries. The left atrial appendage (LAA) is the most typical origin for intracardiac thrombus formation when associated with atrial fibrillation. Here, we examined whether increased LAA volume detected with cardiac computed tomography (cCT) constitutes a risk factor in cryptogenic stroke patients. METHODS: This study included 82 stroke/TIA patients (57 males; mean age, 58 years) with a diagnosis of cryptogenic stroke after extensive radiological and cardiological investigations. Cases were classified using the TOAST criteria modified by European Association of Echocardiography recommendations for defining cardiac sources of embolism. Forty age- and gender-matched control subjects without cardiovascular diseases were selected for pair-wise comparisons (21 males; mean age, 54 years). LAA volume adjusted for body surface area was measured three dimensionally by tracing the LAA borders on electrocardiogram-gated CT slices. RESULTS: In control subjects, mean LAA volume was 3.4±1.1 mL/m(2). Mean+2SD, which was considered the upper limit for normal LAA volume was 5.6 mL/m(2). In paired Student t-test between the patient group and matched controls, LAA volume was 67% larger in cryptogenic stroke/TIA patients (5.7±2.0 mL/m(2) vs. 3.4±1.1 mL/m(2); P

BACKGROUND: MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods. OBJECTIVE: To compare FTD with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy. METHODS: Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups. RESULTS: We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55). CONCLUSION: Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.

BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas. METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness. CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.