Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study.

OBJECTIVE--To compare the abnormalities shown by magnetic resonance imaging of the brain in three clinically distinct groups of patients with multiple sclerosis, and to correlate the extent of abnormality with the degree of clinical disability in the three groups. DESIGN--All patients underwent magnetic resonance imaging and full neurological examination, and their disability was scored according to the expanded Kurtzke disability state scale. SETTING--National Hospital for Nervous Diseases (Multiple Sclerosis NMR Research Group). PATIENTS--Three groups of patients with confirmed multiple sclerosis were studied: 12 patients with minimal disability despite a long (greater than 10 years) duration of illness (benign multiple sclerosis), 16 who had developed progressive disability after a relapsing and remitting course (secondary progressive multiple sclerosis), and 13 who had had progressive disability from the onset of the disease (primary progressive multiple sclerosis). MAIN OUTCOME MEASURES--Number and size of lesions in 17 anatomically defined sites; total lesion load, estimated with an arbitrary scoring system weighted for the size of lesions; and disability score. RESULTS--Magnetic resonance imaging showed that all 41 patients had abnormalities. These were extensive in the groups with secondary progressive and benign disease compared with the group with primary progressive disease. The lesions in the patients with secondary progressive disease were larger and more confluent than those in the two other groups (p = 0.007). Most lesions (85%) in the patients with primary progressive disease were under 5 mm in diameter; this percentage was higher than that in the two other groups (p = 0.032). Consequently the patients with primary progressive disease had the lowest mean lesion load (36.7); that in the patients with benign disease was 52.7 and that in the patients with secondary progressive disease 64.6 (p = 0.05). No correlation existed between disability and total lesion load. The distribution of brain lesions and of detectable lesions of the spinal cord, and the frequency of cortical atrophy, were similar in all groups. CONCLUSIONS--No relation was found between the degree of clinical disability and the extent of abnormality shown by magnetic resonance imaging: patients with clinically benign disease often had extensive abnormalities and those with primary progressive disease had surprisingly few lesions. Though magnetic resonance imaging increases knowledge of the disease process in multiple sclerosis and is invaluable in diagnosis, it is not helpful in predicting disability in individual patients.     

VCAM-1-targeted magnetic resonance imaging reveals subclinical disease in a mouse model of multiple sclerosis

Diagnosis of multiple sclerosis (MS) currently requires lesion identification by gadolinium (Gd)-enhanced or T(2)-weighted magnetic resonance imaging (MRI). However, these methods only identify late-stage pathology associated with blood-brain barrier breakdown. There is a growing belief that more widespread, but currently undetectable, pathology is present in the MS brain. We have previously demonstrated that an anti-VCAM-1 antibody conjugated to microparticles of iron oxide (VCAM-MPIO) enables in vivo detection of VCAM-1 by MRI. Here, in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we have shown that presymptomatic lesions can be quantified using VCAM-MPIO when they are undetectable by Gd-enhancing MRI. Moreover, in symptomatic animals VCAM-MPIO binding was present in all regions showing Gd-DTPA enhancement and also in areas of no Gd-DTPA enhancement, which were confirmed histologically to be regions of leukocyte infiltration. VCAM-MPIO binding correlated significantly with increasing disability. Negligible MPIO-induced contrast was found in either EAE animals injected with an equivalent nontargeted contrast agent (IgG-MPIO) or in control animals injected with the VCAM-MPIO. These findings describe a highly sensitive molecular imaging tool that may enable detection of currently invisible pathology in MS, thus accelerating diagnosis, guiding treatment, and enabling quantitative disease assessment.     

Magnetic resonance imaging and magnetic resonance spectroscopy in a patient with amyotrophic lateral sclerosis and frontotemporal dementia

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have been investigated in a single neurodegenerative disease manifesting as either amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) alone, but have not been examined in combined disorders such as ALS with FTD (ALS-FTD). To our knowledge, this study is the first attempt to demonstrate relationship between MRI abnormalities and MR spectroscopic metabolite changes of the motor cortex, frontal white matter and corticospinal tract in a patient with the diagnosis of ALS with probable upper motor neuron signs (ALS-PUMNS) and FTD. Patient presented underwent MRI of the brain and MRS. The ratio of N-acetylaspartate (NAA) to creatine (Cr), choline to Cr, myo-inositol (ml) to Cr and glutamate-glutamine (Glx) to Cr were derived from peak area measurement. Spectra from the right motor cortex, frontal white matter and corticospinal tract were obtained. MR images were evaluated for sulcus centralis enlargement, corticospinal tract hyperintensity and frontal lobes atrophy. Spectra showed reduced NAA/Cr and Glx/Cr ratio, yet the ratio of Cho/Cr exhibited significant elevation. MR images revealed sulcus centralis enlargement, high signal intensity of corticospinal tract and atrophy of both frontal lobes. Proton spectroscopic metabolic changes in a current patient fully correlate with previously reported MRS metabolic changes in ALS alone. Surprisingly, normal ml (glial marker) values have been found in almost all measured voxels of interest except in the frontal white matter. These findings differ from the previous findings in ALS or FTD alone. In conclusion, these findings support the concept that ALS, FTD and ALS-FTD may represent different manifestations of a single pathological continuum.     

Molecular imaging of brain lipid environment of lymphocytes in amyotrophic lateral sclerosis using magnetic resonance imaging and SECARS microscopy

This paper highlights some of the key technologies of using two innovative molecular imaging modalites, magnetic resonance imaging (MRI) and nonlinear optical microscopy, for imaging intravenously injected ultra small paramagnetic iron oxide nanoparticles cross linked with antibodies (CLUSPIO) in the amyotrophic lateral sclerosis (ALS) experimental model in vivo or ex vivo, respectively. Intensive efforts have been made in investigating the causes of abnormalities in lipid metabolism, monitored in some neurodegenerative disorders systems. It has been shown that an abnormal accumulation of some common lipids in motor nerve cells may play a critical role in the development of amyotrophic lateral sclerosis. The presented experiments were performed on brain specimens from the transgenic rat model expressing multiple copies of mutated (G93A) human SOD-1 gene, after CD4+ lymphocytes were magnetically labeled with i.v.i. CLUSPIO antibodies. In vivo MRI revealed marked signal intensity enhancements in specific pathological regions of the ALS rat brain as compared to the wild type. Surface-enhanced coherent anti-Stokes Raman scattering (SECARS) microscopy indicated cellular interactions based on lipids association to anti-CD4 CLUSPIO.     

Dynamic magnetic resonance of the wrist in psoriatic arthritis reveals imaging patterns similar to those of rheumatoid arthritis

This dynamic magnetic resonance imaging (MRI) study is concerned with a prospective evaluation of wrist synovitis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. Fifteen consecutive patients with PsA, 49 consecutive patients with RA, 30 RA patients matched for disease severity with those with PsA, and 8 healthy controls were studied. MRI was performed with a low-field (0.2T), extremity-dedicated machine. After an intravenous bolus injection of gadolinium-diethylenetriaminepentaacetic acid, 20 consecutive fast spin-echo axial images of the wrist were obtained every 18 s. The enhancement ratio was calculated both as rate of early enhancement (REE), which shows the slope of the curve of contrast uptake per second during the first 55 s, and as relative enhancement (RE), which indicates the steady state of enhancement. The REE was 1.0 ± 0.6 in patients with PsA, 1.6 ± 0.7 in consecutive patients with RA, and 0.1 ± 0.1 in controls (p <0.001). The RE was 87.1 ± 39.2 in patients with PsA, 125.8 ± 48.0 in consecutive RA patients, and 15.5 ± 19.2 in controls (p <0.001). However, the same figures in matched RA patients were 1.3 ± 0.7 and 107.3 ± 48.2, respectively (not significant in comparison with PsA). Rheumatoid-like PsA and oligoarticular PsA did not differ from each other in terms of synovial enhancement. Dynamic MRI shows the same pattern of synovitis in patients with PsA and RA when the two groups are matched for disease severity. This technique cannot be used to differentiate PsA from RA. However, REE and RE were significantly higher in PsA than in normal controls, with only one instance of overlap between values found for the two groups.     

The usefulness of magnetic resonance imaging of the hand and wrist in very early rheumatoid arthritis

Introduction  

Magnetic resonance imaging (MRI) was used to study the hand and wrist in very early rheumatoid arthritis (RA), and the results were compared with early and established disease.     

Role of magnetic resonance imaging in the detection of chondral and osteochondral lesions in chronic juvenile arthritis

Chronic juvenile arthritis (CJA) is the most common inflammatory disease of joints in children. There are numerous studies showing the limited informative value of X-ray in the evaluation of CJA progression. Contrast-enhanced magnetic resonance imaging (MRI) using intravenous gadolinium is currently in the foreground in diagnosing arthritis in children, in infants in particular. Knee joints are most frequently afflicted in CJA, showing significant manifestations of the disease. The purpose of the study was to describe the patterns of changes in the nonossified epiphyseal and articular cartilages in the distal epiphyses of femurs in the knee joints of patients with manifestations of chronic juvenile arthritis and to define the role of contrast-enhanced MRI in evaluating the epiphyseal changes in this disease. Sixty-nine patients aged 1.5-14 years who have clinical laboratory and ultrasound signs of CJA lasting 6 months to 5 years underwent contrast-enhanced MRI for the evaluation of changes in the articular and nonossified epiphyseal cartilages. Intravenous contrast enhancement identified several specific features and patterns of epiphyseal changes: subchondral hyperemia of epiphyses and recorded thickened epiphyseal chondral vascular channels, chondral and osteochondral erosions as manifestations of changes in the growing epiphyseal cartilage and articular one in children with chronic arthritis. Thus, contrast-enhanced MRI allows differentiation of different patterns of epiphyseal changes in CJA.     

Differences in regional brain activation patterns assessed by functional magnetic resonance imaging in patients with systemic lupus erythematosus stratified by disease duration

The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.     

Detection of bone erosions in rheumatoid arthritis wrist joints with magnetic resonance imaging, computed tomography and radiography

Background

The objectives of the present study were, with multidetector computed tomography (CT) as the reference method, to determine the performance of magnetic resonance imaging (MRI) and radiography for the detection of bone erosions in rheumatoid arthritis wrist bones, and to test whether measuring volumes of erosions on CT and MRI is reproducible and correlated to semiquantitative assessments (scores) of erosions on CT, MRI and radiography.

Methods

Seventeen patients with rheumatoid arthritis and four healthy control individuals underwent CT, MRI and radiography of one wrist, performed on the same day. CT was performed on a Philips Mx8000IDT unit (voxel size 0.4 mm × 0.4 mm × 1 mm) and MRI was performed on a Philips Panorama 0.6T unit (voxel size 0.4 mm × 0.4 mm × 0.4 mm). Images were evaluated separately for erosions in all wrist bones and were scored according to the principles of the Outcome Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (CT and MRI) and the Sharp/van der Heijde (radiographs) scoring methods. Measurements of erosion volumes of all erosions were performed twice with a 1-week interval.

Results

With CT as the reference method, the overall sensitivity, specificity and accuracy (concordance) of MRI for detecting erosions were 61%, 93% and 77%, respectively, while the respective values were 24%, 99% and 63% for radiography. The intramodality agreements when measuring erosion volumes were high for both CT and MRI (Spearman correlation coefficients 0.92 and 0.90 (both P < 0.01), respectively). Correlations between volumes and scores of individual erosions were 0.96 for CT and 0.99 for MRI, while they were 0.83 (CT) and 0.80 (MRI) for persons' total erosion volume and total score (all P < 0.01).

Conclusion

With CT as the reference method, MRI showed moderate sensitivity and good specificity and accuracy for detection of erosions in rheumatoid arthritis and healthy wrist bones, while radiography showed very low sensitivity. The tested volumetric method was highly reproducible and correlated to scores of erosions.     

Cellular magnetic resonance imaging: potential for use in assessing aspects of cardiovascular disease

There is rapidly increasing interest in the use of magnetic resonance imaging (MRI) to track cell migration in vivo. Iron oxide MR contrast agents can be detected at micromolar concentrations of iron, and offer sufficient sensitivity for T2*-weighted imaging. Cellular MRI shows potential for assessing aspects of cardiovascular disease. Labeling in vivo and tracking macrophages using iron oxide nanoparticles has been a goal for cellular MRI because macrophages play a pivotal role in the pathophysiology of many human diseases, including atherosclerosis. Cellular MRI has also been using to track transplanted therapeutic cells in myocardial regeneration. This review looked at iron oxide nanoparticles, methods of cell labeling, image acquisition techniques and limitations encountered for visualization. Particular attention was paid to stem cells and macrophages for the cardiovascular system.     

Use of magnetic resonance imaging in the study of goat mammary glands in vivo

A technique is described for the in-vivo determination of mammary gland size and gross composition in goats by using nuclear magnetic resonance imaging (MRI). The volume of test objects determined with MRI had an error of +0.4 +/- 1.6% of the actual volume. In lactating goats the in-vivo MRI estimate of mammary parenchymal volume was significantly greater than, but highly significantly correlated with, the weight of parenchyma determined post mortem (for the whole udder, r = 0.88, P less than 0.001; for individual glands, r = 0.85, P less than 0.001). MRI-determined estimates of the volume of fluid within the mammary gland were within 1.2% of the volume of milk removed from the udders after imaging. The spin-lattice (T1) relaxation time of the whole udder correlated closely with the volume of fluid within the udder. The T1 relaxation time of parenchymal tissue measured in vivo did not differ significantly from that determined immediately after post-mortem excision.     

Prevalence of comorbidities in systemic sclerosis versus rheumatoid arthritis: a comparative,multicenter, matched-cohort study

Background

Comorbidities are common in chronic systemic connective tissue diseases and are associated with adverse outcomes, increased morbidity and mortality. Although the prevalence of comorbidities has been well-studied in isolated diseases, comparative studies between different autoimmune diseases are limited. In this study, we compared the prevalence of common comorbidities between patients with systemic sclerosis (SSc) and patients with rheumatoid arthritis (RA).

Methods

Between 2016 and 2017, 408 consecutive patients with SSc, aged 59?±?13?years (87% women), were matched 1:1 for age and gender with 408 patients with RA; mean disease duration was 10?±?8 and 9?±?8?years, respectively. Rates of cardiovascular risk factors, coronary artery disease, stroke, chronic obstructive pulmonary disease (COPD), osteoporosis, neoplasms and depression were compared between the two cohorts.

Results

The prevalence of dyslipidemia (18.4% vs 30.1%, p?=?0.001) and diabetes mellitus (5.6% vs 11.8%, p?=?0.007) and body mass index (p?=?0.001) were lower in SSc compared to RA, while there was no difference in arterial hypertension or smoking. While there was a trend for lower prevalence of ischemic stroke in SSc than in RA (1.1% vs 3.2%, p?=?0.085), coronary artery disease was comparable (2.7% vs 3.7%). No differences were found between patients with SSc and patients with RA in the prevalence of COPD (5.2% vs 3.7%), osteoporosis (24% vs 22%) or neoplasms overall (1.1% vs 1.7%); however lung cancer was the most prevalent cancer in SSc (7/17, 41%), whereas hematologic malignancies (7/19, 36%) and breast cancer (7/19, 36%) predominated in RA. Depression was more prevalent in SSc (22% vs 12%, p?=?0.001), especially in diffuse SSc.

Conclusions

Despite the prevalence of dyslipidemia and diabetes mellitus in SSc being almost half that in RA, the cardiovascular comorbidity burden appears to be similar in both. The overall prevalence of neoplasms is no higher in SSc than in RA, but SSc has a more negative impact on quality of life, as clearly, more SSc patients develop depression compared to patients with RA.

     

A longitudinal study of radiation-induced changes in tumor vasculature by contrast-enhanced magnetic resonance imaging

Dynamic contrast-enhanced MRI with two different-sized contrast agents, Gd-DTPA and Gadomer-17, was used to study the effects of radiation on the pharmacokinetics of the paramagnetic enhancement of water relaxation in the rat R3230 AC adenocarcinoma tumor model. The kinetics of enhancement was analyzed by a two-compartment pharmacokinetic model to derive parameters related to vascular volume (V(b)) and permeability (K(2)). Rats implanted with tumors were divided into two groups; one received 5 Gy and the other received 20 Gy (137)Cs gamma rays. Sequential dynamic contrast-enhanced MRI studies were performed, one before irradiation, one at day 1 after irradiation, and another at day 3 after irradiation, to investigate the effect of the radiation dose and the changes that occurred over time. The analysis was performed on a pixel-by-pixel basis to study the heterogeneity within the tumor. The pixel distribution profiles of V(b) and K(2) from each tumor were obtained to assess the regional radiation-induced effects on vascular volume and permeability. No significant change in vascular volume was detected with either Gd-DTPA or Gadomer-17 after irradiation of the tumor; however, a small dependence of K(2) on the radiation dose was observed. After low-dose (5 Gy) irradiation, the mean value of K(2) decreased by 46% at day 1 compared to the baseline, presumably due to cell swelling, and decreased further by 67% from the baseline on day 3. When the dose was increased to 20 Gy, the mean value of K(2) measured with Gadomer-17 did not show any significant changes at either day 1 or day 3 after irradiation. The value of K(2) measured with Gd-DTPA did not show any significant changes after either the low or the high radiation dose.     

Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study

IntroductionSystemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselected cohorts of SSc and MCTD.MethodsSera of SSc patients (N = 298) and MCTD patients (N = 162) from two longitudinal Norwegian cohorts were included. Blood donors were included as controls (N = 100). Circulating VEGF and endostatin were analyzed by enzyme immunoassay.ResultsMean endostatin levels were increased in SSc patients 93.7 (37) ng/ml (P < .001) and MCTD patients 83.2 (25) ng/ml (P < .001) compared to controls 65.1 (12) ng/ml. Median VEGF levels were elevated in SSc patients 209.0 (202) pg/ml compared to MCTD patients 181.3 (175) pg/ml (P = .017) and controls 150.0 (145) pg/ml (P < .001). Multivariable analysis of SSc subsets showed that pulmonary arterial hypertension (coefficient 15.7, 95 % CI: 2.2–29.2, P = .023) and scleroderma renal crisis (coefficient 77.6, 95 % CI: 59.3–100.0, P < .001) were associated with elevated endostatin levels. Multivariable analyses of MCTD subsets showed that digital ulcers were associated with elevated endostatin levels (coefficient 10.5, 95 % CI: 3.2–17.8, P = .005). The risk of death increased by 1.6 per SD endostatin increase (95 % CI: 1.2–2.1, P = .001) in the SSc cohort and by 1.6 per SD endostatin increase (95 % CI: 1.0–2.4, P = .041) in the MCTD cohort after adjustments to known risk factors.ConclusionsEndostatin levels were elevated in patients with SSc and MCTD, particularly SSc patients with pulmonary arterial hypertension and scleroderma renal crisis, and MCTD patients with digital ulcers. Elevated endostatin levels were also associated with increased all-cause mortality during follow-up in both groups of patients. We propose that endostatin might indicate the degree of vascular injury in SSc and MCTD patients.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0756-5) contains supplementary material, which is available to authorized users.     

The developmental process of xylem embolisms in pine wilt disease monitored by multipoint imaging using compact magnetic resonance imaging

In pine wilt disease (PWD), embolized tracheids arise after virulent pine wood nematodes (PWN), Bursaphelenchus xylophilus, invade the resin canal of pine tree; infected pine trees finally die from significant loss of xylem water conduction. We used a compact magnetic resonance imaging system with a U-shaped radio frequency (rf) probe coil to reveal the developmental process of the xylem dysfunction in PWD. Multiple cross-sectional slices along the stem axis were acquired to periodically monitor the total water distribution in each 1-year-old main stem of two 3-year-old Japanese black pines (Pinus thunbergii) after inoculation of PWN. During the development of PWD, a mass of embolized tracheids around the inoculation site rapidly enlarged in all directions. This phenomenon occurred before the significant decrease of water potential. Some patch-like embolisms were observed at all monitoring positions during the experimental period. Patchy embolisms in a cross-section did not expand, but the number of patches increased as time passed. When the significant decrease of water potential occurred, the xylem dysfunctional rate near the inoculation point exceeded 70%. Finally, almost the whole area of xylem was abruptly embolized in all cross-sections along the stem. This phenomenon occurred just after water conduction was mostly blocked in one of the cross-sections. Thus, it appears that the simultaneous expansion of embolized conduit clusters may be required to induce a large-scale embolism across the functional xylem. Consequently, xylem dysfunction in infected trees may be closely related to both the distribution and the number of PWN in the pine stem.     

人脑功能磁共振成像及其在认知神经科学研究中的应用

目录一、磁共振成像原理简介二、脑激活（一）Ｔ２变化（二）Ｔ１变化三、功能磁共振信号特点（一）信号强度（二）时间分辨率（三）空间分辨率四、ＦＭＲＩ研究中的一些技术问题（一）实验设计与数据处理（二）头动问题五、ＦＭＲＩ在认知神经科学研究中的应用（一）感...     

Nuclear magnetic resonance monitoring of treatment and prediction of outcome in multiple sclerosis

Magnetic resonance (MR) techniques provide an objective, sensitive and quantitative assessment of the evolving pathology in multiple sclerosis. There is an increasing definition of the pathological specificity of newer techniques, and more robust correlations with clinical evolution are emerging. As the pathophysiological basis of in vivo nuclear MR signal abnormalities is further elucidated, it is likely that the importance of MR as a tool to monitor new therapies will increase.