Hippocampal unified multi-atlas network (HUMAN): protocol and scale validation of a novel segmentation tool.

In this study we present a novel fully automated Hippocampal Unified Multi-Atlas-Networks (HUMAN) algorithm for the segmentation of the hippocampus in structural magnetic resonance imaging. In multi-atlas approaches atlas selection is of crucial importance for the accuracy of the segmentation. Here we present an optimized method based on the definition of a small peri-hippocampal region to target the atlas learning with linear and non-linear embedded manifolds. All atlases were co-registered to a data driven template resulting in a computationally efficient method that requires only one test registration. The optimal atlases identified were used to train dedicated artificial neural networks whose labels were then propagated and fused to obtain the final segmentation. To quantify data heterogeneity and protocol inherent effects, HUMAN was tested on two independent data sets provided by the Alzheimer's Disease Neuroimaging Initiative and the Open Access Series of Imaging Studies. HUMAN is accurate and achieves state-of-the-art performance (Dice[Formula: see text] and Dice[Formula: see text]). It is also a robust method that remains stable when applied to the whole hippocampus or to sub-regions (patches). HUMAN also compares favorably with a basic multi-atlas approach and a benchmark segmentation tool such as FreeSurfer.

Multiple RF classifier for the hippocampus segmentation: Method and validation on EADC-ADNI Harmonized Hippocampal Protocol.

The hippocampus has a key role in a number of neurodegenerative diseases, such as Alzheimer's Disease. Here we present a novel method for the automated segmentation of the hippocampus from structural magnetic resonance images (MRI), based on a combination of multiple classifiers. The method is validated on a cohort of 50 T1 MRI scans, comprehending healthy control, mild cognitive impairment, and Alzheimer's Disease subjects. The preliminary release of the EADC-ADNI Harmonized Protocol training labels is used as gold standard. The fully automated pipeline consists of a registration using an affine transformation, the extraction of a local bounding box, and the classification of each voxel in two classes (background and hippocampus). The classification is performed slice-by-slice along each of the three orthogonal directions of the 3D-MRI using a Random Forest (RF) classifier, followed by a fusion of the three full segmentations. Dice coefficients obtained by multiple RF (0.87 ± 0.03) are larger than those obtained by a single monolithic RF applied to the entire bounding box, and are comparable to state-of-the-art. A test on an external cohort of 50 T1 MRI scans shows that the presented method is robust and reliable. Additionally, a comparison of local changes in the morphology of the hippocampi between the three subject groups is performed. Our work showed that a multiple classification approach can be implemented for the segmentation for the measurement of volume and shape changes of the hippocampus with diagnostic purposes.

Ascertainment bias in dementias: a secondary to tertiary centre analysis in Central Italy and conceptual review.

BACKGROUND AND AIMS: Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. METHODS: To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. RESULTS: The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. CONCLUSION: The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.

Ultrasound measurements at the proximal phalanges in male patients with psoriatic arthritis.

Bone ultrasound parameters at the proximal phalanges of the hands were measured in 55 male patients with psoriatic arthritis (PA) (39 with peripheral radiologic involvement and 16 with axial involvement), comparing the findings with those in 16 rheumatoid arthritis (RA) patients, 20 ankylosing spondylitis (AS) patients and 55 age- and sex-matched normal controls. Mean values of amplitude-dependent speed of sound (Ad-SoS) and ultrasound bone profile score (UBPS) were significantly lower in RA (p < 0.001 and p < 1 x 10(-5)) and PA (p < 0.03 and p < 1 x 10(-6)) patients than in controls, while there was no statistically significant difference between AS patients and healthy subjects. Ultrasound parameters showed a significant negative correlation with age in all groups. In each patient group ultrasound values were unrelated either to disease duration or to inflammatory indices such as erythrocyte sedimentation rate and C-reactive protein. Moreover no significant differences were observed between ultrasound parameters of the dominant and the nondominant hand. PA patients with and without axial radiologic changes did not show any differences in ultrasound parameters. However, PA subjects with peripheral involvement only had significantly higher Ad-SoS (p < 0.04) and UBPS (p < 0.04) values than RA patients. PA patients with axial lesions had significantly lower (p < 0.04 and p < 0.01) ultrasound values than AS patients. These findings suggest that PA ultrasound techniques performed at the peripheral level are of value to speculate on bone involvement, although we think that ultrasound measurements cannot yet be recommended for monitoring bone involvement in these patients.

Comparison of the Health Assessment Questionnaire and Arthritis Impact Measurement Scale in patients with psoriatic arthritis.

OBJECTIVE: To determine which of two instruments, the Health Assessment Questionnaire (HAQ) and the Arthritis Impact Measurement Scales (AIMS), was more closely correlated with the main parameters reflecting activity and severity of psoriatic arthritis. METHODS: Both instruments were administered to 72 consecutive patients with psoriatic arthritis. RESULTS: Global HAQ and AIMS scores were closely correlated with each other (rs = 0.747; P < 0.00001). AIMS physical function scales--namely physical activity, dexterity, social activity and activities of daily living--were moderately or closely correlated with the main clinical disease activity parameters, most notably morning stiffness of axial joints (rs = 0.271-0.551). Scales measuring psychological status yielded weaker correlations with disease activity parameters (rs = 0.241-0.277) and were also correlated with the visual analog scale score for skin lesion severity. Morning stiffness of peripheral joints was correlated only with two AIMS scales, namely pain (rs = 0.532) and activities of daily living (rs = 0.303). Severity of radiological damage of peripheral and axial joints was most closely correlated with the scales of physical function, most notably physical activity. The global and scale HAQ scores showed moderate to close correlations with the main clinical disease activity parameters, most notably morning stiffness of axial joints. The global HAQ score was also correlated with radiological carpal involvement and with the radiological severity of peripheral joint involvement, whereas only the arising and hygiene scales were (moderately) correlated with the radiological severity of spinal involvement. CONCLUSION: Although both the HAQ and the AIMS were useful in assessing health status in psoriatic arthritis patients, only the AIMS captured some of the effects of the skin lesions. Our data also suggest that the AIMS may be more effective than the HAQ for evaluating the effect of radiological lesions produced by psoriatic arthritis.

Ultrasound transmission velocity of the proximal phalanxes of the non-dominant hand in the study of osteoporosis.

The aim of our study was to evaluate a quantitative ultrasound technique for measuring bone tissue at the proximal phalanxes of the non-dominant hand. We correlated the mean value of the amplitude-dependent speed of sound (AD-SoS) measured at the distal metaphysis of the last four proximal phalanxes with age, months since menopause and bone mineral density (BMD) of the lumbar spine in 264 women. We further assessed the ability of the AD-SoS to discriminate between normal and osteoporotic subjects with documented vertebral fractures. We found a positive correlation between the AD-SoS and the lumbar spine BMD, whereas the AD-SoS negatively correlated with age and months since menopause. The AD-SoS showed a higher correlation with age changes and months since menopause than BMD. The AD-SoS was significantly higher in healthy females than in osteoporotic ones (p < 0.001). Multiple logistic regression analysis showed for age-adjusted values that AD-SoS decrease is significantly associated to the presence of fracture. Our results suggest that AD-SoS is valuable in assessing age and menopause related bone loss and is useful for diagnosing osteoporosis.

Relationship of soluble interleukin-2-receptor and interleukin-6 with class-specific rheumatoid factors during low-dose methotrexate treatment in rheumatoid arthritis.

We studied the effect of a 6-month treatment with low-dose MTX in 22 RA patients, with the purpose of investigating the relationship of sIL-2R and IL-6 serum changes with those of class specific RFs. The patients with RA had higher serum levels of sIL-2R (p < 0.0001), and IL-6 (p < 0.0005) than healthy volunteers. We found that the levels of IgM-RF (p < 0.0004), IgA-RF (p < 0.002), IgG-RF (p < 0.025), sIL-2R (p < 0.017) and IL-6 (p < 0.044) as well as the main clinical and laboratory variables, were significantly reduced in RA patients treated with low dose MTX for six months. The changes from baseline of IgM-RF correlated with those of IL-6 (p < 0.023), suggesting that MTX may affect IL-6 and IgM-RF production in part by a common mechanism. In conclusion our results show that there is a relationship between IL-6 and IgM-RF changes from baseline during MTX therapy, but the hypothesis of a link between the effects of this drug on cytokine network and RF production needs further investigation.

Life-table analysis of cyclosporin A treatment in psoriatic arthritis: comparison with other disease-modifying antirheumatic drugs.

OBJECTIVES: The aim of this study was to determine the cumulative probability of taking CsA in comparison to other DMARDs, as well as the reason for discontinuation of each DMARD, in a large cohort of PsA patients. METHODS: We prospectively studied 172 consecutive patients with a diagnosis of PsA who had been admitted to our rheumatological unit since 1984. We collected information about treatment with DMARDs including: number, dose, duration and causes of withdrawal, including side effects or inefficacy. Cumulative survival analysis was performed by the Kaplan-Meier test and the differences between these survival curves were determined by the Mantel-Hanszel test. RESULTS: The probability curve of continuing to take CsA was significantly lower than that of MTX (p < 0.046). The rate of adverse effects responsible for stopping DMARD therapy was higher in the CsA group, especially with respect to the antimalarial group (p < 0.014). The most common cause of CsA withdrawal was hypertension. The rate of withdrawal due to inefficacy in the CsA group was not significantly different from those observed in the other groups. Nevertheless, the total frequency of discontinuation due to toxicity and inefficacy in the MTX group was significantly lower compared to the gold salts (p < 0.05) and CsA groups (p < 0.01). CONCLUSION: Life-table analysis suggests that PsA patients taking CsA are less likely than patients on MTX to continue long term treatment. Therefore CsA, which seems to be less safe than the antimalarials, could be considered a useful drug in the treatment of PsA, but does seem to represent the drug of first choice, particularly when compared to MTX.

Interleukin-6 and soluble interleukin-2-receptor in psoriatic arthritis: correlations with clinical and laboratory parameters.

OBJECTIVE: In this study we evaluated the relationships of IL-6 and sIL-2R levels with the main clinical and laboratory parameters in PsA patients with peripheral polyarthritis. METHODS: Serum levels of IL-6 and sIL-2R were measured by an enzyme immunoassay kit in patients with peripheral (< 4 joints) PsA (n = 47), with RA (n = 41), or with psoriasis (N = 15) and in healthy volunteers (n = 15) RESULTS: The patients with PsA had higher serum levels of IL-6 and sIL-2R than healthy volunteers and psoriatic patients, while they showed lower levels of IL-6 and sIL-2R than RA patients. We found abnormal values for IL-6 and sIL-2R in 63.8% and 57.4% of PsA patients, respectively. IL-6 levels correlated with the number of painful and swollen joints, RAI, physician's assessment, CRP and ESR, while sIL-2R levels correlated only with the number of swollen joints, the physician's assessment and ESR. IL-6 and sIL-2R correlated with each other. CONCLUSION: Our study shows that IL-6 and sIL-2R may play a role in the pathogenetic mechanism of psoriatic arthritis.

Interleukin-6 and soluble interleukin-2 receptor in juvenile chronic arthritis: correlations with clinical and laboratory parameters.

We sought to determine whether levels of interleukin-6 and soluble interleukin-2 receptor were correlated with clinical parameters including functional capacity indices such as Steinbrocker's class and the Juvenile Arthritis Functional Assessment Report (JAFAR) score, with tests for inflammation, and/or with immunological parameters in 24 patients with active polyarticular or pauciarticular juvenile chronic arthritis. Levels of interleukin-6 and soluble interleukin-2 receptor were significantly higher in juvenile chronic arthritis patients than in healthy controls (p < 0.005 and p < 0.00005, respectively). Interleukin-6 levels were correlated with the following parameters: number of painful joints (p < 0.025); Ritchie's index (p < 0.025); visual analog scale pain score (p < 0.025); Steinbrocker's class (p < 0.025); JAFAR score determined by patients (p < 0.05); JAFAR score determined by parents (p < 0.05); erythrocyte sedimentation rate (p < 0.0002); and serum levels of C-reactive protein (p < 0.0003), hemoglobin (p < 0.05), albumin (p < 0.025), and alpha 2-globulins (p < 0.025). Levels of soluble interleukin-2 receptor did not correlate with any of the parameters studied. Levels of interleukin-6 and soluble interleukin-2 receptor were not correlated with each other. Abnormal levels of interleukin-6 or soluble interleukin-2 receptor were not significantly associated with the presence of antinuclear antibodies, IgM-rheumatoid factor, IgA rheumatoid factor or anticardiolipin antibodies. Our findings suggest that interleukin-6 is a useful parameter for assessing juvenile chronic arthritis and that the potential clinical value of elevated levels of soluble interleukin-2 receptor in this disease needs to be further evaluated in longitudinal studies.

Comparison of cyclosporin A and methotrexate in the treatment of psoriatic arthritis: a one-year prospective study.

OBJECTIVE: To compare the effectiveness and toxicity of cyclosporin A (CsA) vs low-dose methotrexate (MTX) over a period of one year in the treatment of psoriatic arthritis (PsA) with peripheral involvement. METHODS: Thirty-five patients with PsA were enrolled in a prospective, controlled, randomized trial. CsA was initially given in doses of 3 mg/kg/day to a maximum permitted dose of 5 mg/kg/day; MTX was given in oral doses of 2.5 mg every 12 hours for 3 consecutive doses each week up to a maximum dose of 15 mg/weekly. Clinical and laboratory evaluations were performed at entry and monthly thereafter. RESULTS: After 6 and 12 months the number of painful joints, the number of swollen joints, the Ritchie index, the duration of morning stiffness, grip strength, CRP, the patient's and the physician's assessment of PsA activity, as well as the PASI, were significantly improved in both treatment groups. ESR values were significantly reduced only in the MTX group (p < 0.01), which also showed a significantly increase of liver enzymes. The changes in the main clinical and laboratory parameters during the course of CsA or MTX treatment were not significantly different except for the AST and ALT levels (p < 0.05). After one year of therapy CsA and MTX were withdrawn in 41.2% and 27.8% of the patients respectively, but these differences were not statistically significant. CONCLUSION: Our one-year prospective trial shows that low-dose CsA and MTX are both effective in the treatment of PsA, but the differences in the tolerability of these drugs must be considered at the start of therapy.