Xingchen Wu | Tampere University (original) (raw)

Papers by Xingchen Wu

NMR in Biomedicine, 2011

To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemo... more To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non-Hodgkin's lymphoma (NHL), eight patients with histologically proven diffuse large B-cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole-body screening using T(1) - and T(2) -weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T(2) -weighted images. The maximum standardized uptake value (SUV(max) ) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre-therapy ADC was 0.71 × 10(-3) mm(2) /s; it increased by 77% at E2 (p < 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p < 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p < 0.05) and 65% more at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean SUV(max) of 20. The SUV(max) decreased by 60% at E2 (p < 0.05) and 59% more at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden decreased by 66% at E2 (p < 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUV(max) (p < 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p < 0.05). In conclusion, the results of DWI in combination with whole-body MRI were comparable with those of integrated PET/CT.

Acta Neurologica Scandinavica, 2005

Increased disability and MRI lesions after discontinuation of IFN-b-1a in secondary progressive MS.

The Lancet Neurology, 2011

Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partl... more Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly eff ective. We aimed to establish whether add-on of simvastatin, a statin with anti-infl ammatory properties, improves this effi cacy.

International Immunology, 2004

Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC no... more Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens—two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-g (IFN-g-DC) exhibit therapeutic potential on acute experimental allergic

Medicina (Kaunas, Lithuania)

BACKGROUND AND OBJECTIVE. Brain size, white matter hyperintensity, and the development of brain a... more BACKGROUND AND OBJECTIVE. Brain size, white matter hyperintensity, and the development of brain atrophy are known to be highly heritable. The decrease of brain volume starts from the very onset of multiple sclerosis and is 10-fold compared with normal aging. The aim of this study was to assess whether the brain and spinal cord volumes and the volume of white matter lesions differed between twins with multiple sclerosis and their asymptomatic co-twins. MATERIAL AND METHODS. A co-twin control method was used to evaluate whether the brain and spinal cord volumes differ between twins with multiple sclerosis and their co-twins. Nineteen twin pairs were studied neurologically, and the volumes of T1, T2, FLAIR, and gadolinium-enhanced lesions and those of the brain and the spinal cord were obtained by magnetic resonance imaging. RESULTS. Significant differences in the brain (P=0.064) or spinal cord (P=0.648) volumes were not detected. Four of the 7 monozygotic and 5 of the 12 dizygotic co-...

Acta Oncologica, 2014

(18)F-FDG-PET/CT has been widely used in the staging of malignant lymphomas, and accepted as a to... more (18)F-FDG-PET/CT has been widely used in the staging of malignant lymphomas, and accepted as a tool for response assessment. Among PET parameters, the most frequently studied is maximal standardized uptake value (SUVmax). Metabolic tumor burden (MTB) is a parameter in which both metabolic tumor volume (MTV) and tumor activity are integrated. Here, we analyzed the prognostic value of SUVmax, SUVsum (sum of the SUVmax), whole-body MTV (MTVwb) and MTBwb from baseline and interim PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). Twenty-nine patients with histologically proven DLBCL were imaged by PET/CT before treatment (Exam I), and one week after the first dose of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy (Exam II). Biopsy specimens were examined by an expert hematopathologist, the Ki-67 proliferation index (PI) was estimated for each biopsy site from the MIB-1 stained sections. The response evaluation was performed after chemotherapy completion (6-8 cycles). All patients had one or more visualized lymphomatous lesions on (18)F-FDG-PET/CT. The SUVmax of the whole-body (BmSUVmax) was higher than the SUVmax at biopsy site (BxSUVmax) (mean: 20.1 vs. 17.3, p < 0.01). The PI correlated with the BxSUVmax (p < 0.05). One week after chemotherapy, SUVmax, SUVsum, MTVwb, and MTBwb decreased significantly (p < 0.01, respectively), SUVsum, MTVwb and MTBwb at Exam II correlated with chemotherapy response at treatment completion (p < 0.05, respectively). SUVmax is more accurate to detect tumor aggressiveness than biopsy in DLBCL, since BmSUVmax represents the most aggressive tumor of the patient. Interim PET/CT as early as one week after R-CHOP therapy predicts response. Thus, it could be used as a tool for guidance of risk stratification in DLBCL.

International immunology, 2004

Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC no... more Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens-two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-gamma (IFN-gamma-DC) exhibit therapeutic potential on acute experimental allergic encephalomyelitis (EAE) in Lewis rats, and on chronic-relapsing EAE in B6 and SJL/J mice. During incipient EAE [day 5 post-immunization (p.i.) in rats, day 7 p.i. in mice], IFN-gamma-DC were injected s.c. Severity of clinical signs of EAE was dramatically inhibited in animals injected with IFN-gamma-DC, showing normal magnetic resonance imaging (MRI) of the spinal cord and brain. In contrast, the EAE rats receiving PBS or naive DC had severe clinical signs with multiple and extensive MRI lesions in the spinal cord and brain. IFN-gamma-DC triggered an antigen-s...

Multiple Sclerosis International, 2013

The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callos... more The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callosum and pyramidal tract in normalappearing white matter (NAWM) and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined whether these metrics are associated with clinical measures and the serum levels of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were significantly higher than in controls in all six studied NAWM regions in SPMS, 4/6 regions in RRMS and PPMS and 2/6 regions in CIS. In contrast, decreased fractional anisotropy (FA) values in comparison to controls were detected in 2/6 NAWM regions in SPMS and 1/6 in RRMS and PPMS. In RRMS, the level of neurological disability correlated with thalamic FA values ( = 0.479, = 0.004). In chronic progressive subtypes and CIS, ADC values of NAWM and NADGM were associated with the levels of MIF, sFas, and sTNF-. Our data indicate that DTI may be useful in detecting pathological changes in NAWM and NADGM in MS patients and that these changes are related to neurological disability. of Hindawi Publishing Corporation

NMR in Biomedicine, 2013

To compare different MRI sequences for the detection of lesions and the evaluation of response to... more To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL), 18 patients with histology-confirmed DLBCL underwent 3-T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T 1 -weighted pre-and post-contrast, T 2 -weighted with and without fat suppression, and a single-shot echo-planar diffusion-weighted imaging (DWI) with two b values (0 and 800 s/mm 2 ). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T 2 -weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T 2 -weighted image with fat suppression decreased significantly (p < 0.01), and that of the T 1weighted pre-contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 Â 10 -3 mm 2 /s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = À0.62, p < 0.01). In conclusion, this study indicates that T 2 -weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI.

Neurological Research, 2014

To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in... more To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS). Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including the expanded disability status scale (EDSS), were performed at baseline, month 24, and at year 7. Baseline cortical NAA/Cr correlated inversely with EDSS at month 24 (r = -0·61, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05). Baseline cortical NAA/Cr also correlated inversely with EDSS at the 7-year follow-up (r = -0·56, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05). Baseline brain parenchymal fraction (BPF) correlated inversely with EDSS at month 24 (r = -0·61, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05), but not with EDSS at year 7. Cortical NAA/Cr in early RRMS correlated with clinical disability after 2 and 7 years and may be used as a predictor of long-term disease outcome.

Multiple Sclerosis Journal, 2013

Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortica... more Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

Molecular Imaging and Biology, 2011

The purpose of this study is to evaluate the time course of early chemotherapy response in patien... more The purpose of this study is to evaluate the time course of early chemotherapy response in patients with aggressive non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lymphoma (NHL) by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). Eight patients with histologically proven aggressive NHL were imaged by MRI and PET/CT before treatment (E1), 1 week (E2), and two cycles (E3) after chemotherapy. The mean tumor volume on MRI was 276 mL at baseline; it decreased 58% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 65% further at E3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), giving a total decrease of 84% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean maximum standardized uptake value (SUV(max)) of 20. The SUV(max) decreased 60% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 59% further at E3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), giving a total decrease of 83% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The active tumor burden (mean 229 mL) decreased 66% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The tumor volume on MRI correlated with the active tumor volume on fused PET/CT images in the same region of interest at both E1 and E2 (r = 0.88, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, respectively). Standard chemotherapy causes rapid decrease of both tumor metabolic activity and volume as early as 1 week, which continues to decline during therapy. Both volumetric MRI and PET/CT are valuable tools for early treatment response evaluation of aggressive NHL.

Leukemia & Lymphoma, 2012

Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by [18F]-fluorod... more Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT). The maximum SUV of the whole-body (BmSUV(max)) reflects the tumor aggressiveness in non-Hodgkin lymphoma. To evaluate the correlation between SUV(max) at biopsy site (BxSUV(max)) and proliferation potential of tumor cells in untreated diffuse large B-cell lymphoma (DLBCL), fifteen pre-therapy PET/CT scans in patients with histologically proven DLBCL were retrospectively analyzed together with Ki-67 proliferation index. The BmSUV(max) and BxSUV(max) were evaluated from the fused PET/CT images. Ki-67 proliferation index was measured in the biopsy specimens using an immunohistochemical technique in archival paraffin-embedded sections. The BmSUV(max) was significantly higher than the BxSUV(max) (mean 19.6 vs.16.6, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). The BxSUV(max) correlated with the Ki-67 proliferation index (r = 0.7, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), but no correlation was detected between the BmSUV(max) and the Ki-67 proliferation index. The results indicate that tumor proliferation potential might be predicted in vivo by FDG-PET/CT images. Thus, PET/CT is useful to guide biopsy by selecting sites with the BmSUV(max) when clinically appropriate.

The Lancet Neurology, 2011

Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partl... more Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly eff ective. We aimed to establish whether add-on of simvastatin, a statin with anti-infl ammatory properties, improves this effi cacy.

Journal of Neuroscience Research, 2004

A photochemical lesion was induced in the right sensory motor cortex of rat brains. We examined a... more A photochemical lesion was induced in the right sensory motor cortex of rat brains. We examined at various time points the occurrence of different types of neuronal death with respect to a potential therapeutic window. The lesion appearance was documented by magnetic resonance imaging, and functional recovery was evaluated by behavioral tests showing recovery at 48 hr after lesioning. At 0.5, 1, 3, 6, 12, 24, 48, and 72 hr postlesion, cortical layers IV and V were examined by light and electron microscopy. Ultrastructural changes, which corresponded well to light microscopy findings, were found in both hemispheres. In the lesioned area, the neuropil appeared disorganized at 0.5 hr, and apoptotic and necrotic cell death was found at 0.5-3 hr. After 3 hr, the tissue was disintegrated. On the contralateral side, chromatin clumping appeared at 0.5-3 hr. At 3 hr, ruptured membranes were found, a sign of irreversible cell death. At 6 -72 hr, the membranes were intact, and the chromatin was not clumped but heterogeneously distributed. The nuclei contained dispersed nucleoli at 48 -72 hr. The morphology correlated well with magnetic resonance images and functional behavior. Our study demonstrates that a photochemical lesion is a useful model for studying morphological changes in injured cells. It results in a permanent infarction within 3 hr. In that the morphology on the contralateral side drastically changed between 3 and 6 hr, the cellular alterations at these time points might represent a break point at which cells either progress toward cell death or recover.

The Journal of Immunology, 2004

Identification of polymorphic genes regulating inflammatory diseases may unravel crucial pathogen... more Identification of polymorphic genes regulating inflammatory diseases may unravel crucial pathogenic mechanisms. Initial steps to map such genes using linkage analysis in F 2 intercross or backcross populations, however, result in broad quantitative trait loci (QTLs) containing hundreds of genes. In this study, an advanced intercross line in combination with congenic strains, was used to fine-map Eae18 on rat chromosome 10 in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Myelin oligodendrocyte glycoprotein-induced EAE is a chronic relapsing disease that closely mimics key features of multiple sclerosis. Congenic DA.ACI rat strains localized Eae18 to an ϳ30-Mb large region. Fine-mapping was then performed in an advanced intercross line consisting of a (DA ؋ PVG.1AV1)F 7 intercross, resulting in two adjacent EAE-regulating QTLs designated Eae18a and Eae18b. The two QTLs span 5.5 and 3 Mb, respectively, and the 3-Mb Eae18b contains as few as 10 genes, including a cluster of chemokine genes (CCL1, CCL2, CCL7, and CCL11). Eae18a and Eae18b are syntenic to human chromosome 17p13 and 17q11, respectively, which both display linkage to multiple sclerosis. Thus, Eae18 consists of at least two EAE-regulating genes, providing additional evidence that clustering of disease-regulating genes in QTLs is an important phenomenon. The overlap between Eae18a and Eae18b with previously identified QTLs in humans and mice further supports the notion that susceptibility alleles in inflammatory disease are evolutionary conserved between species.

European Journal of Radiology, 2011

Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic re... more Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) are oncologic feasible techniques for evaluating the malignancy of tumors. Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by PET/CT. Apparent diffusion coefficient (ADC) measured by DWI can provide information about tissue cellularity. The aim of the study was to evaluate the correlation between SUV and ADC in untreated diffuse large B-cell lymphoma (DLBCL). Fifteen pre-therapy patients with histologically proven DLBCL underwent PET/CT and DWI examinations within two days. Tumor glucose metabolism was evaluated by the maximum and mean SUV (SUV(max) and SUV(mean)) on the PET/CT images. The mean ADC value was measured directly on the parametric ADC maps. In total, 28 lymphoma lesions with best match PET/CT and DWI were identified and evaluated. The mean SUV(max) and SUV(mean) were 16.8 and 11.1, respectively; the mean ADC was 0.74 × 10(-3)mm(2)/s. There was no correlation between the mean ADC and the SUV(max) or SUV(mean). SUV determined from PET/CT and ADC value measured from DWI are different indices for the diagnosis of tumor malignancy, they may provide complimentary functional information of tumor tissue.

NMR in Biomedicine, 2011

To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemo... more To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lymphoma (NHL), eight patients with histologically proven diffuse large B-cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole-body screening using T(1) - and T(2) -weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T(2) -weighted images. The maximum standardized uptake value (SUV(max) ) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre-therapy ADC was 0.71 × 10(-3) mm(2) /s; it increased by 77% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 65% more at E3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), giving a total decrease of 84% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean SUV(max) of 20. The SUV(max) decreased by 60% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 59% more at E3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), giving a total decrease of 83% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The active tumor burden decreased by 66% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUV(max) (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In conclusion, the results of DWI in combination with whole-body MRI were comparable with those of integrated PET/CT.

Acta Neurologica Scandinavica, 2005

Increased disability and MRI lesions after discontinuation of IFN-b-1a in secondary progressive MS.

The Lancet Neurology, 2011

Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partl... more Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly eff ective. We aimed to establish whether add-on of simvastatin, a statin with anti-infl ammatory properties, improves this effi cacy.

International Immunology, 2004

Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC no... more Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens—two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-g (IFN-g-DC) exhibit therapeutic potential on acute experimental allergic

Medicina (Kaunas, Lithuania)

BACKGROUND AND OBJECTIVE. Brain size, white matter hyperintensity, and the development of brain a... more BACKGROUND AND OBJECTIVE. Brain size, white matter hyperintensity, and the development of brain atrophy are known to be highly heritable. The decrease of brain volume starts from the very onset of multiple sclerosis and is 10-fold compared with normal aging. The aim of this study was to assess whether the brain and spinal cord volumes and the volume of white matter lesions differed between twins with multiple sclerosis and their asymptomatic co-twins. MATERIAL AND METHODS. A co-twin control method was used to evaluate whether the brain and spinal cord volumes differ between twins with multiple sclerosis and their co-twins. Nineteen twin pairs were studied neurologically, and the volumes of T1, T2, FLAIR, and gadolinium-enhanced lesions and those of the brain and the spinal cord were obtained by magnetic resonance imaging. RESULTS. Significant differences in the brain (P=0.064) or spinal cord (P=0.648) volumes were not detected. Four of the 7 monozygotic and 5 of the 12 dizygotic co-...

Acta Oncologica, 2014

(18)F-FDG-PET/CT has been widely used in the staging of malignant lymphomas, and accepted as a to... more (18)F-FDG-PET/CT has been widely used in the staging of malignant lymphomas, and accepted as a tool for response assessment. Among PET parameters, the most frequently studied is maximal standardized uptake value (SUVmax). Metabolic tumor burden (MTB) is a parameter in which both metabolic tumor volume (MTV) and tumor activity are integrated. Here, we analyzed the prognostic value of SUVmax, SUVsum (sum of the SUVmax), whole-body MTV (MTVwb) and MTBwb from baseline and interim PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). Twenty-nine patients with histologically proven DLBCL were imaged by PET/CT before treatment (Exam I), and one week after the first dose of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy (Exam II). Biopsy specimens were examined by an expert hematopathologist, the Ki-67 proliferation index (PI) was estimated for each biopsy site from the MIB-1 stained sections. The response evaluation was performed after chemotherapy completion (6-8 cycles). All patients had one or more visualized lymphomatous lesions on (18)F-FDG-PET/CT. The SUVmax of the whole-body (BmSUVmax) was higher than the SUVmax at biopsy site (BxSUVmax) (mean: 20.1 vs. 17.3, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). The PI correlated with the BxSUVmax (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). One week after chemotherapy, SUVmax, SUVsum, MTVwb, and MTBwb decreased significantly (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, respectively), SUVsum, MTVwb and MTBwb at Exam II correlated with chemotherapy response at treatment completion (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, respectively). SUVmax is more accurate to detect tumor aggressiveness than biopsy in DLBCL, since BmSUVmax represents the most aggressive tumor of the patient. Interim PET/CT as early as one week after R-CHOP therapy predicts response. Thus, it could be used as a tool for guidance of risk stratification in DLBCL.

International immunology, 2004

Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC no... more Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens-two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-gamma (IFN-gamma-DC) exhibit therapeutic potential on acute experimental allergic encephalomyelitis (EAE) in Lewis rats, and on chronic-relapsing EAE in B6 and SJL/J mice. During incipient EAE [day 5 post-immunization (p.i.) in rats, day 7 p.i. in mice], IFN-gamma-DC were injected s.c. Severity of clinical signs of EAE was dramatically inhibited in animals injected with IFN-gamma-DC, showing normal magnetic resonance imaging (MRI) of the spinal cord and brain. In contrast, the EAE rats receiving PBS or naive DC had severe clinical signs with multiple and extensive MRI lesions in the spinal cord and brain. IFN-gamma-DC triggered an antigen-s...

Multiple Sclerosis International, 2013

The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callos... more The aim of this study was to evaluate diffusion tensor imaging (DTI) indices in the corpus callosum and pyramidal tract in normalappearing white matter (NAWM) and the caudate nucleus and thalamus in deep grey matter (NADGM) in all MS subtypes and clinically isolated syndrome (CIS). Furthermore, it was determined whether these metrics are associated with clinical measures and the serum levels of candidate immune biomarkers. Apparent diffusion coefficients (ADC) values were significantly higher than in controls in all six studied NAWM regions in SPMS, 4/6 regions in RRMS and PPMS and 2/6 regions in CIS. In contrast, decreased fractional anisotropy (FA) values in comparison to controls were detected in 2/6 NAWM regions in SPMS and 1/6 in RRMS and PPMS. In RRMS, the level of neurological disability correlated with thalamic FA values ( = 0.479, = 0.004). In chronic progressive subtypes and CIS, ADC values of NAWM and NADGM were associated with the levels of MIF, sFas, and sTNF-. Our data indicate that DTI may be useful in detecting pathological changes in NAWM and NADGM in MS patients and that these changes are related to neurological disability. of Hindawi Publishing Corporation

NMR in Biomedicine, 2013

To compare different MRI sequences for the detection of lesions and the evaluation of response to... more To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL), 18 patients with histology-confirmed DLBCL underwent 3-T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T 1 -weighted pre-and post-contrast, T 2 -weighted with and without fat suppression, and a single-shot echo-planar diffusion-weighted imaging (DWI) with two b values (0 and 800 s/mm 2 ). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T 2 -weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T 2 -weighted image with fat suppression decreased significantly (p < 0.01), and that of the T 1weighted pre-contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 Â 10 -3 mm 2 /s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = À0.62, p < 0.01). In conclusion, this study indicates that T 2 -weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI.

Neurological Research, 2014

To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in... more To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS). Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including the expanded disability status scale (EDSS), were performed at baseline, month 24, and at year 7. Baseline cortical NAA/Cr correlated inversely with EDSS at month 24 (r = -0·61, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05). Baseline cortical NAA/Cr also correlated inversely with EDSS at the 7-year follow-up (r = -0·56, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05). Baseline brain parenchymal fraction (BPF) correlated inversely with EDSS at month 24 (r = -0·61, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0·05), but not with EDSS at year 7. Cortical NAA/Cr in early RRMS correlated with clinical disability after 2 and 7 years and may be used as a predictor of long-term disease outcome.

Multiple Sclerosis Journal, 2013

Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortica... more Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

Molecular Imaging and Biology, 2011

The purpose of this study is to evaluate the time course of early chemotherapy response in patien... more The purpose of this study is to evaluate the time course of early chemotherapy response in patients with aggressive non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lymphoma (NHL) by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). Eight patients with histologically proven aggressive NHL were imaged by MRI and PET/CT before treatment (E1), 1 week (E2), and two cycles (E3) after chemotherapy. The mean tumor volume on MRI was 276 mL at baseline; it decreased 58% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 65% further at E3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), giving a total decrease of 84% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean maximum standardized uptake value (SUV(max)) of 20. The SUV(max) decreased 60% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 59% further at E3 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), giving a total decrease of 83% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The active tumor burden (mean 229 mL) decreased 66% at E2 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The tumor volume on MRI correlated with the active tumor volume on fused PET/CT images in the same region of interest at both E1 and E2 (r = 0.88, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, respectively). Standard chemotherapy causes rapid decrease of both tumor metabolic activity and volume as early as 1 week, which continues to decline during therapy. Both volumetric MRI and PET/CT are valuable tools for early treatment response evaluation of aggressive NHL.

Leukemia & Lymphoma, 2012

Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by [18F]-fluorod... more Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT). The maximum SUV of the whole-body (BmSUV(max)) reflects the tumor aggressiveness in non-Hodgkin lymphoma. To evaluate the correlation between SUV(max) at biopsy site (BxSUV(max)) and proliferation potential of tumor cells in untreated diffuse large B-cell lymphoma (DLBCL), fifteen pre-therapy PET/CT scans in patients with histologically proven DLBCL were retrospectively analyzed together with Ki-67 proliferation index. The BmSUV(max) and BxSUV(max) were evaluated from the fused PET/CT images. Ki-67 proliferation index was measured in the biopsy specimens using an immunohistochemical technique in archival paraffin-embedded sections. The BmSUV(max) was significantly higher than the BxSUV(max) (mean 19.6 vs.16.6, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). The BxSUV(max) correlated with the Ki-67 proliferation index (r = 0.7, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), but no correlation was detected between the BmSUV(max) and the Ki-67 proliferation index. The results indicate that tumor proliferation potential might be predicted in vivo by FDG-PET/CT images. Thus, PET/CT is useful to guide biopsy by selecting sites with the BmSUV(max) when clinically appropriate.

The Lancet Neurology, 2011

Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partl... more Background Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly eff ective. We aimed to establish whether add-on of simvastatin, a statin with anti-infl ammatory properties, improves this effi cacy.

Journal of Neuroscience Research, 2004

A photochemical lesion was induced in the right sensory motor cortex of rat brains. We examined a... more A photochemical lesion was induced in the right sensory motor cortex of rat brains. We examined at various time points the occurrence of different types of neuronal death with respect to a potential therapeutic window. The lesion appearance was documented by magnetic resonance imaging, and functional recovery was evaluated by behavioral tests showing recovery at 48 hr after lesioning. At 0.5, 1, 3, 6, 12, 24, 48, and 72 hr postlesion, cortical layers IV and V were examined by light and electron microscopy. Ultrastructural changes, which corresponded well to light microscopy findings, were found in both hemispheres. In the lesioned area, the neuropil appeared disorganized at 0.5 hr, and apoptotic and necrotic cell death was found at 0.5-3 hr. After 3 hr, the tissue was disintegrated. On the contralateral side, chromatin clumping appeared at 0.5-3 hr. At 3 hr, ruptured membranes were found, a sign of irreversible cell death. At 6 -72 hr, the membranes were intact, and the chromatin was not clumped but heterogeneously distributed. The nuclei contained dispersed nucleoli at 48 -72 hr. The morphology correlated well with magnetic resonance images and functional behavior. Our study demonstrates that a photochemical lesion is a useful model for studying morphological changes in injured cells. It results in a permanent infarction within 3 hr. In that the morphology on the contralateral side drastically changed between 3 and 6 hr, the cellular alterations at these time points might represent a break point at which cells either progress toward cell death or recover.

The Journal of Immunology, 2004

Identification of polymorphic genes regulating inflammatory diseases may unravel crucial pathogen... more Identification of polymorphic genes regulating inflammatory diseases may unravel crucial pathogenic mechanisms. Initial steps to map such genes using linkage analysis in F 2 intercross or backcross populations, however, result in broad quantitative trait loci (QTLs) containing hundreds of genes. In this study, an advanced intercross line in combination with congenic strains, was used to fine-map Eae18 on rat chromosome 10 in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Myelin oligodendrocyte glycoprotein-induced EAE is a chronic relapsing disease that closely mimics key features of multiple sclerosis. Congenic DA.ACI rat strains localized Eae18 to an ϳ30-Mb large region. Fine-mapping was then performed in an advanced intercross line consisting of a (DA ؋ PVG.1AV1)F 7 intercross, resulting in two adjacent EAE-regulating QTLs designated Eae18a and Eae18b. The two QTLs span 5.5 and 3 Mb, respectively, and the 3-Mb Eae18b contains as few as 10 genes, including a cluster of chemokine genes (CCL1, CCL2, CCL7, and CCL11). Eae18a and Eae18b are syntenic to human chromosome 17p13 and 17q11, respectively, which both display linkage to multiple sclerosis. Thus, Eae18 consists of at least two EAE-regulating genes, providing additional evidence that clustering of disease-regulating genes in QTLs is an important phenomenon. The overlap between Eae18a and Eae18b with previously identified QTLs in humans and mice further supports the notion that susceptibility alleles in inflammatory disease are evolutionary conserved between species.

European Journal of Radiology, 2011

Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic re... more Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) are oncologic feasible techniques for evaluating the malignancy of tumors. Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by PET/CT. Apparent diffusion coefficient (ADC) measured by DWI can provide information about tissue cellularity. The aim of the study was to evaluate the correlation between SUV and ADC in untreated diffuse large B-cell lymphoma (DLBCL). Fifteen pre-therapy patients with histologically proven DLBCL underwent PET/CT and DWI examinations within two days. Tumor glucose metabolism was evaluated by the maximum and mean SUV (SUV(max) and SUV(mean)) on the PET/CT images. The mean ADC value was measured directly on the parametric ADC maps. In total, 28 lymphoma lesions with best match PET/CT and DWI were identified and evaluated. The mean SUV(max) and SUV(mean) were 16.8 and 11.1, respectively; the mean ADC was 0.74 × 10(-3)mm(2)/s. There was no correlation between the mean ADC and the SUV(max) or SUV(mean). SUV determined from PET/CT and ADC value measured from DWI are different indices for the diagnosis of tumor malignancy, they may provide complimentary functional information of tumor tissue.