RESUMO
OBJECTIVES: The central nervous system disorder in systemic lupus erythematosus (SLE), called neuropsychiatric lupus (NPSLE), is one of the most severe phenotypes with various clinical symptoms, including mood disorder, psychosis and delirium as diffuse neuropsychological manifestations (dNPSLE). Although stress is one of the aggravating factors for neuropsychiatric symptoms, its role in the pathogenesis of dNPSLE remains to be elucidated. We aimed to investigate stress effects on the neuropsychiatric pathophysiology in SLE using lupus-prone mice and patients' data. METHODS: Sleep disturbance stress (SDS) for 2 weeks was placed on 6-8-week-old female MRL/lpr and control mice. Behavioural phenotyping, histopathological analyses and gene and protein expression analyses were performed to assess SDS-induced neuroimmunological alterations. We also evaluated cytokines of the cerebrospinal fluid and brain regional volumes in patients with dNPSLE and patients with non-dNPSLE. RESULTS: SDS-subjected MRL/lpr mice exhibited less anxiety-like behaviour, whereas stressed control mice showed increased anxiety. Furthermore, stress strongly activated the medial prefrontal cortex (mPFC) in SDS-subjected MRL/lpr. A transcriptome analysis of the PFC revealed the upregulation of microglial activation-related genes, including Il12b. We confirmed that stress-induced microglial activation and the upregulation of interleukin (IL) 12/23p40 proteins and increased dendritic spines in the mPFC of stressed MRL/lpr mice. IL-12/23p40 neutralisation and tyrosine kinase 2 inhibition mitigated the stress-induced neuropsychiatric phenotypes of MRL/lpr mice. We also found a higher level of cerebrospinal fluid IL-12/23p40 and more atrophy in the mPFC of patients with dNPSLE than those with non-dNPSLE. CONCLUSIONS: The microglial IL-12/23 axis in the mPFC might be associated with the pathogenesis and a promising therapeutic target for dNPSLE.
Assuntos
Lúpus Eritematoso Sistêmico , Microglia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Interleucina-12 , Subunidade p19 da Interleucina-23/metabolismo , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Camundongos , Camundongos Endogâmicos MRL lpr , Microglia/metabolismo , Estresse Fisiológico , TYK2 QuinaseRESUMO
OBJECTIVES: Voxel-based morphometry (VBM) is widely used to quantify the progression of Alzheimer's disease (AD), but improvement is still needed for accurate early diagnosis. We evaluated the feasibility of a novel diagnosis index for early diagnosis of AD based on quantitative susceptibility mapping (QSM) and VBM. METHODS: Thirty-seven patients with AD, 24 patients with mild cognitive impairment (MCI) due to AD, and 36 cognitively normal (NC) subjects from four centers were included. A hybrid sequence was performed by using 3-T MRI with a 3D multi-echo GRE sequence to obtain both a T1-weighted image for VBM and phase images for QSM. The index was calculated from specific voxels in QSM and VBM images by using a linear support vector machine. The method of voxel extraction was optimized to maximize diagnostic accuracy, and the optimized index was compared with the conventional VBM-based index using receiver operating characteristic analysis. RESULTS: The index was optimal when voxels were extracted as increased susceptibility (AD > NC) in the parietal lobe and decreased gray matter volume (AD < NC) in the limbic system. The optimized proposed index showed excellent performance for discrimination between AD and NC (AUC = 0.94, p = 1.1 × 10-10) and good performance for MCI and NC (AUC = 0.87, p = 1.8 × 10-6), but poor performance for AD and MCI (AUC = 0.68, p = 0.018). Compared with the conventional index, AUCs were improved for all cases, especially for MCI and NC (p < 0.05). CONCLUSIONS: In this preliminary study, the proposed index based on QSM and VBM improved the diagnostic performance between MCI and NC groups compared with the VBM-based index. KEY POINTS: ⢠We developed a novel diagnostic index for Alzheimer's disease based on quantitative susceptibility mapping (QSM) and voxel-based morphometry (VBM). ⢠QSM and VBM images can be acquired simultaneously in a single sequence with little increasing scan time. ⢠In this preliminary study, the proposed diagnostic index improved the discriminative performance between mild cognitive impairment and normal control groups compared with the conventional VBM-based index.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Diagnóstico Precoce , Substância Cinzenta , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVES: This study noninvasively examined the electrical conductivity (σ) characteristics of diffuse gliomas using MRI and tested its validity. METHODS: MRI including a 3D steady-state free precession (3D SSFP) sequence was performed on 30 glioma patients. The σ maps were reconstructed from the phase images of the 3D SSFP sequence. The σ histogram metrics were extracted and compared among the contrast-enhanced (CET) and noncontrast-enhanced tumour components (NCET) and normal brain parenchyma (NP). Difference in tumour σ histogram metrics among tumour grades and correlation of σ metrics with tumour grades were tested. Validity of σ measurement using this technique was tested by correlating the mean tumour σ values measured using MRI with those measured ex vivo using a dielectric probe. RESULTS: Several σ histogram metrics of CET and NCET of diffuse gliomas were significantly higher than NP (Bonferroni-corrected p ≤ .045). The maximum σ of NCET showed a moderate positive correlation with tumour grade (r = .571, Bonferroni-corrected p = .018). The mean tumour σ measured using MRI showed a moderate positive correlation with the σ measured ex vivo (r = .518, p = .040). CONCLUSIONS: Tissue σ can be evaluated using MRI, incorporation of which may better characterise diffuse gliomas. KEY POINTS: ⢠This study tested the validity of noninvasive electrical conductivity measurements by MRI. ⢠This study also evaluated the electrical conductivity characteristics of diffuse glioma. ⢠Gliomas have higher electrical conductivity values than the normal brain parenchyma. ⢠Noninvasive electrical conductivity measurement can be helpful for better characterisation of glioma.
Assuntos
Neoplasias Encefálicas/patologia , Condutividade Elétrica , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Feminino , Glioma/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: The objective of this study was to show the effect of the number of sampling points (NS) and the maximum b value (bmax) on fiber crossing detection in diffusion spectrum imaging (DSI) in clinical practice. METHODS: We performed 3-Tesla DSI in which we changed the NS (62-258) while keeping bmax at 8000 s/mm and in which we changed the bmax (4000-8000 s/mm) while keeping the NS at 129. The superior longitudinal fasciculus volume and the proportion of nerve voxels in which at least 2 (Rcr2) or 3 (Rcr3) nerve fiber bundles crossed were calculated. RESULTS: When bmax was set to 8000 s/mm, mean Rcr2 and Rcr3 values and superior longitudinal fasciculus volumes significantly increased with higher NSs, but they did not significantly change when we varied bmax with 129 NS. CONCLUSIONS: Depiction sensitivity of nerve fiber crossing in DSI improves at higher NS and bmax settings, but a bmax insensitivity appears at an intermediate NS such as 129.
Assuntos
Encéfalo/anatomia & histologia , Imagem de Tensor de Difusão/métodos , Fibras Nervosas/ultraestrutura , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Vias Neurais/anatomia & histologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Diffusion tensor imaging (DTI) of skeletal muscles has been reported as capable to characterize physiological properties, tissue microstructure and architectural organization. However, the DTI indices may vary with the contractile state of the muscles, and in the rotator cuff muscles, a change in forearm position can result in variation of the DTI indices. The purpose of this study was to examine the influence of forearm position on the major DTI indices of the rotator cuff muscles. The DTI of right rotator cuff was acquired under the neutral position and external and internal rotation of the forearm in nine healthy volunteers. Fractional anisotropy (FA) and mean diffusivity (MD) of each muscle were calculated and compared among the three forearm positions. FA and MD were significantly different between external and internal rotation in infraspinatus, teres minor and subscapularis (p<0.05). We considered that this difference was due to the change in cross-sectional area of muscle fibers based on their contractile state. That is, when the muscle is contracted, its cross-sectional area is increased and the muscle fiber density in the short axis direction becomes less. This causes a change in FA and MD due to increase in λ2 and λ3 through increased diffusion of intercellular water in the short axis direction. In conclusion, the DTI indices of the rotator cuff muscles are affected by the forearm position.
Assuntos
Braço , Imagem de Tensor de Difusão/métodos , Manguito Rotador/diagnóstico por imagem , Adulto , Imagem de Tensor de Difusão/instrumentação , Humanos , Masculino , Postura , Rotação , Adulto JovemRESUMO
OBJECTIVE: To develop and validate a volume-based, quantitative imaging marker by integrating multi-parametric MR images for predicting glioblastoma survival, and to investigate its relationship and synergy with molecular characteristics. METHODS: We retrospectively analysed 108 patients with primary glioblastoma. The discovery cohort consisted of 62 patients from the cancer genome atlas (TCGA). Another 46 patients comprising 30 from TCGA and 16 internally were used for independent validation. Based on integrated analyses of T1-weighted contrast-enhanced (T1-c) and diffusion-weighted MR images, we identified an intratumoral subregion with both high T1-c and low ADC, and accordingly defined a high-risk volume (HRV). We evaluated its prognostic value and biological significance with genomic data. RESULTS: On both discovery and validation cohorts, HRV predicted overall survival (OS) (concordance index: 0.642 and 0.653, P < 0.001 and P = 0.038, respectively). HRV stratified patients within the proneural molecular subtype (log-rank P = 0.040, hazard ratio = 2.787). We observed different OS among patients depending on their MGMT methylation status and HRV (log-rank P = 0.011). Patients with unmethylated MGMT and high HRV had significantly shorter survival (median survival: 9.3 vs. 18.4 months, log-rank P = 0.002). CONCLUSION: Volume of the high-risk intratumoral subregion identified on multi-parametric MRI predicts glioblastoma survival, and may provide complementary value to genomic information. KEY POINTS: ⢠High-risk volume (HRV) defined on multi-parametric MRI predicted GBM survival. ⢠The proneural molecular subtype tended to harbour smaller HRV than other subtypes. ⢠Patients with unmethylated MGMT and high HRV had significantly shorter survival. ⢠HRV complements genomic information in predicting GBM survival.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , DNA de Neoplasias/genética , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVES: To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) and diffusional kurtosis imaging (DKI) parameters in nasal or sinonasal squamous cell carcinoma (SCC) patients to determine local control/failure. METHODS: Twenty-eight patients were evaluated. MR acquisition used single-shot spin-echo EPI with 12 b-values. Quantitative parameters (mean value, 25th, 50th and 75th percentiles) of IVIM (perfusion fraction f, pseudo-diffusion coefficient D*, and true-diffusion coefficient D), DKI (kurtosis value K, kurtosis corrected diffusion coefficient Dk) and apparent diffusion coefficient (ADC) were calculated. Parameter values at both the pretreatment and early-treatment period, and the percentage change between these two periods were obtained. RESULTS: Multivariate logistic regression analysis: the percentage changes of D (mean, 25th, 50th, 75th), K (mean, 50th, 75th), Dk (mean, 25th, 50th), and ADC (mean, 25th, 50th) were predictors of local control. ROC curve analysis: the parameter with the highest accuracy = the percentage change of D value with the histogram 25th percentile (0.93 diagnostic accuracy). Multivariate Cox regression analyses: the percentage changes of D (mean, 25th, 50th), K (mean, 50th, 75th), Dk (mean, 25th, 50th) and ADC (mean, 25th, 50th) are predictors. CONCLUSIONS: IVIM and DKI parameters, especially the D-value's histogram 25th percentile, are useful for predicting local control. KEY POINTS: ⢠Noninvasive assessment of treatment outcome in SCC patients was achieved using IVIM/DKI. ⢠Several IVIM and DKI parameters can predict the local control. ⢠Especially, the D-value's histogram 25th percentile has high diagnostic accuracy.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Nasais/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Cavidade Nasal/diagnóstico por imagem , Curva ROC , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
PURPOSE: To develop and independently validate prognostic imaging biomarkers for predicting survival in patients with glioblastoma on the basis of multiregion quantitative image analysis. MATERIALS AND METHODS: This retrospective study was approved by the local institutional review board, and informed consent was waived. A total of 79 patients from two independent cohorts were included. The discovery and validation cohorts consisted of 46 and 33 patients with glioblastoma from the Cancer Imaging Archive (TCIA) and the local institution, respectively. Preoperative T1-weighted contrast material-enhanced and T2-weighted fluid-attenuation inversion recovery magnetic resonance (MR) images were analyzed. For each patient, we semiautomatically delineated the tumor and performed automated intratumor segmentation, dividing the tumor into spatially distinct subregions that demonstrate coherent intensity patterns across multiparametric MR imaging. Within each subregion and for the entire tumor, we extracted quantitative imaging features, including those that fully capture the differential contrast of multimodality MR imaging. A multivariate sparse Cox regression model was trained by using TCIA data and tested on the validation cohort. RESULTS: The optimal prognostic model identified five imaging biomarkers that quantified tumor surface area and intensity distributions of the tumor and its subregions. In the validation cohort, our prognostic model achieved a concordance index of 0.67 and significant stratification of overall survival by using the log-rank test (P = .018), which outperformed conventional prognostic factors, such as age (concordance index, 0.57; P = .389) and tumor volume (concordance index, 0.59; P = .409). CONCLUSION: The multiregion analysis presented here establishes a general strategy to effectively characterize intratumor heterogeneity manifested at multimodality imaging and has the potential to reveal useful prognostic imaging biomarkers in glioblastoma.
Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Meios de Contraste , Feminino , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND AND PURPOSE: The mechanisms underlying frontal lobe dysfunction in moyamoya disease (MMD) are unknown. We aimed to determine whether chronic ischemia induces subtle microstructural brain changes in adult MMD and evaluated the association of changes with neuropsychological performance. METHODS: MRI, including 3-dimensional T1-weighted imaging and diffusion tensor imaging, was performed in 23 adult patients with MMD and 23 age-matched controls and gray matter density and major diffusion tensor imaging indices were compared between them; any alterations in the patients were tested for associations with age, ischemic symptoms, hemodynamic compromise, and neuropsychological performance. RESULTS: Decrease in gray matter density, associated with hemodynamic compromise (P<0.05), was observed in the posterior cingulate cortex of patients with MMD. Widespread reduction in fractional anisotropy and increases in radial diffusivity and mean diffusivity in some areas were also observed in bilateral cerebral white matter. The fractional anisotropy (r=0.54; P<0.0001) and radial diffusivity (r=-0.41; P<0.01) of white matter significantly associated with gray matter density of the cingulate cortex. The mean fractional anisotropy of the white matter tracts of the lateral prefrontal, cingulate, and inferior parietal regions were significantly associated with processing speed, executive function/attention, and working memory. CONCLUSIONS: In adult MMD, there were more white matter abnormalities than gray matter changes. Disruption of white matter may play a pivotal role in the development of cognitive dysfunction.
Assuntos
Isquemia Encefálica/diagnóstico , Transtornos Cognitivos/diagnóstico , Doença de Moyamoya/diagnóstico , Substância Branca/patologia , Adulto , Encéfalo/patologia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/psicologia , Doença Crônica , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Imagem de Tensor de Difusão/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/psicologia , Estudos Prospectivos , Adulto JovemRESUMO
PURPOSE: To investigate the feasibility of tumor blood flow (TBF) measurement in head and neck squamous cell carcinoma (HNSCC) using pseudo-continuous arterial spin labeling (pCASL) in a comparison with dynamic contrast-enhanced (DCE) perfusion. MATERIALS AND METHODS: We prospectively scanned 18 patients with HNSCC using 3T magnetic resonance imaging (MRI) with both pCASL and DCE perfusion. Quantitative TBF value in the whole-tumor region of interest (ROI), and regional TBF in the ROIs of the central and peripheral areas in the tumor were respectively measured. Relative TBF value in the whole-tumor ROI was also calculated. We determined the correlation and agreement between each measured TBF by pCASL and DCE perfusion using Pearson's correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman analysis. RESULTS: In the whole-tumor ROIs, significant correlation was observed between the absolute TBF values (r = 0.72, P < 0.01), with an ICC of 0.72; moreover, higher correlation was observed in the relative TBF (r = 0.79). The correlation was higher in the peripheral ROI (r = 0.70) than the central ROI (r = 0.65), with an ICC of 0.62 and 0.54, respectively. Bland-Altman plots revealed the underestimation of TBF by pCASL in central ROIs. CONCLUSION: TBF measurement by pCASL was feasible in patients with HNSCC. J. Magn. Reson. Imaging 2015;41:1-1. © 2014 Wiley Periodicals, Inc.
Assuntos
Algoritmos , Velocidade do Fluxo Sanguíneo , Carcinoma de Células Escamosas/fisiopatologia , Neoplasias de Cabeça e Pescoço/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Neovascularização Patológica/fisiopatologia , Idoso , Carcinoma de Células Escamosas/patologia , Meios de Contraste , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de Spin , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
PURPOSE: To investigate the feasibility of tumor blood flow (TBF) measurement in head and neck squamous cell carcinoma (HNSCC) using pseudo-continuous arterial spin labeling (pCASL) in a comparison with dynamic contrast-enhanced (DCE) perfusion. MATERIALS AND METHODS: We prospectively scanned 18 patients with HNSCC using 3T magnetic resonance imaging (MRI) with both pCASL and DCE perfusion. Quantitative TBF value in the whole-tumor region of interest (ROI), and regional TBF in the ROIs of the central and peripheral areas in the tumor were respectively measured. Relative TBF value in the whole-tumor ROI was also calculated. We determined the correlation and agreement between each measured TBF by pCASL and DCE perfusion using Pearson's correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman analysis. RESULTS: In the whole-tumor ROIs, significant correlation was observed between the absolute TBF values (r = 0.72, P < 0.01), with an ICC of 0.72; moreover, higher correlation was observed in the relative TBF (r = 0.79). The correlation was higher in the peripheral ROI (r = 0.70) than the central ROI (r = 0.65), with an ICC of 0.62 and 0.54, respectively. Bland-Altman plots revealed the underestimation of TBF by pCASL in central ROIs. CONCLUSION: TBF measurement by pCASL was feasible in patients with HNSCC.
Assuntos
Velocidade do Fluxo Sanguíneo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/fisiopatologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/fisiopatologia , Angiografia por Ressonância Magnética/métodos , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/fisiopatologia , Idoso , Carcinoma de Células Escamosas/complicações , Meios de Contraste , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/etiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de Spin , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
To investigate whether the neurocognitive function at 4 months could be a relevant primary endpoint in clinical trials dealing with brain metastases, we created a Japanese neurocognitive battery and examined the changes in patients' neurocognitive function for 1 year after their brain radiotherapy. In this prospective pilot study, we enrolled 27 patients (20 patients who received whole-brain radiation therapy [WBRT] and seven who received stereotactic irradiation [STI] alone) between March 2009 and December 2010. The follow-up neurocognitive data at 4, 8 and 12 months were available in 22 (17 WBRT, 5 STI), 19 patients (14 WBRT, 5 STI) and 13 patients (9 WBRT, 4 STI), respectively. Among the patients who received WBRT, significant deterioration in delayed memory compared to the baseline (p = 0.04) was observed at 4 months, and at 8 months, significant improvements were observed in immediate memory compared to the baseline (p = 0.008) and 4-months scores (p = 0.005). At 12 months, however, the immediate memory scores had returned to the baseline. Similar trends were observed in other functions (delayed memory, attention and executive functions). In these patients, the correlations between 4-months scores of neurocognitive functions and 12-months scores were significant in immediate memory (γ = 0.68, p = 0.004), delayed memory (γ = 0.738, p = 0.023) and attention (γ = 0.817, p = 0.007). Among the patients who received STI, no significant changes were observed in any functions. These results suggest that 4-months changes in neurocognitive functions were transient but could also be a premonitory index for predicting the neurocognitive function 1 year or later after brain radiation therapy.
Assuntos
Neoplasias Encefálicas/radioterapia , Cognição/efeitos da radiação , Irradiação Craniana , Memória/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Testes Neuropsicológicos , Projetos Piloto , Prognóstico , Estudos Prospectivos , Radiocirurgia , Adulto JovemRESUMO
Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.
Assuntos
Alginatos , Modelos Animais de Doenças , Degeneração do Disco Intervertebral , Disco Intervertebral , Animais , Cães , Alginatos/química , Alginatos/farmacologia , Disco Intervertebral/cirurgia , Disco Intervertebral/patologia , Disco Intervertebral/efeitos dos fármacos , Coelhos , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/terapia , Estudo de Prova de Conceito , Géis , Células da Medula Óssea/citologia , Células-Tronco Mesenquimais/citologia , Imageamento por Ressonância Magnética , Masculino , Transplante de Medula Óssea/métodosRESUMO
BACKGROUND: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. METHODS: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). FINDINGS: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. CONCLUSIONS: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. FUNDING: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).
Assuntos
AVC Isquêmico , Imageamento por Ressonância Magnética , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , AVC Isquêmico/terapia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Transplante Autólogo/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Resultado do Tratamento , Adulto , Estudos de ViabilidadeRESUMO
OBJECTIVE: This study aimed to compare the diagnostic performance in the detection of brain metastases between contrast-enhanced T1-weighted volume isotropic turbo spin echo acquisition (T1-VISTA) and 3-dimensional T1-weighted fluid-attenuated inversion recovery (3D-T1-FLAIR) imaging at 3 T. METHODS: Two neuroradiologists selected 129 true (metastases) and 70 false (vessels and artifacts) lesions on the contrast-enhanced T1-VISTA and 3D-T1-FLAIR images of 14 cancer patients with hyperintense brain lesions. Four blinded neuroradiologists distinguished between the true and false lesions, using a 5-point confidence rating scale. The receiver operating characteristic analysis was performed to compare the diagnostic performance. Contrast-to-noise ratio of the true lesions was also compared between the 2 sequences by using paired t tests. RESULTS: For lesions less than 3 mm, the area under curve and sensitivity achieved by T1-VISTA imaging were significantly greater than 3D-T1-FLAIR imaging. The contrast-to-noise ratio was also significantly greater with T1-VISTA imaging. CONCLUSIONS: The contrast-enhanced T1-VISTA imaging is better suited than 3D-T1-FLAIR imaging, for detection of small metastases.
Assuntos
Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Área Sob a Curva , Artefatos , Neoplasias Encefálicas/secundário , Meios de Contraste , Feminino , Gadolínio , Gadolínio DTPA , Compostos Heterocíclicos , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Whether diurnal variation exists in quantitative MRI indices such as the T1rho relaxation time (T1ρ) of the intervertebral disc (IVD) is yet to be explored. This prospective study aimed to evaluate the diurnal variation in T1ρ, apparent diffusion coefficient (ADC), and electrical conductivity (σ) of lumbar IVD and its relationship with other MRI or clinical indices. Lumbar spine MRI, including T1ρ imaging, diffusion-weighted imaging (DWI), and electric properties tomography (EPT), was conducted on 17 sedentary workers twice (morning and evening) on the same day. The T1ρ, ADC, and σ of IVD were compared between the time points. Their diurnal variation, if any, was tested for correlation with age, body mass index (BMI), IVD level, Pfirrmann grade, scan interval, and diurnal variation in IVD height index. The results showed a significant decrease in T1ρ and ADC and a significant increase in the σ of IVD in the evening. T1ρ variation had a weak correlation with age and scan interval, and ADC variation with scan interval. Diurnal variation exists for the T1ρ, ADC, and σ of lumbar IVD, which should be accounted for in image interpretation. This variation is thought to be due to diurnal variations in intradiscal water, proteoglycan, and sodium ion concentration.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Estudos Prospectivos , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Disco Intervertebral/diagnóstico por imagemRESUMO
Whether brain temperature noninvasively extracted by magnetic resonance imaging has a role in identifying brain changes in the later phases of mild to moderate traumatic brain injury (TBI) is not known. This prospective study aimed to evaluate if TBI patients in subacute and chronic phases had altered brain temperature measured by whole-brain magnetic resonance spectroscopic imaging (WB-MRSI) and if the measurable brain temperature had any relationship with cognitive function scores. WB-MRSI was performed on eight TBI patients and fifteen age- and sex-matched control subjects. Brain temperature (T) was extracted from the brain's major metabolites and compared between the two groups. The T of the patients was tested for correlation with cognitive function test scores. The results showed significantly lower brain temperature in the TBI patients (p < 0.05). Brain temperature derived from N-acetylaspartate (TNAA) strongly correlated with the 2 s paced auditory serial addition test (PASAT-2s) score (p < 0.05). The observation of lower brain temperature in TBI patients may be due to decreased metabolic activity resulting from glucose and oxygen depletion. The correlation of brain temperature with PASAT-2s may imply that noninvasive brain temperature may become a noninvasive index reflecting cognitive performance.