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1.
BMC Musculoskelet Disord ; 25(1): 144, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360606

RESUMO

BACKGROUND: Investigation of the association between leg axis alignment and biochemical MRI in young professional soccer players in order to identify a potential influence of the leg axis on cartilage regions at risk. METHODS: Sixteen professional soccer players (21 ± 3 years) underwent static and dynamic leg axis analysis via radiation free DIERS formetric 4 D as well as 3-T MRI examination of both knees. Quantitative T2* mapping of the knee cartilage was performed and T2* values were evaluated as 144 regions of interest. Subgroup analysis was performed in players with severe varus alignment (> 6°). RESULTS: Analysis of the leg axis geometry revealed a mean static alignment of 6.6° ± 2.5 varus and a mean dynamic alignment of 5.1° ± 2.6 varus. Quantitative T2* mapping showed significantly increased T2* values in the superficial cartilage layer compared to the deeper region (p < 0.001) as well as a significant increase in relaxation times in the femoral cartilage from anterior to intermediate to posterior (p < 0.001). Combination of both methods revealed a significant correlation for the degree of varus alignment and the femoral, posterior, deep region of the medial knee compartment (r = 0.4; p = 0.03). If severe varus alignment was present this region showed a significant increase in relaxation time compared to players with a less pronounced leg axis deviation (p = 0.003). CONCLUSION: This study demonstrates that varus alignment in young soccer players is associated with elevated T2* relaxation times in the deep cartilage layer of the medial, posterior, femoral compartment and might therefore be a contributing factor in the early pathogenesis of manifest cartilage lesions. Therefore, these findings should be considered in the development of preventive training programs.


Assuntos
Cartilagem Articular , Futebol , Humanos , Perna (Membro) , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos
2.
Ann Oncol ; 32(8): 983-993, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34272041

RESUMO

BACKGROUND: Guidelines recommend atezolizumab plus nab-paclitaxel (A + nP) for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer expressing programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (IC), based on IMpassion130. We report the final overall survival (OS) and safety of that study as per the prespecified analysis plan. PATIENTS AND METHODS: Patients were randomized to nP 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) with atezolizumab 840 mg (A + nP) or placebo (P + nP; days 1 and 15), until progression or unacceptable toxicity. Coprimary endpoints were progression-free survival [intention-to-treat (ITT) and PD-L1 IC-positive populations] and OS (tested hierarchically in the ITT population and, if significant, in the PD-L1 IC-positive population). RESULTS: Each arm comprised 451 patients; 666 (73.8%) had died by the final OS analysis cut-off (median follow-up, 18.8 months; interquartile range, 8.9-34.7 months). Median OS in the ITT population was 21.0 months [95% confidence interval (CI), 19.0-23.4 months] with A + nP, and 18.7 months (95% CI, 16.9-20.8 months) with P + nP [stratified hazard ratio (HR), 0.87; 95% CI, 0.75-1.02; P = 0.077]. Exploratory analysis in the PD-L1 IC-positive population showed a median OS of 25.4 months (95% CI, 19.6-30.7 months) with A + nP (n = 185) and 17.9 months (95% CI, 13.6-20.3 months) with P + nP (n = 184; stratified HR, 0.67; 95% CI, 0.53-0.86). Safety outcomes were consistent with previous analyses and the known toxicity profiles of each agent. Immune-mediated adverse events of special interest were reported in 58.7% and 41.6% of patients treated with A + nP and P + nP, respectively. CONCLUSION: Although the OS benefit in the ITT population was not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed with A + nP in PD-L1 IC-positive patients, consistent with prior interim analyses. This combination remained safe and tolerable with longer follow-up.


Assuntos
Neoplasias de Mama Triplo Negativas , Albuminas , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Paclitaxel , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
3.
Ann Oncol ; 32(8): 994-1004, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34219000

RESUMO

BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. CONCLUSION: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.


Assuntos
Neoplasias de Mama Triplo Negativas , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Paclitaxel/uso terapêutico , Intervalo Livre de Progressão , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
4.
J Eur Acad Dermatol Venereol ; 35(5): 1143-1151, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33617042

RESUMO

BACKGROUND AND OBJECTIVE: Anti-IL-17A IgG/κ monoclonal antibody CJM112 binds both IL-17A and IL-17AF. The purpose of this First-in-Human study was to assess CJM112 effects on safety and efficacy in patients with moderate to severe plaque psoriasis. METHODS: This study had two parts: single ascending doses of 5-450 mg subcutaneous (s.c.) CJM112 (SAD) and multi-dose parallel groups of CJM112 15 mg, 50 mg and 150 mg s.c. low frequency or high frequency (MD). SAD/MD were double-blind, randomized and placebo-controlled; MD also included a secukinumab 150 mg s.c. arm as an active comparator. Patients 18-65 years with moderate to severe psoriasis were included in this study. The efficacy outcome was the change in Psoriasis Area Severity Index (PASI) from baseline to Week 4 in the SAD part of the study, and from baseline to Week 12 in the MD part. RESULTS: 96 patients were enrolled in this study (SAD, n = 42; MD, n = 54). In SAD, CJM112 doses from 15 mg and above demonstrated higher PASI responses compared with placebo at Week 12. CJM112 450 mg did not add further efficacy, but efficacy duration was prolonged compared with CJM112 150 mg. CJM112 MD resulted in a dose-dependent decrease in PASI over time to Week 12. CJM112 150 mg high frequency did not exceed the effect of CJM112 150 mg low frequency and had similar efficacy to secukinumab 150 mg. The safety profile of CJM112 was as expected for an antibody targeting IL-17A/IL-17AF. CONCLUSIONS: CJM112 had clinical efficacy in moderate to severe psoriasis and was generally safe and well tolerated in the doses tested. Additional neutralization of IL-17AF did not translate to increased clinical efficacy compared with secukinumab.


Assuntos
Interleucina-17 , Psoríase , Anticorpos Monoclonais/efeitos adversos , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Anaesthesist ; 67(3): 177-187, 2018 03.
Artigo em Alemão | MEDLINE | ID: mdl-29230501

RESUMO

BACKGROUND: The annual number of physician-based emergency missions reported is continuously increasing. Data from large cities concerning this development over long periods is sparse. MATERIAL AND METHODS: In this retrospective study the charts of all ground-based physician-staffed emergency missions in the city of Leipzig for the first quarters of 2003 and 2013 were analyzed. Patient characteristics, injury and illness severities, mission location, hospital admission rate, as well as emergency interventions were collated. The emergency mission rate was calculated as rescue missions per 1000 inhabitants per year. RESULTS: The number of physician-staffed emergency missions increased by approximately 24% between 2003 and 2013 (6030 vs. 7470, respectively). The emergency mission rate was 48 vs. 58 in the 2 study periods. The median patient age increased from 66 to 70 years. The number of geriatric patients (age ≥ 85 years: n = 650 (11%) vs. n = 1161 (16%), p < 0.01) also increased. The corresponding number of emergency missions in nursing homes showed a fourfold (n = 175, 3% vs. n = 750, 10%, p < 0.01). The percentage of hospital admissions also increased (n = 3049, 51% vs. n = 4738, 66%, p < 0.01). A change in patient distribution to level I hospitals was noticed (n = 1742, 29% vs. n = 3436, 46%, p < 0.01). CONCLUSION: The findings suggest that the necessity for the high number of physician-staffed emergency missions should be verified, especially in the context of strained emergency healthcare resources. The basis of an optimized use of resources could be a better inclusion of alternative, especially ambulant, healthcare structures and the implementation of a structured emergency call questionnaire accompanied by a more efficient disposition of the operating resources, not least in view of the economic aspects. Taking the concentrated patient allocation to level 1 hospitals into consideration, there is a need for optimized patient distribution strategies to minimize the overload of individual institutions and thereby improve the general quality of care at the interface between preclinical and clinical emergency medicine.


Assuntos
Serviços Médicos de Emergência/organização & administração , Médicos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/estatística & dados numéricos , Criança , Pré-Escolar , Cidades , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Alemanha , Recursos em Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Admissão do Paciente/estatística & dados numéricos , Trabalho de Resgate , Estudos Retrospectivos , Adulto Jovem
8.
Neurobiol Dis ; 69: 54-64, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24825317

RESUMO

Human immunodeficiency virus-1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons.


Assuntos
Proteína gp120 do Envelope de HIV/metabolismo , Lectina de Ligação a Manose/metabolismo , Neurônios/metabolismo , Organelas/metabolismo , Western Blotting , Linhagem Celular Tumoral , Células Cultivadas , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Proteína gp120 do Envelope de HIV/genética , HIV-1 , Humanos , Imunoprecipitação , Lectina de Ligação a Manose/genética , Microscopia Confocal , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neurônios/efeitos dos fármacos , Nocodazol/farmacologia , Organelas/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Vesículas Transportadoras/efeitos dos fármacos , Vesículas Transportadoras/metabolismo , Moduladores de Tubulina/farmacologia
9.
IEEE Trans Nucl Sci ; 60(1): 44-52, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24077642

RESUMO

Positron emission tomography (PET) detectors based on continuous scintillation crystals can achieve very good performance and have a number of practical advantages compared to detectors based on a pixelated array of crystals. Our goal is to develop a thick continuous detector with high energy and spatial resolution, along with high γ-photon capture efficiency. We examine the performance of two crystal blocks: a 46 × 46 × 14 mm3 and a 48 × 48 × 25 mm3 block of LYSO (Lutetium Yttrium Orthosilicate). Using Maximum Likelihood (ML) positioning based upon the light response function (LRF) in the 14 mm thick crystal, we measure a spatial resolution of 3 mm in the central region of the crystal with degradation near the edges due to reflections off the crystal sides. We also show that we can match the spatial resolution achieved using a 14 mm thick crystal by using a 25 mm thick crystal with slots cut into the gamma entrance surface to narrow the LRF. We also find that we can improve the spatial resolution performance near the detector edges by reducing the reflectivity of the crystal sides, albeit with some loss in energy resolution.

10.
Scand J Rheumatol ; 39(2): 99-108, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20337545

RESUMO

Pregnancy can create a challenge for physicians caring for women with rheumatic diseases. For many women with rheumatoid arthritis (RA), pregnancy can provide a reprieve from long-term joint pain and inflammation, but others will not experience remission and will continue to need medication. Systemic lupus erythematosus (SLE) may remain quiet in some women, but in others may become more aggressive during pregnancy, putting both mother and foetus at risk. Women with limited scleroderma can do remarkably well, but scleroderma renal crises can be difficult to manage. A third of pregnancies in women with antiphospholipid syndrome (APS) may be refractory to our best therapy. In general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes.


Assuntos
Doenças Reumáticas/terapia , Feminino , Monitorização Fetal , Humanos , Gravidez , Complicações na Gravidez/terapia
11.
Sci Rep ; 10(1): 7480, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366912

RESUMO

Temperature-resolved magnetic particle imaging (MPI) represents a promising tool for medical imaging applications. In this study an approach based on a single calibration measurement was applied for highlighting the potential of MPI for monitoring of temperatures during thermal ablation of liver tumors. For this purpose, liver tissue and liver tumor phantoms embedding different superparamagnetic iron oxide nanoparticles (SPION) were prepared, locally heated up to 70 °C and recorded with MPI. Optimal temperature MPI SPIONs and a corresponding linear model for temperature calculation were determined. The temporal and spatial temperature distributions were compared with infrared (IR) camera results yielding quantitative agreements with a mean absolute deviation of 1 °C despite mismatches in boundary areas.


Assuntos
Hipertermia Induzida , Raios Infravermelhos , Neoplasias Hepáticas , Nanopartículas de Magnetita , Tomografia Óptica , Animais , Galinhas , Fígado , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia
12.
Sci Rep ; 10(1): 15355, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948810

RESUMO

The tibial tuberosity-trochlear groove (TT-TG) distance is a radiographic measurement that is used to quantify malalignment of the patellofemoral joint (PFJ) in cross-sectional imaging. There is an ongoing debate about the impact of the TT-TG-distance on lateral patellar instability and the initiating of cartilage degeneration. In this prospective study, the association of T2* relaxation times and TT-TG distances in professional soccer players was analyzed. 36 knees of 18 professional soccer players (age: 21 ± 2.8 years) were evaluated. Participants underwent knee MRI at 3 T. For qualitative image analysis, fat-saturated 2D PD-weighted Fast Spin Echo (FSE) and T1-weighted FSE sequences were used. For quantitative analysis, T2* measurements in 3D data acquisitions were performed. In a qualitative analysis there was no structural cartilage damage and no abnormalities of the patellar and trochlea shape. The highest T2* values (26.7 ± 5.9 ms) were observed in the central compartment of the patella. The mean TT-TG distance was 10 ± 4 mm (range 3-20 mm). There was no significant correlation between TT-TG distance and T2* relaxation times in all three compartments of the retropatellar cartilage. Our study shows that so long as patellar and trochlear morphology is normal, TT-TG distance alone does not affect the tissue structure of the retropatellar cartilage in professional soccer players.


Assuntos
Cartilagem/fisiologia , Articulação do Joelho/fisiologia , Imageamento por Ressonância Magnética/métodos , Patela/fisiologia , Articulação Patelofemoral/fisiologia , Futebol/estatística & dados numéricos , Tíbia/fisiologia , Adulto , Humanos , Masculino , Estudos Prospectivos , Relaxamento , Adulto Jovem
13.
Methods Mol Biol ; 547: 139-53, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19521842

RESUMO

We have developed a rapid in vitro propagation system, via axillary shoot formation from nodal explants of Swertia chirata Buch Ham. Culture medium supplemented with 2 mg/L. BAP is best for direct shoot regeneration initially formed adventitious buds from axils of the nodal explants after 30 days. The reduced BAP concentration 0.5 mg/L proliferate shoots effectively. Kept the number of hyperhydrated shoots to minimal and induced on an average 22-38 shoots per flask (4.3 cm average length). The regenerated shoots (5- to 6-m long) formed roots very well in Murashige and Skoog (MS) medium devoid of any growth regulator and followed by acclimatization of plants in pre-sterilized sand containing 1% Trichoderma viride and Azatobactor chrococcum as bioinoculants. The regenerated plants don't show any genomic alterations. This protocol also outlines procedure of assessment of marker iridoid glycosides (amarogentin and amaroswerin) from callus, roots, multiple shoots, regenerated plants, and mother plant. High propagation frequency, reproducibility of procedure, molecular, and phenotypic and chemical stability ensures the efficiency of the developed protocol.


Assuntos
Glicosídeos/metabolismo , Swertia/metabolismo , Biomarcadores , Cromatografia Líquida de Alta Pressão , Meios de Cultura , Espectroscopia de Ressonância Magnética , Reação em Cadeia da Polimerase , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Swertia/crescimento & desenvolvimento , Técnicas de Cultura de Tecidos
14.
Physiol Meas ; 40(10): 105002, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31519009

RESUMO

OBJECTIVE: Magnetic particle imaging (MPI) is a new, fast 3D imaging technique, which is considered promising for angiographies. As available MPI scanners suffer from restricted spatial resolution and are mostly constructed for small animal imaging, no vessels within one organ have been depicted by MPI, yet. The purpose of this study was to develop an ex vivo organ perfusion system to display vessels within one organ of human size by MPI and to compare the results to an established 3D imaging technique. APPROACH: An ex vivo porcine kidney perfusion system compatible with digital subtraction angiography (DSA), magnetic resonance tomography and MPI was developed. DSA was used to exemplarily prove intact vessel structures under ex vivo perfusion in two organs. Perfusion in nine organs was displayed by the 3D imaging techniques magnetic resonance angiography (MRA) and MPI angiography. All visible vessels in MRA and MPI were counted and their number compared between both techniques. MAIN RESULTS: The ex vivo organ perfusion system allowed us to perform angiographies by DSA, MRA and MPI. With it, organs of human size could be imaged in small animal scanners, which permitted us to depict vessels within one organ by MPI for the first time. In comparison to MRA, 33% of all vessels were visible in MPI, a difference probably caused by restricted spatial resolution in MPI. SIGNIFICANCE: The presented ex vivo organ perfusion system can serve to practically evaluate MPI's potential for angiography in human-sized organs. This is especially relevant as long as available, for angiography-suited MPI scanners still suffer from size and spatial resolution restrictions.


Assuntos
Imageamento Tridimensional/métodos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Animais , Humanos , Suínos
15.
Cell Death Differ ; 14(2): 296-305, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16841089

RESUMO

The chemokine receptors CCR5 and CXCR4 serve, in addition to CD4, as coreceptors for human immunodeficiency virus-1 (HIV-1), and infection with HIV-1 can cause dementia. In brain-derived cells, HIV-1 envelope glycoprotein gp120 initiates a signaling cascade that involves p38 mitogen-activated protein kinase and leads to neuronal cell death. Using mixed neuronal/glial cultures from rats and mice genetically deficient in one or both HIV coreceptors, we show here that CCR5, CXCR4 or both can mediate HIV/gp120 neurotoxicity depending on the viral strain. Paradoxically, we also found evidence for a CCR5-mediated neuroprotective pathway. We identify protein kinase Akt/PKB as an essential component of this pathway, which can be triggered by the CCR5 agonists macrophage inflammatory protein-1beta and regulated-and-normal-T-cell-expressed-and-secreted. Moreover, these CCR5 ligands prevent neuronal cell death induced by stromal cell-derived factor-1, a CXCR4 agonist. Both neurons and glia coexpress CXCR4 and CCR5. Ca2+ imaging experiments demonstrate that engagement of CCR5 prevents CXCR4-triggered increases in intracellular free Ca2+. This finding suggests that CCR5 ligands can protect neurons at least, in part, by modulating CXCR4-mediated toxicity through heterologous desensitization.


Assuntos
HIV-1/imunologia , Neurônios/citologia , Neurônios/patologia , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Quimiocina CXCL12 , Citocinas/toxicidade , Proteína gp120 do Envelope de HIV/toxicidade , Infecções por HIV/virologia , Imidazóis/farmacologia , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Modelos Imunológicos , N-Metilaspartato/toxicidade , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Neurônios/virologia , Neurotoxinas/toxicidade , Piridinas/farmacologia , Ratos , Receptores CCR5/deficiência , Receptores CXCR4/deficiência , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
16.
AJNR Am J Neuroradiol ; 28(8): 1547-51, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17846209

RESUMO

BACKGROUND AND PURPOSE: Our aim was to compare different field strengths monitoring physiologic changes due to oral stimulation of parotid glands by using diffusion-weighted (DW) echo-planar imaging (EPI). MATERIALS AND METHODS: Twenty-seven healthy volunteers were examined with a DW-EPI sequence at 1.5T and 3T before and after oral stimulation with commercially available lemon juice. The b factors used were 0, 500, and 1000 s/mm(2). Apparent diffusion coefficient (ADC) maps were evaluated with a manually placed region of interest including the entire parotid gland. For comparison of results, a Student t test was used on the basis of the mean of the volunteer median values. To compare both field strengths, we calculated the Pearson correlation coefficient (r). RESULTS: DW-EPI MR imaging visualized the parotid glands of all volunteers. With 1.5T, the mean ADC before stimulation was 1.12 x 10(-3) mm(2)/s +/- 0.08 x 10(-3) mm(2)/s. After stimulation with lemon juice, the ADC increased to 1.18 x 10(-3) mm(2)/s +/- 0.09 x 10(-3) mm(2)/s. For 3T, the ADC before stimulation was 1.14 x 10(-3) mm(2)/s +/- 0.04 x 10(-3) mm(2)/s, with an increase to 1.17 x 10(-3) mm(2)/s +/- 0.05 x 10(-3) mm(2)/s after stimulation. For both field strengths, the increase in ADC after stimulation was significant (P < .001). High correlations between both field strengths were found pre- and poststimulation (r = 0.955, and 0.936, respectively). CONCLUSION: DW-EPI MR imaging allows monitoring of physiologic changes due to oral stimulation of parotid glands by using DW imaging with high correlation between 1.5T and 3T.


Assuntos
Imageamento por Ressonância Magnética , Glândula Parótida/fisiologia , Paladar/fisiologia , Adulto , Citrus , Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Valores de Referência
17.
Rofo ; 179(5): 473-9, 2007 May.
Artigo em Alemão | MEDLINE | ID: mdl-17436181

RESUMO

PURPOSE: To assess the detectability of single magnetically labeled mesenchymal stem cells (MSC) in-vitro on a clinical 3T MR scanner using a small animal volume coil. MATERIALS AND METHODS: GFP-transfected MSC were magnetically labeled with superparamagnetic iron oxide particles (SPIO) while applying different dosages of iron (56 vs. 560 microg Fe/ml). The cellular iron content was determined with atomic absorption spectrometry (AAS). Single labeled MSC were displayed in a culture flask using MR imaging and microscopy. Special cell phantoms were designed to examine the detection of labeled MSC with MR imaging in a spatial model. A T2*-weighted 3D gradient echo sequence with isotropic spatial resolution of 150 to 500 microm (3) was used for image acquisition. The detection of labeled MSC in the cell phantoms was quantitatively evaluated using an automated image analysis. Statistical analysis was performed with a significance level of p < 0.05. RESULTS: The labeling of MSC yielded a mean cellular iron content of 1.5 +/- 0.17 pg Fe/cell (56 microg Fe/ml) and 8.3 +/- 1.85 pg Fe/cell (560 microg Fe/ml). Examination of the culture flasks showed single magnetically labeled MSC centered in much larger MR signal voids. The detection and quantification of single MSC in cell phantoms were feasible for spatial resolutions of 150 microm and 200 microm. Cells with a lower SPIO content (1.5 +/- 0.17 pg Fe/cell) were detected in 14.2 +/- 4.2 % (150 microm) and 7.7 +/- 3.8 % (200 microm). MSC with a higher cellular SPIO content (8.3 +/- 1.85 pg Fe/cell) revealed significantly higher occurrences at both spatial resolutions with 81.4 +/- 5.8 % (150 microm) and 59.9 +/- 12.4 % (200 microm), respectively. Regarding the spatial resolution (150 vs. 200 microm), significantly different detection rates were determined only for MSC with the higher SPIO content (8.3 +/- 1.85 pg Fe/cell). CONCLUSION: Detection of single magnetically labeled MSC is feasible on a clinical 3T MR scanner with a small animal volume coil at isotropic spatial resolutions of 150 microm and 200 microm. The number of detected cells is influenced by the cellular iron content and the spatial resolution.


Assuntos
Meios de Contraste , Óxido Ferroso-Férrico , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Células-Tronco Mesenquimais/ultraestrutura , Animais , Estudos de Viabilidade , Compostos Férricos/análise , Imagens de Fantasmas , Ratos , Ratos Sprague-Dawley , Espectrofotometria Atômica
18.
IEEE Trans Med Imaging ; 36(7): 1511-1521, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28207386

RESUMO

The temporal resolution of the tomographic imaging method magnetic particle imaging (MPI) is remarkably high. The spatial resolution is degraded for measured voltage signal with low signal-to-noise ratio, because the regularization in the image reconstruction step needs to be increased for system-matrix approaches and for deconvolution steps in x -space approaches. To improve the signal-to-noise ratio, blockwise averaging of the signal over time can be advantageous. However, since block-wise averaging decreases the temporal resolution, it prevents resolving the motion. In this paper, a framework for averaging motion-corrupted MPI raw data is proposed. The motion is considered to be periodic as it is the case for respiration and/or the heartbeat. The same state of motion is thus reached repeatedly in a time series exceeding the repetition time of the motion and can be used for averaging. As the motion process and the acquisition process are, in general, not synchronized, averaging of the captured MPI raw data corresponding to the same state of motion requires to shift the starting point of the individual frames. For high-frequency motion, a higher frame rate is potentially required. To address this issue, a binning method for using only parts of complete frames from a motion cycle is proposed that further reduces the motion artifacts in the final images. The frequency of motion is derived directly from the MPI raw data signal without the need to capture an additional navigator signal. Using a motion phantom, it is shown that the proposed method is capable of averaging experimental data with reduced motion artifacts. The methods are further validated on in-vivo data from mouse experiments to compensate the heartbeat.


Assuntos
Movimento (Física) , Algoritmos , Animais , Artefatos , Processamento de Imagem Assistida por Computador , Camundongos , Razão Sinal-Ruído
19.
Phys Med Biol ; 62(9): 3470-3482, 2017 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-28035904

RESUMO

Magnetic particle imaging (MPI) facilitates the rapid determination of 3D in vivo magnetic nanoparticle distributions. In this work, liver MPI following intravenous injections of ferucarbotran (Resovist®) was studied. The image reconstruction was based on a calibration measurement, the so called system function. The application of an enhanced system function sample reflecting the particle mobility and aggregation status of ferucarbotran resulted in significantly improved image reconstructions. The finding was supported by characterizations of different ferucarbotran compositions with the magnetorelaxometry and magnetic particle spectroscopy technique. For instance, similar results were obtained between ferucarbotran embedded in freeze-dried mannitol sugar and liver tissue harvested after a ferucarbotran injection. In addition, the combination of multiple shifted measurement patches for a joint reconstruction of the MPI data enlarged the field of view and increased the covering of liver MPI on magnetic resonance images noticeably.


Assuntos
Meios de Contraste/química , Dextranos/química , Processamento de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Imagem Molecular/métodos , Animais , Calibragem , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Dextranos/administração & dosagem , Dextranos/farmacocinética , Fígado/metabolismo , Nanopartículas de Magnetita/administração & dosagem , Camundongos , Distribuição Tecidual
20.
Eur J Radiol ; 86: 105-111, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28027735

RESUMO

OBJECTIVE: Recent investigation has underlined the potential of quantitative MR imaging to be used as a complementary tool for the diagnosis of cartilage degeneration at an early state. The presented study analyses T2* relaxation times of articular cartilage of the knee in professional athletes and compares the results to age- and BMI (Body Mass Index)-matched healthy amateur athletes. MATERIALS AND METHODS: 22 professional football players and 22 age- and BMI-matched individuals were underwent knee Magnetic Resonance Imaging (MRI) at 3T including qualitative and quantitative analysis. Qualitative analysis included e.g. meniscal tears, joint effusion and bone edema. For quantitative analysis T2* (22 ET: 4.6-53.6ms) measurements in 3D data acquisition were performed. Deep and superficial layers of 22 predefined cartilage segments were analysed. All data sets were postprocessed using a dedicated software tool. Statistical analysis included Student t-test, confidence intervals and a random effects model. RESULTS: In both groups, T2* relaxation times were significantly higher in the superficial compared to the deep layers (p<0.001). Professional athletes had significantly higher relaxation times in eight superficial and three deep cartilage layers in the predefined cartilage segments (p<0.05). Highly significant differences were found in the weight-bearing segments of the lateral superficial femoral condyle (p<0.001). CONCLUSION: Elevated T2* values in cartilage layers of professional football players compared to amateur athletes were noted. The effects seem to predominate in superficial cartilage layers.


Assuntos
Cartilagem Articular/fisiologia , Futebol/fisiologia , Esportes/fisiologia , Adolescente , Adulto , Traumatismos em Atletas/patologia , Traumatismos em Atletas/fisiopatologia , Índice de Massa Corporal , Cartilagem Articular/patologia , Feminino , Fêmur/fisiologia , Humanos , Traumatismos do Joelho/patologia , Traumatismos do Joelho/fisiopatologia , Articulação do Joelho/patologia , Articulação do Joelho/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos Prospectivos , Suporte de Carga/fisiologia , Adulto Jovem
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